Movement Disorders
Vol. 30, Suppl 1, 2015, pp. S1S567
2015 International Parkinson and Movement Disorder Society
POSTER SESSION 1
Monday, June 15, 2015
12:3014:00
Grand Hall
Parkinsons disease: Neuroimaging and
neurophysiology
1 of diffuse, prolonged AAT to that of known CVD. Prolonged AAT
Neurovascular status in idiopathic Parkinsons disease; an MRI
study
S. Al-Bachari, H.C.A. Emsley, R. Vidyasagar, L.M. Parkes (Man-
chester, United Kingdom)
Objective: To determine whether novel magnetic resonance
imaging (MRI) techniques can reveal altered neurovascular status
(NVS) in idiopathic Parkinsons disease (IPD) phenotypes, compar-
ing findings to established cerebrovascular disease (CVD).
Background: Vascular mechanisms are rapidly emerging as key
players in the neurodegenerative process in IPD in preclinical stud-
ies, yet results of clinical studies are equivocal. MRI arterial spin
labelling (ASL) is rapidly emerging as a suitable, non-invasive tool
for quantifying cerebral haemodynamics including measurements of
cerebral blood flow (CBF) and arterial arrival time (AAT) and may
help to overcome the discrepancies in clinical data.
Methods: Participants were recruited into 4 study groups; the
tremor dominant [TD] IPD, postural instability and gait dominant
(PIGD) IPD, CVD and control (C) groups. All participants under-
went a 3T MRI scan protocol including structural and physiological
measures of NVS including ASL.
Results: 12 subjects with CVD (manifesting as minor stroke or
TIA within the previous 2 years), 19 TD IPD subjects (mean age
67.2 6 0.6), 17 PIGD IPD subjects (mean age 70.7 6 6.6) and 23 C
subjects (mean age 65.1 6 5.7) completed the scanning protocol.
The number of cerebrovascular risk factors for the control (mean
Fig. 1. (1).
S1
1.36 1.0), TD (mean 1.9 6 1.6) and PIGD (mean 1.5 6 1.3) groups
were matched, but the CVD group had significantly more (mean
3.66 1.1). The results revealed a significant widespread increase in
baseline AAT in both the IPD phenotypes (TD and PIGD) and the
CVD group when compared to controls [figure1]. There were also
significant differences in voxel-based analysis of CBF revealing focal
hypoperfusion, predominantly posteriorly, in the TD, PIGD and the
CVD groups when compared to controls.
Conclusions: Despite significantly fewer CV risk factors, IPD
subjects of both the TD and PIGD phenotypes had similar patterns
has been attributed to increased collateral circulation, chronic vasodi-
latation and/or increased tortuosity of vessels in other studies. Col-
lectively these results provide evidence in a clinical setting of an
alteration in NVS in IPD warranting further investigation.
2
Apathy in Parkinsons disease (PD) as a disconnection
syndrome A resting state fMRI study
S. Appel-Cresswell, A. Liu, S.J. Lin, N. Baradaran, T. Kang, J.Z.
Wang, M.J. McKeown (Vancouver, BC, Canada)
Objective: to improve the understanding of network pathology in
PD apathy.
Background: Apathy is one of the most debilitating non-motor
features in PD yet underlying mechanisms are not entirely eluci-
dated, preventing the development of much needed specific treat-
ments. Changes in limbic and variable other brain regions have been
identified to be associated with apathy. Although apathy implies a
network malfunction, studies so far have focused on individual brain
regions; connectivity and network characteristics of apathy are
largely unknown.
Methods: 13 subjects diagnosed with idiopathic PD but without
depression (BDI <14) or cognitive impairment (MoCA<=26) were
assessed with the Apathy Scale. Other clinical indices collected
included the UPDRS motor and H&Y scores, and dopaminergic
medication. Resting state fMRI (3T) in the OFF state was performed
Movement Disorders, Vol. 30, Suppl. 1, 2015
S2 POSTER SESSION
and connectivity inferred with Bayesian network analysis. Apathy scores
were correlated with connection strength between two brain regions and
relevant connections were identified to predict apathy scores.
Results: Severity of apathy was positively correlated with the fol-
lowing connections: left (L) sup. frontal cortex (FC) to L middle FC
(p50.01), L sup. parietal cortex (PC) to L inf PC (p<0.05), L middle to
L inf. temporal cortex (TC) (p<0.05), L hippocampus to right (R) amyg-
dala (p<0.05), L amygdala to L entorhinal (p<0.05). Negative correla-
tions were found for L to R inf. TC (p<0.01), L caudate to L accumbens
(p<0.01), R sup FC to R middle FC (p<0.01), L to R insula (p50.01), L
lat. orbitofrontal cortex (OFC) to L insula (p<0.05), R supramarginal PC
to R post cingulate (p<0.05), L to R post central cortex (p<0.05), R ant
cingulate cortex (ACC) to R inf FC (p<0.05), and R to L middle FC
(p<0.05). Predicted apathy scores based on the connectivity analysis cor-
related to true apathy scores with 0.91. Apathy correlated with motor
severity and bradykinesia subscores but not with disease stage.
Conclusions: Apathy is a network disorder, mainly affecting con-
nections between limbic and cognitive areas, despite the clinical corre-
lation to motor severity and bradykinesia. In apathy, interhemispheric
connections appear to be weakened whereas mostly local connections
are strengthened, possibly acting as compensation.
3
Cortical metabolic alterations underlying cognitive decline in
Parkinsons disease
T. Baba, Y. Hosokai, Y. Nishio, A. Kikuchi, T. Hasegawa, K.
Hirayama, K. Suzuki, M. Aoki, Y. Itoyama, S. Takahashi, H. Fukuda,
A. Takeda, E. Mori (Sendai, Japan)
Objective: To clarify cortical metabolic pattern underlying longi-
tudinal cognitive decline in Parkinsons disease.
Background: Cognitive impairment is common in patients with
Parkinsons disease (PD). Mild cognitive impairment (PD-MCI) is
thought as an intermediate stage before PD dementia (PDD). The
International Parkinson and Movement Disorders Society (MDS)
recently published the criteria for PD-MCI. However, neuroimaging
evidence of progressive neuronal dysfunction associated with the
proposed neurocognitive stages is still lacking.
Methods: We analyzed the data from a 3-year longitudinal study
of patients with Parkinsons disease at Tohoku University. Briefly,
data of 46 PD patients who did not have dementia at baseline and
completed 3-year follow-up with 18F-fluorodeoxyglucose-PET scans
were retrospectively analyzed. In this study, patients were classified
as PD-MCI and PDD based on the MDS criterias. We analyzed cort-
ical metabolic alterations associated with longitudinal change in
these cognitive status by using SPM8 software (Wellcome Depart-
ment of Cognitive Neurology).
Results: At baseline, 29 patients were classified as cognitively
normal PD, and 17 patients fulfilled PD-MCI level I criteria. At
follow-up, 28 patients were classified as cognitively normal group,
12 patients were classified as PD-MCI, and 6 patients were classified
as PDD. Dementia converting rate was much higher in the PD-MCI
group compared with that in the cognitively normal PD group
(17.6% vs 10.3%). All dementia converters showed metabolic abnor-
malities in bilateral parietal lobe at baseline independently of initial
cognitive stage.
Conclusions: Current PD-MCI criteria is useful in predicting
dementia in PD, but which yet offers a satisfactory predictive accuracy
for PDD. In this study, we demonstrated that cortical metabolic abnor-
malities in bilateral parietal lobe are associated with dementia conver-
sion within 3 years. A combination of PD-MCI criteria and imaging
biomarker can improve predictive accuracy for dementia in PD.
4 by the means of standardized 3T MRI scans. ii) For the electrophysi-
Corpus callosal atrophy in Parkinsons disease
I.O. Bledsoe, G.T. Stebbins, B.A. Bernard, J.G. Goldman (Chicago,
IL, USA)
Movement Disorders, Vol. 30, Suppl. 1, 2015
Objective: To evaluate the volume of the corpus callosum on
structural magnetic resonance imaging (MRI) in Parkinsons disease
(PD) subjects with varying degrees of cognitive impairment.
Background: Approximately 80% of PD patients develop demen-
tia (PDD), which is often preceded by a prodromal phase of mild
cognitive impairment (PD-MCI). Neuroimaging studies in other
forms of cognitive impairment (e.g., Alzheimers Disease, amnestic
MCI) show volume loss of the corpus callosum, but little is known
about this structure in PD cognitive impairment. The corpus cal-
losum is of particular interest given its critical role in interhemi-
spheric communication and cognitive function.
Methods: 101 PD subjects and 25 healthy controls (HC) under-
went clinical/neuropsychological evaluations and MRI brain scans.
PD subjects underwent cognitive classification by The International
Parkinson and Movement Disorder Society criteria (cognitively nor-
mal (PD-NC), n529; mild cognitive impairment, n547; demented,
n525). Z-scores for cognitive domains (attention/working memory,
executive function, memory, language, visuospatial function) were
calculated. T1-weighted sequences were processed by FreeSurfer,
and volumes for total and corpus callosum subsections (anterior,
mid-anterior, central, mid-posterior, posterior) were computed and
normalized by total intracranial volume. Total callosal and subsec-
tion volumes were compared between PD and HC using an inde-
pendent t-test and among PD cognitive groups using ANOVAs,
correcting for multiple comparisons as appropriate. Stepwise regres-
sion analyses were performed on cognitive domain scores and cal-
losal segment volumes.
Results: Total corpus callosal volume was smaller in PD subjects
than in HCs (p5.008), particularly in central (p5.003) and mid-
anterior (p5.008) segments. PDD showed smaller volumes than PD-
NC in mid-posterior (p5.025), central (p5.009), mid-anterior
(p5.014), and anterior (p5.002) segments. In the regression models,
anterior callosal segment volumes showed the highest relationship
with the cognitive domains.
Conclusions: The corpus callosum demonstrates atrophy in PD
subjects compared to HCs. Among PD cognitive subgroups, smaller
callosal volumes were found in more anterior regions and especially
those PD with greatest cognitive deficits. Greater anterior callosal
atrophy in PD cognitive impairment may suggest abnormalities in
connectivity, particularly to frontal cortical regions.
5
The role of the supplementary motor area in freezing of gait - A
theta-burst stimulation study in Parkinsons disease
F. Brugger, R. Wegener, S. Bohlhalter, E. Abela, S. H
agele-Link, J.
Walch, G. Kagi (St. Gallen, Switzerland)
Objective: To assess the role of the supplementary motor area
(SMA) in Parkinsons disease related freezing of gait (FOG) by
using a multimodal approach including i) a morphological, ii) an
electrophysiological and iii) an interventional part.
Background: The SMA is crucial for the planning and control of
complex motor sequences. Previous studies showed that structural
and functional abnormalities in this brain region are related to FOG
in PD.
Methods: PD patients were categorized into freezers and non-
freezers according to the FOG questionnaire and the patients his-
tory. Gait, FOG and FOG-associated parameters were assessed in the
joint gait lab of the Kantonsspital and Childrens Hospital St.Gallen.
FOG-provoking tasks included starting, passing tight quarter, turning
and reaching destinations. i) For morphological assessment grey mat-
ter changes (GM) were calculated using voxel-based morphometry
ological assessment of the SMA we recorded the Bereitschaftspoten-
tial in the off and on state. iii) For the interventional part we applied
bilateral intermittent theta burst stimulation (iTBS), a facilitating
rTMS protocol, over the SMA in the off state. Gait was analyzed
 POSTER SESSION
before and immediately after iTBS. The interventional part was
designed as a sham-controlled cross-over study.
Results: 12 PD patients with FOG, 13 without FOG and 13
healthy controls were analyzed. i) PD- and FOG-related gait character-
istics correlated with GM changes in the SMA with additional clusters
in the frontal and parietal brain regions as well as the pedunculopon-
tine nucleus. ii) the late component of the BP showed smaller ampli-
tudes in PD patients with FOG. The administration of dopaminergics
led to group specific changes of early premotor and postmotor compo-
nents of the BP. iii). Intermittent TBS resulted in significant changes
of few gait parameters, particularly on turning tasks.
Conclusions: We conclude that cortical alterations not only in
the SMA, but in a widespread network including frontal and parietal
brain regions are involved in the pathophysiology of PD-related gait
impairment and FOG, respectively. However, specific BP patterns
and alteration of FOG-associated gait parameters after iTBS over the
SMA supports the notion that this brain region is essentially involved
in locomotion.
6
A sensory geste-like movement to stop tremor in Parkinsons
disease A clinical and electrophysiological case report
F. Brugger, B. Balint, R. Erro, F. G
overt, E. Antelmi, J.C. Rothwell,
K.P. Bhatia (London, United Kingdom)
Objective: To describe the clinical and electrophysiological fea-
tures in a patient with Parkinsons disease (PD) who uses a sensory
geste-like movement to stop his tremor.
Background:: Resting tremor at a frequency of 4-6 Hz is a com-
mon clinical sign in PD. Tremor intensity can be modulated by dif-
ferent factors including stress, expectation, distraction as well as by
superimposed voluntary muscle activation (also known as re-
emergent tremor). Sensory gestes as they are observed in dystonic
conditions, however, have never been described in PD.
Methods: We describe the clinical and electrophysiological find-
ings in a PD patient who uses a geste-like movement to stop his rest-
ing tremor. Surface EMG of the biceps and triceps was used to
record tremor activity. NeuroSpec 2.0 software was used to analyse
time-dependent spectra and coherence.
Results: We report a 58-year old patient who came to medical
attention due to a right-sided resting tremor of about 6 Hz. Tremor
activity was most prominent in the right biceps and triceps. Interest-
ingly, he was able to stop his tremor by a slight touch of the right
hand with the contralateral hand, similar to a sensory geste in dys-
tonic conditions. Auto- and crossspectra revealed maxima in the 6
Hz band at the time when the patient was showing the tremor.
Coherence analysis revealed a high synchronisation of muscle activ-
ity in the pair of antagonists within one second before he touched
the right hand and thus stopped the tremor. The frequency of the
muscle activity then shifted from the 6 Hz more towards a 15-25Hz
band.
Conclusions: This PD patient shows an intriguing strategy to
stop his resting tremor which rather resembles a sensory geste as it
is observed in dystonic conditions. As the electrophysiological fea-
tures change even before the patient touches the shaking hand,
expectation can be assumed to play an important role in the control
of tremor here. The occurrence of muscle activity in the 15-25 Hz
frequency band relates to voluntary muscle activation and is thought
to originate from the contralateral motor cortex. These results from
the coherence analysis are of interest as they allow insights into the
modulation of tremor in PD.
7 Results: Although antiParkinsonian medication improved visual
Disruption of resting state functional connectivity with
Parkinsons disease progression
M.C. Campbell, J.M. Koller, A.Z. Snyder, J.S. Perlmutter (St. Louis,
MO, USA)
S3
Objective: The purpose of this study was to examine longitudinal
changes in resting state networks in Parkinsons disease (PD).
Background: Previous research on resting-state functional con-
nectivity in Parkinsons disease (PD) has consistently demonstrated
disruption of cortico-striatal motor networks. Yet most studies have
focused on cross sectional evaluation and not determined whether
such alterations change over time.
Methods: Resting-state BOLD scans (Seimens 3T Trio) were
obtained from non-demented PD participants (N 5 21) while off
medication and from controls (N 5 10), matched for age and head
movement. Follow-up resting-state BOLD scans were obtained
within 1-3 years after the initial scans. For each of the primary rest-
ing state networks (default mode, dorsal attention, control, salience,
somatomotor), composite scores were computed based on the corre-
lations among network nodes and compared across groups and across
time points.
Results: PD participants demonstrated significantly lower func-
tional connectivity than the controls in the somatomotor network at
baseline (p 5 .05), as expected, but significantly greater functional
connectivity within the dorsal attention network than controls
(p < .01). Over time, PD participants showed significant reductions
in functional connectivity within the default mode network (p 5 .03)
and the dorsal attention network (p 5 .01). Interestingly, functional
connectivity of the somatomotor network in the PD participants did
not change significantly (p 5 .76), whereas functional connectivity
increased in controls (p 5 .04). Controls had no other significant
changes in network connectivity (all ps > .34).
Conclusions: These data demonstrate reduced cortical motor net-
work functional connectivity in PD. Within network functional con-
nectivity longitudinally decreased in the default mode network and
the dorsal attention network in PD participants without further loss
in the cortical motor network. We speculate that such changes in
cortical resting state networks may be sensitive to the non-motor fea-
tures associated with disease progression in PD.
8
Visual motor control in patients with Parkinsons disease
J. Chen, S.L. Ho, M.C. Lee, S.K. Chang, Y.Y. Pang, L. Li (Hong
Kong, Hong Kong)
Objective: To understand how Parkinsons disease(PD) and anti-
Parkinsonian medication affect the perceptual and motor abilities in
visual motor control using a control-theoretic approach.
Background: Although previous studies have suggested deterio-
rated visual motor control in PD is likely due to deficits in both the
perceptual and motor systems, none of them has directly separated
the effects of deficits in the perceptual and neuromuscular systems
on visual motor control. In addition, no study has directly measured
the effects of antiParkinsonian medication on the perceptual and neu-
romuscular systems for visual motor control.
Methods: We tested 20 PD patients ON and OFF mediation and
20 healthy controls with a typical closed-loop compensatory manual
control task in which participants used a joystick to keep a red target
centered on a CRT display (37 Hx21 V) as its horizontal position
was perturbed by the sum of seven harmonically-unrelated sinusoids
(0.1-2.19Hz). The time series of target position and joystick displace-
ment were Fourier analyzed and averaged across six trials. The per-
formance data were fit by an extensively validated Crossover Model
(McRuer et al., 1965) to evaluate how PD and antiParkinsonian med-
ication affect the perceptual system that processes visual information
to generate the control command and the neuromuscular system that
executes the control command.
motor control in PD patients, they still showed significantly less con-
trol precision (measured by RMS error) and response amplitude
(gain) as well as more response delay (phase) compared with the
healthy controls. The Crossover-Model-based analysis showed that
PD patients impaired visual motor control was due to (1)
Movement Disorders, Vol. 30, Suppl. 1, 2015
S4 POSTER SESSION
deteriorated perceptual sensitivity to input visual error signal for
online motor control, (2) impaired perceptual ability to anticipate the
input error to generate control response ahead of the error signal,
and (3) decreased stability of the neuromuscular system. AntiParkin-
sonian medication improved the former two but not the latter.
Conclusions: PD affects patients perceptual ability to process
visual information for online motor control and the stability of the
neuromuscular system to execute the online motor control. The effect
of antiParkinsonian medication on visual motor control appears to be
primarily through improving perceptual processing.
9 sion scale (p50.26). The neuropsychological variables were not dif-
The impact of amyloid deposition on brain network functional
connectivity in Parkinsons disease
L. Christopher, M. Criaud, A. Kucyi, Y. Koshimori, P. Rusjan, N.
Lobaugh, A.E. Lang, S. Houle, A.P. Strafella (Toronto, ON, Canada)
Objective: The objective was to measure amyloid-b deposition in
the brain with [11C] Pittsburgh compound B (PIB) PET in Parkin-
sons disease (PD) and whether this is associated with functional
connectivity (FC) changes in core neurocognitive brain networks.
Background: The presence of amyloid in the brain has been
linked to cognitive decline in PD. There is growing evidence that
amyloid deposition contributes to alterations in the FC of brain net-
works in healthy aging and neurodegenerative diseases. Cognitive
decline in PD could be associated with amyloid deposition and the
resulting effects on brain network function.
Methods: PD patients (n58) were recruited and each underwent
a [11C] PIB PET scan to measure amyloid retention and resting state
MRI scan to measure FC in comparison to a group of healthy con-
trols. [11C] PIB non-displaceable binding potential (BPND) was
measured in the cortex and striatum. Regions demonstrating
increased binding were used as covariates in a seed-based FC analy-
sis to investigate how amyloid impacts FC within and between our
networks of interest.
Results: [11C] PIB BPND was highest in the striatum and the
cingulate cortex in PD. [11C] PIB binding in the striatum was asso-
ciated with reduced FC between the ACC and frontal pole/superior
frontal gyrus. [11C] PIB in the striatum was also associated with
reduced FC between the right DLPFC and the bilateral lateral occipi-
tal cortex/angular gyrus as well as the bilateral precuneus. [11C] PIB
in the cingulate cortex was associated with reduced FC between the
right DLPFC and the frontal pole, angular gyrus and right ACC.
Conclusions: Our findings demonstrate an association between
level of [11C] PIB binding in the striatum and cingulate cortex, and
reduced FC between networks, primarily between the executive and
salience networks, and between the executive and default mode net-
works. Striatal [11C] PIB was also associated with reduced FC
within the central executive network. [11C] PIB was not associated
with any increases in FC. These findings suggest that amyloid depo-
sition contributes to reductions in FC within and between cognitive
brain networks in PD.
10
Gray matter changes in Parkinsons disease with freezing of gate
M. Delgado-Alvarado, L. Garca-Penton, H. Jim enez-Urbieta, B.
Gago, C. Caballero, M. Carreiras, M.C. Rodriguez-Oroz (San
Sebasti
an, Spain)
Objective: To investigate differences in white (WM) and gray
matter (GM) integrity between patients with Parkinsons disease
(PD) with freezing of gate (FOG1) and without FOG (FOG-) with a
similar cognitive profile.
Background: FOG is one of the most disabling features of PD
whose pathophysiology remains unclear. MRI studies have shown
that FOG1 patients have more cerebral GM and WM abnormalities
than FOG- patients. However, in these studies FOG1 patients
Movement Disorders, Vol. 30, Suppl. 1, 2015
showed more severe cognitive impairment, as they are frequent
comorbidities.
Methods: 27 FOG1 patients (age 71.67 6 8.05), 21 FOG- (age
70 6 5.81) and 21 healthy controls (age 66.24 6 7.16) were eval-
uated. FOG1 was defined as a score 1in the item 3 of the FOG
questionnaire (Giladi et al. 2000). A MRI study (3-T Magnetom Trio
Tim scanner, Siemens AG, Erlangen, Germany) was obtained in
each participant. T1-MRI and DW-MRI images were obtained.
Results were considered statistically significant at a conservative
threshold of p<0.01 corrected.
Results: There were no differences between FOG1 and FOG- in
age (p50.4), years of education (p50.5), gender (p50.1) and depres-
ferent between them, i.e., mean composite z scores for attention and
working memory (p50.551), executive function (p50.808), memory
(p50.165), visuospatial function (p50.323) and (language p50.607).
Respect to controls, FOG1 and FOG- separately had a similar pat-
tern of impaired neuropsychological tests. The FOG1 group had lon-
ger disease duration (9.93 vs 6.81 years; p50.02) and higher score
in the UPDRS-II (20.93 6 7.75 vs 12.57 6 6.39; p50.000), and
UPDRS-III (28.67 6 11.27 vs 18.43 69.60; p50.02). Compared with
controls, FOG1 group had a reduction of GM volume in the in right
inferior temporal, fusiform, Heschls, inferior frontal and superior
parietal gyri, in the right temporal pole, superior temporal sulcus and
right/left amygdala. No difference between FOG1 and FOG- and
between FOG- and controls were observed. TBSS did not reveal any
significant difference in WM among groups.
Conclusions: To our knowledge, this is the first study comparing
groups of FOG1 and FOG- patients with a similar cognitive profile,
showing that there are no differences in GM or WM between them.
In contrast, the presence of FOG is associated with GM atrophy
mainly in the right hemisphere, in areas involved in cognitive proc-
essing such as the temporal areas as well as in amygdala bilaterally.
11
Cerebral mechanisms underlying initiation and propagation of
Parkinsons tremor A dynamic causal modeling study
M.F. Dirkx, H.E. Den Ouden, E. Aarts, M. Timmer, R. Cools, R.A.
Esselink, B.R. Bloem, I. Toni, R.C. Helmich (Nijmegen, Netherlands)
Objective: To determine the cerebral mechanisms underlying
causation and propagation of Parkinsons resting tremor.
Background: Resting tremor in Parkinsons disease is linked to
pathophysiological changes both in the basal ganglia and in the
cerebello-thalamo-cortical circuit. We previously showed transient
brain activity at the onset of tremor episodes in the internal globus
pallidus (GPi), and tremor amplitude-related activity in the cerebello-
thalamo-cortical circuit. This led to the hypothesis that pathological
activity in the basal ganglia drives the cerebello-thalamo-cortical cir-
cuit into producing tremor. This hypothesis remains to be tested,
because the presence of tremor-related activity may be the cause or
consequence of tremor. Accordingly, here we used dynamic causal
modeling (DCM), allowing us to make causal inferences on inter-
regional interactions within the tremor circuit.
Methods: Using concurrent functional MRI and electromyogra-
phy (EMG), we tested two independent cohorts of tremor-dominant
Parkinsons patients (n519 and n522). We compared four different
model families where transient activity at the onset of tremor epi-
sodes (assessed using the EMG regressor) influences the tremor cir-
cuit either through the GPi, motor cortex, thalamus, or cerebellum.
Furthermore, we tested whether the GPi influences the cerebello-
thalamo-cortical network through the motor cortex or the cerebellum.
Results: We found that in both cohorts, activity at the onset of
tremor episodes causally influenced the tremor circuit through the
GPi. The magnitude of the influence was larger in patients with a
more dopamine-responsive tremor. Finally, the GPi causally influ-
enced the cerebello-thalamo-cortical circuit through the motor cortex,
not the cerebellum.
 POSTER SESSION
Conclusions: Our findings indicate that the basal ganglia initiate
tremor in the cerebello-thalamo-cortical circuit through the motor
cortex. This suggests that tremor may be treated by uncoupling the
basal ganglia from the cerebello-thalamo-cortical circuit. The differ-
ence between patients with relatively dopamine-resistant and
dopamine-responsive tremor suggests that regions outside the basal
ganglia may trigger dopamine-resistant tremor.
12
Derivation of a levodopa-related pattern with metabolic imaging
in idiopathic Parkinsons disease
C. Dresel, C. Tang, D. Eidelberg (Manhasset, NY, USA)
Objective: To derive a Levodopa-related pattern (LDRP) from
metabolic brain images in patients with idiopathic Parkinsons dis-
ease (PD).
Background: Principle component analysis (PCA) allows extract-
ing disease-related spatial covariance patterns by comparing [F-18]flu-
oro-deoxy glucose positron emission tomography (FDG PET) images
between patients and healthy subjects. These patterns may serve as bio-
markers for better differential diagnosis or prognosis of PD or other
neurodegenerative disorders, as well as for objective evaluation of ther-
apeutic interventions. For example, levodopa (LD) modulates the
expression of the PD-related pattern (PDRP) associated with motor
improvement in PD patients. Ordinal trend canonical variates analysis
(OrT/CVA) is a variant of supervised PCA designed for deriving pat-
terns of monotonic changes within subjects across conditions or over
time. The goal of the present study is utilizing the OrT/CVA method to
derive an LD-related pattern that is less dependent on the underlying
PD pathology and more specific for the therapeutic intervention itself.
Methods: We applied OrT/CVA to FDG PET scans of a heteroge-
neous group of 15 PD patients with moderately advanced disease
acquired before and after LD treatment. An LDRP was derived to cap-
ture levodopa-specific metabolic changes in the brain of PD patients.
Results: OrT/CVA on this preliminary PD sample revealed a sig-
nificant LDRP (p<0.005, non-parametric permutation test) character-
ized by LD-induced metabolic decreases in the bilateral pons,
midbrain and posterior putamen, and concurrent metabolic increases
in the inferior parts of the primary sensorimotor cortex. Bootstrap re-
sampling of the data demonstrated a significant stability of this pat-
tern (inverse coefficient of variation ICV=[-2.50, 12.39], p<0.008).
Conclusions: The LDRP contains regions known to be involved in
or linked to nigrostriatal dopaminergic neurotransmission and LD
pathology. In the long run, this pattern may allow for direct and puta-
tively more accurate assessment of treatment-associated changes in PD.
It may be used as an imaging biomarker for monitoring LD effects or
for developing customized treatment plans for individual patients.
13
Differential audiovisual processing in Parkinsons disease
C. Fearon, J. Butler, C. McDonnell, I. Killane, R. Reilly, T. Lynch
(Dublin, Ireland)
Objective: To investigate auditory and visual processing in Par-
kinsons disease using an audiovisual task.
Background: Altered visual processing occurs in PD, as evi-
denced by both clinical and electrophysiological data, often correlat-
ing with disease duration and severity. In addition, multisensory
integration becomes enhanced in older adults. In particular, visual
reaction times tend to be faster than auditory ones, with the greatest
multisensory gain attributed to the visual modality. This is likely a
strategy to compensate for loss of peripheral sensory processing but
may be maladaptive. We hypothesize that a similar adaptive process
occurs in PD to compensate for loss of automaticity of movement.
Methods: We studied PD patients under three stimulus condi-
tions: auditory, visual and audiovisual. Participants were presented
with a tone or a red disc or both simultaneously on a laptop. The
S5
stimulus conditions were randomized in 3 blocks of 100 trials with
random interstimulus interval. Participants were asked to press a but-
ton in response to all stimuli. Reaction times were computed for
each stimulus condition and the Miller Race model was tested to
evaluate the multisensory integration contribution to the audiovisual
condition. A regression analysis was performed to assess for correla-
tion of the behavioral measures with clinical/neurocognitive scores.
Results: Mean visual reaction time was slower than for auditory
and the audiovisual condition was significantly faster. Testing of the
Miller Race model revealed that audiovisual responses were facili-
tated by enhanced multisensory integration. To account for variabili-
ty in motor response times, the auditory and visual reaction times
were normalized by subtracting the audiovisual reaction time. A
regression analysis showed that the normalized visual reaction time
correlated with disease duration (r=0.62, p<0.05), whereas the nor-
malized auditory reaction time correlated with multisensory integra-
tion measures (r=0.69, p<0.05).
Conclusions: Sensory processing is altered in PD with slower visual
reaction times and patients becoming more reliant on the auditory modal-
ity for multisensory processing. The changes in visual processing speed
correlate with disease duration and contrast with healthy older adults
who tend to have faster visual reaction times and visual dominance for
multisensory integration. These findings support progressive adaptive
sensory processes in PD, which differ from that of normal aging.
14
Transcranial static magnetic field stimulation (tSMS) decreases
cortical excitability in Parkinsons disease
G. Foffani, M.C. Carrasco-L opez, J.C. Segundo-Rodriguez, N.
L
opez-Ariztegui, F. Alonso-Frech, M.J. Catalan-Alonso, A. Oliviero
(Mostoles, Spain)
Objective: To test the hypothesis that transcranial static magnetic
field stimulation (tSMS) reduces motor cortex excitability in patients
with Parkinsons disease.
Background: We recently introduced tSMS as a novel non-
pharmacological, non-invasive, DBS-compatible, low-cost neuromodu-
lation technique to decrease cortical excitability in humans (Oliviero
et al., J Physiol 2011). The present study is the first step of a larger project
that aims to test the therapeutic potential of tSMS to manage levodopa-
induced dyskinesias, supported by the Michael J. Fox Foundation.
Methods: A randomized double-blind sham-controlled cross-over
study was performed to assess cortical excitability before and imme-
diately after 10-min of tSMS or sham applied to the motor cortex in
patients with Parkinsons disease. Patients were studied off medica-
tion after overnight withdrawal of dopaminergic drugs. Cortical
excitability was quantified by the amplitude of motor evoked poten-
tials (MEPs) elicited by transcranial magnetic stimulation (TMS).
MEPs were simultaneously measured in two muscles: the first dorsal
interosseus (FDI), which was the hot spot, and the abductor pollicis
brevis (APB). The EMG background was used to exclude trials with
muscle pre-activation, often present in tremulous patients.
Results: In our preliminary data, MEP amplitudes were signifi-
cantly reduced by 28.7 6 15.0% in FDI and by 27.9 6 26.3% in APB
in the first 4 min after tSMS compared to sham (FDI, 6.9 6 16.9%,
paired t-test p50.0415; APB, 0.6 6 31.1%, p50.0102).
Conclusions: These preliminary results suggest that tSMS is able
to decrease cortical excitability in Parkinsons disease.
15
Comparative study of anatomical connectivity of prelemniscal
radiations in healthy subjects and Parkinsos disease patients
M.G. Garca-Gomar, F. Velasco, L. Concha (Queretaro, Mexico)
Objective: Characterize the anatomic connectivity of prelemnis-
cal radiations (Raprl) and identify differences in the fiber populations
that conform the Raprl using probabilistic tractography.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S6 POSTER SESSION
Background: The Raprl have been proposed as a neurosurgical
target for deep brain stimulation (DBS) for the treatment of PD since
1970s. Despite its clinical usefulness the anatomic connectivity of
the Raprl remains unknown.
Methods: Images from 12 healthy subjects and 6 PD patients
were acquired using a 3T Philips Achieva scanner. Diffusion-
weighted images were acquired using 120 unique diffusion-gradient
directions with b=2000s/mm2 (voxel size of 2x2x2mm3). Con-
strained spherical deconvolution was performed, followed by the cre-
ation of track-density images using MRtrix (Brain Research Institute
Australia), resulting in final resolution of 0.2x0.2x0.2mm3; these
images were crucial for the accurate manual segmentation of subtha-
lamic structures. We seeded 50000 streamlines at the level of the
Raprl, differences of streamlines interconnecting the Raprl between
groups were assessed by Students t-test.
Results: All subjects showed Raprl connectivity with cortical and
subcortical structures, when these fiber bundles enter the posterior
limb of internal capsule they show a clear spatial organization
according to their targets, from anterior to posterior as follows: 1)
orbitofrontal cortex, 2) globus pallidus (GP) 3) supplementary motor
area and 4) primary motor cortex and cerebellum. In 87.5% of
healthy subjects GP showed connectivity with the contralateral dorsal
brainstem in a region that corresponds to the location of the contra-
lateral pedunculopontine nucleus (PPN), the same connectivity pat-
tern is present in 83.3% of PD patients. The number of reconstructed
streamlines obtained showed differences between groups in the con-
nectivity to pallidum (left p50.017, right p50.045) and in thalamus
(left p50.02, right p50.006).
Conclusions: PD patients that have undergone Raprl-DBS show
an improvement on gait that also occurs after unilateral GP-DBS,
which could be explained because of the bilateral connections from
Raprl to PPN through fibers crossing the midline at lower midbrain.
Our findings provide new insights into subthalamic connectivity that
allow explaining clinical benefits obtained after Raprl-DBS.
16
Neural correlates underlying turning during a virtual reality task
in patients with Parkinsons disease and freezing of gait
M. Gilat, J.M. Shine, J.M. Hall, C.C. Walton, S.J.G. Lewis (Sydney,
Australia)
Objective: To investigate the pathophysiology underlying turning
as a trigger for freezing of gait in Parkinsons disease.
Background: Difficulty with turning often causes injuring falls in
Parkinsons disease patients. More specifically, turning is recognized
to be the most provocative trigger for freezing of gait, a debilitating
symptom that affects around half of patients with Parkinsons dis-
ease. Previous studies have used fMRI in combination with saccade
tasks or gait imagery to better understand turning in Parkinsons dis-
ease, yet no consensus has been reached regarding its underlying
pathophysiology.
Methods: This study therefore utilized a validated virtual reality
task in combination with fMRI to explore the neural correlates
underlying turning in 17 Parkinsons disease patients with clinically
confirmed freezing of gait and 10 non-freezers, both off their dopa-
minergic medications. During fMRI, patients navigated through a vir-
tual environment as presented on a screen that consisted of a straight
corridor with 90 degrees turns in both directions. Forward progres-
sion through this corridor was accomplished by depressing left and
right foot pedals. This allowed for BOLD responses and behavioral
footstep latencies to be compared between groups during periods of
straight walking and periods of turning. BOLD data was analyzed
using a mixed-effects analysis in SPM8.
Results: Patients with freezing of gait were more variable and
experienced longer delays in their footstep latencies during the turn-
ing task compared to the non-freezers group (p < 0.05). In addition,
a significant group x task interaction effect revealed that compared
to straight walking, turning was associated with altered BOLD
Movement Disorders, Vol. 30, Suppl. 1, 2015
responses in the cohort of freezers in key regions that have previ-
ously been associated with turning and freezing of gait, such as fron-
tal regions, even when behavioral freezing episodes were removed
(p < 0.001; k > 10). Peak ROI analyses also revealed highly signifi-
cant functional connectivity between the bilateral mesenchephalic
locomotor regions during periods of turning in the group of freezers.
Conclusions: Combining fMRI with a virtual reality task allowed
for the investigation of neural correlates underlying turning deficits
in patients with Parkinsons disease and freezing of gait.
17
White matter abnormalities as a marker of Parkinsons disease
cognitive impairment: A diffusion tensor imaging study
J.G. Goldman, D. Merkitch, B. Bernard, G.T. Stebbins (Chicago, IL,
USA)
Objective: To investigate markers of white matter (WM) micro-
structural integrity across the Parkinsons disease (PD) cognitive
spectrum using diffusion tensor imaging (DTI) measures of fractional
anisotropy (FA) and mean diffusivity (MD).
Background: Dementia develops in about 80% of PD patients in
longitudinal studies. Abnormalities in WM may contribute to PD
cognitive impairment and can be identified with neuroimaging tech-
niques. Thus, DTI holds promise as a biomarker for advancing our
understanding of the neural substrates of PD cognitive impairment
and for identifying those at risk for PD cognitive decline.
Methods: Sixty-three PD patients underwent clinical/neuropsy-
chological evaluations, T1- and diffusion-weighted magnetic reso-
nance imaging brain scans, and cognitive classification by the
International Parkinson and Movement Disorder Society criteria
(cognitively normal (PD-NC), n520; mild cognitive impaired (PD-
MCI), n528; demented (PDD), n515). DTI data were processed
with mrDiffusion, and wholebrain comparisons of the resulting
smoothed FA and MD maps, controlling for PD duration, were ana-
lyzed in SPM8 (p<0.001, uncorrected, k=10).
Results: The groups differed in PD duration (mean [SD]: PD-NC
8.8 [3.6], PD-MCI 9.4 [4.2], PDD 13.4 [5.5] years, p50.007), but
not in gender, age (73.4 [6.2] years) or education (15.3 [3.1] years).
The PD-MCI group showed decreased FA in frontal, temporal, parie-
tal, and occipital lobes, including the anterior corona radiata, anterior
thalamic radiation, inferior fronto-occipital fasciculus, and uncinate
fasciculus, and increased MD in frontal, parietal, and temporal lobes,
including the superior longitudinal fasciculus, compared to PD-NCs.
The PDD group had decreased FA in similar regions but also the
posterior corona radiata, and increased MD in frontal, temporal/pari-
etal, and limbic lobes, including corpus callosum splenium and supe-
rior longitudinal fasciculus, compared to PD-NCs. Comparisons of
PD-MCI and PDD groups revealed no significant FA/MD
differences.
Conclusions: WM microstructural abnormalities occur in cogni-
tively impaired PD patients, particularly in those brain regions under-
lying attention/working memory, executive function, memory, and
visuospatial processing. Furthermore, greater disruption of WM path-
ways in posterior regions may signify greater PD cognitive impair-
ment and thus, provide a biomarker for impending cognitive decline.
18
Attentional modulation of activity in the nucleus basalis of
Meynert in patients undergoing deep brain stimulation for
Parkinsons disease dementia and Lewy body dementia
J. Gratwicke, A. Oswal, S. Little, M. Beudel, V. Litvak, L. Zrinzo, M.
Hariz, P. Brown, M. Jahanshahi, T. Foltynie (London, United
Kingdom)
Objective: To investigate the role of the human nucleus basalis
of Meynert (NBM) in mediating different modes of attention by
 POSTER SESSION
examining in vivo local field potential (LFP) recordings during the
resting-state and during two types of attention task.
Background: The NBM is the major source of cholinergic inner-
vation to neocortex, and lies just below the globus pallidus internus
(GPi) bilaterally. Lesions to the NBM in animals lead to impaired
performance on attention tasks, implicating a key role for the NBM
in this cognitive domain. However, how activity in the NBM relates
to performance on attention tasks is unknown.
Methods: We recorded bilateral LFPs simultaneously from the
human NBM and from the GPi in patients enrolled in two ongoing
clinical trials of NBM deep brain simulation for Parkinsons disease
dementia (PDD) and dementia with Lewy bodies (DLB). The deepest
contact on each electrode was located in NBM, with higher contacts
in the GPi directly above. Recordings were obtained during the rest-
ing state, and also while the patients performed two tasks; one test-
ing orienting of attention (Posners covert attention task), and the
other testing sustained attention (Sustained attention to response
task). Spectral analysis of the data was subsequently performed using
MATLAB software and open-source academic toolboxes.
Results: Resting state recordings in all hemispheres demonstrated
peaks in delta (0.1-3Hz) and theta (4-7Hz) activity in the NBM,
which progressively diminished as contacts moved up into the GPi.
During task performance NBM activity was differentially modulated
Fig. 1. (19).
S7
depending on the mode of attention employed and this modulation
was distinct from that seen in GPi, which corresponded more with
motor components of the task.
Conclusions: Our data indicate that while activity in the human
GPi reflects movement, activity in the human NBM is more closely
related to the mode of attention employed. Deficits in orienting and sus-
tained attention are characteristic symptoms of both PDD and DLB,
and the NBM is known to degenerate severely in both conditions.
Therefore, our data support the hypothesis that damage to the NBM is
a mechanism underlying attentional impairments in PDD and DLB.
19
Structural and functional neuroimaging analysis of Parkinsons
disease
R.P. Guimar~aes, K. Larcher, L. Campos, L. Piovasana, P.C. Azevedo, Y.
Zeighami, A.C.F. DAbreu, F. Cendes, A. Dagher (Campinas, Brazil)
Objective: Our main purpose was to explore structural and func-
tional abnormalities in Parkinsons disease (PD) patients through
resting state fMRI and cortical thickness analysis.
Background: Parkinsons disease (PD) is the second most neuro-
degenerative disease worldwide. Cortical Thickness (CT) and resting
Movement Disorders, Vol. 30, Suppl. 1, 2015
S8 POSTER SESSION
Fig. 2. (19).
state functional MRI (rs-fMRI) are well defined MRI techniques that
assess the brains structure and functionality. Most studies use a
Regions of Interest (ROI) based analysis, however ROI identification
is based on a priori hypothesis, and this approach is, to some degree,
prone to user-introduced bias. We employed a data driven approach
focusing on structural and functional abnormalities.
Methods: 58 patients with PD (60.31, SD 8.99) according to the
UK Parkinsons disease Society Brain Bank criteria were compared
with 33 healthy controls (HC) (57.77 6 10.06). T1-weighted MRI
and EPI images were obtained on a 3T scanner. All fMRI analyses
were implemented with the NIAK software. (Neuroimaging Analysis
Kit) release 0.7 (Bellec et al. 2010, NIAK website), and CT data was
processed with the CIVET pipeline (version 1.1.10; Montreal Neuro-
logical Institute at McGill University, Montreal, Quebec, Canada).
Results: Areas showing lower FC in PD when compared to con-
trols were: cerebellum, basal ganglia, postcentral and precentral gyrus,
occipital lobe, SMA and substantia nigra. The results are shown in
[figure1]. For the CT analysis we stratified patients into 3 subgroups,
early PD (EPD), moderate PD (MPD) and severe PD (SPD).
The comparison between EPD and HC revealed decreased CT in
left superior temporal gyrus, left gyrus rectus and left olfactory cor-
tex (p<0.05); MPD group, the areas with lower CT were right post-
central gyrus, right SMA and right inferior frontal gyrus (P<0.05).
SPD patients had significant lower CT in left inferior frontal gyrus,
left precentral and postcentral gyrus, left SMA, left inferior frontal
Movement Disorders, Vol. 30, Suppl. 1, 2015
gyrus, left gyrus rectus, right temporal pole, right fusiform gyrus,
right middle temporal gyrus, and right occipital gyrus (P<0.05).
There were no areas of increased CT. Results are shown in [figure2].
Conclusions: The structural and functional abnormalities found
in corresponding areas demonstrate that PD involves a great number
of neuronal circuits, including areas responsible for visual process-
ing. A better understanding of the involved areas may further refine
our comprehension of the disease and its clinical subtypes.
20
Population analysis of beta band local field potential (LFP)
oscillations as a physiomarker in Parkinsons disease (PD)
R. Gupta, S. Stanslaski, T. Denison, P. Stypulkowski (Minneapolis,
MN, USA)
Objective: To investigate in a multi-center population of PD
patients the characteristics of the LFP oscillations in the beta band
(13-35 Hz) and their relevance as a physiomarker of PD.
Background: Abnormal synchronization in the beta band of
LFPs within the basal ganglia has been proposed as a pathophysio-
logical hallmark of PD. A population level analysis of this physio-
marker across multiple centers with different surgical workflows is
necessary to understand its generalizability and potentially learn
best-practices. Through our Activa PC1SV R brain sensing program,
 POSTER SESSION
we have the opportunity to look at a population database of LFP sig-
nals from PD patients collected via a number of investigator-
sponsored studies.
Methods: We analyzed LFP data recorded from the STN of 17
PD patients (4 centers) while the patients were asked to be awake
and at rest. Data were collected using a fully implanted chronic DBS
research device (Activa PC1SV R ) that can record brain activity via
the standard stimulation electrodes. This device is not FDA-approved
in the United States. Data were inspected for the presence of record-
ing artifacts and then analyzed via power spectral analysis techniques
to investigate the frequency content.
Results: A distinct peak in the beta band was detected in 12/17
patients (70.6%). Average amplitude of the peaks was 2.471/- 1.66
uV RMS (calculated as average over 1/-1 Hz around the detected
peak). Considerable inter-center variability was observed in the
amplitude of the peaks, possibly reflecting different surgical targeting
approaches and target placements. Furthermore, the peaks were
often, but not always, consistent across different follow-up visits. A
subgroup analysis revealed that the contact pair with the highest beta
power matched the contact selected as the stimulation cathode to
deliver therapy. This is consistent with findings from prior studies.
The analysis also revealed that patients with higher beta power were
programmed to higher stimulation voltages, contrary to prevailing
hypothesis.
Conclusions: Our data suggest the prevalence of a peak in the
beta band to be 70.6% across a multi-center population of PD
patients. Both inter-patient and intra-patient variability were observed
in the characteristics of the beta band power. Such variability needs
to be taken into consideration when designing algorithms that use
this physiomarker as a feedback signal.
21
Does side onset influence neural reserve in patients with
Parkinsons disease?
J.H. Ham, Y. Lee, J.J. Lee, P.H. Lee, Y.H. Sohn (Seoul, Korea)
Objective: Handedness is the most prominent human behavioral
asymmetry.9 The dominant motor cortex (M1) has a greater disper-
sion of elementary movement representations with more profuse hor-
izontal connections than does the non-dominant M1.10-12 Therefore,
it is conceivable that the dominant hemisphere could have more effi-
cient motor networks with greater neural reserve to cope with patho-
logical changes in PD. We performed this study to investigate
whether dominant-side onset PD has a greater neural reserve, and
shows less motor deficits despite of similar pathological changes
than non-dominant-side onset PD.
Background: Parkinsons disease (PD) symptoms do not develop
until 50-60% of dopaminergic neurons in the substantia nigra are
lost, suggesting the presence of a significant neural reserve in the
motor system affected by PD. Since neural reserve may depend on
the resilience of pre-existing neural networks, the dominant hemi-
sphere with more efficient networks could have more resilience in
the face of PD-related changes in the brain, and could attenuate
motor deficits despite similar degree of dopamine reduction than the
non-dominant hemisphere.
Methods: We included the data of 157 consecutive, de novoPD
patients with documented right-handedness(mean age, 64.7 6 7.7
years; range, 46 84 years; 47 men) who underwent dopamine trans-
porter PETscans for an initial diagnostic work-up. Among them, 118
patients who showed significant asymmetry of motor deficits were
selected for the analyses.
Results: Dominant-side patients (i.e., greater motor deficits on
the right-side) showed significantly less motor deficits than non-
dominant-side patients (18.0 6 8.1 and 22.9 6 10.1, respectively;
p 5 0.005). Other variables including symptom duration and striatal
dopaminergic activities were comparable between the two groups. A
general linear model showed this difference in motor deficits
remained statistically significantafter controllingthe patients age,
S9
gender, symptom duration, and striatal dopaminergic activity in the
posterior putamen (p 5 0.010).
Conclusions: These results suggest that dominant-side PD
patients have a greater neural reserve to cope with PD-related patho-
logical changes (i.e., less motor deficits despite of similar dopamine
reduction) compared to non-dominant-side patients.
22
The changes of the visual evoked magnetic field using the
magnetoencephalography and its connectivity using MRI in
aging and Parkinsons disease
M. Hirayama, Y. Fujisawa, S. Goto, J. Uemura, M. Hoshiyama, S.
Yamada (Nagoya, Japan)
Objective: To clarify a pathophysiology of visual processes in
Parkinsons disease (PD), visual evoked magnetic cortical fields
(VEFs) and diffusion weighted MRI were recorded in patients with
PD, age-matched healthy control and young subjects.
Background: Patients with PD often complain hallucination,
which is one of the non-motor symptoms in PD. Histological degen-
erative changes in retina and visual tract have been reported in
patients with PD. Functional abnormality of the visual processes in
PD remains unclear.
Methods: Twenty nine healthy subjects (13 younger and 16
elderly) and 10 PD patients participated in this study. We measured
visual evoked magnetic field (VEF) using the magnetoencephalogra-
phy (MEG). Checker pattern reversal (CPR) and monotonous grating
pattern (MGP) stimulation were used. MRI was performed to mea-
sure the current source position estimation of VEF component and
analyzed brain size and tractogram. Cognitive function test, the smell
test and UPDRS were evaluated in the PD.
Results: Four VEF components (1M, 2M, 3M, 4M) were seen
until the stimulus after 250ms. In CPR stimulus, the latency of 2M
and 3M had significantly delayed in the elderly, which compared to
the younger. The current of 1M, 2M and 3M were significantly
greater and the latency of 1M was delayed markedly in the PD,
which compared to the elderly. In MGP stimulus, no significant dif-
ference between elderly and the younger was observed. The current
of 1M was significantly greater than elderly. In the PD, 1M latency
correlated with UPDRS-1, 3 in both stimuli, and it also correlated
with the smell test in CPR stimulus. Brain volume using MRI, no
difference was not observed, while diffusion tensor imaging was sig-
nificantly different between younger and elderly, but no difference
was found between PD and elderly.
Conclusions: It was suggested that conduction delay correspond-
ing to the checker stimulus occurred in peripheral than the primary
visual cortex. Degeneration of Midget cells might be involved in the
retina. It is suggested that degeneration of the retina with aging
occurred more in PD.
23
Manifestation of Parkinsonian rest tremor is associated with
changes in high frequency oscillation power in the subthalamic
nucleus
J. Hirschmann, M. Butz, C.J. Hartmann, N. Hoogenboom, J. Vesper,
L. Wojtecki, A. Schnitzler (D
usseldorf, Germany)
Objective: To investigate the potential relationship between Par-
kinsonian rest tremor and high frequency oscillations (HFOs; 200 to
500Hz) in the subthalamic nucleus (STN).
Background: Neuronal oscillations in the STN are related to
motor control and undergo drastic changes in patients with Parkin-
sons disease. While alterations of oscillatory activity in lower fre-
quency bands are well characterized, the role of HFOs is less clear.
Recent findings suggest that HFO power is modulated by voluntary
movement and administration of levodopa.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S10 POSTER SESSION
Methods: Local field potentials were recorded from 17 STNs in
12 patients with tremor-dominant Parkinsons disease. Simultane-
ously acquired forearm EMG allowed for the identification of
tremor-containing and tremor-free epochs. Spectral power in the
HFO band was computed using a multi-taper approach and normal-
ized by mean band power. For each STN, the channel with the high-
est HFO peak was selected for further analysis, and power and
phase-amplitude coupling were compared between tremor-containing
and tremor-free epochs.
Results: The average power spectra revealed a slow HFO rhythm
(sHFO) of around 260Hz and fast HFO rhythm of around 340Hz
(fHFO). sHFO power was stronger in tremor-containing epochs than
in tremor-free epochs, while the opposite was true for fHFO power.
Eight of eight peaks above 300Hz decreased during tremor, and
seven of nine peaks below 300Hz increased during tremor. Notably,
peak frequency was stable in all cases, i.e. the change in relative
power was not due to peak shift. In addition, some STNs showed a
clear change in beta-HFO PAC. However, this change was not sig-
nificant on the group level.
Conclusions: These results demonstrate an association between
STN HFO power and tremor manifestation. The data further support
the existence of two distinct HFO rhythms, which seem to be inver-
sely related. The relationship reported here is strikingly reminiscent
of the association between HFO power and medication state (Ozkurt
et al., Experimental Neurology 2011). Thus, it seems plausible that
changes in the sHFO/sHFO power ratio reflect dynamic changes of
the endogenous dopamine level, which might influence the likelihood
of tremor emergence.
24
GBA variations accelerate degeneration of the nigrostriatal
pathway in Parkinsons disease: An [123I]FP-CIT study
I. Huertas-Fernandez, S. Jesus, P. Gomez-Garre, F.J. Garcia-Gomez,
I. Bernal-Bernal, M. Bonilla-Toribio, M.T. Caceres-Redondo, F. Car-
rillo, D. Garcia-Solis, P. Mir (Seville, Spain)
Objective: To compare the [123I]FP-CIT SPECT between Par-
kinsons disease (PD) patients with variations in glucocerebrosidase
gene (GBA) and other sporadic PD cases.
Background: PD patients with mutations in GBA show an ealier
onset, a more rapid progression of the motor symptoms and an
increased risk of developing cognitive decline and other psychiatric
symptoms. We hypothesized that [123I]FP-CIT SPECT would be
more affected in PD patients with variations in GBA.
Methods: We included a total of 45 GBA variation carriers PD
patients and a control group of 60 non-carriers PD patients. We
stratified patients based upon disease durarion when underwent
[123I]FP-CIT SPECT and compared age-matched groups in early
stages (27 GBA variation carriers and 30 non-carriers, mean 2 years)
and mid stages (18 GBA variation carriers and 30 non-carriers, mean
8 years). Images were processed and normalised to the MNI atlas
with Statistical Parametric Mapping (SPM) and we calculated mean
[123I]FP-CIT BPND in bilateral putamen, caudate, and nucleus
accumbens. The inter-group statistics were done with T-test.
Results: We found in the subgroup of PD patients at mid stages
a decreased [123I]FP-CIT BPND in GBA variation carriers com-
pared to non-carriers in bilateral putamen, caudate, and nucleus
accumbens. Differences were more pronounced in the regions ipsilat-
eral to the most-affected side (p<0.001) than those contralateral
(p<0.01). Conversely, no significant differences were found in the
early-stage subgroup comparisons.
Conclusions: This study shows that GBA variation carriers PD
patients have a more severely affected nigrostriatal pathway in the
mid stages. However, a similar affection is found in the early stages.
Our results suggest that GBA variation carriers PD patients do not
have a more aggressive onset than other sporadic PD but in few
years they experience higher rates of degeneration.
Movement Disorders, Vol. 30, Suppl. 1, 2015
25
Impact of datscan on clinical decision making: Diagnosis and
management of clinically uncertain Parkinsonian syndromes
J.R. Isaacson, S.H. Isaacson (Boca Raton, FL, USA)
Objective: To assess changes in clinical diagnosis and/or treat-
ment of 100 consecutive patients with clinically uncertain Parkinso-
nian syndromes who underwent DaTscan imaging with ioflupane for
striatal dopamine transporter degeneration.
Background: Clinically, the differentiation of Parkinsonism can
be challenging due to numerous factors, including symptom overlap
and variable response to treatment. It is not uncommon for patients
to be initially treated, but later to have diagnosis revised and treat-
ment changed. Striatal dopamine transporter is a marker of presynap-
tic dopaminergic neuroterminals. Datscan imaging can identify loss
of striatal dopamine transporters, indicative of dopaminergic degen-
eration. Striatal dopamine transporter imaging can help distinguish
between Parkinsonian disorders with (PD, SND, PSP, etc) and with-
out (drug-induced, ET, vascular, etc) dopaminergic degeneration.
Methods: Retrospective ongoing analysis of 100 consecutive
patients whose clinical diagnosis was unclear and in whom a Move-
ment Disorder specialist ordered DATscan imaging to clarify diagno-
sis by determining whether dopaminergic degeneration was present.
All patients had assessment of % likely abnormal scan prior to imag-
ing based on clinical examination and prior treatment response. After
DaTscan imaging, changes to clinical diagnosis and treatment were
assessed.
Results: Overall, approximately half of patients had an uncertain
provisional diagnosis confirmed, one-third of patients had clarifica-
tion between two provisional diagnoses, and one-fifth of imaged
patients had a provional diagnosis changed. We identified several
clinical scenarios where Datscan imaging seem most useful: drug-
induced; prominent action tremor; lower extremity predominant;
early subtle signs with nonmotor symptoms; and clinically stable
and/or without fluctuations after 5 years. Changes in treatment fol-
lowed clarification of clinical diagnosis and whether dopaminergic
degeneration was identified on Datscan.
Conclusions: In several clinical scenarios in which diagnosis of
Parkinsonian syndromes is unclear, visualization of striatal dopamine
transporters using DaTscan can differentiate between disorders with
and without nigrostriatal dopaminergic degeneration, clarifying diag-
nosis and impacting treatment.
26
Cortical excitability changes induced by L-dopa mirror the
unbalanced nigro-striatal denervation in Parkinsons disease
I.U. Isaias, F. Turco, M. Rosanova, G. Marotta, G. Frazzitta, C.
Landi, A. Perretti, L. Giusti del Giardino, M. Canesi, M. Massimini,
G. Pezzoli, S. Casarotto (Wurzburg, Germany)
Objective: To evaluate the effects of acute administration of L-
dopa on cortical excitability in frontal and parietal cortices and to
assess the asymmetry of this effect in relation to nigro-striatal dopa-
minergic denervation.
Background: L-dopa is an effective and established treatment for
Parkinsons disease (PD). However, its indirect effects on cortical
functions have not been fully uncovered, but could be very important
to understand the pathophysiology of some L-dopa-related adverse
effects (e.g. dyskinesia).
Methods: Thirteen PD patients were investigated by Single Pho-
ton Computed Tomography (SPECT) and [123I]FP-CIT. The brain
side (hemisphere H) with lower/higher striatal-specific binding ratio
was labeled as H-/H1. Cortical potentials evoked (TEPs) by trans-
cranial magnetic stimulation (TMS) were recorded by means of
high-density EEG (hdEEG) from each patient 12 hours after with-
drawal of all dopaminergic drugs (meds-off) and at 90 minutes after
oral intake of 200 mg of fast-released soluble L-dopa (meds-on).
TMS was delivered to the supplementary motor area (SMA) and
 POSTER SESSION
superior parietal lobule (SPL) bilaterally. Cortical excitability was
measured by the immediate response slope (IRS) and immediate
response area (IRA) computed from TEPs averaged across region-of-
interest neighboring channels. The effects of acute L-dopa intake
were measured as the percentage change of IRS and IRA (D%)
between meds-off and meds-on conditions. D%IRS and D%IRA
were compared between H- and H1 at the group level.
Results: The morphology of TMS-evoked potentials was similar
across patients and characterized by an early positive wave between
12-35 ms followed by a negative peak at about 45 ms. D%IRS and
D%IRA on the same side of the stimulation target was significantly
higher in H- as compared to H1 only when SMA was targeted
(p<0.05 for IRS; p<0.02 for IRA). The same analysis performed on
the opposite side of the stimulation target did not reveal any signifi-
cant difference between H- and H1 for stimulation of either SMA or
SPL.
Conclusions: Acute administration of L-dopa specifically
increases neuronal excitability of premotor cortex on the brain side
with greater nigro-striatal dopaminergic denervation. This study also
demonstrates the feasibility of measuring cortical excitability in PD
patients by means of TMS together with hdEEG.
27
Differential diagnosis of Parkinsonism using two PD-related
metabolic patterns
V.A. Jourdain, C.C. Tang, D. Eidelberg (Manhasset, NY, USA)
Objective: To determine whether individual subjects with idio-
pathic Parkinsons disease (PD) can be distinguished from atypical
Parkinsonian syndromes (APS) based on differences in expression
values for established PD metabolic covariance patterns relating to
motor and cognitive disease manifestations.
Background: Accurate discrimination of patients with PD vs.
APS (represented mainly by progressive supranuclear palsy (PSP)
and multiple system atrophy (MSA)) can be clinically challenging.
We have found that PD is characterized by increases in PDRP and
PDCP expression, with greater expression of the former relative to
the latter in individual subjects. However, these network changes are
uncommon in APS.
Methods: 167 Parkinsonian patients (96 PD, 41 MSA and 30
PSP) with uncertain clinical diagnosis, in which 55 (30 PD, 11 MSA
and 14 PSP) had disease duration of 2 years, underwent FDG PET.
Final diagnoses for these patients were made after a clinical follow-
up of 2.6 years. For each patient, we calculated expression values
(subject scores) for the PDRP and PDCP networks, as well as delta
PDRP-PDCP, the difference in the two scores. Logistic regression
was followed by ROC analysis. Area under the curve (AUC) was
used to determine the accuracy of delta PDRP-PDCP as a predictive
classifier for PD, MSA, and PSP.
Results: Delta PDRP-PDCP was a significant classifier
(AUC=0.82, p<0.0001) that distinguished PD from APS patients. A
similar result was obtained (AUC=0.78, p50.002) in the short dura-
tion patients. This measure, however, did not differentiate MSA from
PSP (AUC=0.52, p>0.57) in either the whole sample or the short
duration subgroup. Classification was overall less accurate with this
logistic algorithm than with one based on individual subject scores
for previously validated metabolic patterns for PD, MSA, and PSP
(Tang et al., 2010).
Conclusions: Delta PDRP-PDCP is a potentially useful network
classifier for the differential diagnosis of Parkinsonism. This measure
is consistently positive (delta>1) in classical PD, reflecting Braaks
pathological timeline. In PD, relatively greater PDRP expression
may represent earlier subcortical involvement (analogous to Braak
Stage V), while consistently smaller PDCP levels reflect the later
development of neocortical pathology (analogous to Braak Stage VI).
This network timeline, represented by delta PDRP-PDCP, is specific
for classical PD, thereby providing accurate differential diagnosis.
S11
28
Levodopa-induced changes in neurovascular reactivity in
Parkinsons disease
V.A. Jourdain, F. Holtbernd, C.C. Tang, V. Dhawan, D. Eidelberg
(Manhasset, NY, USA)
Objective: To determine whether the difference in levodopa-
induced increase in striatal levels of dopamine between dyskinetic
and non-dyskinetic patients depends, at least in part, on functional
and structural alterations of the brain microvasculature.
Background: In our original study of 8 subjects without
levodopa-induced dyskinesia (LID) and 3 with LID (Hirano et al., J
Neurosci 2008;28:4201-9), we demonstrated that blood flow/metabo-
lism dissociation was created by levodopa in dopa-decarboxylase-
rich brain regions in putamen and internal globus pallidus (GPi), and
in the dorsal pons.
Methods: Eleven LID and 5 non-LID PD subjects, as well as 14
healthy volunteers underwent dual tracer [15O]-H2O and [18F]-FDG
PET to measure cerebral blood flow (CBF) and cerebral metabolic
rate for glucose (CMR) at baseline (OFF) and during an intravenous
levodopa infusion (ON) to replicate the original observations. We
also measured the OFF-levodopa CBF under normocapnic and hyper-
capnic (5% CO2, rebreathing up to 5 minutes) conditions in the cur-
rent PD cohort to measure whether LID is associated with abnormal
hypercapnic response (an index of underlying capillary density) in
areas of levodopa-mediated flow metabolism dissociation.
Results: The regions identified in the original voxel-based analy-
sis were highly concordant with those identified in the new PD
cohort. As in the original study, significant levodopa-mediated flow
metabolism dissociation was also seen at the network level for the
PD motor-related pattern (PDRP). When combining both cohorts (14
LID, 13 non-LID, 8 test-retest PD and 14 healthy controls),
levodopa-mediated flow metabolism dissociation was greater in LID
relative to non-LID subjects in the putamen/GPi, as well as the net-
work level. These results were mainly driven by an increase in CBF
in the ON-state. Under normocapnic conditions, no difference was
observed between controls and PD or between LID and non-LID
subjects. Normal and PD subjects both exhibited increased CBF dur-
ing hypercapnia with a significantly greater increase in LID patients.
Conclusions: The findings suggest that LID subjects have greater
flow metabolism dissociation in response to levodopa treatment than
their non-LID counterparts. Moreover, the increase in capillary
reserve seen with LID suggests that this side effect is associated with
underlying microvascular changes in key brain regions.
29
Alternations of human brain connectome in Parkinsons disease
using network based statistics (NBS)
A. Kamalian, M.H. Aarabi (Tehran, Iran)
Objective: To determine impaired interconnecting fibers of
patients with Parkinsons disease using Diffusion Tensor Imaging
(DTI) and a statistical approach Network Based Statistics (NBS)
to analyze brain connectivity matrices.
Background: Neuroimaging is an accurate method to examine the
areas engaged in PD neurodegeneration. Previous DTI studies had
used topological features e.g. degree and clustering coefficient to
investigate PD-correlated brain network alterations. However, we com-
puted average tract length and fiber volumes as measures of white
matter integrity. In addition, we adopted a novel statistical approach to
conduct group connectivity analyses between PD patients and healthy
controls.
Methods: Data Acquisition:
Data used in the preparation of this abstract were obtained from
the Parkinsons Progression Markers Initiative (PPMI) database
(www.ppmi-info.org/data) with permission. For up-to-date informa-
tion on the study, visit www.ppmi-info.org.
Methods:
Movement Disorders, Vol. 30, Suppl. 1, 2015
S12 POSTER SESSION

TABLE 1. Significant Pathways (Volume of Fibers) TABLE 2. Significant Pathways (Average Tract Length)
Pathway T stat Pathway T stat
Frontal_Sup_Orb_L to Frontal_Mid_R. 2.96 Supp_Motor_Area_L to Cingulum_Post_L 3.20
Frontal_Mid_R to Frontal_Inf_Tri_R. 3.07 Frontal_Sup_L to Hippocampus_L 2.98
Frontal_Inf_Oper_R to Frontal_Inf_Tri_R. 3.86 Cingulum_Post_L to ParaHippocampal_L 2.96
Frontal_Inf_Oper_R to Insula_R. 3.68 Frontal_Inf_Orb_R to Occipital_Sup_L 4.06
Frontal_Inf_Tri_R to Insula_R. 2.92 Occipital_Mid_L to Occipital_Mid_R 2.98
Cingulum_Post_L to Cingulum_Post_R. 3.13 ParaHippocampal_L to Fusiform_L 3.01
Cingulum_Post_L to Hippocampus_L. 3.10 Frontal_Inf_Orb_L to Parietal_Sup_L 4.02
Cingulum_Ant_R to Hippocampus_R. 3.48 Frontal_Inf_Orb_R to Parietal_Sup_R 3.57
Olfactory_R to ParaHippocampal_L. 3.13 Cingulum_Post_R to Parietal_Sup_R 3.63
Frontal_Inf_Orb_R to Occipital_Sup_L. 2.99 Occipital_Mid_L to Parietal_Sup_R 3.10
Cuneus_L to Occipital_Mid_R. 3.53 Occipital_Inf_R to Parietal_Sup_R 3.10
Occipital_Sup_L to Occipital_Mid_R. 3.04 Hippocampus_L to Precuneus_L 3.17
Occipital_Inf_R to Parietal_Sup_R. 3.33 ParaHippocampal_L to Precuneus_L 2.92
Frontal_Inf_Tri_L to Precuneus_L. 2.91 Fusiform_L to Precuneus_L 2.97
Cingulum_Post_L to Precuneus_L. 3.06 Parietal_Sup_R to Precuneus_L 3.06
Cingulum_Post_R to Precuneus_L. 3.00 Parietal_Sup_R to Putamen_L 4.41
Cingulum_Post_R to Precuneus_R. 2.99 Parietal_Sup_R to Pallidum_L 3.81
Hippocampus_R to Precuneus_R. 3.12 Frontal_Inf_Orb_L to Pallidum_R 3.02
Occipital_Mid_R to Precuneus_R. 3.55 Rolandic_Oper_L to Heschl_L 3.64
Frontal_Inf_Orb_R to Putamen_R. 2.94 Hippocampus_L to Temporal_Pole_Sup_L 3.20
Parietal_Sup_R to Pallidum_L. 3.28 ParaHippocampal_L to Temporal_Pole_Sup_L 3.39
Precuneus_L to Pallidum_L. 3.14 Precuneus_L to Temporal_Pole_Sup_L 3.26
Heschl_L to Temporal_Sup_L. 3.15 Pallidum_R to Temporal_Pole_Sup_L 3.43
Olfactory_R to Temporal_Pole_Sup_L. 3.09 Heschl_L to Temporal_Pole_Sup_L 3.37
Cingulum_Post_R to Temporal_Pole_Sup_L. 2.95 ParaHippocampal_L to Temporal_Inf_L 2.92
Precuneus_L to Temporal_Pole_Sup_L. 3.00 Parietal_Sup_R to Vermis_3 3.05
Pallidum_R to Temporal_Pole_Sup_L. 3.27
Heschl_L to Temporal_Pole_Sup_L. 3.01
Insula_R to Temporal_Pole_Sup_R. 3.13
Putamen_R to Temporal_Pole_Sup_R. 3.18 DWI data were analyzed for 18 patients (73.34 6 3.94) and 12
controls (71.5 6 3.45) using ExploreDTI . The diffusion tensors were
estimated based on weighted linear least squares and for EPI-
distortion and head motion correction, DWI data were rigidly regis-
tered with MNI atlas. Deterministic full brain tractography was

Fig. 1. (29).

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
Fig. 2. (29).
performed using a stopping criterion of 0.2 FA and 30 curvature
threshold. The whole-brain fiber tract reconstructions of the previous
step were parcellated using the automated anatomical labeling (AAL)
atlas. By applying the ROI masks to the reconstructed fiber tracts
using the ExploreDTI, the volume and average tract length that origi-
nated in one ROI (i) and terminated in another one (j) was deter-
mined, creating a 116 3 116 connectivity matrix . Then, we used
NBS for group analysis. NBS is a method to control the family-wise
error rate (in the weak sense). The overall workflow is illustrated
in Figure 1.T-test statistics were applied and significant results
(p-values < 0.05) were reported.
[Figure 1]
Results: The regions exhibiting significantly diminished intercon-
nections including: cingulum, hippocampus, parahippocampus,
olfactory lobe, occipital lobe, cuneus, and basal ganglia are pre-
sented extensively in Tables I,II, and Figure 2.
[Figure 2]
Conclusions: Our results confirm prior studies reporting fibers
interconnecting olfactory lobe, occipital lobe, cingulum, hippocampus,
parahippocampus, and basal ganglia as major sites of damage in PD.
30
Importance of proper window setting on visual assessment of
dopamine transporter image
A. Kim, H.J. Kim, B.S. Jeon (Seoul, Korea)
Objective: To describe a young male patient with Park2 mutation
whose FP-CIT PET was misinterpreted as normal initially.
Background: Diagnosis of neurological conditions associated with
disturbances of dopaminergic functioning can be challenging, especially
in the early stages or atypical manifestation. In those cases, dopamine
transporter imaging can assist the early diagnosis. Although there are
quantitation methods for dopamine transporter image assessment, they
are laborious and generally are not used for routine clinical practice.
Therefore, visual assessment is used in routine clinical practice.
Methods: Case report.
Results: A 17 year-old man presented with progressive gait dis-
turbance, cervical dystonia and head tremor. His neurologic examina-
tion showed mild rigidity and resting tremor of bilateral legs which
was slightly dominant on the left side. 18F-FP-CIT positron emission
tomography (PET) was done and interpreted as normal at other hos-
pital, and his diagnosis remained elusive. He visited our hospital sev-
eral months later, and the FP-CIT PET image was reviewed by the
radiologist in our hospital, who also interpreted it as normal. How-
ever, we reviewed his FP CIT-PET image because his clinical pic-
ture was strongly suggestive of juvenile Parkinsonism. After
S13
adjusting the window setting of the PET image, we could appreciate
the decreased uptake in the bilateral basal ganglia. Thus he was
finally diagnosed as juvenile Parkinsonism. Gene test confirmed that
his Parkinsonism was due to Park2 gene mutation.
Conclusions: Proper window setting is important during visual
assessment of dopamine transporter imaging.
31
Putaminal dopamine turnover in de novo Parkinsons disease
predicts levodopa-induced motor complications
M. L
ohle, J. Mende, M. Wolz, B. Beuthien-Baumann, L. Oehme, J.
van den Hoff, J. Kotzerke, H. Reichmann, A. Storch (Dresden,
Germany)
Objective: To investigate the predictive value of baseline striatal
dopamine metabolism in de novo Parkinsos disease for the onset of
later motor complications.
Background: Long-term therapy with levodopa is associated with
motor complications, such as wearing-off and levodopa-induced dys-
kinesias (LID), for which treatment options are still limited. Patho-
logical and neuroimaging studies have not completely unravelled the
underlying pathogenesis of these complications, which hinders reli-
able prediction and potential prevention.
Methods: We performed a retrospective, observer-blind, long-
term follow-up study in 31 patients with early, drug-nave Parkin-
sons disease, who had originally received quantitative 18F-dopa PET
imaging to estimate striatal 18F-dopa uptake (Kocc) and effective
dopamine distribution volume ratio (EDVR) as the inverse of dopa-
mine turnover prior to treatment allocation. The onset of wearing-off
and LID was estimated based on blinded clinical assessments and
patient records. The predictive value of baseline PET results of stria-
tal subregions for the development of motor complications (wearing-
off, LID and any motor complication) was evaluated using Cox pro-
portional hazard models.
Results: Over a mean observation period of 6.8 years, 18
(58.1%) patients developed wearing-off, 11 (35.5%) LID and 20
(64.5%) any motor complication. Patients with LID and any motor
complication showed lower EDVR (higher dopamine turnover) in the
putamen than those without LID and any motor complication, with
differences most markedly present in the posterior putamen. EDVR
in the whole and the posterior putamen predicted development of
motor complications with an increasing risk with lower EDVR
(higher dopamine turnover), whereas EDVR in other regions and
Kocc did not correlate with motor complications. Kaplan-Meier
curves showed reduced survival from motor complications in patients
Movement Disorders, Vol. 30, Suppl. 1, 2015
S14 POSTER SESSION
with lower baseline EDVR (higher dopamine turnover) in the poste-
rior putamen with ongoing levodopa treatment and disease duration.
Conclusions: Elevated putaminal dopamine turnover in de novo
Parkinsons disease is associated with an increased risk for later
motor complications. This increase in putaminal dopamine turnover
might constitute an early compensatory mechanism and could play
an important role in the development of levodopa-related motor com-
plications as a disease-intrinsic predisposing factor.
32
Understanding the effects of subthalamic nucleus (STN) deep
brain stimulation (DBS) with preoperative diffusion tensor
imaging (DTI)
P.M. Lauro, N. Vanegas, Z. Kareem, L.I. Codrin, S.S. Ziad, H.G.
Silvina (Bethesda, MD, USA)
Objective: We aimed to characterize the specific stimulator-
neuronal connectivity associated with favorable clinical outcomes
using preoperative DTI and stereotactic electrode locations.
Background: DBS is an effective therapy for treating Parkinsons
disease (PD). Symptom relief is achieved by targeting specific areas
of the STN. Studies have suggested that stimulation of white matter
structures adjacent to the main target have similar beneficial effects.
Methods: Twenty patients (9 male, average age: 57.9 6 9.49,
average disease duration: 13.25 6 6.69) with idiopathic PD who
received STN DBS surgery at the NIH were studied. All patients
underwent preoperative MRI including diffusion-weighted imaging
(b=1000 s/mm2, 32 directions). Postoperative CT images were co-
registered to preoperative T1, T2, and DTI for DBS lead localization.
Diffusion images were processed with TORTOISE and tensors were
estimated non-linearly with AFNI. Grey-matter ROIs were created
from preoperative T1 images with Freesurfer and aligned to DTI
volumes.
Monopolar screening of DBS contacts was performed one month
after implantation to determine voltages for clinical benefit. The con-
tact with the largest therapeutic window was chosen as the stimulat-
ing contact. The volume of tissue activated (VTA) was estimated as
a sphere whose radius was calculated using contact impedance and
voltage. Probabilistic tractography was used to determine the number
of streamlines from each VTA to selected gray-matter ROIs using
FATCAT. To adjust for differences in conduction volume, the num-
ber of streamlines was scaled by VTA size.
Results: Tractography networks were determined for all chronic
stimulation contacts and for contacts with side effects and no clinical
benefit. The total percentage of connections with three gray matter
structures (ventral diencephalon, caudate and thalamus) ipsilateral to
the stimulating contacts (left 81.46 6 14.83%; right 79.03 6 15.09%)
was higher compared with the one obtained for contacts without clin-
ical benefit (left 63.45 6 17.48%; right 66.45 6 18.48%).
Conclusions: By co-registering preoperative DTI and postopera-
tive CT, we were able to determine specific connectivity patterns
that characterize clinically effective DBS electrodes. This type of
network analysis provides a potential targeting and prospective pro-
gramming approach for DBS therapy.
33
Gender difference in depletion of presynaptic nigrostriatal
dopamine in de novo Parkinsons disease
J.J. Lee, J.S. Oh, J.H. Ham, D.H. Lee, I. Lee, P.H. Lee, J.S. Kim,
Y.H. Sohn (Seoul, Korea)
Objective: To explore whether a gender difference in presynaptic
nigrostriatal dopaminergic density in patients with de novo Parkin-
sons disease (PD) using a quantitative analysis of 18F-FP-CIT posi-
tron emission tomography(PET) scans.
Background: Several antecedent studies have been reported of
gender difference in PD including different clinical characteristics of
Movement Disorders, Vol. 30, Suppl. 1, 2015
motor and non-motor symptoms, response to deep brain stimulation
and even those in plasma a-synuclein concentrations. The neuropro-
tective influence of estrogen to dopaminergic neurons, and male-
female difference of brain morphology and functions are suggested
as possible mechanisms of those distinction.
Methods: This study included 307 drug-nave patients (152 men
and 155 women) with de novo PD who completed an 18F-FP-CIT
PET scan at initial diagnosis. Quantitative analyses of dopamine
transporter (DAT) activities were performed based on volumes of
interests, and thus each unilateral striatum was divided into 6 subre-
gions of which comprised with 2 caudate subregions (anterior and
posterior), ventral striatum, and 3 putaminal subregions (anterior,
posterior, and ventral). Gender difference of DAT activities in each
striatal subregion as increase of age at onset was assessed using lin-
ear regression analyses.
Results: We found no significant male-female differences in age
at onset, disease duration and Unified PD rating scale (UPDRS) part
III. In scatter plot of age at onset versus DAT activities, the DAT
activities were reduced with increase of the age at onset and those in
female were higher than those in male in all striatal subregions. In
linear regression analysis adjusting for age at onset, disease duration
and UPDRS III, the degree of gap of DAT activities between male-
to-female was reduced as increase of age at onset in all striatal sub-
regions, and these gaps were in significance in anterior putamen
(Estimated slope [ES], -0.005 vs -0.018; p50.001), anterior (ES, -
0.021 vs -0.039; p<0.001) and posterior (ES, -0.013 vs -0.025;
p<0.001) caudate but not in ventral striatum, posterior and ventral
putamen.
Conclusions: We found that nigrostriatal dopamine neurons are
significantly more preserved in anterior part of the basal ganglia in
female with exception of posterior part which is well known suscep-
tible region for Lewy body degeneration. These findings suggest that
neuroprotective effect in female may not be associated with PD
pathogenesis per se.
34
Evaluation of saccadic eye movements in patients with
Parkinsons disease: Effect of levodopa
A. Lenka, K.R. Jhunjhunwala, R. Kotikalapudi, P.K. Pal (Bangalore,
India)
Objective: To assess the saccadic eye movements in patients
with Parkinsons disease (PD) and to investigate the effect of levo-
dopa on saccadic eye movements.
Background: Cortical and subcortical brain regions which control
saccadic eye movements, are known to be involved in PD. Though
abnormalities of saccadic eye movement have been reported in PD,
the effect of levodopa on saccadic eye movements is not clear.
Methods: Eye movements of 15 patients (10 men) with PD
patients and 15 age and gender matched controls were recorded by
an IVIEW X HI-SPEED eye tracker (SensoMotoric Instruments
GmbH, Germany) using a Visually Guided Stimulus (VGS) task.
Various saccadic parameters such as latency, average velocity, peak
velocity, average acceleration and peak acceleration were assessed in
drug OFF and best ON states in PD patients and compared with
healthy controls. ANOVA was used to compare the saccadic parame-
ters between three groups a) OFF state b) ON state c) Controls.
Paired t test was used to compare between ON and OFF state in PD
patients. Since saccadic latency does not have a normal distribution,
median of reciprocals of latencies were taken which showed a Gaus-
sian distribution.
Results: The mean age of the patients was 52.9 6 11.6 years and
that of controls was 51.7 6 7.4 years. The mean age at disease onset
was 48.2 6 12.1 years and mean duration of illness was 4.1 6 2.5
years. The mean UPDRS- OFF and ON scores of PD patients were
35.4 6 8.4 and 20.1 6 10.4 respectively. On comparison between the
three groups (a, b and c) there was no significant difference in all
the saccadic parameters except average acceleration, which was
 POSTER SESSION
significantly lower in OFF state compared to controls
(8344.5 6 2944.2 /sec2, vs 10327.3 6 2971.1 /sec2, p50.039). On
comparison, though the saccadic parameters improved from OFF to
ON state, the differences were not statistically significant: reciprocal
latencies (2.9 6 0.9 sec-1 vs 3.1 6 0.8sec-1), average velocity
(200.8 6 56.1 /sec vs 207.8 6 63.8 /sec), peak velocity
(389.6 6 135.1 /sec vs 397.2 6 157.3 /sec), average acceleration
(8344.5 6 2944.2 /sec2 vs 9546.3 6 3286.5 /sec2) and peak accelera-
tion (16501.6 6 5818.1 /sec2 vs 17885.1 6 6318.6 /sec2).
Conclusions: PD patients during OFF state had reduced average
acceleration of the saccades compared to controls. Levodopa did not
significantly improve any of the saccadic parameters, though larger
cohort need to be studied.
35
Resetting tremor by single and paired transcranial magnetic
stimulation in Parkinsons disease and essential tremor
M.K. Lu, S.M. Chiou, U. Ziemann, H.C. Huang, Y.W. Yang, C.H.
Tsai (Taichung, Taiwan)
Objective: To investigate whether tremor in Parkinsons disease
(PD) and essential tremor (ET) is differentially modulated by pertur-
bation of the motor-related cortices.
Background: The pathogenesis of tremor in PD and ET is not
fully understood. This study tested the role of primary motor cortex
(M1), supplementary motor area (SMA) and cerebellar cortex on PD
Fig. 1. (36).
S15
and ET tremor by single- and paired-pulse transcranial magnetic
stimulation (TMS).
Methods: Ten PD patients with resting tremor, six of them also
with postural tremor, and 10 ET patients with postural tremor were
studied. Randomized single- and paired-pulse TMS with an intersti-
mulus interval of 100 ms were delivered over M1, SMA and cerebel-
lum. TMS effects were evaluated by calculating a tremor-resetting
index (RI).
Results: Single- vs. paired-pulse TMS showed no difference. M1-
TMS and SMA-TMS but not by cerebellar TMS induced a signifi-
cant RI in PD and ET. M1-TMS resulted in a significantly higher RI
in PD than ET. Furthermore, M1-TMS in PD but not in ET resulted
in a significantly higher RI than SMA-TMS.
Conclusions: Findings suggest a stronger involvement of M1 in
resting and postural tremor in PD than postural tremor in ET. RI pro-
vides a useful marker to explore the differential functional role of
M1, SMA and cerebellum in PD versus ET tremor.
36
White matter microstructure damage in tremor-dominant
Parkinsons disease patients
C. Luo, X. Guo, W. Song, H. Shang, Q. Gong (ChengDu, Peoples
Republic of China)
Objective: The current study aims to investigate the differences
in white matter integrity in Parkinsons disease (PD) patients with
Movement Disorders, Vol. 30, Suppl. 1, 2015
S16 POSTER SESSION
and without tremor and to identify possible structural correlates of
rest tremor.
Background: Rest tremor is a hallmark of PD, yet its pathogene-
sis is incompletely understood. Several lines of evidence suggest
tremor may have different underlying pathophysiology processes
from those of bradykinesia and rigidity. It is unclear whether PD
patients with and without tremor are also different concerning white
matter integrity.
Methods: We recruited two carefully matched groups of PD
patients that had either absent or prominent resting tremor, but who
all displayed similar levels of akinesia and rigidity (30 with tremor-
dominant PD and 30 with nontremor-dominant PD), and 26 normal
controls. All participants underwent clinical, neuropsychological
assessment and diffusion tensor MRI. We used tract-based spatial
statistics to investigate white matter integrity across the entire white
matter tract skeleton.
Results: Compared with both healthy controls and nontremor-
dominant PD patients, tremor-dominant PD patients were character-
ized by increased MD and AD along multiple white matter tracts
within cortico-cerebello-thalamo-cortical (CTC) pathway and some
regions of association fibers. Mean MD value in white matter tracts
Fig. 1. (37).
Movement Disorders, Vol. 30, Suppl. 1, 2015
correlated with tremor scores in tremor-dominant PD patients. There
was no significant difference between nontremor-dominant PD
patients and controls. [figure1]
Conclusions: Our results support the notion that tremor in PD as
a distinct condition in which significant microstructural white-matter
changes exist and provide evidence for the involvement of CTC in
tremor genesis of PD. These findings suggest that objective measures
of white matter integrity may be useful in future genotype-phenotype
analyses and in targeted therapeutic trials focused on PD subtypes.
37
The trajectory of disturbed resting-state cerebral function in
Parkinsons disease at different Hoehn & Yahr stages
C. Luo, W. Song, X. Guo, H. Shang, Q. Gong (Chengdu, Peoples
Republic of China)
Objective: We aim to investigate the disturbance of neural net-
work associated with the different clinical stages of Parkinsons dis-
ease (PD).
 POSTER SESSION
Fig. 2. (37).
Background: Studies using advanced methods of time series
analysis of oscillatory brain activity have demonstrated that synchro-
nization of neuronal activity within and between distributed neuronal
populations is an important mechanism in a variety of cognitive and
motor functions, including movement preparation, sensorimotor inte-
gration and attention. It has been suggested that PD is characterized
by changing patterns of disturbed neural synchrony that appear to be
dependent on the stage of disease. Resting-state fMRI (rfMRI) allows
the interrogation in vivo of the neural synchrony disturbance. How-
ever, few experiments have utilized rfMRI to depict the changing
course of abnormal functional integration in PD.
Methods: We recruited 80 patients at different H&Y stage of PD
(28 at H&Y stage I, 28 at H&Y stage II, 24 at H&Y stage III) and
30 normal controls. All participants underwent resting-state fMRI
scans on a 3-T MR system. The amplitude of low-frequency fluctua-
tion (ALFF) of blood oxygen level-dependent signals was used to
characterize regional cerebral function. Functional integration across
the brain regions was evaluated by a seed voxel correlation
approach.
Results: PD patients had deceased regional activities in left occi-
pital and lingual regions; these regions show decreased functional
connection pattern with temporal regions, which is deteriorating as
H&Y stage ascending . Functional integrity in occipital-temporal
S17
circuits is negatively correlated with UPDRS III score. In addition,
PD patients, especially those at stage II, exhibit increased regional
activity in the posterior regions of default mode network (DMN),
increased anti-correlation between posterior cingulate cortex (PCC)
and cortical regions outside DMN, and higher temporal coherence
within DMN. Those indicate more highly functioned DMN in PD
patients at stage II. [figure1] [figure2]
Conclusions: Our study demonstrated the trajectories of resting-
state cerebral function disturbance in PD patients at different H&Y
stages. Impairment in functional integration of occipital-temporal
cortex might be a promising measurement to evaluate and potentially
track functional substrates of disease evolution of PD.
38
Difference between brain activations for self- and cue-initiated
movements in people with Parkinsons disease
M.K. Mak, V. Cheung, D. Wang, C. Wong, Z.L. Lu, L. Shi, W. Lou,
V. Mok, W.C.W. Chu (Hong Kong, Peoples Republic of China)
Objective: To compare the brain activation patterns during self-
and cue-initiated movements in healthy subjects and people with Par-
kinsons disease (PD).
Movement Disorders, Vol. 30, Suppl. 1, 2015
S18 POSTER SESSION
Background: It has been reported that people with PD had diffi-
culties in performing self-initiated movements and the application of
external cues improved the speed and/or amplitude of the move-
ments. It is hypothesized that, due to dysfunctions of the basal gan-
glia, PD patients use the dorsal visual pathway, including the parietal
cortex, pre-motor cortex and cerebellum, to replace the supplementary
motor area-basal ganglia cortical pathways. Previous studies reported
that PD patients could perform well-learnt sequential finger move-
ments by activating more brain areas than healthy subjects (Wu et al.
2005). However, no study has compared the brain activation patterns
between self- and cue-initiated movements in patients with PD.
Methods: Twelve PD patients and seventeen healthy subjects were
instructed to perform finger tapping with their left index finger in 2
conditions while their brain activity was recorded by fMRI. During the
self-initiated condition, subjects had to tap their index finger at an inter-
val of 3s to 5s. During the cue-initiated condition, subjects had to make
a tap when they saw a 1 on the computer screen. Data were acquired
in self-initiated, cue-initiated, and rest conditions using a block design.
There were 5 self- and 5 cue-initiated blocks and 10 rest blocks.
Results: During self-initiated movements, PD patients activated
the dorsolateral prefrontal cortex, anterior cingulate cortex and the
declive of the cerebellum whilst healthy controls activated the sup-
plementary motor area and the declive of the cerebellum (corrected,
p<0.05). During cue-initiated movements, PD patients activated the
inferior parietal lobe and mid-cingulate cortex and healthy controls
activated the supplementary motor area and the culmen and declive
of the cerebellum (corrected, p<0.05).
Conclusions: PD patients had hypoactivation of the supplemen-
tary motor areas during self-initiated movement. In both self- and
cue-initiated movements, PD subjects activated the cingulate cortex,
suggesting that they used more attention than healthy subjects to per-
form both types of movements. The findings suggest that PD patients
may activate the attention network to compensate for their disrupted
basal ganglia-cortical pathways in generating body movements.
39
18F-FDG PET/CT imaging in the diagnosis of Parkinsons
disease
Z. Mao, S. Ji, Q. Yang, H. Ye, Z. Xue (Wuhan, Peoples Republic of
China)
Objective: To investigate imaging characteristics of 18F-FDG
PET/CT in patients with Parkinsons disease (PD), exploring its value.
Background: 11C-CFT dopamine transporer (DAT) positron
emission tomography (PET) has important value on the diagnosis of
Parkinsons disease, but the imaging agent is expensive and scarce,
18F-FDG is the most common imaging agent,and its role in Parkin-
sons disease is to be developed.
Methods: (1) Using UPDRS-III score, Hoehn-Yahr (HY) score to
evaluate disease duration, severity of 30 PD patients, 10 age- and
sex-matched without central nervous system disorders patients as
controls;
(2) 30 PD patients and 10 controls underwent brain tomography
imaging by intravenous injected 18F-FDG to get the respective ratio
of radioactive count per unit area of caudate nucleus, putamen, thala-
mus, frontal lobe, temporal lobe, parietal lobe, occipital lobe and cer-
ebellum (Rcl/cb). According to H-Y score 30 PD patients were
divided as the early, middle and late stage, compare if there were
difference in ratio of radioactive count between different stages of
the caudate nucleus/cerebellum, putamen/cerebellum, thalamus/cere-
bellum, substantia nigra red nucleus/cerebellum by ANOVA;
According to UPDRS-III score 30 PD patients were divided into
tremor-predominant (TDT), rigidity and bradykinesia predominant
(ART), mixed type (MT), the correlation between UPDRS-III score
and radioactivity ratio of substantia nigra and red nucleus in PD
patients with different clinical symptoms were analyzed.
Results: (1) Metabolic imaging of each brain lobe, caudate
nucleus, putamen, thalamus, cerebellum, cerebral were of symmetri-
Movement Disorders, Vol. 30, Suppl. 1, 2015
cal distribution in control group, while in PD group each lobe of the
brain hemispheres, caudate nucleus, putamen, thalamus were asym-
metry reduction.
(2)The uptake of 18F-FDG PET/CT in nigrostriatal system of PD
patients gradually reduced with increases on the severity of the dis-
ease, a negative correlation (r 5 -0.709, P < 0.05) with UPDRS-
IIIscores; the longer the duration, the lower uptake ratios of caudate
nucleus/cerebellum, putamen/cerebellum, thalamus/cerebellum, the
substantia nigra red nucleus/cerebellum in PD;
(3) The UPDRS-IIIscores in ART, MT, TDT patients had no sig-
nificant correlation with 18F-FDG uptake ratio.
Conclusions: 18F-FDG PET/CT imaging can be used for early
diagnosis and disease stage in PD.
40
F-DOPA PET reveals a rostro-ventral striatal dopaminergic
depletion in Parkinsons disease with impulse control disorders
A. Mari, M.C. Rodriguez Oroz, C. Juri, R. Gonzalez-Redondo, J.
Arbizu, E. Prieto, J.A. Obeso (Pamplona, Spain)
Objective: To ascertain the striatal pattern of dopaminergic
depletion by L-3,4-Dihydroxy-6-[18F] fluorophenylalanine
18
([ F]FDOPA) Positron Emission Tomography (PET) in Parkinsons
disease patients with and without impulse control disorders(ICD).
Background: ICD occur in a significant number of PD partients.
While these abnormal behaviours are associated with dopaminergic
treatments, a differential pattern of nigro-striatal dopaminergic dener-
vation has been suggested by findings in DAT-scan. However, most
studies are confounded by the effect of dopaminergic drugs on the
activity and uptake of the dopamine transporter protien.
Methods: Thirty PD-ICD patients with ICD and 30 PD patients
without a life history for ICD were matched for age and disease
severity and were ascertained with the UPDRS and the Questionnaire
for Impulsive-Compulsive Disorders in PD (QUIP), A voxel-based-
analysis using automated Anatomical Labeling map and a self-made
ventral striatum Volume of Interest were applied to measure 18F-
FDOPA uptake (Ki) in all patients.
Results: All PD patients showed a typical striatal denervation
pattern with predominance reduction in 18F-FDOPA uptake in the
caudal putamen. 18F-FDOPA uptake was significantly reduced in the
anterior and ventral striatum in ICD-PD patients compared to those
without ICD. (p<0,01). Total Levodopa equivalent dose was higher
(p50,006) in ICD-PD patients (mean 957,2) compared to the non-
ICD group (mean 501,27). No significant difference was found in the
mean dose of dopaminegic agonist LEDs.
Conclusions: This study confirms previous findings with DAT-
scan showing a significant reduction in ventral striatal dopaminergic
activity in ICD-PD patients by F-dopa PET which is less influnced
by drug treatments. However, the ICD-PD group received higher
dose of dopaminergic agents. The interaction between denervation
and treatment probably defines in the origin of ICD in PD.
41
Multimodal MRI changes in Parkinsons disease over one year
T.R. Melzer, D.J. Myall, M.R. MacAskill, L. Livinston, T.L. Pitcher,
R. Watts, R.J. Keenan, J.C. Dalrymple-Alford, T.J. Anderson (Christ-
church, New Zealand)
Objective: To investigate brain changes associated with Parkin-
sons disease (PD) over one year with structural, diffusion tensor
imaging (DTI) and perfusion magnetic resonance imaging (MRI).
Background: Previous studies demonstrate that MRI can effec-
tively stage PD in terms of both motor severity and cognitive status.
However, the contribution of MRI parameters to monitor disease pro-
gression over short time periods is uncertain.
Methods: Twenty-three non-demented PD (19 with normal cogni-
tion and 4 with MCI) and 23 age-matched control participants
 POSTER SESSION
completed extensive neuropsychological and disease assessment in
addition to multimodal 3T MRI scanning at baseline and one year
later. Global cognition was expressed as an aggregate z score derived
from the entire neuropsychological battery. SPM was used to prepro-
cess structural (grey matter) and perfusion scans, while FSL and
TBSS were used to assess DTI metrics along major skeletal white
matter tracts. A voxel-based approach assessed change over time and
any group by time interactions for each modality.
Results: Compared to controls, PD participants showed greater
grey matter atrophy over one year in bilateral inferior and right mid-
dle temporal, and left orbito-frontal cortices. There was no significant
perfusion change over time. While PD and control participants
exhibited similar change in DTI metrics and global cognition over
time, grey matter atrophy and change in DTI metrics were associated
with change in global cognition in the PD group over time.
Conclusions: Our results suggest that disease-specific progression
in non-demented PD patients across one year is associated with
regional grey matter changes, but not changes in diffusion or perfu-
sion MRI. Larger studies following patients for longer durations, and
those with patients showing more severe cognitive decline, may
show the utility of multimodal MRI to track progression in PD.
42
Neuroanatomical correlates of cognitive functioning across the
Parkinsons disease cognitive spectrum
D.V. Merkitch, G.T. Stebbins, B. Bernard, J.G. Goldman (Chicago,
IL, USA)
Objective: To investigate relationships of gray matter atrophy on
structural magnetic resonance imaging (MRI) to cognitive domains
in Parkinsons disease (PD).
Background: Cognitive dysfunction is a frequent and debilitating
consequence of PD. Detecting neuroanatomical correlates of different
aspects of cognitive functioning on brain MRI may provide bio-
markers that can predict cognitive decline in PD.
Methods: 101 PD subjects underwent clinical/neuropsychological
evaluations, T1-weighted MRI brain sequences, and cognitive classifi-
cation by The International Parkinson and Movement Disorder Society
criteria (cognitively normal, n529; mild cognitive impairment, n547;
demented, n525). Z-scores for the cognitive domains (attention/work-
ing memory, executive function, memory, language, visuospatial func-
tion) were calculated. Whole-brain voxel-based morphometry analyses
were conducted using SPM8, covarying for age, PD duration, and scan
type. Gray matter volume differences between subject groups were
identified, and significant clusters were assigned to a priori-proposed
neuroanatomically-based cognitive systems: frontostriatal cognitive-
control, medial temporal memory, dorsal spatial-based, ventral object-
based, and cerebellar. Stepwise multiple regressions were performed
adjusting for age and PD duration with the regional gray matter vol-
umes as criterion variables and cognitive domain z-scores as predictor
variables.
Results: Multiple regression analyses demonstrated significant brain-
behavior correlates: executive function domain scores best predicted atrophy
in the frontostriatal cognitive-control (R2=.28, p<0.005) and ventral object-
based systems (R2=.37, p<0.005), memory domain scores best predicted
atrophy in the medial temporal memory system (R2=.38, p<0.005), lan-
guage domain scores best predicted atrophy in the dorsal spatial-based sys-
tem (R2=.06, p50.02), and attention and working memory domain scores
best predicted gray matter atrophy in the cerebellum (R2=.08, p5.01).
Conclusions: These atrophy patterns follow brain-behavior corre-
lates of cognitive dysfunction and thus, may be useful biomarkers
for measuring progression of PD cognitive decline and treatment
effects. Furthermore, they provide insights on neuroanatomical and
neuropathological differences responsible for clinical heterogeneity
with some patients having greater attention/executive dysfunction
and others, greater memory deficits.
S19
43
Neural correlates of the effect of cueing on writing skills in
Parkinsons disease
E. Nackaerts, E. Heremans, R.C. Pineda, B.C.M. Smits-Engelsman,
S.P. Swinnen, W. Vandenberghe, A. Nieuwboer (Leuven, Belgium)
Objective: This study investigated for the first time the neural
correlates of visual cueing on writing performance in Parkinsons
disease (PD).
Background: Patients with PD often experience handwriting dif-
ficulties. As the basal ganglia (BG) are important for internally-
generated movements, it was hypothesized that patients may benefit
from external cueing to enhance motor output via the use of compen-
satory brain networks.
Methods: Seventeen PD patients and 14 healthy controls (CTRL)
performed cued (reference lines) and uncued writing tasks on a
touch-sensitive tablet in the MRI scanner. At the behavioral level a 2
(GROUP) x 2 (CUE) ANOVA was used to compare writing size and
speed. BOLD responses were analyzed using two-sample t-tests to
compare groups while writing either with or without cues and to
compare cued and uncued writing in each group separately (p<.001,
uncorrected).
Results: Behaviorally, no differences were found between groups.
Both groups wrote smaller and slower with cues compared to with-
out. Comparing brain activity during cued and uncued writing,
increased activity in bilateral medial and inferior occipital cortex,
left superior parietal cortex, including precuneus, and left cerebellum
lobule VI in CTRLs was found. Uncued writing by CTRLs led to
increased activity in bilateral orbitofrontal (OFC), ventrolateral pre-
frontal (VLPFC) and anterior cingulate cortex and left postcentral
gyrus. A similar pattern of brain activity was present in PD, with
additionally increased activation of the right hippocampus during
cued writing. When comparing both groups during cued writing,
CTRLs showed increased activation of the left OFC and putamen,
while in PD there was increased activity in left precuneus compared
to CTRLs. During uncued writing, CTRLs presented increased activ-
ity in bilateral VLPFC and right precentral gyrus compared to
patients, whereas patients showed increased activity in left
precuneus.
Conclusions: Contrary to our hypothesis, adding cues imposed
extra task difficulty in both groups. Overall, these results suggest
that the BG and prefrontal cortex showed less activity during cued
writing in PD, consistent with the affected frontostriatal system. Fur-
ther analysis will reveal whether the strikingly increased BOLD
response in the precuneus operates as part of a dorsomedial compen-
satory network, and not a dorsolateral one as suggested in previous
studies.
44
Chronic recordings of subthalamic oscillatory activity using an
implanted pulse generator in patients with Parkinsons disease
W.J. Neumann, F. Staub, J. Schanda, A. Horn, G.H. Schneider, P.
Brown, A.A. K
uhn (Berlin, Germany)
Objective: To investigate the stability of beta oscillatory activity
in the subthalamic nucleus (STN) and its modulation by deep brain
stimulation (DBS) in patients with Parkinsons disease (PD) over
time.
Background: Oscillatory synchronisation recorded from the sub-
thalamic nucleus in the b-band (13-30 Hz) has previously been
shown to be a biomarker for PD symptoms. DBS suppresses this
activity in parallel with alleviation of motor symptoms. However,
most previous studies have only investigated b-band activity directly
after the implantation of DBS electrodes before the implantation of
the impulse generator (IPG). Hence, little is known about the long
term fluctuations of b-band activity and its modulation by DBS.
Methods: Subthalamic recordings from 7 PD patients (age 65.6
years 6 1.8 SEM; disease duration 9.4 6 1.3 years) after withdrawal
Movement Disorders, Vol. 30, Suppl. 1, 2015
S20 POSTER SESSION
of dopaminergic medication were obtained using a new stimulation
device (Medtronic Activa PC1S) that allows for chronic recordings
of local field potentials (LFP). Rest recordings were conducted
directly (baseline) and three months after the IPG implantation (fol-
low-up) with and without DBS, respectively. Bipolar STN LFP
recordings from 10 contact pairs (0-2) were visually inspected for
artefacts and taken into the frequency domain using FFT. Power
spectra were normalized to 7-45 and 55-95 Hz total power after
removal of frequency bands prone to stimulation artefacts. b-band
activity (13-30 Hz) was averaged and subjected to a 2x2 (STIMU-
LATION x TIMEPOINT) repeated measures ANOVA.
Results: All power-spectra showed discrete peaks in the b-band
in the OFF stimulation condition at baseline (mean frequency:
19.7 6 1.5 Hz) and follow-up (mean frequency: 19.8 6 1.6 Hz). Sta-
tistical analysis of averaged b-band activity revealed a significant
main effect for the factor STIMULATION (p 5 0.004). No signifi-
cant results were obtained for the main effect of factor TIMEPOINT
(p50.157) and no significant interaction was found (p50.268). b-
band power was suppressed by 19.2% (post-hoc t-test: p 5 0.001).
Conclusions: Our results suggest that subthalamic b-band activity
in PD is stable over 3 months after IPG implantation and is continu-
ously suppressed by DBS.
45
A new manual ROI improves diagnostic accuracy for cardiac
sympathetic neuronal dysfunction in Parkinsons disease
H. Odagiri, T. Baba, Y. Nishio, O. Iizuka, M. Matsuda, K. Inoue, M.
Iwasaki, Y. Taki, E. Mori (Sendai, Japan)
Objective: The purpose of this study was to determine the diag-
nostic impact of 123I-MIBG cardiac SPECT/CT imaging compared
with conventional scintigraphic evaluation in the diagnosis of PD.
Background: 123I-metaiodobenzylguanidine (123I-MIBG) car-
diac scintigraphy is now widely used to assess cardiac sympathetic
neuronal dysfunction in Parkinsons disease (PD) and dementia with
Lewy bodies(DLB). Manually defined regions of interest (ROIs) on
planar images are conventionally used to assess myocardial uptake
of 123I-MIBG (the heart-to-mediastinum ratio; H/M ratio). However,
arbitrary placing of ROIs on planar image leads to decrease the
accuracy.
Methods: We studied 28 patients with PD and 19 patients with
idiopathic normal pressure hydrocephalus (iNPH), which is a non-
neurodegenerative Parkinsonian disorder as controls. We calculated
the H/M ratio both from planar images and fused SPECT/CT images
obtained with a hybrid SPECT/CT system, then we compared diag-
nostic accuracy of these two methods.
Results: Difference in the H/M ratio between PD group and
iNPH group was significantly higher in the SPECT/CT method(Early
p<0.0001, Delayed p<0.0001) compared with conventional planar
method(Early p50.082, Delayed p50.041). The sensitivity and spec-
ificity between PD group and iNPH group was significantly higher in
the SPECT/CT method (sensitivity 92.9%, specificity 57.9%) com-
pared with conventional planar method (sensitivity 67.9%, specificity
47.4%).
Conclusions: The SPECT/CT method is useful in differentiation
of the neurodegenerative disease.
46
The effect of deep brain stimulation (DBS) on cortico-
subthalamic nucleus coupling in Parkinsons disease (PD)
A. Oswal, A. Jha, S. Neal, A. Reid, P. Limousin, T. Foltynie, L.
Zrinzo, M. Hariz, V. Litvak, P. Brown (London, United Kingdom)
Objective: To evaluate the effect of DBS on functional connec-
tivity within a network comprising the subthalamic nucleus (STN)
and cortical regions in PD.
Movement Disorders, Vol. 30, Suppl. 1, 2015
Fig. 1. (46).
Background: DBS is an effective treatment for PD, yet its
mechanisms of action and influences on cortico-STN networks are
unknown. It has previously been shown that two spectrally and spa-
tially distinct resting STN-cortical networks exist in PD: 1) An STN-
temporo-parietal alpha band (7-12Hz) network and 2) An STN-pre-
motor/motor beta (13-30 Hz) band network. We sought to examine
the effect of DBS on these networks.
Methods: We performed simultaneous magnetoencephalography
(MEG) and bilateral STN local field potential recordings (LFPs) in
15 post-operative PD patients, whose DBS electrodes had been tem-
porarily externalised for recording. Using a purpose built amplifier
we were able to simultaneously stimulate the STN and record its
electrical activity during concurrent MEG recording. Source recon-
struction of cortical signals was performed using beamforming to
allow the computation of coherence between cortical regions and the
STN signal.
Results: Unilateral monopolar DBS at 130 Hz suppressed low
beta power (12-20Hz) locally within the STN and also suppressed
low beta (12-15 Hz) coupling between both STNs. Furthermore, low
beta coupling (13-22 Hz) between the STN and the premotor peak of
resting beta activity was suppressed by 130 Hz DBS, despite cou-
pling in the high beta range (22-35 Hz) remaining unchanged. Figure
1 shows STN power and STN-premotor coherence results averaged
across all subjects and hemispheres [figure1]. We are currently corre-
lating the observed spectral changes with clinical parameters on and
off DBS.
Conclusions: Our results highlight that DBS preferentially sup-
presses low rather than high beta activity in cortico-STN motor cir-
cuits in PD. This finding suggests that low beta may be an important
pathological process in PD, suppressed by both levodopa and DBS.
47
Multimodal MRI markers discriminate Parkinsons disease from
multiple system atrophy patients
P. Peran, M. Sierra, A. Pavy-Le Traon, O. Rascol (Toulouse,
France)
Objective: Using multimodal MRI, the aims of the study were (i)
to compare changes in patients with idiopathic Parkinsons disease
(iPD) compared to multiple system atrophy (MSA) patients with
 POSTER SESSION
Fig. 1. (47).
Parkinsonian syndrome (MSA-P) and with cerebellar syndrome
(MSA-C) (ii) to discriminate iPD patients from MSA patients.
Background: Multimodal MRI approach is based on combination
of MRI parameters sensitive to different tissue characteristics (e.g.
volume atrophy, iron deposition, microstructural damage). Previous
findings revealed that multimodal MRI is able to discriminate iPD
patients from healthy control subjects with high accuracy (Peran
et al., Brain, 2010). The combination of different MR biomarkers could
help to discriminate different pathologies with Parkinsonian syndrome.
Methods: 26 iPD patients with and 29 MSA patients (16 MSA-P,
13 MSA-C) underwent 3-T MRI comprising: T2*-weighted, T1-
weighted and diffusion tensor imaging scans. We used the same
method as in the previous work (Peran et al., Brain, 2010) to extract
MRI markers (volume, R2* value, mean diffusity and fractional ani-
sotropy). Comparisons between groups were performed using statisti-
cal region-based (sub-cortical structures) analysis and whole brain
voxel-based analysis. Logistic regressions and ROC curves were
computed using results from the previous voxel-based analysis.
Results: Concerning region-based analysis, the main results
showed significant changes in brainstem and in putamen in MSA
patients compared to PD patients. The sub-group of MSA-P showed
a loss of microstructural integrity (higher mean diffusity) in putamen
compared to iPD or compared to MSA-C. The sub-group of MSA-C
showed a loss of microstructural integrity (higher mean diffusivity)
in brainstem compared to iPD or compared to MSA-P. Voxel-based
analysis confirmed the previous localizations and identified differen-
ces for all markers in the cerebellum. Predictive analysis showed
that markers for discriminating iPD from MSA-P were mainly the
grey density of putamen, the mean diffusivity in the cerebellum and
the fractional anisotropy in the superior corona radiata. [figure1]Fig-
ure: MSA-P vs iPD (voxel-based). red: " R2* green: " MD blue: #
FA yellow: # grey density.
Conclusions: This study demonstrates that multimodal MRI is
able to discriminate patients with iPD from MSA with a high accu-
racy. The combination of different MR biomarkers could be a great
tool to follow disease progression.
48
Phase-amplitude coupling heterogeneity in the Parkinsonian
sensorimotor cortex
E. Pe~na, L. Rosedahl, T.M. Mohammed, F. Al-Mohammed, L.
Soualmi, M.D. Johnson, J.A. Bajwa (St. Paul, MN, USA)
Objective: To investigate magnetoencephalographic (MEG)
measures of phase amplitude coupling in sensorimotor cortex on and
off medication in Parkinsons disease (PD) patients.
Background: The phase amplitude coupling (PAC) measure
describes the degree to which oscillatory activity in one frequency
band phase-locks to oscillatory activity in a lower frequency band.
Such coupling is thought to be indicative of information transfer
between neuronal populations at different spatiotemporal scales, and
has been shown to play a critical role in cognitive processes such as
learning. In some cases, this type of coupling may be pathological,
and recent intraoperative studies in PD patients have noted strong
coupling between the amplitude of gamma/high-frequency oscillatory
activity and the phase of beta-band oscillations in primary motor cor-
S21
tex, in subthalamic nucleus, and between both structures. Here, we
used MEG recordings in PD patients to investigate (1) the inter-
subject variation in such coupling within sensorimotor cortex off and
on medication, and (2) whether such coupling is also present in
healthy control subjects.
Methods: Resting-state MEG data was acquired on an Elekta
Neuromag from 6 healthy controls and 8 PD patients (ages 55-70,
disease duration of 2-9 years), both on and off medication. PAC
comodulograms were constructed (phase: 12-30Hz, amplitude: 90-
300Hz) based on source-space estimations of oscillatory activity in
three gyri (precentral, postcentral, superior frontal) and two sulci
(central, superior frontal) from both hemispheres. Regression analysis
between the PAC comodulogram results and the clinical evaluation
scores using the modified Unified Parkinsons disease Rating Scale
(UPDRS) were performed.
Results: Significant PAC was found in 2/8 PD patients in the off
medication state, and in both cases, Levodopa-Carbidopa reduced the
PAC values in conjunction with improvement in Parkinsonian motor
signs. Another patient had significant PAC values only after the
administration of Levodopa-Carbidopa, but the patient also had wors-
ened tremor after medication. No significant PAC was found in any of
the control subjects. Across the cohort, inter-subject regression analy-
sis showed no correlation between PAC and motor signs (R2 < 0.2).
Conclusions: Significant PAC, while present in some PD patients,
was not found to be consistent in the sensorimotor cortex for all PD
patients in this study.
49
Aberrant cerebral network topology and mild cognitive
impairment in early Parkinsons disease
J.B. Pereira, D. Aarsland, C. Ginestet, A. Lebedev, L.O. Wahlund, A.
Simmons, G. Volpe, E. Westman (Stockholm, Sweden)
Objective: The aim of the current study was to assess whether
mild cognitive impairment (MCI) is associated with disruption in
large-scale structural networks in newly diagnosed, drug-nave
patients with Parkinsons disease (PD).
Background: Mild cognitive impairment has a strong impact on
quality of life and frequently progresses to dementia in patients with Par-
kinsons disease. Although the study of network disruption could provide
an important insight into the cortical and subcortical patterns underlying
cognitive decline in Parkinsons disease, the organization of the brains
structural architecture has not been assessed in these patients to date.
Methods: Graph theoretical analyses were applied to 3T MRI data
from 123 PD patients and 56 controls from the Parkinsons Progression
Markers Initiative (PPMI). Thirty-three patients were classified as hav-
ing MCI using the International Parkinson and Movement Disorders
Society Task Force criteria, while the remaining ninety patients were
classified as cognitively normal. Global measures (clustering coeffi-
cient, characteristic path length, global efficiency, small-worldness) and
regional measures (local clustering coefficient, local efficiency, hubs)
were assessed in the structural networks that were constructed based on
cortical thickness and subcortical volume data in each group.
Results: Patients with MCI showed a marked reduction in the
average correlation strength between cortical and subcortical regions
compared to controls. These patients had larger characteristic path
length and reduced global efficiency in addition to a lower local effi-
ciency in frontal and parietal regions compared to cognitively normal
patients and controls. A reorganization of the highly connected
regions in the network was observed in patients with and without
cognitive deficits.
Conclusions: This study shows the earliest stages of cognitive
decline in PD are associated with a disruption of the large-scale
coordination of the brain network and with a decrease of the effi-
ciency of parallel information processing. These changes are likely
to herald further cognitive decline and provide support to the view
of PD as a disconnection syndrome capable of spreading along the
connections of the cerebral network.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S22 POSTER SESSION
50
Progressive cerebellar atrophy in patients with tremor-
predominant Parkinsons disease
C.C. Piccinin, L.G. Piovesana, R.P. Guimaraes, M.C.A. Santos, B.M.
Campos, T.J.R. Rezende, L.S. Campos, P.C. Azevedo, F. Torres,
M.C. Franca, A.C. Amato-Filho, I. Lopes-Cendes, F. Cendes, A.
DAbreu (Campinas, Brazil)
Objective: Our aim was to identify whether the cerebellar grey
matter (GM) atrophy presented in tremor-predominant Parkinsons
disease (PD) patients is associated to disease severity using a specific
cerebellar tool for voxel-based morphometry (VBM) analysis.
Background: Recent neuroimaging studies comparing tremor-
predominant-PD versus bradykinesia-predominant-PD demonstrated
decreased GM in the cerebellum of tremor-predominant-PD patients
only, underlying a potential cerebellar role in the physiopathology of
PDs tremor.
Methods: We divided our tremor-predominant-PD patients group
into three groups in according to the progression of symptoms and
level of disability (trough Hoehn and Yahr rating scale H&Y) and
compared each group with an age-gender-matched healthy control
(HC) group. Group 1 included 9 early PD patients (mean age
61.89 6 10.6) with H&Y scores between 1 and 1.5 and 9 HC (mean
age 61.33 6 9.85); group 2 was comprised of 21 patients
(58.52 6 12.46) with H&Y scores between 2 and 2.5 - and 21 HC
(58.81 6 12.24); and group 3 presented 15 patients (58.87 6 9.16)
with H&Y score  3 and 15 HC (58.80 6 9.18). We acquired T1
weighted scans at a 3T scanner and compared the paired groups
using VBM in SPM8. We used the SUIT tool (Spatial Unbiased
Infratentorial Template) for a specific and detailed evaluation of the
cerebellar GM. Statistics were done applying p5.001, uncorrected
and extent-threshold  20 voxels.
Results: We detected no changes in the cerebellar GM in patients
classified as early and moderate tremor-predominant-PD. The severe
group however, demonstrated large GM decreased in the right ante-
rior lobe, in the left crus I and bilaterally in the lobules V, VI
(including the vermis) and VIIIa.
Decreased GM areas in the cerebellum demonstrated in the
severe group of patients (H&Y score  3)
AREA LOBULE CLUSTER SIZE*
Right Hemisphere I - IV 61
Left Hemisphere V 98
Right Hemisphere V 536
Left Hemisphere VI 294
Vermis VI 57
Right Hemisphere VI 193
Left Hemisphere Crus I 316
Left Hemisphere VIIIa 51
Right Hemisphere VIIIa 82
*in voxels
Conclusions: We concluded that the decreased cerebellar GM
observed in tremor-predominant-PD patients using a special tool for
cerebellar analysis parallels the progression of the clinical symptom-
atology and it is possibly only detectable in patients with bilateral
disease and some level of postural instability (H&Y3).
51
Impact of the disease and medication on resting state functional
connectivity in Parkinsons disease
I. Rektorova, N. Elfmarkova, M. Gajdos, M. Mrackova (Brno, Czech
Republic)
Movement Disorders, Vol. 30, Suppl. 1, 2015
Objective: We acquired rs-fMRI data in PD patients in the ON
and OFF medication conditions and age-matched HC and used the
seed Partial Least Squares Correlation (PLSC) analysis to assess
impact of the disease and medication on connectivity strength from
our seeds of interest.
Background: Resting state functional connectivity within the
large-scale brain networks between healthy subjects (HC) and PD
patients in the ON (PD_ON) and OFF (PD_OFF) medication condi-
tions has not been systematically studied.
Methods: We inluded 19 non-demented and non-depressed males
with PD (age 64.6 6 7.5 years, disease duration 29 6 6 months,
levodopa-equivalent dose 1092.7 6 353.8 mg) and 15 matched HC
males (age 62.9 6 8.2 years). PD subjects were scanned before and
after administration of their first morning dose of DA medication.
fMRI data were preprocessed using SPM8. Based on literature and
our previous work we chose 2 coordinates for motor seeds (left pri-
mary motor cortex for hand [L hand SM1] and right primary orofa-
cial cortex [R orofacial SM1], and 6 coordinates for non-motor seeds
(precuneus, anterior cingulate cortex [ACC], right middle temporal
gyrus/middle occipital gyrus [MTG/MOG], right insula [RI], right
inferior frontal gyrus [IFG], R caudate). We extracted the BOLD sig-
nal as the first eigenvariate from a sphere with radius of 6 mm.
These seed signals were used to compute seed correlation matrices.
Results: The PLSC analysis revealed significant impact of the
disease (but not medication) on the connectivity strength of spatial
correlation maps seeded by R caudate (p 5 0.047), ACC (p 5 0.006),
MTG/MOG (p 5 0.045), and R orofacial SM1 (p 5 0.025). The RI
and L hand SM1 almost reached statistical significance (p 5 0.058
and 0.076, respectively). In PD patients the connectivity within all
studied networks decreased in most of the brain regions as compared
to HC. In motor networks the connectivity differences were most
prominent between PD_OFF and HC while in all studied non-motor
networks the major connectivity differences were found between
PD_ON and HC.
Conclusions: We observed impact of the disease (PD vs. HC sta-
tus) while the impact of medication (PD_ON vs. PD_OF states) did
not reach statistical significance. Connectivity in PD was decreased
as compared with HC and was detected in a number of large-scale
brain networks including the motor, insular, ventral visual, and the
default mode networks.
52
The neural correlates underlying dual tasking in Parkinsons
disease
K. Rosenberg-Katz, I. Maidan, Y. Jacob, S. Shema, N. Giladi, T.
Hendler, H.M. Jeffrey, A. Mirelman (Tel Aviv, Israel)
Objective: The aim of this study was to use functional MRI
(fMRI) to study the neural mechanisms underlying dual tasking (DT)
in PD.
Background: The ability to divide attention plays an important
role in DT and in the so called DT decrement. In the context of
gait, this decrement has major negative consequences as it impacts
safe ambulation, increases fall risk, and restricts functional independ-
ence. The DT decrement is generally exaggerated with ageing and in
Parkinsons disease (PD), however, the understandings of its underly-
ing brain mechanisms are still lacking.
Methods: Twenty-two patients with PD (mean age: 72.69 6 4.17
yrs) and 14 healthy controls (mean age: 71.18 6 5.97 yrs) were stud-
ied using an fMRI paradigm that included three conditions that were
presented in a block design: 1) alternating feet movements against
foot pedals (single task), 2) subtracting 3s from a predefined number
(single task), and 3) performing both tasks simultaneously (DT). DT
related brain activations were examined by comparing the DT condi-
tion with both of the single tasks conditions. DT related brain activa-
tions were further correlated with measures related to attention and
task switching, the Trail Making Test (TMT), and with DT gait
speed decrement (i.e., usual walking gait speed minus DT speed).
 POSTER SESSION
Results: Both groups showed significant increase in DT related
activations in the middle frontal gyrus, precentral gyrus, inferior
frontal gyrus (Brocas areas), thalamus, and superior parietal lobe
(SPL) (p FWEcorr <0.05). Compared to the healthy elderly, patients
with PD had significantly lower DT related activations in the occipi-
tal cuneus and lingual gyrus (p FWEcorr <0.05), SPL, middle frontal
gyrus, medial frontal gyrus/anterior cingulate and right caudate
nucleus (p<0.0005, uncorrected). The SPL fMRI beta values of DT
related activations were negatively correlated with the time to com-
plete the TMT part b (r=-0.412, p<0.01, corrected for age) but not
with TMT part a duration (r=-0.247, p50.159, corrected for age). In
addition, higher SPL beta values were correlated with lower DT gait
speed decrement (r= -0.345, p<0.05).
Conclusions: These findings suggest that part of the difficulties
that patients with PD have during DT are related to a decreased abil-
ity to recruit brain regions including occipital, parietal, frontal and
motor regions. Our results support the involvement of the SPL as a
principal factor in DT.
53
Evaluation of striatal PDE10 expression in Parkinsons disease
(PD) using [18F]MNI-659 PET imaging
D.S. Russell, D.L. Jennings, O. Barret, G.D. Tamagnan, D. Alagille,
J.P. Seibyl, K.L. Marek (New Haven, CT, USA)
Objective: To evaluate the feasibility of [18F]MNI-659 PET, a
striatal PDE10A imaging tracer, as a biomarker in early PD and PD
with motor fluctuations.
Background: PDE10 is highly and specifically expressed in brain
in striatal neurons, primarily medium spiny neurons. This enzyme
plays a critical role in striatal dopaminergic function via regulation
of cyclic nucleotides. [18F]MNI-659 PET is a well-validated, highly
specific PET radioligand targeting PDE10A.
Methods: Eight PD subjects participated, de novo (n52) and
treated with dopaminergics (n56). All subjects were imaged with
[18F]MNI-659 for 90 minutes. Standard uptake values were deter-
mined for the basal ganglia and component subnuclei. Binding
potentials (BPnd) were estimated using SRTM (cerebellum as refer-
ence). MRI imaging was also acquired on all subjects and co-aligned
with the PET images for anatomical localization.
Results: Participants (7M, 1F) had a mean age of 65.7 y (range
61.6-69.0 y) and mean duration of diagnosis of 8.0 (range 1.5-12.7).
Treated subjects all manifest dyskinesia and on-off phenomena.
Mean total UPDRS score was 42.3 (range 7-80) and motor subscale
25.9 (range 5-52). The mean striatal BPnd among the PD subjects
was 2.29 (S.D. 0.30) compared to mean 2.45 (S.D. 0.21, P=0.34)
among older HS (n55, >40 yrs). No correlation was noted between
striatal BPnd and diagnosis duration (R2 5 0.04), total UPDRS score
(R2 5 0.02), or motor subscale score (R2 5 0.02). Mean striatal BPnd
for untreated did not differ from treated (2.27, S.D. 0.034 vs. 2.30,
S.D. 0.32, P=0.91). Comparison between more affected putamen
(2.93; S.D. 0.36) and less affected putamen (2.98; S.D. 0.45) did not
detect a difference (P=0.66).
Conclusions: In this limited cohort of de novo and treated PD
subjects, there is good brain penetration and binding of [18F]MNI-
659 in the striatal regions. While this study is limited by its small
sample size, no significant difference in [18F]MNI-659 binding was
detected when compared to a similarly aged HS.
54
Decreased gray matter volume in the brainstem: A potential
biomarker of Parkinsons disease?
C.D. Schroeder, G.T. Stebbins, J.G. Goldman (Chicago, IL, USA)
Objective: To investigate regional brainstem atrophy on struc-
tural magnetic resonance imaging (MRI) in Parkinsons disease
(PD).
S23
Background: The neuropathology of PD is hypothesized to have
early changes in the brainstem, particularly the medulla oblongata,
followed by changes in the midbrain and eventually the neocortex.
Structural MRI provides an opportunity to examine differences in
brainstem volumes between PD patients and healthy controls. Brain-
stem atrophy detected on MRI scans could potentially be used as a
biomarker of PD progression.
Methods: Twenty-nine clinically diagnosed, cognitively normal
PD patients and 24 age-matched, healthy controls underwent clinical
evaluations and MRI brain scans (1.5T GE Signa, T1-weighted
sequences [MPRAGE, IR-FSPGR]). Whole brain voxel-based mor-
phometry analyses were conducted using SPM8. Images were
smoothed with a 6mm kernel. Regions of interest for midbrain, pons,
and medulla gray matter volumes were extracted from modulated
non-linear scans using the Wake Forest University Pickatlas. Gray
matter differences between the PD and control groups were exam-
ined using a MANCOVA, covarying for scan sequence and gender
with significance set at p<0.05. Logistic regression and receiver
operating curve (ROC) analyses were used to measure the specificity
and sensitivity of brainstem volume for group discrimination.
Results: The PD and healthy control subjects did not differ sig-
nificantly in age (mean [SD] PD 70.66 [4.65] years, Controls 71.75
[6.07] years). The PD group had a mean PD duration of 8.38 [2.99]
years. The PD group exhibited significant voxel-wise differences
with decreased gray matter volume in the gray matter of the mid-
brain (mean [SD] PD 0.16 [0.03] Controls 0.22 [0.04], p<0.0005).
There were no significant differences found in the other brainstem
regions. Logistic regression with midbrain volume significantly pre-
dicted PD/control classification (v2=34.29, p<0.0005). ROC analyses
revealed an area under the curve of 0.84, and a midbrain relative
volume threshold of 0.188 optimally differentiated PD from controls
with a sensitivity of 79% and specificity of 83%.
Conclusions: Patterns of brainstem atrophy on MRI, particularly
in the midbrain, can distinguish cognitively normal PD patients from
healthy controls. This finding may reflect underlying PD-related neu-
rodegeneration and thereby, has potential as a biomarker for diagnos-
ing PD and monitoring disease progression.
55
Early diagnosis of multiple system atrophy in patients with
Parkinsons disease and orthostatic hypotension by 123I-IBZM
SPECT
D.E. Shan, S.J. Wang, K.K. Liao, H.H. Hu (Taipei, Taiwan)
Objective: To evaluate the probability of 123I-IBZM, a ligand
for D2-receptor binding, SPECT in make the differential diagnosis
between patients with multiple system atrophy (MSA) and patients
with Parkinsons disease with orthostatic hypotension (PD1OH).
Background: Some patients with Parkinsons disease have auto-
nomic dysfunction, including orthostatic hypotension. Differential
diagnosis between these PD1OH patients and those with MSA is a
difficult but important issue.
Methods: Twelve PD1OH patients were recruited into an 123I-
IBZM SPECT study and compared with the data from 9 patients
with MSA, 6 patients with idiopathic PD (IPD), and 3 normal con-
trols. To make the diagnosis of MSA, the lowest data from normal
controls were used as the cut-off values, i.e. the striatum/occipital
(S/O) ratio was set at 1.03 and the putamen/occipital (P/O) ratio was
set at 0.95. It was assumed that any patients with an S/O or P/O ratio
below these cut-off values were likely to be cases with MSA. The
data from two patients with PD1OH were excluded from analysis
because they had taken pramipexole or antipsychotic within 5 days
before SPECT examination.
Results: According to the S/O ratio from the worst side of lesion,
one patient with IPD (16.7%), three patients with MSA (33.3%) and
four patients with PD1OH (40%) were below the cut-off value.
According to the P/O ratio from the worst side of lesion, none with
IPD (0%), six patients with MSA (66.7%) and two patients with
Movement Disorders, Vol. 30, Suppl. 1, 2015
S24 POSTER SESSION
PD1OH (20%) were below the cut-off value. Although the initial
autonomic dysfunction in one of the two PD1OH patients below the
cut-off value of the P/O ratio was not severe enough to meet the
diagnostic criteria of MSA, her follow-up studies showed poorly
levodopa-responsiveness, progressive worsening of orthostatic hypo-
tension and the development of hot cross-bun sign on MR imaging,
which made her diagnosis to be revised to MSA.
Conclusions: The P/O ratio of 123I-IBZM SPECT is more sensi-
tive and more specific than the S/O ratio in making the diagnosis of
MSA. The diagnosis of PD1OH should be made cautiously, particu-
larly in those patients with a short duration of illness. Our study
reveals that one-tenth of them may be an early manifestation of
MSA. 123I-IBZM SPECT may help in making the correct diagnosis
early in the course. This work was supported by grants (#NSC- 98-
2314- B- 075- 034) from the National Science Council, ROC, grants
(#INIBA071213) from the Institute of Nuclear Energy Research,
ROC, and grants (#140-V-B-030) from the Taipei Veterans General
Hospital - National Yang-Ming University Excellent Physician Sci-
entists Cultivation Program.
56
Fiber tract atrophy in idiopathic Parkinsons disease
F.M. Skidmore, T. Anthony, J. Marstrander, Y. Liu, G. Cutter, D.
Standaert (Birmingham, AL, USA)
Objective: To evaluate changes in fiber tract caliber and frac-
tional anisotropy in Parkinsons disease, using diffusion tensor imag-
ing (DTI).
Background: During image registration, fiber tracts are morphed
and matched across subjects. This is a necessary process to localize
structures in, but information may be lost. We analyzed changes in
fiber tract caliber (radial to the primary fiber direction) in idiopathic
Parkinsons disease compared to healthy controls, by evaluating mor-
phological changes during image registration to a common template.
DTI data was collected from the Parkinsons Progressive Markers
Initiative (PPMI) dataset.
Methods: DTI images from the PPMI dataset were downloaded
and processed using the NIH Tortoise suite. A visual quality control
Fig. 1. (57).
Movement Disorders, Vol. 30, Suppl. 1, 2015
step was performed, and acceptable images (68 controls, 105 PD)
were analyzed using the analysis of functional neuro-imaging (afni)
imaging suite. The afni package 3dQwarp is being iteratively
recoded to to allow more fine grain registration of images, and we
analyze the transformation matrix for evidence of difference in fiber
caliber between groups. Fractional anisotropy in the registered
images was also analyzed.
Results: At the time of this abstract, adequate registration is
available in 37 controls and 77 subjects with PD. Among these sub-
jects, fiber tract caliber differs in PD subjects compared to controls
in the fornix, basal forebrain (including the anterior commissure),
and adjacent to deep cerebellar nuclei. Fractional anisotropy differed
in the midbrain, including in the peri-nigral regions, as well as in the
pons and medulla.
Conclusions: Our data suggest that individuals with PD have
measurable morphological changes in caliber of white matter struc-
tures. Nonlinear image registration protocols, which accurately regis-
ter structures, can obscure important disease related information in
disorders where atrophy of white matter structures is occurring.
However, this information can be retrieved by developing measures
to analyze individual subject transformation matrices. In PD, we find
that in addition to previously described FA changes in peri-nigral
regions, individuals with PD show changes in fiber tract caliber in
multiple structures, including limbic structures.
57
Increased dopamine turnover: A possible contributor to the
increased risk of Parkinsons disease in LRRK2 mutation
carriers
V. Sossi, R. Nandhagopal, D. Wile, M. Schulzer, J. McKenzie, K.
Dinelle, M. Farrer, Z.K. Wszolek, J. Aasly, A.J. Stoessl (Vancouver,
BC, Canada)
Objective: To investigate the role of the impaired dopamine
(DA) storage capacity or its inverse, DA turnover in the asymptom-
atic stage of subjects with LRRK2 mutations, which increase the risk
of Parkinsons disease (PD).
 POSTER SESSION
Background: An increase in dopamine turnover has been previ-
ously demonstrated in asymptomatic LRRK2 mutation carriers [1].
Whether such increase would represent an initial compensatory reac-
tion to incipient disease or be pathogenic by itself is still a matter of
speculation.
Methods: 17 asymptomatic subjects with LRRK2 mutations
(Y1699C, R1441C, G2019S, N1437H, G2019S and I2020T, age
49 6 12 yrs) and 4 mutation negative subjects (age 61 6 8) yrs
underwent a positron emission tomography (PET) scan with the
dopamine transporter (DAT) marker 11C-methylphenidate (MP),
quantified with the tissue input binding potential BPND and a pro-
longed 18F-fluorodopa (FD) scan to evaluate the effective dopamine
distribution volume (EDV), the inverse of DA turnover. The decrease
in EDV and DAT binding relative to age matched normal controls
were compared.
Results: Unlike previous studies performed in early PD subjects,
which showed a very strong positive correlation between DAT bind-
ing and EDV[2], no correlation was found for the mutation carriers.
EDV was significantly (p< 0.001) more decreased compared to DAT
binding (40% vs 19%). The mutation negative subjects had normal
values for both tracers (figure 1).
Conclusions: Given the established correlation between DAT
density and dopaminergic terminal deficit, these data support the
hypotheses that impaired DA storage, which could lead to excess
levels of DA in the cytosol, might be an independent mechanism
leading to an increased risk of PD, consistent with recent findings in
animal models [3]. Further work is required to establish if very
recently observed alterations of the serotonergic innervation may
influence the measurement of dopamine turnover.
References:
1. Sossi, V. et al., Mov Disord, 2010. 25(16): p. 2717-23.
2. Sossi, V. et al., Ann Neurol, 2007. 62(5): p. 468-74.
3. Shen, J. et al., Neurodegenerative Diseases, 2010. 7(1-3): p.
80-83.
58
Motor and nonmotor symptoms in drug-naive de novo
Parkinsonian patients and their relationship to dopaminergic and
serotonergic lesions
S. Thobois, A. Maillet, E. M et
ereau, H. Klinger, E. Lhomm ee, E.
Schmidt, A. Bichon, P. Pelissier, C. Caire, V. Fraix, D. Le Bars, E.
Broussolle, P. Krack (Bron, France)
Objective: To investigate the respective involvement of DA and
5-HT neurotransmission dysfunction in the pathophysiology of both
motor and nonmotor features in drug-naive de novo PD patients,
using Positron Emission Tomography (PET) imaging.
Background: Beyond the well-known dopaminergic (DA) deple-
tion, several lines of evidence indicate that serotonergic (5-HT) neu-
rons also degenerate in Parkinsons disease (PD). Previous works
have suggested a link between the alteration of the 5-HT system and
the occurrence of motor (tremor, dyskinesia) and nonmotor (depres-
sion, fatigue) signs in moderate-to-advanced PD. Nevertheless, little
is known regarding the role of 5-HT dysfunction in the expression of
both motor and nonmotor symptoms at early stages of PD, without
the confounding effect of antiParkinsonian treatment.
Methods: Twenty-nine untreated and recently diagnosed (< 2
years disease duration) PD patients, and fifteen age-matched healthy
controls, were enrolled. Fourteen de novo PD patients presented apa-
thy (LARS score  -21) with/without depression or anxiety. All sub-
jects underwent two PET-scans using DAT and SERT transporters
ligands ([11C]-PE2I and [11C]-DASB, respectively). We used
regions-of-interest (focused on caudate, putamen, ventral striatum)
approach to explore the causal role of these two systems in PD
symptomatology.
Results: Compared to controls, non-apathetic patients exhibited
reduced bilateral DAT binding in anterior and posterior parts of puta-
men, globus pallidus and substantia nigra, but no alteration of SERT
S25
binding. Apathetic patients had reduced bilateral DAT and SERT
binding in anterior caudate nuclei, anterior putamen, ventral striatum,
substantia nigra, as well as a specific decreased DAT binding in pos-
terior caudate nuclei, posterior putamen and globus pallidus. The
comparison between apathetic and non-apathetic patients revealed a
greater 5-HT and DA denervation in caudate nuclei. Our data also
suggest a link between the severity of rigidity and the 5-HT denerva-
tion in putamen and anterior caudate nuclei in all patients. The
severity of apathy and depression seem to be mainly associated with
DA and 5-HT disruption in ventral striatum.
Conclusions: Altogether, these preliminary findings highlight
both DA and 5-HT dysfunction in de novo drug-naive PD patients
suffering from neuropsychiatric signs with a specific contribution of
the caudate nucleus.
59
Transcranial sonography in LRRK2 G2019S mutation carriers

D. Vilas, L. Ispierto, R. Alvarez, C. Pont-Sunyer, M.J. Mart, F. Vall-
deoriola, Y. Compta, O. De F abregues, J. Hern andez-Vara, V.
Puente, M. Calopa, S. Jaum a, J. Campdelacreu, M. Aguilar, P.
Qulez, P. Casquero, F. Lome~ na, E. Tolosa (Barcelona, Spain)
Objective: To assess the echogenicity of the substantia nigra
(SN) in LRRK2 G2019S mutation carriers.
Background: Hyperechogenicity of the SN has been proposed as
a risk marker of Parkinsons disease (PD). Asymptomatic LRRK2
mutation carriers (aLRRK21) are subjects at high risk for develop-
ing PD.
Methods: Transcranial sonography was performed in twenty-six
LRRK2 G2019S PD patients and 50 of their first-degree relatives.
Twenty-four of them were aLRRK21. Thirty-one idiopathic PD
(IPD) patients and 26 unrelated control subjects age and sex matched
with the aLRRK21 were also studied. Echographic measures were
made by an independent investigator blinded to the clinical and
genetic status of subjects, who had not been involved in the TCS
examinations.
Results: 75% of the LRRK2-PD patients and 95.5% of the IPD
patients showed SN1 (p50.087). The age of the aLRRK21, first-
degree relatives non mutation carriers and controls was similar (45
[38; 50], 45 [38; 51 and 45 [40; 60], respectively]. aLRRK21 sub-
jects had a higher frequency of SN1 than first-degree relatives non
carriers (58.3% vs 25%, p5 0.039) and controls (58.3% vs 12.5%;
p5 0.002). aLRRK21 had a larger area of SN echogenicity than the
first-degree relatives non mutation carriers (0.22 cm2 [0.16; 0.25] vs
0.16 cm2 [0.1; 0.2]; p5 0.030) and controls (0.11 cm2 [0.09; 0.15];
p< 0.001).
Conclusions: Hyperechogenicity of the SN is present in most
LRRK2-PD patients and in approximately sixty percent of the
asymptomatic LRRK2 G2019S mutation carriers. Properly designed
prospective studies should clarify whether hyperechogenicity of the
SN is a risk marker for development of Parkinsonism in asymptom-
atic LRRK2 mutation carriers.
60
Cerebral blood oxygenation changes in the frontal lobe caused
by deep brain stimulation in Parkinsons disease: A functional
near infrared spectroscopy study
K. Vyas, E. Sanchez, D. Smith, F. Vale, T. Malapira, T. Zesiewicz,
R. Murtagh, G.A. de Erausquin (Tampa, FL, USA)
Objective: We study the patterns of cerebral blood oxygenation
changes in the frontal lobe caused by electrical stimulation of subtha-
lamic nucleus (STN) in patients with Parkinsons disease (PD) using
a new imaging method called functional near infrared spectroscopy
(fNIRS).
Background: Deep Brain Stimulation (DBS) surgery for idio-
pathic PD is a well established treatment. Studies with PET scan
Movement Disorders, Vol. 30, Suppl. 1, 2015
S26 POSTER SESSION
have shown that electrical stimulation of STN causes changes in cer-
ebral blood flow in various cortical areas. NIRS opticallly measures
oxyhemoglobin and deoxyhemoglobin concentration changes in cere-
bral vessels by means of characteristic absorption spectra of hemo-
globin in near infrared range. Previously, NIRS activation studies
have shown that neuronal activation causes increases in oxyhemoglo-
bin, decrease in deoxyhemoglobin at the activated cortical area. We
attempt to understand the hemodynamic changes in the frontal cortex
during STN-DBS using fNIRS.
Methods: Seven patients with Parkinsons disease were evaluated
with electrodes implanted in the subthalamic nucleus. We measured
changes in oxyhemoglobin and deoxyhemoglobin in the bilateral fron-
tal and prefrontal lobes during 2 stimulation conditions, stimulation-
on and stimulation-off. We recorded time locked near infrared optical
signals using 24 photoiodide channels arranged bilaterally over frontal
and prefrontal lobes for optical detection (NIRx Medical Technolo-
gies, Los Angeles) with a sensitivity of <1 pW NEP and a dynamic
range of 90 dBopt, using 760nm and 850 nm wavelengths.
Results: High frequency electrical stimulation of STN consis-
tently increased deoxyhemoglobin with decreases in oxyhemoglobin
in the frontal lobe in a time dependent manner when the patients
were in the optimal electrode setting. There was an immediate
increase in deoxyhemoglobin with the onset of stimulation. By con-
trast, when the stimulation was turned off, there was an increase in
oxyhemoglobin.
Conclusions: Our study showed various frontal lobe hemody-
namic changes associated with electrical stimulation of subthalamic
nucleus. This might be due complex neuronal connections between
the frontal lobe and basal ganglia. Thus fNIRS offers a new way to
investigate superficial brain activation and neural connectivity.
61
Striatal and cortical elevations in serotonin transporter binding
precede motor onset in asymptomatic patients with LRRK2 gene
mutations
D.J. Wile, K. Dinelle, J. McKenzie, N. Heffernan, M. Adam, Q.
Miao, C. Zabetian, Z. Wszolek, J. Aasly, M. Farrer, V. Sossi, A.J.
Stoessl (Vancouver, BC, Canada)
Objective: To compare serotonin (5HT) function using PET
imaging in asymptomatic and symptomatic patients with dominantly
inherited pathogenic gene mutations for Parkinsons disease (PD)
and apparently sporadic PD.
Background: The earliest (premotor) neurochemical changes in
subjects who will develop PD are incompletely understood but may
involve nondopaminergic systems including the 5HT system. 5HT neu-
rons share monoamine biosynthetic components with dopamine (DA)
neurons and are known to contribute to DA processing in the dener-
Fig. 1. (62).
Movement Disorders, Vol. 30, Suppl. 1, 2015
vated PD striatum (Politis et al. 2014); binding of the 5HT transporter
(5HTT) reduces after onset (Politis et al. 2010). Patients at high genetic
risk for PD including those with leucine-rich repeat kinase 2 (LRRK2)
mutations provide a unique opportunity to compare the presymptomatic
and symptomatic state of 5HT function in vivo. We hypothesized that
in LRRK2 mutation carriers, changes in 5HTT would precede both
phenoconversion to PD and striatal DA denervation.
Methods: 10 subjects with LRRK2 mutations (5 asymptomatic, 5
with manifest PD) and 7 with sporadic PD were compared to 7
healthy controls. 5HTT binding was assessed using PET with [11C]
(N,N-dimethyl-2-(2-amino-4-cyanophenylthio) benzylamine (DASB),
and DA innervation in striatum with (1)[11C]dihydrotetrabenazine
(DTBZ). DASB binding potentials were calculated for regions of
interest in cortex, striatum, diencephalon and brainstem. Regional
binding was compared between presymptomatic mutation carriers,
symptomatic carriers and sporadic PD using ANOVA.
Results: Unaffected mutation carriers had widespread increases
in DASB binding, significant in anterior cingulate cortex (ACC)
compared to affected carriers (p50.02) and sporadic PD (p50.04),
in amygdala (p50.003, p50.008), and putamen (p50.05, p50.003).
No significant group differences were seen in other cortical, striatal,
diencephalic or brainstem sites or between the two affected groups.
All affected patients showed reduced striatal DTBZ binding. DASB
binding correlated significantly with DTBZ binding in the more
denervated putamen (R2 5 0.28, p50.03).
Conclusions: Compared with patients with LRRK2 PD and spo-
radic PD, unaffected LRRK2 mutation carriers have elevated 5HTT
binding in the putamen, amygdala and ACC. 5HT neurons may pro-
vide an alternate means of DA biosynthesis as an early compensatory
mechanism before the motor onset of PD.
62
Co-ordinate based meta-analysis of motor activation deficits in
people with Parkinsons and its relation to medication and
attentive demand
Y. Xing, M. Wongwandee, C.R. Tench, N. Bajaj, D.P. Auer
(Nottingham, United Kingdom)
Objective: To investigate (1)changes in motor brain activation pat-
tern(BAP) in people with Parkinsons disease(PwP) relative to elderly
healthy controls(HC); (2)the influence of attention and dopaminergic
medication on BAP using co-ordinate based meta-analysis(CBMA).
Background: Dopaminergic deficiency in the nigrostriatal path-
way is established as the major driver of motor dysfunction in PwP.
Previous motor task(MT) studies have identified some consistent
areas related to this defect. However, they also yielded numerous
divergent results, which might be associated with study-wise
differences.
 POSTER SESSION
Fig. 2. (62).
Methods: We undertook a systematic review searching all year
Medline, ScienceDirect and Neurosynth databases for functional neu-
roimaging studies involving PwP and age-matched HC. The search
identified 25 articles(110 MT experiments) suitable for aggregation
and CBMA[Tench, CR et al., 2013&2014, PLOS one]. The experi-
ments were grouped based on subject feature(HC/PwP), medication
status(on/off), and attentional factors(self/external instructions and
freely select/conducting fixed movement).
Results: We identified differences between the common BAP
during right upper extremity MT in elderly HC(1st row in Fig1)
compared with PwP, which was most prominent for PwPoff(2nd row
in Fig1). PwPoff showed significantly hypoactivation than HC in the
precentral gyrus, postcentral gyrus, putamen, medial frontal gyrus,
inferior parietal lobule and thalamus(Fig2). We also confirmed a
medication effect as PwPon showed higher BAP in putamen, frontal
gyrus and thalamus versus PwPoff, more consistent with a elderly
HCs BAP. Furthermore, we found a significant effect of attention in
PwP but not HC: significantly hyperactivation in medial frontal gyrus
and amygdala when attention was demanded for MT.
[figure1]
Motor-related BAP in HC(1st row) and PwPoff(2nd row).
CBMA results for HC>PwPoff.
[figure2]
Conclusions: CBMA demonstrated a consistent BAP of known
motor networks in HC, and the expected cortico-striato-thalamic hypo-
activation in PwP. We also found supporting evidence for the consistent
role of limbic system and frontal lobes in compensatory mechanism
related to motor planning and attention. The less disparate BAP
between PwPoff and HC provides proof for the symptomatic effect of
dopaminergic drugs at the neural network level, and a caveat for report-
ing functional BAP for both on- and off-medication in future studies.
Fig. 1. (64).
S27
63
Withdrawn by Author
64
Diagnostic flowchart using FP-CIT and MIBG scintigraphy in
differentiating Parkinsonian syndromes in Japan
M. Yogo, S. Omoto, K. Kawasaki, M. Ariizumi, M. Suzuki (Tokyo,
Japan)
Objective: The aim of this study was to propose a diagnostic
flow chart for differentiating Parkinsonian syndromes (PS) in routine
clinical practice.
Background: [123I]FP-CIT SPECT (FP-CIT) was approved in Japan
for clinical use for suspected PS in 2014. Thus, in vivo nuclear imaging of
presynaptic nigrostriatal neuronal degeneration and sympathetic cardiac
innervation with SPECT is now available to distinguish idiopathic Parkin-
sons disease (PD) from other atypical Parkinsonian disorder (APD). How-
ever, the use of these nuclear methods as stand-alone diagnostic means is
not adequate for differentiating different types of PS.
Methods: A consecutive series of 49 patients with PS attending
our clinic was prospectively recruited between May and November
in 2014. First,we performed brain MRI to exclude advanced morpho-
logical changes due to APD, and then divided into 4 groups, Group1:
cases presenting gross morphological changes on MRI, Group2:
cases showing normal findings on MRI and FP-CIT, Group3: cases
presenting abnormal findings on FP-CIT and low MIBG uptake,
Group4: cases showing abnormal findings on FP-CIT and preserved
Movement Disorders, Vol. 30, Suppl. 1, 2015
S28 POSTER SESSION
uptake of MIBG. We proposed PS diagnostic flow chart based on
these conditions. (Figure 1).
Results: Among the 49 Parkinsonism patients in whom a final
diagnosis could be made, there were 5 patients with advanced APD
such as multiple system atrophy, progressive supranuclear palsy, and
cortico basal degeneration in group 1, 19 with drug induced Parkin-
sonism, essential tremor, vascular PD, scan without evidence of
dopaminergic deficits in group 2, 17 with Lewy body disease such as
PD, dementia with Lewy bodies, and incidental Lewy body disease
in group 3, 8 with very early stage of degenerative PS in group 4.
Conclusions: This provisional flow chart including FP-CIT and
MIBG SPECT might assist clinicians in making an accurate clinical
diagnosis and minimizing costs and radiation exposure. Because the
present data are based on a small sample size from 1 center, confir-
mation of this flow chart in a large population is warranted using a
multicenter design.
65
The relative preservation of the nigral dopaminergic neuroal loss
of the patients with Parkinsons disease having dopamine-
unresponsive resting tremor
S. You, H.W. Kim (Daegu, Korea)
Objective: To evaluate the influenc of dopaminergic neuronal
loss to dopa-responsiveness of resting tremor in Parkinsons disease
patients.
Background: It has not been reported yet that whether there is a dif-
ference of dopaminergic neuronal loss between Parkinsons disease (PD)
patients with dopamine-unresponsive and -responsive resting tremor.
Methods: Between September 1st 2012 and April 30th 2014,
seven tremor dominant PD cases were obtained from neurology
clinic stipulating: no other abnormal neurological signs or exposure
to tremor reducing drugs. We defined the dopamine-responsiveness
of resting tremor as a reduction of at least two points for more than
3 months in the UPDRS tremor score of the limb with prominent
resting tremor. All patients had underwent [18F] FP-CIT PET on
OFF state within 1 year after PD diagnosis. We also executed the
quantitative analyses of FP-CIT PET in all patients cases. FP-CIT
PET images were quantitatively analyzed using 12 striatal subregions
and two substantia nigra VOI templates. Subregional binding ratio
(BR), inter-subregional ratio of BR (ISR) and subregional asymmetry
index were compared between patients with dopamine-unresponsive
resting tremor and -responsive resting tremor.
Results: There were 3 men and 4 women (Average
age=60.9 6 10.9). The mean age of onset was 59.7 6 10.2 years. The
mean disease duration was 1.29 6 0.49 years. Five patients resting
tremor showed an improved performance after the medical therapy,
yet the other two patients resting tremor remained still. On quantita-
tive analysis of FP-CIT PET, BR for the substantia niagra of the
more affected side in patients with dopamine-unresponsive resting
tremor was significantly higher than that in patients with dopamine-
responsive resting tremor (0.7163 6 0.08 vs. 0.43 6 0.02, P < 0.005).
The BR for all striatal subregions in patients with dopamine-
unresponsive resting tremor were higher than those in patients with
dopamine-responsive resting tremor, but those were not significant.
Conclusions: This study suggests that nigral dopaminergic neuro-
nal loss in PD patients having dopamine-unresponsive resting tremor
can be less severe. This is a preliminary study, and the further
research is needed for sure.
66
L-Dopa effect on power and variability of Parkinsons tremor is
influenced by the behavioral setting
H. Zach, M.F. Dirkx, J.W. Pasman, B.R. Bloem, R.C. Helmich
(Vienna, Austria)
Movement Disorders, Vol. 30, Suppl. 1, 2015
Objective: To investigate L-Dopa effects on resting tremor (RT)
parameters, influenced by behavioral settings.
Background: Parkinsons disease (PD) RT responds variably to
dopaminergic treatment.However,the influencing factors on the L-Dopa
effect are unclear. In contrast to many other PD symptoms,RT varies
depending on behavioral context like cognitively demanding tasks.
Methods: In 42 tremordominant PD patients(RT score>2UPDRS
pts.)clinical scores(UPDRS,tremor rating scale) and accelerometry in
the 2 contexts:rest(3x60s) and cognitive coactivation(COCO;counting
backwards in steps of three;3x60s)were collected in ON and OFF
state. RT power at individual RT frequency was estimated in Field-
trip by calculating time frequency representations between1-
20Hz.For the RT variability we calculated the coefficient of variation
of the resulting RT amplitude regressor.Using repeated measures
ANOVA,we analyzed the effect of factors TREATMENT(OFF vs.
ON),CONTEXT (rest vs.counting) and REPETITION(3 episodes)on
average RT power and tremor variability.
Results: We found a clear L-Dopa effect:total UPDRS 43vs.26,
clinical RT scores 3.2vs.2.4 pts(p<0.001);tremor constancy3.2vs.1.8
pts(p<0.001). L-Dopa reduced RT power(p<0.001), while COCO
increased it(p<0.001). The L-Dopa effect was sign.smaller during
COCO than during rest(TREATMENTxCONTEXT interaction,-
p=0.036).In fact, RT power during COCO ON L-Dopa was similar
to RT power at rest OFF L-Dopa(p>0.1). RT power correlated sig-
nificantly with clinical RT scores in both conditions(correlation coef-
ficient>0.5;Spearmans q<0.001). RT variability increased after L-
Dopa(p<0.001) and was smaller during COCO than rest(p<0.001);
there were no sign. interactions. RT variability was inverse related to
clinical tremor constancy(correlation coefficient<-0.6;Spearmans
q<0.001).
Conclusions: A cognitively demanding task reduces the L-Dopa
effect on RT(inconsistent with a previous study(Sturman
et al.,2007)).This emphasizes the importance of a simple counting
task in clinical practice,as measurements at rest will overestimate the
treatment effect.L-Dopa increased RT variability, indicating that
patients experience more alternations between rest and tremor epi-
sodes. Both factors may contribute to the subjective experience of
many patients that L-Dopa is ineffective for RT.Future research is
aimed to identify clinical, electrophysiological and cerebral factors
influencing the L-Dopa effect on RT.
Parkinsons disease: Pathophysiology
67
Auto-antibodies to a-synuclein are present in Parkinsons disease
biofluids
R.S. Akhtar, K.C. Luk, J.Q. Trojanowski, V.M.Y. Lee (Philadelphia,
PA, USA)
Objective: To develop an assay for auto-antibodies to a-
synuclein (a-syn) in biological fluid samples, and to measure auto-
antibody titers in CSF and serum from Parkinsons disease (PD)
patients and healthy participants as a potential disease biomarker.
Background: Biomarkers hold great promise in allowing early
detection of PD and in identifying sub-populations within an otherwise
clinically similar cohort of patients. Endogenous auto-antibodies to
amyloidogenic proteins like a-syn have been proposed as biomarkers
in several neurodegenerative conditions, including PD. We hypothe-
sized that a-syn auto-antibodies could be a biomarker for PD.
Methods: To measure auto-antibodies, we developed an enzyme-
linked immunosorbent assay (ELISA) using purified recombinant a-
syn as a capture substrate. We optimized this ELISA by systemati-
cally testing incubation parameters and blocking reagents to maxi-
mize the signal-to-noise ratio. We then assessed serum and CSF
samples from PD patients and age-matched healthy controls (HC) for
a-syn auto-antibodies. Each sample was analyzed at least three times
in independent experiments.
 POSTER SESSION
Results: CSF samples from 54 HC and 93 PD patients and serum
samples from 8 HC and 22 PD patients were analyzed. Titers of a-
syn auto-antibodies were elevated in both PD patient serum and CSF
as compared to HC samples. Auto-antibody titers did not correlate
with participant sex or age. In 15 serum-CSF sample pairs, there was
a significant correlation in auto-antibody titer. Serum auto-antibody
titers were significantly higher in participants with at least one
APOE e4 allele as compared to those without this allele. In contrast,
CSF titers were not affected by presence of the APOE e4 allele. In
the PD patients, there was no association between CSF auto-antibody
titers and cognitive impairment at the time of sample collection.
There was also no association between titer and cognitive and motor
performance, as measured by the Dementia Rating Scale-2 and Uni-
fied Parkinsons disease Rating Scale, respectively.
Conclusions: Auto-antibodies to a-syn are enriched in both
serum and CSF of PD patients as compared to age-matched healthy
participants. Further studies are necessary to determine if auto-
antibodies that bind pathological forms of a-syn can also be detected
in PD patient biofluid samples. Furthermore, studies of longitudinally
collected samples will determine whether auto-antibodies change
with respect to disease progression.
68
Admixing of two mice strains with differential susceptibility to
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) positively
modulates the nigral dopaminergic phenotype
P.A. Alladi, D.J. Vidyadhara, H. Yarriephang, T.R. Raju (Bangalore,
India)
Objective: Systematic neuroanatomical evaluation of dopaminer-
gic (DA) neurons of Substantia Nigra pars compacta (SNpc) in
C57BL/6 mice (MPTP susceptible), CD-1 mice (MPTP resistant) and
their crossbreds to delineate the phenomenon of differential suscepti-
bility to MPTP induced neurotoxicity.
Background: An interesting aspect of Parkinsons disease (PD) is
that it has differential prevalence among different ethnic groups. For
example, PD is less prevalent in Asian-Indians compared to Caucasians.
Further, Anglo-Indians the admixed population of European and Asian
Indian origin are 5 times lesser vulnerable than Indians. We aim to under-
stand the phenomenon of varying prevalence using mice strains with dif-
ferential susceptibility to develop MPTP induced Parkinsonian features.
Methods: The DA neurons of the SNpc of adult C57BL/6 mice,
CD-1 mice and the first filial generation of the reciprocal crosses
(F1X1 & F1X2) were studied (n56/group). Unbiased stereology of
tyrosine hydroxylase (TH) immunostained serial midbrain sections
provided the absolute neuronal numbers; densitometry based image
analysis and immunoblotting revealed protein expression levels; and
morphometry revealed their cellular character.
Results: Stereological quantification showed significantly higher
number of nigral DA neurons in CD-1 and the crossbred mice com-
pared to C57BL/6. Further, there were insignificant differences in the
neuronal densities except for the F1X2 crossbreds. Both, densitomet-
ric analysis and immunoblots revealed significantly higher TH
expression in the crossbreds compared to C57BL/6. The neuronal
nuclear and soma area of F1X1 and C57BL/6 matched well; while
those of FIX2 and CD-1 were similar.
Conclusions: The presence of higher number of nigral neurons in
CD-1 mice provides anatomical basis for its resistance to MPTP
induced toxicity. The comparability of numbers in crossbreds and CD-
1 mice, complemented by higher TH expression, argue for similar neu-
roprotection in the crossbreds. The morphological differences in dopa-
minergic neurons of susceptible and resistant strains indicate that
neuronal size may be a decisive factor of vulnerability. Thus, our study
provides neuroanatomical basis for differential MPTP susceptibility in
mice and the admixing provides an interesting experimental paradigm
to study the human phenomenon of differential prevalence of PD.
S29
69
Dopaminergic fibers from the substantia nigra to the olfactory
bulb in the rat
D. Alvarez-Fischer, O. Arias-Carrion, C. Klein, W.H. Oertel, G.U.
Hoeglinger (Luebeck, Germany)
Objective: To elucidate the neuroanatomical basis of hyposmia
in the pre-motor stage of Parkinsons disease (PD) and to investigate
the impact of the dopaminergic system on olfaction using a rat
model.
Background: PD is a neurodegenerative disorder characterized
by a marked loss of midbrain dopaminergic neurons. Whereas onset
of motor impairments reflects a rather advanced stage of the disor-
der, hyposmia is considered as a very early non-motor symptom of
the disease. Little is known about the role of nigral dopaminergic
projection system in olfaction under physiological conditions and
about the anatomical basis of hyposmia in PD. Yet, the early occur-
rence of olfactory dysfunction implies that pathogens such as envi-
ronmental toxins could incite the disease via the olfactory system.
Methods: We performed axonal tracing studies, retrograde intoxi-
cations and behavioral studies in rats.
Results: Anterograde and retrograde tracing studies identified a
direct dopaminergic projection from the substantia nigra pars com-
pacta to the core of the olfactory bulb. Ablation of the nigral projec-
tion led to impaired olfactory perception, as evidenced in two
independent test paradigms (using unconditioned appetitive and con-
ditioned aversive stimuli). Hyposmia following dopaminergic deaf-
ferentiation was reversed by means of pharmacological activation of
dopamine receptors.
Conclusions: We demonstrate here the existence of a direct dopa-
minergic projection into the olfactory bulb and identify its origin in
the substantia nigra pars compacta of rats. These observations may
provide a neural basis for toxin or pathogen invasion into the basal
ganglia and for hyposmia as an early and frequent symptom in Par-
kinsons disease.
70
Gait patterns associated with freezing of gait in patients with
Parkinsons disease
M. Amboni, L. Iuppariello, I. Lista, R. Rucco, P. Varriale, M.
Picillo, A. Iavarone, G. Sorrentino, P. Barone (Baronissi (Salerno),
Italy)
Objective: To investigate gait patterns associated with freezing
of gait (FOG) in Parkinsons disease (PD).
Background: FOG is a common and debilitating symptom in
patients with PD. FOG refers to paroxysmal events in which a sub-
ject is unable either to initiate locomotion and to turn or to walk
through a doorway. Beyond freezing episodes, inconsistent walking
abnormalities have been reported.
Methods: Thirty PD patients were enrolled. All patients were nei-
ther demented nor depressed. The clinical assessment included H&Y
stage, MDS-UPDRS I, II and IV at on state, MDS-UPDRS III both
at on and off state, Mini Mental State Examination (MMSE) and
Frontal Assessment Battery (FAB). Quantitative gait analysis was
performed by means of a motion capture system (Qualisys, Sweden).
The following conditions were investigated during off state: 1) nor-
mal gait (Gait-off); 2) cognitive dual task (Cog-off); 3)motor dual
task (Mot-off). Any freezing episode was excluded by the analysis.
Statistical analysis was carried out by means of the Mann-Whitney
test followed by a logistic regression analysis.
Results: Based on the objective assessment of FOG during gait
analysis, fourteen subjects were classified as patients with FOG
(FOG1) and sixteen subjects were classified as patients without
FOG (FOG-). There were no significant differences on age, gender,
disease duration, H&Y stage during on, MDS-UPDRS I, II, III (dur-
ing on), MMSE and FAB scores between the two groups. The two
groups differed on MDS-UPDRS III during off and MDS-UPDRS
Movement Disorders, Vol. 30, Suppl. 1, 2015
S30 POSTER SESSION
IV. The following gait parameters significantly differed between the
two groups: 1) velocity during all conditions (Gait-off: p50.02; Cog-
off: p50.0001; Mot-off: p50.015); 2) step length during all condi-
tions (Gait-off: p50.016; Cog-off: p50.001; Mot-off: p50.005); 3)
step length variability during Gait-off (p50.03); 4) single/double
support time ratio during Cog-off (0.04); 5) Symmetry ratio during
Gait-off (p50.026) and Cog-off (p50.005). The logistic regression
analysis showed that reduced velocity during Cog-off represents the
best predictor of FOG.
Conclusions: As compared to FOG-, FOG1 PD patients dis-
played reduced velocity, step length and symmetry and altered
dynamic stability as revealed by increased step length variability and
reduced single/double support time ratio. Reduced velocity during
cognitive dual task would represent the stronger walking parameter
associated with FOG, beyond freezing episodes.
71
Staining for unphosphorylated alpha-synuclein in the colon
mucosa. No difference between patients with Parkinsons disease
and healthy controls
L. Antunes, S. Frasquilho, M. Ostaszewski, J. Weber, L. Longhino,
P. Antony, A. Baumuratov, P. Derkinderen, R. Balling, N.J.
Diederich (Luxembourg City, Luxembourg)
Objective: To search for alpha-Synuclein in the colon mucosa in
patients with idiopathic Parkinsons disease (IPD) and in healthy
controls (HC).
Background: The gut has been proposed as the starting point of
IPD. Due to barrier leakage, a toxin could pass the mucosa and trig-
ger the disease process by misfolding alpha-Synuclein. However,
there are only scarce and so far controversial data on the presence of
alpha-Synuclein in the mucosa of the gut.
Methods: Twenty IPD patients (age: 66.9 6 8.4 yrs.; mean disease
duration: 6.95 6 6.8yrs., 50% male) and 8 HC (age: 65.6 6 3.9yrs.,
25% male) were willing to undergo total colonoscopy within the
nation-wide colon cancer screening program. In each subject biopsies
were obtained separately for the left and right part of the colon. Mucosa
was separated from submucosa, immunostaining for unphosphorylated
alpha-Synuclein was performed with alpha-Synuclein (Syn204) Mouse
mAb. Presence of alpha-Synuclein was evaluated in a semi-quantitative
manner (no presence, weak, medium, strong presence). The examiners
were blinded for the status of the subject (IPD versus HC).
Results: Sufficient biopsy samples (left and right colon part) and
adequate immunostaining were present in 27 subjects: 19 IPD
patients and 8 HC. Unphosporylated alpha-Synuclein was present in
18 of 19 IPD patients and in all controls. The difference in inten-
Fig. 1. (71).
Movement Disorders, Vol. 30, Suppl. 1, 2015
Fig. 2. (71).
sities was not significant. However, stronger and more frequent
immunostaining was present in the right than in the left colon
(p50.04).
Conclusions: Our data support the results of two other recent
studies: unphosphorylated alpha-Synuclein is present in the colon
mucosa of both IPD patients and HC. However, the staining is more
abundant in the proximal part of the gut, suggesting that the risk for
disease generation may be segment-dependent. Importantly, these
data need confirmation by screening for phosphorylated alpha-
Synuclein as well.
Immunostaining with alpha-Synuclein (Syn204) Mouse mAb;
x200 in a healthy control subject; Figure 1: medium presence of
unphosporylated alpha-Synuclein in the right colon; Figure 2: weak
presence of unphosporylated alpha-Synuclein in the left colon.
72
Endemic vitamin D deficiency, impact on incidence and
prevalence of Parkinsons disease
J.A. Bajwa, S. Nahrir, T.M. Muhammad, M.S. Bashir, A. Mujtaba,
S.R. Siddiqui (Riyadh, Saudi Arabia)
Objective: To evaluate vitamin D (Vit. D) deficiency in Parkin-
sons disease (PD) cohort of Arab ancestry.
Background: Over the last decade, there is tremendous evidence
linking Vit. D and adverse brain outcomes. Studies have looked at
the relationship between PD symptoms and Vit. D levels. Generally
it appears that 1,25(OH)2D3 can both induce factors involved in
dopamine synthesis and storage as well as perhaps induce an anti-
oxidant effect to protect dopamine neuron integrity. The prevalence
of Vit. D deficiency appears to be higher in patients with PD than
other disease populations. Arab population is well known to be Vit.
D deficient despite having decent sunlight throughout the year sec-
ondary to many causative and contributing factors.
Methods: A single center retrospective observational study was
conducted by reviewing patient charts enrolled in the Movement Dis-
orders registry at King Fahad Medical City, Riyadh, Saudi Arabia.
Chart review was used to retrieve demographics and Vit. D data.
The study was approved by IRB. The Statistical analysis was done
on SPSS version 22.
Results: A Total of 71 diagnosed PD patients were identified
with 42 males (59.2%) and 29 females (40.8%). 24 (33.8%) had PD
onset at age less than 50 y while 44 (62%) had PD onset after age
50 y. There was statistically significant (p 5 0.016) association
between gender and serum level of Vit. D deficiency however, there
was no statistically significant association of Vit. D deficiency with
 POSTER SESSION
symptoms of PD. There was higher trend for Vit. D deficiency in PD
patients with age of onset being less than 50 y.
Conclusions: Vit. D deficiency could be a potential modifiable
risk factor in PD. Endemic Vit. D deficiency may have implications
on PD incidence and prevalence, progression and treatment. Further
controlled studies are required in larger sample size to assess the
role of Vit. D in PD pathophysiology and treatment.
73
Gait impairment and cholinergic dysfunction in early PD: Does
vascular risk play a moderating role?
S.F. Bartlett, B. Galna, R.A. Lawson, S.E. Lord, R.E. Morris, A.J.
Yarnall, D.J. Burn, L. Rochester (Newcastle upon Tyne, United
Kingdom)
Objective: To compare the relationship between short latency
afferent inhibition (SAI) and quantitative gait characteristics in Par-
kinsons (PD) subjects with high and low vascular risk.
Background: Cholinergic dysfunction contributes to gait impair-
ment in PD. Recently, cardiovascular risk factors have been impli-
cated in higher level gait disorders in PD. We hypothesised that the
relationship between gait and SAI would be moderated by cerebro-
vascular damage to cholinergic pathways.
Methods: Forty one incident PD subjects and 44 age-matched
controls were assessed as part of the ongoing ICICLE-GAIT study, a
collaborative study with ICICLE-PD. Mean age 69.3 6 10.1 years in
PD, 68.5 6 8.4 years in controls (p50.695). Subjects past medical
history was obtained and relative cardiovascular risk quantified as 10
year risk compared to expected risk for age and sex, using the
QRISK2 calculator. This was used as a proxy for risk of cerebrovas-
cular damage. Low risk was defined as a relative risk ratio 1 and
high risk as a ratio >1, or existing cardiovascular disease. Choliner-
gic function was quantified by short latency afferent inhibition (SAI).
A 7m instrumented walkway (GAITrite) measured 16 gait character-
istics, including: gait speed, step length, stance time, gait variability
and asymmetry. SPSS 21 was used to perform Pearsons bivariate
correlations and linear regression models.
Results: SAI was higher (more impaired) in PD than controls
(75.53 6 23.72 vs. 58.67 6 22.17, p50.001). Gait was impaired in
PD subjects, who showed reduced velocity (p50.005), step length
(p50.005), increased step length variability (p50.017) and stance
time asymmetry (p50.027). There was no difference in SAI or gait
characteristics between high (n517) and low risk (n524) PD groups
(p50.611) . Despite this, SAI explained 45.7% of variance in step
length in high risk PD compared to only 2.6% in low risk PD and
0.2% in high risk controls.
Conclusions: Our findings suggest that vascular burden may
underpin gait impairment associated with cholinergic dysfunction in
PD. This relationship was only observed in those with PD and high
vascular risk and was not observed in high risk control participants
so is unlikely to be related to fitness or cerebrovascular burden alone.
Rather, it may represent a cumulative burden of cerebrovascular
parenchymal damage, dopaminergic loss, and cholinergic dysfunc-
tion, with implications for early gait impairment.
74
Quantification of beta activity with disease progression in EEG
recordings in Parkinsons disease patients
C.E. Behrend, B.E. Mace, L. Gauger, B.J. Kolls, W.M. Grill
(Durham, NC, USA)
Objective: To determine how beta frequency oscillatory activity
varies with disease progression and severity in human Parkinsons
disease (PD) patients using cortical electroencephalogram (EEG).
Background: PD is a progressive disease in which loss of dopa-
minergic neurons results in increased burst and oscillatory firing in
the cortical-basal ganglia loop and symptoms of tremor, bradykine-
S31
sia, and rigidity. Exaggerated oscillations are observed in PD patients
in local field potentials in a 13-30Hz band termed the beta band
and are correlated with emergence of bradykinesia. However, the
relationship between beta band oscillations and symptom progression
in PD remains unclear.
Methods: We recorded cortical EEG in fifteen PD patients of
varying disease durations (< 3, 5-10, >10yrs) and severities after
overnight medication withdrawal. We recorded EEG at rest (eyes
open and closed) and during hand motor tasks, which included both
unilateral and bilateral isometric grip and rapid movement tasks. We
quantified total percent of spectral power (TPSP) in the beta fre-
quency band for each cortical channel with respect to motor state,
disease duration, and off-medication Unified PD Rating Scale
(UPDRS) part 3 score. UPDRS 3 scores were categorized as mild (0-
20), moderate (21-40), and severe (>40). Repeated measures
ANOVA and post-hoc Tukey HSD tests were used to assess all out-
come measures.
Results: Across all subjects and channels, TPSP in the beta band
decreased significantly with eye closure at rest and varied little
across motor tasks. Across disease duration cohorts, TPSP in the
beta band averaged across tasks and channels was significantly
increased in the 5-10yr and >10yr cohorts (p<0.0001) as compared
to the < 3yr cohort. No significant difference was found between the
5-10yr and >10yr groups (p50.365). Across UPDRS 3 categories,
TPSP in the beta band averaged across tasks and channels was sig-
nificantly lower in the moderate group as compared to the mild
group (p<0.0001) and lower in the severe group as compared to
the moderate group (p<0.0001). Regression analysis of average
beta band TPSP as a function of UPDRS 3 score revealed a small,
significant negative slope (p<0.0001) and an R^2 of 0.054.
Conclusions: Our data suggest that increasing beta band power
may be a marker for disease duration but does not appear to be
related to degree of motor impairment.
75
Cerebellar theta-burst stimulation for the evaluation of the
pathophysiology and the therapeutic potential for rest tremor in
Parkinsons disease
D. Benninger, J. McNames, F. Herrmann, F. Medlin, F. Vingerhoets,
M. Stephan (Lausanne, Switzerland)
Objective: To investigate whether functional activation or inhibi-
tion of the cerebellum by transcranial magnetic stimulation modu-
lates rest tremor in Parkinsons disease.
Background: Rest tremor in Parkinsons disease (PD) is dis-
abling and responds often incompletely to conventional therapy. The
pathogenesis remains largely unknown and therapeutic alternatives
are needed. Functional imaging, neurophysiology and structural stud-
ies, and stereotactic surgery point to an involvement of the cerebel-
lum and the cerebello-thalamo-cortical pathway in generation of
Parkinsonian tremor, but the precise nature of the functional disturb-
ance remains unknown.
Methods: In a randomized, double-blind, sham-controlled, cross-
over study design, 15 PD patients with rest tremor underwent single
sessions of continuous TBS (cTBS, inhibitory), intermittent (iTBS,
excitatory) and sham stimulation of both cerebellar hemispheres.
Assessment of rest tremor, motor function and neurophysiology were
performed before and after each intervention including a 14-day
monitoring of tremor and motor activity.
Results: Continuous TBS, intermittent TBS and sham stimulation
of the cerebellum had no effects on tremor and motor performance
and failed to restore cerebello-cortical inhibition in Parkinsons
disease.
Conclusions: The contribution of cerebellar dysfunction in the
pathophysiology of Parkinsons disease remains undetermined, but
cerebellar stimulation may not offer a therapeutic alternative for
tremor.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S32 POSTER SESSION
76
Progressive nigrostriatal neurodegeneration associated with a-
synuclein pathology induced by AAV-mediated overexpression of
mutant a-synuclein in mice, rats and marmosets
M. Bourdenx, S. Dovero, M. Engeln, S. Bido, C. Piron, M. Bastide,
I. Vollenweider, L. Baud, Q. Li, V. Baekelandt, D. Scheller, A.
Michel, T. Boraud, P.O. Fernagut, F. Georges, G. Courtine, E.
Bezard, B. Dehay (Bordeaux, France)
Objective: Animal models are an essential asset for basic patho-
physiological research as well as validation of therapeutic strategies
of human diseases.
Background: The absence of adequate in vivo experimental mod-
els has severe repercussions for therapeutic intervention success. To
date, no mammalian model recapitulates the required age-dependent
phenotypes associated with Parkinsons disease (PD). Both the spe-
cies and age-related differential susceptibility of dopaminergic neu-
rons was assessed by comparing the extent and pattern of neuronal
loss, as well as occurrence of age-dependent intracellular inclusions
a-synuclein formation, in mice, rats and monkeys.
Methods: We selected a series of models of ascending complex-
ity with three different strains of mice (i.e. C57Bl/6, senescence-
accelerated prone mouse (SAMP8), as a model of aging and their lit-
termate controls, senescence-accelerated resistant mouse (SAMR1)),
adult rats and young versus aged marmoset monkeys. Each model
received a stereotatic injection in the substantia nigra pars compacta
(SNpc) of high-titer (1010 vg/g of body weight) bolus of adeno-
associated virus serotype 9 carrying mutant human a-synuclein
(A53T) under the neuron specific synapsin promoter including a
WPRE enhancer element. Sixteen weeks after injection, we systemi-
cally investigated both species specifics and age-dependent differen-
tial susceptibility of dopamine neurons regarding the extent and
pattern of neuronal loss and kinematic analysis for rats. We also
assessed a-synuclein expression levels, pathological state (i.e. S129
phosphorylation) and occurrence of intracellular inclusion formation.
Results: We successfully induced dopaminergic degeneration in
all species. Mice were less susceptible to a-syn-mediated toxicity
compared to rats and monkeys. Both SAMP8 and SAMR1 present a
strong a-syn staining which was not correlated with the occurence of
degeneration. High-resolution kinematic analyses revealed that rats
exhibited the hallmarks of Parkinsonian syndromes during gait,
including periods of freezing, postural instability, and reduced speed
of motion. In marmosets, old animals were more susceptible to
degeneration at both fibers and cell body levels.
Conclusions: According to the species used, we observed differ-
ences in the PD-related neurodegeneration progression over time
associated with a-synucleinopathy.
77
In utero delivery of scAAV9 mediates widespread brain
transduction in rats and monkeys: Towards new models of PD
M. Bourdenx, L. Chansel-Debordeaux, S. Dovero, V. Grouthier, J.
Uranga, N. Dutheil, S. Brun, A. Espagna, L. Groc, Q. Li, C. Jimenez,
E. Bezard, B. Dehay (Bordeaux, France)
Objective: Transgenic mammals allow to study brain function
and diseases.
Background: The adeno-associated virus serotype 9 (AAV2/9)
crosses the blood brain barrier, is capable of transducing developing
cells and neurons after intravenous injection in many species, and
mediates a long-term stable transduction. Ability to transduce brain
decreases over time, being maximum at P1 and decreasing dramati-
cally by P10 already suggesting a developmental period in which
AAV2/9 transduction has maximal efficacy. While P1 is an attractive
(and easily accessible) time point, in utero gene delivery has clearly
demonstrated that a wide transduction of neurons is possible at
embryonic stages compatible with the development of the targeted
area.
Movement Disorders, Vol. 30, Suppl. 1, 2015
Methods: To test this hypothesis, we injected intracerebroventric-
ularly (i.c.v.) high-titer bolus of AAV2/9 carrying either mutant
human a-synuclein (A53T) or enhanced green fluorescent protein
(EGFP) under the synapsin or CMV immediate enhancer/b-actin
(CAG) promoter respectively, at embryonic day 16.5 for rat and
around 100 days fetal age for monkeys under ultrasound imaging
guidance. Animals after birth have then be behaviourally followed-
up and were terminated at regular interval to access the brain
pathology.
Results: We characterized the regional distribution of GFP
immuno-positivity in brain structures and peripheral organs. We
observed transduction of neurons in most regions of the brain i.e.
within hippocampus, thalamus, spinal cord, striatum, globus pallidus,
substantia nigra, choroid plexus, cerebellum, and cortex- 25 days
after injection in rats. Moreover, the efficacy of transduction seems
dependent on the brain structure. Transduction of mutated a-
synuclein was then characterized as was defined the specific brain
lesions in both rats and monkeys.
Conclusions: Overall, these results indicate that an engineered
AAV serotype 9 variant (scAAV9) injected in utero in rats or rhesus
macaques results in efficient, neuronal and widespread transduction
of the brain. Altogether, this proof of concept study could facilitate
and offer unique opportunities for modelling brain diseases in rats
and rhesus macaques by targeting mutant genes with tissue-specific
gene expression, not mentioning future clinical applications for in
vivo correction of monogenic diseases or abnormalities in humans.
78
Does the side of onset in Parkinsons disease correlate with
interleukins levels?
L.S. Campos, F. Pradella, A.S. Farias, G.A.D. Moraes, R.F.O. de
Paula, F. Von Glehn, L.G. Piovesana, P.C. Azevedo, A.S. Moraes,
M.D. Andrade, A. DAbreu, L.M.B. Santos (Campinas, Brazil)
Objective: Evaluate interleukins levels- anti- and proinflamma-
tory- in subjects with Parkinsons disease (PD) and correlate those
with clinical manifestations.
Background: Several studies showed altered cytokine levels in
Parkinsons disease (PD). However, the role of those cytokines in
the pathophysiology of PD has not yet been established.
Methods: We evaluated 21 subjects who fulfilled the Brain Bank
Criteria for PD diagnosis . All patients answered a structured stand-
ardized clinical questionnaire and the following scale: UPDRS, The
modified Hoehn and Yahr staging, Schwab and England Scale,
SCOPA cognition (SCOPA-COG), SCOPA-Psychiatric complications
(SCOPA-PC) and Non-Motor Symptoms Scale (NMSS). We classi-
fied subjects into two clinical subtypes: tremor-dominant (TD) and
rigid-akinetic (RA) . We measured the following serum citokines
levels: IL-6, TNF-a, TGF-b, IL-10.
Results: Lelves of IL-6 (0.0053411 6 0.0059566 versus
0.0012878 6 0.0017099; p50.0362) and TNF-a (0.0298595 6
0.0174282 versus 0.0140438 6 .009449; p50.0102) were signifi-
cantly higher in subjects with a left-sided onset compared to those
with a right-sided onset. There was no significant difference in age,
sex distribution, age of onset, prevalence of dementia, depression,
and other clinical scale scores between subjects with left-sided onset
compared to those with a right-side one. We also observed higher
levels of IL-6 in subjects with dementia when compared to those
with normal cognition (0.0019666 6 0.0032651 versus .0064117 6
.0064288, p50.0496).
Conclusions: We found higher levels of proinflamamtory cyto-
kines in subjects with a left-side onset compared to those with a
right-side onset and in those with dementia compared to those with
normal cognition. Those cytokines likely mediate neuronal degenera-
tion, and their levels probably correlate with the differential clinical
presentation previously observed in clinical studies considering side-
of-onset.
 POSTER SESSION
79
Dyskinesias are associated with a narrowband 70 Hz activity as
revealed by chronic cortical and subcortical recordings in
Parkinsons disease patients
C. de Hemptinne, N. Swann, S. Miocinovic, S. Qasim, S. Wang, N.
Ziman, J. Ostrem, M. San Luciano, N. Galifianakis, P. Starr (San
Francisco, CA, USA)
Objective: To investigate the electrophysiological characteristics
of cortical and subcortical activity associated with dyskinesias in Par-
kinsons disease (PD).
Background: Levodopa-induced dyskinesias (LID) are one of the
most frequent and disabling motor complications of long-term dopa-
mine replacement in patients with PD. Deep brain stimulation (DBS)
can also exacerbate or induce dyskinesia, especially shortly after
implantation, limiting the therapeutic efficacy of PD treatments. In
order to improve these therapies it is crucial to investigate the patho-
physiology underlying these periods of involuntary movements that
is still largely unknown.
Methods: Two PD patients with severe motor fluctuations, mini-
mal tremor and experiencing periods of dyskinesias have been
implanted with an investigational, totally implanted neural interface
capable of both recording and stimulation. This device was con-
nected to a standard quadripolar DBS electrode placed in the subtha-
lamic nucleus (STN) and one subdural quadripolar strip electrode
placed over the primary motor cortex (M1). Cortical and subcortical
signals were recorded simultaneously in the outpatient clinic over
multiple visits, in the on and off medication state and on and of
stimulation, during both dyskinetic and non dyskinetic states. Signals
were sampled at 800 Hz, stored internally, downloaded noninvasively
by radiotelemetry then analyzed.
Results: Periods of dyskinesias were associated with the emer-
gence of a narrow-band peak in spectral power at about 70 Hz in
both M1 and STN signals, although most prominent in M1. An
increase in coherence between both structures was also observed at
the same frequency. This pattern has been reliably observed during
periods of levodopa induced dyskinesias over multiple visits. Prelim-
inary results also suggest that stimulation induced dyskinesias is
characterized by a similar pattern of activity.
Conclusions: Dyskinesias are characterized by a narrowband 70
Hz rhythm at the cortical and subcortical level. This signal, could be
used in a closed loop DBS paradigm that would automatically adjust
the DBS settings, based on this biomarker, to reduce stimulation
amplitude or active configuration so as to optimize dyskinesia
control.
80
Neuroprotective effect of incretin in rat model of Parkinsonism
with pre-existing diabetes
E.A. Elbassuoni (Minia, Egypt)
Objective: The goal of this work is to study the effect of pre-
existing streptozotocin-induced diabetes on the severity of 1-methyl-
4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) -induced Parkinsonism
in male albino rats, and to find out if GLP-1 could improve symp-
toms of Parkinsonism in the diabetic animals, and work out how it
might do this.
Background: Previous studies have suggested associations
between midlife diabetes mellitus (DM) and neurodegenerative dis-
eases, DM contributes to cognitive impairment in the elderly, but its
effect in Parkinsonism is not well studied. Glucagon-like peptide-1
(GLP-1), as a member of the incretin family, has roles in glycemic
control and satiety. In addition, it appears to exert several additional
effects on many tissues via the widespread expression of its receptor.
Methods: 40 adult male albino rats were divided into 4 equal
groups: control untreated group, MPTP group, diabetic MPTP group,
and diabetic MPTP group1 exenatide (a synthetic GLP-1 mimetic).
At the end of the experiment striatal dopamine, tumor necrosis factor
S33
alpha (TNF-a), glutathione reductase, malondialdehyde, nitric oxide
and catalepsy score were measured.
Results: MPTP induced Parkinsonism in all rats proved by the
significant increase in catalepsy score and the significant decrease in
striatal dopamine level. Pre-existing of diabetes before Parkinsonism
induction worse the condition and increase the severity of Parkinson-
ism. Exenatide administration to diabetic MPTP rats induced signifi-
cant increase in the striatal dopamine, glutathione reductase with a
significant decrease in striatal TNF-a level, nitric oxide and malon-
dialdehyde level with significant improvement in the catalepsy score
better than the non-treated diabetic MPTP group, and the MPTP
group.
Conclusions: Diabetes mellitus increases the severity of impair-
ment in Parkinsonism disease. The benefits of incretin extend beyond
their hypoglycemic effects since it success as a neuroprotective agent
in rats with Parkinsonism through multiple mechanisms of action
including the anti-inflammatory, antioxidant and anti-apoptotic effect
largely independent of its hypoglycemic effects.
81
UPDRS asymmetry is higher for the upper extremities compared
to the lower extremities in Parkinsons disease
G. Foffani, J.A. Obeso (Mostoles, Spain)
Objective: To test whether left-right clinical asymmetry is differ-
ent for the upper extremities compared to the lower extremities in
Parkinsons disease.
Background: The clinical onset of Parkinsons disease typically
affects one body side with progression towards the other side taking
place some few years later. Whether this clinical asymmetry differs
between upper and lower extremities remains unknown.
Methods: Data were obtained from the Parkinsons Progression
Markers Initiative (PPMI) database (www.ppmi-info.org/data). We
analyzed the UPDRS III scores of the full cohort of patients with
Parkinsons disease included in the PPMI database at their baseline
screening. Left and right UPDRS scores were separately obtained for
the lower and upper extremities by summing the corresponding later-
alized UPDRS items for rigidity, bradykinesia and tremor (3.3b-e,
3.4a-b, 3.5a-b, 3.7a-b, 3.8a-b, 3.17a-d). To minimize floor effects,
we considered only patients in which the sum of these UDPRS items
was 10 (n5252). Clinical asymmetry was measured as the absolute
value of left-right UPDRS scores, expressed as a percentage of the
corresponding left1right scores.
Results: Left1right UPDRS scores were higher for the upper
extremities (9.01/-3.0) compared to the lower extremities (6.11/-
2.7; paired t-test: p<0.0001). As expected, clinical asymmetry
decreased from 54.5% to 29.7% as left1right UPDRS scores
increased from 6 to 10 (2-way independent-measures ANOVA, factor
UPDRS: F(4,286)=6.6, p<0.0001). More importantly, clinical asym-
metry was significantly higher for the upper extremities (54.61/-
30.1%) compared to the lower extremities (42.81/-31.1%; factor
EXTREMITIES: F(1,286)=33.8, p<0.0001). In the small subset of
patients whose left1right UPDRS scores were identical for the lower
and upper extremities (n517), clinical asymmetry was higher for the
upper extremities (47.61/-35.3%) compared to the lower extremities
(37.31/-28.5%; paired t-test: p50.0134).
Conclusions: Parkinsons disease seems clinically more asymmet-
rical in the upper extremities compared to the lower extremities.
This clinical observation could reflect a different UPDRS sensitivity
between upper and lower limbs, or could suggest that motor progres-
sion advances somatotopically in a caudal-to-rostral direction.
82
Fixin to die: A common death pathway in catecholamine
neurons
D.S. Goldstein, C. Holmes, P. Sullivan, Y. Sharabi, I.J. Kopin
(Bethesda, MD, USA)
Movement Disorders, Vol. 30, Suppl. 1, 2015
S34 POSTER SESSION
Fig. 1. (82).
Objective: We tested whether across a variety of diseases,
including familial and sporadic Parkinsons disease (PD) and multi-
ple system atrophy (MSA), neuroimaging and neurochemical evi-
dence for a vesicular storage defect and decreased aldehyde
dehydrogenase (ALDH) activity accompany catecholaminergic dener-
vation, independently of the initial disease process.
Background: Several neurodegenerative diseases such as PD
involve prominent loss of catecholamine neurons. Determinants of
vulnerability of catecholamine neurons have been obscure. We
hypothesized that decreased vesicular storage and decreased ALDH
activity constitute a common final pathway in catecholamine neuro-
nal death. The combination would be expected to build up levels of
3,4-dihydroxyphenylacetaldehyde (DOPAL), the autotoxic metabolite
of dopamine. DOPAL and alpha-synuclein may be nodes in a com-
plex homeostatic nexus, in which cumulative abnormalities at multi-
ple sites could induce lethal positive feedback loops. [figure1]
Methods: We analyzed data from catecholaminergic neuroimag-
ing and neurochemistry and post-mortem tissue neurochemistry in
patient groups with catecholaminergic denervation in the brain or
periphery (e.g., PARK1, PARK4, Gaucher/PD, sporadic PD, MSA,
pure autonomic failure, progressive supranuclear palsy) and in
groups without catecholaminergic denervation.
Results: Accelerated loss of 18F-dopamine-derived radioactivity
was found specifically in groups with cardiac sympathetic denerva-
tion, and accelerated loss of putamen 18F-DOPA-derived radioactiv-
ity was found specifically in groups with Parkinsonism. Myocardial
norepinephrine depletion was associated with decreased vesicular
storage in cardiac sympathetic nerves and putamen dopamine deple-
tion with decreased vesicular storage in nigrostriatal terminals.
Decreased putamen ALDH activity and low CSF 3,4-dihydroxyphe-
nylacetic acid levels were found in Parkinsonian but not in non-
Parkinsonian groups.
Conclusions: Diseases involving catecholaminergic denervation
entail a pattern of decreased vesicular storage and decreased ALDH
activity, regardless of the disease etiology or initial disease process,
consistent with a common death pathway in catecholaminergic
neurons.
83
Contribution of striatal interneurons to L-DOPA induced
dyskinesia development in an animal model of Parkinsons
disease
G. Gomez, I.R. Taravini, M.G. Murer, O.S. Gershanik (Ciudad
Aut
onoma de Buenos Aires, Argentina)
Movement Disorders, Vol. 30, Suppl. 1, 2015
Objective: To determine changes in number and activity of the
different populations of striatal interneurons in a mouse model of
hemiParkinsonism and L-DOPA induced dyskinesias.
Background: The administration of 3,4-dihydroxyphenyl-l-ala-
nine (L-DOPA) still remains as the preferred treatment for Parkin-
sons disease (PD) despite its propensity to induce severe motor
complications, known as L-DOPA-induced dyskinesias (LID). Mal-
adaptive changes in the striatum, as well as in other brain areas, are
thought to underlie the development of LID. Even though interneur-
ons comprise only 5% of all striatal neurons, they strongly modu-
late striatal output. Therefore, changes in striatal microcircuits may
contribute to basal ganglia dysfunction in a number of Movement
Disorders such as PD and in LID development.
Methods: C57 mice were injected with 6-hydroxydopamine (6-
OHDA) or vehicle in the medial forebrain bundle and treated daily
with a dyskinetogenic dose of L-DOPA or saline solution. LID and
reversal of forelimb asymmetry (a measure of anti-Parkinsonian
response) were assessed on days 1, 4, 8, 12 and 14. Fixed tissue sec-
tions from the striatum and substantia nigra pars compacta were
obtained and the severity of the dopaminergic lesion was analyzed
by tyrosine hydroxylase immunohistochemistry. The density of each
type of interneuron population was determined in the different exper-
imental groups by performing immunohistochemical stains for spe-
cific interneuron markers. The activity of each interneuron type was
assessed by colocalization of each interneuron marker with c-fos.
Results: Changes in c-fos and interneuron markers were observed
both after dopaminergic depletion and LID development. 6-OHDA
lesion led to reduced number of parvalbumin positive interneurons
and this change was not reversed by L-DOPA administration. On the
other hand, no significant changes were observed in the number of
cholinergic interneurons within the different experimental groups.
Conclusions: Our findings suggest that changes in striatal inter-
neurons contribute to the maladaptive state that occur after dopamine
depletion. In addition, chronic treatment with L-DOPA fails to rees-
tablish the initial physiological scenario. Further functional studies
are required to elucidate if these changes are just an epiphenomenon
or if they actually contribute to LID development.
84
L-DOPA induced motor changes in alpha-synculein model of
Parkinsons disease in C. elegans
D.K. Gupta, X. Hang, Z. Feng (Cleveland, OH, USA)
Objective: To establish a C. elegans model for L-DOPA-induced
dyskinesia in Parkinsons disease.
Background: L-DOPA induced dyskinesia (LID) is a disabling
complication of dopaminergic therapy in Parkinsons disease (PD).
There is a lack of simple animal models of LID that can capture this
clinical phenomenon and enable mechanistic study and high-
throughput drug screening. C. elegans, which has a short lifecycle
( 3 weeks) and rich genetic resource, is a robust animal model to
study pathophysiology of PD.
Methods: We used alpha-synuclein expressing C. elegans model of
PD, which exhibits progressive degeneration of dopaminergic neurons
and loss of motor activity. Day 1 worms from this model and wild type
N2 controls were divided into three groups based on their exposure to
L-DOPA (1mM): no exposure, continuous exposure (day 2-10) and
alternating exposure (starting day 2). Using automated worm behavioral
analysis system, we quantified worms locomotion speed (LS), body
bending (BR), physical displacement per body bend (PDBD) of worms
(5 minutes per worms, 6 worms per group) on day 2, 4, 6, 8 and 10.
[figure1]
Results: Compared to controls, a progressive, age-related reduc-
tion in LS was observed in PD worms, which was alleviated by both
continuous and alternating L-DOPA exposure (figure 1a). In contrast,
BR was not altered in PD worms. However, BR of PD worms was
significantly increased by L-DOPA exposure, with more dramatic
effect on alternating exposure (figure 1b). PD worms also exhibited
 POSTER SESSION
Fig. 1. (84).
an age-related reduction in PDBD compared to controls. PDBD of
PD worms was not changed by continuous L-DOPA exposure but
was further reduced by alternating L-DOPA exposure (figure 1c).
Conclusions: PD worms exhibit progressive, age-related loss of
motor activity, which is alleviated by L-DOPA treatment. However
treatment with L-DOPA leads to dynamic modulation of motor activ-
ity depending on continuous versus alternating exposure. These find-
ings are consistent with the current understanding of LID
pathophysiology and may potentially represent motor phenotype of
LID in C. elegans. These findings need be further validated as such
simple animal model of LID in C. elegans may have important
implications for discovering molecular mechanisms and performing
high-throughput drug screenings for LID.
85
Is handedness correlated to Parkinsons disease side of onset?
S. Hanif, M.S. Hassan, R.A.l. Sharif, Z.G. Aljohani, J.A. Bajwa
(Riyadh, Saudi Arabia)
Objective: To describe correlation between handedness and onset
of motor symptoms in Parkinsons disease patients at Movement
Disorders center, National Neuroscience Institute, King Fahad Medi-
cal City, Riyadh, Saudi Arabia.
Background: Parkinsons disease (PD) characteristically presents
with asymmetrical motor symptoms. One hypothesis is that motor
asymmetry can be an epiphenomenon of underlying anatomical
asymmetry. Multiple factors could be involved in asymmetric presen-
tation of disease like age, sex, disease duration and handedness. Pub-
lished data postulates that PD motor symptoms emerge more often
on the dominant hand side. Asymmetric motor symptoms onset cor-
related to dominant hand side has not been yet investigated in Arab
cohort.
Methods: Seventy four PD patients and their charts were
reviewed to get demographic details like age, sex, disease related
parameters i.e duration of PD, subtype of PD, initial motor symptom
of tremor, rigidity, bradykinesia and family history. Patients were
also interviewed over the phone to specifically ask about first motor
symptom, sidedness and handedness.
Results: The majority (87.8%) of our patients were right handed
among who 55 (74.5%) were male and 19 (25.7%) were females.
97% of all patients were above the age of 45 y at the time of diagno-
sis. Tremor was the first motor symptom in 65%, bradykinesia in
23% and rigidity in 13.5%. There was a significant association
between handedness and site of initial symptom. 63.1% of right
handed patients experienced their first symptom on the right side and
36% on their left side. Similarly 87.5% of the left handed patients
reported their initial symptom on the left side and remaining 12.5%
on their right side (P-value 0.009).
S35
Conclusions: Like published data, our cohort also shows strong
association between handedness and side of initial symptom (P-value
0.009) even though the sample size was small. Further research is
required to determine PD side of onset, symptom at onset and corre-
lation with hand dominance.
86
Identification of novel biomarkers for Parkinsons disease by
metabolomics technologies
T. Hatano, S. Saiki, A. Okuzumi, N. Hattori (Tokyo, Japan)
Objective: The pathogenesis of Parkinsons disease (PD) involves
complex interactions between environmental and genetic factors.
Metabolomics can shed light on alterations in metabolic pathways in
many diseases, including neurodegenerative diseases. In the present
study, we attempted to elucidate the candidate metabolic pathway(s)
associated with PD.
Background: Although the pathomechanisms underlying neuronal
degeneration in PD remain unknown, various PD-related genetic-
environmental interactions may contribute to the pathogenesis of this
disease. Previous studies revealed the diagnostic value of measuring
a-synuclein and DJ-1 levels in cerebrospinal fluid; however, useful
biomarkers related to genetic and environmental factors have not yet
been elucidated. Serum/plasma metabolomics is a useful tool for
understanding metabolic pathways and networks in neurodegenera-
tive diseases.
Methods: Serum samples were collected from 35 individuals
with idiopathic PD without dementia; 18 males, mean age
69.1 6 10.8 years; mean Hoehn & Yahr (H-Y) 2.9 6 1.1 and 15
healthy age-matched and sex-matched control subjects without PD: 7
males, age 70.7 6 9.7 years. This analysis was based on a combina-
tion of three independent platforms: ultrahigh-performance liquid
chromatography/tandem mass spectrometry (UHPLC/MS/MS) opti-
mized for basic species, UHPLC/MS/MS optimized for acidic spe-
cies, and gas chromatography/mass spectrometry.
Results: The metabolomic profiles of PD were clearly different
from normal controls. PD profiles had significantly lower levels of
tryptophan, caffeine and its metabolites, bilirubin, ergothioneine, and
significantly higher levels of levodopa metabolites and biliverdin
than those of normal controls. Alterations in bilirubin/biliverdin ratio
and ergothioneine can indicate oxidative stress intensity and may
suggest elevated oxidative stress and/or insufficient ability for scav-
enging free radicals which could contribute to PD pathogenesis.
Decreased serum tryptophan level is associated with psychiatric
problems in PD. A decrease in serum caffeine levels is consistent
with an inverse association of caffeine consumption with develop-
ment of PD based on past epidemiological studies.
Conclusions: Metabolomics analysis detected biomarkers associ-
ated with PD pathogenesis and disease progression.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S36 POSTER SESSION

Fig. 1. (87).

87 Results: Reduced mitochondrial maximal and spare respirations,

mass, number of mitochondria per synaptosome, and disrupted
Parkin mediated mitochondrial quality control in nigrosriatal mitochondrial ultra structure were observed in parkin null mice -. In
dopamine neurons contrast, parkin overexpression via rAAV-hParkin in WT mice did
H.Y. Hawong, J.R. Patterson, K.J. Lookingland, J.L. Goudreau, not affect mitochondrial respiratory function.
Michigan State University (East Lansing, MI, USA)
Objective: Parkin prevents DA neurodegeneration by maintaining
mitochondrial homeostasis in central DA neurons. Mitochondrial bioenergetics with parkin overexpression
Background: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Respiration Sham F-Parkin
(MPTP) is a mitochondrial Complex I inhibitor that recapitulates (OCR) (pMoles/min) (pMoles/min)
Parkinsonian features in human and various animal models.
Increased parkin expression is associated with resistance of tuberoin- Basal 151 6 6.73 134 6 8.35
fundibular dopamine (TIDA) neurons following acute MPTP expo- Maximum 514 6 47.2 497 6 23.4
sure, whereas parkin expression decreases in susceptible nigrostriatal Spare 362 6 46.8 361 6 16.2
(NS) DA neurons. Parkin is a 52 kDa cytosolic protein identified by
linkage analysis in autosomal recessive early onset PD. Parkin is
reported to mediate mitochondrial quality control through autophagy
of mitochondria. However, parkin overexpression prevented inhibition of maxi-
Methods: Mitochondrial ultrastructure, mass, membrane potential mum and spare respirations and loss of mitochondrial protein Cox
and respiratory capacities in NSDA neurons were investigated in par- IV following MPTP exposure - [figure2].
kin null mice using Seahorse XF 24 analyzer, flow cytometry, and Conclusions: Mitochondria in striatal synaptosomes had impaired
transmission electron microscopy. Parkin was overexpressed in sub- function, ultrastructure and lower mass in the absence of parkin.
stantia nigra by introducing rAAV-hParkin stereotaxically in wild- This may be due to loss of parkin-mediated mitochondrial quality
type (WT) mice. Mitochondrial respiratory capacities and mitochon- control in NSDA neurons. Parkin overexpression maintained func-
drial protein levels were measured using Seahorse XF 24 analyzer tional mitochondria, likely through autophagy of mitochondria fol-
and Western blot in parkin overexpressed WT mice following acute lowing acute neurotoxicant exposure. Therefore, loss of parkin
MPTP exposure. mediated mitochondrial quality control may contribute to loss of

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
Fig. 2. (87).
NSDA neurons in a neurotoxicant model of DA neuronal degenera-
tion similar to that which occurs in PD.
88
Insights into freezing of gait from wearable sensors
F.B. Horak, J.G. Nutt, M. Mancini (Portland, OR, USA)
Objective: To characterize the muscle activation patterns and leg
movements prior and during freezing episodes to better understand
the neural mechanisms responsible for Freezing of Gait (FoG).
Background: We hypothesize that FoG is due to lack of release
of hip abductor muscle activity for lateral anticipatory postural
adjustments (APAs) in preparation for stepping during gait and
turning.
S37
Methods: Five subjects with idiopathic PD with FoG (FoG1,
UPDRS III: 51 6 13) and 5 idiopathic PD without FoG (FoG-,
UPDRS III: 40 6 16) walked a course with gait initiation, passes
through a doorway, and 180 turns while wearing 3 Opal inertial
sensors mounted on the posterior trunk and on each ankle, and 6
wireless EMG sensors on bilateral tibialis anterior (TA), gastrocne-
mius medialis (GM) and at the hip on the tensor fasciae latae (TFL).
Heel-strike (Hs) and toe-off (To) events for right and left steps were
extracted from the shank angular velocities. The FoG ratio (power
spectral density ratio between high and low frequencies of shank
acceleration) and gait speed were calculated. Onset of activity from
Hs for the TA, GM, and contralateral TFL, offset of activity for the
ipsilateral TFL; as well as duration of EMG activity were calculated
for the 5 steps preceding the turn.
Results: All FoG1 subjects showed FoG. The FoG ratio was sig-
nificantly larger in FoG1 compared to FoG- (1.25 6 0.3 vs
Movement Disorders, Vol. 30, Suppl. 1, 2015
S38 POSTER SESSION
0.5 6 0.3, p50.007) although gait speed, excluding turns, was similar
(0.67m/s60.23 vs 0.88m/s60.13, p50.11). In the steps before a turn:,
i) the ipsilateral TFL offset and the contralateral TFL onset were simi-
lar between groups, whereas the subsequent, ipsilateral TFL onset was
later in the FoG1 for the step prior to a freezing episode; ii) the ipsilat-
eral TFL activity was reduced during stance but increased during swing
in FoG1; iii) the contralateral TFL activity was larger during stance
and reduced during swing in FoG1. The medio-lateral acceleration
traces were similar in amplitude, but less variable in FoG1.
Conclusions: We observed increased ipsilateral TFL activity and
reduced contralateral TFL activity in FoG1 compared to FoG-, con-
sistent with a lack of release of APA inhibition and inadequate pos-
tural preparation for a step. These observations suggest that abnormal
temporal muscle activation patterns during FoG episodes may be due
to abnormal coupling of anticipatory postural adjustments with step-
ping rather than a disruption of central pattern generators.
89
AAV1/2 overexpression of A53T a-synuclein in the substantia
nigra results in behavioural deficits and degeneration of the
nigrostriatal system: A new mouse model of Parkinsons disease
C.W. Ip, L.C. Klaus, V. Maltese, J. Volkmann, J.M. Brotchie, J.B.
Koprich (Wuerzburg, Germany)
Objective: To generate and characterize a mouse model of Par-
kinsons disease (PD) based on AAV1/2 driven expression of human
A53T a-synuclein (aSyn) in the substantia nigra (SN).
Background: a-synuclein is a protein implicated in the patho-
physiology of PD. To mimic this aspect of the disease it has been
shown in rat and monkey models that AAV1/2 mediated overexpres-
sion of human A53T aSyn leads to degeneration of SN dopaminergic
neurons, decline of striatal dopamine (DA) and tyrosine hydroxylase
(TH), elevation of DA turnover and behavioural abnormalities.
Knowing the advantages of a species amendable to genetic manipula-
tion, we aimed to translate the AAV1/2 A53T aSyn model to mouse.
Methods: AAV1/2 A53T aSyn or AAV1/2 empty vector (EV) at
a concentration of 5.1 x 10exp12 gp/ml were unilaterally injected
into the right SN of male adult C57BL/6 mice. Clinical examination
in both groups was longitudinally performed by open field and
rotarod analysis on a weekly basis for 8 weeks after AAV injection.
Paw use asymmetry was examined by cylinder test at weeks 5 and 9
after injection. Post-mortem analysis was performed by immunohis-
tochemistry to analyze aSyn and TH expression in the SN, striatal
dopamine transporter (DAT) levels by autoradiography and dopa-
mine metabolism by high performance liquid chromatography.
Results: Significant paw use asymmetry was observed in the A53T
aSyn injected group with preference of the right front paw when com-
pared to EV controls at both 5 and 9 weeks post injection (both
p<0.05). Neurochemically, a significant reduction in striatal DAT bind-
ing (by 23%), DA (by 36%) and DOPAC (by 36%) levels in A53T
aSyn mice was shown as well as an increase in DA turnover (HVA/
DA; by 60%) compared to controls (all p<0.05). Immunohistochemical
double staining for TH and aSyn showed that the A53T injected mice
had widespread nigral expression of aSyn and a reduction in SN DA
neurons. No significant effects were detected on the open field analysis
(velocity or distance moved) or on rotarod performance.
Conclusions: These data show that unilateral injection of AAV1/
2 A53T aSyn into the mouse SN leads to persistent behavioral defi-
cits and neurodegeneration of the nigrostriatal DA system similar to
that observed in the rat. This aSyn based model of PD is now in a
position to conduct investigations using transgenic mice.
90
Motor behaviour and neuronal network activity after lesions of
the anterior or posterior pedunculopontine nucleus in a rat
model of Parkinsons disease
X. Jin, J.K. Krauss, M. Alam, K. Schwabe (Hannover, Germany)
Movement Disorders, Vol. 30, Suppl. 1, 2015
Objective: We investigated the effect of anterior or posterior cho-
linergic lesions of the pedunculopontine nucleus (PPN) in rats with
6-hydroxydopamine (6-OHDA) lesions on gait-related motor behav-
ior, and on neuronal network activity of the cuneiform nucleus
(CNF) and the basal ganglia (BG) output region, the entopeduncular
nucleus (EPN).
Background: Loss of cholinergic neurons in the mesencephalic
locomotor region, comprising the PPN and the CNF, are related to
gait disturbances in late stage Parkinsons disease (PD).
Methods: Bilateral anterior and posterior PPN lesions were
induced by stereotaxic microinjection of the cholinergic toxin
AF64A in male Sprague Dawley rats with or without 6-OHDA-
induced bilateral retrograde nigrostriatal degeneration of dopamine
neurons, a model of PD. Movement impairments were assessed using
rotarod and open field test. Thereafter, in vivo electrophysiology
recording were carried out in the CNF and the EPN and single unit
(SU) activity was analysed.
Results: Bilateral nigrostriatal dopamine depletion significantly
decreased the latency in the rotarod test, which was further deterio-
rated by anterior PPN lesions (P<0.05). In the activity box 6-OHDA
lesions had no effect on spontaneous locomotion, but additional pos-
terior PPN lesions reduced this measure (P<0.05). In the EPN nigro-
striatal dopamine lesions led to significantly higher coefficient of
variation of the inter-spike interval (P<0.001) coupled with more
bursting firing pattern (P<0.05), which were reversed after anterior
and posterior PPN lesions. In the CNF the neuronal discharge rate
was increased after anterior PPN lesions (P<0.001) with no effect of
nigrostriatal dopamine lesions. The CNF bursting pattern was
reduced after 6-OHDA lesions, additional PPN lesions further
reduced this measure (P<0.05).
Conclusions: Combined nigrostriatal and anterior or posterior
PPN lesions had different impact on motor behaviour. The complex
effects on neuronal activity of the CNF and the BG network may
contribute to elucidate the pathophysiology of PD gait disturbances.
91
Development and evaluation of closed-loop deep brain
stimulation (DBS) in a primate model of Parkinsons disease
(PD)
L.A. Johnson, S.D. Nebeck, C.M. Hendrix, M.D. Johnson, K.B.
Baker, J.L. Vitek (Minneapolis, MN, USA)
Objective: To develop a recording and stimulation system that
enables closed-loop control of DBS in an animal model of Parkin-
sons disease (PD) and to evaluate the behavioral and physiological
effects of closed-loop DBS (CL-DBS) relative to traditional DBS
(tDBS) and off-DBS conditions.
Background: tDBS systems are always on, continuously deliver-
ing pulsed stimulation at a high rate (i.e., >100 Hz) regardless of the
clinical state. A promising approach to improve DBS therapy for PD
is to incorporate feedback control of DBS based on real-time meas-
ures of brain activity. In particular, local field potential (LFP) activ-
ity in the beta range (13-35Hz) has been implicated as a potential
biomarker to use for closed-loop control of DBS.
Methods: The rhesus macaque 1-methyl-4-phenyl-1,2,3,6-
tetrahydropyridine (MPTP) model of PD was used. A scaled version
of the human DBS lead was implanted in the subthalamic nucleus
(STN), and LFPs from the STN were recorded differentially from
two DBS contacts, processed in real-time, and used to control the
timing of stimulation at an adjacent contact. High frequency stimula-
tion (135 Hz) was delivered whenever the amplitude of beta-band
LFP envelope was above a predetermined threshold level. The rela-
tive efficacy of CL-DBS, tDBS and off-DBS conditions were com-
pared using blinded rating scales and objective measures of motor
performance during a cued reaching task.
Results: CL-DBS was as effective as tDBS at reducing rigidity in
the contralateral limbs. However, CL-DBS was not as effective as
tDBS in improving performance on the reaching task, as measured
 POSTER SESSION
by total movement time. Physiology recordings revealed that the
beta-band envelope sharply decreased during the cued reach, such
that in the CL-DBS condition stimulation was least likely to be
delivered during the reach and beginning of the return epoch.
Conclusions: Our results illustrate the importance of using multi-
ple objective measures when comparing new and traditional DBS
methods, and also motivate exploration of more robust biomarker
sites and signals for closed-loop DBS, such as oscillations in other
frequency bands (e.g. gamma) or relationship between frequency
bands. The model we developed will be extremely useful to investi-
gate the optimal parameters for feedback control of DBS and to
understand the neural mechanisms underlying the therapeutic benefit
of DBS.
92
The sex-specific role of biometals in the risk of Parkinsons
disease
M.J. Kim, J.Y. Lee, J. Kim, K. Kim, H.S. Ryu, A.I. Bush, S.J. Chung
(Seongnam, Korea)
Objective: To investigate the association between biometals and
the risk of Parkinsons disease (PD) and clinical characteristics of
PD.
Background: There has been growing evidence of the participa-
tion of biometals in neurobiological processes, such as the regulation
of synaptic transmission and abnormal protein aggregation. However,
experimental and clinical evidence for the association of biometals
with PD is still limited.
Methods: We studied 325 patients with PD (175 men and 150
women) and age- and sex-matched 304 controls (141 men and 163
women). We collected clinical data of PD patients, including age at
onset of PD, disease duration, Hoehn and Yahr stage (H-Y stage),
motor fluctuation, dyskinesia, freezing, hallucination, and mini-
mental status examination (MMSE) score. The levels of biometals
(iron, copper, zinc, cobalt, and strontium) in serum were assayed by
inductively coupled plasma-mass spectrometry.
Results: The age at onset of PD was 58.26 6 9.20 years
(mean 6 SD) and the duration of PD was 6.95 6 4.63 years. The
mean H-Y stage was 2.3. The serum level of copper was significantly
lower in PD patients compared with controls (13.40 6 2.43 lmol/L vs
13.88 6 2.62 lmol/L, respectively; P 5 0.016), but this difference was
not significant in sex-specific analyses (men-only and women-only
analyses). The serum levels of cobalt and strontium were not different
between PD patients and controls in overall analysis. In women-only
analysis, the serum level of cobalt was significantly higher in PD
patients compared with controls. In men-only analysis, the serum level
of strontium was lower in PD patients compared with controls. The
higher serum level of copper (OR 5 1.26, 95% CI 5 1.04 - 1.53,
P 5 0.019) and the lower serum level of iron (OR 5 0.88, 95%
CI 5 0.82 - 0.95, P 5 0.001) increased the risk of dyskinesia in
women-only analysis, with adjustment for age, disease duration and
H-Y stage. The serum level of copper was negatively correlated with
MMSE score in PD patients (b=-0.151, P 5 0.006). The serum level
of cobalt was positively correlated with disease duration in women-
only analysis and H-Y stage in men-only analysis.
Conclusions: This study showed a sex-specific association
between biometals and PD risk and clinical characteristics of PD.
Further experimental studies are needed to confirm these findings.
93
Leukocyte b-glucocerebrosidase and b-hexosaminidase activity is
not altered in sporadic and genetic Parkinsons disease
H.J. Kim, B.S. Jeon, J.Y. Kim, H. Park, W.W. Lee, C.W. Shin (Seoul,
Korea)
Objective: To examine whether the activity of b-
glucocerebrosidase and b-hexosaminidase in peripheral blood leuko-
S39
cyte of patients with sporadic and genetic Parkinsons disease is
altered compared with healthy subjects.
Background: Mutations in GBA is one of the most common
genetic risk factor for Parkinsons disease (PD). The proposed patho-
mechanisms by which GBA mutation leads to the development of
PD is impaired degradation of pathologic a-synuclein and subsequent
accumulation of toxic a-synuclein species and formation of Lewy
body. In this regard, it is tempting to hypothesize that b-
glucocerebrosidase activity is decreased even in patients with spo-
radic PD without GBA mutation.
Methods: Fifty-one patient with PD or Parkinsonism (36 patients
with sporadic PD, 5 patients with PARK2 mutation, and 10 patients
with spinocerebellar (SCA) 17 with Parkinsonism) and 20 healthy
controls were included. Activity of b-glucocerebrosidase and b-
hexosaminidase in peripheral blood leukocyte was measured using
standard protocol used in the screening test for Gauchers disease.
Results: There was no difference in the age between patients and
controls. Neither activity of b-glucocerebrosidase nor b-
hexosaminidase in peripheral blood leukocyte was different between
patients and control. Subgroup analysis also showed that the activity
of both enzymes in patients with sporadic PD, PARK2 mutation, and
SCA17 with Parkinsonism was not different from that in controls.
This was also true when only the patients with sporadic PD with
abnormal FP-CIT-PET (n527) were counted.
Conclusions: The activity of b-glucocerebrosidase and b-
hexosaminidase in peripheral blood leukocyte does not differentiate
the patients with PD from healthy controls.
94
3D-EM characterisation of axonal swellings in the engrailed-1
heterozygous mouse model of Parkinsons disease
Z. Kurowska, G.J. Kidd, E. Benson, P. Brundin, S. Medicetty, B.D.
Trapp (Cleveland, OH, USA)
Objective: Our goal was to better characterize swellings of mid-
brain dopaminergic axons in the Engrailed-1 heterozygous mouse
model of Parkinsons disease.
Background: Engrailed-1 (En1) is a transcription factor impor-
tant for development and maintenance of dopaminergic neurons.
Polymorphisms in this gene are associated with sporadic PD. En11/-
mouse model presents slow progressive degeneration of nigro-striatal
pathway. Between 2 and 8 weeks of age, before most of other path-
ologies can be detected, progressive dopaminergic terminal defects
(axonal swellings) in En11/- mice accumulate.
Methods: 3-dimentional electron microscopy (3D-EM) and
immunohistochemistry of dopaminergic axons in dorso-medial stria-
tum at 2, 4, and 8 weeks in En11/- mice.
Results: Several weeks before the cell bodies of nigral dopamine
neurons degenerate, their terminals become dystrophic, swollen and
filled with electron dense bodies consistent with abnormal autophagic
vacuoles. We have measured the size of the swellings and identified
three different types of swellings: early, immediate and mature,
based on their size and morphology.
Conclusions: Our findings support a progressive retrograde degener-
ation of En11/- nigrostriatal neurons, akin to what is suggested to occur
in PD. We conclude that using axonal swelling quantification in En11/-
mouse is highly relevant for testing PD-related therapies, as indicated by
a pathological progression that closely mimics that in patients.
95
Metabolomic biospecimen analysis for measuring PD progression
P.A. LeWitt, J. Li, M. Lu, L. Guo, P. Auinger (West Bloomfield, MI,
USA)
Objective: To determine if untargeted profiling of small-molecule
(<1.5 kDa) constituents of CSF and plasma can yield useful state
biomarkers of PD.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S40 POSTER SESSION
Background: Since PD is associated with mitochondrial and
other metabolic alterations, metabolomic analysis (measuring hun-
dreds of biochemicals present in minute concentrations) has the
potential for recognizing disease-specific patterns that might offer
correlations to PD severity and insight into the disease process.
Methods: Specimens were collected from 49 unmedicated
DATATOP study PD subjects. CSF and plasma was sampled twice
using a standardized protocol (at up to 24 months apart) and at times
when UPDRS ratings were conducted. Assays used ultrahigh-
performance liquid chromatography combined with tandem mass
spectrometry. A spectral reference library provided chemical identifi-
cations. Data underwent extensive curation and quality-control meas-
ures before application of several bioinformatics statistical
approaches.
Results: From 1st to 2nd specimen collections, the data provided
indications for decreased efficiency in glucose and fatty acid metabo-
lism, elevated oxidative stress, and variation in gut microflora metab-
olism. To find a panel of biospecimen constituents that predicted
changes over time and in UPDRS Parts 2 1 3 scores, marker selec-
tion in CSF and plasma samples was conducted using Least Absolute
Shrinkage and Selection Operator (LASSO). Compounds chosen by
LASSO were fitted into a multiple linear regression. A composite
index was created, based on each markers coefficient (and which
was a linear combination of concentrations for each of the markers).
We found that, for plasma constituents, the correlation coefficient
was highly positively correlated with measured change in UPDRS
Parts 2 1 3 scores (0.87 for 15 compounds, p52.2e-16), while for
CSF, the correlation coefficient was only moderately positively cor-
related (0.58 for 3 compounds, p51.3e-5). There was no biomarker
differentiation of two PD clinical sub-types (postural instability-gait
disorder as compared with tremor-dominant Parkinsonism). A metab-
olomic pathway analysis of the data was not informative.
Conclusions: Metabolomic profiling of PD plasma specimens
provided findings that were highly predictive of PD severity. Our
data detected a panel of biomarkers that could be useful for gauging
PD progression in easily-sampled biospecimens.
96
Freezing of gait early in Parkinsons: Atypical versus typical
Parkinsons disorders
A. Lieberman, A. Deep, R. Dhall (Phoenix, AZ, USA)
Objective: Freezing of Gait Early in Parkinson: Atypical versus
Typical Parkinsons Disorders.
Background: Freezing of gait (FOG) is an episodic, often dra-
matic, gait pattern characterized by an abrupt inability to walk, in
which the patients feet appear to be stuck, while the upper body
often continues to move. The events preceding and during a freezing
episode are characterized by a decrease in postural stability, a
decrease in step length, a decrease in range of movement of the hips,
knees, and ankles, and an increase in fall risk.
Methods: 850 patients were examined at Muhammad Ali Parkin-
sons Center (MAPC) with a diagnosis of Parkinsons disease (PD)
over a period of 18 months.
Results: Among 850 patients, 212 patients (25%), had had PD
for < 5 years, and 27 of these (12.7%) had freezing of gait (FOG).
Among the 850 patients 40 patients, 4.7% of the total, had atypical
Parkinsonism. Among these 40 patients, all of whom had had symp-
toms for  5 years, 12 had FOG.
FOG improved with levodopa treatment in 21/27 patients with
typical PD, but FOG did not improve with levodopa in the 12
patients with atypical PD. Although FOG appears to be a problem in
locomotion, our results suggest that impaired postural stability rather
than impaired locomotion is the main problem, and balance training
rather than gait training is more likely to be helpful in patients with
FOG.
Conclusions: Primary progressive freezing of gait (PPFG) is
viewed as arising from a disconnection between the frontal lobes and
Movement Disorders, Vol. 30, Suppl. 1, 2015
basal ganglia. In three patients with PPFG, whose FOG did not
respond to levodopa, DaTscans revealed an absence of presynaptic
dopamine in the basal ganglia.
97
Neuroprotective effects of sodium butyrate against rotenone
neurotoxicity in both wild-type and VMAT2 heterozygote
knockout mice
L. Liu, N. Xiong, J. Huang, G. Zhang, X. Xu, C. Han, J. Li, H.
Jiang, J. Yang, Y. Shen, T. Wang (Wuhan, Peoples Republic of
China)
Objective: To examine whether administration of sodium butyr-
ate can exert significant neuroprotective effects in animal model of
Parkinsons disease (PD) induced by chronic rotenone administration
in both wild-type and VMAT2 heterozygote knockout mice.
Background: Previous studies indicate that VMAT2-deficient
mice display motor deficits and progressive neurodegeneration in the
substantia nigra, as observed in PD. Histone deacetylase (HDAC)
inhibitors have recently become a promising therapeutic candidate in
PD and other neurodegenerative diseases because there is growing
evidence that HDAC inhibitors can exert neuroprotective effects by
various mechanisms. Sodium butyrate, a HDAC inhibitor, has shown
efficacy for neuroprotection in animal models of stroke and Hunting-
tons disease.
Methods: Wild-type and VMAT2 heterozygote knockout male
C57BL/6 mice aged 12-months were divided into the following
groups: rotenone-administrated (30 mg/kg/d, p.o.) and rotenone-
administrated (30 mg/kg/d, p.o.) with sodium butyrate (0.3 g/kg/d,
i.p.) for eight weeks. Then, animals were subjected to behavioral
(Rotarod and pole test), neurochemical (striatal content of DA,
DOPAC and HVA) and immunohistochemical (tyrosine hydroxylase,
a-synuclein and ubiquitin) evaluations.
Results: Administration of sodium butyrate significantly attenu-
ated rotenone-induced motor deficits, depletion of striatal dopamine
and loss of tyrosine hydroxylase-positive neurons in the substantia
nigra in both wild-type and VMAT2 heterozygote knockout mice.
Moreover, administration of sodium butyrate significantly reduced
accumulation of a-synuclein and ubiquitin in dopaminergic neurons,
which was elevated in rotenone-treated mice.
Conclusions: Our study indicates that sodium butyrate, a well-
known HDAC inhibitor, exerts neuroprotective effects through mod-
ulation of a-synuclein expression in both wild-type and VMAT2 het-
erozygote knockout mice treated by rotenone. These findings provide
further evidence that administration of sodium butyrate may be a
promising approach for the treatment of PD.
98
Risk of Parkinsons disease onset in patients with diabetes,
hypertension, dyslipidemia and obesity in Mexican population
R. Llorens-Arenas, M. Rodriguez-Violante, A. Cervantes-Arriaga, H.
Calderon-Fajardo, G. Neri-Nani, R. Millan-Cepeda, I.E. Estrada-
Bellmann, D. Pi~na-Fuentes, G. Pagano, M. Tagliati (Mexico City,
Mexico)
Objective: To describe the prevalence of metabolic comorbidities
(hypertension [HT], diabetes [DM], dyslipidemia [DL], and obesity)
in Mexican PD patients. To establish associations between these
comorbidities and the occurrence of PD and its clinical course.
Background: Previous studies have suggested an association
between PD and metabolic comorbidities. However, the evidence is
inconclusive and contradictory, with both risk and protective effects
reported. The prevalence of these comorbidities in Mexican general
population is 9.2% for DM, 13% for DL and 32% for HT.
Methods: Patients from the Mexican PD Registry (ReMePARK)
were enrolled from February through October 2014. Demographic
data and history of comorbidities were recorded. Blood analysis was
 POSTER SESSION
performed screening for DM, DL and end organ damage. Results
from the National Health and Nutrition Survey 2012 were used as
controls. T test and OR were calculated to compare prevalence of
comorbidities between PD patients and general population. In the
subgroup of patients in which comorbidities were diagnosed at least
1 year prior to the onset of PD a covariate analysis was performed to
determine the effect of these comorbidities and the blood results on
the clinical course, correlating with LEDD, MDS-UPDRS, Hoehn-
Yahr scale, NMSS and SEND-PD.
Results: 452 patients were recruited. Prevalence of comorbidities
was 33.6% for HT, 14.2% for DM, 19.5% for DL, 41.6% for over-
weight, and 20.3% for obesity. Both HT and DM were diagnosed
significantly earlier than the onset of PD, at least 1 year prior to its
onset. Patients had significantly higher prevalence of HT (OR 2.11,
p < 0.0001, CI 95% 0.11-0.53), DM (OR 1.54, p < 0.001, CI 95%
1.33-2.12), DL (OR 1.50, p < 0.001, CI 95% 1.39-2.06), and over-
weight (OR 1.45, p < 0.0001, CI 95% 1.65-2.12) compared to gen-
eral population. Covariate analysis did not establish associations
between comorbidities or blood test results and clinical course.
Conclusions: DM, HT, DL and overweight are significantly higher
in PD patients than in general population. These comorbidities are
diagnosed prior to the onset of PD, suggesting altered metabolic path-
ways as possible risk factors. Nevertheless, the presence and severity
of these comorbidities does not seem to influence the clinical presenta-
tion of PD. Further studies are warranted to clarify these associations.
99
Measurement of CSF proteins suggested by gene expression
studies as potential Parkinsons disease biomarkers
D. Loeffler, P. LeWitt, J. Aasly, L. Smith, M. Coffey (Royal Oak, MI,
USA)
Objective: To determine if cerebrospinal fluid (CSF) concentra-
tions of 5 proteins previously identified by gene expression studies
as PD biomarker candidates, and/or the concentration of nrf2, a key
activator of anti-oxidant mechanisms, might offer potential PD
biomarkers.
Background: No reliable biomarkers have been found for early
diagnosis of PD or its neuropathological progression. A previous
study (Molochnikov et al., 2012) identified 5 genes as optimal pre-
dictors of PD: aldehyde dehydrogenase family 1 subfamily A1
(ALDH1A1), heat shock 70-kDa protein 8 (HSPA8), p19 S-phase
kinase-associated protein 1A (SKP1A), huntingtin interacting
protein-2 (HIP-2), and 19S proteasomal protein PSMC4. A sixth pro-
tein, nuclear factor (erythroid-derived 2)-like 2 (nrf2), was included
in this study because it is a major antioxidant response regulator.
Methods: ELISAs were used to measure SKP1A, ALDH1A1,
HSPA8, PSMC4, HIP2, and nrf2 in CSF samples from subjects with
idiopathic PD (n 5 20), Parkinsonian LRRK2 gene mutation carriers
(n 5 9), healthy non-Parkinsonian LRRK2 carriers (n 5 20), aged
subjects with other neurological disorders (n 5 16), and healthy aged
control subjects (n 5 19).
Results: Only HSPA8 and nrf2 were detected; no statistically sig-
nificant differences between groups were found for concentrations of
either protein. HSPA8 and nrf2 levels were weakly associated
(rho 5 -.30) for all subjects. When associations between the two pro-
teins were examined for subgroups formed by diagnostic group or
gender, moderate negative associations were detected for women
(rho 5 -.51; p 5 .001) and for PD of either type (rho 5 -.42;
p 5 .023).
Conclusions: Our inability to detect SKP1A, ALDH1A1,
PSMC4, and HIP2 in CSF underscores obstacles in PD CSF
hypothesis-driven biomarker studies: proteins identified as potential
biomarkers based on brain or blood studies may not be detectable in
CSF, and if they are detectable, their measurements may not reflect
their alterations in PD brain. The negative association in PD patients
between HSPA8, which binds to newly formed proteins to facilitate
correct folding, and nrf2, a regulator of the response to oxidative
S41
stress, is intriguing and will be examined in additional CSF samples.
Longitudinal CSF measurements of these proteins are planned to
evaluate possible PD progression-related changes.
100
Gait outcomes characterize people with Parkinsons disease who
transition to falling within the first year
S. Lord, D. Burn, L. Rochester (Newcastle upon Tyne, United
Kingdom)
Objective: To compare the clinical features of people with Par-
kinsons disease (PD) who transition to falling within 12 months
from diagnosis with those of non-fallers.
Background: Falls are common in PD and associated with loss
of independence and mortality. Understanding the evolution of falls
from diagnosis will assist in accurate prediction and effective early
management.
Methods: One hundred and twenty-one consecutive incident PD
subjects were assessed in Newcastle-upon-Tyne as part of the
ongoing ICICLE-GAIT study, a collaborative study with ICICLE-
PD. Falls data were collected in newly diagnosed PD prospectively
over 12 months via a falls diary and telephone follow-up. A compre-
hensive battery of motor, cognitive, self-efficacy and gait measures
was used to assess performance and Mann-Whitney U test examined
differences between new fallers and non-fallers. Participants who
self-reported falling at baseline were not included in the analysis.
Results: At 12 months, 70 subjects were non-fallers and 27 were
new fallers. Respective age was 67.4 6 9.3 v 69.4 6 10.9 years;
UPDRS score 24.3 6 10.5 v 24.4 6 9.1 and PIGD score .53 6 .33 v
.71 6 .36. Time to first fall was positively skewed, with mean (and
SD) of 92 days. Significant differences were found for PIGD score
(P 5 0.019), stance time variability (P 5 0.028), and step time and
stance time (P 5 0.047) and (P 5 0.033) respectively.
Conclusions: These (preliminary) results suggest that gait out-
comes discern new fallers from non-fallers one year after diagnosis
of PD. Cognitive outcomes were not significantly different between
groups. This may change as disease advances and non-motor symp-
toms emerge. Additional analysis will report prospective falls data
over 30 months and identify predictors of first fall.
101
Effect of visual cue timing on gait initiation in Parkinsons with
freezing of gait
C. Lu, S. Amundsen, P. Tuite, J. Vachon, C.D. MacKinnon
(Minneapolis, MN, USA)
Objective: The purpose of this study was to examine the effect
of different visual cue timings on anticipatory postural adjustments
(APAs) preceding and accompanying gait initiation in Parkinsons
disease (PD) patients with and without freezing of gait (FOG).
Background: External cueing can markedly facilitate movement
initiation or unfreeze the patients with FOG, even when they are
off medication. These observations provide compelling evidence that
PD patients retain the capacity to initiate movement via non-
dopaminergic pathways. However, the utility of using cues is com-
promised by inconsistency of effects and habituation. Currently there
are no guidelines or standardized protocols for how cues should be
presented to patients with FOG.
Methods: We studied twenty patients with PD, 11 freezers and 8
non-freezers, in the off medication state. Step initiation was visually
cued using three different instructed-delay (warning go) timing
protocols: fixed delay period (3 s), random delay period (4-12 s) and
countdown (3-2-1-go, 1 s between cues). Subjects also performed
self-initiated stepping trials. The primary dependent APA timing var-
iables were: time to peak amplitude of the stepping foot loading
force, and initial excursions of the net center of pressure in both the
mediolateral (COPml) and anteroposterior (COPap) directions. Data
Movement Disorders, Vol. 30, Suppl. 1, 2015
S42 POSTER SESSION
were analyzed using a 2 x 4 repeated measures analysis of variance
with factors of group and cue timing (fixed delay, random delay,
countdown and self-initiated).
Results: There was a significant main effect (p<0.005) of cue
timing for all APA timing variables. Post-hoc tests showed that the
time to peak loading of the stepping leg and peak excursions of the
CoP in the lateral and posterior directions were significantly reduced
in the countdown and fixed-delay compared with the self-initiated
condition (p < 0.009). Loading force and COPap timing were also
significantly improved for the countdown compared with the random
delay condition (p < 0.024).
Conclusions: The data demonstrate that visual cueing protocols
that incorporate predictive timing (countdown and fixed delay)
improve the timing of APAs compared to self-initiated steps in both
freezers and non-freezers.
102
Reduction of alpha-synuclein in the substantia nigra of the non-
human primate results in neurodegeneration
F.P. Manfredsson, D.E. Redmond, Jr., J.W. Lipton, R.M. Malpass,
T.J. Collier (Grand Rapids, MI, USA)
Objective: To determine whether loss of functional alpha-
synuclein (a-syn) is a causative event in dopaminergic
neurodegeneration.
Background: a-syn aggregation and pathology is integral to both
idiopathic and familial Parkinsons disease (PD). The correlation
between a-syn and PD has led many to describe aggregates as
directly toxic, resulting in efforts to eliminate a-syn as a therapy for
PD. However, removal of a-syn from rodent nigral neurons via
recombinant adeno associated virus (rAAV)-mediated delivery of a-
syn shRNA results in neurodegeneration. Thus, we formulated the
hypothesis that a-syn aggregates are not directly toxic; rather a-syn
aggregation produces toxicity by reducing levels of functional a-syn.
This hypothesis was tested by reducing a-syn expression in midbrain
neurons of the non-human primate.
Methods: African Green monkeys (n51) were injected unilater-
ally in the substantia nigra (SN) with low (5E12 vector genomes
(vg)/ml) or high (2E13vg/ml) titer AAV2/5 expressing a shRNA
designed against a-syn or scrambled (SCR) shRNA as control. The
vectors also contained GFP as a transduction marker. Animals were
monitored for behavioral deficits indicative of nigrostriatal denerva-
tion for three months until sacrifice. Brains were analyzed for striatal
catecholamine content and neuropathology of the SN.
Results: The animal treated with high-dose a-syn shRNA exhib-
ited a progressive deficit in a summary score of healthy behaviors,
but no increase in overt Parkinsonian signs. Analysis of tissue indi-
cated that all a-syn shRNA treated animals exhibited reduced striatal
dopamine levels. Reductions in TH1 neurons were observed prefer-
entially in the ventral tier of the a-syn shRNA treated SN. No such
decrements were observed in animals treated with equivalent doses
of a SCR-shRNA. GFP1 neurons were observed throughout the SN
of SCR-shRNA treated subjects. In contrast, GFP was only seen in
dorsomedial neurons of a-syn shRNA treated animals, ostensibly due
to the loss of ventral tier TH1 neurons. Additionally, a loss of TH
phenotype as measured by several TH-/neuromelanin1 neurons was
observed with a-syn shRNA treatment.
Conclusions: Our findings indicate that non-human primate nigral
dopamine (particularly ventral tier) neurons are sensitive to the loss of
a-syn. This sensitivity is not due to non-specific shRNA toxicity. Our
results suggest that (functional) a-syn is crucial to neuronal survival.
103
Iron and oxidative stress in Parkinsons disease: In search of
injury biomarkers
M.S. Medeiros, M.R. Fighera, A.S. Schuh, C.M. Rieder (Porto
Alegre, Brazil)
Movement Disorders, Vol. 30, Suppl. 1, 2015
Objective: To determine peripheral levels of iron, ferritin and
transferrin in Parkinsons disease (PD) patients and to evaluate
whether iron accumulation in the substantial nigra (SN) could be
related to serum levels. To determine reliable peripheral biomarkers
of oxidative/nitrative stress.
Background: Parkinsons disease pathophysiology is associated
with oxidative/nitrosative stress. Iron accumulates in the SN of PD
patients and is related to this damage along with oxygen and nitro-
gen reactive species (ROS, RNS) through Fenton reaction. ROS and
RNS are normally produced in cell and inflammatory processes and
are controlled by antioxidant systems.
Methods: Forty PD patients and 46 controls were selected to
compare serum levels of iron, ferritin, transferrin and oxidative/nitra-
tive stress biomarkers: superoxide dismutase (SOD), catalase, nitric
oxide (NOx), thiobarbituric acid reactive substances (TBARS), non-
protein thiols, advanced oxidation protein products (AOPP), ferric
reducing ability of plasma (FRAP), NTPDases (ATP and ADP),
ecto-5-nucleotidase, adenosine deaminase (ADA), myeloperoxidase,
ischemic-modified albumin (IMA) and vitamin C.
Results: Iron levels were decreased in patients with PD, while
ferritin and transferrin were not different. Oxidative stress bio-
markers such as TBARS, AOPP, NTPDases, IMA and myeloperoxi-
dase were significantly higher in PD patients, while FRAP, vitamin
C and non-protein thiols were significantly lower. SOD, catalase,
ecto-5-nucleotidase were not different between the groups and bio-
markers NOx and ADA were significantly increased in controls. No
correlation was found between biomarkers and sociodemographic
and disease characteristic data.
Conclusions: Plasmatic levels of iron are decreased in patients
with PD compared to healthy controls. Biomarkers TBARS, AOPP,
NTPDases, IMA and myeloperoxidase presented as reliable to mea-
sure oxidative/nitrative damage, while non-protein thiols, FRAP and
vitamin C show a significant decrease in the antioxidant capacity in
PD.
104
Hypochlorite converts dopamine into redox cycling cytotoxic
products
N.J. Mehta, K.A. Beningo, D. Njus (Detroit, MI, USA)
Objective: To study the redox cycling of dopamine oxidized
metabolites and investigate the mechanism by which they cause oxi-
dative stress and kill nerve cells.
Background: Parkinsons disease is caused by the death of dopa-
minergic neurons in the substantia nigra, but the reason those neu-
rons die is unknown. Contributing factors are thought to include
oxidative stress, mitochondrial dysfunction, dopamine oxidation and
microglial inflammation. Specific mechanisms relating these dispar-
ate factors have been elusive. The missing piece may be hypochlo-
rite, which we suggest plays a central role linking dopamine
oxidation, oxidative stress and microglial activation.
Methods: Redox Cycling Assay Redox cycling activity was
assayed as ascorbate-dependent oxygen consumption, monitored
using a Clark-type oxygen electrode.
Superoxide Assay Superoxide generation in cells was observed
using MitoSOX Red, a fluorogenic dye highly selective for detection
of superoxide in the mitochondria of live cells.
Trypan Blue Exclusion Assay Cell viability was determined
using 0.4% trypan blue 24 hours after the cells were exposed to the
desired concentration of redox cycler.
Results: Hypochlorite reacts with the dopamine oxidation prod-
ucts cysteinyl-dopamine and cysteinyl-DOPAC and converts them
into compounds that redox cycle and produce oxidative stress. In
fact hypochlorite is unique in its ability to form redox cycling com-
pounds; other oxidants such as hydrogen peroxide and Fe31 are not
effective. These redox cycling compounds are also formed in the
presence of myeloperoxidase and its substrates, H2O2 and Cl-, which
produces hypochlorite. The product made by hypochlorite treatment
 POSTER SESSION
of cysteinyl-dopamine is nearly as effective in the mitochondrial
redox cycling assay as the synthetic compounds 3-methyl-5-anilino
quinone and 9,10-phenanthrenequinone. These compounds all gener-
ate superoxide in cells as indicated by Mitosox Red fluorescence.
These compounds are also all cytotoxic at micromolar concentra-
tions, and the LD50 correlates with mitochondrial redox cycling
activity. Moreover, evidence suggests that cells undergo apoptosis
when treated with these dopamine metabolites.
Conclusions: This raises the possibility that hypochlorite, pro-
duced by microglial myeloperoxidase, creates redox cycling com-
pounds that lead to oxidative stress and the consequent death of
dopaminergic neurons in Parkinsons disease.
105
Association between locus coeruleus pathology and gait
dysfunction in Parkinsons disease: A clinical-pathological
preliminary analysis
K.A. Mills, Z. Mari, C. Bakker, G.M. Pontone, J.C. Troncoso, L.S.
Rosenthal (Baltimore, MD, USA)
Objective: To correlate the degree of Lewy body pathology and
neuronal loss in the locus coeruleus (LC) and degree of gait dysfunc-
tion seen in patients with Parkinsons disease (PD).
Background: Gait disorders such as freezing of gait (FOG),
hypokinetic stride, imbalance, and postural instability all increase the
risk for falls in PD. Impaired mobility is the largest factor determin-
ing a decline in quality of life and increased health care expendi-
tures. Animal studies suggest that norepinephrine secreted from the
locus coeruleus has a significant role in postural tone and
locomotion.
Methods: Clinical rating scales and brain pathology have been
collected prospectively as part of the Clinical Core of the Morris K.
Udall Center of Excellence for Parkinsons disease Research at Johns
Hopkins University. PD patients with at least one UPDRS score and
a timed up-and-go (TUG) score who participated in the longitudinal
brain donation study were included. UPDRS items 14 (freezing), 29
(gait), 30 (postural stability), and 31 (body bradykinesia), as well as
the TUG time were analyzed for association with Lewy body scores
in the LC and frontal lobe, LC neuronal loss or gliosis, LC pigment
loss, LC neurofibrillary tangles (NFT), and LC pallor using either
ordinal logistic regression, Chi-square, or ANOVA models.
Results: Of participants with a LC LB score and frontal LB
score, 15 subjects had at least one UPDRS Part III score and 14 sub-
jects had at least one TUG time. 46 participants had neuronal loss or
gliosis scores and a UPDRS or TUG score. FOG was positively asso-
ciated with the degree of neuronal loss or gliosis in the LC (LR
X2 5 7.17, p 5 0.03) and a trend for an association with LC LB score
(LR X2 5 7.13, p 5 0.07) was found. The presence of any Lewy
bodies in the LC was associated with more severe gait impairment
on the UPDRS Part III gait item (p 5 0.03). Surprisingly, an inverse
association between LC Lewy LB load and TUG time was found
(F 5 4.68, p 5 0.03). Neither frontal Lewy body load nor LC NFT
score was associated with any of the UPDRS gait measures or TUG
time.
Conclusions: Exploratory analysis of a longitudinal clinical-
patholological autopsy series indicates that LC Lewy body load and
neuronal loss may be associated with freezing of gait. The relation-
ship between LC pathology and gait speed is less clear and may war-
rant further investigation.
106
Differential effect of 6-OHDA on different regions of rat brain:
Oxidative stress and behavioral parameters
N. Mishra, D. Sharma, N. Mishra (New Delhi, India)
Objective: To evaluate (1) behavioral anomalies (motor behavior,
spatial cognition, fear, anxiety, emotional state and sociability) and
S43
(2) oxidative stress (superoxide dismutase=SOD, glutathione peroxi-
dase=GPx, glutathione reductase=GR, lipid peroxidation=LP, protein
oxidation=PO and total thiol content=TT), in different regions of rat
brain, in 6-OHDA rat model of Parkinsons disease.
Background: 6-hydroxydopamine (6-OHDA) has been widely
used to produce lesions in the rat brain, specially substantia niagra
pars compacta, and generate animal models of Parkinsons disease
for drug development and understanding the pathophysiology of the
disease. There have however, not been any exhaustive studies on the
effects of 6-OHDA on motor and non-motor behaviors associated
with the disorder as well as the oxidative stress generated in different
regions of the brain. This is important to assess the proximity of the
animal pathophysiology and the extent to which it can be extrapo-
lated to the human condition.
Methods: 4ll of 6-OHDA (5lg/ml) or saline was stereotaxically
administered to six male Wistar rats (6-8months) in the substantia
nigra. After two weeks of recovery, righting reflex, open field test,
Morris water maze test, light and dark chambered test and three
chambered social behavior test were performed. Thereafter, animals
were sacrificed; their brains micro-dissected into hippocampus,
amygdala, cortex, midbrain, cerebellum and medulla. SOD, GR,
GPx, LP, PO and TT were estimated. Data were expressed as mean
standard deviation (S.D.) Statistical comparison was performed by
Students t- test followed by Holm-Sidak pairwise analysis.
Results: There was 2fold decline in motor function, 20fold
greater mean latency time, 5fold more fear, anxiety and emotional
anomaly in the test rats as compared to the controls. All rats were
social but the test rats had preference for social novelty as apposed
to controls that showed greater inclination towards the familiar rat.
Greater oxidative stress was generated in all parts of the rat brain as
compared with the controls (SOD=1.5fold, GPx=1.5fold, GR=2fold,
LP=2fold, PO=2fold, TT=1.5fold; average of all brain regions).
Conclusions: Our data suggests sustained effects of 6-OHDA in
the rat brain and on the behavior of the animal, and this model can
be extrapolated to the human Parkinsons disease state.
107
Turning the head red: Intracranial application of near-infrared
light improves behaviour and is neuroprotective in a non-human
primate model of Parkinsons disease
J. Mitrofanis, C. Moro, F. Darlot, N. El Massri, D.M. Johnstone, C.
Chabrol, C.L. Peoples, H.D.T. Anastacio, F. Reinhart, D. Agay, N.
Torres, T. Costecalde, V.E. Shaw, J. Stone, A.L. Benabid (Sydney,
Australia)
Objective: To examine whether intracranially delivered near-
infrared light (NIr) treatment improves the behaviour and neuropro-
tects midbrain dopaminergic cells in the MPTP (1-methyl-4-phenyl-
1,2,3,6-tetrahydropyridine) monkey model of Parkinsons disease.
Background: NIr has been shown to be an effective neuroprotec-
tive agent in various rodent models of Parkinsons disease (Johnstone
et al; ChronoPhysiology & Therapy, 2014:4 1-14). In this study, we
show - for the first time - that NIr has positive therapeutic effects in
the much larger primate brain. We used an intracranial optical fibre
device, one that delivered sufficient NIr signal to the diseased dopa-
minergic cells located deep in the brain of macaque monkeys.
Methods: A NIr laser (670nm) optical fibre device was implanted
surgically into the midline midbrain of macaque monkeys, close to
the substantia nigra of both sides. MPTP injections (1.5-2.1kg total)
were then made over a five to seven day period, during which time
the NIr device was turned on (5sec/60sec; 10mW power; global dose
of 25-35J). This was followed by a three week survival period. Mon-
keys were evaluated clinically for motor activity and their brains
were processed subsequently for immunohistochemistry and stereo-
logical analysis.
Results: The MPTP-NIr-treated monkeys (n59), although not
quite to control levels, achieved substantially better clinical scores
(80%) than the MPTP-treated monkeys (n511). The NIr was not
Movement Disorders, Vol. 30, Suppl. 1, 2015
S44 POSTER SESSION
toxic to the surrounding brain tissue and neuroprotected many dopa-
minergic cells (30-40%) and their striatal terminations (40%) against
MPTP insult. The neuroprotective effect was stronger in the lower
MPTP dose regime (1.5mg/kg) than the higher one (2.1mg/kg).
Conclusions: NIr improved behaviour dramatically and was neu-
roprotective after MPTP insult, particularly at milder doses. Our find-
ings indicate NIr as an effective therapeutic agent in a primate model
of the disease and lay the template for translation into clinical trial.
108
The effects of dual task on finger tapping in Parkinsons disease
A. Miyake, T. Yamamoto, T. Furuya, K. Ikeda, K. Takahashi, N.
Tamura, N. Araki (Iruma-gun, Japan)
Objective: To evaluate quantitatively repetitive finger tapping
(FT) performance during a repetitive pronation-supination of the
forearm and to clarify the relationship between the changes of FT
motion by dual task and severity of Parkinsonian symptoms.
Background: Decreased performance of FT during dual task has
been well known in patients with Parkinsons disease. However, it is
not clear what components of FT motion are impaired.
Methods: The subjects consisted of 23 patients with PD and age-
matched 13 healthy controls. The motion of finger- to-thumb tapping
with the rigid dominant side hand for 10 sec was recorded with
high-speed video camera, with and without simultaneous pronation-
supination of the opposite side forearm. Key parameters for a cycle
of FT were finger separation amplitude, velocity, and duration, as
well as the coefficient of variation [CV; (standard deviation)/(mean
value) 3100)] of these parameters. To find the relationship between
each parameter of the FT motion and severity of Parkinsonian symp-
toms, PD patients were divided into two groups based on disease
duration ( 6Y, 6Y >) and UPDRS part III scores ( 25, 25 >),
and those parameters were compared between the two groups.
Results: I. PD patients:1. Amplitude was decreased and its CV
was increased by dual tusk (p<0.05, p<0.05, respectively). 2. Veloc-
ity and its CV did not change. 3. Duration showed no change, but its
CV was increased (p<0.05). II Controls: 1.Amplitude did not
change, but its CV was increased by dual tusk (p<0.05); the change
was smaller as compared to that in PD patients. 2. Velocity slowed
and its CV was increased (p<0.05, p<0.05). 3.Duraition was
increased (p<0.05) and its CV did not change. III There was no rela-
tionship between the changes of FT motion by dual task and disease
duration or UPDRS part III scores in all parameters.
Conclusions: 1. The differences in the changes of FT perform-
ance by dual tusk between PD patients and controls may be caused
by dysfunction of the basal ganglia.
2. The Impaired FT performance may have already existed in the
earlier stage of PD.
109
Detection and quantification of freezing of gait and falls in
Parkinsons disease patients using a wearable motion sensor
Y. Okuma, H. Mitoma, M. Yoneyama (Izunokuni, Japan)
Objective: The aim of the present study is to objectively detect
and quantify freezing of gait (FOG) and falls in Parkinsons disease
(PD) patients during everyday activities.
Background: FOG and recurrent falls are disabling features of
PD and have a significant negative impact on the patients quality of
life. Recently, we have found that FOG is the most common cause
of falls in advanced PD. However, there are few objective methods
for detecting FOG and falls outside of the clinic.
Methods: Patients were selected from among 36 patients who par-
ticipated in our previous prospective study on falls. We developed a
motion recorder (body-fixed 3D accelerometer) with a long-lasting
battery. First, healthy volunteers simulated FOG and falls, and accel-
eration signals were analyzed. Then movements of recurrent PD fall-
Movement Disorders, Vol. 30, Suppl. 1, 2015
ers with severe FOG were recorded during their everyday activities
and in the outpatient clinic. A newly developed freezing index (cross
correlation calculation based on pattern matching) was also calculated
and compared with the previous index (ratio of power spectrum).
Results: Characteristic patterns of acceleration signals were
recorded for simulated falls. Falls were associated with abrupt
changes in trunk angle. Knee trembling was recorded as a rapid
oscillation of acceleration, and the freezing index increased during
knee trembling. In PD patients, actual falls in everyday life were
also detected as abrupt trunk angle changes, and knee trembling was
recorded when patients reported FOG-induced falls. The freezing
index increased during the start and turning hesitations, similarly to
the index calculated using methods proposed by Moore et al.
Conclusions: Motion recording using our wearable sensor is use-
ful for detecting FOG and falls in everyday life in PD fallers, and cal-
culating the freezing index may improve the quantification of FOG.
110
Humoral response against small heat shock proteins in
Parkinsons disease
E. Papuc, E. Kurys-Denis, W. Krupski, K. Rejdak (Lublin, Poland)
Objective: The aim of the study was to check whether Parkinsons
disease (PD) has the ability to elicit immune response against small
heat shock proteins (sHSP), subsequent to their increased expression.
Antibodies titers against HSP60 and alpha B-crystallin were assessed.
Background: HSPs are functionally and immunologically highly
conserved molecules present in almost all living organisms. Their
expression in the cell increases under the circumstances that are
potentially harmful to cells, for example, high temperature. This
increased HSP expression is present in cells exposed to mild stress
and this protects them against subsequent stress. Anti-HSP antibodies
are present in different disorders with involvement of inflammatory
process. In the light of evidence for the increased heat shock proteins
expression in neurodegenerative disorders, the presence of the adapt-
ive humoral response of the immune system can be expected.
Methods: IgG and IgM autoantibodies against alpha B-crystallin
were assessed in 26 PD patients 26 healthy subjects. Serum samples
from PD patients were collected twice, at baseline and after mean of
13 months follow up. For the assessment of anti-HSP IgG autoanti-
bodies serum samples from 31 Parkinsonian patients and 31 healthy
control subjects were collected.
Results: Both IgM and IgG autoantibodies against alpha B-
crystallin in PD patients were significantly higher compared to
healthy controls (p<0.05). We also found statistically significant
increase in antibodies titers against alpha B-crystallin over the time
of 13 months, both for IgG (p50.021) and for IgM (p<0.0001).
Additionally, PD patients presented higher levels of anti-HSP IgG
autoantibodies than healthy controls (p50.02).
Conclusions: Anti-HSP IgG autoantibodies belong probably to the
natural auto-antibodies, as they are present in healthy people, neverthe-
less chronic neurodegenerative process may have additional inducing
effect on humoral response involving anti-HSP autoantibodies, which is
reflected by significantly higher levels of anti-HSP 60 autoantibodies in
PD patients compared to healthy controls. Increase in IgG and IgM
antibodies titers against alpha B-crystallin over the investigated period
of time reflects activation of the immune response, probably secondary
to widespreading neurodegenerative process and may suggest the
involvement of the immune system in the disease progression.
111
Zinc dyshomeostasis underlies impairment of cellular energy
metabolism in ATP13A2 (PARK9)-associated Parkinsons disease
J.S. Park, B. Koentjoro, C.M. Sue (St. Leonards, Australia)
Objective: To investigate the pathophysiological effect of human
ATP13A2 deficiency, we assessed the change in Zn21 levels and its
 POSTER SESSION
effect on both mitochondrial and glycolytic function in ATP13A2-
deficient Kufor-Rakeb syndrome (KRS) patient-derived cell models.
Background: Mutations in ATP13A2 (PARK9) have been associ-
ated with KRS, an autosomal recessive early-onset, levodopa-respon-
sive Parkinsons disease (PD). Although ATP13A2 has been shown
to regulate Mn21 metabolism in yeast, its substrates in humans still
remain uncharacterised. Recently, we reported mitochondrial dys-
function in KRS patient cells harbouring compound heterozygous
ATP13A2 mutations (c.3176T>G/c.3253delC). However, the molec-
ular mechanism by which loss of ATP13A2 cause mitochondrial dys-
function is unknown.
Methods: We tested toxicity of several biometals in KRS patient-
derived human olfactory neurosphere cells and examined changes in
intracellular Zn21 levels ([Zn21]i). Then, we assessed the effect of
altered Zn21 levels on mitochondrial and glycolytic function in
these cells.
Results: Among the biometals tested, KRS patient cells showed
an increased sensitivity to Zn21. Subsequently, we identified low
[Zn21]i, altered expression of Zn21 transporters and impaired
sequestration of Zn21 into LC3-positive vesicles, indicating zinc
dyshomeostasis. Pharmacological treatments that increased [Zn21]i
induced the elevated production of H2O2 and aggravation of both
functional deficits and morphological changes in mitochondria that
resulted in ATP depletion and cell death. In addition, KRS patient
cells showed evidence of glycolytic dysfunction as demonstrated by
reduced glycolytic capacity and reserve in extracellular flux analysis,
reduced pyruvate/lactate production and NAD1/NADH ratio, which
were exacerbated by increased [Zn21]i. The toxic effect of Zn21
on mitochondrial and glycolytic function was efficiently blocked by
ATP13A2 overexpression, Zn21 chelation, promotion of mitochon-
drial fusion and treatment of an antioxidant and pyruvate.
Conclusions: Our data indicate that human ATP13A2 deficiency
results in zinc dyshomeostasis and impaired cellular energy metabo-
lism. These findings provide valuable insights into the molecular
mechanisms underlying zinc dyshomeostasis and its contribution to
impaired bioenergetic function in PD with ATP13A2 as a molecular
link between these two distinctive aetiological factors.
112
Impact of Levodopa and motor task on beta band coupling of
subthalamic nucleus and spinal motoneuron pool in Parkinsos
disease
R. Reese, F. Steigerwald, M.M. Reich, C. Matthies, I.U. Isaias, J.
Volkmann (Wuerzburg, Germany)
Objective: To describe the impact of movement task and dopami-
nergic medication on the oscillatory coupling between subthalamic
nucleus (STN) and spinal motor neurons in the beta frequency range
in Parkinsos disease (PD).
Background: Coupling of neuronal activity in the beta band (10-
30Hz) is common but its relevance in health and disease is contro-
versial. The degree and magnitude of beta band activity have been
positively correlated with the severity of the akinetic rigid (AR)
motor symptoms in PD.
Methods: We recorded local field potentials (LFP) from the STN
in six AR-PD patients via telemetry through a fully implanted system
for deep brain stimulation (DBS) 14 weeks after implantation. We
furthermore assessed the coherence between STN-LFP and contralat-
eral spinal motor neuron activity (EMG of the forearm extensors) in
two simple motor tasks: submaximal tonic wrist extension (tonic)
and self paced alternating wrist flexion and extension (alternate) in
motor OFF and motor ON (after a levodopa challenge; DBS OFF in
all conditions). The brain hemisphere exhibiting most prominent
STN beta band activity in the motor OFF resting state was chosen
for recordings (right n53, left n53). PD patients were selected for
STN-DBS by established clinical criteria and gave their written
informed consent. They were then asked to additionally participate
in the studies related to chronic LFP recordings. The study was
S45
approved by the local ethics committee. Medtronic provided all
materials and software under a research agreement.
Results: There was no significant modulation of STN beta band
power, neither by the motor task nor by Levodopa. STN-EMG coher-
ence in the lower beta band (10-20Hz) was suppressed by alternating
movements irrespective of the dopaminergic state (tonic vs. alternate:
motor OFF: p<0.0001, motor ON: p50.0001; Mann-Whitney-Test).
In medicated patients there was significantly stronger coupling com-
pared to motor OFF (tonic, motor OFF vs. motor ON: p50.0123).
Conclusions: Long-range beta band synchronisation between
STN and spinal motoneurons may subserve the control of sustained
postures and is facilitated by dopamine. This challenges the hypothe-
sis of beta band activity to be a state or disease marker in PD.
113
Mid-life milk consumption and substantia nigra neuron density
at death
G.W. Ross, R.D. Abbott, H. Petrovitch, K.H. Masaki, L.J. Launer,
L.R. White, J. Nelson, C.M. Tanner (Honolulu, HI, USA)
Objective: The purpose of this report is to examine the associa-
tion between mid-life milk intake and substantia nigra (SN) neuron
density in brains from an unselected series of deceased Honolulu-
Asia Aging Study participants.
Background: The bioaccumulation of organochlorine pesticides
in milk may partially explain findings of an association between the
intake of dairy products and the incidence of Parkinsons disease
(PD). Whether this association exists with early nigral degeneration,
a pathological hallmark of PD, is unknown.
Methods: Data on milk intake were collected in the Honolulu
Heart Program from 1965 to 1968 in 449 men aged 45 to 68 years
with later postmortem examinations. Autopsies were performed from
1992 to 2004. Neuron density (count/mm2) was measured in quad-
rants from a transverse section of the SN. Measures also included
brain residues of heptachlor epoxide, an organochlorine pesticide
reported to be found at excessive levels in the milk supply in
Hawaii.
Results: Neuron density in all quadrants was lowest in nonsmok-
ing decedents who consumed the most amounts of milk (>16 oz/d).
After removing cases of PD and dementia with Lewy bodies,
adjusted neuron density in all but the dorsomedial quadrant was
41.5% lower for milk intake >16 oz/d versus intake that was less
(95% confidence interval: 22.7-55.7%, p<0.001). Among those who
drank the most milk, residues of heptachlor epoxide were found in
almost all brains (9/10) as compared to 63.4% (26/41) for those who
consumed no milk (p50.017). For past and current smokers, an asso-
ciation between milk intake and neuron density was absent.
Conclusions: Milk intake is associated with neuronal loss in the
SN even among brains from participants unaffected by PD. While
these results support the idea that contamination of milk with orga-
nochlorine pesticides may cause SN degeneration, more study is
needed.
114
Exploring Fyn as a novel molecule in levodopa induced
dyskinesias
S. Sanz-Blasco, E. Avale, S. Campana, A. Damianich, M.D. Sabo-
rido, G. Gomez, I.R. Taravini, O.S. Gershanik, J.E. Ferrario (Buenos
Aires Capital Federal, Argentina)
Objective: To determine the role of the kinase Fyn in levodopa
induced dyskinesias.
Background: The administration of L-DOPA is the most effec-
tive symptomatic pharmacological therapy for Parkinsons disease
(PD). Despite its benefits, most patients develop side effects known
as L-DOPA induced dyskinesias (LID). One of the current great
challenges in PD therapy is to control LID. To reach this goal it is
Movement Disorders, Vol. 30, Suppl. 1, 2015
S46 POSTER SESSION
necessary to better understand the multiple cellular and molecular
mechanisms that take place during LID. Although some protein and
gene changes have been described within the dyskinetic striatum, the
functions and/or mechanism in which they are involved are not fully
understood. In our laboratory we have shown that Pleiotrophin and
its receptor RPTPz/b are upregulated as a consequence of dopaminer-
gic cell loss and L-DOPA treatment. RPTPz/b belongs to the post
synaptic density complex, where it interacts with PSD95 and regu-
lates the protein kinase Fyn, a key molecule in postsynaptic signaling
and reorganization. Several evidences suggest Fyn as a potential can-
didate involved in LID.
Methods: We have determined the amount of Pleiotrophin immu-
nopositive neurons and analyzed the amount of Fyn protein and its
phosphorylation state by western blot in striata of dyskinetic rats.
Also, we have developed the model of LID in both Fyn knock-out
(KO) and WT mice, in which we have performed behavioral tests,
determined abnormal involuntary movements (AIMs) and performed
histological determinations such as tyrosine hydroxylase and FosB/
DFosB.
Results: We found that the number of PTN positive neurons is
increased and that Fyn is highly phosphorylated in the striatum of
dyskinetic rats, while Fyn KO mice show a significant reduction in
the development of AIMs in comparison to WT controls.
Conclusions: Our data suggest that Fyn might be involved in the
development of LID, yet further work is still necessary to determine
the mechanism in which it may be involved and if it could be tar-
geted to control LID.
115
Uric acid levels and disease duration in REM sleep behavior
disorder and Parkinsonian syndromes
M. Schiess, J. Suescun, B. Copeland, T. Ellmore, E. Furr-Stimming,
R. Castriotta (Houston, TX, USA)
Objective: Compare uric acid (UA) levels between presympto-
matic REM sleep behavior disorder (RBD) subjects with idiopathic
Parkinsons disease (iPD), Parkinsons Syndrome (PS) and age-
matched control subjects. Determine the role of UA in disease pro-
gression by comparing measures over time between groups.
Background: UA is a recognized risk factor for the development
of iPD with clinical evidence supporting its actions as a CNS antiox-
idant with neuroprotective potential in preventing the progression of
motor symptoms. There is little information on how UA behaves in
the high risk prodromal idiopathic RBD patient and whether UA lev-
els could be manipulated in order to confer neuroprotective potential
in preventing the development of PD.
Methods: Prospective, longitudinal case-control study with intent
to follow at 6-month intervals 37-85 year old men and women; 28
early to moderate iPD, 21 RBD, 19 PS and 18 age-matched Control
subjects. A single-night video polysomnogram was performed at
baseline and all visits included neurological and cognitive exams,
Unified Parkinsons Rating Scale, Hoehn & Yahr, PDQ-39 survey
and plasma UA levels. The primary outcome was measurement of
plasma UA levels with comparison between groups; secondary out-
come was measurement of plasma UA levels over time with compar-
ison between groups and correlations between disease duration,
rating scales, disease disability and quality of life.
Results: Significantly lower UA levels were observed in male PD
subjects,mean 4.54 mg/dl, compared to Controls, PS and RBD. A
significant lower prevalence of PD was found in the 3rd and 4th
quartiles (higher level of UA) (OR: 0.20, 95%CI: 0.047- 0.837; OR:
0.028, 95% CI: 0.029-0.277, p<0.01). There was a significant nega-
tive correlation between UA levels and disease duration in the RBD
subjects, PD and PS subjects (p < 0.01), r-values= -0.50, -0.28, -0.3.
There were no significant differences between groups for female
subjects.
Conclusions: Our study results confirm previous findings of a
relationship between low UA and PD in men, and indicate low levels
Movement Disorders, Vol. 30, Suppl. 1, 2015
of UA in RBD but not PS subjects. The negative correlation between
disease duration and UA levels found in RBD, PS and PD, suggests
a risk for RBD subjects to convert to PD based on declining UA lev-
els over time. Our results support targeting UA levels in RBD sub-
jects as a disease risk modifier to develop PD.
116
Beta band oscillatory activity in the subthalamic nucleus is not
correlated with levodopa motor improvement in patients with
Parkinsons disease
E. Sellaiah, A. Buot, S. Fernandez Vidal, M.L. Welter, C. Karachi,
B. Lau (Paris, France)
Objective: To identify correlations between changes in subthala-
mic nucleus (STN) local field potential (LFP) power in the 8-35 Hz
frequency band and motor improvement in Parkinsons disease (PD)
patients highly responsive to levodopa.
Background: Recordings in the STN of PD patients during deep
brain stimulation (DBS) procedures have revealed excessive oscilla-
tory beta band activity (8-35Hz), which is reduced by levodopa treat-
ment (Brown et al., 2001). One hypothesis is that the degree of
reduction in oscillatory beta activity on levodopa is causally related
to the degree of improvement in Parkinsonian bradykinesia and rigid-
ity (Eusebio & Brown, 2009). However, the significance of these
changes in beta activity remains controversial.
Methods: We included 27 PD patients selected for DBS between
2009 and 2014 (mean age 59 years). Mean preoperative UPDRS III
scores were 36.6 OFF levodopa and 9.5 ON levodopa, with a mean
improvement ON levodopa of 75.8% (all patients >45%). We
recorded STN LFPs OFF and ON levodopa 4 days after DBS sur-
gery. We tested for correlations between clinical change and beta
power change by selecting for each side the contact pair with the
maximum power between 8-35Hz OFF levodopa and calculating a
percentage change using the same frequency ON levodopa. We
measured clinical change using hemibody scores for bradykinesia
and rigidity contralateral to each selected contact.
Results: We did not find significant correlations between
levodopa-induced beta power suppression and clinical change
(p>0.05), nor did we find significant correlations when using average
power between 8-35Hz to define beta power change. Finally, a direct
search for correlations at each frequency in the 8-35Hz range
revealed a significant reduction in beta power ON levodopa (10-
25Hz, p<0.001), but did not yield any significant correlations
between clinical scores and LFP power at any frequency in this band
ON or OFF levodopa (p>0.1).
Conclusions: Our results do not support the hypothesis that
reductions in STN oscillatory activity in the 8-35 Hz range are cau-
sally linked to levodopa motor improvement in PD patients who are
highly responsive to levodopa treatment. This highlights the diffi-
culty in understanding the link between STN beta oscillatory activity
and levodopa responsiveness, as well as the role of beta oscillations
in the pathophysiology of PD.
117
Beneficial effects of histone deacetylase inhibition in 6-OHDA
induced behavioral and biochemical abnormalities in rats
S. Sharma, R. Taliyan (Pilani, India)
Objective: To evaluate the therapeutic potential of HDAC inhibi-
tor, Trichostatin A in 6-OHDA induce Parkinsons disease (PD) in
rats.
Background: Recent studies have investigated the involvement
of epigenetic modifications in PD. Histone acetylation regulates the
expression of various neuroprotective genes. Reduced histone acety-
lation has been reported in PD. Therefore, we hypothesized that ele-
vating histone acetylation by HDAC inhibition could prove to be
beneficial in PD.
 POSTER SESSION S47

Methods: To produce motor deficit, 6-OHDA was administered

unilaterally in rats. These animals were then treated with HDAC
inhibitor, trichostatin A (TSA) for 2 weeks. Motor performance was
evaluated using narrow beam walk test, rotarod activity and wire sus-
pension task. Biochemically oxidative stress and neuroinflammatory
markers were evaluated. To explore the molecular mechanism and to
confirm the involvement of HDACs, we measured the level of his-
tone acetylation.
Results: 6-OHDA administration results in motor deficits along
with significant elevation in oxidative stress and neuro-inflammatory
markers in rat striatum. Treatment with HDAC inhibitor, TSA,
results in significant improvement in motor performance and rotarod
activity. Moreover, HDAC inhibition results in attenuation of oxida-
tive stress and neuroinflammation.
Conclusions: Our data suggest that modulation of histone acety-
lation by HDAC inhibition could be beneficial in attenuation of oxi-
dative stress and neuroinflammation in PD. Thus, we conclude that
HDAC inhibition could be a novel approach to treat PD.

118
Patterns of peripheral immune activity in prodromal
asymptomatic and symptomatic Parkinsonism
K.C. Smith, J.S. Ocampo, D.L. Bick, M.C. Schiess (Houston, TX,
USA)
Objective: To identify and compare cytokines associated with
innate and adaptive immune response in idiopathic Parkinsons dis-
ease (PD), asymptomatic prodromal REM sleep behavior disorder
(RBD) subjects, and age-matched controls, and to determine changes
of these cytokines over time and with duration of disease (DOD).
Background: There is evidence that neuroinflammation plays a
role in PD pathogenesis. RBD is recognized as a prodromal stage
along the PD spectrum, however, neuroinflammatory response in
RBD subjects has not been demonstrated.
Methods: PD (N 5 16), RBD (N 5 14), and age-matched control
(N 5 13) subjects were enrolled in a longitudinal biomarker study
and underwent exams and blood draw every 6 months. Concentra-
tions of 37 different cytokines/chemokines were determined using a
Millipore Multiplex MAP kit. Log-rank, linear regression with Spear-
mans correlation, and multivariant logistic regression analyses were
employed to compare trends in cytokine secretions between groups.
Results: Overall plasma concentrations of 11/37 cytokines were
increased in RBD subjects; only three of these were also increased
in PD subjects compared to controls. IL-6,IL-1a, and IL-1RA, which
are associated with inflammation were significantly increased in
RBD but not PD subjects. Cytokines associated with Th2 adaptive
immune response including IL-4 and IL-5 were most significantly
increased in RBD and PD. Evaluation of cytokine secretion by indi-
vidual subjects over time revealed that 50% of PD and RBD sub-
jects expressed consistently high levels of cytokines. [figure1] The
monocyte-associated chemokines CCL4 and CCL22 positively corre-
lated with DOD in RBD subjects, while both inflammatory and
lymphocyte-associated cytokines decreased over DOD in the PD
Fig. 2. (118).
group. Subject age affected cytokine production in the PD but not
the RBD group.
Conclusions: These results provide evidence for increased innate
and adaptive immune activation in asymptomatic RBD subjects as
well as in symptomatic PD subjects. Inflammation and lymphocyte-
associated cytokines as well as monocyte attracting chemokines
remained steady or slightly increased with increasing DOD in RBD
subjects, in contrast to the decreased secretion of cytokines observed
over DOD in PD subjects. These results support the concept of an
evolving role for the immune system in the spectrum of the neurode-
generative process that can be detected in peripheral blood.
119
Isradipine rescues alpha-synuclein toxicity in a zebrafish model
of Parkinsons disease by upregulating autophagy
M.C. Stahl, S. Prabhudesai, A. Lulla, J. Bronstein (Hershey, PA,
USA)
Objective: To investigate the effect of isradipine, an L-type cal-
cium channel blocker of the dihydropyridine class, on a genetic
model of Parkinsons disease pathology in zebrafish.
Background: Epidemiological data support the potential disease-
modifying effect of exposure to dihydropyridine calcium channel
blockers in Parkinsons disease. Prior studies suggest this effect may
be mediated through modulation of calcium toxicity in pacemaker
dopaminergic neurons, despite the presence of Lewy pathology in
other neuron types. Meanwhile, several L-type calcium-channel
blockers have also been shown to induce autophagy, the lysosome-
dependent process by which cells dispose of damaged organelles and
protein aggregates. This process, implicated in a range of neurodege-
nerative disease, can dispose of toxic oligomers of alpha-synuclein.

Fig. 1. (118).

Movement Disorders, Vol. 30, Suppl. 1, 2015

S48 POSTER SESSION

Methods: Zebrafish overexpressing human alpha-synuclein were
treated with isradipine and the effects on overall survival, induction
of autophagy, and synuclein accumulation were measured. These
results were also compared to those obtained in zebrafish in which
autophagy was inhibited by morpholino knockdown of the
autophagy-related protein LC3.
Results: Isradipine treatment upregulated autophagy as assessed by
GFP-LC3 and significantly improved the survival of alpha-synuclein over-
expressing zebrafish. The rescue was abrogated by knockdown of LC3.
Conclusions: Isradipine treatment rescues neuronal toxicity in an
alpha-synuclein overexpression model of Parkinsons pathology in an
autophagy-dependent fashion.
less cognitive deficits despite severe pathological lesions. Parkinsons dis-
ease (PD) is mainly characterized by motor dysfunction related to striatal
dopaminergic depletion. Similar to the concept of the CR in relation to
neurodegenerative disorders, we hypothesize the presence of the motor
reserve (MR) in relation to PD; the MR can explain individual differences
in motor deficits despite similar pathological changes.
Methods: We assessed the degree of engagement in premorbid
leisure exercise in 102 drug nave PD patients who had been initially
diagnosed at our hospital by dopamine transporter scanning. Patients
were classified into the tertile groups based on the frequency, dura-
tion, and intensity of the exercises engaged.

Clinical characteristics and dopamine transporter activity in the

120 posterior putamen
Alpha-synuclein immunohistochemistry studies in gastrointestinal Lowest Middle Highest
tissue from preclinical Parkinsons disease patients tertile tertile tertile
M.G. Stokholm, E.H. Danielsen, S.J. Hamilton-Dutoit, P. Borgham- (n534) (n534) (n534) p-value
mer (Aarhus, Denmark)
Age (years) 62.2 6 10.9 62.5 6 9.0 64.0 6 8.2 0.714
Objective: (1) To determine the distribution of pathological Gender 32.4 41.2 73.5 0.002
aggregated a-synuclein (a-syn) and phosphorylated a-synuclein (p- (% men)
a-syn) in the peripheral nervous system of both PD patients and
Symptom 1.6 6 1.9 1.3 6 1.1 1.1 6 0.7 0.349
preclinical PD patients. (2) To examine any differences in the distri-
duration
bution between pathological aggregated a-syn and pathological p-a- (years)
syn in the peripheral nervous system. Education 9.0 6 5.8 10.1 6 5.3 11.8 6 4.7 0.114
Background: It is hypothesized that a-syn pathology is initiated
duration
in the enteric nervous system 10-20 years prior to debut of motor
(years)
symptoms and enters the CNS through preganglionic fibers originat- MMSE score 26.9 6 3.0 27.0 6 2.3 27.3 6 2.2 0.763
ing in the dorsal motor nucleus of the vagus nerve. BDI score 13.7 6 9.3 14.7 6 12.9 13.8 6 9.4 0.920
Using different immunohistochemistry techniques recent studies
UPDRS-motor 22.1 6 8.4 24.7 6 10.9 22.3 6 11.0 0.503
showed a-syn in the gastrointestinal tract of preclinical PD patients,
score
PD patients, and healthy controls with variable results. BPnd in the 1.27 6 0.41 1.15 6 0.36 1.14 6 0.40 0.364
Methods: Tissue material removed several years prior to PD posterior
diagnosis and post diagnosis time was included. We included 120
putamen
different tissue blocks from 67 patients diagnosed with PD and 116
tissue blocks from 116 matched control subjects. The tissue included; Data are means 6 standard deviations; UPDRS, unified Parkin-
nasal mucosa, oral mucosa, salivary gland, esophagus, ventricle, sons disease rating scale; BPnd, non-displaceable binding poten-
small intestine, appendix, and colon. Aggregated a-syn and p-a- tial of dopamine transporter activity.
synuclein was visualized using immunohistochemistry with Protein-
ase K pre-treatment and antibodies against p-a-syn. The distribution
of a-syn was evaluated on one single slide from each tissue block.
Results: Aggregated a-syn was found in 56,7% of the PD cases
compared to 42,2% of the control cases (p50.0267; Chi-square test).
Cases with tissue material from surgical resection containing sub-
mucosal or myenteric ganglia more frequently displayed positive
immunoreactivity compared to superficial mucosa biopsies.
In the individual organs, a near-significant between-group differ-
ence was seen in the colon (p50,054; Fishers Exact Test).
Staining for phosphorylated a-synuclein is pending.
Conclusions: This study demonstrated that significantly more
pathological aggregated a-synuclein was present in the gastrointesti-
nal tract of preclinical PD patients compared to matched controls.

121
Premorbid exercise engagement and motor reserve in
Parkinsons disease
M.K. Sunwoo, J.E. Lee, J.Y. Hong, B.S. Ye, H.S. Lee, J. Oh, J.S.
Kim, P.H. Lee, Y.H. Sohn (Seongnam, Korea)
Objective: We investigated whether the amount of premorbid
exercise engagement affects the relationship between striatal dopami-
nergic depletion and severity of motor deficits in early, drug-nave,
patients with PD.
Background: The concept of the cognitive reserve (CR) explains the
differences between individuals in their susceptibility to age-related brain
changes or pathologies related to Alzheimers disease (AD). An enhanced
CR may slow cognitive aging, reduce the risk of dementia, and lead to Fig. 1. (121).

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
Results: When the striatal dopaminergic activity reduction was
mild to moderate (above the median dopaminergic activity), the
highest tertile group showed significantly lower motor scores
(15.53 6 6.25) despite similar degree of dopamine reduction com-
pared to the other groups (21.57 6 8.34, p 5 0.01), but showed a
more rapid decline in motor function in relation to the reduction of
striatal dopaminergic activities (p 5 0.002 with the middle tertile
group and p 5 0.001 with the lowest tertile group).
Interaction effect between the exercise group and dopamine
transporter activity in the posterior putamen
Unadjusted Adjusted
B (S.E.) p-value B (S.E) p-value
BPnd -18.99 (4.43) <0.001 -23.78 (5.02) <0.001
Exercise group
Highest tertile Reference Reference
Middle tertile -15.50 (7.86) 0.052 -22.47 (8.13) 0.007
Lowest tertile -19.52 (7.86) 0.015 -26.01 (8.41) 0.002
Interaction effect
BPnd*Highest Reference Reference
tertile
BPnd*Middle 15.34 (6.15) 0.014 21.80 (6.81) 0.002
tertile
BPnd*Lowest 14.77 (5.85) 0.013 22.04 (6.59) 0.001
tertile
B, estimated slope; S.E., standard error; BPnd, non-displaceable
binding potential of dopamine transporter activity in the poste-
rior putamen; Model I analysis is a general linear model for
UPDRS motor score using BPnd and exercise group as predic-
tors; Model II analysis is a general linear model to investigate
the interaction effect between BPnd and exercise group in the
Model I analysis; , interaction effect between the exercise group
and BPnd; , adjusted for age, gender, symptom duration, educa-
tion duration, and MMSE score.
[figure1]
Conclusions: These results suggest that premorbid exercise
engagement acts as a proxy for an active reserve in the motor
domain (i.e., motor reserve) in patients with PD.
122
Relationship among degeneration of the cardiac sympathetic
nerve, clinical features and neuropathological findings in
dementia with Lewy bodies
M. Takahashi, A. Nakamura, T. Uchihara, M. Yoshida, K.
Wakabayashi, A. Kakita, H. Takahashi, S. Orimo (Tokyo, Japan)
Objective: To examine the relation among degeneration of the
cardiac sympathetic nerve (CSN), clinical features and neuropatho-
logical findings in dementia with Lewy bodies (DLB).
Background: Reduced MIBG uptake is a useful diagnostic bio-
marker to differentiate DLB from other dementia. However, MIBG
uptake is occasionally preserved in patients with DLB.
Methods: In this study, we immunohistochemically examined
heart tissues from 58 subjects with pathologically-verified DLB (lim-
bic and neocortical type) to see whether there are subjects with pre-
served CSN. We quantified tyrosine hydroxylase and neurofilament
immunoreactive axons in epicardial nerve fascicles and examined the
relationship among degeneration of the CSN, clinical features and
neuropathological findings.
Results: All the subjects showed degeneration of the CSN. How-
ever, 4 subjects showed relatively preserved CSN. Their clinical
diagnoses were Alzheimer disease (AD)(2) and DLB (2), and the
mean disease duration was 4.9 years (4.5-6). Neuropathologically,
S49
Lewy pathology was neocorical type in 3 subjects and limbic type in
one subject. In 3 subjects of neocortical type, AD pathology (Braak
& Braak stage and senile plaque stage) was strong, but in one sub-
ject of limbic type, AD pathology was weak.
Conclusions: These findings suggest degeneration of the CSN
occurs in DLB, whereas a few subjects show relatively preserved
CSN, who are subjects with short disease duration.
123
Evaluation of neural connectivity between parvalbumin-
expressing interneurons and medium spiny neurons in the
lesioned striatum of dyskinetic mice
I.R. Taravini, G. Gomez, M.V. Escande, M.G. Murer, O.S. Gershanik
(Ciudad Autonoma de Buenos Aires, Argentina)
Objective: To establish whether the development of dyskinesias
induced by L-DOPA modifies the connectivity of parvalbumin-
expressing interneurons with medium spiny neurons in the lesioned
striatum of transgenic mice expressing fluorescent proteins under the
control of the D1 and D2 receptor promoter.
Background: Dyskinesias are a debilitating side-effect of
chronic L-DOPA administration, despite of which, the drug remains
as the gold standard for symptomatic treatment of Parkinsons dis-
ease (PD). Abnormal stimulation of dopaminergic receptors by L-
DOPA correlates with long-term functional synaptic changes in
striatal medium spiny neurons (MSNs) deprived of dopaminergic
innervations which may contribute to the development of dyskine-
sias (LID). Parvalbumin striatal interneurons modulate and control
differentially the activity of MSNs expressing either D1 or D2
receptors and therefore contributing to the imbalance between these
pathways both in PD and LID. However, the state of the connectiv-
ity between these cell populations in the dyskinetic condition
remains elusive.
Methods: Transgenic mice expressing red (tomato) or green
(EGFP) fluorescent markers in striatal neurons containing either the D1
or D2 receptor promoter were lesioned unilaterally with 6-OHDA in the
mfb and treated with L-DOPA to induce severe dyskinesias. Parvalbu-
min was determined by immunofluorescence on fixed striatal tissue sec-
tions using Cy5 as fluorochrome. The number of synaptic contacts of
parvalbumin positive terminals on D1 or D2 MSNs was quantified on
confocal microphotograph using the ImageJ software (NIH).
Results: Lesioned mice developed severe dyskinesias after L-
DOPA administration. Preliminary results show that the number of
perisomatic parvalbumin synapses on D1 and D2 MSNs remains
unaltered after 6-OHDA lesion. Conversely, a dyskinetogenic dose of
L-DOPA reduces the number of parvalbumin contacts onto D2 but
not D1 MSNs.
Conclusions: These results suggest that L-DOPA affects the syn-
aptic connectivity of parvalbumin interneurons with both types of
MSNs differentially. These are clear evidences that L-DOPA treat-
ment induces alterations at structural and functional levels that lead
to a new pathophysiologic condition in the basal ganglia circuits.
Further analysis will help to clarify if these structural adaptations are
directly related to the development of dyskinesias.
124
Cognitive dysfunction due to over-expression of alpha-synuclein
in hippocampus by using viral vector based approach: Modeling
cognitive decline in PD
B. Tel, G. Yalcin Cakmakli, E. Cinar, S.U. Mutluay, G. Telli, E.
Saka, A. Ulusoy, B. Elibol (Ankara, Turkey)
Objective: In this study, we aimed to reproduce the cognitive
decline observed in the majority of PD patients at different stages, in
the AAV (adeno-associated virus) mediated alpha-synuclein (a-syn)
over-expression model by stereotactic viral injection into the dentate
Movement Disorders, Vol. 30, Suppl. 1, 2015
S50 POSTER SESSION

gyrus of hippocampus (DG). This will allow us to better understand
the behavioral correlates of PD as in the natural course of the disease.
Background: In PD, pathological intracellular aggregation of a-
syn plays a key role in the neurodegenerative process. There is
strong evidence showing that non-motor findings including cognitive
dysfunction, are related to the spread of a-syn pathology from the
lower brainstem to the cortex.
Methods: In female Wistar rats (200-250g), AAV carrying either a-
syn or green fluorescent protein (GFP) gene were stereotactically injected
into DG either unilaterally (n5 6 a-syn, 3 GFP) or bilaterally (n5 5 a-
syn, 3 GFP). The animals were tested with novel object recognition test
(NOR) for memory; Morris water maze (MWM) for spatial learning; ele-
vated plus maze (EPM) for anxiety between week 13-16. The intensity of
a-syn aggregates/GFP in hippocampi and possible neuronal loss were
evaluated by a-syn, GFP and NeuN immunohistochemistry.
Results: The well-known PD model induced by AAV mediated a-
syn over-expression in substantia nigra has been successfully realized in
our laboratory before. In this study, we have detected marked short-term
memory dysfunction in the unilateral DG a-syn group compared to GFP
(p<0.05) but this difference did not reach significance in the bilateral DG
a-syn group. The results of MWM and EPM did not show any statistical
significant difference between groups. We observed a-syn and GFP over-
expression at each injection site, the intensity of a-syn staining did not
correlate with behavioral test results. NeuN staining showed no signifi-
cant neuronal loss either in the a-syn or GFP group. Therefore, the func-
tional loss which is prominent in short-term memory is thought to be due
to synaptic dysfunction which takes place just before neuronal death.
Conclusions: Hippocampal AAV-mediated a-syn over-expression
may be a promising model to study the cognitive dysfunction seen in
PD. Our future plans are to increase the number of animals in each
group and to study the synaptic changes which are thought to be
responsible from the functional loss.
Background: SE is a feature of bradykinesia and refers to the
rapid decrement in speed and amplitude of sequential movements
in PD. It impairs many motor functions, e.g., handwriting, voice,
and gait. SE does not seem to respond to dopamine, but SE in
gait improves with visual feedback. Loss of motor energy, under-
scaling of movements, and central fatigue are proposed
mechanisms.
Methods: We tested 12 right-handed, non-demented PD patients
(5 females) with mild-to-moderate bilateral disease (6 left- and 6
right-onset) and 12 right-handed matched healthy volunteers (HV) (6
females) on an isometric motor task using a hand-clench dynamome-
ter. Participants squeezed the dynamometer repetitively to a metro-
nome cue at 1.25 Hz and at 50% of their maximum force (F50) for
 90 s. The initial 30 s segment was analyzed.
All participants performed the task with both hands, first without
visual feedback (VF-) relying on perceived effort required for F50,
then with VF (VF1) trying to match the F50 target on the computer
screen. PDs were tested twice: (1) After at least 12-hr washout of
dopaminergic medication (off) and (2) at the peak of dopaminergic
effect (on). We also administered the Beck Depression and Spiel-
berger Anxiety Inventories to all participants, and the Unified PD
Rating and Fatigue Severity Scales to PDs.
Results: The mean age was 63 (6 6.4) for PDs, and 62.75 (6
6.9) for HVs. PDs demonstrated significantly higher state anxiety
and depression scores compared to HVs. Dopamine significantly
improved overall disability and motor functioning in PDs.
Clinical Data
UPDRS UPDRS
total motor
Group BDI STAI-S STAI-T FSS off/on off/on

HV 1.9 22.2 26.8 - - -

125
(3.2) (2.8) (7.3)
Sequence effect (SE) in Parkinsons disease (PD) is dopamine- PD 7.0 29.3 34 39.8 52.2 (8.5)/ 32 (4.8)/
independent and improves with visual feedback (3.1) (9.2) (10.2) (11.4) 39.1 (10.9) 23.4 (6.9)
S. Tinaz, A. Pillai, M. Hallett (Bethesda, MD, USA)
Objective: (1)To better characterize SE, (2) assess its response to
dopamine and visual feedback systematically, and (3) examine its Mean and (SD) values. BDI: Beck Depression Inventory, STAI:
relationship to motor impairment, fatigue, and mood. Spielberger S: State T: Trait Anxiety Inventory, FSS: Fatigue

Fig. 1. (125).

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
Severity Scale, UPDRS: Unified Parkinsons disease Rating
Scale
PDs showed a stronger negative slope in the on/VF- condition for
both hands (left > right) compared with HV. [figure1] Higher starting
F50 correlated with steeper negative slope in both groups. VF
improved the slope in both groups. Medication had no effect on the
slope in PDs. Left-hand slopes correlated positively with STAI-T and
FSS in the off/VF- and with STAI-T in the on/VF- conditions in PDs.
Conclusions: SE is observed within 30 s in a repetitive isometric
task in PD. Medication increases initial motor energy, but does not
improve SE. Only VF improves SE. Elevated perception of anxiety
and fatigue may lead to overcompensation.
126
Connectivity of pedunculopontine and sub-thalamic nuclei in
patients with Parkinsons disease
C.H. Tsai, Y.T. Hsu, H.Y. Lai, S.M. Chiou, M.K. Lu, Y.C. Lin, Y.Y.
Chen (Taichung, Taiwan)
Objective: To investigate: 1. through which frequency band(s)
are the two nuclei bridged? 2. Which nucleus leads the other one if
there is functional connectivity between them?
Background: There is anatomical connectivity between sub-thalamic
nucleus (STN) and pedunculopontine nucleus (PPN) in humans. However,
the functional linkage between the two has not been fully explored.
Methods: Three patients with Parkinsons disease (PD) underwent
bilateral STN and left PPN deep brain stimulation (DBS) were recruited
for the investigation on the 2nd day after operation. The local field poten-
tials (LFPs) were recorded from the externalized electrodes in resting
states during patients off and on states . The coherence and cross-
power spectral density estimates were conducted for signal analysis.
Results: There is a strong coherence at alpha frequency between
STN and PPN LFP. The analysis of phase spectra over the alpha fre-
quency showed significant coherence between STN and PPN and
PPN led STN at this frequency by 5.9, 7.3 and 5.1 ms, respectively,
in three subjects were detected. After levodopa treatment, the leading
time increased in subject 2 and 3 (13.7 and 9.5 ms).
Conclusions: There is functional connection between PPN and
STN with PPN in leading position through alpha frequency band in
PD. Levodopa administration lengthened the leading time of PPN. It
seems that the increase of dopamine levels may open another route,
probable via basal ganglia, for the connection of the two nuclei and
this lead to a longer duration for the cross talk to occur.
127
In silico drug discovery for Parkinsons disease by using genome-
wide association study (GWAS) data
T. Uenaka, W. Satake, C.P. Chieng, Y. Okada, T. Toda (Kobe, Japan)
Objective: To discover neuroprotective drugs for sporadic Parkin-
sons disease (PD).
Background: Sporadic Parkinsons disease (PD) is a complex
disorder caused by multiple genetic risk factors. Twenty four risk
loci for sporadic PD were reported from a meta-analysis of Cauca-
sian genome-wide association studies (GWAS) (Nalls MA et al,
Nature Genet 2014). Although those data from GWAS have provided
valuable biological insights, the translation of the genetics findings
from GWAS into the clinic remains limited. A new method of drug
discovery utilizing risk genes and computational database was pro-
posed in rheumatoid arthritis (Okada Y et al, Nature 2014). We
applied this method to discovery of drugs for sporadic PD.
Methods: We obtained 871 drug target genes from drug data-
bases (DrugBank and Therapeutic Target Database). Using a protein-
protein interaction (PPI) database, we extracted genes which show
PPI with PD-risk genes reported by GWAS.
S51
Results: We detected 761 genes as 24 PD-risk genes and its PPI-
genes. Among those, using drug databases, we found 77 genes which
are targeted by 54 approved-drugs for other diseases.
Neuroprotective effects in vitro or in vivo had been already
reported in 16 of those 54 approved-drugs (30%), including raloxi-
fene, an approved-drug for osteoporosis. In order to examine whether
these drugs have neuroprotective effects, we performed LDH assay
and cell viability assay using SH-SY5Y cells with exposure of rote-
none. We confirmed a neuroprotective effect of raloxifene in LDH
assay. Furthermore, we found that 2 drugs significantly improved
LDH release (p50.01) and cell viability (p50.01) under the condi-
tion of rotenone exposure, which suggests that these 2 drugs have a
neuroprotective effect.
Conclusions: In silico drug discovery using GWAS-data is an effi-
cient manner to extract candidates of neuroprotective drugs for PD.
128
Postural instability and gait disorder subtype in early to mid-
stage Parkinsons disease: Beyond axial motor control
impairment
G. Vervoort, A. Bengevoord, E. Nackaerts, E. Heremans, W.
Vandenberghe, A. Nieuwboer (Leuven, Belgium)
Objective: To clarify the validity of PD subtypes by investigating
behavioral outcomes at multiple levels.
Background: Clinical subtypes in Parkinsons disease (PD) are
founded on the heterogeneity of symptoms and are based on the
presence of clustered motor symptoms. The postural instability and
gait disorder (PIGD) subtype is associated with rapid disease pro-
gression, predominantly axial motor involvement and increased cog-
nitive impairment while the tremor dominant (TD) subtype is
characterized by slow disease progression and the presence of signifi-
cant tremor. It is, however, unclear if subtypes represent distinct
underlying pathologies or rather are a reflection of disease
progression.
Methods: 73 patients and 20 age-matched controls were recruited
for this study. Patients were classified as PIGD (n543), TD (n522)
or indeterminate (n58) based on MDS-Unified Parkinsons disease
rating scale (UPDRS) III scores. Patients in the indeterminate group
were excluded Spatiotemporal kinematics of gait, upper and lower
limb repetitive movements in combination with a balance and cogni-
tive assessment were recorded while off medication.
Results: Surprisingly, PIGD patients only had gait impairment in
few parameters, i.e. reduced step length and gait speed compared to
TD patients. In contrast, impairments in postural control and cogni-
tion were present across the board as shown by lower scores on the
mini-BESTest and the Frontal Assessment Battery (FAB) and trail
making test (TMT) B in PIGD patients compared to controls. Motor
scaling and coordination of distal movements were impaired in
PIGD compared to TD patients during foot and finger tapping. TD
patients were not significantly different from controls, except for a
greater asymmetry of repetitive movements.
Conclusions: These results indicate a widespread motor impair-
ment within the PIGD group that is not restricted to axial motor con-
trol, but also involves distal motor control. These findings suggest
refining the PIGD subtype to a more complex motor profile.
129
Salivary alpha-synuclein: A new biomarker for Parkinsons
disease?
G. Vivacqua, A. Latorre, M. Nardi, A. Suppa, G. Fabbrini, C.
Colosimo, A. Berardelli (Rome, Italy)
Objective: To investigate whether salivary monomeric and oligo-
meric alpha-synuclein (a-syn) concentration can differentiate Parkin-
sons disease (PD) patients from healthy controls.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S52 POSTER SESSION
Background: Increasing evidence support the hypothesis that a-
syn, a 140 aminoacids protein closely related to the pathogenesis of
PD, might be considered a biomarker for the diagnosis and follow-
up of PD. In addition to cerebrospinal fluid (CSF), a-syn can be eas-
ily detected in several extra-neuronal tissues and biological fluids
including saliva.
Methods: We collected salivary samples from 26 PD patients and
26 age- and sex-matched healthy subjects. Patients were recruited
from the Movement Disorder clinic of Sapienza University of
Rome. PD patients were clinically evaluated before starting each
experimental session. Motor signs were scored using the motor sec-
tion of the Unified Parkinsons disease Rating Scale (UPDRS) and
the Hoehn & Yahr (H&Y) scale. Non-motor symptoms were eval-
uated by Non Motor Symptoms Assessment Scale (NMSS) and Ham-
ilton Depression Rating Scale (HDRS). Cognitive functions were
tested by Montreal Cognitive Assessment (MOCA) and Frontal
Assessment Battery (FAB). Samples of saliva were collected and
immediately centrifugated at 5000 x g for 20 minutes, followed by a
further centrifugation at 15000 x g for other 20 minutes. Supernatant
was pre-treated with a buffer inhibiting protease activity (Sigma
Aldrich, St.Luis, MO, USA, Cat # P2714, concentration: 100 lL for
1 ml salive). Samples were subsequently analyzed by specific anti-
monomeric and anti-oligomeric a-syn ELISA kits (SensoLyte Anti-
alpha-Synuclein Quantitative ELISA and Rabbit a-syn oligomer
ELISA kit).
Results: Compared with healthy subjects, PD patients have a sig-
nificantly reduced concentration of salivary monomeric a-syn
(p<0.01). By contrast, oligomeric a-syn concentrations in PD
patients resulted similar to those observed in healthy subjects. For
each patient correlation between biochemical and clinical evaluation
have been performed.
Conclusions: The observation that monomeric a-syn is signifi-
cantly reduced in salivary samples of patients with PD might be
interpreted as a result of a-syn aggregation in PD. Finally, salivary
oligomeric a-syn concentration is comparable in PD and healthy sub-
jects probably because in PD, a-syn aggregation is not only due to
free a-syn oligomers but also to intracellular aggregation of the
protein.
130
Can we predict motor subtype fidelity in patients with
tremor-dominant Parkinsons disease?
R. von Coelln, E. Barr, A.L. Gruber-Baldini, S.G. Reich, M.J. Arm-
strong, B. Hanna-Pladdy, L.M. Shulman (Baltimore, MD, USA)
Objective: To identify predictors of whether Parkinsons disease
(PD) patients initially classified as tremor-dominant (TD) later con-
vert to the postural instability/gait difficulty (PIGD) or indeterminate
(ID) motor subtype of PD.
Background: TD, PIGD, and ID are commonly-used PD motor sub-
types. Stability of these subtypes over time and predictors of subtype
fidelity have not been studied systemically. Identifying valid and stable
subtypes is important for future biomarker-phenotype correlation studies.
Methods: We performed a longitudinal analysis of 183 PD
patients, applying an established PD motor subtype algorithm (Jan-
kovic 1990) at baseline (within 5 yrs of diagnosis) and follow-up
(FU)  5 yrs later. Patients classified as TD at baseline, but re-
classified as PIGD or ID at FU, were compared to patients remaining
in TD subtype at FU. We also compared the change in TD and
PIGD scores from baseline to FU between the two groups. Logistic
regression models evaluated predictors of subtype fidelity after con-
trolling for time between study visits.
Results: At baseline, 103 out of 183 patients were classified as
TD. At FU, 49% of those 103 TD patients were re-classified as
PIGD, and 15% as ID (total of 64% converters). Only 36% of
patients remained in the TD subtype (non-converters). Significant
baseline predictors of TD subtype fidelity included younger age
(57.5 vs. 60.9 yrs., p50.04), higher TD score (0.75 vs. 0.57,
Movement Disorders, Vol. 30, Suppl. 1, 2015
p50.02), and higher TD/PIGD ratio (3.3 vs. 2.6, p50.05), but PIGD
scores were not predictive (0.11 vs. 0.14, p50.47). Between baseline
and FU, the TD score increased in non-converters, while decreasing
in converters (10.18 vs. -0.21, p50.0003). Increase in PIGD score
(non-converters vs. converters: 0.18 vs. 0.86, p<0.001) and decrease
in TD/PIGD ratio (-0.3 vs. -2.1, p50.003) predicted conversion over
time. Gender, disease duration, H&Y, MMSE, depression, anxiety
(BSI-18), SF-12 health scores, and ADL/IADL disability (OARS)
were not significant predictors of subtype fidelity.
Conclusions: Our data suggest that the TD subtype of PD is not
stable over time. Older age and less severe tremor at baseline pre-
dicted conversion from TD to PIGD over 5 years. Conversely,
increase of tremor over time, coupled with minimal progression pos-
tural and gait problems, predicted TD subtype fidelity. These results
suggest two distinct subgroups of TD patients which might be rele-
vant for biomarker-phenotype correlation studies.
131
Characterization of PINK1 knockin mouse model for
Parkinsons disease
T.H. Yeh, C.C. Chiu, H.L. Wang, S.C. Lai, H.C. Chang, C.S. Lu
(Taipei, Taiwan)
Objective: To generate PINK1 knockin mouse model to investi-
gate the molecular mechanism of Parkinsons disease.
Background: Parkinsons disease (PD) is the most common neu-
rodegenerative motor disorder. PINK1 is the second most frequent
causative gene in early-onset PD, which is believed to regulate mito-
chondrial functions of dopaminergic neurons in substantia nigra pars
compacta (SNpc). Clinical features exhibited by PINK1-mutation
carriers are indistinguishable from those observed in sporadic PD
patients. Thus investigating PARK6 mutant PINK1-induced Parkin-
sonism is important to unveil the common pathogenic mechanism of
PARK6 and sporadic PD.
Methods: In this study, we generate PINK1-knockin mice
expressing common PARK6 mutant (G309D). Homologous recombi-
nation was used to replace the exon 4 of Pink1 gene with mutated
(G308D) exon 4 in embryonic stem (ES) cells in C57BL/6J genetic
background which were injected into the C57BL/6-C2J blastocysts.
Then, chimeric mice were mated with wild-type albino C57BL/6-
C2J mice and bred to obtain F1 heterozygous mutant mice express-
ing PARK6 mutant (G308D). The LoxP-flanked neomycin selection
cassette was removed by crossing the F1 mice with Pink1 knockin
(G308D) allele with Cre deleter (EllA-Cre) transgenic mice to gener-
ate Pink1G308D/G308D homozygous mice. The behavior test and
histopathology were performed.
Results: We have generated Pink1G308D/G308D homozygous
knock-in mice. Similarly to motor signs displayed by PD patients,
12-month-old Pink1G308D/G308D knockin mouse exhibited an
impaired motor performance and the phenomenon of bradykinesia.
The homozygous Pink1G308D/G308D knockin mouse also exhibited
progressive degeneration of SNpc dopaminergic neurons.
Conclusions: This humanized knockin mice expressing PARK6
mutant could be used for investigating the molecular pathogenesis of
neurodegeneration caused by PINK1 mutations.
132
Vitamin D deficiency and endothelial dysfunction in Parkinsons
disease
J.H. Yoon, S.W. Yong, J.M. Hong, J.S. Lee, I.S. Joo (Suwon, Korea)
Objective: To evaluate the relationship between serum 25-
hydroxyvitamin D (25(OH) D) levels and flow mediated dilatation
(FMD) in patients with a Parkinsons disease.
Background: In recent years, increasing evidence has shown that
individuals with Parkinsons disease (PD) have lower levels of
25(OH) D relative to healthy controls. Vitamin D insufficiency is
 POSTER SESSION
associated with endothelial dysfunction in human, irrespective of tra-
ditional risk burden. Flow mediated dilatation (FMD) is widely used
as a clinical marker of endothelial function.
Methods: We enrolled 82 patients with PD patients and 45
healthy controls. Clinical information and disease duration were col-
lected. PD severity was assessed using the motor Unified Parkinsons
Disease Rating Stage (UPDRS).
Results: The results indicated that the mean serum 25(OH) D lev-
els were significantly lower in PD patients as compared to controls
(21.3 6 3.2 ng/ml VS 24.36 5.6 ng/ml) (p<0.05). FMD was signifi-
cantly lower in PD patients (6.2% 6 2.2%) than in controls
(8.6 6 2.7%, p < 0.05). FMD was significantly associated with serum
25(OH) D independently of BMI, CVD risk factor, motor UPDRS,
disease duration and homocysteine (r=0.232, p50.03).
Conclusions: These findings provide evidence that vitamin D
play a role in endothelial dysfunction in patients with PD and iden-
tify specific outcome measure for detecting effect of vitamin D.
133
Parkinsons disease-linked mutation in DNAJC13 causes specific
trafficking defect in endosomal pathway
S. Yoshida, T. Hasegawa, E. Miura, R. Oshima, N. Sugeno, A.
Kikuchi, A. Takeda, M. Aoki (Sendai, Japan)
Objective: The aim of this study is to investigate the effect of
mutant DNAJC13 on the vesicle transport machinery using cultured
cellular model.
Background: Recently, a missense mutation (p.N855S) in
DNAJC13 gene has been identified in patients with autosomal domi-
nant, rare familial forms of Parkinsons disease (PD). DNAJC13 is a
Dnaj-domain-containing protein that is tightly associated with endo-
somal membrane.
Methods: Human wild-type (wt) and Mutant DNAJC13 cDNAs
were subcloned into the pEGFP-C1 eukaryotic expression vector.
Human Rab5A, Rab7 and Rab11A cDNAs were introduced into
pmStrawberry vector. COS7 were transiently transfected with GFP-
tagged DNAJC13 as well as mStrawberry-tagged Rab GTPase con-
structs using the NEPA gene square-wave electroporator. The expres-
sion and subcellular localization of DNAJC13 were examined using
laser scanning microscopy (LSM) and Western blot analyses in com-
bination with density-gradient centrifugation. To determine how the
DNAJC13 mutant affect on the different endosomal pathway, cells
overexpressing wt or mutant DNAJC13 were incubated in the culture
media containing Alexa555-labeled reference molecules including
transferrin, EGF and Shiga Toxin 1B subunit.Time-lapse images of
internalized reference molecules were acquired using LSM at 15 sec
intervals.
Results: While wt DNAJC13 was exclusively co-localized with
rab5A-positive early endosome, part of DNAJC13 p.N855S was mis-
localized from Rab5A to Rab11A-positive recycling endosome.
Transport assay using reference molecules showed abnormal endoso-
mal trafficking in cells overexpressing DNAJC13 p.N855S.
Conclusions: PD-linked DNAJC13 mutation impairs specific
endosomal trafficking and would thereby contribute to the pathogene-
sis of disease.
134
Relative sparing from the death of serotonergic fibers in
ipsilateral striatum is related with development of levodopa-
induced dyskinesia in hemi-Parkinsonian rats
J. Youn, M.Y. Jeon, T.O. Son, J.W. Cho (Seoul, Korea)
Objective: To investigate the relationship between serotonergic
cell death and development of levodopa-induced dyskinesia (LID).
Background: Although, dopaminergic medication is the most
effective therapy in Parkinsons disease (PD), LID presents com-
monly with chronic treatment, and has great impacts on quality of
S53
life. Recently, there are growing evidences about the role of seroto-
nergic system in development of LID. However, the specific molecu-
lar mechanisms about the pathogenesis of LID are not clearly
elucidated.
Methods: In present study, chronic levodopa treatment (12mg/Kg)
was done for 3 weeks after making unilateral mid-forebrain bundle
lesion with 6-hydroxydopamine in male F344 SD rats. Levodopa-
treated rats were divided into two groups based on the LID develop-
ment using abnormal involuntary movement scale (AIMS). We com-
pared dopaminergic cell and serotonergic fibers between two groups
using immunohistochemistry and western blotting.
Results: There was no difference in dopaminergic cell wipe-out
in striatum between hemi-Parkinsonian rat models with and without
LID. When we compared the number of 5-HT positive cells in dorsal
raphe nucleus, there was no significant difference between two
groups. However, rats without LID showed 21.7% reduction of 5-HT
transporter (SERT) in striatum compared with those with LID. There
were no correlations between AIMS score, and 5-HT positive cell
count or SERT.
Conclusions: These findings suggest relative sparing from the
death of serotonergic fibers in ipsilateral striatum could be related
with development of LID in PD.
135
Withdrawn by Author
136
Neuronal oscillatory activity in the ventrolateral thalamus in
patients with Parkinsonian tremor and essential tremor
P. Zhuang, M. Hallett, T. Liu, Y. Zhang, J. Li, Y. Li (Beijing,
Peoples Republic of China)
Objective: To characterize oscillatory activity in the ventrolateral
thalamus (VL) in patients with Parkinsonian tremor and essential
tremor (ET).
Background: The pathophysiology of Parkinsons disease (PD)
and ET is unclear.
Methods: 26 patients with PD and 14 patients with ET who
underwent thalamic surgery were studied. Microelectrode recordings
in the VL and EMG of contralateral limbs were performed. Single
unit analysis and interspike interval was used to assess neuronal
mean firing rate (MSFR) and pattern. Spectral characteristics were
evaluated. Coherence analysis was used to explore the relationship
between oscillatory activity and EMG.
Results: Of total neurons (n5224) obtained from 26 tracts of PD
patients, 66.4% neurons were oscillatory. Of these neurons, 71.1%
neurons (n5109) with bursting activity at mean tremor frequency of
4.5 6 0.9 Hz were correlated with tremor and defined as TFB oscilla-
tory neurons; 28.8% neurons (n544) with frequency oscillation at
16.6 6 8.9Hz were defined as FB oscillatory neurons. Of total neu-
rons (n572) obtained from 14 tracts in ET, 63.9% neurons were
oscillatory. Of these, 89.1% (n541) TFB neurons had burst activity
frequently correlated with postural tremor at mean frequency of
6.8 6 4.5 Hz; 10.9% neurons (n55) had FB oscillation at mean of
18.4 67.9 Hz. The proportion of FB oscillatory neurons in PD
were significant higher than that of FB oscillatory neurons in ET
(p<0.05). Moreover, MSFR of oscillatory neurons in PD were signif-
icantly lower than that of oscillatory neurons in ET (26.7 66.8 Hz
vs. 42.3 615.6 Hz, p<0.05).
Conclusions: The proportion of thalamic FB oscillatory neu-
rons is higher in PD supporting that FB oscillatory neurons are
associated with dopaminergic deficits in the basal ganglia circuit.
Compared with normal MSFR (estimated to be 30 Hz from record-
ings in normal monkeys), the MSFR of oscillatory neurons in the VL
are likely high in ET suggesting an etiologic role of the thalamus
in ET.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S54 POSTER SESSION
Parkinsons disease: Psychiatric
manifestations
137
Prevalence study of impulse control disorders and compulsive
behaviours in Parkinsons disease in a single centre:
Association with premotor signs and clinical characteristics
A. Acarer, Z. Colakoglu (Izmir, Turkey)
Objective: We aim to determine prevalence of impulse con-
trol disorders (ICDs) and compulsive behaviours (CBs) in Par-
kinsons disease (PD) patient seen in our Movement Disorders
outpatient clinic (Department of Neurology, Ege University
Medical Faculty, Izmir, Turkey) between years 2005 2013 and
their associations with premotor signs and clinical characteristics
of PD.
Background: Impulse-control disorders and compulsive behav-
iours occur in patients with Parkinsons disease, especially in
younger patients on dopamine therapies. Studies indicate a preva-
lence of impulse control disorders in Parkinsons disease of 6-16%.
ICDs including pathological gambling, compulsive buying, sexual
behaviour and eating. CBs are punding, hobbyism, dopamine dysre-
gulation syndrome (DDS) and walkabout.
Methods: In this study, we investigated prevalence of ICDs and
CBs among 477 PD patients seen our Movement Disorders outpa-
tient clinic between years 2005 2013. 477 patients were questioned
using a semi-structured questionnaire directed to patients and their
caregivers based on the DSM IV criteria. We directed questions to
our patients with PD and their caregivers about premotor signs
(REM sleep behaviour disorder, constipation and smell problems).
We also investigated 477 patients records. There were 40 PD
patients with ICDs and CBs. These 40 patients records were again
examined to determine premotor signs and clinical characteristics
of PD.
Results: Impulse control disorders and compulsive behaviours
were identified in 40 patients (prevalence, 8,3%). Some patient have
multiple behaviour symptoms of ICDs and CBs. Pathological gam-
bling was observed in 7 patients with PD, hypersexuality in 11, com-
pulsive buying in 14, punding in 11, dopamine dysregulation
syndrome in 15, hobbyism in 4, compulsive internet use in 2, walk-
about in 2, compulsive eating in 2. We determined risk factors
regarding ICDs and CBs. These were male sex, younger age,
younger age at PD onset, a pre-PD history of ICDs and gambling
problems. There were not any associations between ICDs and premo-
tor signs.
Conclusions: ICDs and CBs are common among Parkinsons
patients. These behaviours can possibly lead to serious psychosocial
consequences. Therefore, it is extremely important to detect and
manage these behaviours.
138
Susceptibility to visual hallucinations in Parkinsons disease: A
fMRI study
G. Baille, S. Lefebvre, D. Pins, L. Defebvre, K. Dujardin (Lille,
France)
Objective: To assess the propensity to hallucinate in Parkinsons
disease (PD) by comparing the access to consciousness of visual
inputs between PD patients with and without visual hallucinations
(VH) and healthy subjects.
Background: Despite their frequency and their impact, patho-
physiology of VH in PD remains unknown. Several studies have
reported a disturbance in processing of visual inputs. Nevertheless,
the role of more elaborated cognitive processes need to be
determined.
Methods: Seventeen healthy subjects, 14 PD patients without VH
and 15 PD patients with minor VH participated in the study. None
Movement Disorders, Vol. 30, Suppl. 1, 2015
had dementia. During a fMRI session, all participants performed a
task of visual detection. A detection threshold was determined,
defined as the duration of presentation for which 50% of the stimuli
were seen and 50% not seen. The contrast of the seen and
not seen conditions for a same stimulus presented at threshold
allowed the evaluation of BOLD signal variations at time of access
to consciousness of visual inputs.
Results: The visual detection threshold was significantly lower
for healthy subject in comparison with PD patients with and without
VH (57 vs 159 and 173 ms respectively, p<0.05). This threshold did
not differ in both groups of PD patients. Compared with PD patients
without VH, access to consciousness of visual inputs in PD patients
with minor VH was characterized by a higher involvement of the
left anterior cingulate gyrus and the left prefrontal dorso-lateral cor-
tex, as well as a lower involvement of the left fusiform gyrus and
the left inferior temporal gyrus.
Conclusions: In PD patients with minor VH, access to conscious-
ness of visual inputs is characterized by a hyperactivation of brain
areas involved in high level cognitive processes, and by a hypoacti-
vation of regions involved in low level visual processes.
139
Impact of depression on the rate of progression of impairment,
disability and quality of life in early Parkinsons disease: NET-
PD LS1 cohort
D. Bega, S. Luo, H. Fernandez, K. Chou, M. Aminoff, S. Parashos,
H. Walker, D.S. Russell, C. Christine, R. Dhall, C. Singer, I. Bodis-
Wollner, A. Nicholas, R. Hamill, D. Truong, Z. Mari, S. Glazman, E.
Houston, T. Simuni, On Behalf of the NET-PD LS1 Investigators
(Chicago, IL, USA)
Objective: To characterize the relationship between depressive
symptoms as measured by the baseline Beck Depression Inventory
(BDI) and multiple measures of symptom progression in PD using
data from the NINDS Exploratory Trials in PD Long-Term Study
1 (NET-PD LS1) cohort, which involved early, treated PD
patients.
Background: Depression is one of the most common non-motor
symptoms associated with Parkinsons disease (PD) and the major
factor contributing to impairment of disease related quality of life
(QOL). Yet limited data exist on the impact of depression on pro-
gression of PD disability.
Methods: Using baseline and longitudinal data from LS1, BDI
scores from participants were correlated with change in multiple
measures of disability, impairment, and QOL over a 5-year period.
In order to assess which variables have the greatest contribution to
the BDI in a multivariate model the analysis was reversed using
change in BDI as the outcome measure.
Results: Of 1741 participants, 746 had completed 5-year assess-
ments and were included in this analysis. Their mean age was
62.00 years (SD 9.22) and mean disease duration was 1.69 years
(SD 1.16). Mean baseline BDI score was 6.24 (SD 5.02) and
increased to 8.57 (SD 6.60) at 5 year follow-up. At baseline 11.8%
(n5206) of subjects had a BDI  14, and 22.0% of subjects were
using antidepressants. Baseline BDI score was strongly associated
with the rate of change in all examined measures of disease sever-
ity, disability, and QOL. In a multivariate analysis using change in
BDI as the outcome measure, baseline BDI was associated with 5-
year UPDRS Part I (with depression item removed) (p<0.01) but
not UPDRS ADL (p50.28) or UPDRS motor scores (p50.19). It
was also associated with QOL measures, PDQ-33 (p<0.01) and
EQ-5D (p50.02), but not cognitive measures (p50.17 for SCOPA-
COG). This was a fairly robust model, with these 4 significant var-
iables (Total Functional Capacity, UPDRS part I, PDQ-33, and EQ-
5D) explaining about 68.8% of the variance of the BDI score 5-
year change.
Conclusions: Worse baseline BDI scores, even in the absence of
depression, are associated with a decline in multiple measures of
 POSTER SESSION
disease severity and symptomatology in PD. Change in the BDI at 5
years was associated with the change in UPDRS Part I and QOL
measures, rather than motor and cognitive measures.
140
Psychiatric and psychosocial outcome after bilateral deep brain
stimulation of the globus pallidus pars interna and subthalamic
nucleus for advanced Parkinsons disease
J.A. Boel, V.J.J. Odekerken, G.J. Geurtsen, B. Schmand, D.C. Cath,
M. Figee, R.J. de Haan, P.R. Schuurman, R.M.A. de Bie, The
NSTAPS Study Group (Amsterdam, Netherlands)
Objective: To assess psychiatric and psychosocial outcome 12
months after bilateral deep brain stimulation (DBS) of the globus
pallidus pars interna (GPi) and subthalamic nucleus (STN) for
advanced Parkinsons disease.
Background: Concerns have been raised regarding the psychiat-
ric side-effects of DBS, especially STN DBS. The effects on mood
and behaviour could be the deciding factors in the choice between
the two targets (GPi vs. STN).
Methods: We randomly assigned patients to receive either GPi
DBS (n565) or STN DBS (n563). Standardized psychiatric and psy-
chosocial questionnaires were assessed at baseline and after 12
months. Patients and study assessors were masked to treatment allo-
cation. We performed between-group, within-group, and descriptive
analyses.
Results: No differences were found between GPi DBS and STN
DBS on psychiatric evaluation investigating, mania, mood, personal-
ity, and affect. Within-group comparisons showed small, but statisti-
cally significant changes on several measures in both groups. Mania
scores and positive affect decreased after GPi DBS. Positive affect
scores decreased after STN DBS. Descriptive analyses indicated
slight changes in work status, social participation, and social rela-
tions. Marital satisfaction of patients and partners remained relatively
stable after GPi DBS and STN DBS.
Conclusions: We found neither clinically relevant differences in
psychiatric and psychosocial outcome between GPi DBS and STN
DBS, nor any relevant within-group differences before and after DBS.
141
The Parkinsons active living (PAL) program: A behavioral
intervention targeting apathy in Parkinsons disease
L.C. Butterfield, C.R. Cimino, R.D. Salazar, C.S. Lee, W.E. Haley, J.
Sanchez-Ramos, M.S. Okun, D. Bowers (Gainesville, FL, USA)
Objective: (1) To develop protocol materials to facilitate treat-
ment delivery, (2) to determine ease of training interventionists, (3)
to assess feasibility, acceptability, and estimated effect of a 6-week,
primarily telephone-based activity scheduling/monitoring intervention
on reducing apathy in non-demented, apathetic Parkinsons (PD)
patients.
Background: Apathy, reflecting motivation and self-initiation
impairment, is common in PD and associated with a host of negative
associates, including reduced cognitive and daily functioning, treat-
ment compliance, and quality of life, and increased caregiver stress.
While some studies have evaluated pharmacologic approaches to
treating apathy, few have evaluated non-pharmacologic approaches.
To our knowledge, this is the first behavioral intervention program
designed to target apathy in a PD population.
Methods: 34 non-demented, apathetic PD patients participated. 1)
An interventionist manual outlining treatment protocol and a patient
workbook were created. 2) Interventionists were trained and eval-
uated for protocol adherence. 3) A one-arm uncontrolled trial was
conducted to estimate treatment effect on self-rated apathy, depres-
sion, ADLs, QoL, and caregiver burden. Intervention consisted of
one in-person Planning Session to identify and schedule tailored
goals, and 6 weekly phone sessions. Outcomes were assessed at
S55
baseline, post-test, and 1-month follow-up. Paired t-tests examined
differences in outcomes by time point.
Results: Treatment delivery, feasibility, and acceptability data
reflected strong interventionist adherence, expected attrition, and high
patient satisfaction. Apathy, depression, and QoL significantly improved
post-treatment with medium to large effects and clinically meaningful
changes. Improvements in apathy and depression were maintained at
follow-up. Response to treatment was associated with higher baseline
executive function, novelty seeking, and self-awareness.
Conclusions: A promising manualized intervention designed to
target self-generational deficits common in PD is presented. Prelimi-
nary results showed improved motivation, mood, and QoL in PD
through a telehealth intervention. A randomized controlled trial is
needed to further investigate the efficacy of the PAL program.
142
Problematic mobile gaming: A previously unreported impulse
control disorder
E.A. Byrd, N.B. Galifianakis, C.A. Racine (San Francisco, USA)
Objective: To present a case of dopaminergic medication-
induced problematic mobile gaming, a previously unreported impulse
control disorder (ICD) behavior.
Background: ICDs are a known side effect of dopaminergic
medications used in the treatment of Parkinsons disease (PD), esti-
mated to occur in 10-40% of individuals with PD. Previous studies
have largely focused on the following behaviors: pathological gam-
bling, hypersexuality, hobbyism/punding, compulsive eating and
excessive spending. Recent reports have also described problematic
internet use, but our case extends ICD behavior into excessive gam-
ing on mobile devices.
Methods: Single case report.
Results: A 64-year-old woman with a 5 year history of PD who
was taking levodopa and pramipexole presented with an ICD that
manifested primarily as playing a video game on her mobile device
for 2-4 hours per day. She spent $600/month on within-app pur-
chases, which allowed her to continue playing after running out of
lives. Playing allowed her to take her mind off everything and
was an escape for her. She was successfully treated with educa-
tion, deleting the game, and strict monitoring by her daughter who
had moved in with her. However, 10 months later on return visit she
had started playing another mobile game, spending $800-900/month.
She was again treated by deleting the game. Tapering her dopamine
agonist was not possible in this case due to painful foot dystonia and
truncal dystonia that was minimally responsive to botulinum toxin.
Conclusions: To our knowledge, this is the first report of prob-
lematic mobile gaming, an ICD behavior with several unique charac-
teristics which may lead to potentially serious financial
consequences. First, mobile games are exquisitely designed with
entertaining graphics, music, and sometimes subtle within-app pur-
chasing options to maximize game use and profit. Perhaps more
importantly, smart phones and other mobile devices are ubiquitous,
which makes problematic mobile gaming readily available in almost
any time and place. This ubiquity, combined with the fact that gam-
ing does not usually have the stigma associated with gambling and
other ICDs, make this behavior an important new ICD to actively
screen with our PD patients. Furthermore, currently available ques-
tionnaires and scales do not address this behavior.
143
Relation between farmachological treatment and impulse control
disorder in patients with Parkinsons diseases of recent diagnose
H. Duran Meza, D. Santana Vargas, D. Trejo Martnez (M exico
City, Mexico)
Objective: Identify the relation between pharmachological treat-
ment and the presence of Impulse Control Disorder.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S56 POSTER SESSION

Background: Most of drugs being used for Parkinsons disease
treatment are being oriented to reestablish the content of dopamine
in the striatum. Levodopa and Dopamine Agonists improve motor
symptoms. Agonists are related to Impulse Control Disorder
(ICD), which has been related its presence between 15% to 20%
of patients. This disorder includes pathological gambling, hyperse-
cuality, compulsive buying, and binge eating, compulsive and
repetitive behaviors, hobbyist, walkabout, and compulsive use of
medication. Regarding time frame where ICD appeared, there is
controversy. About gender difference there is not clear an esteaby
pattern.
Methods: 31 patients with PD recruited from the outpatients
Neurologic department at the General Hospital from Mexico, (15
women and 16 men), without data indicating depression according
to the Yesavage scale, or showing severe dementia according to
the Minimental test (Folstein, 1975) or specific items from UPDRS.
All patients were under stable pharmachological treatment for at
least three months before testing and rated at stages 2 and 3 of the
Hoenh and Yarh scale. Patients belonged to one of two groups:
a)levodopa-carbidopa or b)levodopa with dopaminergic agonist
(Pramipexole). Analysis were conducted using the Statistical Pack-
age for the Social Sciences (SPSS) for Windows version 17, to
find relation between treatment type and the QUIP score and one
factor ANOVA for tratment effect. Significant level were set at
a0.05.
Results: Neither Spearman correlation nor significat effect for
ANOVA test were significant for levodopa or levodopa plus dopa-
minergic teatment effect and QUIP score. However, differences
were found when comparisons were performed by sex. Spearman
correlation coefficient showed positive high correlation for women
(0.701) and significative at 95%IC (p50.004). One factor ANOVA
was also signifficant for women showing higher scores for levo-
dopa plus pramipexole than for levodopa alone (F (13,1) 5 4.827,
p50.047).
Conclusions: Based in previous results we have found, for this
sample that there is not changes between both groups but when we
separate by sex, we found positive correlation that indicates, the
Dopaminergic Agonist has a positive relation with the presence of
Impulse Control Disorder in women.
144
Improvement of obsessive-compulsive symptoms after bilateral
subthalamic stimulation in Parkinsons disease
F.M.C. Fonoff, E.T. Fonoff, E.R. Barbosa, R.B. Machado, R.G.
Cury, M.G.G. dos Santos, M.J. Teixeira, D. Fuentes (S~
ao Paulo,
Brazil)
Objective: To investigate the effects of deep brain stimulation
(DBS) over Obsessive-compulsive symptoms (OCS) and other neuro-
psychiatric changes in patients with Parkinsons disease.
Background: OCSs are fairly common in Parkinsons disease
patients. OCSs have been a concern when indicating DBS for Parkin-
sonian patients.
Methods: Thirty-three Parkinsons disease patients were eval-
uated before surgery and 12 months after implantation of deep brain
stimulation in subthalamic nucleus, using scales and standardized
tests.
Results: It was observed improvement in depression (from
11.27 6 4.32 to 8.24 6 4.40; 26.88%; p50.004), anxiety (from
15.39 6 6.55 to 11.27 6 6.45; 26.77%; p50.002), attentional impul-
sivity (from 18.43 6 3.16 to 16.84 6 3.39; 8.61%; p50.031) and in
obsessive-compulsive symptoms (from 4.38 6 4.78 to 0.90 6 2.23;
79.34%; p50.001) 12 months after bilateral stimulation. No signifi-
cant changes were observed in neuropsychological tests that assess
attention, mental flexibility, decision making, planning.
Conclusions: In this series, stimulation of the subthalamic
nucleus did not affect the cognitive performance, relieved signifi-
cantly depression, anxiety, impulsivity but the most significant
impact was observed in obsessive-compulsive symptoms.
145
Assessment of current treatment approaches for patients with
Parkinsons disease psychosis (PDP)
D. Fredericks, J. Norton, R. Suresh, R. Mills (San Diego, CA, USA)
Objective: To survey physicians who treat PDP and characterize
current treatment approaches and drivers.
Background: PDP is a prevalent neuropsychiatric manifestation
with a lifetime prevalence of up to 50% in patients who have been
diagnosed with Parkinsons disease (PD). Typically, patients charac-
terized as having disruptive psychotic symptoms are more likely to
receive treatment. This study aims to provide insight into current
treatment approaches.
Methods: 201 physicians (109 neurologists, 46 psychiatrists, and
46 primary care physicians) were surveyed to understand current
treatment approach for PDP.
Results: The decision to treat is driven primarily by the per-
ceived disruptiveness of psychotic symptoms. Fifty percent of
patients characterized with non-disruptive symptoms of PDP were
treated, and the decision to treat was driven mainly by concern
that psychotic symptoms would worsen or by patient/family request
for treatment.
For PDP patients characterized as disruptive who were treated,
adjustment of PD medication was the primary treatment approach
(55%) and most common amongst neurologists (63%). These PD
medication adjustments were typically made over a period of 2
weeks to 3 months, and were successful in controlling psychosis
in less than 25% of cases, at which point almost half (45%)
were prescribed an atypical antipsychotic (AP). In cases where an
AP was prescribed, quetiapine was the preferred agent (60%).
Twenty-eight percent of PDP patients who were prescribed an AP
eventually were switched to a second AP, and 19% of those to a
third AP. In cases where an AP was not utilized, patients
received anti-dementia or anti-depressant agents approximately
20% of the time as it is commonly believed that managing
dementia and depression may help resolve psychosis; however,
permanent adequate control was achieved in only approximately
15% of these cases.
Conclusions: The main factors that influence whether a PDP
patient will receive treatment for psychotic symptoms are the per-
ceived degree of disruption of the symptoms and the level of concern
about impact on motor control. The primary method of treatment
was reduction of PD medication, followed by the addition of an AP,
usually quetiapine, or, less commonly, anti-dementia or anti-
depressant agents. The results show that PDP is undertreated, espe-
cially in cases considered non-disruptive, and that treatment options
are currently limited in their usefulness.
146
Dopamine agonist induced impulse-control behaviors in
Parkinsons disease are not dose-dependent
T.J. Gupta, M.E. Gomez, L. Yang, S. Cen, D. Togasaki, J.S. Hui (Los
Angeles, CA, USA)
Objective: To prospectively assess Impulse Control Behaviors
(ICBs) in PD patients initiating dopamine agonist (DA) therapy, and
to examine the association between peak LEDD and cumulative DA
exposure and the development of ICBs.
Background: DA are widely used in the management of Parkin-
sons disease (PD). Recent evidence suggests that DA therapy in PD
is associated with the development of one or more impulse-control
behaviors (ICBs). While there appears to be a class effect for DA in
the development of ICBs, studies have been inconsistent in

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
implicating medication-specific or dose-specific effects with DA use.
There have been few prospective, longitudinal studies which examine
the effect of peak levodopa-equivalent dose (LEDD) and cumulative
lifetime dose of DA on expression of ICBs.
Methods: Participants were recruited from a pool of patients
identified as candidates for therapy with a non-ergot DA. Peak
LEDD of and cumulative exposures to ropinirole (RPL) or pramipex-
ole (PPX) during the study period were calculated using drug
accountability logs and analyzed via independent-samples t-test and
ANOVA respectively.
Results: Of 18 subjects starting agonist therapy, 9 received
RPL and 9 PPX. 8/18 (44%) subjects developed ICBs. Mean time
to develop ICBs was 10.1 months (SD 11.3). There was no differ-
ence in either peak or cumulative doses administered between
RPL and PPX. The peak LEDD medication was not associated
with expression of ICBs (p50.98). Repeated measures ANOVA
showed that there was no statistical interaction between drug type,
presence of ICBs, and overall cumulative dose over time
(p50.36). All (100%) subjects who developed ICBs were also tak-
ing levodopa, compared to only 10% of subjects who did not
develop ICBs.
Conclusions: While ICB expression may be a class effect of
non-ergot DA, it does not appear to demonstrate dose-related or
medication-specific effects, and may be influenced by polyphar-
macy of DA with levodopa. Further elucidation of ICB risk factors
may provide insight for clinicians who manage patients on DA
therapy.
147
Symptoms of depression and anxiety in Parkinsons disease
patients and a population based elderly cohort
K. Huckelheim, E.J. Vollstedt, S. Tunc, V. Tadic, A. Lorwin, J.
Hagenah, J. Graf, C. Klein, M. Kasten (Luebeck, Germany)
Objective: To address the prevalence, severity, and subtype of
depression and anxiety in Parkinsons disease (PD) patients and a
population based-control group including controls with other disor-
ders according to different assessment tools.
Background: Depression and anxiety in the context of PD have
been established as prominent predictors for quality of life in several
studies. However, broad ranges (3-90%) of prevalences are reported
partially due to variable assessment methods and different definitions
of the terms depression and anxiety. patients. This specific pattern of brain degradation might serve as a
Methods: After a postal screening of 10,000 citizens of Lue-
beck, 729 participants were examined, PD diagnostic criteria
checked according to the UK Brain Bank Criteria, medication
intake and psychiatric symptoms recorded. We applied the Struc-
tured Clinical Interview (SCID) screening questions for anxiety,
the Beck Depression Inventory (BDI), the UPDRS I depressive
symptoms question, and the State-Trait-Anxiety Inventory
(STAI).
Results: The sample comprised 385 men and 344 women (mean
age 661/-8 years), 283 healthy controls, 260 disease controls, 74
persons with mild Parkinsonian signs (MPS), and 112 PD patients.
Using antidepressive medication, self-reported prior diagnosis of
depression, or BDI (9) as indicator of depression, frequency ranged
from 5%-42%. A BDI9 was present in 35% of healthy controls,
51% of controls with other diseases, and 43% of PD patients. STAI
scores were increased in PD patients compared to healthy but not to
disease controls. The SCID screening showed similar numbers of
anxiety subtypes across groups. Anxiety and depression markers
were highly correlated in the BDI and STAI, whereas the SCID
screening only mildly correlated with the BDI and STAI results. In
binary logistic regression for the outcome BDI9 the predictors
were history of prior depression, PD diagnosis, and presence of mild
Parkinsonian signs.
Conclusions: The question how to measure depression and anxi-
ety in PD is partially unresolved and syndromes not represented in
S57
DSM and ICD may be of clinical interest. A prior depression could
be a valuable red flag for risk of depression in a clinical setting.
Assessment method and cut-off for anxiety and depression need to
be specified and harmonized between comparison groups in future
studies. Additional data is needed to specify the prevalence of
depression and anxiety in PD in comparison to other chronic
conditions.
148
Depressive symptoms in Parkinsons disease correlate with brain
gray matter thinning over time
A. Hanganu, M.A. Bruneau, C. Degroot, C. Bedetti, B. Mejia-
Constain, A.L. Lafontaine, O. Monchi (Calgary, AB, Canada)
Objective: To evaluate the correlation between depressive symp-
toms and gray matter changes in the brain over time in patients with
Parkinsons disease (PD).
Background: Depression is one of the most common non-motor
symptoms in PD accounting for up to 40% of patients at the begin-
ning of the disease. However this condition is under-diagnosed in
PD with only 25% of patients who will actually receive effective
antidepressant treatment.
Methods: 24 non-demented patients with PD were studied twice
at 19.8 months apart by receiving a comprehensive neuropsycholog-
ical assessment and an MRI session at two time points. Using an
automated processing and analysis of MRI data, we performed a
longitudinal study and measured the rate of change of cortical
thickness over time in our group. Additionally, a correlation
between depressive symptoms score (Beck Depression Inventory)
and the rate of change of gray matter over time has been
performed.
Results: Depression was negatively correlated with the rate of
change of cortical thickness and subcortical volumes over time after
Monte-Carlo correction at p50.05. More specifically, a higher BDI
depression score was associated with a thinner cortical gray matter
in the rostral frontal, tempo-parietal and lingual regions. Additionally
negative correlations have been revealed with the hippocampus,
amygdala and nucleus accumbens volumes. Non-corrected clusters at
p50.001 were revealed in the supplementary motor, primary motor
and premotor regions.
Conclusions: Our data suggest a significant effect of depressive
symptoms over the cortical gray matter changes over time in PD
marker for evaluating the treatment effect in PD as well as to pre-
vent further cortical degradation.
149
Long-term effectiveness of pimavanserin in PD psychosis: Data
from 2 open-label studies
S. Isaacson, J.P. Azulay, J. Ferreira, D. Kreitzman, T.V. Ilic, K. Chi-
Burris, H. Williams, R. Mills (Boca Raton, FL, USA)
Objective: Two open-label studies (OLS) have assessed the long-
term safety of pimavanserin in PD Psychosis (PDP); continued effec-
tiveness was also evaluated.
Background: Psychosis is common in PD and increases with dis-
ease duration. It is associated with increased morbidity/mortality,
complicates management of motor symptoms and often leads to
long-term care placement. Pimavanserin is a potent, selective 5-
HT2A inverse agonist that has shown antipsychotic benefit with
improvements on night/day-time sleep and caregiver burden in 6-
week PDP RCTs. Long-term persistence of benefit may confer
improved patient and caregiver quality of life and help delay/prevent
institutionalization.
Methods: Patients completing a previous RCT could roll into a
OLS to receive pimavanserin QD for as long as the Investigator
considered it beneficial. In a Phase 2 OLS (N=39), long-term
Movement Disorders, Vol. 30, Suppl. 1, 2015
S58 POSTER SESSION

efficacy measures were limited to CGI-Severity (CGI-S), while in a

Phase 3 OLS (n5459), the Scale for Assessment of Positive Symp- Comparison of neuropsychiatric scales before and after
toms (SAPS) was used at Week 4 and CGI-S, CGI-Improvement dopaminergic treatment
(CGI-I), and caregiver burden score (CBS) were assessed at all PRE- POST-
visits. SCALE TREATMENT TREATMENT P VALUE
Results: 498 PDP patients were evaluated for a median period of
15 months (longest >8 years). In the Phase 2 OLS, improvement PDQUALIF-33 41.2 (9.7 SD) 31.6 (7.9 SD) <0.001
in CGI-S continued through Week 24, then maintained through MDS-UPDRS 32.3 (13.2 SD) 19.0 (7.6 SD) <0.001
Week 72 (with >50% subjects still active). At Week 96, with 34% MOCA 26.0 (2.8 SD) 27.0 (1.9 SD) <0.002
of subjects remaining, further improvement in mean CGI-S was BPRS 24.3 (2.8 SD) 24.1 (2.7 SD) 0.486
seen. In the larger ongoing Phase 3 OLS, subjects were enrolled HASD-A 4.9 (3.7 SD) 4.0 (2.5 SD) 0.006
from 114 international sites and receive once-daily pimavanserin HADS-D 4.9 (3.3 SD) 3.4 (2.1 SD) <0.001
40mg. SAPS-PD scores by blinded, independent raters at Week 4 DEX-sp 13.7 (9.9 SD) 9.4 (7.3SD) <0.001
(i.e., 10 weeks total treatment duration from core baseline) suggest QUIP-RS 6.81(9.5 SD) 6.83 (6.5 SD) 0.976
that effect is improved among patients previously treated with pla- LARS -18.7 (9.5 SD) -21.4 (6.3SD) 0.002
cebo (or low pimavanserin doses) and maintained in subjects previ-
ously treated with pimavanserin 40mg. Discontinuation for lack of
efficacy is <20%. Subjects who remain on study at 2 years main- In 46.8%, pramipexole was started. On the follow up-visit (n547),
tained an average CGI-I score of 2.5-2.7 (minimally-much improvement was found in quality of life, total MDS-UPDRS,
improved) and mean CGI-S showed minimal fluctuation (60.2). depression, anxiety, dysexecutive funtion, apathy and cognitive
CBS also shows stable benefit over time. function. No significant changes were found in the BPRS and QUIP-
Conclusions: In addition to efficacy in pivotal 6-week RCTs, RS. Worsening of disease severity, in terms of HY, was also found.
these two OLS provide support for durability of antipsychotic effect
and CBS in PDP. Pimavanserin may offer long-term benefit for Conclusions: Dopaminergic therapy has a statistically significant
patients with PDP with a demonstrated safety/tolerability profile effect on neuropsychiatric symptoms, with the exception of psychotic
appropriate for chronic use. symptoms and impulse control disorders. The latter symptoms are
associated with dopaminergic treatment.

150
Improvement of neuropsychiatric symptoms after initiation of
dopaminergic treatment in drug-naive patients with Parkinsos
disease
S. Isais-Millan, D. Pi~ na-Fuentes, A. Cervantes-Arriaga, M.
Rodriguez-Violante, C. Guzman-Astorga, R. Llorens-Arenas, H.
Calderon-Fajardo (Mexico, Mexico)
Objective: To determine the prevalence of neuropsychiatric dis-
orders in patients with Parkinsons disease before and after initiation
of dopaminergic antiParkinsonian treatment.
Background: Parkinsons disease is accompanied by a wide
range of psychiatric disturbances, some of which have been associ-
ated to dopamine replacement therapy.
Methods: A prospective study was carried out. Patients with
untreated PD were evaluated using Hoehn and Yahr scale (severity),
MDS-UPDRS (motor function), MoCA (cognitive impairment),
BPRS (psychosis), Dex-sp (dysexecutive), HADS (depression/anxi-
ety), LARS (apathy) and QUIP-RS (impulse control). Patients were
re-evaluated 6 months after initiating antiParkinsonian treatment
using the same scales. Scores pre-and post-treatment diagnosis and
scale score were compared using paired T test.
Results: A total of 63 patients were included in the basal
evaluation (61.9% men and 38.1% women). Mean age was 57.8
years (610.2 SD). Mean disease duration was 21.7 months
(615.8 SD).
Total MDS-UPDRS mean score was 40.52 (622.6 SD),
PDQUALIF-33 score was 40.6% (612.7 SD), Global HRQoL was
55.3% (620.9 SD). The mean BPRS score was 25.52 (65.4 SD),
while scores in the HADS anxiety and depression were 5.7 (64.4
SD) and 5.6 (64), respectively. Using the MOCA, a total of 41.3%
patients resulted in cognitive impairment (MCI in 80% of them).
According to the DEX-sp (Dys-executive Questionnaire), 19.5%
patients had dysexecutive impairment, 7.9% mild-moderate, 6.3%
moderadate-severe, and 4.8% severe. Using the LARS, a total of
20% subjects were diagnosed with apathy. Finally, the QUIP-RS
showed an ICD overall prevalence of 12.6%. Comparison of the
mean scores of all the scales before and after antiParkinsonian treat-
ment is shown in Table 1.
151
Clinical implications of psychotic syndrome diagnosis for patients
with Parkinsons disease
R.B.G. Kauark, P.C. Gordon, C.D. Miranda, M.O. Okada, F.
Godinho, M.S.G. Rocha (S~ ao Paulo, Brazil)
Objective: This study aimed to perform a clinical analysis of dif-
ferent subgroups of patients with Parkinsons disease (PD) and psy-
chotic symptoms.
Background: A significant percentage of PD patients show
changes of perception and thought characteristic of psychotic syn-
dromes, however only in some cases these phenomena will present
any clinical impact, and antipsychotic treatment indication.
Methods: Patients with idiopathic PD were selected. A neurolo-
gist evaluated each case for diagnosis confirmation and data collec-
tion, including unified Parkinsons disease rating scale (UPDRS),
sleep symptoms scales, NIH criteria for psychosis in PD, and cogni-
tive screening. A psychiatrist evaluated subjects using the structured
clinical interview for DSM disorders and the brief psychiatric rating
scale. Subjects underwent a formal neuropsychological evaluation,
with further diagnosis of dementia according with MDS criteria. Sub-
jects were divided into 3 groups: 1) Psychotic: subjects who meet
DSM-IV criteria for psychotic disorder; 2) Subsyndromal symptoms:
subjects who have psychotic symptoms according to NIH criteria,
but not classified as psychotic; 3) Non-psychotic: subjects without
any perception disturbance. Statistical analysis between groups
involved MANOVA and a post hoc analysis.
Results: There were 94 subjects (64.9% men), with a mean age
of 64.1 years (6 10.1) and mean duration of PD of 7.7 years (6
4.8). Fourteen (14.9%) subjects met the criteria for psychosis, and 35
(37.2%) had subsyndromal psychotic phenomena. UPDRS, cognitive,
sleep and psychopathological symptoms were significantly different
between the groups. Post-hoc analysis showed that the group
psychosis had higher rates of psychopathology, PD symptoms,
sleep disorder symptoms, and higher prevalence of dementia than the
groups subsyndromal symptoms and non-psychotic. There was
no difference between subsyndromal symptoms and non-
psychotic groups.
Conclusions: Although sleep and cognitive disturbances have been
associated with psychotic features in PD, not enough attention has

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
been paid to diagnosis of the psychotic disorder. Results suggest that
patients who meet the formal diagnosis of psychotic syndrome make
up a separate category with more psychopathological symptoms, sleep
disorders and low cognitive performance. This result is clinically
important for diagnostic criteria, with therapeutic and prognostic
implications.
152
Cognitive and psychometric properties of drug-induced
Parkinsonism and Parkinsons disease
J.S. Kim, J.M. Kim (Cheongju-si, Korea)
Objective: To investigate the cognitive and psychiatric aspects of
drug-induced Parkinsonism(DIP) and Parkinsons disease(PD).
Background: DIP is the second most common cause of Parkin-
sonism after PD and can be clinically indistinguishable from idio-
pathic PD, especially in early stages. Among clinical manifestations,
cognitive and psychiatric features that distinguish degenerative from
pharmacologic Parkinsonism are needed.
Methods: The sample consisted of consecutive patients who ful-
filled the clinical criteria for DIP and PD. General characteristics
include medication history were obtained. The clinical severity was
evaluated at first visit and after 6 months based on the activities of
daily living, score on the Unified Parkinsons disease Rating Scale,
and the Hoehn and Yahr scale. The patients cognitive state were
evaluated with the mini-mental state examination (MMSE), the Mon-
treal Cognitive Assessment (MoCA), Clinical Dementia Rating scale,
and mood disorders were screened by Hamilton Depression Rating
(HAM-D) scale, Hamilton Anxiety Rating scale, Sheehan disability
scale, and Liebowitz Social Anxiety Scale.
Results: Over 12 months, a total of 114 were included. Fifty one
patients (44.7%) were DIP patients, and 63 (55.3%) were PD patients.
The patients with DIP showed significantly lower educational level. In
addition, the number of comorbidities and taking medications were
more in DIP patients than PD. The score of MMSE and MoCA were
also lower in DIP patients who committed more errors than PD patients
on orientation and executive functions. In addition, higher HAM-D
scores were associated with DIP patients.
Conclusions: These findings suggested that cognitive impairment and
depression are common among DIP patients than PD. In addition, lower
educational level and disorientation, various comorbidities and many kinds
of medical pills might affect the drug induced medical problems.
153
Neuropsychiatric disorders in idiopathic Parkinsons disease
M.U. Kulsum, A. Dutt, S. Choudhuri, S.S. Anand, C. Sengupta, B.
Mondal, P. Chatterjee, H. Kumar (Kolkata, India)
Objective: 1. To study prevalence of various psychiatric disor-
ders in patients with PD.
2. To compare the prevalence of psychiatric disorders in Tremor
dominant (TD) variant of PD with that in postural instability gait dif-
ficulty (PIGD) variants of PD.
Background: Psychiatric and behavioral symptom associated with
Parkinsons disease (PD) is a frequently encountered problem which
may affect the quality of life of PD patients. By reason of inadequate
accessibility of reports in this ethnic population; we intended to assess
the frequency and determinants of PD associated psychiatric disorders.
Methods: In this cross sectional study conducted in a Movement Dis-
order and psychiatry Out Patient Department, we have evaluated 150
patients with PD (diagnosed by UK Brain Bank Criteria) on socio-
demographic and clinical profile. The PD symptoms were objectively quan-
tified using Unified Parkinsons disease Rating Scale (UPDRS), Modified
Hoehn and Yahr staging and Schwab and England activities of daily living
scale. Cognitive assessment was done by Mini Mental state examination
(MMSE). The Mini International Neuropsychiatric Interview was used to
screen for psychiatric illness and the National Institute for Neurological dis-
S59
order and Stroke, National Institute of Health (NIND and NIMH) criteria
was used to assess Parkinsons associated psychosis. Psychotic symptoms
and depression were rated using Brief psychosis rating scale (BPRS) and
Patient Health Questionnaire 9 (PHQ9) score respectively.
Results: 49.3% patients had one or more co morbid psychiatric dis-
orders. Depression (33.3%) was the most common diagnosis followed
by psychotic illness (24.7%) and anxiety disorder (20.7%). Patients
with psychiatric disorder had significantly higher UPDRS and H&Y
score (median score 2.5 Vs 2, p value 0.0001). Daily living was signifi-
cantly more impaired among patients with psychotic symptoms. These
patients had significantly higher daily dose requirement of dopaminer-
gic drugs. Psychotic symptoms were more frequent in Postural Instabil-
ity/gait difficulty (PIGD) variant of PD patients.
Conclusions: Psychiatric disorders are prevalent among patients
with relatively severe PD. Patients with PIGD variant of PD had a
higher risk of having psychiatric disorders as compared to tremor
dominant (TD) variant.
154
Relationship between cognition and the self-assessment of the
psychological symptom in PD
A. Kumon, Y. Kobayashi, M. Saruwatari, N. Kawashima, K.
Hasegawa (Sagamihara, Japan)
Objective: Investigate to clarify the relationship between cogni-
tion and self-assessment of depression in patients with Parkinsons
disease (PD).
Background: In patients with PD, depression is one of the most fre-
quent psychiatric symptoms and examined by several subjective scales.
But it is known there were the cases that those patients have difficulty in
self-assessment of the symptom or state such as posture and volume of
voice. Based on the results of our previous study about apathy, it is likely
to indicate a similar tendency in psychiatric symptoms.
Methods: Subjects were 124 patients with PD (male:
female=60:64, mean age 68.6 years old, MMSE24, HAMD<7),
who had been examined frontal lobe function, everyday memory and
subjective depression using FAB, RBMT, SDS, BDI-II.
Results: Subjects were divided into two groups according to
results tendency of SDS and BDI. 88 subjects whose results showed
same tendency were discrepancy (-) group. Other 38 subjects whose
results showed different tendency were discrepancy (1) group. Com-
pared with the discrepancy (-) and (1) group there were no signifi-
cant differences in age, Hoehn and Yahr Scale, HAMD and RBMT.
FAB score in discrepancy (-) group (14.5 6 2.4) was significantly
higher than in discrepancy (1) group (13.8 6 2.3) (p5 .032).
Conclusions: In 31% of PD patients maintaining a certain level of
cognitive function and without obvious depression, the results of self-
assessment of depression differed depending on the scale being used. And
the difference related to not everyday memory but frontal lobe function.
In PD patients, even though they have no problems with everyday mem-
ory, we should carefully evaluate results of subjective scale of depression.
Hereafter we will investigate other factors affecting the difference.
155
Psychotic symptoms in Thai patients with Parkinsons disease:
Prevalence and associated factors
P. Lolekha, K. Kulkantrakorn (Pathumthani, Thailand)
Objective: To determine the prevalence and associated factors of
neuropsychiatric symptoms in Thai Parkinsons disease (PD)
patients.
Background: Hallucinations, Sense of Presence (SoP) and delu-
sions are frequent neuropsychiatric symptoms that reduce quality of
life of PD patients. While the pathophysiology of these neuropsychi-
atric phenomena is not well understood, it is commonly believed as
a side-effect of dopaminergic treatment in combination with the
underlying brain pathology of PD patients.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S60 POSTER SESSION
Methods: One-hundred and thirty patients with PD were included
in the study. Demographic and clinical variables were recorded,
including Schwab & England Activity of Daily Living (SE-ADL
scale), UPDRS motor score, Hoehn & Yahr stage (H&Y), Levodopa
Equivalent Dose (LED), Thai Mental State Examination (TMSE),
and Thai Geriatric Depression Scale-15 (TGDS-15). Hallucinations,
SoP and delusions were assessed by Thammasat University Non-
Motor Symptoms Questionnaire (TU-NMSQuest).
Results: Of 130 PD patients, 33.1% (n543) had experienced psy-
chotic symptoms: hallucinations (21.5%, n528), SoP (17.7%, n523),
and delusions (20%, n526). Among the patients with psychotic
symptoms, 21% (n59) had isolated hallucinations, 7.1% (n53) had
isolated SoP, and 18.6% (n58) had isolated delusions. Auditory hal-
lucinations were found in 7.7% (n59) and all were combined with
visual hallucinations. The psychotic symptoms in PD patients were
significantly associated with poorer SE-ADL scale, lower TMSE
score, higher TGDS-15 score, higher TU-NMSQuest score, advanced
age, higher H&Y stage, and higher UPDRS motor score. Multiple
linear regression analysis showed severe cognitive impairment,
depression, anxiety disorder and advanced disease stage were the
most significant factors for psychotic symptoms in PD. Duration of
PD, type of antiParkinsonian medication and LED were not signifi-
cantly associated with these symptoms.
Conclusions: Hallucinations, SoP and delusions are common in
Thai PD patients and are likely to be multifactorial in origin.
Advanced disease stage, cognitive impairment, depression and anxi-
ety disorder are the most significant factors of psychotic symptoms
in Thai PD patients, regardless of disease duration, type and dosage
of antiParkinsonian medication.
156
Efficacy and tolerability of pimavanserin in PD psychosis:
Analysis of an integrated phase 3 placebo-controlled dataset
R. Mills, J.H. Friedman, W. Ondo, R. Pahwa, K. Black, K. Chi-
Burris, H. Williams (San Diego, CA, USA)
Objective: Pooling of efficacy data across studies can provide a
more precise estimate of overall treatment effect, treatment effect for
endpoints measured infrequently, and variation of effect across sub-
groups of interest. A pooled analysis of two Phase 3, placebo-
controlled studies was conducted to further evaluate the efficacy of
pimavanserin in PD Psychosis (PDP). The dataset comprised 268 N.
American subjects who received once-daily blinded treatment for up
to 6 weeks.
Background: Psychosis is common in PD and increases with dis-
ease duration. It is associated with increased morbidity/mortality,
complicates management of motor symptoms and often leads to
long-term care placement. Pimavanserin is a potent, selective 5-
HT2A inverse agonist being developed as a first-line treatment for
PDP.
Methods: Pooling is appropriate only for homogeneous popula-
tions, where the same treatment duration, comparator and treatment
regimens were used. These conditions were met for Studies ACP-
103-020 and -012 (North America, pimavanserin 40mg and placebo
groups). The analysis included 133 placebo- and 135 pimavanserin-
treated subjects.
Results: Pimavanserin 40mg demonstrated a 6.21-point improve-
ment in psychosis at Week 6 as measured by blinded, independent
raters using the PD-adapted Scale for Assessment of Positive Symp-
toms (SAPS-PD; primary change from baseline analysis [MMRM]).
The treatment difference was 2.87 points over placebo (p<0.001)
and was clinically meaningful. Pimavanserin 40mg also showed stat-
istically greater benefit over placebo on all SAPS supportive meas-
ures and sensitivity analyses as well as on CGI-Severity, CGI-
Improvement (CGI-I), CGI-I responder analysis, SCOPA-nighttime
sleep and daytime wakefulness measures, and caregiver burden score.
Results were consistent across all subgroups of interest, showing
greater improvement with pimavanserin 40mg over placebo, regard-
Movement Disorders, Vol. 30, Suppl. 1, 2015
less of age, sex, race group, or screening MMSE score. There was
no worsening of Parkinsonism as measured by UPDRS II1III, and
the adverse event profile was virtually identical to placebo.
Conclusions: Pimavanserin appears effective, safe and well-
tolerated for PDP based on individual study data (previously pub-
lished) and in this pooled analysis of Phase 3 placebo-controlled
data.
157
Othello syndrome in a Parkinsons disease patient with dementia
initiating Donepezil therapy: A case report
O.A. Molokwu, I.O. Onwuekwe, A.C. Nwabueze (Enugu, Nigeria)
Objective: To report a case of Othello syndrome in a Parkinsons
disease patient with dementia following commencement of
Donepezil.
Background: Psychiatric presentations such as depression, delu-
sional disorders etc. have been described in patients with Parkinsons
disease (PD). Othello syndrome (OS) describes a psychiatric condi-
tion characterized by morbid jealousy in which the sufferer holds a
strong delusional belief of spousal or sexual partners infidelity with-
out having any significant proof to back up such claim.The causes of
OS cuts across psychiatric illness, alcoholism, drug abuse, neurologi-
cal illness including PD and/or in association with its drug treatment
etc. Few case reports have described the occurrence of OS in PD
patients.OS impacts negatively on marital relationship and increases
caregiver strain. OS increases the risk for violence and aggression
towards spouse which if not tackled may lead to suicide and/or
homicide.
Methods: We report a case of Othello syndrome in a PD patient
who was initiating treatment with Donepezil for recently diagnosed
dementia and to review literature on the condition.
Results: A 62 year old man who was diagnosed of PD with
dementia and was commenced on Donepezil. About a week there-
after, he developed morbid jealousy associated with delusional belief
that his wife was having an affair with his bosom friend. He engaged
in confirmatory behaviors such as checking his wifes phone call list
and messages. He was aggressive sometimes, then later became
depressed.The temporal association with initiation of Donepezil
tended to suggest that the OS was an adverse drug reaction (ADR).
However,Naranjo score for ADR probability was 2 which implies a
probable ADR.He was admitted into the ward and did haemogram,
liver function test, biochemical panel test which were unremarkable.
CT scan done showed age related brain atrophy. He was reviewed
by the psychiatrist and was tried on some neuroleptics and antide-
pressants with minimal improvement. He was later discharged on
request by the relatives and was lost to follow up.
Conclusions: Prompt recognition and treatment of Othello syn-
drome is imperative in other to prevent the untoward knock-on nega-
tive effect on marital relationship and patient outcome. while
checkmating the increased risk of violence against partner, suicide
and/or homicide seen in this condition.
158
Effect of dopaminergic medication on BOLD fMRI in
Parkinsons disease patients with visual hallucinations during a
visuoperceptual task
A.J. Muller, C. OCallaghan, J.M. Shine, S.J.G. Lewis (Sydney,
Australia)
Objective: To investigate neural mechanisms affected by dopami-
nergic Parkinsons disease (PD) medications during visual misper-
ception events in patients with visual hallucinations (VH).
Background: Although VH are extremely common in PD, their
neural mechanisms remain poorly understood. First line of treatment
of VH in PD usually involves a reduction of dopaminergic medica-
tion dose; however the direct effects of dopaminergic medication on
 POSTER SESSION
the neurobiology underlying hallucinatory events has yet to be
established.
Methods: We performed functional MRI combined with the
Bistable Percept Paradigm (BPP), a visuoperceptual task capable of
eliciting visual misperceptions in patients with VH. All 15 patients
reported VH and were assessed in a randomised order both on their
regular treatment and on a separate occasion after overnight with-
drawal of their dopaminergic medication. Task-based functional MRI
data was analysed to investigate the neural activity patterns associ-
ated with correct perceptions on the task versus visual mispercep-
tions, in both the ON and OFF states. Correction for multiple
comparisons was performed by controlling FWE<0.05, with 20-
voxel extent threshold.
Results: Misperceptions were associated with significantly differ-
ent neural activity patterns in the ON versus OFF states. These
included a significant increase of activation in the right parietal lobe,
and left inferior parietal lobe, cuneus, precuneus and dorsal posterior
cingulate area. A significant decrease of activation was shown in the
left superior frontal gyrus. Behaviourally, there was no difference in
the amount of misperceptions experienced in the ON and OFF states,
although patients exhibited significantly higher levels of mispercep-
tions on the BPP compared to established performance in healthy
age matched controls (p < .01).
Conclusions: Whilst behavioural results did not show significant
differences within patients, these results indicate that dopaminergic
medication mediates neural activity associated with hallucinatory
events. The left-lateralised inferior parietal lobule, precuneus, and
dorsal posterior cingulate regions potentially implicate dopaminergic
modulation of the default mode network during visual misperceptions
in PD with VH; a network normally involved in introspection and
self-referential tasks. The present results have implications for the
understanding and management of VH in PD.
159
Investigation of factors associated with distinct psychiatric
symptoms in patients with advanced Parkinsons disease
K. Nakahara, R. Kurisaki, T. Sakamoto, K. Yi, T. Yamashita, K.
Uekawa, Y. Ando (Uki, Japan)
Objective: To investigate factors associated with individual psy-
chiatric symptoms in patients with advanced Parkinsons disease
(PD).
Background: Psychiatric symptoms are serious complications in
patients with advanced PD.
Methods: Ninety-nine patients with PD who had Hoehn and
Yahr (HY) scale scores 3 were treated as outpatients or inpatients
in our institute between April 1 and November 30, 2013. Among
these, seven patients who underwent stereotactic brain surgery or had
insufficient data were excluded from the study.
Based on the medical interviews and examinations performed by
neurologists, relationships between psychiatric symptoms (hallucina-
tion, dementia, depression, delusion) and other clinical parameters
were assessed in a retrospective cross-sectional analysis.
Results: Demographic characteristics of patients with PD were:
male, 34, female, 58; mean age, 72.7 6 10.9 years old; mean dura-
tion of PD, 9.8 6 6.3 years; and mean HY stage, 3.9 6 0.8 (stage 3:
46 patients, stage 4: 25 patients, stage 5: 21 patients). Psychiatric
symptoms were diagnosed in 36 patients (39.1%); of these 19 had
hallucinations; 18, dementia; 10, depression; and 5, delusion. Uni-
variable logistic regression analysis revealed that the presence of hal-
lucination significantly correlated with the duration of PD, urinary
incontinence (UI), and dyskinesia (Dys); presence of dementia signif-
icantly correlated with duration of PD, HY stage, and UI; and delu-
sion significantly correlated with Dys. Depression did not correlate
with other clinical parameters. Multivariable logistic regression anal-
ysis (explanatory variable: every item showing a significant differ-
ence by each analysis) revealed that hallucination significantly
correlated with UI [Odds ratio (OR), 4.489; 95% confidence interval
S61
(CI), 1.432 to 14.617; p 5 0.010] and dementia significantly corre-
lated with HY stage 5/3 (OR, 5.304; 95% CI, 1.327 to 22.948;
p 5 0.018).
Conclusions: Our results suggest that among patients with PD,
the presence of hallucination, dementia, and delusions may be related
to UI, HY stage, and Dys, respectively.
160
Parkinsons disease psychosis (PDP): Characteristics of the PDP
patient in clinical practice
J. Norton, D. Fredericks, R. Suresh, R. Mills (San Diego, CA, USA)
Objective: To characterize the typical PDP patient across a vari-
ety of dimensions.
Background: PDP is a prevalent neuropsychiatric manifestation
with lifetime prevalence in Parkinsons disease (PD) patients of up
to 50%. The PDP patients care is complex due to the need to not
only manage the symptoms of Parkinsons but also a variety of non-
motor issues, including psychosis.
Methods: 214 physicians (132 neurologists, 37 psychiatrists, and
45 primary care physicians) were asked to participate in a question-
naire on PDP patients. Patients with Schizophrenia, Schizo-affective
disorder or Bipolar disorder were ruled out. Patient records were
required to include:
2 records for patients currently being treated with an
antipsychotic.
1 record for patients currently being treated with either an anti-
psychotic, anti-depressant or anti-dementia agent.
1 record for patients managed through modification of PD
medications.
A total of 716 patient records were collected and reviewed.
Results: The chart review revealed that the typical PDP patient
was 74 years of age, male (63%), and on Medicare (74%). The
majority of PDP patients were living at home and being managed in
an office setting (54%), while 19% were in a long term care setting.
89% had some type of caregiver support, typically by an unpaid
caregiver. The reported psychotic symptoms varied, with 50% report-
ing hallucinations, 33% delusions, 33% lack of impulse control, 32%
paranoia, and 25% aggressive behavior. In 60% of the PDP patients,
the onset of psychotic symptoms developed at an average age of 67
and within 4 years of initial PD diagnosis. The PDP patient typically
had more severe PD and a higher incidence of comorbidities, partic-
ularly Alzheimers disease and renal dysfunction. Additionally, 71%
of PDP patients suffered from sleep disorders.
Conclusions: The PDP patient is typically older and has a signifi-
cant number of comorbidities adding to the complexity of their treat-
ment. Current literature suggests that PDP patients suffer primarily
from hallucinations within the latter half of the first decade after
diagnosis; however, this study found that delusions, impulse control
issues, paranoia and aggressive behavior are also common and occur
earlier in the course of the disease. Because of the severity of these
symptoms treatment should be considered earlier.
161
Risk factors for psychosis in patients with Parkinsons disease
M.S.G. Rocha, R.G. Borges, C.D.M. Costa, M.O. Oliveira, S.M.D.
Brucki, F.F. Godinho, P.C. Gordon (Sao Paulo, Brazil)
Objective: The aim of this study is to evaluate risk factors, par-
ticularly sleep alterations and dementia, associated with psychosis
diagnosis in PD.
Background: Parkinsons disease (PD) patients frequently present
psychotic symptoms that have been associated with old age, duration
of PD, and cognitive impairment. Depression and sleep abnormalities
are also related to these factors.
Methods: This is a cross-sectional evaluation of 94 consecutive
patients from a Movement Disorders clinic. A neurologist performed
Movement Disorders, Vol. 30, Suppl. 1, 2015
S62 POSTER SESSION
clinical evaluation. Behavioral questionnaires were applied by a psy-
chiatrist, who used structured interview with both patient and care-
giver to define psychosis diagnosis (PC) in accordance with DSM-4
criteria. Clinical evaluation included UPDRS, sleep scales (SCOPA-
sleep, Epworth and REM sleep behavior disorder), quality of life
(PDQ-39), depression (Beck Inventory), and NINDS criteria for psy-
chosis in PD. Subjects underwent a formal neuropsychological evalua-
tion, with further diagnosis of dementia according with MDS criteria.
Results: Among 94 PD patients (64.5% male, mean
age 5 64.1 6 10.1), psychosis was present in 13.8% of cases (13);
individuals with PC had significant differences (p<0.01) in relation
to patients without PC in relation to diurnal sleep quality (SCOPA-
Sleep), more severe diurnal hyper somnolence (Epworth scale),
worse quality of life (PDQ39), and more severe depression. Demen-
tia was significantly higher between PC patients (84.6%) than those
without psychosis (24.5%). There was no significant difference in
severity of REM sleep behavior disorder between groups. Logistic
regression analysis, including age, sex, PD duration, UPDRS total
score, Hoehn & Yahr stage, daily levodopa equivalent dosage, Beck
depression inventory score, sleep scales scores, and postural instabil-
ity gait disorder score, showed that only dementia and Epworth score
were independently associated with PC in PD (p50.002 for demen-
tia, and p50.016 for Epworth score).
Conclusions: Our data show that the presence of dementia and diur-
nal somnolence are strongly associated with PC in PD and reaffirm that,
in most patients, psychotic symptoms are probably part of a full spectrum
of dementia associated with PD, and not an isolated syndrome.
162
Incidence and severity of impulse control disorders in
Parkinsons disease patients treated with dopamine agonists
M.C. Rodrguez-Oroz, R. Ribacoba Montero, A. Rojo-Sebastian, A.
Sesar Ignacio, M. Delgado-Alvarado, B. Ares Pensado (San Sebas-
tian, Spain)
Objective: Evaluate the incidence and severity of Impulse Con-
trol Disorders (ICDs) among Parkinsons disease (PD) patients
treated with dopamine agonists (DAs).
Background: Chronic use of DAs is often associated with side
effects among which ICDs are common.
Methods: An observational, descriptive, cross-sectional study was
conducted in 4 hospitals in Spain. A total of 159 patients treated
with ropinirole, pramipexole or rotigotine were consecutively
recruited, 53 patients in each treatment arm. Patients with PD on
treatment with a DA for a minimum of 2 years or less if an ICD
occurred were eligible to participate. Demographic and clinical data
of patients, previous history of DAs and treatment at the time of the
study and when an ICD occurred were collected. Clinical features
were evaluated using the following scales: Hoenh and Yarh Scale,
Unified Parkinsons disease Rating Scale (UPDRS), Questionnaire
for Impulsive-Compulsive Disorders (QUIP-PD), QUIP- Rating Scale
(QUIP-RS), Barratt Impulsiveness Scale, Novelty Seeking Test, Hos-
pital Anxiety and Depression Scale (HADS) and Parkinsons disease
questionnaire (PDQ-8). Patient analysis sets: pramipexole-ropinirole
(group A) and rotigotine (group B).
Results: 151 patients were analysed: pramipexole (51), ropinirole
(49), rotigotina (51). 64% were male with a mean age of 68 6 8.8.
ICD by clinical criteria occurred in 11% and 14% of patients in
groups A and B respectively (p50.62). QUIP questionnaire showed
more gambling and less hobbyism (p<0.05) in group B (gambling A
4% and B14%; hobbyism A 37% and B 20%) without differences in
the (QUIP-RS) between the groups. No differences in incidence of
ICDs were seen for different cumulative doses of DA Patients in
group A were younger and had less years of evolution of the disease
(age: A: 67 6 8.9 and B: 70 6 8.3; years of disease: A: 8 6 5.1 and
B: 10 6 5.3). UPRDS and PDQ-8 scores were higher in group B
(UPDRS II: A: 12 6 6.0, B: 16 6 8.3; UPDRS III: A: 19 6 9.6, B:
28 6 13.4; UPDRS IV, A: 2 62.3, B: 3.5 6 2.9; PDQ-8: A: 27 6 18,
Movement Disorders, Vol. 30, Suppl. 1, 2015
B: 35 6 22). There were no differences in the rest of scales except
for HADS (A: 5 6 3.9, B: 6 6 4.4), although these scores were below
clinical significance.
Conclusions: The incidence of ICD was similar with the different
DAs. Rotigotine was more frequently associated with gambling and
less with hobbyism than pramipexole and ropinirole but the severity
of all ICDs was not different among groups.
163
Left temporal lobe focal EEG abnormalities in Parkinsons
disease with visual hallucinations
G.J. Schwartz, M.L. Gordon (Stony Brook, NY, USA)
Objective: To describe electroencephalography (EEG) abnormal-
ities in a cohort of Parkinsons disease (PD) patients with visual hal-
lucinations (VHs).
Background: The cause of VHs in PD remains poorly under-
stood. While dopaminergic medications have been implicated, there
is a growing body of evidence suggesting that VHs may be a mani-
festation of the underlying disease itself. One study has suggested
that left hemispheric dysfunction in particular is associated with VHs
in PD. Furthermore, the phenomenology of temporal lobe ictal hallu-
cinations resembles those of VHs in PD.
Methods: We conducted a retrospective chart review of PD patients
with VHs, who had routine EEGs available for review. This cohort of
patients had no clinical evidence of seizures. They underwent routine
clinical EEGs to determine whether some of these patients might have
electroencephalographic evidence of temporal lobe seizures.
Results: Forty nine EEGs were available for review in 28 patients
with PD and VHs. The male:female ratio was 1.5:1, the average age
was 79 years, and Parkinsonian motor signs were right-predominant in
70% (p 5 0.10 by Chi-square). The mean duration of PD, dopaminer-
gic pharmacotherapy, and VHs was 10, 8 and 3 years, respectively.
Formed VHs were present in all patients, although 11% had elemen-
tary VHs as well. They were predominantly diurnal, although in 14%
of patients they were only hypnopompic. At least one abnormal EEG
was found in 85% of patients: generalized background slowing in
79%, intermittent delta activity in 21%, and focal temporal lobe spikes
or sharp-waves in 14%. Lateralized focal EEG abnormalities were
detected in 17% (n 5 5), all of which appeared in the left temporal
lobe. The probability of lateralized abnormalities occurring exclusively
on the left by chance alone would be less than 4% (p 5 0.03).
Conclusions: We found left temporal lobe focal EEG abnormal-
ities in a subset of PD patient with VHs, findings which are consist-
ent with a potential for left temporal lobe epileptogenicity.
Furthermore, in this cohort of PD patients with VHs, we found a dis-
proportionate number of those with left hemisphere-predominant Par-
kinsonism. These findings suggest that left temporal lobe dysfunction
may predispose to VHs in PD.
164
Limitations of the BDI-II in PD evaluation: Concordance with
the GDS-30
M.J. Sollman, I. Ul Haq, S.S. Kramer, J.F. Cook, J.G. Hesse, M.S.
Siddiqui, A.W. Laxton, S.B. Tatter (Winston Salem, NC, USA)
Objective: To evaluate diagnostic utility and operating character-
istics of the BDI-II in Parkinsons disease (PD) patients undergoing
neuropsychological assessment as part of routine care or Deep Brain
Stimulation surgery (DBS) evaluation.
Background: The presence of Depression in PD has relevance to
QOL (Jones et al., 2014), suicidal ideation, and DBS planning. A
high estimated prevalence of minor or major depression in PD (20-
45%) suggests strong need for routine screening. Tremendous
research has supported use of the BDI-1a as a screening instrument
in this population. Less knowledge is available about the BDI-II,
while very similar to its predecessor (see Inoue et al., 2010).
 POSTER SESSION
Methods: We examined concordance between the BDI-II and GDS-
30, another well-validated measure of depression that places significantly
less emphasis on somatic symptoms (Ertan et al., 2015; Schrage et al.,
2007). Participants were 204 PD-positive, well-educated older adults
(mean education 14 [SD=2.9] years) undergoing full neuropsychological
evaluation as a part of routine care or DBS work-up(71%). The Interna-
tional Parkinson and Movement Disorder Society (MDS) Task Force-
recommended score of 9/10 (Schrage et al., 2007) was used for the GDS-
30, and published cut score of 14/15 was used for the BDI-II.
Results: In the overall sample, 33.0% of patients screened positive
with the GDS-30 compared to only 6.7% with the BDI-II, despite its
inclusion of somatic symptoms. Concordance in 120 patients adminis-
tered both screens suggests a BDI-II sensitivity of .71 and a specificity of
1.0 (GDS-30 5 28.3%, BDI-II 5 8.3%, hit rate 5 .80). The rate of detec-
tion was not grossly different in the subset of 86 pre-DBS patients
(26.7% versus 5.8%). The sample had similar prevalance of apathy
(30%) as found in other studies (e.g., Zahodne et al., 2012). Maximizing
sensitivity of the BDI-II while maintaining adequate specificity required
a cut score of < 4 in this sample (AUC=.915, Sn=1.0, Sp 5 .826).
Conclusions: Our data suggest the BDI-II grossly underestimates
the likelihood of current minor or major Depression in PD patients
using validated cut scores. This does not appear to be due to presen-
tation management of pre-DBS patients. Lowering the BDI-II cut
score to maximize sensitivity was not a reasonable solution in this
sample. The GDS-30 is felt to be additionally beneficial in offering
two questions of hopelessness.
165
Brain regions associated with neuropsychiatric symptoms in
patients with Parkinsons disease: An analysis of cerebral blood
flow using 123I-iodoamphetamineSPECT
H. Tachibana, K. Kawabata, T. Yamanishi, H. Nishimura, T.
Tokunaga, T. Nakajima (Nishinomiya, Japan)
Objective: To analyze correlations between rCBF and neuro-
psychiatric symptoms such as cognitive impairment, depression, apa-
thy, and anxiety.
Background: Mental impairments and neuropsychiatric symp-
toms can appear in patients with Parkinsons disease (PD), which
may affect regional cerebral blood flow (rCBF).Previous human
imaging studied failed to achieve a consensus regarding regional
changes associated with these symptoms in patients with PD.
Methods: Thirty-three patients with PD (mean age, 71.7 years)
underwent brain SPECT using 123I-iodoamphetamine.SPECT images
were constructed using the 3D-SSP program. Correlational analyses
between rCBF reduction and the degree of neuropsychiatric symp-
toms were performed using SSPcor.exe program. In voxel-by-voxel
correlation between rCBF and clinical parameters, the statistical
results were expressed as Z score on surface projections maps. PD
patients completed the Beck Depression Inventory 2nd edition (BDI-
II),the State-Trait Anxiety Inventory (STAI), and Starksteins Apathy
Scale (AS) . The Hoehn and Yahr (HY) staging, the Unified Parkin-
sons disease Rating Scale (UPDRS) and Mini-Mental State-Exami-
nation (MMSE) were administered on the same day.
Results: The mean scores of MMSE,BDI-II, AS and STAI were
27.4, 17.0, 17.4 and 49.4, respectively. The mean values of duration
of illness and HY scale were 7.4 years and 2.9, respectively. Signifi-
cant correlations between rCBF and MMSE score were found partic-
ularly in bilateral frontal cortices. Significant negative correlations
between rCBF and BDI-IIscores were noted in bilateral temporal,
parietal and occipital cortices, precuneus, posterior cingulated cortex
and cerebellum. Correlations in similar areas were observed between
rCBF and AS scores. In the STAI score, negative correlations were
found in bilateral parieto-temporo-occipital cortices, medial part of
frontal cortex and cerebellum.
Conclusions: Present results suggest that there are some differen-
ces in associated brain regions among these major neuropsychiatric
symptoms and cognitive impairment in PD patients.
S63
166
Dopaminergic medication increases risky choice via decreasing
loss aversion in depressed but not in non-depressed Parkinsonian
patients
M. Timmer, G. Sescousse, P. Piray, R. Esselink, R. Cools (Nijmegen,
Netherlands)
Objective: To investigate dopaminergic drug effects on loss aver-
sion defined as the relative weighting of gains and losses during
risky choice in depressed and non-depressed patients with Parkin-
sons disease (PD).
Background: Dopaminergic medication is known to trigger undesir-
able side effects such as impulse control disorders (ICDs) in patients
with PD. However, these side effects only occur in a subgroup of
patients, presumably reflecting an underlying vulnerability related to ven-
tral striatal function. Depression, which is associated with ventral striatal
dysfunction, is a frequent non-motor symptom of PD. Here we hypothe-
size that it might constitute a vulnerability factor for developing ICDs
following dopaminergic medication, eventually leading to risky behavior.
Methods: Depressed and non-depressed PD patients performed a
well-established gambling task designed to measure loss aversion during
risky choice. Dopaminergic drug effects on loss aversion were investi-
gated using a within-subject design, in which patients were assessed on
two occasions - once after taking their normal dopaminergic medication
(ON) and once after withdrawal of their medication (OFF).
Results: Dopaminergic medication induced differential effects on
loss aversion in depressed and non-depressed PD patients. While
there was no clear drug effect on loss aversion in non-depressed PD
patients, dopaminergic medication significantly reduced loss aversion
(i.e. increased risky choice) in currently depressed PD patients. Fur-
thermore, the degree to which medication reduced loss aversion cor-
related with current depression severity and with drug effects on
depression scores. Medication-related reductions in loss aversion
were greater in more severely depressed patients and in patients who
exhibited greater medication-related decreases in depression scores.
Conclusions: Dopaminergic medication increases risky choice via
decreasing loss aversion in depressed but not in non-depressed PD
patients. These data suggest that side effects of dopaminergic medi-
cation in the domain of risky choice might differ between depressed
and non-depressed PD patients.
167
Withdrawn by Author
POSTER SESSION 2
Monday, June 15, 2015
12:3014:00
Coronado Ballroom
Parkinsons disease: Clinical trials,
pharmacology and treatment
168
Repeated intravenous amantadine infusions in advanced
Parkinsonism: The preliminary Tel-Aviv Medical Center
experience
M. Abu Snineh, T. Nussbaum, A. Hindi, A. Rosenberg, J. Knaani, A.
Ezra, N. Giladi, T. Gurevich (Tel Aviv, Israel)
Objective: To summarize our experience with repeated intrave-
nous Amantadine in patients with advanced Parkinsonism.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S64 POSTER SESSION
Background: Few studies have examined the effect of intrave-
nous amantadine infusions in advanced Parkinsonism.
Methods: The medical files of 30 patients were reviewed. They
received IVAM once every 3-4 weeks in the setting of neurological
day care service. Patients and caregivers participated in a structured
interview on clinical global impression of changes scale (CGICS)
regarding various symptoms. Treatment was initiated by a loading
dose of 200/400 mg for 5 days followed by a once every 2-3 weeks
dosage of 200/400 mg depending on the duration of treatment effect.
Results: Thirty patients (12 females) participated in the study.
Nineteen had PD, 5 had multiple system atrophy (MSA) Parkinsonian
type, 3 had MSA cerebellar type, 2 had vascular Parkinsonism, and 1
had diffuse Lewy body disease. Their mean age was 73.27 6 9.67
years, average disease duration 5.5 6 4.8 years, and H&Y score
3.16 6 0.87. The average levodopa dose was 1051 6 1782 mg. The
mean IVAM treatment duration was 22.9 6 11.26 months. Most
(76%) of the patients reported an improvement in tremor and rigidity,
and an improvement in stability and falling reduction (79%).
An unexpected significant improvement of constipation was
reported by 4 patients (20%, p =0.012). Overall 91% of the patients
and 81% of the caregivers reported improvement in general functio-
ning.The main advantages of the treatment according to the patients
was gait improvement and decrease in the dosage of antiParkinsonian
drugs (8 patients). Three patients reported treatment-related confu-
sion and urinary complaints.
Conclusions: The results of this retrospective open-label study
indicated that repeated IVAM were effective and safe in patients
with Parkinsonism. Controlled double blind studies for exclusion of
a placebo effect are warranted.
169
A randomized controlled trial of telemedicine for Parkinsons
disease (Connect.Parkinson) in the United States: Interim
assessment of investigator and participant experiences
M.A. Achey, C.A. Beck, D.B. Beran, C.M. Boyd, P.N. Schmidt, A.W.
Willis, S.S. Riggare, R.B. Simone, K.M. Biglan, E.R. Dorsey, J.
Aldred, J. Ayan, M.T. Bull, J. Carter, K. Duderstadt, B. Dunlop,
N.B. Galifianakis, P. Hickey, C.B. Hunter, J. Jimenez-Shahed, H.T.
Keenan, R.E. Korn, Z. Mari, N.I. Meijia, J.C. Morgan, M.A. Nance,
S.A. Parashos, I.H. Richard, L.C. Shih, M.A. Spindler, C. Wielinski,
C. Zadikoff (Rochester, NY, USA)
Objective: The Connect.Parkinsons study aims to assess the fea-
sibility, efficacy, impact on quality of care, and value to patients and
families of home telemedicine visits for Parkinsons disease (PD).
Background: This is the first national randomized comparative
effectiveness study of telemedicine for PD.
Methods: Participants are recruited via PD community website and
social media outreach, e-mails to advocacy groups, and outreach to pri-
mary care providers in underserved areas. Participants are randomly
assigned to usual care or usual care plus 4 telemedicine visits with a
specialist. Primary outcomes include feasibility, measured by percent-
age of telemedicine visits completed, and efficacy, measured by change
in PDQ-39. Secondary outcomes include blinded MDS-UPDRS scores.
Here we report preliminary enrollment, retention, and satisfaction.
Results: As of January 2015, 87 people (44% of 200 planned) are
enrolled and 61 (70%) have been randomized. Four have withdrawn,
due to disappointment at randomization to control (n51), preference
TABLE 1. Mean Pharmacokinetics of APL-130277 and SC Apomorphine
Dose Cmax (ng/ml) Tmax (min)
APL-130277 10 mg 5.45 34.2
SC apomorphine 2 mg 9.78 20.4
APL-130277 15 mg 8.02 39.2
SC apomorphine 3 mg 16.2 26.7
Movement Disorders, Vol. 30, Suppl. 1, 2015
of local provider (n51), and technology incompatibility (n52). Partic-
ipants mean age is 65, mean disease duration is 8 years (range 1-22),
and 51% are women. The 29 telemedicine participants are younger
(mean 63) than the 32 usual care participants (mean 67) (p<0.05),
while gender distribution and disease duration are similar (p>0.05).
To date, 27 telemedicine visits have been completed, 93% as
scheduled. Median visit duration is 51 minutes, 42 (82%) of which
are spent with investigators. Participants report spending 120 minutes
(median) away from home for their last in-person appointment, 30
(25%) with a provider. All participants report being very satisfied
or satisfied with the care, comfort, and overall experience of tele-
medicine. Video quality remains a limitation: for 38% of initial tele-
medicine visits, investigators were highly unsatisfied (14%) or
unsatisfied (24%) with their ability to perform the MDS-UPDRS
motor assessment. However, 21 visits (78%) were rated highly sat-
isfactory or satisfactory overall by investigators.
Conclusions: Participants are highly satisfied with telemedicine
visits. Investigators are modestly satisfied, but connection quality
remains a challenge. Future results of participant-reported and blinded
outcomes will enable comparison of telemedicine care to usual care.
170
Pharmacokinetics, safety and tolerability of sub-lingually
administered APL-130277 compared to subcutaneous
apomorphine in healthy volunteers
A. Agro, J. Dubow, L. Toong-Chow, A. Giovinazzo (Toronto,
Canada)
Objective: To evaluate the pharmacokinetics, safety and toler-
ability of 2 doses of Sub-lingually administered APL-130277 (APL)
compared to subcutaneous apomorphine (SC Apo) in healthy
volunteers.
Background: Parkinsons disease (PD) patients suffer from a
variety of Off episodes as the disease progresses. These consist of
wearing off, delayed-On or dose failures, sudden Offs and morning
akinesia. The only acute and effective rescue medication for these
Off episodes is apomorphine administered subcutaneously. Easier
to administer rescue treatments are needed. APL is a soluble film
strip of apomorphine delivered sub-lingually, designed to deliver
apomorphine rapidly through absorption from the oral cavity.
Methods: This was a single-center, Phase 1 trial in healthy vol-
unteers that assessed the single-dose pharmacokinetics, safety and
tolerability of APL administered to two cohorts (10mg and 15 mg)
in a cross over design as compared to 2 mg and 3 mg of SC Apo
(10 mg APL received 2 mg SC Apo and 15 mg APL received 3 mg
of SC Apo). Subjects were dosed with APL film strip on the under-
side of the tongue with the drug layer facing the bottom of the
tongue. Subjects were pre-medicated with 3 days of domperidone,
which was continued during treatment.
Results: The mean Cmax, Tmax, T1/2 and AUC for APL 10 mg
(N=13), APL 15 mg (N=12), SC Apo 2 mg (N=13) and SC Apo
3 mg (N=12) are outlined in Table 1. Mean plasma levels are pre-
sented in Figure 1. The time spent above 3 ng/ml (the typical plasma
level for a patient to go from Off to On) was longer for APL
compared to SC Apo and the number of subjects reaching the mini-
mal toxic concentration (8.5 ng/ml) was lower for APL compared to
SC Apo.
[figure1]
T1/2 (min) AUCLast (min*ng/ml) AUCinf (min*ng/ml)
56.5 509 543
42.1 597 612
54.7 804 854
40.1 996 1022
 POSTER SESSION S65

TABLE 2. Number and Percentage of Subjects With Adverse Events On APL-130277 Compared to Subcutaneous Apomorphine
Adverse Event APL 10 mg N(%) N=13 SC Apo 2 mg N(%) N=13 APL 15 mg N(%) N=14 SC Apo 3 mg N(%) N=14
Any AE 5(38) 11(85) 13(93) 12(86)
Related AE 5(38) 9(69) 11(79) 12(86)
Moderate AE 2(15) 5(38) 4(29) 11(79)
Sleepiness 0 3(23) 11(79) 10(71)
Nausea 2(15) 4(31) 3(21) 8(57)
Dizziness 3(23 4(31) 7(50) 7(50)
Vomiting 0 0 2(14) 5(36)
Yawning 0 0 0 3(21)

Fig. 1. (170).

APL was safe and well-tolerated. A higher incidence of AEs of
nausea and vomiting were reported when subjects crossed over from
APL to SC Apo (Table 2). There was a higher incidence of related
AEs and moderate AEs with SC APO than with APL and the only
severe AE of seizure occurred with SC APO 3 mg. There were no
discontinuations due to AE.
Conclusions: Sub-lingually administered APL reaches therapeutic
blood levels comparable to SC Apo but remains in the therapeutic
window for a longer duration of time with less dopaminergic and
severe adverse events compared to SC Apo. APL-130277 may offer
an easy to administer, rapid, on-demand treatment of Off episodes
in PD patients.
soluble film strip of apomorphine delivered sub-lingually, designed
to deliver apomorphine systemically through absorption from the
oral cavity. This is the highest dose of APL studied in healthy
volunteers.
Methods: This was a single-center, randomized, double-blind,
placebo-controlled Phase 1 trial in healthy volunteers assessing the
single-dose pharmacokinetics, safety and tolerability of APL 25 mg.
Subjects were pre-medicated with 3 days of the anti-emetic domperi-
done, which was continued during treatment.

171
Pharmacokinetics, safety and tolerability of high-dose sub-
lingually administered APL-130277 in healthy volunteers
A. Agro, J. Dubow, L. Toong-Chow, A. Giovinazzo (Toronto, Canada)
Objective: To evaluate the pharmacokinetics, safety and toler-
ability of sub-lingually administered APL-130277 (APL) 25 mg in
healthy volunteers.
Background: Parkinsons disease (PD) patients suffer from a
variety of Off episodes as the disease progresses. These consist of
wearing off, delayed-On or dose failures, sudden Offs and morning
akinesia. The only acute and effective rescue medication for these
Off episodes is apomorphine administered subcutaneously. Easier
to administer, convenient rescue treatments are needed. APL is a Fig. 1. (171).

Movement Disorders, Vol. 30, Suppl. 1, 2015

S66 POSTER SESSION
Results: Eleven subjects were dosed with APL and two with pla-
cebo. The mean Cmax was 11.2 ng/ml, Tmax was 41.5 minutes, t1/2
was 62.2 minutes, AUCLast was 1102 min*ng/ml, and AUCinf was
1204 min*ng/ml. The mean plasma concentration over time is pre-
sented in Figure 1. It took approximately 7 minutes to reach the min-
imum threshold concentration necessary to achieve efficacy in
patients (3 ng/ml). A concentration greater than this threshold was
maintained for 154 minutes. [figure1]
Incidence of adverse events reported with APL 25 mg are pre-
sented in Table 1. The events were mostly mild to moderate in
severity, except for dizziness, which was reported to be severe in
three subjects. No serious adverse events occurred.
Incidence of Adverse Events with APL 25 mg in 2 or more
Subjects
Type of AE N(%) N=11
Any AE 11(100)
Related AE 11(100)
Dizziness 9(82)
Sleepiness 9(82)
Nausea 4(36)
Vomiting 4(36)
Feeling Cold 2(18)
Hypotension 2(18)
Conclusions: APL 25 mg administered sub-lingually demon-
strates a favorable PK profile to support a rapid and sustained effect
for the relief of OFF episodes in Parkinsons disease patients.
Time to reach a minimum efficacious concentration was under 10
minutes and apomorphine levels were maintained above this concen-
tration for over 2.5 hours. Although dopaminergic AEs were rela-
tively high in healthy volunteers, these are expected to be lower in
PD patients already on dopaminergic medications and with impaired
dopamine production. APL-130277 may offer easy to use, rapid, on-
demand management of Off episodes in PD patients.
172
Therapeutic dancing for people with Parkinsons disease: A
systematic review of its effects on mobility and quality of life
L.C. Aguiar, M.E. Morris (Melbourne, Australia)
Objective: This systematic review evaluated studies on the out-
comes of different dance genres for mobility and quality of life in PD
(1). The emphasis was on walking speed, freezing and participant
wellbeing. The feasibility and safety of trials were also examined (2).
Background: Therapeutic dancing has recently been advocated
as an effective adjunct to conventional physical therapies for people
living with Parkinsons disease (PD).
Methods: Studies were identified through a detailed search of online
databases including CINHAL (1982-2014), Medline (1922-2014), Sco-
pus (1996-2014), Web of Science (2002-2014), Embase (2007-2014),
PEDro (1999-2014) and the Cochrane Library (1996-2014). Parkinsons
disease, Paskinson*, Parkinsonism, dance, dance therapy, dance genres,
safety, feasibility, quality of life. Two independent investigators (LA &
PR) completed the full text assessment. Only randomized controlled tri-
als (RCTs), quasi-RCTs and case series were included.
Results: We found that therapeutic dancing was beneficial for
improving motor performance, mobility and balance in some people
living with PD. Dancing also had a positive impact on quality of life
and adherence to physical activity over the long term. Dancing may
improve freezing of gait, walking speed and participant wellbeing in
some individuals However, just a few studies described thoroughly
the evaluations of these outcomes. Little was reported on the effects
of partnered versus non-partnered dancing, the use of different dance
genres in mixed dancing classes, efficacious scheduling of therapy,
Movement Disorders, Vol. 30, Suppl. 1, 2015
the frequency of dance therapies, the effects of different music gen-
res, participant satisfaction with therapy, socialisation, or retention of
improvements associated with therapeutic dance intervention. More-
over there was little information about the advantages of caregiver
participation on the therapy, which may be closely correlated with
participant compliance. Therefore, more research is needed to com-
prehensively evaluate these aspects of dancing programs.
Conclusions: There was emerging evidence that dance therapy is
safe and feasible for people with mild to moderately severe PD, with
beneficial effects on walking speed, freezing and health related qual-
ity of life in some individuals.
173
Efficacy of safinamide in early Parkinsons disease: Results of
pooled analysis
R. Anand, R.D. Hartman, V. Lucini, E. Forrest, R. Giuliani, M.
McBride (St. Moritz, Switzerland)
Objective: Analyses were performed to determine if the signifi-
cant benefits noted with safinamide as an add-on to early-stage PD
patients in three DA-agonist monotherapy (ESPD) trials extend to
multiple measures of clinical relevance in pooled data analyses.
Background: Safinamide (50 and 100mg/day) add-on to DA-
agonist monotherapy given in non-fluctuating patients (Studies 009,
015 and MOTION) demonstrated significant benefit on the primary
efficacy measure (UPDRS III) and selected secondary measures.
Methods: Analyses of data pooled from ESPD studies were per-
formed on a modified Intent-to-Treat Population (mITT). Patients
were assigned to a treatment group based on the randomized targeted
dose (placebo; safinamide 50 or 100 mg/day). The difference
between treatment groups was compared using Mixed Model
Repeated Measures (MMRM) and Analysis of Covariance
(ANCOVA) for continuous measures (UPDRS I, II, III, II1III and
I1II1III) and logistic regression (chi-square test) for categorical
ones (improvements of  30%, 40%, 50% in UPDRS III,  20% and
30% in UPDRS II1III, and improvement in CGI-Change [CGI-C]).
Results: The pooled analyses included 649 patients on safinamide
and 349 on placebo without significant differences between treatment
groups in demographics, disease characteristics (PD duration, Hoehn
&Yahr stage, UPDRS scores, CGI-S, dosage/type of DA-agonist).
Statistically significant improvements were noted for the MMRM
and ANCOVA analyses for safinamide 100mg/day, compared with
placebo, for the mean change (LS diff vs. placebo) in UPDRS Sec-
tions II (-0.5, p50.0011), III (-1.2, p50.0003), II1III (-1.6,
p50.0001) and I1II1III (-2.0, p50.0035). A significantly (p<0.05)
greater proportion of patients in both safinamide group met each of
the above responder criteria. The percentages of patients meeting the
most stringent responder criteria were:  50% in UPDRS III [50 mg:
11.4% (p50.027), 100 mg: 14.4% (p50.003), Pbo: 7.6%];  30% in
UPDRS II1III [50 mg: 25.4% (p50.005), 100 mg: 29.3%
(p50.003), Pbo: 20.1%]; and any improvement in CGI-C [50 mg:
45.5% (p50.018), 100 mg: 48.2% (p50.016), Pbo: 39.6%].
Conclusions: Pooled analyses of safinamide studies in patients on
DA-agonist monotherapy demonstrated statistically significant and
clinically relevant benefits for motor symptoms, activities of daily
living, and global evaluation for both the 50 and 100mg/day doses
compared with DA-agonist monotherapy.
174
Early onset and duration of effect of safinamide in patients with
motor fluctuations
R. Anand, R.D. Hartman, V. Lucini, E. Forrest, R. Giuliani, M.
McBride (St. Moritz, Switzerland)
Objective: To determine the onset of efficacy of safinamide on
key efficacy measures by analysis of the data at all study visits in
both the 016 and SETTLE studies.
 POSTER SESSION
Background: Safinamide add-on to levodopa in fluctuating patients
demonstrated significant superiority over standard of care in the 24-
week studies 016 and SETTLE on the primary (ON Time without trou-
blesome dyskinesia) and secondary (OFF Time, UPDRS III) measures.
Study 016/018 also demonstrated persistence of benefit for 2 years.
Methods: The two studies differed in the visit schedules and dos-
ing. In Study 016 patients were randomized to fixed doses of 50 or
100mg/day of safinamide or placebo; in the SETTLE patients were
randomized to placebo, or a starting dose of safinamide 50 mg/day that
was increased to 100 mg/day not earlier than 2 weeks. Additionally, the
first assessment visit for 016 and SETTLE was at Week 4 and Week 2,
respectively. These differences precluded data pooling for determining
both onset of efficacy and duration of benefit. Analyses (t-tests) were
performed to determine the change in ON and OFF Time in
safinamide-treated patients compared to placebo (ITT population).
Results: In both studies 016 (n5669) and SETTLE (n5559), the
mean ON and OFF Time at baseline were comparable among all treat-
ment groups. Statistically significant differences between safinamide
and placebo were evident at all post-baseline visits for ON and OFF
Time. The first post-baseline assessment visit at Week 2 for SETTLE
showed a highly statistically significant (p50.0003) increase in median
ON Time of 1 hr for safinamide, compared with 30 min for placebo,
and a decrease in median OFF time (p<0.0001, 1 hr for safinamide and
30 min for placebo). Similarly, in Study 016 the first post-baseline
assessment visit at Week 4 showed a statistically significant (p50.017)
increase in median ON Time [40 min for safinamide (50 and 100 mg/
day) compared with 20 min for placebo], and a decrease in median
OFF Time (p<0.01, 45 min for safinamide and 15 min for placebo).
Onset of efficacy for the UPDRS III was first noted at Week 4.
Conclusions: Safinamide was associated with statistically signifi-
cant benefit already at the first assessment (Week 2 or 4) for ON and
OFF Time. These rapid improvements in patients on standard of care
suggest that safinamides dual mechanism produces benefits that will
be appreciated by patients, caregivers and physicians.
175
Efficacy and safety of levodopa-carbidopa intestinal gel in
patients with less than 10 years of Parkinsons disease Interim
results from the GLORIA long-term registry
A. Antonini, K.R. Chaudhuri, L. Bergmann, A. Yegin, K. Onuk, W.
Poewe (Venice, Italy)
Motor and Non-Motor Efficacy Measures in a Relatively Early Disease
Subgroup and Total Population of Advanced Parkinsons disease Patients
Total Population at
BL (n5343)(a)
Efficacy and Quality of Mean 6 SD
Life Assessments
Unified Parkinsons disease
Rating Scale (UPDRS):
Part II (activities of daily living score) 16.3 6 9.9
Part III (motor score) 24.5 6 11.9
Part IV item 32 (hours of dyskinesia/day) 4.4 6 3.8
Part IV item 39 (hours of off time/day) 6.0 6 3.2
Non-Motor Symptom Scale 69.2 6 42.1
(NMSS) total score
8-item Parkinsons disease 46.5 6 18.7
Questionnaire (PDQ-8) total score
a Ref 1; b Defined as advanced PD patients <60 years old and with <10 years of disease; *Two-sided P<0.05, ***Two-sided P0.0001;
BL 5 baseline, 12M 5 month 12; SD 5 standard deviation.
S67
Objective: To evaluate the efficacy of Levodopa-Carbidopa Intes-
tinal Gel (LCIG) in a subgroup of advanced Parkinsons disease
(PD) patients of relatively younger age and shorter disease duration.
Background: LCIG is a long-term treatment option for advanced
PD patients. The efficacy and safety of LCIG in <60 year-old
advanced PD patients with <10 years of disease have not been
reported.
Methods: This 24-month prospective, observational study of
LCIG included 374 patients with advanced PD at 75 centers in 18
countries. A post-hoc subgroup analysis was conducted on safety and
efficacy data collected on/before 3rd January 2014 from patients who
were <60 years old with <10 years of disease at baseline. Efficacy
and quality of life (QoL) were evaluated by the mean change from
baseline to 12 months (12M) on the Unified Parkinsons disease Rat-
ing Scale (UPDRS) part II, III, IV (items 32 and 39), Non-Motor
Symptoms Scale (NMSS) total score and 8-item Parkinsons disease
Questionnaire (PDQ-8) total score. Adverse drug reactions (ADR)
were evaluated throughout the study. Baseline was the first visit
before the start of LCIG infusion.
Results: There were 28 (8.2%) patients in the subgroup of
patients who were <60 years old with <10 years of disease, 15
(53.6%) of which completed 12M of the study. At baseline, this
subgroup had a mean (SD) age of 52.5 (5.7) years, 6.1 (1.9) years
disease duration, and 19 (67.9%) were male. At baseline this sub-
group had mean (SD) levodopa dose of 914.0 (396.0) mg and a
higher level of off time and lower level of UPDRS sections II and
III scores relative to the total population (Table 1).[ref1] There were
significant decreases from baseline to 12M in hours of off time and
NMSS total score, and no significant changes in hours of dyskinesia
or QoL scores. In this subgroup, there were 12 (42.9%) patients with
1 ADR, 5 (17.9%) with 1 serious ADR, and 1 (3.6%) who dis-
continued due to an ADR.
Conclusions: Although the sample sizes were limited, LCIG
reduced off time and non-motor symptoms in a subgroup of
patients in a relatively early disease stage. The observed ADR profile
in this subgroup was consistent with the established safety profile of
LCIG.
176
Efficacy of rotigotine at different stages of Parkinsons disease
symptom severity and disability: Post hoc analysis according to
baseline Hoehn & Yahr staging
M. Asgharnejad, L. Bauer, F. Woltering (Raleigh, NC, USA)
Earlier Disease Sub-
Earlier Disease group(b) Change from
Subgroup(b) at BL (n526) Baseline at 12M
Mean 6 SD n Mean 6 SD
11.4 6 7.5 12 -2.7 6 6.4
18.0 6 9.8 14 -4.9 6 9.2
4.3 6 4.7 11 -1.5 6 3.1
8.0 6 3.3 10 -6.7 6 2.2***
76.3 6 40.3 13 -32.9 6 46.5*
44.2 6 18.2 12 13.8 6 32.1
Movement Disorders, Vol. 30, Suppl. 1, 2015
S68 POSTER SESSION

TABLE 1. Demographic and baseline characteristics by HY stage at baseline

HY stage 3 (mild/
HY stage 1 (unilateral moderate disabil- HY stage 4 (severe dis-
involvement, minimal/no HY stage 2 (bilateral ity, impaired pos- ability, but able to
functional disability) involvement, no impair- tural reflexes) walk/stand unaided)
Full analysis set N=274 ment of balance) N=1304 N=692 N=93
Age, mean 6 SD, years 58.9 6 10.5 62.8 6 9.6 65.3 6 10.0 69.0 6 8.4
Male, n (%) 176 (64.2) 872 (66.9) 417 (60.3) 56 (60.2)
Caucasian 261 (95.3) 1110 (85.1) 601 (86.8) 85 (91.4)
Time since PD diagnosis, mean 6 SD, years 1.3 6 1.72 5.0 6 4.24 6.8 6 4.94 10.4 6 5.43
Receiving levodopa at baseline, n (%) 17 (6) 775 (59) 560 (81) 93 (100)
Levodopa dose at baseline (mg/day), 473.5 6 256.25 698.6 6 449.51 724.7 6 405.04 809.9 6 418.61
mean 6 SD
UPDRS II1III total score, mean 6 SD 22.4 6 8.67 32.2 6 12.76 42.6 6 16.67 65.0 6 18.27
UPDRS, Unified Parkinsons disease Rating Scale; SD, standard deviation

Mean (6SD) change from

Full analysis set, last Mean (6SD) baseline score baseline LS mean [95% CI]
observation carried treatment difference vs
forward Placebo Rotigotine Placebo Rotigotine placebo, ANCOVA* p-value
HY stage 1 22.1 6 7.25 (n580) 22.5 6 9.20 (n5194) -2.0 6 6.88 -5.6 6 8.85 -3.17 [-5.19,-1.16] 0.002
HY stage 2 32.2 6 12.60 (n5409) 32.2 6 12.83 (n5895) -2.2 6 10.62 -7.3 6 10.47 -5.03 [-6.19,-3.87] <0.001
HY stage 3 42.0 6 16.63 (n5211) 42.8 6 16.70 (n5481) -3.1 6 13.57 -8.1 6 11.83 -5.18 [-7.10,-3.26] <0.001
HY stage 4 65.8 6 18.62 (n532) 64.7 6 18.23 (n561) -3.8 6 9.74 -15.3 6 13.93 -11.33 [-16.43,-6.22] <0.001
*Analysis of covariance (ANCOVA) model adjusted for baseline UPDRS score and study. All p-values presented are exploratory in nature and
do not infer statistical significance. UPDRS, Unified Parkinsons disease Rating Scale; CI, confidence interval; SD, standard deviation; LS, least
squares

Objective: To investigate the efficacy of rotigotine transdermal
patch across different stages of Parkinsons disease (PD) symptom
severity and functional disability.
Background: The efficacy of rotigotine has been demonstrated in
studies of patients with early-stage PD (defined as not receiving levo-
dopa) and advanced-stage PD (defined as receiving levodopa). Here
we aimed to further investigate the benefit of rotigotine throughout the
PD patient journey, based on symptom severity and disability accord-
ing to baseline Hoehn & Yahr (HY) stage. The HY is a descriptive
five-point staging scale that provides an estimate of clinical function
in PD (motor symptom severity and relative level of disability); it
ranges from 1: unilateral involvement, minimal/no functional disabil-
ity, to 5: confined to bed/wheelchair unless aided [1].
Methods: Post hoc analysis of 7 placebo-controlled studies of
rotigotine in patients with early-PD (SP506, SP512, SP513; rotigo-
tine 8 mg/24h) or advanced-PD (SP511, SP515, SP650, SP921;
rotigotine 16 mg/24h), with maintenance phase 7 weeks. Data
from the studies were pooled, and patients stratified according to HY
stage at baseline (HY stage 1, 2, 3, or 4). For each HY stage, change
from baseline to end of maintenance is reported for Unified Parkin-
sons disease Rating Scale (UPDRS) II1III total score, and UPDRS
II and III subscores. P-values are exploratory only.
Results: Data were available for 2363 patients: HY stage 1,
n5274; HY 2, n51304; HY 3, n5692; HY 4, n593. Compared to
patients at a lower HY stage, patients at higher HY stages were gen-
erally older, had a longer time since PD diagnosis, more likely to be
receiving levodopa (and at higher doses), and higher baseline
UPDRS II1III total scores (Table 1). Rotigotine improved UPDRS
II1III total score vs placebo for each individual HY stage (p<0.01
for all individual HY stages) (Table 2). Similar results were observed
for UPDRS II and III subscores (p<0.01 for individual HY stages).
Conclusions: This post hoc analysis suggests that rotigotine
transdermal patch is efficacious in patients with PD across the stages
of the disease from mild symptoms/minimal functional disability
(HY stage 1) to increasing symptom severity and disability (HY
stage 4). These data support the use of rotigotine across the progres-
sive stages of PD.
1. Goetz CG, et al. Mov Disord. 2004;19:1020-8.
177
Adverse effects of amantadine in patients of Parkinsons disease-
A cross sectional study
K. Bahrani, V. Goyal, G. Shukla, M. Vanathi, M. Behari (New Delhi,
India)
Objective: To evaluate the adverse effects of amantadine in
patients of Parkinsons disease with special reference to corneal
endothelial toxicity.
Background: In outpatient door consultation, some patients com-
plain of visual problems on changing dose of amantadine. Anti-
cholinergic drugs also cause visual blurring and are usually co-
prescribed, which creates problem that which drug is causing visual
symptoms. Amantadine can rarely cause corneal endothelial cell
degeneration leading to visual loss, which is partially reversible.
Methods: A total of 120 Parkinsons patients with 90 patients on
amantadine (6 months) & 30 amantadine nave Parkinsons patients
along with 30 age and gender-matched healthy controlswere enrolled.
The amantadine treated group was divided into 3 sub-groups accord-
ing to daily dosage of amantadine, with 30 subjects in each subgroup
on 200 mg/300 mg/400 mg of amantadine daily.
Endothelial indices were compared between Parkinsons patients
on amantadine (6 months), amantadine nave Parkinsons patients
& age-gender matched healthy controls. Other signs & symptoms of
amantadine induced pedal edema, livedoreticularis (LR), visual hallu-
cinations were also screened.

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
Outcome Measures: Endothelial cell density, Coefficient of varia-
tion, Hexagonality, proportion of Parkinsons patients with pedal
edema/livedoreticularis on amantadine.
Results: The amantadine group had lower ECD (mean 6 SD;
2584.78 6 350.95 vs. 2707.37 6 220.68, p50.07), lower hexagonality
(mean 6 SD; 45.23 6 6.55 vs. 47.87 6 7.45, p50.06) & larger coeffi-
cient of variation (mean 6 SD; 43.27 6 9.35 vs. 41.50 6 6.07,
p50.33) compared with amantadine nave Parkinsons patients. Sub-
group on high dose amantadine (400 mg) had significantly lower
ECD (p50.01)& lower %Hex (p50.001) as compared to low dose
amantadine (200 mg & 300 mg) group. Among the subgroups of
Parkinsons patients on amantadine with peripheral adverse effects,all
the subgroups had nearly equal number of patients with pedal edema
& livedoreticularis.
Conclusions: Amantadine is more likely to have effect on corneal
endothelial cells in a dose dependent manner when used long term.
Our study is the first of its kind to show dose-dependent toxicity of
amantadine in patients of Parkinsons disease from tertiary care hos-
pital in INDIA.
178
R ) in
The effect of the Lee Silverman voice treatment (LSVT V
Filipino Parkinsons disease patients: A pilot study
J.M.P. Bautista, C.K.A. Cuadro, R.D.G. Jamora (Quezon City,
Philippines)
Objective: The primary aim is to determine the effect of
LSVTV R in the Filipino Parkinsons disease (PD) patient based on
two measured parameters: vocal intensity and length of time of
sustained phonation. Another objective of this study is to corre-
late the subjects clinical PD profile to their response to
treatment.
Background: As much as 89% of PD patients develop voice
and speech disorders. This is characterized by decreased vocal
intensity, monotonous speech, and imprecise articulation, collec-
tively called hypokinetic dysarthria. The Lee Silverman Voice
Treatment (LSVT V R ) is an intensive therapeutic course focused on
improving the voice of PD disease patients. This program is rela-
tively new in the Philippines with very few certified LSVT speech
pathologists. No studies have yet been done on LSVT and the Fili-
pino PD patient.
Methods: This is a cross-sectional study of PD patients in a sin-
gle institution in the Philippines. All records of PD patients inde-
pendent of disease and speech disorder severity who completed the
LSVT course were retrieved. Data on vocal intensity and length of
time of sustained phonation at different vocal pitches were measured
at baseline and during all 16 sessions of LSVT. Baseline data and
the mean of all sixteen sessions were compared and statistically
analyzed.
Results: From 9 PD patients referred for LSVT, only 7 patients
completed the whole course of 16 sessions. For vocal intensity, 5
out of 7 subjects showed louder vocal intensity compared to base-
line on at least 1 vocal pitch. The remaining 2 out of the 7 subjects
did not show any improvement in vocal loudness on any of the 3
vocal pitches. For the length of time of sustained phonation, 5 out
of 7 subjects were noted to have significantly longer sustained pho-
nation on at least 1 vocal pitch. The remaining 2 subjects failed to
show any improvement from their baseline time on any of the three
pitch levels.
Conclusions: Among Filipino PD patients who completed the
LSVT, majority showed significant improvement in either vocal
intensity or in length of time of sustained phonation. Significant
improvement was seen more on the patients habitual pitch com-
pared to lower or higher pitch levels. Most improvement was also
seen in patients with mild PD and mild speech disorder. This
implies that LSVT may have most benefit in this category of PD
patients.
S69
179
A study of the pharmacological chaperones targeting
glucocerebrosidase mutations in human fibroblast models of
Parkinsons disease
M. Beavan, S.Y. Yang, K.Y. Chau, R. Shahar-Golan, D. Hughes, A.
Mehta, A. Schapira (London, United Kingdom)
Objective: We have extended our investigation into the efficacy
of existing pharmacological chaperones (PC) for manipulating the
activity of glucocerebrosidase enzyme (GCase), and their potential to
reverse the underlying molecular events in the pathogenesis of Par-
kinsons disease (PD).
Background: After aging, the most important risk factor known
for the development of PD is certain mutations of the glucocerebrosi-
dase gene (gba).
Methods: Human skin fibroblast cultures from individuals carry-
ing heterozygous N370S (n 5 5) or L444P (n55) gba mutations,
with and without PD, and those with mutation-negative idiopathic
PD were treated with selected concentrations of PC ambroxol and
isofagomine. GCase enzyme activity, levels of glucocerebrosidase
protein (GBA) and gene expression, and related lysosomal and auto-
phagic proteins were characterized.
Results: We observed a 50-70% decrease in GCase activity, 50%
lower GBA levels and 50% gba expression in fibroblasts obtained
from the heterozygous gba mutation carriers, associated with bio-
chemical abnormalities including defective localization of GBA and
lysosomal autophagy. Optimised treatment of skin fibroblast cultures
with ambroxol and isofagomine resulted in significant restoration of
GCase activity, GBA protein and gba gene expression in all cell
lines, and correction of GBA localization. Autophagic compromise
associated with the pathogenesis of PD was identified and we are in
the process of assessing the influence upon drug treatment.
Conclusions: We have demonstrated that the PC ambroxol and
isofagomine are able to modulate GCase function. It is unclear
whether the treatment alone may be able to overcome all biochemi-
cal defects due to mutations in gba, due to the limitation of fibro-
blasts as a model for interrogating the complete pathway in PD.
180
Yoga versus resistance training in Parkinsons disease: A 12-
week pilot feasibility study
D. Bega, D. Corcos, J. Stein, D. Victorson, C. Zadikoff, B.
Jovanovic, T. Simuni (Chicago, IL, USA)
Objective: To explore the safety and feasibility of a 12-week
biweekly course of gentle Iyengar yoga in patients with PD, and to
collect pilot data on efficacy compared to resistance exercise.
Background: Yoga is a mind-body intervention which may
address the motor and non-motor needs of patients with Parkinsons
disease (PD). Despite the wide utilization of yoga there is little evi-
dence in support of its use.
Methods: Prospective randomized controlled single blinded study
in patients with mild to moderate PD (H&Y stage 1-3). Patients
selected a site in downtown Chicago or the suburbs and were
randomized 1:1 to yoga or resistance classes within each site. Groups
were matched for age, gender, and disease severity. Assessments
were performed at screening and after the final session. Safety and
attendance data was collected by phone every 3 weeks. The main
exploratory outcome measures were change in Timed-Up-And-Go
(TUG), UPDRS part III, and PDQ-39.
Results: 23 patients were screened and 17 were eligible (11
downtown, 6 suburbs). Demographics of the groups were similar,
with mean age of the cohort 67.3 (SD 9.8) years, and mean UPDRS
III score of 24.2 (SD 7.0). There were 3 withdrawals (2 yoga, 1
resistance) unrelated to the intervention. There were no major
adverse events. 16% of yoga classes were missed compared to 8% of
resistance classes (p50.04). Significantly more classes were missed
at the downtown campus compared to the suburbs (14.8% vs 7.5%).
Movement Disorders, Vol. 30, Suppl. 1, 2015
S70 POSTER SESSION
Upon completion of the trial both groups improved on mean TUG
time, UPDRS score, and PDQ-39 score compared to baseline,
although the standard deviations for all values were wide and none
of the between-group differences was statistically significant. With
the exception of 1 subject in each group, participants stated that they
benefited from the intervention, and they would have continued the
intervention beyond 12 weeks.
Conclusions: The feasibility of a 12-week group yoga interven-
tion in a cohort with mild-moderate PD was somewhat limited, with
better attendance seen for resistance classes. The suburban location
was associated with significantly better compliance. Pilot exploratory
outcome data suggest comparable improvement in motor and non-
motor outcome measures in both groups, but a larger study powered
to detect these differences is needed. Feasibility data will need to be
taken into account in designing such a study.
181
Clinical predictors of functional decline in early treated
Parkinsons disease: NET-PD LS1 cohort
D. Bega, S. Kim, Y. Zhang, J. Elm, J. Schneider, R. Hauser, A.
Fraser, T. Simuni, On Behalf of the NET-PD LS1 Investigators (Chi-
cago, IL, USA)
Objective: Current data regarding predictors of functional decline
in Parkinsons disease (PD) are largely based on studies of de novo
populations at baseline, often limited to the use of motor outcomes
which fail to capture the full scope of the disease. We aimed to
determine the clinical predictors of decline in early treated PD as
defined by a novel multi-domain outcome measure.
Background: Clinical predictors of functional decline in PD are
prognostically important in the absence of validated biomarkers of
disease progression. Older age at disease onset and PD symptom
subtype have been identified as the strongest predictors of more rapid
rate of progression.
Methods: We used data from NINDS Exploratory Trials in Par-
kinsons disease Long-Term Study 1 (NET-PD LS1), a large multi-
center cohort of early treated PD patients followed for 5-7 years.
Decline was defined by a global outcome metric that consists of the
following 5 domains of disability, quality of life, motor and cogni-
tive impairment: Schwab and England ADL scale (S&E), Parkin-
sons disease Quality of Life Scale (PDQ-39), Unified Parkinsons
disease Rating Scale (UPDRS) Ambulatory Capacity Score, Symbol
Digit Modalities Test (SDMT), and Modified Rankin Scale (mRS).
Linear mixed models were used to test the association of predictors
of interest, with a standardized rank-sum of the global outcome (GO)
in both univariate and multivariate models.
Results: Of 1700 subjects who entered the study between 2007
and 2012, 765 had 5 year data and were included in the analysis.
Older age at disease onset (p<0.0001), higher baseline levodopa
equivalent dose (p50.01), and lower/worse Scales for Outcomes of
Parkinsons disease Cognition (SCOPA-COG) score (p50.001) at
baseline were the strongest predictors of functional decline (worsen-
ing GO) in multivariate analysis. PD symptom subtype was not a
significant predictor of outcome (p50.42).
Conclusions: This is the largest study to systematically assess
predictors of functional decline in early treated PD over a period as
long as five years, and the first study to use a multi-domain outcome
measure of decline. Older age at disease onset was confirmed as a
predictor of decline, but PD symptom subtype was not.
182
Prefrontal repetitive transcranial magnetic stimulation in
Parkinsons disease: Pilot study of motor and neurophysiology
outcomes
M.C. Biagioni, G.S. Dacpano, S. Agarwal, K.R. Sticklor, W.R. Small,
J.N. Chimienti, P. Kumar, A. Loggini, J.Y. Singleton-Garvin, E.R.
Movement Disorders, Vol. 30, Suppl. 1, 2015
Friedman, M. Brys, R.M. Gilbert, A. Di Rocco (New York City, NY,
USA)
Objective: To explore clinical and electrophysiology outcomes of
low frequency repetitive Transcranial Magnetic Stimulation (rTMS)
of two prefrontal stimulation targets in patients with PD.
Background: rTMS trials showed promising results improving
motor symptoms of PD with a class-I trial reporting motor improve-
ment with low frequency (LF) rTMS over the supplementary motor
area (SMA). Neurophysiology (NPh) studies suggest that motor cor-
tex excitability in PD is abnormal and can be modulated with rTMS;
particularly LF rTMS over dorsal premotor cortex (PMd) can nor-
malize motor excitability abnormalities. Optimizing rTMS treatment
strategies is challenging and NPh may help with understanding the
TMS effects and optimizing design of novel rTMS treatment
protocols.
Methods: 8 PD patients with H&Y score of 2 or 3 participated in
this parallel, double-blind pilot study of four weekly LF rTMS ses-
sions over prefrontal areas and were assessed at 1 and 4 weeks post-
treatment. The stimulation targets included either active rTMS over
PMd and SMA (PMd1SMA group), or realistic sham on PMd and
active rTMS on SMA (SMA group). UPDRS III was used to mea-
sure motor outcomes. Cortical silent period (SP), short interval intra-
cortical inhibition and intra-cortical facilitation measures were used
to asses NPh outcomes.
Results: No significant adverse effects reported. At week 4 post-
treatment, UPDRS III decreased in both groups, in PMd1SMA
group from 30.25 (sd=12.7) to 24.5 (sd=11.4); in SMA group from
30.0 (sd=6.7) to 24.5 (sd=5.3), both approaching significance [p <
0.1]; magnitude of decrease was greater in PMd1SMA group but
did not reach significance. Neurophysiology results revealed a trend
towards a significant difference [p < 0.1] between both groups SP
at week 4 post-treatment (prolongation of SP in the PMd1SMA
group and shortening of SP in the SMA group). Other NPh results
were not significant. [figure2]
Conclusions: Both rTMS interventions were well tolerated and
improved UPDRS motor scores. Improvement was sustained up to
four weeks post-treatment. Combined PMd1SMA rTMS prolonging
SP may indicate increased activity of inhibitory circuits in this group
which may reflect a more effective intra-cortical modulation by LF
rTMS (as SP is abnormally shorter in PD patients). Larger studies
are needed to better define the effects of prefrontal LF rTMS on NPh
measures and potential clinical interactions in PD.
Fig. 1. (182).
 POSTER SESSION
Fig. 2. (182).
183
Utilizing remote blood pressure monitoring in a phase III clinical
drug trial for Parkinsons disease
R.A. Biemiller, K.J. Andrzejewski, M.T. Bull, K. Helles, B. Greco, D.
Oakes, T. Simuni, K.M. Biglan (Rochester, NY, USA)
Objective: To determine the feasibility of remote blood pres-
sure monitoring in a phase III clinical trial for Parkinsons
disease.
Background: Orthostatic hypotension is common in Parkinsons
disease (PD). Clinical trials for PD have used home blood pressure
(BP) monitoring for participant safety and enrollment eligibility.
Monitoring typically involves patients keeping a home log, which is
presented at interim in-person visits to research staff for review.
These home logs may be subject to inaccuracies due to errors in
transcribing results or non-compliance. This has the potential to
impact study validity and participant safety.
Safety, Tolerability, and Efficacy Assessment of Isradipine for
Parkinsons disease (SteadyPD3) is a phase III double-blinded
study of isradipine, a dihydropiridine calcium channel antagonist,
as a potential neuroprotective agent in PD. Given the mechanism
of isradipine, STEADYPD3 requires frequent BP monitoring prior
to drug initiation and during drug titration to ensure participant
eligibility and safety. The use of a BP monitor that can instantly
send readings remotely to researchers allows for real time data
capture and analysis and has the potential to improve validity and
safety of the trial.
Methods: Participants in SteadyPD3 take twice-daily orthostatic
BP readings during screening and drug titration. Patients are given a
BP monitor (Carematix) and a MiFi unit (Verizon). The unit auto-
matically sends BP readings to an online database, which is remotely
monitored by the research team. The database tags all BP readings
outside the prespecified safety range for review. We report on our
initial findings on the feasibility and challenges of remote BP
monitoring.
Results: SteadyPD3 began enrollment in November 2014. It has
enrolled 29 and screened 46 patients who have utilized the remote
BP units and have successfully transmitted to the online database.
The main complications have been: spurious readings due to patient
error, extra reported readings from researchers instructing patients on
the use of the units and an excessive amount of BP reads that require
dedicated personnel to review.
Conclusions: Remote blood pressure monitoring in an ongoing
Phase III trial of PD has been feasible. Remote BP monitoring has
the potential to increase safety and validity in PD studies but will
require further testing.
S71
184
Shared decision making in advanced Parkinsons disease (PD);
protocol of a feasibility study
B.R. Bloem, M.J. Faber, F.A.P. Nijhuis, D.L.M. Radder (Nijmegen,
Netherlands)
Objective: We developed a shared decision making (SDM) inter-
vention to create equal accessibility to all treatment options for
advanced PD patients, and to improve patient involvement in the
decision making process (DMP). Here we describe a study where
this intervention will be evaluated on feasibility by analyzing 1) the
impact on the decision making process; and 2) the barriers and facili-
tators for uptake of the intervention.
Background: For many PD patients, it eventually becomes diffi-
cult to manage motor complications with adjustments in oral medica-
tion. For these patients, Deep Brain Stimulation, Continuous
Duodenal Levodopa Infusion and Continuous Subcutaneous Apomor-
phine Infusion are the cornerstones for therapeutic management. A
decision aid (DA) aims to improve decision making and should lead
to a quality decision. The choice for one of the treatments is an indi-
vidual decision, based on patients personal preferences and values.
The notion that the patients perspective and participation in decision
making is needed for a quality decision, was the starting point for us
to develop a SDM intervention comprising a DA and a training for
professionals.
Methods: The SDM intervention will be tested in clinical prac-
tice. The aim is to select 40 patients; 20 after introducing the SDM
intervention, and 20 according to usual care. At baseline, the usual
DMP is followed and the patient will receive care as usual. After
this, professionals will get a theoretical and hands-on training in
SDM and use of the online DA. With the next 20 patients, they will
work according to the SDM intervention.
Feasibility of this intervention will be measured in both patients
and professionals by means of questionnaires, interviews, observa-
tions of the DMP and logging behavior of the online decision aid.
Results: Important outcomes will be the level of SDM in the con-
sultations and informed preference as a measure of the quality of
decision making.
Conclusions: The results of this project will inform the imple-
mentation of the new SDM approach, which could be evaluated in a
larger RCT in clinical practice. Our long-term goal is to create equal
accessibility to all advanced therapies and offer patients the opportu-
nity to actively participate in this complex medical decision. This
should reduce the under treatment of patients with advanced PD and
improve treatment compliance.
185
Designing a decision aid for patients in advanced Parkinsons
disease (PD): The user test experiences
B.R. Bloem, M.J. Faber, F.A.P. Nijhuis, D.L.M. Radder (Nijmegen,
Netherlands)
Objective: To optimize a newly developed decision aid (DA) for
patients with PD in the advanced stage, we conducted a user test
with PD patients. The aim was to test the DA on 1) quality of the
information; and 2) ease of use.
Background: For many PD patients, it eventually becomes diffi-
cult to manage motor complications with adjustments in oral medica-
tion. For these patients, Deep Brain Stimulation, Continuous
Duodenal Levodopa Infusion and Continuous Subcutaneous Apomor-
phine Infusion are the cornerstones for therapeutic management. The
choice for one of the treatments is an individual decision, based on
patients personal preferences and values. The notion that the
patients perspective and participation in decision making is needed
for a quality decision, was the starting point for us to develop a
SDM intervention comprising a DA and a training for professionals.
Methods: For testing the DA, 25 patients were approached, of
which 19 responded. All participants received a personal login code,
Movement Disorders, Vol. 30, Suppl. 1, 2015
S72 POSTER SESSION
testing the DA for one week. Afterwards, the patients received an
evaluation questionnaire. Four of them were interviewed at home to
obtain more extensive qualitative feedback.
Results: Most patients scored the content of the DA as good
(overview of treatment options (79%), information on the risks of
treatments (68%)). Less than half (47%) rated the information on the
effects of the treatments as good. Patients judged the language as
comprehensible (95%) and the length of the DA (68%) and quantity
of information (63%) were optimal. Patients felt that the DA offered
well-balanced information about the specific treatments (88%). All
participants would use the DA if they were faced with the choice
(100%). Moreover, patients provided several instructions for improv-
ing the DA, particularly to include more experiences of patients that
underwent one of the treatments, and to include practical information
about how the devices are used at home.
Conclusions: Patients rated the DA as a useful tool in making
the decision and as easy to use. Obviously, it differs per patient how
much information they wish to receive. Therefore patients have
access to the information pages for both patients and professionals,
allowing patients in need of more information to read the more
extensive scientific knowledge for professionals. We have incorpo-
rated the feedback into a new version of the DA, which will be
tested in a feasibility study.
186
Short-term benefits of a progressive aerobic exercise and skill
acquisition program for people with mild to moderate
Parkinsons disease in a community group setting
E.E. Borchers, E. Ferrigni, K. Krauss, B.G. Farley (Tucson, AZ,
USA)
Objective: To examine the short-term effects of a progressive
aerobic exercise and skill acquisition program conducted at The Par-
kinsons Wellness Recovery Gym (PWR!GymV R ), a community based
exercise center devoted to improving quality of life for people with
Parkinsons disease (PD).
Background: Progressive aerobic exercise has been shown to
improve endurance, gait, balance, and executive function as well as
decrease fatigue and depression in people with Parkinsons disease
(PD). Prior research suggests that vigorous aerobic exercise in com-
bination with skill acquisition augmented with feedback improves
function and can mediate brain health and repair mechanisms in peo-
ple with PD. Limited research has been done on the effectiveness of
this type of exercise program implemented in a community group
setting.
Methods: Sixteen members of the PWR!GymV R with mild to
moderate PD participated for 7 weeks. Volunteers provided individu-
alized education and feedback regarding perceived effort based on
the Modified Borg scale correlated with heart rate. Group 1, which
included 8 participants with moderate stage PD, exercised 3 times
per week with total cardio times increasing from 30 to 40 minutes.
Group 2, which included 8 participants with mild to moderate stage
PD, exercised 3 times per week with total cardio times increasing
from 40 to 50 minutes. Both groups utilized treadmills and stationary
bicycles followed by various PWR!MovesV R for skill acquisition for
the remaining time to total a one hour class.
Results: Preliminary findings suggest improvements in motor and
cognitive assessments as well as non-motor symptoms associated
with PD. The majority of participants improved in the 6 Minute
Walk Test, 2 Minute Walk Test, Timed Up and Go, and 5 Times Sit
to Stand suggesting benefits in the domains of endurance and func-
tional mobility. Improvements were also found in verbal fluency and
trailmaking tasks. In addition, subjects reported less fatigue,
improved sleep quality, better mood, less pain, and higher quality of
life after participating in this program.
Conclusions: These findings suggest that a 7 week progressive
aerobic group exercise and skill acquisition program based upon the
Modified Borg scale at high-intensity intervals and the
Movement Disorders, Vol. 30, Suppl. 1, 2015
PWR!MovesV R can benefit motor, cognitive, and non-motor symp-
toms of PD.
187
Treatment of apomorphine-induced skin reactions: A pilot study
R.W.K. Borgemeester, G.F.H. Diercks, M.F. Jonkman, T. van Laar
(Groningen, Netherlands)
Objective: To evaluate the efficacy of four treatment strategies,
including massage, dilution of apomorphine, treatment with topical
hydrocortisone, and pre-treatment with subcutaneous administration
of hydrocortisone, in Parkinsons disease (PD) patients with
apomorphine-induced skin reactions.
Background: Apomorphine-induced skin reactions (i.e. erythema,
swelling and/or subcutaneous nodule formation) are a common side-
effect of continuous subcutaneous apomorphine infusion. However,
the pathogenesis of apomorphine-induced skin reactions is poorly
understood, which explains the absence of proven treatment
strategies.
Methods: An open-label, sequence-fixed, cross-over study with
four treatment arms including local massage, dilution of the apomor-
phine concentration from 0.5% to 0.25%, topical hydrocortisone 1%
and pre-treatment with subcutaneous 10 mg hydrocortisone, was
designed in 20 patients being treated with subcutaneous infusion of
apomorphine. Each treatment arm started after a wash-out period of
2 weeks. The efficacy of each treatment was evaluated after 2 weeks
by determining patient satisfaction, local erythema and nodule size,
as well as skin tissue characteristics. Two skin biopsies were taken
after each treatment modality, at 2 sites, consisting of 1 site 3 days
after infusion and another site 14 days after apomorphine infusion.
Results: Massage and dilution of apomorphine seem to have a
good effect on the nodule formation of apomorphine, whereas the
hydrocortisone creme was less effective as compared with the subcu-
taneous pre-treatment with hydrocortisone. Several biopsies showed
an allergic component as well, consisting of eosinophils.
Conclusions: To our knowledge, this is the first study examining
various treatment strategies in apomorphine-induced skin reactions in
PD. Local treatment with massage, dilution of apomorphine and pre-
treatment with subcutaneous hydrocortisone are effective measures in
reducing the skin problems associated with apomorphine. Therea-
bove, anti-allergic drugs like anti-histamines might play a role in the
treatment of apomorphine-induced skin reactions in the future.
188
Long-term evaluation of 24 hour ambulatory blood pressure
monitoring in patients with Parkinsons disease and symptomatic
neurogenic orthostatic hypotension treated with droxidopa
S. Brillman, S. Husain, S.H. Isaacson (Boca Raton, FL, USA)
Objective: To determine if the effect of droxidopa on clinical
symptoms and systolic blood pressure are durable.
Background: Neurogenic Orthostatic Hypotension due to auto-
nomic dysfunction in Parkinsons disease (PD) not uncommonly
complicates clinical management. Treatment options are limited, due
both to limited symptomatic efficacy in some patients and to
increases in supine hypertension (sHTN) in others. Studies using
droxidopa to raise standing systolic blood pressure (sSBP) in patients
with PD and nOH have identified short term improvement in symp-
toms and in sSBP, but clinical durability beyond 1-2 weeks has been
limited by study design and other factors.
Methods: Droxidopa, a synthetic precursor converted to norepi-
nephrine, was administered to five patients with PD and symptomatic
nOH. During routine clinic visits, patients were assessed with 24
hour ambulatory blood pressure monitoring (ABPM) Orthostatic
Hypotension Questionnaire Question #1 (OHQ-Q1) before and 3-6
month after beginning treatment with droxidopa.
 POSTER SESSION
Results: Retrospective analysis of baseline ABPM demonstrated
marked fluctuations in sSBP in all treated patients, and overnight
sHTN. After treatment with droxidopa, most patients had a reduction
in the number of sSBP lower than 90mmHG measurements on 24
hour ABPM at the post-treatment assessments. Improvement in
OHQ-Q1 (lightheadedness/dizziness) was also. However, fluctuations
in ABPM sSBP measurements and in OHQ-Q1 persisted among
patients at all timepoints.
Conclusions: In this cohort of patients treated with droxidopa for
symptomatic NOH, efficacy and imrpoved s-SBP was maintained
months after beginning treatment. Variabilty in blood pressure and
symptoms persist though, pointing to an underlying difficulty in the
clinical assessment of patients with PD and autonomic dysfunction.
189
Chemogenetic inhibition of the subthalamic region of
Parkinsonian mice improves motor function
L. Broom, T. Samardzic, A. Worley, C. Joanne, O. Yo, D.K. Simon,
C.B. Saper, V. VanderHorst (Boston, MA, USA)
Objective: To test whether chemogenetic inhibition of the subtha-
lamic region improves motor function in a Parkinsonian mouse model.
Background: Deep brain stimulation is an effective treatment of
motor symptoms in Parkinsons disease (PD). Chemogenetic
approaches provide an alternative without limitations of hardware and
unintended stimulation of fiber tracts. One such approach makes use
of Ivermectin (IVM) channels, which are mutated nematode glutamate
gated chloride channels that can be delivered locally via microinjec-
tion of an adeno-associated viral vector (AAV). IVM channels are
inert in mammals due to a mutation, but can be specifically and rever-
sibly targeted by the drug IVM, leading to inhibition of transfected
neurons. We apply this strategy to the subthalamic region (STN),
which is overactive in PD, to assess the feasibility of this approach to
ameliorate motor function in an acute Parkinsonian mouse model.
Methods: We placed micro-injections of AAV10-CMV-IVM-GFP
into the STN region of male C57Bl6J mice. Following transfection,
we injected vehicle or IVM i.p. to assess the effect of inhibition of
the STN region on motor function. We did this first in the intact CNS
and following injection of 6-hydroxydopamine (6OHDA) into the sub-
stantia nigra of the same mice. Motor tests included high speed gait
and kinematic analysis, and assessment of complex motor behavior
using rotarod, balance beam, horizontal ladder, open field testing, and
grip strength. After the behavioral tests, we used immunohistochemis-
try to visualize GFP1 transfected neurons in the STN region and tyro-
sine hydroxylase (TH) neurons and fibers. Behavioral test results were
correlated with injection sites, and the loss of TH staining.
Results: The results show that chemogenetic inhibition of the STN
region in non-lesioned mice induces small enhancements of motor
performance such as an increase in gait speed. Following 6OHDA-
induced dopaminergic cell loss and worsening of motor performance,
inhibition of the STN region results in marked improvements of motor
function. The effects are reversible and dose dependent.
Conclusions: These findings represent a proof of concept for this
novel technology to ameliorate motor function in a Parkinsonian
mouse model. The results demonstrate its potential as a treatment in
PD and other neurological conditions that involve an imbalance in
neural circuitries.
190
No benefit from multifocal repetitive transcranial magnetic
stimulation on motor and mood symptoms of Parkinsons disease
compared to sham stimulation: Results of the MASTER-PD
study
M. Brys, M. Biagioni, S. Agarwal, G. Dacpano, P. Kumar, E.
Pirraglia, Z. Gray, D.K. Simon, A. Wu, H. Fernandez, R. Chen, A.
Wagle Shukla, J.S. Lou, A. Di Rocco, A. Pascual-Leone (New York,
NY, USA)
S73
Objective: To determine efficacy and duration of benefits of
motor and prefrontal cortex high frequency rTMS on motor and
mood symptoms of PD.
Background: Several studies suggest that high frequency rTMS
(HF rTMS) to the motor cortex improves motor symptoms of PD
and HF rTMS to left dorsolateral prefrontal cortex (DLPFC)
improves depression. Yet, there are no appropriately powered, sham
controlled studies targeting depression and motor dysfunction con-
currently despite the frequent co-morbidity.
Methods: 71 PD subjects with motor dysfunction and depression
despite optimized medication treatment consented to participation
and were randomized in this multicenter, double-blind, sham-con-
trolled, parallel-group study of real or realistic (electrical) sham HF
rTMS to primary motor cortex bilaterally, left DLPFC alone or con-
currently. Patients received 2000 stimuli (50 x 4-sec trains of 40
stimuli at 10Hz) for 10 days and were evaluated in standard OFF
state at baseline, at 1 week and at 1, 3 and 6 months post treatment.
Hamilton Depression (HAM-D) scale was used for depression out-
come and UPDRS III for motor outcome.
Results: 59 subjects completed the treatment, 46 subjects (78%)
completed all study visits (real M1-sham DLPFC n513, real
DLPFC-sham M1 n510, real M11DLPFC n521, double sham
n515). There was a significant, sustained decrease in HAM-D in all
study participants regardless of stimulation status (p<0.001), while
UPDRS III improved transiently (p50.03) and reverted to baseline
by month 6. As compared to sham stimulation, no change in UPDRS
III or HAM-D was found 1 month post treatment completion in par-
ticipants receiving real TMS (p5ns). Similarly, no study group dif-
ference was shown when all study visits were analyzed (rANOVA,
p5ns).
Conclusions: Multifocal M1 and/or DLPFC HF rTMS was no
better than sham stimulation for motor or mood symptoms of PD.
Sustained improvement of depression, regardless of stimulation sta-
tus, points to universal benefit from study participation or from a
perceived intervention. Transient improvement of UPDRS III indi-
cates strong placebo response (perhaps related to salient electrical
sham stimulation) precluding further conclusions regarding multi-
target rTMS efficacy. Better understanding of sham rTMS response
in this particular population may help in the design of future efficacy
studies.
191
Effect of antidepressants on the motor symptoms of Parkinsons
disease
H. Calderon, R. Llorens-Arenas, D. Pi~ na-Fuentes, A. Cervantes-
Arriaga, M. Rodriguez-Violante (Mexico City, Mexico)
Objective: To evaluate the effect of antidepressants in the motor
symptoms of Parkinsons disease.
Background: Depressive syndromes occur in an average of 40%
of patients with Parkinsons diseaseDepressive. However, they are
often not identified.
Depression and anxiety disorders are the most common neuro-
psychiatric syndromes in people with PD.
To date, few studies have evaluated the effect of antidepressant
treatment on motor symptoms in patients with Parkinsons disease
(PD) and results have been controversial.
Methods: A longitudinal analytical study was conducted. Patients
were evaluated and divided into two groups: non-depressed (con-
trols), and untreated depression. The diagnosis of depression was
based on the DSM-IV. Treatment with SSRI was initiated in patients
with depression. Patients were assessed 10 weeks after the start of
antidepressants; no adjustment was made antiParkinsonian drugs dur-
ing this time. All patients were evaluated with the MDS-UPDRS.
Other scales applied were: NMSS (scale non-motor symptoms of
PD) and PDQ8 (scale of quality of life PD), HAM-D (Hamilton
depression Scale, HAS (Hamilton anxiety Scale), LARS (scale
Movement Disorders, Vol. 30, Suppl. 1, 2015
S74 POSTER SESSION

Motor and non-motor symptoms scales in depressed patients before and after treatment with antidepressants including controls

P (Post-treatment vs. P (Post-treatment

Scale Pre-treatment Post-treatment pre-treatment) Controls vs. controls)
MDS-UPDRS I 17.4 6 4 14.7 6 3.6 <0.001* 8.5 6 6 <0.001*
MDS-UPDRS II 14.5 6 9 13.4 6 7 0.294 10.7 6 9 0.828
MDS-UPDRS III 30.4 6 13 27.9 6 11 0.213 25.5 6 11 0.095
MDS-UPDRS IV 2.5 6 4 2.6 6 3.8 0.285 2.1 6 3.4 0.828
NMSS 109.4 6 53 100 6 50 <0.001* 40.3 6 36 <0.001*
HAM-D 24.4 6 7 15.8 6 6 <0.001*
HAS 24.0 6 11 20.5 6 9 0.002*
PDQ8 36.6 6 26 34.9 6 24 0.079 19.5 6 18 0.024*
LARS 14.5 6 11 15 6 10 0.170
MOCA 24.1 6 5 24 6 5 0.846
NPI 26.0 6 11 19.5 6 7 <0.001*

apathy Lille), MOCA (Montreal Cognitive Assessment) and the NPI
(neuropsychiatric Inventory).
Results: A total of 48 patients were included (34% male) with a
mean age of 70 6 9) years for men and a mean age of 64 6 13 for
women. The mean disease duration was 7.3 6 3.8 years.
The analysis of the results in depressed patients after 10 weeks of
treatment with antidepressants showed no statistical significance
between groups regarding the MDS-UPDRS motor was found
(30.4 6 13 vs 27.9 6 11 points respectively, P=0.213). There was no
significant difference between the groups in terms of bradykinesia
(P=0.083), tremor (P=0.203) or stiffness (P=0.202). In regards to the
HAM-D scale, NMSS, HAS and NPI a statistical significant differ-
ence was observed between groups (P=<0.001, P=<0.001, P=0.002,
and P=<0.001 respectively. Comparison with the controls can be
seen in [Table I]
Conclusions: The use of antidepressants was not associated with
a beneficial or deleterious effect on the symptoms of Parkinsons
motor disease. Furthermore, no change was observed in motor com-
plications assessed by the MDS-UPDRS part IV.
The SSRI antidepressants should be initiated when indicated, as
well as improving mood, also improve anxiety without affecting
motor symptoms.
192
Outcome quality in iSTEP istradefylline Parkinsons disease trial
M. Cantillon, B. Novak, J. Montero, G. Wilson, R. Smith (Livingston,
NJ, USA)
Objective: PD patient diaries have been consistently and reliably
used as a clinical outcome measure, contributing to regulatory
approval of PD medications. However, estimation of ON and OFF
times relies heavily on accurate completion of patient diaries. This
investigation focused on the impact of rater training and central data
review of the ON and OFF Patient Diary data in the iSTEP Phase III
istradefylline trial.
Background: PD diary information and training was prepared.
Methods: A total of 240 raters from 8 countries participated in
the ON and OFF Patient Diary rater training program. This included
in-person training at Investigators Meetings (IM) and online training
for absentee and new raters. Only trained raters were permitted to
conduct diary training and concordance testing with subjects. Find-
ings were categorized and documented by type (e.g. Invalid Diaries,
Batched Data Entry, Concordance Error, etc.). Raters received addi-
tional training and were asked to retrain subjects on appropriate diary
completion conventions.
Results: Of the 292 visits centrally reviewed diaries to date, 64%
contained findings, some significant. Findings included batched data
entry (57%) defined by more than 5 hours of data entered at one
time (excluding Asleep time), followed by prospective data entry
(27%). Additionally, invalid diaries were identified, defined as diaries
containing more than 4 invalid entries, concordance errors, and miss-
ing data findings; these accounted for 16% of all findings.
Conclusions: These results support the use of a stringent training
and centralized data review program to monitors diary completion.
Such continuous training of users and feedback is effective in ensur-
ing quality data.
193
The freezing of gait (FoG) in Parkinsos disease (PD) could be
reduced by a physiotherapy programme with multisensory cues
T.T.C. Capato, N. Agostini, F. Kolozuk, E.R. Barbosa, M.E.P.
Piemonte (S~
ao Paulo, Brazil)
Objective: Was to check the effectiveness of a MC physiotherapy
programme to reduction FoG in PD.
Background: Freezing of gait (FoG) is a disabling clinical phe-
nomenon characterized by brief episodes of inability to step or by
extremely short steps that typically occur on initiating gait or on
turning while walking. Reduction in step length with frequent trem-
bling of the legs during FoG episodes. Medications and physicalther-
apy techniques can alleviate symptoms of FoG in some patients, but
these treatments lack efficacy in patients with advanced FoG. A bet-
ter understanding of the phenomenon is needed to aid the develop-
ment of effective therapeutic strategies. There are evidences that a
physiotherapy treatment with Multisensory Cues (MC) improve func-
tional disturbances of the basal ganglia motor circuit. The mecha-
nisms by which improvement occur in HD remains inexplicable.
Methods: 30 PD, H&Y 3, were assessed by a single blind exam-
iner before and after 10 training sessions (once in a week during 45
min) and after 60 days of the end of the training. Balance was
assessed by Berg Balance Scale (BBS) and Mini BESTest, Pull and
Release Test (PRT). Gait by Time UP and GO (TUG) and 6 min
walk test. FoG was assessed by NFOG-Q and Snijders & Bloem
Freezing of Gait test. The Independence to AVDS and motor per-
formance and cognition were assessed by UPDRS. The subjects
should have PD history of FoG and falls. They were expected to
understand tests and exercises sequences according to inclusion crite-
ria. During the study period there wast medication changing. The
patients were divided on 2 groups according criterial rules; aged
66.41. Group (I) done programme comprised exercises with MC
(stretching, leg strength exercises; gait and balance training with
multisensory cues (visual, auditory and proprioceptive cues) and
functional activities/attention strategies; breathing exercises and trunk
control). The Group II did the same exercises without cues. Group
III receives only orientations. ClinicalTrials.gov Identifier
NCT01960985.

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
Results: The results showed improvement after treatment, accord-
ing to media score for the Group I e II TUG (p50,01), 6 min walk
(p50,00) and BBS (p50,00), Mini BESTest (p50,00),PRT (p50,00)
NFOG-Q (p5 0,01) only to Group I.
Conclusions: The MC physiotherapy programme proposed in this
study connected to medicine was effective to minimize FoG in PD
and postural instability.
194
The impact a belt adaptation in walker stabilize on gait
measures and falls in Huntingtons disease (HD) and Parkinsos
disease (PD)
T.T.C. Capato, M.S. Haddad, R. Guimar~ aes, J. Tornai, M.R.
Goncalves, M.E.P. Piemonte, E.R. Barbosa (S~
ao Paulo, Brazil)
Objective: Examine the effects a belt Adaptation in Walkers Sta-
bilizer (BAWS) on Gait Measures and falls in HD and PD.
Background: Gait and postural instability disturbs lead to bal-
ance loss and falls in individuals with HD e PD. The slowness of
motor responses to unexpected balance disturbances and greater vari-
ation spatial and temporal are related to disorder processing of sen-
sory feedback. Assistive devices (AD) such as walkers are often
prescribed to prevent falls, but their efficacy is unknown. However,
there are no evidence-based guidelines available to prescribe and rec-
ommendations of adaptations.
Methods: Were assessed 05 subjects with HD moderate and 10
PD (H&Y 3-4) as they walked 3 conditions (without AD, Walker
Stabilizer and BAWS). Demographic information, UHDRS and
UPDRS motor scores, and fall history (FES-I) data were obtained
from ambulatory patients with a diagnosis of HD and PD who were
examined by physical therapists at our Movement Disorders Clinic.
Gait and Balance parameters was assessed by TUG, 6 min walk,
Mini BESTest, Push and Release Test (PRT). We used a BAWS
placed in low back region to provide a proprioceptive cue to the
patients. It also acts as a security belt.
Results: In AD condition, there were differences in gait velocity
and balance parameters between the HD and PD and slowness in
both groups. In Walker Stabilizer conditions to HD and PD there
were a significant improvement in gait velocity and balance scores in
comparison between without AD. The higher differences were shown
with BAWS on 6 min walk, TUG and Mini BESTest. These scores
shown with BAWS show decreased fall risk in HD and PD.
Conclusions: Walker Stabilizer can be very helpful for moderate
HD and PD patients. BAWS can reduce falls when used as a pro-
prioceptive cue. BAWS selection, training and adjustments should be
considered and conducted by a physicaltherapist. More researches
are necessary to evaluate the effects on freezing in PD.
195
Efficacy of safinamide as adjunct therapy in mid- to late-stage
fluctuating Parkinsons disease patients: Post-hoc analyses of 016
and SETTLE trials
C. Cattaneo, E. Bonizzoni, R. La Ferla, M. Sardina (Bresso (Milan),
Italy)
Objective: To investigate the clinical effects of safinamide vs.
placebo on cardinal symptoms of Parkinsons disease and on motor
fluctuations in defined patient subgroups using pooled data from
studies 016 and SETTLE.
Background: Safinamide, a unique molecule with a novel mecha-
nism of action (dopaminergic and non-dopaminergic), resulted safe
and effective in two double-blind, placebo-controlled, 6-months trials
(016 and SETTLE) when used as add-on therapy in patients with idi-
opathic Parkinsons disease (PD) and motor fluctuations, treated with
stable doses of levodopa alone or in combination with other anti-
Parkinsons drugs.
S75
Methods: This post-hoc analysis of pooled data from the pivotal
Phase III trials 016 and SETTLE evaluated the effects of safinamide
vs. placebo on individual cardinal symptoms of PD during the ON
phase (bradykinesia, rigidity, tremor, postural stability, gait) and the
mean change from baseline in daily OFF time in subgroups of
patients who were receiving levodopa alone or concomitant treat-
ments with dopamine agonists (DA) or catechol-O-methyltransferase
inhibitors (COMT-I), or who were considered mild fluctuators at
baseline (daily OFF time  4 hours, irrespective of concomitant
medications).
Results: Compared to placebo, safinamide 100 mg/day signifi-
cantly improved bradykinesia, rigidity tremor and gait, and signifi-
cantly reduced mean daily OFF time when used as adjunct therapy
in all subgroups of patients considered without increasing the rate of
adverse events nor the risk to develop troublesome dyskinesia.
Conclusions: Safinamide was an effective and safe drug when
used as add-on therapy in mid- to late-stage fluctuating PD patients:
improvements were seen in OFF time and in almost all cardinal
symptoms in subjects with wearing-off phenomena, despite they
were receiving an optimized dopaminergic treatment regimen, with-
out deteriorating their motor complications.
196
24 hour levodopa-carbidopa intestinal gel may reduce falls from
unresponsive freezing of gait in Parkinsons disease
F.C.F. Chang, D.S.Y. Tsui, N. Mahant, N. Wolfe, S.D. Kim, A.D. Ha,
J.M. Griffith, M. Drury, V.S.C. Fung (Westmead, Australia)
Objective: We report ongoing data on a prospective, open label
study of 24 hour levodopa-carbidopa intestinal gel (LCIG), as treat-
ment for levodopa-unresponsive freezing of gait (u-FOG) and falls in
Parkinsons disease (PD).
Background: FOG associated with PD is a challenging phenom-
enon, in terms of pathophysiology and treatment. Off period FOG
is treated with increased dopaminergic therapy whereas u-FOG is not
responsive to levodopa or deep brain stimulation.
Methods: Patients with u-FOG documented with an oral dose
cycle of levodopa were commenced on continuous 24 hour infusion
through the LCIG pump with the night-time rate at 50 to 80% of
daytime infusion rate. Patients with u-FOG underwent baseline, 3, 6,
9, 12 and 18 month gait assessments, video-taped examination and
FOG questionnaire. The change in falls frequency were recorded and
Friedmans test was used to test for statistical significance for varia-
bles up to 9 months, using SPSS 22.0, defined as p < 0.05.
Results: 7 patients participated, their mean age 67.4 1/- 8.3 with
duration of PD 18.21/-9.1 years. The falls frequency reduced after
24 hour LCIG (p50.048) at 3, 6 and 9 months compared to baseline.
The FOG questionnaire and 360 degree turning time non-
significantly improved compared to baseline after follow-up of up to
18 months. The LCIG daytime infusion rate was unchanged relative
to baseline and two subjects had transient dyskinesia or postural
hypotension. One subject withdrew from the study following persis-
tent visual hallucinations. Otherwise it was well tolerated without
side effects.
Conclusions: Our study provides additional evidence that 24 hour
LCIG infusion reduces motor complications in PD. We offer a novel
therapy that may reduce falls associated with u-FOG due to PD.
However, a larger prospective study is needed for confirmation.
197
Antecollis associated with Parkinsons disease improved
following apomorphine therapy
F.C.F. Chang, N. Mahant, V.S.C. Fung, D.S.Y. Tsui, Z. Aldaajani, R.
Adam, M.A. Hely (Wentworthville, Australia)
Objective: We report improvement in antecollis in a Parkinsons
disease (PD) patient following subcutaneous apomorphine therapy.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S76 POSTER SESSION
Background: Antecollis is dystonia of the neck resulting in
excessive forward flexion, often associated with dysphagia. It is asso-
ciated with later stage of PD and is often refractory to medical and
botulinum toxin therapy.
Results: We report a 70 year old lady with idiopathic PD diag-
nosed 12 years ago. She presented with unilateral levodopa respon-
sive hand tremor with akinesia and rigidity. 12 months ago, during
treatment with levodopa 600 mg daily, pramipexole ER 3 mg daily,
she developed acute antecollis over 24 hours after a fall with minor
head injury. Reduction in pramipexole to 2.25 mg daily made no dif-
ference. Over 8 months she developed gradual worsening of antecol-
lis with reduced oral intake, weight loss and reduce mobility. She
had visual hallucinations with insight. On examination she had nor-
mal neck extensor strength. There was no rigidity and minimal bra-
dykinesia in the extremities. Administration of oral medication via
nasogastric tube was ineffective. An apomorphine challenge was per-
formed after pre-treatment with domperidone. There was acute
improvement in hand function, rigidity and mobility without speech
or neck posture improvement. However, neck posture started to
improve 4 hours post apomorphine. Apomorphine was commenced
regularly at 2mg subcutaneous injections 3 times a day. This was
well tolerated with mild generalized dyskinesia and no hallucina-
tions. At 2 and 4 months followup, the patient had significant
improvement in swallowing and resolution of antecollis. She was
able to feed, transfer herself and play the piano again and gained 8
kilograms. She had presence hallucinations at night with retained
insight. At 7 months followup she had recurrence of antecollis and
dysphagia which improved following cessation of pramipexole and
commencement of an apomorphine 16 hour daytime infusion with
nocturnal rotigotine patch therapy.
Conclusions: Apomorphine therapy may be an useful treatment
for antecollis in PD.
198
Analysis of daily dose of dopaminergic replacement therapy in
patients with Parkinsons disease: Experience of a medical center
in Taiwan
Y.Y. Chang, T.K. Lin, Y.F. Chen, C.S. Su, M.Y. Lan, Y.F. Chen
(Kaohsiung, Taiwan)
Objective: To study the anti-Parkinsonian medication patterns
and investigate the association between the levodopa equivalent daily
dose (LEDD) and the various clinical variables in patients with Par-
kinsons disease (PD).
Background: The pharmacological treatment of PD is individual-
ized based on motor symptom severity, non-motor symptoms, and
benefits and side effects of the medications. Here we analysed data
on the anti-Parkinsonian treatment and clinical characteristics of PD
patients treated by Movement Disorder specialists.
Methods: A territary care medical center cross-sectional survey
was conducted over a defined period. Information on patient demo-
graphics and clinical features including age, age at PD onset, disease
duration, and modified Hoehn and Yahr (H-Y) stage, and LEDD of
anti-Parkinsonian medications was obtained from the patients medi-
cal records.
Results: During the study period, a total of 244 PD patients (156
male, mean age 67.48 6 10.79 years, range from 3092 years) were
included. The mean LEDD in the study population was
654.6 6 412.4 mg/day, which tended to increase depending on the
duration of disease and H-Y stage. The LEDD was not significantly
affected by gender and the influence of age on the LEDD was vari-
able. The most frequently administered drugs were L-dopa (89.3%),
dopamine agonists (DA) (70.9%), entacapone (49.2%), amantadine
(27.9%), selegiline (15.6%), and anticholinergics (13.5%). Besides,
the most frequent pattern was a combination of L-dopa and DA
(66.8%), followed by L-dopa monotherapy (18.4%), DA monother-
apy (4.1%), and other dopaminergic drugs (2.0%) respectively. There
was no difference in mean LEDD with the use of anticholinergics
Movement Disorders, Vol. 30, Suppl. 1, 2015
and selegiline, while the mean LEDD was significantly higher in
cases taking amantadine (982.6 6 453.8 vs. 527.9 6 315.3 mg/day,
p<0.001).
Conclusions: This study provides a systematic analysis of mean
LEDD in a large cohort of Taiwanese patients with PD. Moreover,
our survey shows that the LEDD is positively correlated with the
duration and severity of PD, and is affected by the different pattern
of use of anti-Parkinsonian medications. The comparison of mean
LEDD between different ethnic populations are worth for the further
assessment.
199
Relationship of vitamin B12 status to baseline clinical condition
and outcomes in a large, early Parkinsons disease cohort
(DATATOP)
C.W. Christine, P. Auinger, A. Joslin, R. Green, PSG DATATOP
Investigators (San Francisco, CA, USA)
Objective: To determine the prevalence of low vitamin B12 sta-
tus and its association with cognitive and motor outcomes in early
Parkinsons disease (PD).
Background: Previous studies have identified relationships of
low vitamin B12 levels with neurological features including neuropa-
thy and cognitive impairment in moderately advanced PD. We
sought to determine the prevalence of low vitamin B12 status in
early PD and whether low B12 was associated with greater
morbidity.
Methods: We measured vitamin B12 and methylmalonic acid
(MMA) levels using 680 of the baseline serum samples from the
DATATOP cohort of patients with early, untreated PD. Low B12
status was defined as serum B12 <184 pmol/l (250 pg/ml) and out-
right B12 deficiency was defined as B12 <157 pmol/l (212 pmol/l)
and MMA >400 nM. Outcomes included motor assessments
(UPDRS scores) and cognitive assessments (Symbol Digits Modal-
ities Test and Selective Reminding Test) at baseline and follow-up,
calculated as an annualized rate of change for those who participated
for 9 months to 2 years. T-tests and chi-square tests were used to
compare outcomes between subjects who were deficient to those
who were non-deficient.
Results: A B12 level <184 pmol/l was present in 12.8% of sub-
jects at baseline and 5% had B12 levels <157 pmol/l (regardless of
MMA levels). Fifteen (2%) were B12 deficient. Using either the
threshold of B12 <184pmol/l (82 subjects) or MMA >400 nM (27
subjects), we found lower scores in the selective reminding test for
these groups at baseline. We also found greater clinical deterioration
(measured by the annualized increase in total UPDRS and motor
scores) in those with baseline B12 levels <184 pmol/l. No associa-
tions were found between baseline B12 status and baseline sensory,
gait, or stability outcomes as measured by individual UPDRS items.
Conclusions: In this cohort of early PD subjects, 1 in 8 subjects
had low B12 status. Moreover, low B12 status was associated with
both baseline cognitive defects and more rapid rate of progression of
impairment as measured by the UPDRS. These changes occurred in
the absence of sensory or gait changes, suggesting that serum tests
may be necessary to detect low B12 status. Our data raise the possi-
bility that prevention or early correction of low B12 status may slow
the onset of disability in PD. Supported by MJFOX Foundation,
Grant 8646.
200
Do late-stage Parkinsons disease patients still respond to
levodopa?
M. Coelho, M. Fabbri, D. Abreu, L. Guedes, N. Goncalves, M.M.
Rosa, J.J. Ferreira (Lisbon, Portugal)
Objective: Our aim was to study the response to a levodopa test
in a late stage PD (LSPD) population.
 POSTER SESSION S77

Background: A subgroup of advanced Parkinsons disease (PD)
patients reaches a late disease phase, whose phenotype is dominated by
complete loss of independence and motor and non-motor levodopa-
resistant symptoms. However, it is still open to debate whether the appa-
rent loss of benefit from levodopa is real or the result of downgrading its
dosage due to the occurrence or fear of adverse effects (AE).
Background: Therapeutic options and practice parameters for PD
have changed significantly in the past 15 years, yet prescribing prac-
tices in the U.S. are unknown.
Methods: Retrospective study of 16,785 individuals receiving
pharmacological treatment for PD who were identified in Cerner
Health FactsV R . Our primary outcome was standardized annual preva-

Methods: 20 LSPD patients, with Schwab and England ADL lence of antiParkinsons drug use by drug class from 2001 to 2012.
Scale (SE) < or 5 50 or Hoehn Yahr (HY) Stage >3 (MED ON), We also compared antiParkinsons medication trends and polyphar-
underwent a levodopa challenge test with a supra-maximal dose. macy by age and sex.
MDS-UPDRS-III and the Abnormal Involuntary Movement Scale Results: The most frequently prescribed PD drugs between 2001
were evaluated before and after levodopa. and 2012 were levodopa (83%) and dopamine agonists (29%). Dopa-
Results: We included in the study 9 men and 13 women, with median mine agonist use began to fall in 2007, from 37% to 25% in 2012,
age of 78.8 years (IRQ: 73.5-82), median disease duration of 14 years but the timing of the decline was more closely associated with
(IQR: 10-19.75) and median S&E of 40 (IQR:30-40) during MED ON. adverse event reporting rather than publication of the American
Academy of Neurologys (AAN) practice parameter refuting levo-
dopa toxicity. Despite safety concerns for cognitive impairment and
Motor outcomes before (MED OFF) and after (MED ON) levo- falls, individuals 80 years had stable rates (20%) of dopamine ago-
dopa challenge test in the LSPD population nist use. Polypharmacy was most common in younger individuals.
Conclusions: Dopamine agonist use declined from 2007 to 2012,
MED OFF MED ON p - value
suggesting that increased awareness of safety issues and AAN prac-
MDS-UPDRS-III 67.5 57 [49-64] <0.001 tice parameters influenced prescribing. However, these events
[60.6-78.2] seemed to have little effect on the treatment provided to older adults
with PD. Additionally, use of dopamine agonists did not begin to
Speech 3 [2-4] 3 [2-4] 1
decline until two years after publication of the AANs practice
Rigidity 9 [4-14.25] 3.5 [0-11] <0.001
Bradykinesia 36,50 [33-40] 33 [24.2-37.5] 0.001 parameter, showing that the decline in dopamine agonist use was not
Rest tremor 0 [0-4] 0 <0.05 immediate and may have been impacted by increasing safety
concerns.
Arising from chair 4 [3-4] 3.5 [3-4] 0.157
Freezinf og gait 3 [2-3] 2 [2-2] 0.068
Posture 2 [2-3] 2 [2-3] 1
Postural Stability 3 [3-4] 3 [3-3.75] 0.059 202
Gait 3 [3-4] 3 [3-3.75] <0.05
Axial Signs 19 [17-22.5] 17 [15-19] 0.053 Changes in motor-cortex excitability after different rehabilitation
AIMS 0 [0-0] 1.5 [0-9.5] 0.001 programs in PD patients with freezing of gait: Neurocognitive
S&E 30 [20-40] 40 [30-40] <0.05 rehabilitation with motor Iimagery vs treadmill training
H&Y 4 [4-5] 4 <0.05 A. Cucca, M. Catalan, L. Antonutti, S. Mezzarobba, P. Busan, N.
Koscica (Venice, Italy)
Values are presented as median [IQR, 25th75th percentile].
AIMS: Abnormal involuntary movement scale. Statistical signifi- Objective: Testing the efficacy of two different rehabilitation
cant results are in bold character. Axial Sign: Speech, Freezing, programs in improving FoG in PD patients and studying the impact
Gait and Postural stability. *: S&E scores during ON and OFF of these treatments on cortical excitability.
condition were not evaluated before and after the levodopa chal- Background: Freezing of gait (FoG) is a highly disabling symp-
lenge test but by means of the clinical interview. tom of Parkinsons disease (PD) characterized by brief, episodic
absence or marked reduction of forward progression of the feet dur-
ing walking. FoG pathogenesis is not completely understood and
Table 1 reports on motor response to levodopa. Levodopa signifi- pharmacological treatments generally have a poor outcome. For this
cantly improved the MDS-UPDRS-III score (14.9%), but had no effect reason many rehabilitation treatments have been proposed with con-
on axial signs with exception of gait in a minority of patients. There trasting results. We wanted to test the efficacy of Motor Imagery
was not significant improvement in the SE or HY scales. The response (NR-MI) in reducing FoG, as compared with Treadmill Training
to levodopa positively correlated with the acute appearance of dyskine- (TT).
sias and the MDS-UPDRS-IV score. AE occurred in 7 patients during Methods: 20 PD patients with FoG were enrolled and randomly
the test, the most frequent being moderate drowsiness (n 5 6). assigned to treatment groups. Group 1 performed 20 sessions of a
Conclusions: LSPD patients still show a mild response to a supra- Neurocognitive Rehabilitation program based on NR-MI, while
maximal levodopa dose but frequently associated to AE. Even in this late Group 2 underwent 20 sessions of TT. At baseline and at the end of
disease phase, there is a positive association of levodopa response with the rehabilitation program (T1), patients were evaluated by assessing:
motor fluctuations and dyskinesias, A decrease in the response to a levo- disease stage (H&Y and UPDRS III), FoG (FOGQ), cognitive abil-
dopa test is a potential marker of disease progression in the later stages. ities (e.g. attention, executive functions) and indexes of cortical
excitability evaluated registering from lower limbs, by means of sin-
gle and paired-pulse Transcranial Magnetic Stimulation (TMS).
201 Results: Results at baseline, the groups did not differ for any
AntiParkinsons drug use in response to practice parameter considered variable. After treatment, Group 1 experienced a signifi-
publication, drug availability, and unofficial prescribing forces cant reduction of FoG (p<0.001) while Group 2 did not show any
J.A.G. Crispo, Y. Fortin, M. Emons, L.M. Bjerre, D.E. Kohen, S. Perez improvement. TMS mainly suggested a tendency toward an increase
in the excitability of the motor cortex after both treatments with
Lloret, D.R. Mattison, A.W. Willis, D. Krewski (Ottawa, ON, Canada)
respect to baseline indexes of motor thresholds and motor evoked
Objective: To describe patterns of antiParkinsons drug utiliza- potentials recruitment curves, as well as in intracortical inhibition.
tion between January 2001 and December 2012 in a national cohort On the other hand, a tendency toward a prolongation in the duration
of individuals with Parkinsons disease (PD). We also examined the of the silent period could be observed in both groups, as well as a
impact of practice parameter publication, drug introduction/with- tendency toward a diminution in intracortical facilitation in the TT
drawal, and unofficial prescribing forces on prescribing patterns. group.

Movement Disorders, Vol. 30, Suppl. 1, 2015

S78 POSTER SESSION
Conclusions: Although both rehabilitation programs mainly
induced comparable effects on TMS, only NR-MI showed a signifi-
cant improvement of FoG, suggesting a different mechanisms of
intervention between the two treatments. NR-MI appears to be an
interesting suitable rehabilitation strategy to treat FoG in PD
patients.
203
Use of tDCS as motor cortex stimulation predictor for gait
disorders in advanced Parkinsons disease
E.U. da Silva, L.A. Nilton, Jr., J.C.E. Veiga, J.M.d.A. Silva, H.C. de
Souza (Sao Paulo, Brazil)
Objective: To evaluate the benefit of Epidural Motor Cortex
Stimulation (MCS) in Parkinsonian patients who presented improve-
ment of freezing of gait (FOG) and balance after transcranial motor
cortex stimulation (tDCS).
Background: Gait disturbances such as freezing of gait (FOG),
balance and apraxia are challenging symptons in advanced advanced
Parkinsons disease (PD), generally resistant to conventional drug
and non-drug treatment, can generate loss of autonomy and traumatic
complications. Recently, researches have been directed toward these
devastating symptoms. Traditional deep brain stimulation have been
proved worthless and Pedunculopontinous Nucleus Stimulation, pro-
posed as a new potential target, still havent been widely accepted for
its risks and lack of predictors. Few reports suggested improvement
of bradykinesia and gait after MCS. Lately, the possibility of cortex
modulation with tDCS have leaded to new perspectives and non-
invasive approaches. Many authors reported changes in gait and
motor skills after these modalities. We report the benefit MCS in 4
patients who presented improvement after tDCS and submitted to
MCS.
Methods: We selected 12 PD patients, who presented motor fluc-
tuations, severe gait disturbances, and who showed insufficient
improvement after levodopa trial (30%). All patients were submitted
tDCS, 4 weekly sessions, with 2mA, during 30.
Patients who presented improvement of Gait, balance and brady-
kinesia were considered to underwent Surgical Epidural Motor Cor-
tex Stimulation (MCS) of the left hemisphere. Improovement of gait
was considered as remission of FOG, step larger than a foot, 5 m
walking time, and improove in posture and balance. Patients were
assessed preoperatively and 3 months after surgery.
Fig. 1. (203).
Movement Disorders, Vol. 30, Suppl. 1, 2015
Results: We observed that 33% of patients showed improvement
of gait and balance after TDCS. All selected patients showed expres-
sive gait changes following TDCS and MCS, in a follow-up of 4-18
mo. [figure1]The benefit of MCS was similar to the best response
observed after TDCS which occurred 1-3hrs after the session and
lasted for 3-5 days. There was no change in mean daily medication
intake, and no side effects were observes during this period.
Conclusions: This study suggests that MCS improves FOG, bal-
ance and apraxia in PD similar to TDCS responses, since this modal-
ity provides continuos stimulation, responses are more stable and
lasting. TDCS could be an efficient trial.
204
Eight years experience with continuous intraduodenal levodopa
infusion in Parkinsons disease
O. De Fabregues, J. Dot, A. Abadia, J. Hernandez, M. Ibarria, A.
Ferre, C. Puiggros, J.R. Armengol, M. Quintana, J. Alvarez-Sabin
(Barcelona, Spain)
Objective: To describe our experience of 8 years in the manage-
ment of continuous intraduodenal infusion of levodopa (CIDLI) treat-
ment for Parkinsons disease (PD).
Background: CIDLI is a new treatment for advanced PD that has
demonstrated to improve motor fluctuations. Long-term therapy com-
plications and their management and its effect on sleep, cognition
and behavior and impact in patients quality of life and caregiver
burden are not well established.
Methods: Open and prospective study in patients with advanced
PD with disabling motor fluctuations treated with CIDLI. Motor
scale and patient diaries were used to evaluate the motor condition.
Adverse events and action taken to solve them were collected.
Quality of sleep subgroup (sG): evaluated with Epworth scale,
fatigue scale, Pittsburg quality of sleep questionnaire, Beck depres-
sion scale, and Hamilton anxiety scale, and overnight polysomnogra-
phy study.
Neuropsychological assessment sG: evaluated with a specific neu-
ropsychological battery for cognitive assessment by the same neuro-
psychologist at the same environmental conditions.
Health status, quality of life and caregiver burden sG: evaluated
with quality of life questionnaire in PD (PDQ-39), health status ques-
tionnaires (EQ-5D and EQ-VAS), global clinical impression scale
(CGI) and caregiver burden questionnaire (Zarit Burden index).
 POSTER SESSION
Assessments at baseline, week 1, three, six, twelve months and
one, two, three, four, five, six, seven and eight years.
Results: Thirty patients were included (17M/13F) with advanced
PD. Mean age was 68.5 years (range 54-79) and the mean duration
of the disease was of 13.8 years (range 7-23).
Patients showed a significant and sustained motor improvement
with increase of time ON to more than 80% of their waking time,
and a mean decrease of 5.2 h in OFF time, without deterioration
or with a tendency to an improvement of non-motor disorders stud-
ied. With improvement in the quality of life and reduction of the
caregiver burden, despite several complications and adverse events
most of low and moderate severity, and some serious related to PEG,
to the infusion system or to the treatment itself. All the patients
selected maintained the treatment except 5. Five patients in CIDLI
treatment died by not related cause with the treatment.
Conclusions: We confirm CIDLI as a treatment with sustained
efficacy, where the correct management requires the organization of
a multidisciplinary team.
205
The efficacy and safety of coenzyme Q10 in preventing the
progression of early Parkinsons disease: A meta-analysis
R.C. De Roxas, R.D.G. Jamora (Manila, Philippines)
Objective: The objective of this study is to assess and summarize
the available evidence on the efficacy and safety of Coenzyme Q10
administration in the prevention of the progression of early Parkin-
sons disease.
Background: Coenzyme Q10, also known as Ubiquitone, is a
substance now being used as a dietary supplement in many countries
including the Philippines. It has also been the focus of several
researches as treatment for several diseases including Parkinsons
disease. Several studies have shown that Coenzyme Q10 inhibits
mitochondrial dysfunction in Parkinsons disease, hence delaying its
progression.
Methods: This is meta-analysis of randomized controlled trials
on the use of Coenzyme Q10 in Parkinsons disease. A literature
search in several databases was conducted for relevant studies. Three
randomized controlled trials met the inclusion criteria. The efficacy
of Coenzyme Q10 were measured using the total and the component
scores of the Unified Parkinsons disease Rating Scale on follow-up.
On the other hand, safety were measured using the withdrawal rate
and the associated adverse reactions during the therapy of CoQ10.
The Review Manager Software was utilized for the meta-analysis.
Results: Compared to Placebo, treatment of CoQ10 did not show
any significant difference in the mean scores of the UPDRS mental
and ADL scores. Interestingly, the UPDRS motor score showed a
significant difference between Coenzyme Q10 and placebo, but no
significant difference when a subgroup analysis between high-dose (-
4.03 [-15.07-7.01], p-value= 0.47, I2=67%, P for heterogeneity=0.08)
and low-dose Coenzyme Q10 (0.53 [-0.89-1.94], p-value= 0.47,
I2=34%, P for heterogeneity=0.22) was done. Overall, there was no
significant difference in the total UPDRS score (0.68 [-0.61-1.97], p-
value= 0.30, I2=0%, P for heterogeneity=0.70). The most common
side effects of the use of Coenzyme Q10 are anxiety, back pain,
headache, sore throat, nausea, dizziness and constipation.
Conclusions: CoQ10 treatment was found to be safe with only
minimal side effects but it did not show any significant difference in
the mean scores of the UPDRS total and component scores in
patients with Parkinsons disease.
206
The impact of electrical parameters on bradykinesia of
Parkinsons disease patients after deep brain stimulation surgery
M. Delrobaei, S. Tran, G. Gilmore, K. Ognjanovic, K. McIsaac, M.
Jog (London, ON, Canada)
S79
Objective: (1) To provide an effective approach for monitoring
of Parkinsons disease (PD) patients bradykinesia, (2) to systemati-
cally and objectively identify the clinical effects on the bradykinesia
of 15 PD patients undergone Subthalamic deep brain stimulation
(STN-DBS) over successive programming sessions.
Background: Clinical scale based follow-up of patients under-
going STN-DBS has shown inconsistent effect on bradykinesia in
PD patients. However, quantitative assessment of STN-DBS effects
on bradykinesia has not been done.
Methods: Fifteen PD patients and 15 healthy controls are
recruited. The study has been approved by the local ethics commit-
tee. Each patient is assessed pre-operatively and followed for 6
months post-operatively. At each visit, we test three DBS settings
with enough time between the sessions. The settings are pre-defined
and cover the whole range of device settings in common practice.
The settings are randomized for each patient. The patients are
recorded in the lab environment while wearing a motion capture suit.
A variety of features are extracted from the data to quantify
bradykinesia.
Results: Currently there are 15 patients enrolled in this study
and preliminary analysis has been performed for 3 patients who
have finished all the 9 lab visits as well as 3 healthy controls. We
analyze forearm angular displacement during a hand pronation-
supination task. The extracted features are: standard deviation
(STD), range of motion (ROM), angular velocity (Vel), and vari-
ability in terms of time (Time_Var) and amplitude (Amp_Var).
We define a new bradykinesia index which considers all the fea-
tures: B-Index 5 sqrt(STD*ROM*Vel/Time_Var*Amp_Var). Our
analyses reveal that increasing the frequency of stimulation (volt-
age and pulse width fixed) generally decreases the B-Index.
Increasing the pulse width (voltage and frequency fixed) does not
generally cause a consistent effect on the B-Index. Increasing the
voltage (frequency and pulse width fixed) increases the B-Index.
On average, the B-Index of healthy controls is higher than the
patients.
Conclusions: We conclude that our method provides an effective
approach to quantify PD patients bradykinesia after DBS surgery
which overcomes some of the shortcomings of the other studies. We
show that our approach form an accurate tool to compare the slow-
ness of movement of PD patients and healthy people.
207
Efficacy of IPX066, an extended-release formulation of
carbidopa-levodopa, in advanced Parkinsons disease patients
with troublesome dyskinesia
R. Dhall, L. Struck, R. Rubens, V. Shah, S. Gupta (Phoenix, AZ,
USA)
Objective: Evaluate the efficacy of IPX066 in advanced Parkin-
sons disease (PD) patients with troublesome dyskinesia.
Background: IPX066 is an extended-release formulation of
carbidopa-levodopa (CD-LD) designed to provide a rapid increase in
plasma LD concentrations similar to immediate-release CD-LD, but
with sustained stable concentrations to allow a dosing interval of
every 6 hours. IPX066 has demonstrated improvements in PD motor
symptoms in early and advanced PD.
Methods: IPX066 was administered for 13 weeks in a
double-blind, parallel-group study vs. immediate-release CD-LD
(IR) in advanced PD patients (randomized N=393). This post-
hoc analysis compared the cohort of patients who entered the
study with any reported on time with troublesome dyskinesia,
by patient diary (IPX066, n544; IR, n535). Efficacy measures
included patient diaries and Unified Parkinsons disease Rating
Scale (UPDRS) Parts II (activities of daily living) 1 III (motor
score).
Results: At baseline, these patients had a mean (SD) on time
with troublesome dyskinesia of 1.7 (1.3) hr and 1.9 (1.6) hr, and
mean off time of 5.3 (1.8) hr and 5.5 (1.7) hr, for IPX066 and IR
Movement Disorders, Vol. 30, Suppl. 1, 2015
S80 POSTER SESSION
groups, respectively. Baseline UPDRS Parts II1III scores were 30.3
(14.9) for IPX066 and 34.1 (14.8) for IR. At the end of the 13-week
treatment period, IPX066 treatment produced a significantly greater
improvement in UPDRS Parts II1III scores (-4.9 [10.5] points) com-
pared to IR, which worsened by 11.6 (10.4) points (P<.001).
IPX066 treatment also produced a greater decrease in off time
(-1.4 [2.8] hr) compared to the IR group (-0.7 [2.9] hr), although this
was not statistically significant (P=.13). Both groups showed less
on time with troublesome dyskinesia at the end of treatment, -0.4
(1.9) hr for IPX066 and -0.8 (2.2) hr for IR (P=.40).
Conclusions: Advanced PD patients with troublesome dyskinesia
at baseline demonstrated significantly greater improvement in
UPDRS Parts II1III scores and numerically greater improvement in
off time after treatment with IPX066 compared to IR. These
improvements were not accompanied by increased on time with
troublesome dyskinesia in either treatment group.
208
Feasibility study of an intensive multi-strategy rehabilitation
program for Parkinsons disease
J.M. Domingos, V. Canica, C. Godinho, A. Pinho, D. Guerreiro, J.J.
Ferreira (Torres Vedras, Portugal)
Objective: To assess the feasibility of an intensive multi-strategy
rehabilitation program for individuals with Parkinsons disease (PD)
and to evaluate the responsiveness of multiple outcome measures
that could be candidates to be applied on confirmatory trials.
Background: Increasing research suggests that intensive reha-
bilitation programs can provide both short and long-term benefits
to individuals with PD. Given the variety of rehabilitation pro-
grams that exist, the true acceptability to these programs is still
limited.
Methods: We conducted an exploratory feasibility study in indi-
viduals diagnosed with idiopathic PD. Feasibility was assessed by
level of adherence to the program. Participants were recruited from a
Movement Disorders Unit (Campus Neurol ogico Senior - CNS)
based on their balance and gait impairments. Participants were
assessed with the MDS -UPDRS (part III), Pull-test, Timed-up and
go (TUG) and Balance Berg scale, and Schwab & England Scale.
Our intervention consisted of at least 2 hour individual physiotherapy
sessions per day, 3 times a week for at least 4 weeks. The program
consisted of practicing gait and balance multitask activities with dif-
ferent kinds of motor and cognitive tasks progressively introduced.
Focused attention and multitasking was also explored with resistance
training using plurisports adapted to PD, such as boxing, dancing
and swimming.
Results: The participants included 6 woman and 7 men, mean
age of 72.5, Hoehn and Yahr stages 2 to 4 and with a mean disease
duration of 7 years. Every participant completed the program with
no relevant adverse effects and according to the protocol. The out-
comes with larger effect size were the MDS-UPDRS (Part III) (with
0,78 Cohens effect size); Berg balance scale (0,25 Cohens effect
size); Timed Up and Go (0,25 Cohens effect size); Pull test (0,07
Fig. 1. (209).
Movement Disorders, Vol. 30, Suppl. 1, 2015
Cohens effect size) and Schwab and England (0,03 Cohens effect
size).
Conclusions: Our results suggest that this intensive rehabilita-
tion program had a high adherence level and appears to be feasi-
ble for these individuals with moderately severe PD. Our results
also suggest that the most responsive outcome measure for an
intervention with these characteristics is the MDS-UPDRS
(Part III).
209
Onset and duration of clinical effect of IPX066, an extended-
release formulation of carbidopa-levodopa, in advanced
Parkinsons disease
A. Ellenbogen, R.A. Hauser, N.B. Modi, A. Hsu, S. Khanna, S. Gupta
(Bingham Farms, MI, USA)
Objective: Compare the onset and duration of clinical effect of
IPX066 to immediate-release (IR) carbidopa-levodopa (CD-LD) and
CD-LD 1 entacapone (CL1E) in patients with advanced Parkinsons
disease (PD).
Background: IPX066 is an extended-release, multiparticulate
capsule formulation of CD-LD designed to provide a rapid increase
in plasma LD concentrations similar to IR CD-LD, but with sus-
tained stable concentrations to allow dosing every 6 hours. IPX066
has demonstrated improvements in PD motor symptoms in early and
advanced PD.
Methods: IPX066 and CL1E were compared in a double-blind
crossover study; IPX066 and IR CD-LD were compared in an open-
label randomized crossover study. The Unified Parkinsons disease
Rating Scale (UPDRS) Part III (motor score), Investigator Dyskinesia
Assessment (IDA; rating of off time and on time with or without
dyskinesia), and finger tapping (taps/min) were assessed after a sin-
gle dose of IPX066 or the comparator. Outcomes were assessed pre-
dose and at 30 min (tapping, IDA) or hourly (UPDRS) intervals after
dosing. The time at which patients crossed a threshold of improve-
ment in finger tapping [10, 15, 20%] and UPDRS Part III [2.5, 5, 7,
11 units] were used to determine the onset and duration of clinical
effect. Time to on and duration of on without troublesome dys-
kinesia (on with no or non-troublesome dyskinesia) were analyzed
for the IDA.
Results: For IPX066 vs. CL1E, a subset of 32 patients under-
went pharmacodynamic assessment (of 91 randomized in the larger
study); 27 patients were enrolled for IPX066 vs. IR CD-LD. Time to
on and duration of on using a threshold of 15% increase from
baseline in tapping, and an 11 point improvement in UPDRS were
similar to values obtained on the IDA, and are shown in Table 1.
The pattern of improvements was similar using other improvement
thresholds. [figure1]
Conclusions: The onset of clinical effect for IPX066 was rapid,
similar to that for IR CD-LD and CL1E. The duration of effect for
IPX066 was substantially longer than that for either IR CD-LD or
CL1E.
 POSTER SESSION
210
TDCS and gait training for hypokinetic gait disorders: A pilot
study
T. Emara (Cairo, Egypt)
Objective: Different gait training protocols usually improve gait
speed by 0.1 m/sec. Our objective was to test whether applying
Transcranial Direct Current Stimulation (TDCS) with gait training
may help achieve better gains in walking speed.
Background: Gait problems in patients with Parkinsons
disease or vascular Parkinsonism are often resistant to medical
treatments.
Methods: Nine patients with PD or vascular Parkinsonism were
recruited. 12 20-minute sessions of Anodal TDCS at Cz that were
followed by gait training sessions within a period of 4 weeks were
applied. 10 mts walking speed at self selected pace was measured at
baseline and at the end of the treatment period. Other outcome
measures included degree of assistance (1-7 score similar to the
functional independence measure grading), number of falls, and
functional category according to walking speed (difficult in-home
ambulation less than 0.2 m/s; in-home ambulation 0.2-0.4 m/s, lim-
ited community ambulation 0.4-0.8 m/s; community ambulation
more than 0.8 m/s). No change of medications was allowed during
the study period.
Results: Six cases with PD (5 males and one female) and three
male patients with vascular Parkinsonism with mean age of 68.1 1/-
4.5 and mean duration of illness of 7.5 1/- 2.3 yrs were recruited.
There was a significant change in gait speed (baseline 0.291/-
0.17 m/s, post 0.561/-0.23 m/s; p50.0001), and degree of assistance
needed (p50.001) but not in the number of falls (p50.1). The mean
speed gain was 0.271/-0.14 m/s. 5/9 patients had a 1-2 point change
in their functional category of walking speed, all of them had a start-
ing speed of less than 0.4 m/s.
Conclusions: TDCS may augment the effects of gait training in
patients with hypokinetic gait disorders. The effect is particularly
clear in those with low starting walking speed and results in a func-
tional change of walking ability in those cases. A larger RCT is cur-
rently underway to validate these results and to monitor the
sustainability of this improvement.
211
The influence of baseline disease severity on the efficacy of
IPX066, an extended-release formulation of carbidopa-levodopa,
in advanced Parkinsons disease
A.J. Espay, G. Liang, K. Sharma, R. Rubens (Cincinnati, OH, USA)
Objective: Evaluate whether the clinical efficacy of IPX066 is
influenced by baseline disease severity in clinical trials of advanced
Parkinsons disease (PD), using post hoc subgroup analyses.
Background: IPX066 is an extended-release formulation of
carbidopa-levodopa (CD-LD) designed for a rapid increase in plasma
LD concentrations (similar to immediate-release [IR] CD-LD), but
with sustained stable concentrations to allow dosing every 6 hours.
IPX066 has demonstrated improvements in motor symptoms in early
and advanced PD.
Methods: IPX066 was tested in advanced PD in two random-
ized, double-blind, active comparator-controlled Phase 3 studies
(ADVANCE-PD: IPX066 vs. IR CD-LD for 13 weeks, N=393;
ASCEND-PD: IPX066 vs. CD-LD1entacapone using a 2-week per
period crossover, N=91). Subgroups were dichotomized into more
severe or less severe based on median baseline off time tal regions, we observed a noted improvement in mood, cognitive
(5.67 hr, ADVANCE-PD; 5.0 hr, ASCEND-PD) and median
UPDRS Part II1III (activities of daily living 1 motor score: 32,
ADVANCE-PD; 30, ASCEND-PD). The changes from baseline in
UPDRS II1III scores, off time, and on time with troublesome encouraging for tDCS to be a low-risk, high-yield treatment in the
dyskinesia by PD diary were analyzed by treatment for each
subgroup.
S81
Results: IPX066 significantly improved off time (P<.0001)
and UPDRS II1III scores (P<.03) compared with the active con-
trols in the overall studies. In both studies, numerical improve-
ments from baseline in UPDRS Parts II1III and off time were
seen with IPX066 vs. the comparator in each disease severity
subgroup. In the larger ADVANCE-PD study, the improvements
in off time were significantly greater for IPX066 vs. IR CD-
LD in the more severe off (P<.0001) and in both the more
(P=.02) and less severe (P=.0001) UPDRS subgroups. Greater
improvements in UPDRS II1III were also seen with IPX066 in
the more severe off (P=.0002) and UPDRS (P=.0001) sub-
groups; the approximate 2-fold improvement by IPX066 compared
to IR CD-LD in the less severe off (P=.13) and UPDRS
(P=.18) subgroups did not reach significance, possibly due to a
lower score range (floor effect). For both studies, IPX066 did not
worsen on time with troublesome dyskinesia compared to active
controls in any subgroup (P>.11).
Conclusions: Across disease severity subgroups, IPX066 con-
sistently improved UPDRS Part II1III and off time vs. the
active controls without significantly worsening troublesome
dyskinesia.
212
Impact of tDCS in Parkinsons disease on mood, cognition, and
motor deficits: A randomized, double-blinded, placebo-controlled
trial
R.A. Falconer, S.L. Rogers, Y. Torres-Yaghi, P. Turkeltaub, F. Pagan
(Washington, DC, USA)
Objective: Evaluate the potential for bifrontal transcranial direct
current stimulation (tDCS) to improve mood, cognitive and motor
functioning in patients with Parkinsons disease.
Background: tDCS has demonstrated ability to temporarily
enhance cognitive, motor and affective functions of the brain. Prior
studies have shown definable improvement in post-stroke patients.
This study seeks to examine whether these benefits translate to neu-
rodegenerative conditions. An open-label trail showed potential for
improvement. This study examines the validity of those results in a
placebo-controlled trial.
Methods: Seven patients with Parkinsons disease were randomized
to either a treatment arm or a placebo arm in a double-blinded method.
Pre-stimluation testing included the following: UPDRS, Becks Depres-
sion Screen (BDS), MOCA, and speech assessments. Participants in the
treatment arm were then given tDCS treatments daily for 10 days. These
daily treatments involved 2mA current administered in a bifrontal mon-
tage for 30 minutes, designed to facilitate frontal lobe integration at the
prefrontal cortex. Participants in the placebo-controlled arm received a
brief, 15-second stimulation to mimic treatment, but no other therapy.
After completion of the 10 days, a post-test battery was completed for
comparison. We will complete 1 month post-follow-up with testing and
a full delayed intervention to the placebo group.
Results: Regarding mood, the treatment arm experienced a 65%
improvement on average in BDS, compared to 22% in the placebo
group. For cognition, the treatment group saw a 36% improvement
on average in MOCA score, compared to 4% in placebo group.
Regarding motor functioning, the treatment group saw a 24%
improvement on average in UPDRS, compared to an average decline
of 13% in the placebo group. When comparing treatment and pla-
cebo, improvement was consistently greater in the treatment arm by
a difference of 43% (BDS), 32% (MOCA) and 37% (UPDRS).
Conclusions: With 10 days of tDCS stimulations to the bifron-
and motor scoring that was not reflected in the placebo arm.
Although low sample size is a limitation to this study, the noted
improvement in the treatment arm compared to placebo arm is
Parkinsons community and should propel further tDCS studies in
PD.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S82 POSTER SESSION
213
Leg rest tremor response to acute dopaminergic challenge
predicts long term Parkinsons disease diagnosis
S. Fari~
na, M. Wilken, P. Morisset, D. Cerquetti, M. Rossi, M.
Merello (Buenos Aires, Argentina)
Objective: To evaluate leg rest tremor (LRT) response to acute
dopaminergic challenge and its relationship to subsequent long term
Parkinsons disease (PD) diagnosis.
Background: LRT can be an early sign of PD and other Parkin-
sonisms, such as multiple system atrophy and vascular Parkinsonism.
Its predictive value for PD clinical diagnosis has not been described.
Methods: A retrospective review of medical records from
patients with a short-onset Parkinsonism that were submitted to acute
levodopa challenge for clinical prediction of sustained long-term
dopaminergic response between November 1999 and August 2014.
Data was collected on demographics, levodopa response (a modifica-
tion of UPDRS-III or MDS-UPDRS-III 30% was considered a pos-
itive test and a reduction in at least one point in LRT subscore was
considered a positive response of LRT), clinical manifestations and
final clinical diagnosis after at least one-year follow-up.
Results: A total of 778 patients were evaluated, of which 75
(10%) patients presented LRT. Fifty four (72%) had responsive LRT,
of which 41 (76%) showed a positive response to levodopa acute
challenge and 49 (65%) fulfilled all UKPDSBB criteria at one-year
follow-up. Of the 21 (28%) non-responsive LRTs, only one (5%)
showed a total positive response to acute levodopa challenge and a
final PD diagnosis, whereas 20 (95%) had negative response to acute
challenge, of which 6 (30%) received a PD diagnosis at one-year fol-
low-up (false negatives). A responsive LRT to acute levodopa chal-
lenge obtained a sensitivity of 88%, a specificity of 74% with a
positive and negative likelihood ratio for a final clinical PD diagnosis
of 3.3 and 0.2, respectively. Multivariate analysis revealed the pres-
ence of limb bradykinesia (p<0.0001) and the total UPDRS/MDS-
UPDRS-III response to levodopa acute challenge (p5<0.0001) were
independent factors related to LRT response. No PD patient had iso-
lated (without any akineto-rigid feature) LRT, whereas 5 out of 19
(26%) presented LRT without arm or leg rest tremor. LRT magni-
tude response to levodopa was significantly higher than hand rest
tremor (p50.033).
Conclusions: LRT, although infrequent, can be an early sign of
PD. It was frequently accompanied with hand rest tremor, but
showed a greater magnitude response to levodopa than the latter. Its
positive response to acute levodopa challenge has a high sensitivity
and moderate specificity for PD diagnosis.
214
Benefits of task-specific learning-principled practice to improve
freezing of gait for individuals with Parkinsons disease in a
small group community setting. A case series study
B.G. Farley, K.M. Hamilton, A.B. Messer, K. Greene, L. Rankin
(Tucson, AZ, USA)
Objective: To examine the benefits of task-specific learning-prin-
cipled practice to improve freezing of gait (FOG) for individuals
with Parkinsons disease (PD) in a small community setting.
Background: FOG is one of the most disabling symptoms of
advanced stage PD and is associated with frequent falls and reduced
quality of life (QoL). Researchers and clinicians define FOG as: An
episodic inability to generate effective stepping most commonly
experienced during turning and step initiation, but also when faced
with spatial and time constraints, stress, and distraction. Despite the
multifactorial nature of FOG, task-specific training has not yet been
applied to counteract the multiple motor/cognitive/emotional triggers
that lower threshold for the occurrence of FOG and that may interact
and deteriorate synergistically. In addition, learning principles of
practice have not been applied to task specific antifreeze exercises.
Instead, more general gait and balance training with attentional strat-
Movement Disorders, Vol. 30, Suppl. 1, 2015
egies and external cues are typically used to circumvent freezing
episodes.
Methods: In this case series study, we investigated the effects of
a task-specific learning principled approach that targeted each per-
sons unique triggers directly. In addition to specificity of training,
other learning principles were integrated into the program including:
feedback, intensity through high effort and dosage (5 days; 3 hours/
day), and progressive difficulty by manipulating environment, bal-
ance requirements, distractors, and variability of practice. Attentional
strategies and external cues were integrated to enhance learning by
allowing for greater success during the practice of complex multi-
tasking conditions. The study was held in a community setting with
a small group boot camp approach to take advantage of social/
emotional interactions shown to impact learning and quality of life.
Results: 5/6 subjects showed improvement in the FOG question-
naire and objective measures including dual tasking conditions.
These improvements were related to QoL for 4/5 subjects. One sub-
ject with mild FOG did not show improvement on any FOG
outcomes.
Conclusions: We will report on the trends across 6 individuals
and discuss the implication to future studies and real world
implementation.
215
Preliminary report investigating the benefits of neuroplasticity-
principled community-based exercise programs for people with
Parkinsons disease
B.G. Farley, A. Okurily, J. Bazan-Wigle, K. Moynahan (Tucson, AZ, USA)
Objective: Report preliminary short-term benefits on mobility of
ongoing community-based group exercise programs that implement
progressive aerobic training and Parkinsons disease (PD) specific
skill acquisition forms of training for people of varying disease
severity.
Background: Progressive aerobic training and skill acquisition
have emerged as forms of practice for people with PD that are capa-
ble of not only improving function, but capable of mediating brain
health and repair mechanisms. Translating neuroplasticity-principled
research protocols effectively, thereby counteracting inactivity, is a
challenge. The Parkinsons Wellness Recovery Gym (PWR!GymV R)
offers ongoing specialty group classes and intensive therapies for
people with Parkinsons disease of varying severity in a community
center.
Methods: All participants are provided an initial consult with a
physical therapist to determine the class that will best meet their fit-
ness/cognitive/mobility goals. Intensity and complexity of training
varies across groups from most (HIIT, N=13) to moderate (Circuit,
N=12) to least (MOVES, N=10). Measurements are collected at
initial intake and 6 months thereafter. All classes meet for 1 hour
2-3x/week and target 20 of progressive aerobic training plus 20 of
a functional amplitude-focused training program called
PWR!MovesV R.
Results: MOVES/Circuit both improved in 10 m self-selected
walking (12%) and stand to floor transfer time (17-24%). All
groups improved in backward walking (14-23%) and timed up/
go (TUG) in motor dual task conditions (14%). MOVES
showed greatest change in TUG in both dual task conditions
(motor/cognitive) interference. Circuit was the only group to
show meaningful improvements in 6 walk endurance (16%)
and 10 m fast walking (12%). HIIT showed least improvement
on all measures.
Conclusions: The least challenging class showed the greatest
improvement on functional mobility outcomes. Backward walking
and dual task TUG were most sensitive across groups. Data may
reflect need for more sensitive clinical mobility outcomes, differen-
ces in specificity of training across exercise classes, and need for bet-
ter clinical criteria to predict an individuals response to
manipulations of fitness/learning principles of training.
 POSTER SESSION
216
Initiating intrajejunal infusion of levodopa/carbidopa intestinal
gel: An outpatient model
A. Fasano, L.W.C. Liu, Y.Y. Poon, A.E. Lang (Toronto, ON,
Canada)
Objective: To describe our experience with an outpatient-model
for levodopa/carbidopa intestinal gel (LCIG) treatment in patients
with Parkinsons disease.
Background: Although there are no published procedural guide-
lines on the best model to deliver intrajejunal infusion of LCIG treat-
ment, patients are generally hospitalized and switched from their
conventional pharmacotherapy to LCIG through a percutaneous
endoscopic gastrostomy (PEG) with jejunal tube (PEG-J).
Methods: We propose the nasojejunal test phase for patients
whose potential clinical benefit is uncertain. Patients undergo endo-
scopic PEG/PEG-J placement as outpatients, are sent home 1-2 hours
after and seen by the gastroenterologist the following day to examine
the PEG insertion site and to adjust the bumper position against the
abdominal wall as necessary. A minimum of two weeks later,
Fig. 1. (216).
S83
patients return to the clinic off medications and LCIG dose is slowly
titrated. Patients are sent home at the end of each day; they are seen
again on the following two days, in order to refine the optimal LCIG
dosage as well as to taper off oral drugs. [figure1]
Results: To date, five patients (including 1 with levodopa-
responsive multiple system atrophy, 1 female, age: 61.8 6 8.1 years,
disease duration: 10.0 6 2.6 years) have received the treatment suc-
cessfully and safely with the proposed outpatient model. None
needed the nasojejunal test-phase. All patients reported an improve-
ment of motor fluctuations (on average by 59.7 6 15.3%). One
patient suffered from a stoma infection treated with topical
antibiotic.
Conclusions: Our model is characterized by a delay between the
PEG-J procedure and initiating the LCIG to allow the fistula track to
mature, thus possibly reducing PEG site related complications, fre-
quently reported in clinical trials. We believe that there is no
urgency to start LCIG following the PEG-J procedure, as is often
encouraged in the full inpatient model in order to expedite patients
stay in the hospital.
Avoiding hospitalization has a number of other advantages: 1) it
ensures a faster access to LCIG treatment especially in busy hospi-
tals where elective admissions are often extremely limited due to bed
shortages; 2) it ensures better patient compliance and reduces com-
plications associated with hospitalization, such as delirium or infec-
tions; 3) it is more cost-effective.
Future studies enrolling a larger number of outpatients will likely
prove the value of our approach.
217
Risk factors and safe dosage of levodopa for wearing-off
phenomenon in Chinese patients with Parkinsons disease
T. Feng, H. Chen, J. Fang, F. Li, L. Gao (Beijing, Peoples Republic
of China)
Objective: To investigate risk factors of wearing-off phenomenon
in Parkinsons disease (PD) and propose safe dosage of levodopa to
reduce wearing-off development based on Chinese cohort.
Background: Risk factors of wearing-off in PD were reported
differently and safe dosage to reduce wearing-off has not been indi-
cated via statistic model.
Methods: Patients with PD who had taken levodopa (L-dopa) for
at least 1 month were recruited. Wearing-off was diagnosed based on
validated Chinese version of a patient self-rated 9-question Wearing-
Off Questionnaire (WOQ-9) and clinical definition. Eleven variables
(gender, disease duration at L-dopa initiation, disease duration at
assessment, age at onset, age at assessment, H-Y stage, UPDRS III,
L-dopa daily total dosage and dosage adjusted to weight, duration of
L-dopa treatment, initial drug recipe) were included in our analysis.
Univariate analysis, multivariate logistic regression analysis and
decision tree classification model(DTC) were used to detect risk fac-
tors of wearing-off. Receiver operating characteristic (ROC) curve
and DTC were used to investigate cut-off value of L-dopa to best
predict wearing-off.
Results: Two hundred and thirty four patients were investigated
in our study, among whom 111 developed wearing-off. Patients with
wearing-off tended to receive higher L-dopa dosage and endure lon-
ger duration of L-dopa treatment.
L-dopa dosage as 281mg/day and 4.2mg/kg/day by ROC[figure
1], as well as 269mg/day and 3.2mg/kg/day by DTC[figure 2] were
cut-off values for wearing-off. [figure1] [figure2]
Conclusions: L-dopa dosage and duration of L-dopa treatment
were related to increased wearing-off development. Cumulative L-
dopa dosage and L-dopa daily dosage were better predictive of
wearing-off. Inadequate evidence was present for delayed L-dopa ini-
tiation. L-dopa daily dosage no more than 275 mg or 4.2 mg/kg was
regarded as safe.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S84 POSTER SESSION

TABLE 1. univariate analysis of difference between wearing-off and control

Control(n597) WO(n5111) P p
Demographic profile
gender(male:female)D 53:44 63:48 0.919 0.530
Age at assessment 62.2 6 10.5 62.1 6 10.2 0.986 0.583
Disease profile
H-Y stage(range) 2(1.52.5) 2(1.53) 0.071 0.097
UPDRS III(range) 23(1232) 26.25(1937.63) 0.016* 0.004*
Age at onset 58.0 6 11.3 57.0 6 10.8 0.523 0.873
disease duration at assessment(month, range) 54(3586) 61(4896) 0.007* 0.053
Treatment profile
disease duration at L-dopa initiation(month, range) 26(949) 19(8.2537.75) 0.150 0.155
L-dopa dosage, mg/kg/day(range) 4.2(2.55.6) 6.1(4.38.9) <0.001* <0.001*
L-dopa dosage, mg/day(range) 300(200350) 387.5(300600) <0.001* <0.001*
Duration of L-dopa treatment(range) 21(542) 41(2360) <0.001* <0.001*
Initial therapyD 0.597
L-dopa 68 72
DA 3 5
L-dopa1DA 12 10
others 14 22
*The significance level of average difference is 0.05. Variables were comparing to control group. initial therapy matched comparison varia-
bles with abnormal distribution or unequal variances that underwent Mann-Whitney test D non-numeric variable underwent chi-square test.

218
Effect of levodopa-carbidopa intestinal gel on resting tremor in
patients with advanced Parkinsons disease
H.H. Fernandez, J. Dubow, W.Z. Robieson, K. Chatamra, S. Eaton,
J.A. Benesh, P. Odin (Cleveland, OH, USA)
Objective: To evaluate the effect of levodopa-carbidopa intestinal
gel (LCIG) treatment on resting tremor in patients with advanced
Parkinsons disease (PD) in a 54-week, open-label Phase 3 study.
Background: Resting tremor is prevalent in advanced PD
patients.1 The resting tremor response to dopaminergic therapy is
often regarded as insufficient and underpins one of the reasons deep
brain stimulation may be chosen over other non-oral therapies in
advanced PD.

Fig. 1. (217).
Fig. 2. (217).

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION S85

TABLE 2. multivariate analysis of risk factors for wearing-

off
Hazard
variables P value ratio (OR)
Duration of L-dopa treatment 0.003* 1.024
Disease Duration at assessment 0.241 0.994
(month)
HY stage 0.590 1.168
UPDRS III 0.181 1.024
L-dopa daily dosage adjusted to <0.001* 1.282
weight (mg/kg)
L-dopa Daily total dosage (mg) <0.001* 1.004
*The significance level of average difference is 0.05. was tested Fig. 1. (218).
separately from L-dopa daily dosage adjusted to weight
2
Fernandez H et al. Mov Disord. 2014 Dec 24.

Methods: 354 patients were enrolled in an open-label study, 286 219

had both baseline (BL) and post-PEG-J assessment of unified Parkin-
sons disease rating scale (UPDRS). UPDRS III #20 (resting tremor) Efficacy of opicapone in Parkinsons disease patients with motor
total score (5 categories: arms, legs, and face), safety and diary data fluctuations: A phase III, randomized, double-blind, placebo and
were analyzed post-hoc in 3 subgroups defined by their max BL active-controlled study BIPARK I
tremor score: No BL Tremor, Mild BL Tremor (max score =1 in any J. Ferreira, A. Lees, A. Santos, R. Pinto, N. Lopes, T. Nunes, J.F.
category), and Significant (SIG) BL Tremor (max score 2 in any Rocha, P. Soares-da-Silva (Lisbon, Portugal)
category).
Objective: Investigate the efficacy and tolerability of 3 different
Results: .BL demographics were previously described for the
opicapone (OPC) doses (5, 25 and 50 mg) administered once-daily,
intent-to-treat (ITT) population.2 The majority (69%) of patients
compared with entacapone (ENT) and placebo, in levodopa-treated
(n5286) had No BL Tremor, 13% had Mild BL Tremor and 18%
patients with Parkinsons disease (PD) and motor fluctuations.
had SIG BL Tremor (Table 1). The mean (SD) change from BL to
Background: OPC is a novel once-daily potent and long-acting
final resting tremor total score was -0.79 (2.4) in the ITT, and
peripheral COMT-inhibitor under investigation for Parkinsons
reductions in the Mild BL Tremor and SIG BL Tremor groups were
disease.
substantial. Notably, amantadine use and levodopa dose were con-
Methods: Multinational, multicentre, 14 to 15-week, double-
sistent across subgroups as all PD medications were initially tapered
blind, placebo- and active-controlled study. The primary efficacy
off and could be added back after 28 days. In the Mild BL Tremor
variable was the change from baseline in absolute OFF-time based
group (n538), 79% patients had no tremor at final, while only 2
on patient diaries. The key secondary efficacy endpoint was the pro-
(5%) had an increase max score to 2 at final. In the SIG BL Tremor
portion of OFF- and ON-responders ( 1 hour improvement). Toler-
group (n552), 88% had a reduction in max tremor score to 0 or 1
ability was assessed by adverse events (AEs), laboratory, vital-signs,
at final, while no patients had an increase. Improvements in reduc-
ECG, physical and neurological examinations.
ing off time and increasing on time without troublesome dyski-
Results: A total of 600 patients were randomized to placebo
nesia were comparable between subgroups (Figure 1). Treatment-
(N=121), 5mg-OPC (N=122), 25mg-OPC (N=119), 50mg-OPC
emergent (TE) adverse events (AE) were reported in 91.2% of
(N=116) or ENT (N=122). Both 50mg-OPC and ENT significantly
enrolled patients (n5354), and TE serious AEs reported in 30.5%.
reduced the OFF-time (1.95 h [p=0.0015] 50mg-OPC and -1.61 h
The tremor TEAE was reported in 4 (2.0%) No BL Tremor
[p=0.0141] ENT vs. -0.93 h placebo) and increased the ON-time
(n5196), 1 (2.6%) Mild BL Tremor (n538), and 1 (1.9%) SIG BL
without troublesome dyskinesia (1.82 h [p=0.0016] 50mg-OPC and
Tremor (n552) patient.
1.57 h [p=0.0150] ENT vs. 0.78 h placebo). Significantly more
Conclusions: Tremor remains prevalent in advanced PD
patients receiving 25mg- or 50mg-OPC achieved the OFF-time
patients. LCIG may alleviate resting tremor that was not well con-
responder endpoint (60.3% [p=0.0464] 25mg-OPC and 69.6%
trolled by optimized oral medical treatment in advanced PD
[p=0.0011] 50mg-OPC vs. 47.5% placebo). Both 5mg-OPC and ENT
patients.
1 missed statistical significance for OFF-time responders. A signifi-
Baumann CR. Parkinsonisn Relat Disord. 2012. 18:S90-2.
cantly higher proportion of ON-responders was also found for the

TABLE 1. Mean Change from Baseline to Final UPDRS III #20 Total Score, Levodopa Dose and Amantadine Use in Resting
Tremor Subgroups
UPDRS III #20 Total Score Amantadine Use
Levodopa Dose
BL Resting n (% of BL Mean Mean Change from Mean Change from At BL, During
Tremor Subgroup studya Score 6 SD BL to Final 6 SD BL to Final 6 SD n (%) Study, n (%)
No BL Tremorb 196 (69) 0.00 6 0.0 0.21 6 0.7 423.0 6 646.6 61 (31.1) 20 (10.2)
Mild BL Tremorc 38 (13) 1.69 6 0.8 -1.29 6 1.0 336.4 6 585.4 12 (31.6) 3 (7.9)
SIG BL Tremord 52 (18) 5.25 6 2.6 -4.17 6 3.6 441.0 6 546.0 14 (26.9) 6 (11.5)
a
N=286; bUPDRS III #20 5 0 at baseline; cMaximum UPDRS III #20 score =1 in any category at baseline; dMaximum UPDRS III #20 score 2
in any category at baseline; BL=baseline; UPDRS 5 unified Parkinsons disease rating scale; SD 5 standard deviation

Movement Disorders, Vol. 30, Suppl. 1, 2015

S86 POSTER SESSION
50mg-OPC group (65.2% [p=0.0028]). OPC and ENT were generally
safe and well tolerated.
Conclusions: Opicapone, particularly 50mg-OPC, was effective
in reducing OFF-time in PD patients with a favourable profile com-
pared to ENT.
220
Safety and tolerability of opicapone in the treatment of
Parkinsons disease and motor fluctuations: Analysis of pooled
phase III studies
J. Ferreira, A. Lees, H. Gama, N. Lopes, A. Santos, R. Costa, C.
Oliveira, R. Pinto, T. Nunes, J.F. Rocha, P. Soares-da-Silva (Lisbon,
Portugal)
Objective: Evaluate the safety of opicapone (OPC) in patients
with Parkinsons disease (PD) and motor fluctuations across phase
III studies.
Background: OPC, a novel once-daily peripheral COMT inhibi-
tor, has shown to be effective in reducing OFF-time in PD patients
with motor fluctuations.
Methods: Patient-level data of matching treatment arms of
BIPARK I and II studies was integrated (placebo, 25mg-OPC and
50mg-OPC). Both were multicentre, 14 to 15-week double-blind,
randomised, placebo- and active-controlled studies and had similar
designs and measurement instruments. Safety was assessed by inci-
dence of treatment-emergent adverse events (TEAEs), changes in
laboratory values, ECGs and vital signs.
Results: The pooled safety set included over 750 patients
(N=257, 244 and 265 for placebo, 25mg- and 50mg-OPC). Dopami-
nergic events and other PD symptoms were the most commonly
reported TEAEs: dyskinesia (18.3% OPC vs. 6.2% placebo), consti-
pation (5.7% vs. 1.9%), insomnia (5.1% vs. 1.6%) and dry mouth
(4.7% vs. 1.2%). No dose relationship was observed for the majority
of TEAEs. Serious AEs were reported for few patients: 4.3% placebo
and 3.5% OPC. One death (pneumonia) occurred in the placebo
group. There were no reports of severe diarrhea, myocardial infarc-
tion, prostate cancer, melanoma or any serious hepatic event in OPC
groups. Impulse control disorders were reported by <1% of OPC-
treated patients. No relevant differences compared to placebo were
observed for laboratory parameters, vital signs or ECG readings.
Conclusions: OPC is safe and well tolerated with no apparent
association to known safety concerns of other anti-PD drugs, particu-
larly other COMT inhibitors.
221
Efficacy of opicapone as adjunctive therapy to levodopa in
patients with Parkinsons disease and motor fluctuations:
Analysis of pooled phase III studies
J. Ferreira, A. Lees, A. Santos, N. Lopes, R. Costa, C. Oliveira, R.
Pinto, T. Nunes, J.F. Rocha, P. Soares-da-Silva (S. Mamede do
Coronado, Portugal)
Objective: Evaluate the efficacy of opicapone (OPC) in patients
with Parkinsons disease (PD) and motor fluctuations across phase
III studies.
Background: OPC is a novel once-daily potent and long-acting
peripheral COMT inhibitor under investigation for PD.
Methods: Patient-level data of matching treatment arms of
BIPARK I and II studies was integrated (placebo, 25mg-OPC and
50mg-OPC). Both were multicentre, 14 to 15-week double-blind,
randomised, placebo- and active-controlled studies and had similar
designs and measurement instruments. The primary efficacy variable
was the change from baseline in absolute OFF-time based on
patients diaries. Key secondary measure was the OFF- and ON-time
responder rates ( 1 hour).
Results: The pooled efficacy set included over 750 subjects (pla-
cebo n5255, 25mg-OPC n5241, 50mg-OPC n5262). Treatment
Movement Disorders, Vol. 30, Suppl. 1, 2015
with either 25mg- or 50mg-OPC resulted in a significant reduction
of daily OFF-time (1.56 h [p=0.0106] 25mg-OPC and -1.94 h
[p<0.0001] 50mg-OPC vs. -0.97 h Placebo) and increase in the ON-
time without troublesome dyskinesia (1.43 h [p=0.0083] 25mg-OPC
and 1.80 h [p<0.0001] 50mg-OPC vs. 0.72 h placebo). Significantly
more patients receiving 25mg- and 50mg-OPC achieved the OFF-
and ON-time responders endpoint (60.2% to 64.6% [p<0.005]).
Conclusions: OPC is effective in reducing OFF-time and increas-
ing ON-time without troublesome dyskinesia.
222
Number-needed-to-treat analysis of droxidopa in patients with
symptomatic neurogenic orthostatic hypotension
C. Francois, G.J. Rowse, R.A. Hauser, L.A. Hewitt (Deerfield, IL,
USA)
Objective: To evaluate the safety and efficacy of droxidopa vs
placebo for the treatment of symptomatic neurogenic orthostatic
hypotension (NOH) in terms of the number needed to treat (NNT)
and number needed to harm (NNH).
Background: Droxidopa is a norepinephrine prodrug recently
approved to treat symptomatic NOH caused by primary autonomic
failure (Parkinsons disease, multiple system atrophy, and pure auto-
nomic failure), dopamine b-hydroxylase deficiency, and nondiabetic
autonomic neuropathy. To date, safety and efficacy of droxidopa
have been studied in 6 multicenter, phase 3 trials ranging from 2
weeks to 2 years in duration and involving >600 patients.
Methods: Safety and efficacy data were pooled from 2 phase 3
trials: NOH301 and NOH306. To calculate the NNT, outcome
assessed was the response rate of Item 1 of the Orthostatic Hypoten-
sion Symptom Assessment (OHSA) showing improvement 50% or
2 units at Week 1; to calculate the NNH, outcomes assessed were
adverse events (AEs) with >5% frequency, AE rate leading to drop-
out, and AEs related to falls. NNT and NNH were calculated as the
reciprocal of the risk difference for placebo vs droxidopa. Likelihood
to be helped or harmed (LHH) was calculated as NNH/NNT.
Results: Based on pooled OHSA Item 1 results, the NNT was
significant for improvement 50% (5; 95% CI: 311) and 2 units
(5; 95% CI: 48). The NNH was dependent on outcome assessed. Of
the AEs occurring >5% (headache, dizziness, nausea, fatigue, and
hypertension), the NNH ranged from 23 to 302 and was significant
only for pooled incidence of hypertension (28; 95% CI: 1695). For
AEs related to falls, the NNH was -17 and -12 (not significant) in
NOH301 and NOH306B, respectively, suggesting that placebo was
more likely to cause harm compared with droxidopa. For pooled
dropouts due to AEs, the NNH was 34 (NOH301: 84; NOH306: 24)
and NNT of 5 (responder week 1 OSHA >2 or 50% improvement);
therefore, LHH was calculated as 34/5=6.8.
Conclusions: Droxidopa is 6.8 times more likely to achieve
response than result in a discontinuation because of an AE compared
with placebo.
223
Impact of reduction in falls for patients with PD and NOH: Post
hoc economic analyses of phase 3 clinical trial data on droxidopa
C. Francois, R.A. Hauser, H. Kaufmann, S. Heritier, L.A. Hewitt, R.
Owen, B. Rive, G.J. Rowse (Deerfield, IL, USA)
Objective: To estimate the impact of droxidopa therapy on total
costs in patients with Parkinsons disease (PD) and neurogenic ortho-
static hypotension (NOH) while considering the observed reduction in
the number of falls experienced by patients and droxidopa drug cost.
Background: NOH results from inadequate noradrenergic
response to postural change. It is known to be a substantial risk fac-
tor for falls in patients with PD. Droxidopa is a norepinephrine pro-
drug recently approved to treat symptomatic NOH caused by
primary autonomic failure (PD, multiple system atrophy, and pure
 POSTER SESSION
autonomic failure), dopamine beta-hydroxylase deficiency, and non-
diabetic autonomic neuropathy.
Methods: Cost offset due to a reduction in falls was estimated
using a retrospective, piggyback design of randomized controlled
trial data and published data. Patients with PD in a phase 3 study
underwent double-blind titration up to 2 weeks with droxidopa, fol-
lowed by 8-week maintenance therapy (100600 mg TID) or pla-
cebo. Falls were recorded daily via electronic diaries. Utilizing
probability of falls to be fatal or nonfatal, falls requiring medical
care, and costs from a systematic review of falls data in people 60
years old living in the community, we calculated the average cost/
fall/treatment to estimate the potential cost reduction during 10
weeks of droxidopa therapy vs placebo.
Results: Droxidopa treatment over 10 weeks was associated with
significantly fewer falls per patient-week vs placebo and with fewer
fall-related injuries. The estimated average costs of falls per patient
were $4,573 for droxidopa vs $11,813 for placebo. This results in a
cost reduction of $7,239. The average droxidopa drug cost was
$10,108. Thus the net cost of droxidopa therapy was $2,869. Sensi-
tivity analyses with more conservative estimates of cost of falls or
number of falls increased the net costs to $6,640 and $7,457,
respectively.
Conclusions: This simple model indicates that droxidopa could
reduce falls for PD patients with symptomatic NOH, limiting the
financial impact of droxidopa therapy to $2,869 over 10 weeks of
treatment. Inclusion of other potential benefits on functioning, quality
of life, and associated costs related to negative consequences of fear
of falling may further decrease the overall cost.
224
Cost effectiveness of droxidopa in patients with neurogenic
orthostatic hypotension: Post hoc economic analysis of phase 3
trial data
C. Francois, R.A. Hauser, J. Dorey, E. Kharitonova, S. Aball
ea, L.A.
Hewitt (Deerfield, IL, USA)
Objective: To develop a cost-effectiveness (CE) model to esti-
mate the impact of droxidopa vs the standard of care (SoC) in terms
of US costs and quality-adjusted life-years (QALYs).
Background: Neurogenic orthostatic hypotension (NOH) is
caused by autonomic dysfunction in which there is an inadequate
noradrenergic response upon standing. Droxidopa is a norepinephrine
prodrug that is FDA approved to treat symptomatic NOH. Orthostatic
falls in blood pressure can lead to serious injuries, limited daily
activities, and decreased quality of life, and represent a significant
economic burden on the US healthcare system.
Methods: A Markov model was used to predict risk of falls and
impact of NOH symptom improvement. Probabilities of falls and
treatment responses were from randomized controlled trials
(NOH306A and NOH306B) with Parkinsons disease patients who
underwent 2-week, double-blind placebo or droxidopa dose titration,
followed by 8 weeks of double-blind maintenance treatment. The
placebo arm was assumed to be representative of the SoC since
patients could enter the trials on stable nonpharmacologic measures
and/or stable dosages of fludrocortisone. Severity of falls, utility val-
ues, and injury-related costs were from published studies. Model out-
comes included the number of falls (total and by severity), number
of QALYs, and costs (total, treatment acquisition, fall-related, and
NOH management). The primary CE measures were the incremental
CE ratios (ICERs), calculated as the difference in costs between the
two treatment groups divided by the differences in falls and number
of QALYs. Outcomes were assessed over a 12-month period, based
on a treatment duration of 6 months.
Results: Droxidopa patients had fewer falls in each severity cate-
gory and a higher number of QALYs. Estimated droxidopa costs for
6 months were $30,112, and estimated cost savings due to falls were
$14,574 over 12 months. From a payer perspective, droxidopa was
cost-effective vs the SoC with an ICER of $47,001 per QALY
S87
gained. ICERs per avoided fall with no or minor injury and per
avoided fall with moderate or major injury were $1559 and $24,866,
respectively. Main drivers were the distribution of falls by severity,
fear of fall-related inputs, and costs due to injuries.
Conclusions: Droxidopa is a cost-effective option compared with
the SoC in US clinical practice for the treatment of NOH.
225
Medical near-miss events in hospitalized patients with
Parkinsons disease, using a nationwide online open database in
Japan
T. Furuya, K. Takahashi, A. Miyake, T. Kimura, Y. Ito, T. Sasaki, N.
Araki, T. Yamamoto (Saitama-ken, Japan)
Objective: To investigate medical near-miss events in hospital-
ized patients with Parkinsons disease (PD) in Japan, using a nation-
wide online open database provided by the Japan Council for
Quality Health Care (JCQHC).
Background: Complex medication regimens are often prescribed
to manage PD symptoms. For PD inpatients, safety and adherence to
a regular PD medication schedule are important in achieving optimal
symptom control. Only a few studies have investigated medical near-
miss events in hospitalized PD patients.
Methods: A division of JCQHC has undertaken a project to col-
lect medical near-miss/adverse event information in Japan, and the
collected information and all anonymous individual reports can be
accessed on JCQHCs website (http://www.med-safe.jp). A total of
39,379 medical near-miss events were recorded in this database
between January 2010 and November 2014.
Results: We performed a retrospective analysis and identified 131
cases related to PD inpatients, among which 119 incorrect medication
administrations (90.8%) were included. We found three major catego-
ries associated with inappropriate medications: incorrect time (40
cases), dose omission (30 cases) and preparation errors (12 cases).
The causes of incorrect medications were a lack of confirmation by
medical staff, and drug regimen complexity/polypharmacy. The medi-
cal staff involved in these cases were nurses (113 cases), pharmacists
(12 cases) and others (6 cases). The number of cases related to an
extra dose of PD medication (with the exception of after each meal)
was 21. The incorrect medication time details were as follows: right
after waking up (6 cases), at bed time (2 cases) and others (13 cases).
The numbers of errors in each PD drug category were 50 cases of L-
dopa, 12 cases of dopamine agonists, eight cases of selegiline and
four cases each of entacapone/amantadine/anti-cholinergic drugs. In
two cases, the daily replacement of a transdermal patch was skipped.
Contraindicated medications were ordered for two patients.
Conclusions: Although adherence to complex PD medication
schedules during hospitalization entails various challenges, collabora-
tion for the confirmation of medication administration by interdisci-
plinary medical staff can improve outcomes and help safeguard
against the disruption of PD patients prescribed medication sched-
ules at home.
226
Pharmacokinetic profile of ND0612L (levodopa/carbidopa for
subcutaneous infusion) in patients with moderate to severe
Parkinsons disease
N. Giladi, Y. Caraco, T. Gurevich, R. Djaldetti, Y. Cohen, O.
Yacobi-Zeevi, S. Oren (Tel Aviv, Israel)
Objective: To characterize the pharmacokinetic profile of
ND0612L in PD patients with motor fluctuations.
Background: The symptomatic efficacy of continuous levodopa/
carbidopa (LD/CD) delivery in PD patients with motor fluctuations is
well known. However, intrajejunal infusion systems are associated
with tolerability concerns, and poor LD solubility has prevented devel-
opment as a subcutaneously deliverable formulation. ND0612L is a
Movement Disorders, Vol. 30, Suppl. 1, 2015
S88 POSTER SESSION
proprietary liquid formulation of LD/CD that enables subcutaneous
administration of LD/CD to achieve steady levodopa plasma levels.
Methods: This was a Phase II randomized, placebo-controlled,
double-blind, two-period study of ND0612L in PD patients with
motor response fluctuations. During Period-1 (14 days), 30 patients
received their optimized current oral treatment (dose reductions per-
mitted), and were randomized (2:1) to adjunct ND0612L or placebo.
During Period-2 (7 days), 16 patients were offered open-label
ND0612L and were randomized to ND0612L monotherapy or
ND0612L plus oral entacapone.
Results: Patients treated with adjunct ND0612L had their plasma
LD concentrations consistently maintained above a mean (6SD) of
800 6570ng/ml, as well as a lower peak-to-trough ratio and fluctua-
tion index vs. placebo. Exploratory efficacy analysis showed that
ND0612L treatment reduced OFF time by a mean6SD of
2.42 6 2.62h and 2.13 6 2.24h from baseline according to in-clinic
and home diaries, respectively (vs. 0.41 6 2.62h and 1.39 6 2.33h
with placebo). ND0612L also improved sleep quality (17.1 6 17.58
improvement in PDSS scores from baseline vs. 0.5 6 11.35 with pla-
cebo), quality of life (6.6 6 10.52 improvement in PDQ-39 scores
from baseline vs 1.78 611.10 with placebo), and global impression
(90% of the patients had improved CGI-C scores vs. 36% in pla-
cebo). All 16 patients chose to continue to Period-2 in which plasma
LD levels were maintained at a mean of 550 6 79ng/ml with
ND0612L monotherapy and 800 6144ng/ml with ND0612L plus
oral entacapone. In these patients, the oral LD intake was reduced by
a median of 80%, with 3 of 16 patients completely discontinuing
oral LD therapy.
Conclusions: These data suggest that subcutaneous continuous
delivery of LD/CD with ND0612L, provides relatively stable LD lev-
els with reduced variability compared with oral LD. Efficacy findings
are also promising and warrant further study.
227
Deep brain stimulation and the effect on gait in Parkinsons
disease
G. Gilmore, M. Delrobaei, S. Tran, K. Ognjanovic, M. Jog (London,
ON, Canada)
Objective: To assess the progression of gait changes, following
deep brain stimulation (DBS) intervention, over a year long period
using objective kinematically based gait measures.
Background: Gait impairments contribute to PD patient falls and
reduced quality of life. Specifically, it remains unclear whether PD
gait improves or worsens with DBS intervention over a long-term.
Currently gait changes are monitored using the UPDRS, which is
subjective and qualitative in nature. An objective and quantitative
assessment of gait, using kinematic technology, will allow the clini-
cian to more effectively determine whether gait is affected by DBS.
Kinematic sensor technologies that are targeted to specifically study-
ing gait are a new avenue being explored to monitor the gait changes
with DBS.
Methods: PD patients undergoing bilateral STN-DBS alongside
healthy age-matched controls will be used. Patients are assessed one
week pre-operatively and then up to one year post-operatively. Dur-
ing each programming visit the patient is monitored by a clinician,
and their device is adjusted if required. The patients gait is captured
using the PKMAS gait analysis carpet. The carpet assesses various
aspects of gait, including: stride length, stride width, gait cycle, cen-
ter of mass/pressure and single/double support time. The study has
been approved by the university ethics committee.
Results: Seven of the total patients (N=15) have completed the 6
month session. Preliminary data has shown an improvement in
important areas of gait performance up to 6 months post-operatively.
Stride length (Pre-op: M=94.56 cm, 6 months: M=113.32 cm) and
step length (Pre-op: M=47.53 cm, 6 months: M=59.89 cm) both
increased from pre-operative baseline. Gait cycle is a measure of
time from when one foot touches the ground to when the same foot
Movement Disorders, Vol. 30, Suppl. 1, 2015
touches the ground again. Gait cycle improved from PD pre-
operative baseline (Pre-op: M=1.11 sec, 6 months: M=1.04 sec).
Double support time decreased from Pd pre-operative baseline (Pre-
op: M=.30 sec, 6 months: .26 sec), which better represents control
data (M=.28 sec).
Conclusions: Preliminary data analysis suggests DBS intervention
may improve gait over a 6 month period post-operatively. Further
analysis, up to 1 year post-operation, will better elucidate the long-
term efficacy of DBS intervention on gait. Our method provides the
first objective and quantitative measure of long-term gait variances
in PD patients undergoing DBS treatment.
228
Switch form immediate release pramipexole to extended release
pramipexole: Experience from a tertiary referral center
S.I. Gul, M. Kuzu, O. Herdi, S. Tezcan, N.F. Mercan, C.M.
Akbostanci (Ankara, Turkey)
Objective: To evaluate the safety and efficacy of switch from
immediate release pramipexole (pex) to extended release pramipex-
ole (pex-ER).
Background: Since the avalibility of pex-ER in our country
about a year ago, we could reach satisfactory information from the
files of 69 patients (26 females, 38%) who had switched from pex to
pexER.
Methods: We documented pre and post switch pramipexole and
levodopa-equivalent doses of other antiParkinsonian medication, and
analyzed the frequency and nature of reported adverse effects.
Results: Mean age of patients was 63,3 (range 44-88), and mean
disease duration was 7,1 years (range 1-27). The other drugs were
levodopa (57 patients, 82,6%), entacapone (24 patients, 34,58%),
rasagiline (20 patients, 29%), amantadine (18 patients, 26,1%), apo-
morphine (six patients, 8,7%).
Switch from pex to pexER was uneventful in 59 (92,2%) patients.
Adverse events reported in five (7,2%) patients were ankle swelling
(two patients), nausea (one patient), dyskinesia (one patient), hyper-
sexuality (one patient), and psychosis (one patient). Problems
resolved with further medication change in two patients. Three
patients preferred to went back to pex.
Pre and post switch pramipexole and levodopa-equivalent doses
of the patients.
Pre-Switch Post-Switch
Dose (mg/day) Dose (mg/day) p
Pex to Pex-ER 2,5 (SD 1,3) 3,1 (SD 1,2) ,00
Levodopa-Equivalent 653,2 (SD 498,2) 719,1 (SD 562,9) ,00
Dose
Conclusions: Great majority of patients (92,2%) switched from
three times daily pex to once daily pex-ER uneventfully. A slight
increase in pramipexole daily dose, tailored according to patients
symptomatic needs, resulted in an increase in post-switch levodopa
equivalent doses. Our experience is compatible with previously
reported studies.
229
Effect of medical cannabis in Parkinsons disease: Survey of
patient experiences
T. Gurevich, L. Bar Lev Chleider, A. Rosenberg, J. Knaani, Y.
Baruch, R. Djaldetti (Tel Aviv, Israel)
Objective: To assess the effect of cannabis treatment in patients
with Parkinsons disease (PD).
 POSTER SESSION
Background: Medical cannabis is now widely used for improv-
ing the quality of life of patients with various neurological disorders.
Methods: A telephonic survey was conducted on PD patients
granted medical cannabis treatment licenses from the Israel Ministry
of Health and who had received at least 2 months of treatment prior
to the interview. The structured questionnaire contained epidemiolog-
ical questions and items about the effects of cannabis on different
symptoms.
Results: Thirty-nine patients (31 males, age 63.6 6 9.6 years, dis-
ease duration 11.6 6 8 years) among 76 patients that met the inclu-
sion criteria participated in the survey. Thirteen did not agree to
participate, 20 could not be reached by phone, 4 had passed away.
The mean duration of cannabis treatment was 16.8 6 18.9
months, the mean daily dose - 1.1 6 0.9 grams. The consumption
methods were smoking (n524 [61%]), oil (n56 [15.3%]), smoking
1oil (n54 [10.2%]) and vaporizer (n51 [3%]). Nine patients (23%)
discontinued treatment due to lack of effect or side effects. Thirty
patients (76.9%) reported a positive impact of cannbis on their gen-
eral condition and mood, 25 (64%) reported improvement in pain
and rigidity, 22 (59%) reported decrease in tremor and improved
quality of sleep. The most common reported side effects were cough-
ing due to smoking (n59), hallucinations (n56), restlessness (n56)
and confusion (n55).
Conclusions: Subjective improvement of motor and non-motor
symptoms was reported by most of the survey responders. However,
a significant number of patients had no improvement or experienced
side effects on short-term treatment. The long-term safety profile of
medical cannabis in PD patients is still undetermined. The results of
this retrospective open-label study require confirmation in a double
blind study to exclude the placebo effect and to assess longer-term
safety of cannabis use in PD.
230
LSVT LOUD voice treatment: Training normal healthy loudness
with good quality
A.E. Halpern, L.O. Ramig, E. Peterson (Denver, CO, USA)
Objective: The target voice in LSVT LOUD is normal loudness
with healthy voice quality, not shouting or vocal hyperfunction. This
poster will present a review of a series of data sets which demon-
strate healthy vocal loudness Post LSVT LOUD. Group data will
include 1) physiological measures of laryngeal videostroboscopic 2)
glottographic and aerodynamic tasks, as well as listener perceptual
data. 3) A case study of Pre supraglottic hyperfunction that was
reduced Post LSVT LOUD will be presented. LSVT LOUD strat-
egies for achieving a normal loudness, good quality voice will be
discussed.
Background: LSVT LOUD is a voice and speech treatment that
was developed for Parkinsons disease (PD), and has applications to
other neurological disorders. Over 20 years of research data have
demonstrated the efficacy of this treatment (e.g., Ramig et al, 2001).
LSVT LOUD targets the hallmark PD voice symptoms of decreased
loudness, hoarseness, and breathiness. A key component of LSVT
LOUD is training individuals to achieve normal loudness with a
healthy voice quality that is not hyperfunctional. Due to deficits in
sensory feedback in PD, a normal loudness voice may feel too
loud to the individual with PD. Sensory re-calibration to normal
loudness levels is incorporated into the treatment to address this sen-
sory mismatch.
Methods: Data were collected on individuals with PD, Pre-Post
LSVT LOUD. 1) Laryngeal videostroboscopic data were collected
on 13 individuals. The randomized studies were rated by 4 judges. 2)
Glottographic (EGGW) and aerodynamic measures were collected to
investigate the mechanism of change. Blinded listener perceptual rat-
ings of hoarseness and breathiness were used to assess changes in
voice quality. 3) Laryngeal videostroboscopic data were collected on
an individual with PD pre/post LSVT LOUD who exhibited Pre
supraglottic hyperfunction.
S89
Results: Pre-Post LSVT LOUD findings indicated 1) less glottal
incompetence and no significant change in supraglottal hyperfunction
2) significant improvements in EGGW, aerodynamic and perceptual
measures 3) decreased supraglottic hyperfunction.
Conclusions: The results of these studies and our clinical experi-
ence demonstrate that when providing LSVT LOUD treatment cor-
rectly, the result is a voice with normal healthy loudness that is not
hyperfunctional and is of good quality.
231
Integrated cardiovascular safety profile of droxidopa
R.A. Hauser, W.B. White, G.J. Rowse, L.A. Hewitt (Tampa, FL,
USA)
Objective: To evaluate the cardiovascular (CV) safety profile of
droxidopa in patients with symptomatic neurogenic orthostatic hypo-
tension (NOH).
Background: Droxidopa is a norepinephrine prodrug recently
approved to treat symptomatic NOH caused by primary autonomic
failure (PD, multiple system atrophy [MSA], and pure autonomic
failure [PAF]), dopamine b-hydroxylase deficiency, and nondiabetic
autonomic neuropathy. It is thought that droxidopa raises blood pres-
sure (BP) by causing vasoconstriction.
Methods: CV safety data were integrated from 5 trials (N=666)
of patients with symptomatic NOH and diagnoses of PD, MSA,
PAF, dopamine b-hydroxylase deficiency, or nondiabetic autonomic
neuropathy. Two were short-term, double-blind, randomized,
placebo-controlled trials (RCTs) in patients with autonomic failure; a
third RCT was in patients with PD randomized to 2-week, double-
blind placebo or droxidopa dose titration, followed by 8-week, dou-
ble-blind maintenance treatment. Two studies were long-term, open-
label extensions with patients following completion of one of the
short-term studies. Adverse event (AE) rates were adjusted for treat-
ment duration and calculated by the number of events per patient per
year of mean exposure.
Results: A total of 307 (46%) patients enrolled in any one of the
trials had a preexisting CV disorder at baseline; the most common
diagnoses (n [%]) were arrhythmia (235 [35.3%]), coronary artery
disease (164 [24.6%]), and hypertension (116 [17.4%]). In the trial
in PD patients, over the entire 10 weeks the rates of CV-related AEs
were 0.17 and 0.24 for patients randomized to placebo and droxi-
dopa, respectively; the event rates were nominally higher during
titration vs maintenance for placebo (0.65 vs 0.07) but similar during
titration vs maintenance for droxidopa (0.30 vs 0.29). The rates of
cardiac-related treatment-emergent AEs (TEAEs) were nominally
higher in droxidopa vs placebo patients who had a preexisting CV
disorder (0.34 vs 0.16); similarly, the rates of BP-related TEAEs
were nominally higher in droxidopa vs placebo patients with a preex-
isting CV disorder (1.11 vs 0.62). There were no CV-related AEs
during 1 to 2 weeks of double-blind treatment in the short-term tri-
als. In the long-term extensions, the event rate was 0.13.
Conclusions: There were nominal, modest increases in CV-
related AE rates with droxidopa vs placebo; event rates in the long-
term extension was low.
232
Efficacy of rasagiline in early Parkinsons disease: A meta-
analysis of data from the TEMPO and ADAGIO studies
R.A. Hauser, V. Abler, E. Eyal (Tampa, FL, USA)
Objective: To evaluate the efficacy of rasagiline 1 mg/day versus pla-
cebo in a pooled population of patients with early Parkinsons disease (PD).
Background: TEMPO and ADAGIO were both Phase III studies
that evaluated the symptomatic efficacy of rasagiline versus placebo
in patients with early PD.
Methods: Both studies recruited early, untreated patients with
early PD who were randomized to placebo, rasagiline 1mg/day or
Movement Disorders, Vol. 30, Suppl. 1, 2015
S90 POSTER SESSION

rasagiline 2 mg/day. The placebo-controlled phase was 26 weeks in TABLE 1. Baseline Demographic Data
TEMPO and 36 weeks in ADAGIO. This meta-analysis included
UPDRS efficacy observations from weeks 12, 24 and 36 in ADAGIO Mean Age 61.5 (48-79)
and from weeks 14 and 26 in TEMPO; TEMPO visits were recoded
to weeks 12 and 24 respectively to allow integration with ADAGIO. Male: Female) 14(73.7%):5(26.3%)
The analysis includes 1546 patients who had 1 post baseline effi- Modified Hoehn-Yahr 2.2 (1-3)
cacy observations at the selected weeks. Change from baseline in Mean # of Daily Off Episodes 3.9 (1-7)
UPDRS Total, UPDRS mentation, ADL and Motor sub-scores were Mean # of PD Medications 3.0 (1-5)
evaluated using mixed models repeated measures (MMRM) analyses Mean Daily Levodopa Dose (mg) 836.8 (100-1500)
with baseline efficacy value, age, gender, treatment, categorical week Mean # of Levodopa Doses Per Day 5.3 (1-12)
in study, treatment by week interaction and study, included as fixed
effects. The analysis used an unstructured covariance matrix pattern
for observations within the same subject. Interactions between study
TABLE 2. Mean Change from Pre-dose to Post-dose MDS-
and treatment; and study, treatment and week, were included in the UPDRS Following APL-130277 Administration
model and removed if they were not significant (p>0.10).
Results: Mean 6SD baseline age was 61.9 610.0 years, years Time (min) 15 30 45 60 90
since diagnosis was 0.54 60.75 and Hoehn and Yahr stage was 1.6 ITT -11.5 -14.6 -15.1 -13.5 -9.2
60.5. Baseline mean 6SD UPDRS scores were: 21.58 69.39 for Responders -11.9 -16.7 -17.4 -15.9 -11.9
total, 0.96 61.19 for mentation, 5.47 63.12 for ADL and 15.15 Per Protocol -10.1 -15.5 -15.8 -15.0 -11.2
67.12 for motor. Effects on UPDRS total, motor and ADL scores
were significantly better for both doses of rasagiline compared with
placebo at all time periods. hours of total daily Off time, predictable Off episodes in the
morning on awakening and a Modified Hoehn-Yahr stage I-III in the
On state were included. Patients presented to the clinic in the
1mg/day placebo 2mg/day morning in the Off state and were administered APL 10 mg. If a
Estimate; placebo Estimate; satisfactory response was not seen, the dose of APL was increased in
Variable mean 6SE (p value) mean 6SE (p value) 5 mg increments until a clinically meaningful On was achieved, to
a maximum dose of 30 mg. Patients were dosed up to two times on
UPDRS Total three days. Change in MDS-UPDRS Part III was evaluated from pre-
Week 12/14 -2.18 60.33 (<0.0001) -1.75 60.33 (<0.0001) dose morning Off state to post-dose at 15, 30, 45, 60 and 90
Week 24/26 -3.57 60.40 (<0.0001) -3.17 60.40 (<0.0001) minutes. Patients were pre-medicated for 3 days with trimethobenza-
Week 36 -3.01 60.48 (<0.0001) -3.30 60.48 (<0.0001) mide, which was continued during the study.
UPDRS Mentation Results: Baseline demographic data are presented in Table 1. Fif-
Week 12/14 -0.16 6 0.06 (<0.01) -0.17 6 0.06 (<0.01) teen of 19 patients dosed achieved a satisfactory full On following
Week 24/26 -0.23 6 0.06 (<0.001) -0.32 6 0.06 (<0.0001) APL administration. Mean change from pre-dose to post-dose MDS-
Week 36 -0.21 6 0.08 (<0.01) -0.10 6 0.08 (0.23) UPDRS Part III at full On for responders or last dose for non-
UPDRS ADL responders is presented in Figure 1 and Table 2. Of the 15 respond-
Week 12/14 -0.70 60.12 (<0.0001) -0.67 60.12 (<0.0001) ers, all turned fully On within 30 minutes of dosing and 6 within
Week 24/26 -0.97 60.15 (<0.0001) -0.99 60.15 (<0.0001) 15 minutes. Thirteen of 15 remained fully On for at least 30
Week 36 -0.85 60.18 (<0.0001) -0.96 60.18 (<0.0001) minutes and 9/15 for at least 60 minutes.
UPDRS motor [figure1]
Week 12/14 -1.30 60.25 (<0.0001) -0.88 60.25 (<0.001) Conclusions: APL provided rapid, clinically meaningful improve-
Week 24/26 -2.35 60.30 (<0.0001) -1.82 60.30 (<0.0001) ment in MDS-UPDRS Part III scores for PD patients in the Off
Week 36 -1.90 60.36 (<0.0001) -2.15 60.36 (<0.0001) state. Much of the benefit was sustained through 90 minutes. A range
of doses were utilized but over half of patients responded to the two
lowest doses of APL (10 and 15 mg). APL-130277 may be an effec-
Conclusions: This meta-analysis combines data from two large tive, easy to administer medication for the on-demand management
RCTs and confirms the symptomatic efficacy of rasagiline in early of Off episodes in PD patients.
PD over 36 months.
234
233
Safety analysis by higher and lower total daily dose of IPX066,
Efficacy of sublingual apomorphine (APL-130277) for the an extended-release formulation of carbidopa-levodopa, in
treatment of off episodes in patients with Parkinsons disease advanced Parkinsons disease
R.A. Hauser, J. Dubow, B. Dzyngel, T. Bilbault, A. Giovinazzo, A. V.K. Hinson, N. Stover, P. Agarwal, S. Khanna, S. Kell (Charleston,
Agro (Tampa, FL, USA) SC, USA)
Objective: To evaluate the efficacy of single treatments of APL- Objective: Compare the adverse event (AE) profile in groups tak-
130277 in patients with Parkinsons disease. ing higher (1600 mg/day) or lower (<1600 mg/day) total daily dos-
Background: Parkinsons disease (PD) patients suffer from a vari- ages of IPX066 in clinical trials of advanced Parkinsons disease (PD).
ety of Off episodes as the disease progresses. These consist of wear- Background: IPX066 is an extended-release formulation of
ing off, delayed-On, no-On, unpredictable Offs, and morning akinesia. carbidopa-levodopa (CD-LD) designed to provide a rapid increase in
The only approved, acute medication treatment for these Off episodes plasma LD concentrations (similar to immediate-release CD-LD
is apomorphine given subcutaneously. Easier to administer, convenient, [IR]) and sustained stable LD concentrations to allow dosing every 6
on-demand treatments are needed. APL-130277 (APL) is a soluble film hours. IPX066 has demonstrated improvements in motor symptoms
strip of apomorphine administered sub-lingually and designed to rap- in early and advanced PD.
idly deliver apomorphine through absorption from the oral cavity. Methods: AEs were recorded during IPX066 treatment in two
Methods: This was a multi-center phase 2, open-label single-arm phase 3 studies in advanced PD: ADVANCE-PD (IPX066 vs. IR
study. 19 PD patients with at least one Off episode per day,  2 [N=451]); and ASCEND-PD (IPX066 vs. CD-LD1entacapone

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
Fig. 1. (233).
[N=110]). AEs were compared in patients with a final total daily
dose of IPX066 <1600 (lower dose) or 1600 (higher dose) mg/day.
The most common AEs for each group and AEs with notable differ-
ences between groups are reported.
Results: A total of 161/317 (68.9%) patients in the lower, and
132/241 (54.8%) in the higher dosage group had 1 AE. The most
frequent AEs in the lower dosage group were nausea (6.6%), insom-
nia (5.0%), and headache (4.4%); the most frequent in the higher
dosage group were dyskinesia (10.4%), nausea (6.2%), and dizziness
(5.0%). A greater proportion of higher compared to lower dosage
patients reported dyskinesia (10.4% vs. 3.2%, respectively) and wor-
sening off (4.6% vs. 1.3%, respectively). Five of the reported dys-
kinesia AEs in the higher and two in the lower dosage group, as
well as one of the worsening off AEs in each group were rated as
severe. Insomnia was more frequent in the lower dosage group
(5.0%) than the higher dosage group (2.1%). Nausea (6.2% vs.
6.2%), headache (4.1% vs. 4.4%), and hallucinations (2.5% vs.
2.2%) were similarly reported among higher and lower dosage
groups, respectively. Both somnolence (higher: 0.8% vs. lower:
1.8%) and orthostatic hypotension (higher: 0.8% vs. lower: 0.6%)
were infrequently reported by both groups. AEs most frequently
leading to discontinuation included dyskinesia (n56) for the higher
dosage group and anxiety, nausea, and visual hallucination (n52
each) for the lower dosage group.
Conclusions: The AE profile of IPX066 was consistent with the
known effects of CD-LD in the treatment of PD. No clear patterns
emerged between dosage groups in the frequency of the more com-
mon dopaminergic AEs.
235
Does cognitive dysfunction affect the efficacy of physiotherapy
for Parkinsons disease?
M. Hizume, Y. Hashimoto, T. Hori, Y. Fumimura, K. Kasai, T.
Ichikawa (Ageo, Japan)
Objective: To assess the influence of cognitive decline on the
effectiveness of physiotherapy in hospitalized patients with Parkin-
sons disease (PD).
Background: Physiotherapy is effective in patients with PD to
maintain their activities of daily living as well as medical therapies
and surgical interventions. However it is uncertain about whether
patients with cognitive decline benefit from physiotherapy as well as
patients without it.
Methods: The participants were 64 patients with PD admitted to
our hospital for rehabilitation (34 men and 30 women, age
69.2 6 7.9 years, Hoehn and Yahr scale 3.8[thinsp]6[thinsp]0.9,
length of hospital stay 48.8 6 29.8 days). They were divided into
S91
two groups: patients without cognitive decline (Mini-Mental State
Examination (MMSE) score of 24 or more, n 5 48) and patients with
cognitive decline (MMSE score of 23 or less, n 5 16). We assessed
range of motion (ROM), manual muscle test (MMT), turning in bed,
rising from bed, rising from chair, posture, walking and stair-
stepping by scoring their outcomes of physiotherapy (1: improved, 0:
unchanged, -1: worsened) and compared the efficacy of physiother-
apy for PD between the two groups.
Results: In patients with cognitive decline the effectiveness of
physiotherapy was not inferior to that in patients without cognitive
decline: ROM (0.31 vs 0.53, p 5 0.34); MMT (0.07 vs 0.35,
p 5 0.06); turning in bed (0.13 vs 0.12, p > 0.99); rising from bed
(0.06 vs 0.12, p 5 0.67); rising from chair (0.20 vs 0.23, p > 0.99);
posture (0.29 vs 0.12, p 5 0.15); walking (0.67 vs 0.76, p > 0.99)
and stair-stepping (0.50 vs 0.43, p > 0.99).
Conclusions: Patients with PD can receive benefits from physio-
therapy even though their cognitive functions decline.
236
Effect of hippotherapy on functional capacity and quality of life
in people with Parkinsons disease
R.C.P.P. Homem, Q.J. Almeida, G.P. Tolentino, S. Vidal, R.J.
Oliveira (Braslia, Brazil)
Objective: To assess the effects of hippotherapy on functional
performance and health-related quality of life in people with Parkin-
sons disease.
Background: Motor symptoms associated with Parkinsons dis-
ease impair ones ability to perform daily activities called functional
activities, and consequently decrease quality of life. Hippotherapy is
a strategic alternative physical activity for people with disabilities.
Hippotherapy has been shown as an effective treatment to increase
functional capacity and quality of life in other neurological popula-
tions different of people with PD (Lee et al., 2014; Sunwoo et al.,
2012). Hippotherapy does not require excessive effort or walking
from patients who can no longer coordinate motor actions or exercise
in a standing position.
Methods: The study was conducted with eigtheen people, nine
participants formed the hippotherapy group (HT) which performed a
10 weeks hippotherapy program (2 familiarization 1 8 hippotherapy
weeks, each session lasting thirty minutes), and nine indivuduals
formed the control group (CG) which attended lectures on PD twice
a week for ten weeks, each session lasting thirty minutes. Functional
outcome measures included functional strength, functional mobility,
gait velocity and health-related quality of life. The study was
approved by the Research Ethics Committee of the University of
Brasilia by the number CAAE 17329213.7.0000.0030. The interven-
tion was performed at First Regiment of Cavalry Guard of the Bra-
zilian Army, with the partnership of the Solidario Horse Institute.
Results: The hippotherapy group increased gait velocity
(p  0.05) and improved emotional aspects of quality of life
(p  0.01), as shown in Table 1 and Figure 1. The results of func-
tional mobility and functional strength showed tendency but were
not significant.
Conclusions: Hippotherapy is an effective method to improve
bradykinesia of gait and emotional aspects such as self-confidence
and self-esteem in people with Parkinsons disease.
[figure1]
237
F15599, a 5-HT1A biased agonist with preferential affinity for
post-synaptic receptors, reduces dyskinesia without impairing the
anti-Parkinsonian effect of L-DOPA, in the MPTP-lesioned
macaque
P. Huot, T.H. Johnston, A. Newman-Tancredi, S.H. Fox, J.M.
Brotchie (Montreal, Canada)
Movement Disorders, Vol. 30, Suppl. 1, 2015
S92 POSTER SESSION

TABLE 1. Effect of hippotherapy on Parkinsons disease

RESULT RESULT DIFFERENCE p-VALUE

VARIABLE TEST GROUP Pre Post Post - Pre EFFECT

FUNCTIONAL STRENGH 30CST number of repetition HT 0 (0-7) 3 (0-7) 3 0.47
median (range)
CG 9 (3-20) 8 (0-16) -1
FUNCTIONAL MOBILITY TUG second median (range) HT 10.59 (6.78-27.53) 9.53 (5.97-20.92) -1.06 0.15
CG 8.86 (6.55-29.62) 8.64 (7.15-18.28) -0.22
GAIT SPEED TMW second median (range) HT 9.39 (5.98-25.25) 8.09 (5.09-12.37) -1.3 0.05
CG 5.45 (5.06-15.72) 5.91 (4.35-22.83) 0.46
PARKINSONIAN SYMPTOM PDQLSP mean (SD) HT 2.99 (1) 3.64 (0.4) 0.65 (0.27) 0.46
CG 2.93 (1.32) 3.21 (1.14) 0.28 (0.58)
SYSTEMIC SYMPTOM PDQLSS mean (SD) HT 3.09 (1.11) 3.91 (0.48) 0.82 (1.08) 0.1
CG 3.39 (0.67) 3.42 (0.7) 0.03 (0.33)
EMOTIONAL FUNCTIONING PDQLEF mean (SD) HT 2.92 (0.91) 3.94 (0.67) 1.02 (0.64) 0.01
CG 3.65 (0.94) 3.67 (0.5) 0.02 (0.63)
SOCIAL FUNCTIONING PDQLSF mean (SD) HT 2.98 (1.18) 3.76 (0.4) 0.78 (1.09) 0.34
CG 3.01 (1.14) 3.51 (0.68) 0.5 (0.64)
Hippotherapy intervention results in Parkinsons disease

Objective: To assess the effect of F15599 on L-3,4-

dihydroxyphenylalanine (L-DOPA)-induced dyskinesia and anti-
Parkinsonian action.
Background: L-DOPA is the most effective anti-Parkinsonian
agent available, but upon chronic administration, patients with Parkin-
sons disease (PD) experience abnormal involuntary movements, dys-
kinesia. Modulation of serotonin 1A (5-HT1A) receptors is regarded
as an effective way to alleviate dyskinesia, yet this approach has been
marred by a reduction of the therapeutic effectiveness of L-DOPA.
Based on a post-mortem study we conducted in the 1-methyl-4-
phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned macaque model of
PD, we previously suggested that, in order to alleviate dyskinesia
without diminishing the therapeutic benefit of anti-Parkinsonian drugs,
it may be necessary to modulate selectively certain sub-populations of
5-HT1A receptors. F15599 is a biased 5-HT1A agonist that exhibits
greater affinity for receptors located along the cortico-striatal pathway
compared to raphe-striatal or thalamo-cortical receptors.
Methods: 7 cynomolgus macaques were administered MPTP and
developed severe Parkinsonism. Following chronic administration of
L-DOPA, they developed severe and reproducible dyskinesia.
F15599 (0.003, 0.01, 0.03 and 0.1 mg/kg) or vehicle was adminis-
tered in combination with L-DOPA and its effect on L-DOPA-
induced dyskinesia and anti-Parkinsonian action was assessed.
Results: In combination with L-DOPA, F15599 (0.1 mg/kg) reduced
the severity of peak-dose dyskinesia, by 45% (P<0.001), compared to
L-DOPA alone. F15599 (any dose) had no effect on severity of Parkin-
sonian disability or duration of on-time compared to L-DOPA alone.
While duration of on-time with dyskinesia was unaltered by adding
F15599 to L-DOPA, F15599 at 0.03 and 0.1 mg/kg significantly
reduced duration of on-time with disabling dyskinesia (by 49% and
71%, P<0.05 and P<0.001, respectively) and increased duration of on-
time with non-disabling dyskinesia (by 86% and 87%, both P<0.01).
Conclusions: These results suggest that 5-HT1A agonists display-
ing preferential affinity for cortico-striatal 5-HT1A receptors might
alleviate dyskinesia without exerting a deleterious effect on L-DOPA
anti-Parkinsonian action.

238
Rotigotine for the treatment of Parkinsons disease, the
experience of a tertiary Movement Disorder centre after 1 year
of approval by Health Canada
Fig. 1. (236).
P. Huot, N. Jodoin, M. Panisset (Montreal, Canada)

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
Objective: To gather data about rotigotine use for the treatment
of Parkinsons disease (PD) in a tertiary Movement Disorder clinic
in Canada after 1 year of clinical availability.
Background: Rotigotine is a dopamine agonist that binds prefer-
entially to dopamine D3 > D4 > D2 > D1 receptors, in addition to
alpha-2B adrenoceptors and serotonin 7 (5-HT7) receptors. Rotigo-
tine is available as a transdermal patch that provides constant plasma
levels throughout the day and thus offers the theoretical advantage of
reducing peaks and troughs associated with conventional dopamine
replacement therapies. Rotigotine was administered to early- and
late-stage PD patients and was effective at reducing Parkinsonian
disability in controlled clinical trials. Reported adverse events
include nausea, exacerbation of dyskinesia and impulse-control disor-
der. Rotigotine was approved by Health Canada in 2013 and has
been commercially available in the country for about 1 year. Rotigo-
tine was not approved for reimbursement by Regie de lAssurance
Maladie du Quebec (RAMQ), which limits its use mostly to patients
with private insurance, usually younger patients with early-moderate
PD. We sought to compare the benefit of rotigotine in this circum-
scribed population of PD patients with the results gathered in the
controlled trials that led to rotigotine approval by regulatory
agencies.
Methods: Patients referred to the Andre Barbeau Movement Dis-
order Clinic with idiopathic PD to whom rotigotine was prescribed
were enrolled in this retrospective and observational study.
Results: PD patients were administered rotigotine up to 8 mg/24h
as monotherapy or in combination with rasagiline and/or L-3,4-
dihydroyxphenylalanine (L-DOPA). Rotigotine improved Parkinso-
nian disability and was well tolerated in most cases. Adverse events
reported by patients include impulse-control disorder, nausea and
local skin erythema, and led to drug discontinuation in some cases.
Details regarding patients characteristics, rotigotine titration, and
clinical rating of Parkinsonism with the Unified Parkinsons disease
Rating Scale will be presented at the conference.
Conclusions: One year after its commercialisation in Canada,
rotigotine remains seldom prescribed, mostly because of cost issues.
However, the drug appears to be beneficial to patients who can
afford and tolerate it.
239
Durability of effect with long-term droxidopa treatment in
patients with symptomatic NOH
S. Isaacson, G. Liang, J.P. Lisk, G.J. Rowse (Boca Raton, FL, USA)
Objective: Evaluate the long-term efficacy and safety of
droxidopa.
Background: Neurogenic orthostatic hypotension (NOH) results
from insufficient noradrenergic response to orthostatic challenge.
Droxidopa is a norepinephrine prodrug approved to treat sympto-
matic NOH caused by primary autonomic failure (PD, multiple sys-
tem atrophy, and pure autonomic failure), dopamine beta-
hydroxylase deficiency, and nondiabetic autonomic neuropathy.
Methods: In Study 306, 225 patients with PD were randomized
to 2-week, double-blind placebo or droxidopa dose titration, followed
by 8-week double-blind treatment (100600 mg TID). Study 303
was a long-term, open-label extension study in 102 patients with
symptomatic NOH who completed a short-term, double-blind,
placebo-controlled study of droxidopa; treatment continued 1 year.
Efficacy measures included changes in the Orthostatic Hypotension
Symptom Assessment (OHSA) Item 1 score and standing systolic
blood pressure (SBP).
Results: In 306, OHSA Item 1 score was consistently improved
with droxidopa; relative to baseline, scores were -2.5, -2.2, and -2.3
units at weeks 1, 4, and 8, respectively. Mean change from baseline
to week 1 was significantly greater with droxidopa vs placebo (treat-
ment difference: -1.2 units; P=.008) with a trend favoring droxidopa
at week 8 (treatment difference: -0.8 units; P=.077). Responder anal-
ysis demonstrated that significantly more patients had improvements
S93
1 to 4 units at week 1; more patients also had improvement 4
units at weeks 4 and 8. The increase in standing SBP was signifi-
cantly greater in droxidopa patients vs placebo at week 1 (treatment
difference: 6.8 mmHg; P=.007), but not at week 8 (treatment differ-
ence: 3.0 mmHg; P=.276). In 303, mean changes from baseline in
OHSA Item 1 score were -4.0, -3.9, -3.7, and -3.9 units at 1, 3, 6,
and 12 months, respectively. Increases in standing SBP were sus-
tained: 13.7, 14.0, 10.4, and 12.3 mmHg at 1, 3, 6, and 12 months,
respectively. In both trials, headache (306: 13.2%; 303: 13.7%) and
dizziness (306: 9.6%; 303: 7.8%) were common treatment-emergent
adverse events (TEAEs). Most TEAEs were mild or moderate in
intensity and considered unrelated to study drug.
Conclusions: Clinically relevant improvements in OHSA Item 1
score and standing SBP were consistent and durable with long-term
droxidopa treatment. Droxidopa had a good safety profile and was
well tolerated.
240
Effect of droxidopa on fear of falling
S. Isaacson, C. Francois, G. Peng, G.J. Rowse (Boca Raton, FL,
USA)
Objective: To assess the impact of droxidopa on the fear of fall-
ing in patients with Parkinsons disease (PD) and symptomatic neu-
rogenic orthostatic hypotension (NOH) by a post hoc analysis of the
falls diary.
Background: Symptomatic NOH results from autonomic failure
in which there is an inadequate noradrenergic response to postural
change. NOH is associated with an increased incidence of falls, and
studies suggest that some patients may severely limit their movement
and activity due to high levels of anxiety resulting from previous
falls. Droxidopa is a norepinephrine prodrug recently approved to
treat symptomatic NOH caused by primary autonomic failure (PD,
multiple system atrophy, and pure autonomic failure), dopamine
beta-hydroxylase deficiency, and nondiabetic autonomic neuropathy.
Methods: Patients underwent up to 2 weeks of double-blind titra-
tion of droxidopa or placebo, followed by 8 weeks of double-blind
maintenance treatment (100600 mg 3 times daily). Falls were
recorded daily in electronic diaries. Patients who reported falls were
subsequently asked whether they had a fear of falling. To account
for the intensity of the fear of falling, the cumulative number of fear
of falls was calculated over the 8-week treatment period.
Results: A total of 62 and 58 patients reported a fall on placebo
and droxidopa, respectively; of these, 61 on placebo and 56 on drox-
idopa completed the fear of falls question. More patients on droxi-
dopa reported no fear of falls (57% vs 43%, droxidopa vs placebo;
not significant); the total number for the cumulative fear of falls was
lower in patients on droxidopa (137) vs placebo (249). The correla-
tion between the number of falls and fear of falls was 0.58 (Spear-
man correlation coefficient, P<0.001), suggesting that factors in
addition to falls affect the fear of falling.
Conclusions: These preliminary results suggest a potential effect
of droxidopa in reducing the fear of falling. However, caution is
warranted due to the small sample size and the post hoc nature of
the analysis.
241
Analysis of the incidence of supine hypertension with droxidopa
S. Isaacson, W.B. White, G.J. Rowse, L.A. Hewitt (Boca Raton, FL,
USA)
Objective: To evaluate the incidence of supine hypertension in
patients with symptomatic neurogenic orthostatic hypotension (NOH)
receiving droxidopa.
Background: Droxidopa is a norepinephrine prodrug that is FDA
approved to treat symptomatic NOH. Its mechanism of action likely
raises standing systolic blood pressure (SBP) by causing
Movement Disorders, Vol. 30, Suppl. 1, 2015
S94 POSTER SESSION
vasoconstriction. As supine hypertension is common in patients with
NOH, it is important to understand to what degree droxidopa might
affect supine BP.
Methods: Data from 3 randomized, phase 3 trials that enrolled
patients with symptomatic NOH (N=666) were examined. In 2 stud-
ies, patients with autonomic failure underwent open-label dose titra-
tion with droxidopa; dose titration was followed by 1-week washout
and 1-week, double-blind treatment (study 1) or 7-day, open-label
treatment and 14-day, randomized withdrawal (study 2). In study 3,
patients with Parkinsons disease (PD) underwent double-blind dose
titration followed by 8-week, double-blind maintenance treatment.
Patients underwent an orthostatic standing test (OST) at each visit.
The OST involved 3 supine (30-degree elevation) BP measurements
over a 10-minute period followed by a standing BP measurement
after 3 minutes of standing. Severe, sustained supine hypertension
was defined as SBP >180 mmHg at all 3 supine measurements dur-
ing the OST. Patients with supine SBP >180 mmHg at screening
were not eligible for these trials.
Results: In the 2 studies of autonomic failure patients, the inci-
dence of severe, sustained supine hypertension at end of study was
nominally higher in the droxidopa-treated group (study 1: 4.9%;
study 2: 14.0%) vs placebo-treated group (study 1: 2.5%; study 2:
5.9%). In the study in PD patients (study 3), the incidence of supine
hypertension was nominally higher during titration in the droxidopa-
vs placebo-treated groups (2.6% vs 1.9%) but generally decreased
over the course of the study, with no patients observed to have
severe, sustained supine hypertension at week 4 or week 8. Across
all studies, the incidence of sustained supine SBP >200 mmHg was
extremely low (<0.1%) in the droxidopa-treated groups.
Conclusions: In patients with symptomatic NOH who did not
have severe, sustained supine hypertension at screening, the inci-
dence of sustained supine hypertension with droxidopa treatment was
nominally higher than placebo but did not increase over time.
242
Efficacy of apomorphine subcutaneous injections for the
management of morning akinesia in Parkinsons disease
S. Isaacson, M. Lew, W. Ondo, F. Pagan (Boca Raton, FL, USA)
Objective: This multicenter, two-phase, open-label study assessed
the effect of subcutaneous injection of apomorphine (APO) on first
dose time-to-on (TTO) in Parkinsons disease (PD) patients with
morning akinesia.
Background: Patients with PD & motor fluctuations often have
delayed TTO after a dose of oral L-dopa. Delayed TTO can be due
to gastrointestinal (GI) factors impairing L-dopa absorption, includ-
ing delayed gastric emptying or competitive effects of protein. Deliv-
ery of non-oral (ie subcutaneous) medication may provide a more
rapid and predictable response by avoiding the GI system. Early
morning off periods are common, and delayed TTO after the 1st
morning L-dopa dose can result in a prolonged period of morning
akinesia, delaying the onset of L-dopa response.
Methods: Subjects who reported morning akinesia at a clinic visit
recorded their TTO following each morning dose of L-dopa for 7
days. Subjects who met inclusion criteria of >45 minute delay for
3 of 7 days were then titrated to a APO optimal dose, defined as
providing >90% of motor UPDRS after L-dopa within 15 min, with-
out intolerable AEs. Subjects then recorded their TTO following
each morning dose of APO for 7 days. Mean TTO represented the
primary efficacy variable comparing APO treatment period vs base-
line L-dopa period. Safety and tolerability were also assessed.
Results: The full analysis set included 88 subjects. Mean TTO
reduced from 60.86 6 18.11 minutes after L-dopa to 23.72 6 14.55
minutes after APO (p<0.0001). Significant improvements were also
found in PGI, CGI, & EQ-5L-3D scales. Dose failures (defined as
>60 min TTO) were reported for 144 of 310 (46%) completed diary
entries during the L-dopa baseline week, but only 20 of 307 (7%)
diary entries following APO. Over 40% of subjects had a dose fail-
Movement Disorders, Vol. 30, Suppl. 1, 2015
ure during the 7 day L-dopa period. Overall, the most common AEs
were nausea, dizziness & orthostatic hypotension (most AEs were
mild/moderate & occurred during APO titration); no serious AEs
occurred.
Conclusions: In patients with delayed TTO after the first morning
oral L-dopa dose, subcutaneous injections of APO provided a robust
motor improvement that was rapid, reliable and safe. Dose failures
were significantly reduced and global impression and quality of life
scales also improved. APO was generally well tolerated. Non-oral
delivery may improve motor fluctuations by avoiding GI dysfunction
that can delay L-dopa absorption.
243
Safety of sublingual APL-130277 for the treatment of OFF
episodes in patients with Parkinsons disease
S. Isaacson, J. Dubow, B. Dzyngel, T. Bilbault, A. Giovinazzo, A.
Agro (Boca Raton, FL, USA)
Objective: To evaluate the safety of single treatments of APL-
130277 in 19 patients with Parkinsons disease.
Background: Parkinsons disease (PD) patients suffer from a
variety of predictable and unpredictable OFF episodes throughout the
disease duration. OFF periods reflect end-of-dose wearing off,
delayed time-to-ON, dose failures, and morning akinesia. The only
approved acute, intermittent treatment of OFF episodes is apomor-
phine administered subcutaneously. Treatments that are easier to
administer, convenient, and available on-demand are needed. APL-
130277 (APL) is a soluble film strip of apomorphine that is delivered
sub-lingually, designed to rapidly deliver apomorphine through
absorption from the oral cavity mucosa.
Methods: This was a multi-center phase 2, open-label, single-arm
study. PD patients with motor fluctuations and a Modified Hoehn
and Yahr stage I-III in the ON state were included. All patients had:
at least one OFF episode per day,  2 hours of total daily OFF time,
and predictable OFF episodes in the morning. Subjects were pre-
medicated for 3 days with trimethobenzamide, which was continued
during the study. Subjects presented to the clinic in the morning
OFF state and were initially administered APL 10 mg. If a satisfac-
tory response was not seen, the dose of APL was increased in 5 mg
increments until a clinically meaningful ON was achieved, to a max-
imum dose of 30 mg.
Results: 19 subjects received a total of 77 doses of APL, at doses
ranging 10-30 mg. Overall, 13 (68.4%) patients experienced an AE,
with most experiencing mild AEs (Table 1). The most common AEs
were dizziness (7/19, 36.8%), somnolence (6/19, 31.6%), nausea (4/
19, 21.1%) and yawning (3/19, 15.8%) (Table 2). There were no AEs
of dyskinesia. One patient experienced mild orthostatic hypotension.
One patient had a serious AE of dysphagia deemed not related to
APL by the Investigator. No subjects discontinued due to AE.
Conclusions: Sublingual APL was safe and well tolerated in PD
patients with OFF episodes. The most common AEs were mild or
moderate, and are commonly associated with dopaminergic medica-
tions and/or apomorphine. No discontinuations occurred due to AEs
TABLE 1. Overview of AEs with APL-130277
N=19 n (%)
Any AE 13 (68.4)
Mild AE 13 (68.4)
Moderate AE 4 (21.1)
Severe AE 2 (10.5)
Any Related* AE 11 (57.9)
Any Serious AE 1 (5.3)
*Deemed certainly, probably, or possibly related to APL by the
Investigator
 POSTER SESSION S95

TABLE 2. Treatment Emergent AEs in 2 or More Patients

Preferred Term Any AE Mild AE Moderate AE Severe AE Related* AE
N=19 n (%) n (%) n (%) n (%) n (%)
Dizziness 7 (36.8) 7 (36.8) 0 0 5 (26.3)
Somnolence 6 (31.6) 3 (15.8) 3 (15.8) 1 (5.3) 5 (26.3)
Nausea 4 (21.1) 4 (21.1) 1 (5.3) 0 4 (21.1)
Yawning 3 (15.8) 3 (15.8) 0 0 3 (15.8)
Headache 2 (10.5) 2 (10.5) 0 0 1 (5.3)
Hyperhidrosis 2 (10.5) 2 (10.5) 0 0 2 (10.5)
*Deemed certainly, probably, or possibly related to APL by the Investigator

and no treatment-related SAEs were encountered. This trial suggests Objective: To examine a web-based, computerized tool to quan-
sublingual APL-130277 has demonstrated tolerability and was safe tify fine motor skills in PD. The tool is the Predictive Movement
in PD patients with OFF episodes. Longer phase 3 studies are and Trajectory Tracking or PMATT.
planned to assess efficacy, tolerability, and safety. Background: Candidate biomarkers of pre-motor PD include
anosmia and REM-BD, signs that can antedate the onset of motor
PD by 10 years. In order to design neuroprotective trials that target
244 the onset of motor symptoms, we need metrics that can track PD
Randomized study of the efficacy and safety of pregabalin in the motor physiology closer to diagnosis. Such a tool would have to be
treatment of neuropathy pain in PD significantly more sensitive than the clinical exam and be simple
S. Ji, Z. Mao, H. Han, Q. Yang, Z. Xue (Wuhan, Peoples Republic enough for field administration.
of China) Methods: As a first step towards this goal, we used a modifica-
tion of the web-based, visual-paired comparison task (VPCW: Agich-
Objective: To investigate the clinical Efficacy and Safety of Pre- tein et al 2010 Soc NS Abstract No. 651.6) to examine fine motor
gabalin in the Treatment of Neuropathy pain in PD. control in a cross section of PD subjects (N=23), and in 14 age- and
Background: PD-related neuropathic pain has a higher preva- sex-matched controls. In PMATT, the eye movement recordings of
lence in patients with PD than in the general population (1435% vs. the VPCW are replaced with recordings of time-stamped PC cursor
10%).Pregabalin showed efficacy in various neuropathic pain.The positions as subjects track targets across the screen. PMATT tasks
efficacy of Pregabalin has previously been investigated in many were administered using escalating doses of movement complexity
study, but there are very few published trials that assess the effect of (i.e., stationary, linear, diagonal and sinusoidal) and target size (i.e.,
Pregabalin treatments of PD-related neuropathic pain. small, medium, large) to help segregate individual performance lev-
Methods: 56 patients with Neuropathy pain in PD which were els. The modified Rankin Scale, the motor subset scores of the PDQ-
choosed from 206 patients with Parkinsons disease by NMSS and 39, the MoCA and the PHQ-2 (mood index) were used to correlate
ID Pain during 2013.1.1-2013.12.10 were divided into three with PMATT behavioral metrics. Using machine learning techniques,
groups.27 patients in control group were given vitamin treatment, 29 we calculated the 15 individual motor-behavioral metrics that best
patients in pregabalin group were given pregabalin 150 mg oral- correlated with the above clinical indices of PD severity, and looked
ly 1 vitamin treatment, two times a day for twelve weeks, 29 patients for the ones that best separated PD from controls subjects. We fur-
in gabapentin group were given pregabalin 150 mg orally 1 vitamin. ther refined this separation by implementing a J48 classifier to con-
Patients were recorded their scores by using a visual analogue scale sider the most highly correlated parameters simultaneously.
each week. Visual analogue scale(VAS) was used to assess the cura- Results: The individual behavioral metrics that best correlated
tive effect.The adverse reactions were observed in three groups. with the above clinical indices of PD included time on target, num-
Results: VAS scores in the pregabalin and gabapentin groups ber of entries into target and motor persistence (all with p values
were statistically lower than those in the vitamin group after 3 weeks <0.0001). Using two of these metrics concurrently, the J48 classifi-
of treatment (P < 0.05). In the pregabalin and gabapentin groups, cation model classified 97% of subjects correctly with a sensitivity
most of the scores were near to pronounced improvement (0 5 no of 0.973 and AUC of 0.992.
improvement and 10 5 pronounced improvement) in third week.
VAS scores in the pregabalin and gabapentin groups were lower than
those in the vitamin group,but a significant difference was not Correlation between PMATT behavioral metrics and clinical
observed between the treatment in the first, second week. The per- indices of PD severity
cent of patients with at least one TEAE in the pregabalin (n 5 89, Behavioral Metrics mRS PDQ-39
66.4%) was lower than that in the gabapentin (n 5 88, 65.2%) groups Time on Target
group,although a significant difference was not observed.There were Diagonal movements
more frequently of nausea, hyperhidrosis, decreased appetite and Medium targets -0.4376 -0.4751
vomiting in the gabapentin group as compared with the pregabalin Small targets -0.4128 -0.5147
group (p  0.05).Just one patience has the occurrence of peripheral Sinusoidal movements
oedema in pregabalin group.None of the patients reported blurred Medium targets -0.6447 -0.5412
vision. Small targets -0.5080 -0.5595
Conclusions: Pregabalin seems to offer an efficient, safe and Number Of Entries Into Target
cost-effective treatment for neuropathic pain in PD. These findings Diagonal movements
need to be confirmed in a larger study. Medium targets -0.2695 -0.1437
Small targets -0.2782 -0.2561
245 Sinusoidal movements
Medium targets 0.1467 -0.0759
Assessing fine motor function in Parkinsons disease using a web- Small targets -0.4395 -0.4899
based, computerized tool
J.L. Juncos, N.D. Adler, E. Agichtein (Atlanta, GA, USA) (Continued)

Movement Disorders, Vol. 30, Suppl. 1, 2015

S96 POSTER SESSION
TABLE Continued
Motor Persistence
Diagonal movements
Medium targets -0.4479 -0.4761
Small targets -0.4214 -0.4853
Sinusoidal movements
Medium targets -0.6119 -0.5547
Small targets -0.5038 -0.5668
Data on PD subjects only; Values are Pearson correlation values
(Pearson R); mRS 5 modified Rankin Scale; PDQ-
39 5 Parkinsons disease QoL Questionnaire. Results arranged
by increasing level of task-movement complexity (i.e., diagonal,
sinusoidal; linear not shown) and by decreasing target size (large
not shown); Bold numbers represent strong correlation based on
predefined criteria (>|0.40|)
Conclusions: PMATT may be a helpful tool to measure fine
motor deficits in early stages of PD and could be developed as a tool
to detect pre-clinical motor deficits in individuals at risk of PD.
PMATT is easily scalable to large trials and for use in field studies
with centralized data collection.
246
Medication information needs of patients with Parkinsons
disease
T. Ker
anen, H. J
arvinen, K. Laitinen (Helsinki, Finland)
Objective: To survey medication information needs of patients
with Parkinsons disease (PD) using the database of the Kuopio
Medicines Information Centre (KMIC).
Background: Medical treatment in PD is challenging due to the
age range of the patients, common co-morbidities and complexity of
PD drug regimens. Patient centered information on drugs may reduce
the risk of drug related adverse effects which have detrimental
effects on the quality of life of PD patient.
Methods: The data was collected from requests concerning PD
drugs received at the KMIC during 17.8.2002-14.4.2012. Almost all
inquiries to the KMIC service are made via telephone but the service
can be also reached by fax, e-mail and web form. In the KMIC, the
inquiries and responses are documented electronically. For the pur-
poses of this study only inquiries concerning the ATC-class N04
(anti-Parkinsons drugs), made by PD patients or their relatives, were
included.
Results: Majority of the inquiries concerned levodopa (n5158),
pramipexole (n585) and selegiline (n558). The most common areas
of interests were drug interactions (n5214), dosage and the use of a
PD drug (n567) and adverse effects (n564). Interaction issues con-
cerned mostly drug-drug interactions (n5205), especially possible
interactions between concurrent use of an antipsychotic and a PD
drug or the combination of levodopa and selegiline. Most common
adverse effects mentioned were nausea, vomiting or other gastroin-
testinal symptoms, hypotension, motor symptoms, hallucinations,
fatigue, and somnolence or falling asleep.
Conclusions: This study emphasized three areas in which PD
patients need more guidance on: drug interactions, dosage and the
use of drug and adverse effects. A telepharmacy service, such the
KMIC described here, can supplement the education of given by
other healthcare professionals.
247
The choice of first symptomatic drug treatment in Parkinsons
disease
T. Keranen, L.J. Virta (Helsinki, Finland)
Movement Disorders, Vol. 30, Suppl. 1, 2015
Objective: To examine the choice of first symptomatic drug treat-
ment in Parkinsons disease (PD) during two years, 2005 and 2012
based on the Finnish nationwide prescription register.
Background: Evaluation of prescription patterns in early PD
have shown that Levodopa and dopamine agonists are the most
favored drugs as monotherapy and that the drug preferences are
influenced by the age of the patient. Studies also suggest that initial
drug choices are at least moderately in adherence with recommenda-
tions of recent guidelines in PD. In Finland, the first PD guideline
was published in 2006 and it was updated in 2010. To date, there are
no data on the prescription patterns in PD in Finland.
Methods: Two cohorts of incident PD patients, diagnosed during
2005 (n51,436) and 2012 (n51,607), were identified from a Finnish
nationwide register of special reimbursements for medication costs.
Data on their PD drug purchases (ATC codes N04) during 2003
2006 and 20102013 were obtained from the national Prescription
register, also maintained by the Social Insurance Institution of
Finland.
Results: Overall, levodopa was the most common initial drug in
PD. Levodopa was started as the first drug in more than 80% of the
cases in patients aged over 74 years. Dopamine agonists and MAO-
B inhibitors predominated among patients aged < 60 years and the
frequency of both drug classes decreased with advancing age. Signif-
icant changes in the choice of the first drug occurred from the year
2005 to 2012. The use of MAO-B inhibitors increased in patient
groups aged < 60 years and 60 74 years. The use of levodopa
decreased in patients aged 64 74 years while that of dopamine ago-
nists increased.
Conclusions: The choices of the first drug in PD show significant
age and time period related variation. The patterns of prescription of
the first drug in PD suggest that guidelines have an impact in clinical
practice.
248
Effect of action observation combined with motor training on
learning of reach-to-grasp actions in individuals with Parkinsons
disease
S. Khacharoen, J. Tretriluxana, A. Pisarnpong, P. Chaiyawat
(Nakhon Pathom, Thailand)
Objective: To determine the effects of action observation com-
bined with reach-to-grasp (RTG) training on learning of RTG actions
in Parkinsons disease (PD).
Background: There were findings indicating that action observa-
tion combined with motor training enhanced prehensile execution in
individuals with stroke and PD. PD individuals also have the
impaired RTG planning, kinematics and coordination. It is still ques-
tionable if action observation combined with motor training could
improve these impairments.
Methods: In Pre-training test, 16 PDs were evaluated planning
(measured by reaction time (RT)), kinematics and coordination dur-
ing performing RTG to avoid the barrier. The kinematics were
movement time (MT), maximum velocity (Vmax), maximum aper-
ture (Amax). The coordination of RTG were correlation coefficient
(rmax) from cross correlation analysis between transport velocity and
aperture size, and associated time lag (Tmax). They were also tested
unimanual items of the Wolf Motor Function test (WMFT). Conse-
quently, they were allocated into action observation (AO) or Placebo
(P) groups. Participants in AO groups were asked to observe hand
action for 6 minutes alternate with physical training which using
similar tasks as in WMFT for 4 observation blocks. For P groups,
participants were asked to train as in AO group but observe the natu-
ral landscape instead of hand action. After training, all participants
were tested under alll RTG actions immediately in Post-training
test and 45 minutes later in Retention test.
Results: AtPost-training test, there was a significant decrease in
MT and total time of WMFT in both groups. Moreover, the WMFT
time was different between the 2 groups. However, the decreased
 POSTER SESSION
tmax was shown only in the AO group. At Retention test, RT, MT
and Tmax decreased continuously until reached significant level
when compared to Pre-training test only in AO group. The WMFT
time could be decreased when compared to Pre-training testin both
groups. However, the WMFT time was different between the 2
groups. Moreover, there was a diffrence in the rmax between the 2
groups.
Conclusions: These results indicate that action observation com-
bined with the motor training enhance the learning of RTG planning,
kinematics, co-ordination and function in individuals with PD.
249
Medications reconciliation in hospitalized Parkinsons disease
patients
Y. Kianirad, M. Marvanova, T. Simuni (Chicago, IL, USA)
Objective: To determine the frequency of prescribing errors of
PD medication in hospitalized PD patients.
Background: Parkinsons disease (PD) patients are hospitalized
50 percent more frequently than non-PD patients. One half of these
admissions involve patients in advanced stages of PD. The manage-
ment of the PD medications regimen during hospital admissions is a
challenge. Anti-Parkinsonian medications, dosages and frequency of
administrations are very critical for PD patients; especially for those
in an advanced stage of PD when a complex regime with multiple
PD medications is needed requiring frequent administration.
Methods: We conducted a single-center, retrospective study of
PD patients followed in the Movement Disorder clinics at Northwest-
ern University who were admitted for at least one night between
August 2013 to August 2014. Electronic medical records were
reviewed by a neurology resident.
Results: 103 PD patients (37 Females, mean age of 72.7 (SD
10.6), PD duration 4.6 (2.8) were admitted between August 2013 to
August 2014. Of these patients, 3 were not on any PD medications,
one was on DUODOPA trial. 45 patients (45.45%) remained on their
home PD medications regimen and for the rest of 54 patients
(54.54%), home medications were modified (29 (39%) medications
discontinuation, 22 (30%) change in dose, 15 (20%) change of fre-
quency, 8 (11%) change of dosage form). The reasons for medica-
tions changes were the following: not documented in 30 (41%), 28
(38%) inaccurate home medication documentation by medical staff,
7 (11%) unavailable or none formulary medication, 4 (5%) pharmacy
error and 4 (5%) due to medical reason (NPO, mental status,
dysphagia).
Conclusions: There was a high rate of unintended changes of PD
medications in this cohort of hospitalized PD patients. The data sup-
port importance of on-going staff education and development of
standardized protocols for administration of PD medications in the
hospital setting.
250
An evaluation of istradefylline treatment on motor and cognitive
disabilities in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
(MPTP)-treated macaque models of Parkinsons disease
W.K.D. Ko, Q. Li, Y. Jianzhong, E. Pioli, E. Bezard (Manchester,
United Kingdom)
Objective: To assess the motor and cognitive function in MPTP-
treated macaques following acute administration of istradefylline
(60-100 mg/kg) combined with optimal or sub-optimal doses of L-
DOPA.
Background: Istradefylline (KW-6002), an adenosine A2A recep-
tor antagonist used adjunct with L-3,4-dihydroxyphenylalanine (L-
DOPA), increases ON-time in patients with Parkinsons disease
(PD). However, an effective combined drug treatment strategy for
reducing dyskinesia and cognitive impairments commonly associated
with a therapeutic dose of L-DOPA remains to be determined.
S97
Methods: In this study, acute treatment effects of istradefylline
were evaluated in two monkey models of PD (i) the gold-standard
MPTP-treated macaque model of Parkinsonian and dyskinetic motor
symptoms and (ii) the chronic low dose (CLD) MPTP-treated maca-
que model of cognitive (working memory and attentional) deficits.
Results: Istradefylline treatment with optimal L-DOPA enhanced
motor activity but exacerbated dyskinesia. When combined with sub-
optimal L-DOPA, istradefylline treatment alleviated PD disability to
a similar extent to the optimal dose of L-DOPA alone, while main-
taining a lower severity of dyskinesia. At the same doses tested,
istradefylline alone or in combination with L-DOPA did not improve
cognitive function. However, the lowest dose of istradefylline
(60 mg/kg) prevented cognitive impairment induced by a therapeutic
dose of L-DOPA.
Conclusions: These data support the clinical use of istradefylline
as an adjunct treatment to a sub-threshold dose of L-DOPA in
patients with PD. Such a treatment strategy would help reduce
adverse motor and cognitive complications associated with an opti-
mal dose of L-DOPA, while maintaining a desired anti-Parkinsonian
effect.
251
The effects of clinically used anti-Parkinsonian drugs on whole-
body kinematics in the MPTP-treated macaque model of
Parkinsons disease: Therapeutic validation of a translational
platform for Movement Disorder research
W.K.D. Ko, I. Vollenweider, L. Baud, Q. Li, Y. Jianzhong, G.
Courtine, E. Bezard (Manchester, United Kingdom)
Objective: To assess the functional impact of anti-Parkinsonian
drugs on gait, posture and limb dysfunction in MPTP-treated maca-
ques using biomechanical analyses and objective statistical
procedures.
Background: Anti-Parkinsonian treatment therapies are often
developed in preclinical studies that utilise animal models of Parkin-
sons disease but translation into clinical benefit remains uncommon.
A major contributing factor to this predicament is an inconsistency
in methodological approaches between preclinical and clinical
research. There is a lack of consensus on measures for rating motor
performance and defining useful experimental endpoints.
Methods: We employ the experimental platform of whole-body
kinematic analyses in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
(MPTP)-treated macaques, the gold-standard model for Parkinsonian
motor symptoms, for evaluating clinically used anti-Parkinsonian
agents. Animals were trained to perform unconstrained locomotor
tasks, following which pharmacological treatments were tested in the
same conditions.
Results: These unbiased quantitative analyses of motor function
during unrestricted movement allowed mechanistic identification of
clinically effective treatments against Parkinsonian motor disabilities
(i.e. L-DOPA, pramipexole, ropinirole, amantadine and istradefyl-
line). The high resolution of these analyses dissociates specific clus-
ters of motor control parameters that are improved from those that
remain affected. For example, L-DOPA enhanced movement velocity
and stride length during walking, but had no effect on stance dura-
tion or foot elevation.
Conclusions: These recording methodologies and analytical tools
for assessment of motor control capacities are readily transferable to
a clinical setting, offering an efficient and reliable avenue for pre-
dicting/evaluating therapeutic benefit of novel treatments. This meth-
odological approach, which has been validated in human patients,
bridges the gap between preclinical and clinical research. Together,
these tools support (i) greater translational efficacy of novel thera-
peutic interventions and (ii) objective fine-tuning of existing drug
treatments used in patients with Parkinsonian or other neuro-motor
disorders.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S98 POSTER SESSION
252
The impact of levodopa-carbidopa intestinal gel on health-related
quality of life in Parkinsons disease
N. Kov  G. Deli, E. Bosny
acs, Z. Aschermann, P. Acs, ak, J. Janszky,
S. Komoly (P ecs, Hungary)
Objective: Our aim was to assess the improvement in quality of
life of PD patients treated with LCIG at University of Pecs.
Background: The levodopa/carbidopa intestinal gel (LCIG) ther-
apy can improve the severe fluctuations associated with advanced
Parkinsons disease (PD).
Methods: Eighteen PD patients were evaluated (age: 69.5 6 4,7
years, disease-duration: 15.2 6 6.4 years, duration of fluctuations:
9.1 6 3.0 years). Before the initiation of LCIG treatment and 6 and
12 months later, the health-related quality of life (PDQ-39 and EQ-
5D-5L), severity of PD-related symptoms (MDS-UPDRS, Hoehn-
Yahr Scale, Clinical Global Improvement- Severity) and major non-
motor symptoms (PD Sleep Scale 2nd version: PDSS-2, Epworth
Scale and Montgomery-Asberg Depression Rating Scale:MADRS)
were assessed.
Results: Health-related quality life improved after LCIG treat-
ment measured by both EQ-5D-5L (from 0.278 to 0.673, p50.007)
and PDQ-39 (from 36 to 27 points, p50.038). Meanwhile PD-related
symptoms (MDS-UPDRS total score: from 107 points to 69 points,
p<0.05) sleep quality (PDSS-2: from 27 to 21 points, p<0.05), day-
time sleepiness (Epworth: from 13 to 7 points, p<0.05) and depres-
sion (MADRS: from 29 to 14 points, p<0.05) also improved.
Median ON time improved form 4.5 hours to 10.5 hours; whereas,
the OFF time decreased from 4.05 to 0.5 hours (p<0.05).
Conclusions: Both the quality of life and the clinical features of
PD can be improved by LCIG treatment in advanced PD.
253
A supervised, group-based exercise program to improve gait and
balance in adults with early to mid-stage Parkinsons disease: A
feasibility study
D. Krasteva, P. Mahoney, M. Arango, C. Robinson, A. Sarte (North
Vancouver, BC, Canada)
Objective: To evaluate (1) the effects of a group based exercise
program using the PWR!TM Framework on gait, balance, and quality
of life for people with early to mid-stage Parkinsons disease (PD),
and (2) determine the feasibility of running an ongoing group
program.
Background: Research has shown that regular, ongoing exercise
using specific types of exercise, including large amplitude move-
ments, and cues can lead to improvements in PD motor symptoms
and potentially slow the progression of the disease. Dr. Becky Far-
ley, a physiotherapist and researcher from the US developed the
PWR!TM Framework, which promotes the use of these evidence
based PD-specific exercises.
Methods: We conducted a quantitative, quasi-experimental pre-
post intervention study without a control group. We ran a 12 week,
twice weekly, 60 minute group-based exercise program using the
PWR!TM Framework with 15 participants split into two groups. All
sessions took place in a hospital gym under the supervision of a
physiotherapist and rehabilitation assistant. Participants completed a
battery of standardized assessments, the Functional Gait Assessment
(FGA), Timed up and go (TUG), and 6 min walk test (6MWT), at
pre- and post-intervention, and one month follow-up. Participants
completed the Parkinsons disease Questionnaire -39 (PDQ-39) pre-
and post intervention, and a self-administered questionnaire exploring
satisfaction at the end of the program.
Results: Intervention resulted in statistically significant increases
in the mean FGA score (p<0.01) and 6MWT (p <0.01) and a statis-
tically significant decrease in TUG time (p<0.01) immediately after
intervention. Changes on the FGA (mean change 4.93, SD 2.06) and
the 6MWT (mean change 86.87m, SD 76.7m) exceeded the Minimal
Movement Disorders, Vol. 30, Suppl. 1, 2015
Detectable Change for these measures. Results were not maintained
at one month follow up. No statistically significant changes noted on
the PDQ-39.
Conclusions: We found that a 12 week, twice weekly, 60 minute
supervised group-based exercise program based on the PWR!TM
Framework induced changes in functional mobility among individu-
als with PD. However, these changes were not sustained one month
after the intervention. These findings suggest that there is a need for
ongoing community exercise programs specific to individuals with
PD.
254
Withdrawn by Author
255
Parkinsons disease evaluation of range of motion to vertebral
column and relationship to fall
O.Y. Kusbeci, H. Demirbas, F. Yaman (Afyonkarhisar, Turkey)
Objective: It is aimed that comparing the patients with Parkin-
sons disease of vertebral range of motion (ROM) measurements
with control groups and the effects on fall of Parkinsons patients if
it is affected.
Background: Musculosketal system symptoms frequently
observed in Parkinsons disease. The anteflexion posture indicates
that in Parkinsons patients. Falls in Parkinsons disease frequently
observed and multifactorial. The reduction of spinal flexibility may
be effective in falls.
Methods: Fifty right handed patients with PD, H&Y stage 1-4,
diagnosed by means of the United Kingdom Parkinsons disease
Society Brain Bank Clinical Diagnostic Criteria (referans) were
included in the study. Patients who have neck and back pain, verte-
bral column disease and vertebral column surgery were excluded
from the study. Patients with H&Y Stage 5 were not included into
the study. Fifty right handed subjects were set up and evaluated as
the control group. Cervical Range of Motion meter and inclinometer
used to measure cervical flexion, extension, right-left lateral flexion,
right-left rotation and lomber flexion, extension, and history of fall-
ing of the groups were evaluated. All statistical analyses were per-
formed with the SPSS software (Statistical Package for the Social
Sciences, version 17.0, SSPS Inc, and Chicago, IL, USA).
Results: Twenty six Patients H&Y Stage 1-2 were evaluated as
mild and 24 patients with H&Y Stage 3-4 were evaluated as moder-
ate grup. History of falling at least one time for the last six months
were present in 14 patients. There was statistical difference between
vertebral column ROMs between patient and control groups but there
were no statistically signifcant difference between mild and moderate
groups. These results show that vertebral ROMs are decreased in the
early stages. There were no statistical difference in Parkinsons
patients vertebral range of motionss between who have history of
fall and not fall.
Conclusions: In this study, we found that vertebral ROMs are
decreased at the early stages of the disease and this decrease can
affect balance control and the functionality of the patients. Therefore,
beside the pharmacological therapy, physical therapy and exercise
should not be forgotten.
256
Effects of virtual reality exercise program on balance and
quality of life among patients with Parkinsons disease
G.H. Lee (Cheonan, Korea)
Objective: The purposes of this study were to evaluate the effec-
tiveness of a 8-week virtual reality exercise program designed around
the Nintendo Wii(Wii), in improving balance and quality of life
among patients with Parkinsons disease(PD).
 POSTER SESSION
Background: Few studies were done about the effect of virtual
reality exercise program in balance function and quality of life of
PD patients using posturographic studies.
Methods: The subjects were 30 individuals with PD. 15 patients
were assigned to experimental group to engage an in three 40-minute
Wii balance-training sessions per week, for 8 weeks, and 15 to con-
trol group. They were asked to complete questionnaires including
verbal analogue scale (VAS), activities specific balancing confidence
scale (ABC) and Parkinsons disease Quality of Life (PDQ39) Scale,
fall index assessment before and after the intervention. Quantification
of improvement was conducted utilizing Sensory Organization Test
(SOT) of Computerized Dynamic Posturography (CDP). Statistical
significance was tested in between the patients before and after treat-
ment by ANOVA.
Results: There was a statistically significant improvement in
scores of VAS, ABC, PDQ39, and fall index assessment results
within the experimental group. SOT showed significant difference on
condition 5, 6, and vestibular ratios within the experimental group
from baseline to post-intervention.
Conclusions: Virtual reality exercise program can be an effective
intervention method improving balance, balance confidence, and
qualities of life among individuals with PD.
257
1-year safety of opicapone in patients with Parkinsons disease
and motor fluctuations
A. Lees, J. Ferreira, R. Costa, C. Oliveira, R. Pinto, N. Lopes, T.
Nunes, J.F. Rocha, P. Soares-da-Silva (London, United Kingdom)
Objective: Evaluate the safety of opicapone (OPC) as add-on to
levodopa over 1-year of treatment in Parkinsons disease (PD)
patients with motor fluctuations.
Background: OPC, a novel once-daily peripheral COMT-
inhibitor, has shown to be safe and effective in reducing OFF-time
in PD patients with motor fluctuations.
Methods: Subjects completing the double-blind (DB) part of a
randomized, placebo-controlled study (BIPARK II) were enrolled
into an open-label 1-year extension. Subjects started with 25mg-OPC
irrespective of prior DB treatment. One week after, either OPC (25
or 50mg), levodopa or anti-PD drugs could be adjusted based on
individual response. Safety was assessed by adverse events (AEs),
laboratory, vital-signs, ECG, physical and neurological examinations,
modified Minnesota Impulsive Disorders Interview (mMIDI) and
Columbia Suicide Severity Rating Scale (C-SSRS).
Results: A total of 286 (81%) subjects completed the 1-year treat-
ment. Dopaminergic events or other PD symptoms were the most
commonly reported AEs: dyskinesia (21.5%), (worsening) PD
(17.0%), falls (9.1%), blood CPK increased (7.4%), insomnia (5.7%)
and orthostatic hypotension (5.4%). The majority of AEs were mild to
moderate in intensity. Serious AEs were reported for 11.3% of the
patients. Five deaths occurred, all but one (cerebral hemorrhage after
traumatic brain injury) were considered unrelated to treatment. There
were no reports of urine discoloration, severe diarrhea, myocardial
infarction, prostate cancer or any serious hepatic event. Melanoma
was confirmed in 1 patient. Few significant findings were observed for
laboratory, vital-signs, physical and neurological examinations or ECG
readings. C-SSRS showed no effect on suicidality. Impulsive disor-
ders, as screened by mMIDI, were reported in few subjects (4.0%).
Conclusions: Long-term use of OPC is safe and well tolerated.
258
Efficacy and safety of opicapone in patients over 70 years with
Parkinsons disease and motor fluctuations
A. Lees, J. Ferreira, N. Lopes, R. Costa, A. Santos, C. Oliveira, R.
Pinto, T. Nunes, J.F. Rocha, P. Soares-da-Silva (London, United
Kingdom)
S99
Objective: Evaluate the efficacy and safety profile of opicapone
(OPC) as add-on to levodopa in patients over 70 years with Parkin-
sons disease (PD) and motor fluctuations.
Background: OPC, a novel once-daily peripheral COMT inhibi-
tor, has shown to be safe and effective in reducing OFF-time in PD
patients with motor fluctuations. PD mainly affects older subjects
and the incidence increases with age, being the second most preva-
lent neurodegenerative disease among the elderly.
Methods: Efficacy and safety data from two multicentre, double-blind,
randomised, placebo- and active-controlled studies (BIPARK I and II)
were pooled and evaluated by age (<70 and  70 years). Outcome efficacy
measures included the change from baseline to endpoint in absolute OFF-
time and the OFF- and ON-time responder rates ( 1 hour). Safety was
evaluated by analysis of reported adverse events (AEs).
Results: A total of 221 patients  70 years were analysed (N=69,
66 and 86 for placebo, 25mg- and 50mg-OPC, respectively). The
mean daily OFF-time was reduced by -1.41 h for placebo, 1.77 h
(p50.4086) for 25mg-OPC and -2.26 h (p50.0384) for 50mg-OPC.
Consistently, higher proportions of patients receiving either 25mg- or
50mg-OPC achieved the OFF- and ON-time responders endpoint
(p<0.05 for 50mg-OPC). AEs occurring more frequently in the
elderly (adjusted for placebo) included hallucinations (4.6% vs.
0.1%), visual hallucinations (3.8% vs. 0.1%) and weight decreased
(4.6% vs. 1.1%). The incidence of serious AEs was lower in OPC
treated patients than placebo.
Conclusions: OPC is effective and well tolerated by PD patients
over 70 years old.
259
Predictability of response to apomorphine subcutaneous
injections: Responder analyses from the AM-IMPAKT trial
M. Lew, S. Isaacson, F. Pagan, W. Ondo (Los Angeles, CA, USA)
Objective: To assess the predictability of subcutaneous injections
of apomorphine (APO) on first dose time-to-ON (TTO) in Parkin-
sons disease (PD) patients suffering from morning akinesia.
Background: Impaired gastric emptying likely plays a role in
delayed TTO in PD patients with a fluctuating oral levodopa
response; non-oral medication delivery may provide a more predict-
able response.
Methods: Subjects who reported morning akinesia at a clinic visit
recorded their TTO (in 5 minute intervals) following each morning
dose of levodopa for 7 days. Subjects who met inclusion criteria of
>45 minute delay for at least 3 of 7 days were then titrated to a APO
optimal dose, defined as providing >90% of motor UPDRS after
levodopa within 15 min, without intolerable adverse effects, up to a
maximum of 6 mg. Subjects then recorded their TTO following each
morning dose of APO for 7 days. The primary efficacy variable was
TTO (APO treatment period vs baseline levodopa period). We present
here post-hoc responder analyses of: (a) the percent of diary days
where the subject reported a TTO within 20, 30, 45 and 60 minutes;
and (b) the percent of subjects who recorded a consistent TTO within
20, 30, 45 and 60 minutes on at least 75% of recorded diary days.
Results: 127 subjects were enrolled and included in the safety
population. The full analysis set included 88 patients. In both groups,
compared with levodopa, APO provided quicker, more predictable
TTO.
Conclusions: In PD patients with morning akinesia, APO provided
a more rapid and more reliable onset of benefit than oral levodopa.
260
Inhaled levodopa (CVT-301) provides rapid motor
improvements after administration to Parkinsons
disease patients when OFF
P.A. LeWitt, M.H. Saint-Hilaire, D.G. Grosset, R. Hauser, F. Stocchi,
M.I. Freed, T. DeFeo-Fraulini, M. Leinonen, K. Kieburtz (West
Bloomfield, MI, USA)
Movement Disorders, Vol. 30, Suppl. 1, 2015
S100 POSTER SESSION
Responder analyses of TTO: Percent of diary days and percent of subjects reporting TTO within clinically relevant timeframes (n588)
Percent of diary days
Levodopa APO treatment
TTO within baseline week week
20 minutes 1% 65%
30 minutes 3% 83%
45 minutes 30% 94%
60 minutes 76% 96%
Objective: To evaluate the efficacy and safety of CVT-301
(inhaled levodopa [LD]) when administered during an OFF
state.
Background: LD is the most effective treatment for PD motor
symptoms. Irregularity in intestinal absorption diminishes LD utility
as a reliable therapy to provide rapid motor improvement in PD
patients experiencing OFF states. CVT-301, inhaled LD, is being
developed to treat OFF episodes. Following inhalation, systemic
LD concentrations rise rapidly within 10 minutes to therapeutic
levels.
Methods: This was a 4-week (wk) randomized, double-blind,
placebo (pbo)-controlled study in PD subjects experiencing 2h/
day OFF time (not including morning OFF). Over 4 wks, subjects
used CVT-301 as an adjunct to usual PD medications (including
oral LD) when needed as soon as possible to emergence of OFF
symptoms, up to 3 times daily. Two doses were studied (LD fine
particle doses [FPD]: 35 mg [during wks 1-2]; 50 mg [during wks
3-4]). Serial UPDRS III (0, 10, 20, 30 and 60min) ratings were
performed at in-clinic visits (wks 1, 2 and 4). The primary end-
point was the change in UPDRS III (average 10-60min) score
reduction at wk 4 versus baseline. PD diary data were secondary
endpoints for evaluating daily OFF time and ON time (with or
without dyskinesia).
Results: 86 PD patients (average LD daily intake 770 mg, 6
doses/day, 5.9hr/day daily OFF time) were randomized 1:1 to CVT-
301 or Pbo. Both CVT-301 doses were clinically effective and
showed dose ordering with significant reductions in average
UPDRS III scores over 10-60 min: 35 mg LD FPD -9.9 [-4.6 (95%
CI: -7.9, -1.3) vs Pbo; p50.007]; 50 mg LD FPD, -10.0 [-7.0 (95%
CI -10.3, -3.6 vs Pbo; p <0.001]. Onset of action was evident based
on UPDRS III improvements at the 1st assessment (10 min) and
UPDRS III improvements were significantly different from Pbo at
every time point (10-60 min post-dose). With an average daily out-
patient use of 2 times/day, CVT-301 50 mg LD FPD was associ-
ated with a 1.6hr reduction in daily OFF time (-0.9hr vs Pbo;
p 5 0.045), a 30-35% reduction from baseline during the period of
use, without associated increase in ON time with dyskinesia. CVT-
301 was safe and well tolerated without adverse effects on cardio-
vascular or lung function.
Conclusions: During 4 wks of use, inhaled LD (CVT-301)
provides rapid motor improvement in PD OFF states, and
reduces daily OFF time without worsening time ON with
dyskinesia.
261
The influence of concomitant medication on the efficacy of
IPX066, an extended-release formulation of carbidopa-levodopa,
in advanced Parkinsons disease
P. LeWitt, L. Verhagen Metman, R. Rubens, V. Shah, S. Kell, S.
Gupta (West Bloomfield, MI, USA)
Movement Disorders, Vol. 30, Suppl. 1, 2015
Percent of subjects reporting a consistent TTO
(>75% recorded diary days)
Levodopa
baseline week APO treatment week
0% 51%
0% 74%
9% 94%
66% 95%
Objective: Evaluate whether the efficacy of IPX066 is influenced
by concomitant Parkinsons disease (PD) medication in clinical trials
of advanced PD, using post hoc subgroup analyses.
Background: IPX066 is an extended-release formulation of
carbidopa-levodopa (CD-LD) designed for a rapid increase in plasma
LD concentrations (similar to immediate-release [IR] CD-LD) and
for maintaining sustained LD concentrations, permitting dosing at 6-
hour intervals. IPX066 has demonstrated improvement in motor
symptoms for early and advanced PD.
Methods: IPX066 was evaluated in 2 randomized, double-blind,
active-controlled, Phase 3 studies in advanced PD (ADVANCE-PD:
IPX066 vs. IR for 13 weeks, N=393; ASCEND-PD: IPX066 vs. CD-
LD1entacapone [CL1E] using a 2-week/period crossover, N=91). To
evaluate the effect of concomitant medication on the response to
IPX066, we analyzed efficacy measures (PD diary and Unified PD Rat-
ing Scale [UPDRS] Parts II [activities of daily living] 1 III [motor
score]) in subgroups based on the concomitant use of dopaminergic ago-
nists (DA), monoamine oxidase-B (MAO-B) inhibitors, or amantadine.
Results: Overall, IPX066 improved off time (P<.0001), on
time without troublesome dyskinesia (P<.001), and UPDRS Parts
II1III scores (P<.03) compared with active control in each study. In
both studies, numerical improvements from baseline on each efficacy
measure were seen with IPX066 vs the comparator for each of the
concomitant medication subgroups. In the larger study (ADVANCE-
PD), all improvements in off time were significant (P<.03) for
IPX066 vs. IR, except in the subgroup receiving concomitant aman-
tadine (P=.50). Similar results were seen for UPDRS Parts II1III.
For both studies, IPX066 did not worsen on time with troublesome
dyskinesia as compared to active controls in any subgroup (P>.11).
Conclusions: Based on the findings of 2 randomized studies, the
concomitant use of adjunctive PD medications did not diminish the
efficacy or increase troublesome dyskinesias when IPX066 was com-
pared to IR or CL1E treatment regimens.
262
Prediction of falls and/or near falls by using tandem gait
performance in people with mild Parkinsons disease
B. Lindholm, O. Hansson, P. Hagell, M.H. Nilsson (Malmo, Sweden)
Objective: To investigate whether tandem gait test (TG) can predict
future falls and/or near falls in people with Parkinsons disease (PD).
Background: People with PD have balance problems and an
increased risk for falls. Although TG has been considered a predictor
of falls, no PD-study has controlled results for demographic and
disease-specific characteristics or included near falls when investigat-
ing falls prospectively.
Methods: The study included 141 participants with PD (mean age
and PD-duration, 68 and 4 years, respectively). Those >80 years of
age, requiring support in standing or did not understand the instruc-
tions were excluded. TG includes taking 10 consecutive tandem steps
 POSTER SESSION
along a straight line without walking aids and support, with eyes
open. Performance was scored as follows: no side steps=0; one or
more side steps=1; unable to take 4 consecutive steps=2. If TG was
abnormal (1 side steps) during the first attempt, a second trial was
allowed and the best performance was registered. Anti-Parkinsonian
medications were recorded from medical records. All assessments
were conducted in the on condition. Participants thereafter registered
all falls and near falls by using a diary for six months.
Results: Mean score for UPDRS III was 14 (SD 8.0). The median
(q1-q3) daily total levodopa equivalent (LDE) dose (mg) was 400
(286-600). Sixty-three participants (45%) experienced 1 fall and/or
near fall. The median (q1-q3) TG score was 2 (1-2) for those that
experienced falls and/or near falls and 0 (0-1) for those without any
incidents. Logistic regression (controlling for age, gender, UPDRS
III and daily LDE dose) showed that TG score 2 (OR, 5.40; 95% CI,
1.75-16.70; P=0.003) predicted falls and/or near falls. TG score 1
was not significant (OR, 2.24; 95% CI, 0.84-5.98; P=0.109). This
model correctly classified 39/63 (62%) of individuals with falls and/
or near falls and 64/78 (82%) of individuals without any incidence,
and accounted for 32% of the variability between groups.
Conclusions: The results suggest that TG may be able to predict
a future fall and/or near fall in people with mild PD. Further studies
using larger samples are needed for firmer conclusions and establish-
ment of additional properties in relation to other assessments.
263
Hepatic safety of opicapone in Parkinsons disease patients
N. Lopes, J. Ferreira, A. Lees, H. Gama, A. Santos, C. Oliveira, R.
Costa, T. Nunes, J.F. Rocha, P. Soares-da-Silva (S. Mamede do
Coronado, Portugal)
Objective: Evaluate the effects of opicapone (OPC) on hepato-
biliary function.
Background: OPC, a novel once-daily peripheral COMT-
inhibitor, has shown to be safe and effective in reducing OFF-time
in Parkinsons disease (PD) patients with motor fluctuations.
Methods: Safety data from two multicentre, double-blind, rando-
mised, placebo- and active-controlled studies (BIPARK I and II)
were pooled. Hepatic-related adverse events and changes from base-
line in hepatic laboratory parameters were evaluated.
Results: The pooled safety set included 509 subjects treated with
OPC (25 or 50mg) and 257 with placebo. There were no relevant
changes from baseline to endpoint in mean values for hepatic laboratory
parameters in any treatment group. The incidence of potential clinically
important values (alanine aminotransferase  3xULN, aspartate amino-
transferase  3xULN, total bilirubin  2xULN, alkaline phosphata-
se  1.5xULN) was similar for placebo and OPC groups. Hepatic-related
adverse events were reported by 2.0% of patients in OPC groups com-
pared to 3.5% in placebo. No cases of potential Hys law, hepatitis,
hepatic failure or other severe hepatic injuries occurred in OPC groups.
Conclusions: No association of OPC with clinically relevant
effects on hepatobiliary function is apparent.
264
Exploratory efficacy of opicapone in combination with dopamine
agonists or MAO-B inhibitors on the treatment of motor
fluctuations in Parkinsons disease
N. Lopes, J. Ferreira, A. Lees, R. Costa, A. Santos, C. Oliveira, R.
Pinto, T. Nunes, J.F. Rocha, P. Soares-da-Silva (S. Mamede do
Coronado, Portugal)
Objective: Evaluate the efficacy of opicapone (OPC) in patients
with Parkinsons disease (PD) and motor fluctuations receiving levo-
dopa plus dopamine agonists (DA) or MAO-B inhibitors (MAO-Bi) .
Background: OPC, a novel once-daily peripheral COMT inhibi-
tor, has shown to be safe and effective in reducing OFF-time in PD
S101
patients with motor fluctuations. Patients with PD are commonly
treated with DA or MAO-Bi in association with levodopa.
Methods: Efficacy data from two multicentre, double-blind, rand-
omised, placebo- and active-controlled studies (BIPARK I and II)
was pooled and analyzed by concurrent use of DA or MAO-Bi at
baseline (yes/no). Outcome efficacy measures included the change
from baseline to endpoint in absolute OFF-time and the OFF- and
ON-time responder rates ( 1 hour).
Results: DA were used by 521 (69%) patients (N=185, 158 and
178 for placebo, 25mg- and 50mg-OPC, respectively) and MAO-Bi
by 151 (20%) (N=49, 46 and 56, for placebo, 25mg- and 50mg-
OPC, respectively). The mean placebo-adjusted OFF-time reduction
was -35.5 min (p50.0329) and -25.7 min (p50.4120) for 25mg-OPC
plus DA or MAO-Bi, respectively; -54.6 min (p50.0007) and 63.7
min (p50.0326) for 50mg-OPC plus DA or MAO-Bi, respectively.
Consistently, higher proportions of patients receiving either 25mg- or
50mg-OPC achieved the OFF- and ON-time responders endpoint
(p<0.05 for 50mg-OPC).
Conclusions: OPC improves motor fluctuations in levodopa-
treated PD patients regardless of concomitant use of DA or MAO-
Bi.
265
The ability of Parkinsons disease patients to use dry powder
inhalers during off periods
M. Luinstra, W.A.W.F. Rutgers, H. Dijkstra, F. Grasmeijer, P.
Hagedoorn, J. Vogelzang, H.W. Frijlink, A.H. de Boer (Groningen,
Netherlands)
Objective: The aim of our study was to assess the applicability
of Parkinsons patients to use a dry powder inhaler correctly during
their off periods, when motor function impairments like tremor, bra-
dykinesia and rigidity are present.
Background: Because of its expected rapid onset of effect, pul-
monary administration of levodopa is an interesting alternative to
orally administered levodopa for the rescue treatment of Parkinsons
disease patients in an off period. The inspiratory flow manoeuvre
performed by a patient is crucial for the performance and the suit-
ability of a dry powder inhaler and is therefore assessed.
Methods: After obtaining written informed consent, 15 patients
were asked to postpone there scheduled levodopa dose in order to
become off.
Before the inhalation procedure started, the extent of the off state
was scored by a neurologist, by using the (old) UPDRS motor sec-
tion 3. Patients were asked to simulate an inhalation manoeuvre
through a test inhaler (without drug), with three different resistances
to air flow, in order to obtain information about their ability to inhale
correctly through an inhaler during off periods. The study was
approved by the ethics commitee.
Results: Two patients did not become off and were therefore not
included for analysis. Measurements with the other 13 Parkinsons
patients during off periods showed that patients were able to perform
an inhalation manoeuvre correctly, hold their breath for an accepta-
ble time to facilitate deep lung deposition and create the pressure
drop necessary to achieve a proper dispersion of a dry powder for-
mulation, like levodopa.
Conclusions: The inhalation data gathered in this study set the
limits within which levodopa dry powder inhalation products for the
rescue treatment of Parkinsons disease patients in an off period
should effectively disperse and emit the required dose. They are,
therefore, essential in any development activities towards such a
product. The demonstrated ability of Parkinsons disease patients in
an off period to perform an inhalation manoeuvre is expected to be
sufficient for the successful development of levodopa dry powder
inhalation products for the rescue treatment during an off period of
this particular patient group.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S102 POSTER SESSION

266 TABLE 1. Patient demographics and clinical characteristics

Heterogeneity among patients with Parkinsons disease: Cluster Clinical variables Total (N= 1510)
analysis and genetic association
L. Ma, P. Chan, Z. Gu, F. Li, T. Feng (Beijing, Peoples Republic of Age in years (SD; range) 66.7 (10.5; 2491)
China) Age at onset in year (SD; range) 57.6 (10.9;1285)
Gender (M:F) 1.5:1
Objective: The objectives of our study were to 1) identify PD Disease duration in months 63.9 (51.9; 2.0535.2)
subtypes based on motor and non-motor features by using CA in a (SD; range)
large number of Chinese PD patients and 2) evaluate the association UPDRS-I 2.3 (2.2; 014)
between subtypes and variants in LRRK2 (R1628P) and GBA UPDRS-II 11.8 (6.7; 047)
(L444P) genes. UPDRS-III 26.3 (14.8; 1103)
Background: The clinical heterogeneity of Parkinsons disease UPDRS-IV 3.6 (4.9; 029)
(PD) reveals the presence of several PD subtypes. Apart from empir- Tremor score 0.65 (.56; 03.6)
ical classification, statistical analysis is a crucial way to identify the Rigidity score 1.1 (.85; 04)
different PD subtypes, among which cluster analysis (CA) is com- Hypokinesia score 1.2 (.70; 0.114)
monly used. However, CA in large number PD patients is still PIGD 0.99 (.72; 04)
lacking. Total tremor score/Total non-tremor 0.95 (1.0; 015.2)
Methods: A k-means CA was performed in 1,510 (914 men and score
596 women) Chinese PD patients from the Chinese National Consor- Progression rate 1.2 (1.7; 0.0517.9)
tium on Neurodegenerative Diseases(CNCPD; www.chinapd.cn). The MMSE 26.8 (3.4; 1030)
database contained information on patient demographics, disease pro- HAMD 10.0 (9.1; 066)
gression, motor and non-motor symptom scales. Scores such as PSQI 6.5 (4.3; 019)
tremor, hypokinesia, rigidity and postural instability/gait disorder Constipation 0.59 (0.49; 01)
(PIGD) which were extracted from UPDRS score were used to eval-
uate clinical phenotypes. The analyzed data included age of disease UPDRS: Unified Parkinsons disease Rating Scale; MMSE: Mini
onset, disease progression, stage (HY), motor evaluating scores Mental State Examination; HAMD: Hamilton rating scale for depres-
(tremor, hypokinesia, rigidity, PIGD) and non-motor evaluating sion; PSQI: Pittsburgh sleep quality index.
scores (cognition/MMSE, depression/HAMD, sleep disorder/PSQI,
constipation scores). Pearson correlation analyses were performed to
eliminate uninformative characteristics. Blood samples from 852
patients were obtained for genetic analyses of LRRK2 and GBA. non-motor disturbances; and subtype 4 was tremor-dominant with
Genotypic associations between various subtypes and genetic var- slow disease progression (TD-SP, n5 199; 13.2%).
iants were examined using chi-square test. Subtypes 1, 2, and 4 had similar mean age of onset. No associa-
Results: The demographics and clinical characteristics of 1510 tions were identified between polymorphisms in LRRK2 (R1628P)
PD patients were showed in table 1. and GBA (L444P) genes and the four subtypes (P > 0.05).
We identified four different subtypes: subtype 1 was non-tremor Conclusions: Four distinct PD subtypes were identified by cluster
dominant (NTD, n5 472; 31.3%); subtype 2 had a rapid disease pro- analysis: NTD, RDP-LO, BPM and TD-SP. Polymorphisms in
gression with old onset (RDP-LO, n5 56; 3.7%); subtype 3 had LRRK2 (R1628P) and GBA (L444P) did not contribute to the PD
benign pure motor characteristics (BPM, n5 783; 51.9%) without subtypes.

TABLE 2. Characteristics of the four clusters (post hoc analysis)

Cluster 1:NTD Cluster 2:RPD-LO Cluster 3:BPM Cluster 4:TD-SP P-value
N (%) 469 (31.1%) 67 (4.4%) 778 (51.5%) 196 (13.0%)
Age (years) 68.2 (9.6) 67.9 (8.4) 67.4 (9.3) 67.6 (9.6) <0.001
Age at onset (years) 57.4 (11.0) 63.9 (9.7) 57.3 (10.7) 57.0 (11.1) <0.001
Disease Duration (months) 86.0 (58.2) 7.1 (3.6) 57.7 (42.5) 54.8 (54.7) <0.001
HY stage 2.7 (0.7) 1.9 (0.6) 1.8 (0.6) 1.5 (0.5) <0.001
UPDRS-I 3.5 (2.6) 2.6 (2.1) 1.8 (1.7) 1.1 (1.4) <0.001
UPDRS-II 17.8 (7.0) 11.7 (5.0) 9.6 (4.1) 6.4 (3.3) <0.001
UPDRS-III 42.3 (13.1) 28.7 (10.5) 19.7 (7.8) 13.4 (7.0) <0.001
UPDRS-IV 4.6 (4.7) 3.2 (5.0) 3.2 (5.1) 2.5 (4.7) <0.001
Tremor 1.0 (0.7) 0.7 (0.5) 0.4 (0.4) 0.7 (0.4) <0.001
Rigidity 1.8 (0.8) 1.3 (0.8) 0.8 (0.6) 0.3 (0.4) <0.001
Hypokinesia 1.8 (0.7) 1.2 (0.6) 0.9 (0.4) 0.5(0.3) <0.001
PIGD 1.7 (0.8) 1.0 (0.5) 0.7 (0.4) 0.3(0.3) <0.001
Motor phenotype score 0.7 (0.5) 0.8 (0.5) 0.7 (0.5) 2.7 (1.7) <0.001
Progression rate 0.8 (0.6) 4.8 (2.4) 0.5 (0.5) 0.4 (0.4) <0.001
MMSE 24.9 (4.1) 25.5 (4.3) 27.7 (2.4) 27.8 (2.5) <0.001
HAMD 15.9 (10.6) 10.7 (8.5) 7.6 (6.9) 4.9 (5.7) <0.001
vPSQI 9.0 (4.2) 5.9(4.0) 5.6 (3.8) 3.9 (3.0) <0.001
Constipation 0.8 (0.4) 0.5 (0.5) 0.5 (0.5) 0.4 (0.5) <0.001
Data are expressed as mean (SD).NTD: Non-Tremor Dominant; RDP-LO: Rapid Disease Progression with Late Onset; BPM: Benign Pure Motor;
TD-SP: Tremor-Dominant with Slow Progression. Variables included in CA are marked in bold.

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
267
Impulsivity after administration of the dopamine agonist
ropinirole
H.J. MacDonald, C.M. Stinear, J.P. Coxon, A.X. Ren, S.C. Cramer,
J. Kao, L. Macdonald, B. Snow, W.D. Byblow (Auckland, New
Zealand)
Objective: To identify mechanisms that contribute to the devel-
opment of impulse control disorders when taking commonly pre-
scribed dopaminergic medications for Parkinsons disease.
Specifically, we investigated the effects of ropinirole on objective
measures of cognitive and motor impulsivity in healthy adults, and
whether the effects were dependent on their genetically determined
dopamine profile.
Background: Routine administration of dopamine agonists for
Parkinsons disease can lead to poor inhibitory control, impulsivity
and impulse control disorders. We hypothesised that motor and cog-
nitive measures of impulsivity may be mediated by single nucleotide
polymorphisms of genes involved in dopamine regulation.
Methods: This was a double-blind, randomized, counter-
balanced, placebo-controlled clinical trial (ACTRN12614000046606)
to measure the effect of 0.5mg and 1.0mg doses of ropinirole on
motor and cognitive impulsivity. Our sample comprised healthy
adults of typical age for Parkinsons disease onset, i.e. aged 40 - 75.
At baseline participants completed the Barratt Impulsiveness Scale
(BIS-11) and provided a blood sample for genotyping of catechol-O-
methyltransferase, dopamine transporter genes, and dopamine D1,
D2 and D3 receptor genes (Pearson-Fuhrhop et al., PLoS One,
2013). Motor and cognitive impulsivity were objectively measured
using a response inhibition task and the Balloon Analogue Risk Task
respectively, following medication and placebo administration. Other
executive functions were assessed using components of the Central
Nervous System Vital Signs test battery.
Results: Investigators will be unblinded to medication status in
March 2015. We will report on the associations between measures of
impulsivity and dopamine gene score for each medication status.
Associations with composite measures of executive function will
also be reported.
Conclusions: This will be the first presentation of the trials find-
ings. The results are expected to inform whether behavioural meas-
ures, combined with genotyping, can be used to predict those people
at most risk of developing impulse control disorders, which in turn
could lead to more individualised treatment of Parkinsons disease.
268
High frequency repetitive transcranial magnetic stimulation can
improve the quality of life and depression in Parkinsons disease:
A randomized, double-blind, placebo-controlled study
A. Makkos, E. Pal, Z. Aschermann, J. Janszky, S. Komoly, N. Kov
acs
(P
ecs, Hungary)
Objective: Therefore, we conducted a randomized, double-blind,
placebo-controlled study to evaluate the efficacy of repetitive trans-
cranial magnetic stimulation (rTMS) over bilateral motor cortex Par-
kinsons disease (PD).
Background: The efficacy rTMS of on health-related quality of
life has not been evaluated in PD.
Methods: Forty-six patients with PD an mild-moderate depression
randomly assigned to active (n523) and sham (n523) rTMS. Two
patient in the sham group did not complete the protocol because of
reasons unrelated to the study. High frequency rTMS was applied
over the primary motor cortex for 10 days. An investigator blinded to
the treatment performed three video-taped examinations on each
patient: before stimulation (baseline), 1 day (short term), and 30 days
after treatment session ended (long-term effect). Primary endpoint was
the changes in quality of life measurement (PDQ-39) while secondary
endpoints included depression scales and Movement Disorders Society
Unified Parkinsons disease Rating Scale (MDS-UPDRS).
S103
Results: In the actively-treated group not only the health-related
quality of life improved (from 25.4 to 9.6 points, PDQ-39 summary
index, median values, p<0.001), but also the severity of depression
(from 17 to 7 points, Montgomery-Asberg Depression Rating Scale,
median values, p<0.001). We could also demonstrate an insignificant
improvement in MDS-UPDRS Motor Examination by 6 points
(p50.229). In the sham-treated group none of the examined tests and
scales improved significantly after sham stimulation.
Conclusions: Our results demonstrate the beneficial effects of
high frequency rTMS over the motor cortex on health-related quality
of life and depression in PD. However, this result should be con-
firmed in patients with severe depression by further clinical trials.
269
Management of camptocormia, anterotorticollis, and diplopia in
Parkinsons disease with osteopathic manual therapy and
physical therapy
J.D. Mancini, N. Caruana (Old Westbury, NY, USA)
Objective: To treat camptocormia, anterotorticollis, and diplopia
in a patient with Parkinsons disease (PD) utilizing osteopathic man-
ual therapy (OMT) and physical therapy.
Background: Camptocormia is a severe flexion of the trunk in
the sagittal plane, and may be dependent on position. It most fre-
quently presents with PD, further restricting motor function. Campto-
cormia responds poorly to dopaminergic treatment or deep brain
stimulation, but may be responsive to apomorphine. Diplopia can be
caused by oculomotor dysfunction or poor convergence. OMT
involves using the hands to diagnose and treat joint and soft tissue
disorders to restore healthy physiology, and may be applied to disor-
ders of motor function.
Results: An 82-year-old male presented with PD, camptocormia,
anterotorticollis, and diplopia in a more upright position. The physi-
cian physical exam showed diplopia when looking up and left, pectus
excavatum, sternal intraosseus strain, hypertonic left sternocleido-
mastoid and abdominal muscles, bradykinesia, camptocormia to 90 ,
shuffling gait, anterotorticollis, increased anterior cervical fascial ten-
sion. Somatic dysfunctions of the head were superior vertical and a
left-sided torsion to the sphenobasilar synchondrosis, restriction and
myofascial hypertonicity of the left occipital-mastoid suture, and
restriction of the frontal bone sutures. Initial physical therapy exami-
nation further revealed bilateral trendelenberg, decreased reciprocal
arm swing, right scapular winging and protraction, decreased range
of motion in the extremities. The OMT techniques cranial, myofas-
cial release, and balanced ligamentous tension were applied to the
ventral body from the coronal suture to the pubic symphasis, spheno-
basilar synchondrosis, second cervical vertebra, and left quadratus
lumborum muscle once weekly for 6 weeks. Physical therapy empha-
sized the use of proprioceptive neuromuscular facilitation to the cer-
vical flexors and pectoral muscles and neuro re-education. Patterns
were introduced to recruit core musculature and improve postural
awareness.
Conclusions: The diplopia resolved. There was marked improve-
ment in the joint range-of-motion in the spine and extremities and in
posture. The combination of OMT and physical therapy was a safe
and non-invasive way to improve posture and mobility in this patient
with PD, camptocormia, anterotorticollis, and diplopia.
270
Use of Cuban recombinant human erythropoietin in Parkinsons
disease treatment
A. Mario, P. Ivonne, B. Ma Luisa, M. Liliam, V. Pedro (Havana,
Cuba)
Objective: Assess safety and possible neuroprotective effect of
iorEPOCIM in a group of Parkinsons disease patients.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S104 POSTER SESSION
Background: Recombinant human erythropoietin is used primar-
ily to treat anemia. There is evidence of its neuroprotective capacity
from preclinical studies in Parkinsons disease and other neurodege-
nerative diseases. Recombinant human erythropoietin produced in
Cuba (ior-EPOCIM) is registered and approved for use in humans in
Cuba and in a number of other countries.
Methods: A three-phase exploratory study (proof of concept) was
conducted: preliminary assessment, treatment (weeks 15), and post-
treatment (weeks 635). Participants were 10 Parkinsons disease
patients (8 men, 2 women) from the outpatient clinic at the Interna-
tional Neurological Restoration Center, all at least one year post onset,
aged 4765 years. The ior-EPOCIM was administered subcutaneously
in a once-weekly dose (60 IU/kg body weight) for five weeks.
Hematological parameters and blood pressure were also measured
because of their direct relationship to the medications action. To
evaluate possible neuroprotective activity, variables were included
related to patients motor function and cognitive and affective status,
measured using internationally recognized scales. All variables were
evaluated before, during and after treatment. Data were processed
using a fixed-effects linear model, with a repeated-measures design
(significance level p 0.05).
Results: Three patients experienced mild adverse events (precordial
discomfort and hypertension in one; leg fatigue in another; renal colic
in a third), with a possible causal relationship in the first two that was
neither life threatening nor required hospitalization. Hemoglobin was
the only hematological parameter that showed a growing and signifi-
cant increase (p < 0.001), but without reaching pathological levels.
The other variables presented clinically positive and statistically
significant changes compared to pretreatment assessment: motor func-
tion (p < 0.001), cognitive status (p < 0.001) and mood (p 5 0.013).
Conclusions: At the dosage used, ior-EPOCIM was safe and well
tolerated in these Parkinsons disease patients. Further studies are
needed to corroborate these results and evaluate the medications
possible neuroprotective effect.
271
Systemic plasma biomarkers as a tool to help assess the efficacy
of NBIA clinical trials; results from a pilot trial of deferiprone
chelation to treat a case of PARK14 Parkinsonism/PLA2G6
associated neurodegeneration (PLAN)
M. Minkley, M. Praschberger, A. Jackson, D. Smith, N. Sweeters, C.
Borchers, E. Vichinsky, P. Macleod, P. Walter (Victoria, BC, Canada)
Objective: Systemic plasma biomarkers were used as a tool to
determine the efficacy of deferiprone in a pilot study of iron chela-
tion therapy in a patient with PARK14/PLAN.
Background: Current understanding of systemic biomarkers in
Parkinsons disease and Neurodegeneration with Brain Iron Accumu-
lation (NBIA) disorders is limited. These markers can potentially be
used as diagnostic tools to assess disease severity and evaluate the
outcome of clinical trials; including unique therapies such as deferi-
prone, an iron chelator, which, based on preliminary trials, may mobi-
lize accumulated brain iron and offer symptomatic improvement to
patients.
Methods: The PLAN patient is a 29 year old male with a hetero-
zygous mutation in the PLA2G6 gene that was treated following a 5
year history of progressive, early-onset Parkinsonism. Samples were
studied at baseline and over the course of 37 weeks of deferiprone
treatment (30mg/kg). C-Reactive Protein (CRP), as well as a hemato-
logical panel were measured using laboratory services. Inflammation
(IL-6) was measured using ELISA. Oxidative stress markers malon-
dialdehyde (MDA) and 4-hydroxynonenal (4-HNE) were measured
using an N-methyl-2-phenylindole based assay. Plasma proteins were
measured using multiplex multiple reaction monitoring proteomics.
Results: The patient had increased systemic inflammation at base-
line, including plasma IL-6 that was 4 times higher than control, an
elevated CRP of 4.0 ug/ml and Lipocalin-2 (NGAL) was increased
by 62%. The patient also had a 30% increase in systemic oxidative
Movement Disorders, Vol. 30, Suppl. 1, 2015
stress (MDA and 4-HNE). Over the course of 37 weeks of deferi-
prone treatment IL-6 was reduced by 13%, CRP returned to the nor-
mal range (2.0ug/ml) and MDA was reduced by 16%, however, in 6
months of therapy there was no change in neurodegenerative symp-
toms. Additional biomarker studies in NBIA patients are ongoing.
Conclusions: During deferiprone therapy, biomarker analysis
revealed a reduction in oxidative stress and inflammation in the
absence of any significant change in the clinical presentation of the
disease. Based on previous trials, we suggest that longer treatment
regimes (greater than 37 weeks) and earlier intervention with therapy
may be two important factors in the success of deferiprone in
improving neurodegenerative symptoms.
272
Patient perceptive feedback regarding participation in a
rehabilitation program and its relation to adherence in
Parkinsons disease
T.M. Mohammad, A. Mujtaba, R.A.l. Angari, N.A.l. Shammari,
A.A.A.l. Quraishi, M.S. Bashir, H. Khalil, J.A. Bajwa (Riyadh, Saudi
Arabia)
Objective: To examine patients perceptive feedback about their
participation in a rehabilitation exercise program and association
with their adherence in a cohort of Parkinsons disease (PD) patients.
Background: The benefits of physical rehabilitation in PD are well
documented. Adherance to the prescribed program would be a vital
component to obtain benefits. Patients perceptive feedback can be
important in determing adherance as active involvement of the patient
is essential to the success of the rehabilitation excercise program.
Methods: PD subjects who were referred to rehabilitation therapy at
King Fahad Medical City, Riyadh, Saudi Arabia were asked to attend an
intensive program of an hour long, 4-session weekly for a period of 4
weeks. Following the completion of the program or discontinuation (i.e.
in cases of dropout) a phone survey was completed to specifically capture
subjects perceptive feedback about their participation in the program
(i.e. satisfaction with logistics, appointment, therapist and exercises, per-
ceived improvement and compatibility of the program to the subjects
daily living). Adherence rate and subjects responses on the survey were
dichotomized into categories. Chi-square test was used accordingly to
determine the significant relationship among categorical variables.
Results: Data was collected from 44 subjects (mean age6 SD,
58.8 6 11 years; Hohen & Yahr mean 6 SD, 2.8 6 1.02 units). 53%
of the subjects felt that the program was compatible to their actives
of daily living. At least 45% of the participants perceived improve-
ment in either eating, drinking, walking, self care daily prayers and
activities of daily living. Significant association was noted between
number of attended sessions (i.e. adherence rate) and subjects per-
ceived improvement in activity of daily living (P <0.05). Addition-
ally, satisfaction with all aspects of the program including therapy
logistics, appointment, therapist and exercises was associated with
the number of attended sessions (P<0.0001).
Conclusions: Patient perceived improvement in activity of daily
living as well as satisfaction with a rehabilitation exercise program
are all potentially important determinant of exercise adherence in
people with PD. This data suggests that success of a rehabilitation
program is not only based on professional evaluation and treatment
but also on patients perception and satisfaction.
273
Perception toward exercise and its relation to rehabilitation
exercise adherence in Parkinsons disease
T.M. Mohammad, R.A.l. Angari, A. Mujtaba, N.A.l. Shammari,
A.A.B. AlQurashi, M.S. Bashir, H. Khalil, J.A. Bajwa (Riyadh, Saudi
Arabia)
 POSTER SESSION
Objective: To identify if personal factors or perceptions about
exercise in Parkinsons disease (PD) can influence adherance to a
clinic-based supervised rehabilitation exercise program.
Background: The benefits of exercise in PD are well docu-
mented. Adherance to the prescribed exercises is critical to obtain
benefits. In comparision with research addressing adherance to medi-
cations, there is very limited data on quantifying adherance in the
PD population to prescribed exercise interventions.
Methods: PD subjects who were referred to rehabilitation therapy
at King Fahad Medical City, Riyadh, Saudi Arabia were asked to
attend an hour long, 4-session weekly exercise program for a period
of 4 weeks. Following the completion of the program or discontinua-
tion (i.e. in cases of dropout) a phone survey was completed to spe-
cifically capture subjects overall perception and practices toward
exercise (i.e. importance of exercise for subjects before and after
being diagnosed with PD, frequency and duration of weekly exer-
cise). Adherence rate, subjects responses on the survey and all col-
lected personal data including age, gender, education and duration of
PD were dichotomized into categories. Chi-square test was used
accordingly to determine the significant relationship among categori-
cal variables.
Results: Data was collected from 44 subjects (mean age6 SD,
58.8 6 11 years; Hohen & Yahr mean 6 SD, 2.8 6 1.02 units). Only
14 subjects completed more than 50% of the total number of pre-
scribed sessions. None of the personal factors associated significantly
with the adherence rate. Out of all the responses regarding percep-
tion toward exercise only those related to the importance of exercise
after PD diagnosis associated significantly with the adherence rate.
(P=0.04).
Conclusions: Awareness of benefits and outcome expectations as
reflected by the response on how exercise was important for PD
subjects after being diagnosed with PD are potentially important
factors in promoting adherence to exercise program. These may be
important issues that needs to be addressed by clinicians working
with PD. Interventional strategies that facilitate exercise adherence in
this population requires further investigation.
274
Is excercise compliance, perception and practices different
among Parkinsons disease motor subtypes?
T.M. Mohammad, A. Mujtaba, R. Al-Angari, N. Al-Shammari, A.A.
Al-Qurashi, M.S. Bashir, H. Khalil, J.A. Bajwa (Riyadh, Saudi
Arabia)
Objective: To identify effect on exercise compliance, perception
and practices in motor sub types of Tremor-Dominant (TD) and
Akinetic-Rigid (AR) Parkinsons disease (PD).
Background: Two main clinical motor subtypes can be distin-
guished in PD; a Tremor-Dominant (TD) and an Akinetic-Rigid
(AR) subtype with known different progression and treatment out-
comes. No studies as of yet analyzed the effect on exercise compli-
ance, perception and practices in these 2 motor subtypes of PD.
Methods: PD subjects who were referred to rehabilitation therapy
at King Fahad Medical City, Riyadh, Saudi Arabia were asked to
attend an intensive program of an hour long, 4-session weekly for a
period of 4 weeks. Compliance rate was calculated as the number of
attended sessions in relation to the number of prescribed sessions. A
phone survey was completed to capture subjects perception and
practices toward exercise in general and their perceptive feedback in
specific about their participation in the program. Compliance rate
and subjects responses on the survey were dichotomized into catego-
ries. Cramer V test was used accordingly to determine the significant
association among categorical variables.
Results: Data was collected from 22 AR and 22 TD subjects
(mean age 6 SD: 58.1 6 15.5, 60.7 6 11.3 years respectively). 30
subjects perceived improvement in one or more of activities of daily
living; of those 60% were of AR subtype. Cramer V test showed a
significant association between the motor-subtype and the number of
S105
attended sessions for those subjects who perceived improvement
with a favorable response toward the AR subtype group. Addition-
ally, the PD motor subtypes associated significantly with 5 other
parameters including importance of exercise for family before and
after PD diagnosis, importance of exercise to PD subjects themselves
after PD diagnosis and frequency and duration of weekly exercise
with a response rate that was higher in the AR subtype group
(P<0.05).
Conclusions: PD motor subtypes may exhibit different effect on
exercise compliance, perceptions and practices in this population
with a favorable response rate in the AR subtype group. Further
studies to explore the underpinning of related factors are warranted.
Future longitudinal studies to examine different responses to exercise
interventions in these 2 motor sub types are also required.
275
Objective gait analysis in Parkinsons disease reflecting the effect
of levodopa
B. Mondal, S. Choudhury, P. Chatterjee, M.U. Kulsum, S.S. Anand,
D. Naskar, H. Kumar (Kolkata, India)
Objective: To 1. study the gait parameters in PD patients as com-
pared to healthy volunteers using a validated electronic walkway.
2.evaluate and compare the gait parameters of PD Patients in ON
and OFF levodopa state.
Background: One of the hallmark symptoms of Parkinsons dis-
ease (PD) is gait instability. As an overall clinical outcome the gait
stability improve following levodopa (L-dopa) therapy but the
response remains inconsistent. We have undertaken this study for a
precise gait analysis among PD patients in ON and OFF phase. We
also intended to identify gait variables which respond and those
which do not respond to L-dopa therapy.
Methods: In this analytical cross sectional study we compared
the gait parameters in ON & OFF phases of seventy consecutive PD
patients using automated electronic walkway. L-Dopa response was
assessed using Unified Parkinsons disease Rating Scale (UPDRS).
The gait parameters of 70 PD patients and 37 healthy volunteers
were compared using Mann Whitney U Test.
Results: The mean age of 70 patients was 64.56 (SD 8.81) years
and 75.7% were male. There were significant increase in mean
cadence {D cadence= 1.76 steps/second (p value 0.013)} and veloc-
ity {D velocity= 11.64 cm/sec (p value 0.0001)} following L-Dopa
administration. Most of the temporal and spatial gait parameters
have shown a significant improvement with the administration of L-
Dopa, with an exception of swing time and single support time. Var-
ious gait parameters are significantly different between PD patients
and healthy volunteers including step count, ambulation time, veloc-
ity, step length, stride length, swing time etc. However, mean
cadence, step time, cycle time, stance time, foot length and foot
width are not statistically different in PD patients compared to
healthy volunteers.
Conclusions: In the studied cohort of PD patients, Velocity,
stride length, cadence, single support and double support were sensi-
tive to L-dopa where as swing time and single support time did not
response to L-dopa. Swing time was regarded as a speed-
independent marker of steadiness and fall risk in previous research.
Suggested non-improvement of swing time or single support time
may reflect the incomplete resolution of gait instability and persistent
fall-risk in ON phase among most PD patients.
276
Evaluation of sleep disorders in patients with Parkinsons disease
after administration of melatonin
E.W. Morales-Sanchez, G. Lopez-Armas, R.E. Gonzalez-Casta~ neda,
G.G. Ortiz, F.J. Jimenez-Gil (Tonala, Mexico)
Movement Disorders, Vol. 30, Suppl. 1, 2015
S106 POSTER SESSION
Objective: Assess sleep disorders in patients with Parkinsons s
disease after continuous administration of melatonin for twelve
months.
Background: Parkinsons disease is caused by selective degener-
ation of dopaminergic neurons in the CNS interrupting the nigrostria-
tal pathway and is characterized by the presence of interneuron
inclusions known as Lewy bodies.
The alterations caused by dopaminergic deregulation affects along
brain anatomy, seeing changes that interfere in the regulation and
altered sleep-wake patron.
Under physiological conditions, sleep depends on circadian
rhythms which ones are synchronized by daily light-dark cycles and
the involvement of different brain structures such as the suprachias-
matic nucleus and pineal gland. This gland is particularly important
because it plays a central role in the rhythmic production of
melatonin.
There are many diseases that alter sleep and generate effects on
the prefrontal cortex, amygdala and hippocampus circuit that causes
deterioration of cognitive functions (learning and memory), increased
anxiogenic behavior type among others. Patients with Parkinsons
disease increases these anomalies of sleep disorders mostly insomnia
and daytime sleepiness.
Methods: Selected clinical trial patients with Parkinsons disease,
sleep disorders evaluation was performed by applying the Epworth
Sleepiness Scale at baseline and at the end (12 months) after supple-
mentation of melatonin (group MEL n56) or placebo (group Placebo
n57).
Results: Statistical analysis shows changes between melatonin
supplementation group has a p 5 0.0409 which shows significant
changes between initial and final measurement baselin-end, and
changes in.
Conclusions: Melatonin supplementation modifies sleep disorders
in patients with Parkinsons disease in particular lengthens the night
sleep, evidently decreased daydream whith better quality life.
277
Response to acute dopaminergic challenge of lip and jaw tremor
predicts Parkinsons disease diagnosis
P. Morisset, M. Wilken, S. Fari~ na, D. Cerquetti, M. Rossi, M.
Merello (Buenos Aires, Argentina)
Objective: To evaluate lip/jaw tremor response to acute dopami-
nergic challenge and its relationship to subsequent Parkinsons dis-
ease (PD) diagnosis.
Background: Lip/jaw tremor can be an early sign of PD, other
Parkinsonisms, essential tremor and hereditary geniospasm. Its
response to dopaminergic therapy and further predictive clinical
diagnosis has been scarcely described.
Methods: We conducted a retrospective review of medical
records from patients with a short-onset Parkinsonism that were sub-
mitted to acute levodopa challenge for clinical prediction of sus-
tained long-term dopaminergic response and evaluated with MDS-
UPDRS-III between January 2010 and August 2014. Data was col-
lected on demographics, levodopa response (a modification of MDS-
UPDRS-III  30% was considered a positive test and a reduction in
at least one point in lip/jaw tremor subscore was considered a posi-
tive response of lip and jaw tremor), clinical manifestations and final
clinical diagnosis after at least one-year follow-up.
Results: A total of 559 patients were evaluated, of which 28
(5%) patients with lip/jaw tremor were identified. Thirteen (46%)
had responsive lip/jaw tremor, of which 11 (85%) were in the con-
text of a positive response to levodopa acute challenge and a final
PD diagnosis when fulfilling all UKPDSBB criteria at one-year fol-
low-up. Within non-responsive lip/jaw tremor patients, all 15 pre-
sented a negative response to acute levodopa challenge and all but
one a non-PD diagnosis at one-year follow-up, who was diagnosed
with essential tremor plus PD. A responsive lip/jaw tremor to acute
levodopa challenge obtained a sensitivity of 92% and a specificity of
Movement Disorders, Vol. 30, Suppl. 1, 2015
93% with a positive and negative likelihood ratio for a final PD
diagnosis of 13.9 and 0.1, respectively. Multivariate analysis revealed
that the presence of hand rest tremor (p<0.0001), rigidity (p50.03),
limb bradykinesia (p50.03) and total response to levodopa acute
challenge (p50.001) were independent factors related to lip/jaw
tremor response. No PD patient had isolated lip/jaw tremor, whereas
5 out of 15 non-PD patients (33%) presented lip/jaw tremor without
arm or leg rest tremor.
Conclusions: Lip/jaw tremor, although infrequent, can be an
early sign of PD. It was usually accompanied with hand or leg rest
tremor. Its positive response to acute levodopa challenge has a high
sensitivity and specificity for PD diagnosis.
278
Single center experience for levodopa-carbidopa intestinal gel
pump implantation without naso-duodenal tube trial
A. Mujtaba, A. Al-Lehibi, S. Ahmad, K. Al-Sayari, A. Al-Mtawa,
M.A. Wani, S. Nahrir, T.M. Mohammad, N. Hassan, J.A. Bajwa
(Riyadh, Saudi Arabia)
Objective: To report a case series of Levodopa-Carbidopa Intesti-
nal Gel (LCIG) pump implantation without Naso-Duodenal tube
(NDT) trial.
Background: Parkinsons disease (PD) is a progressive neurode-
generative disorder. The diagnosis is primarily based on the history
and examination. Treatment of advanced levodopa-responsive PD
with severe motor fluctuations and dyskinesias requires utilization
of advanced therapy options like LCIG pump. Appropriate patient
selection based on clinical history, UPDRS off and on scores is
required for clinical efficacy from LCIG pump. The methodology is
similar to how we select patients for Deep Brain Stimulation.
A positive clinical response to LCIG administered via a tempo-
rary NDT is required per guidelines before a permanent tube is
inserted. NDT can be associated with abdominal pain, vomiting and
discomfort related to the tube making therapeutic trial significantly
challenging.
For long-term administration after a positive therapeutic trial, the
gel is administered through a portable pump connected directly to
the third part of jejunum beyond the ligament of trietz by a perma-
nent tube G/J type (gastro/Jejunostomy) inserted via percutaneous
endoscopic gastrostomy. The dose is adjusted through the pump to
an optimal clinical response for each individual patient.
Methods: A retrospective observational chart review study was
conducted to review outcomes of direct implantation of LCIG pump
without prior NDT trial with a sample size of six patients. The first
patient had NDT trial followed by LCIG pump implantation but sub-
sequent 5 patients had direct LCIG pump implantation with only
meeting appropriate patient selection criterias.
Results: Patients 2-6 in the table showing pre and post UPDRS
benefits of direct LCIG pump implantation without NDT trial.
UPRDS PRE AND POST LCIG PUMP IMPLANTATION
UPDRS UPDRS
OFF ON IMPROVEMENT
Patient BEFORE AFTER PERCENTAGE
1 73 38 48% 2 days post LCIG
2 36 17 53% I month post LCIG
3 77 40 48% 3 days post LCIG
4 43 19 56% 3 days post LCIG
5 35 09 74% 3 days post LCIG
6 70 36 49% 4 days post LCIG
Conclusions: Direct LCIG pump implantation without NDT trial
can be considered as an alternative method for appropriately selected
patients in experienced centers.
 POSTER SESSION
279
A 12-week bicycling training regimen improves gait in people
with Parkinsons disease
A. Nadeau, C. Duchesne, O. Lungu, M.E. Robillard, A. Bor e, F.
Bobeuf, A.L. Lafontaine, L. Bherer, J. Doyon (Montreal, QC,
Canada)
Objective: To asses the improvements of such an exercise pro-
gram on motor learning capacity, executive functions and gait
parameters in people with Parkinsons disease (PD) and age-matched
healthy control (HC), as well as to account for the moderating role
of the disease in this process.
Background: In PD, the dopaminergic system dysfunction is
often accompanied by a decrease in motor learning capacity, execu-
tive function impairments and alteration of gait patterns. Different
types of physical activity have been shown to effectively improve
these parameters in PD individuals. Yet, no study examined the
effect of a stationary bicycle training regimen designed to improve
aerobic capacity on these outcome measures.
Methods: Two groups of participants, comprising 19 PD patients
(Hoehn & Yahr 2) and 20 healthy adults, matched on age and sed-
entary level, were recruited and evaluated for their aerobic capacity,
gait pattern, executive functions and motor learning before and after
a 3-month bicycle training regimen (3x 1h/sem.).
Results: Aerobic capacity, inhibition and sequential motor learn-
ing improved significantly in both groups after the 3-month station-
ary bike exercise regimen, but only the PD patients improved
significantly their walking speed. In PD patients, but not in the
healthy group, the training-related increases in aerobic capacity and
sequential motor learning capacity correlated positively with the
improvement in walking speed. Also, only in PD group, both before
and after the training regimen, the cognitive and motor skill learning
measures correlated with each other.
Conclusions: Our results suggest that several motor and func-
tional parameters are improved through a 3-month stationary bicycle
training regimen, both in PD patients and healthy adults. Improve-
ment in various domains was particularly found in PD individuals,
suggesting that physical exercise does have a greater impact in this
population.
280
FS-ZONE. A multi-center, double-blind, phase II study of
pioglitazone in early Parkinsons disease
FS-Zone NINDS NET-PD Investigators (Chicago, IL, USA)
Objective: To assess the impact of pioglitazone on the progres-
sion of Parkinsons disease (PD) in a multicenter, double-blind, pla-
cebo-controlled non-superiority clinical trial.
Background: Pioglitazone, an FDA-approved agent for the treat-
ment of type 2diabetes is a thiazolidinedione (TZDs), a peroxisome
proliferator-activated receptor-gamma (PPAR-g) agonist. Preclinical
data in rodents and non-human primates models of Parkinsonism
demonstrate good CNS penetration and neuroprotective effect of pio-
glitazone at the FDA approved dose for human use. Based on that
data pioglitazone was selected for testing in Phase II clinical trial as
a potential disease modifying compound for PD.
Methods: Participants with the diagnosis of early PD on a stable
regimen of 1mg/day of rasagiline or 10mg/day of selegiline were
randomized 1:1:1 to either (1) 15 mg/day of pioglitazone, (2) 45 mg/
day of pioglitazone, or (3) matching placebo. The primary outcome
was the change in total Unified Parkinsons disease Rating Scale
(UPDRS) score between the baseline and 44 week visits.
Results: 210 subjects from 35 US sites were enrolled between
May 2011 and July 2013. The primary null hypothesis for each dose
arm was that the treatment mean change in UPDRS was less than or
equal to the placebo mean minus 3 points. Using a significance level
of 0.10, we rejected the null hypothesis for the 45 mg arm in favor
of futility (p50.09), but not for the 15 mg arm (p50.19). However,
S107
sensitivity analyses using alternative approaches to handling missing
data and using the completers only sample, suggested that the 15mg
dose may also be futile. Pioglitazone was generally safe in this popu-
lation. The biomarkers (reported in the companion poster) also failed
to demonstrate a separation of the active treatment arms from
placebo.
Conclusions: These findings suggest that pioglitazone at doses
studied here is unlikely to modify progression in early PD. Further
study of pioglitazone in a larger trial in PD is not recommended.
Considering preclinical data, it remains possible that another agent in
the class of PPAR-g agonists might be deserving of further
exploration.
281
Pharmacokinetic factors and levodopa-induced dyskinesia in
Parkinsons disease
T. Oeda, A. Umemura, S. Tomita, M. Kohsaka, K. Park, Y. Mori, H.
Sawada (Kyoto, Japan)
Objective: To clarify which pharmacokinetic parameters of
plasma levodopa concentration contribute to the development of
troublesome dyskinesia (TD) in patients with advanced-stage Parkin-
sons disease (PD).
Background: The first manifestation of dyskinesia in patients
with PD correlates significantly with levodopa intake. On the other
hand, continuous high concentration of plasma levodopa could turn
down levodopa-induced dyskinesia in advanced-stage patients using
intra-intestinal delivery equipment.
Methods: Plasma levodopa concentration at hourly intervals in
the daytime was measured in 100 PD patients. The concentration
was determined by high performance liquid chromatography with
electrochemical detection. We conducted a case-control study by
assigning subjects with TD (defined as 2 points on the Rush Dyski-
nesia Rating Scale) as cases and those without TD as controls. Clini-
cal background features and pharmacokinetic factors were compared
between the cases and the controls. The pharmacokinetic factors that
were associated with TD were identified in multivariate logistic
regression models.
Results: Twenty-six of the subjects had TD. Compared to the
controls, the cases were female dominant, had longer PD duration
and higher daily doses of levodopa per body weight (LD/BW).
Among the levodopa-pharmacokinetic variables, the proportion of
patients with troughs 3 times/day was significantly higher in cases
than in the controls (61.5% in cases and 27.0% in controls,
p50.004). A multivariate model revealed that female and trough
numbers, as factors, were significantly associated with TD, with
adjusted odds ratios (95% CI) of 12.5 (1.5-102.4) and 3.5 (1.2-10.0),
respectively; however, daily doses of LD/BW were not significantly
associated with TD.
Conclusions: The number of troughs in plasma levodopa concen-
tration was found to be more of a contributing factor than daily
doses of LD/BW in the development of TD.
282
Role of clinical nurse educators (CNEs) in levodopa-carbidopa
intestinal gel (LCIG) clinical studies in Parkinsons disease (PD)
E.M. Olson, E. Greene, K. Espay, R. Wagner, K. Chatamra, J.A.
Benesh, J.T. Slevin, A.J. Espay (North Chicago, IL, USA)
Objective: To describe a unique support network provided by
clinical nurse educators (CNEs) to study sites in the LCIG develop-
ment program for patients with advanced PD.
Background: LCIG is delivered via a percutaneous gastrojejunos-
tomy tube (PEG-J) to provide PD patients with more stable levodopa
levels. Execution of clinical trials requiring PEG-J placement for a
novel drug delivery system necessitated a unique multidisciplinary
model.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S108 POSTER SESSION
Methods: The sponsor contracted a clinical research organization
to provide monitoring services of CNEs and provided intensive
LCIG system training. The sponsor then assigned CNEs to study
sites to provide technical support for healthcare professionals
(HCPs); CNEs were not directly involved in patient care.
Results: CNEs technical expertise with PEG-J and LCIG con-
tributed to the design and development of training materials for
investigators, staff, and patients. CNEs trained site staff to use study
devices (PEG-J tubes and infusion pumps) and LCIG. In the endos-
copy suite, CNEs provided real-time support for gastroenterologists
during the initial PEG-J procedure and PEG and J-tube replacements.
Of the 425 PEG-J placements and LCIG dose titrations, CNEs were
present for 391 (92%). CNEs provided broad knowledge of titration
options to HCPs who were performing LCIG titrations. CNEs served
as liaisons between investigators, sites, clinical research associates,
and the sponsor, and functioned as a critical intermediary between
gastroenterologists and neurologists who were unfamiliar with stoma
evaluations. Due to their intermediary role at study sites, CNEs were
able to provide sites with insights and suggestions to resolve tube or
stoma issues. CNEs were the first point of contact for new sites with
regard to PEG-J procedures and LCIG titration and collaborated with
the sponsor to develop a dry-run model for study site initiation
(Figure 1).
[figure1]
Conclusions: Implementation of the CNE model provided bene-
fits to clinicians and clinical research sites, ultimately improving
the patient experience. Involvement of CNEs optimized and
streamlined site initiation, study/product monitoring, issue resolu-
tion, and communication within a multidisciplinary care model.
This approach could be considered for future studies of complex
drug delivery systems that require a multidisciplinary team to opti-
mize patient care.
Fig. 1. (282).
Movement Disorders, Vol. 30, Suppl. 1, 2015
283
Predictors of optimal dose of apomorphine injections: A
secondary analysis of the AM-IMPAKT trial
W. Ondo, S. Isaacson, M. Lew, F. Pagan (Houston, TX, USA)
Objective: To identify demographic, historical and clinical fea-
tures that predict the optimal dose of subcutaneous apomorphine
injections when used for morning akinesia in Parkinsons disease
(PD).
Background: Apomorphine is a potent but short acting dopamine
agonist that can be injected subcutaneously or as a continuous infu-
sion to achieve a rapid ON. Previous studies have not determined
any clear predictors of optimal dosing in individual patients, which
if found, could simplify the apomorphine initiation process.
Methods: The AM-IMPAKT trial evaluated apomorphine injec-
tions in PD subjects with delayed time to ON with first morning L-
dopa dosing. Optimal apomorphine dose was defined as the dose pro-
ducing levodopa-like motor improvement within 15 minutes without
intolerable adverse effects. To determine potential predictors of the
optimal dose, we performed a post-hoc correlation coefficient analy-
sis between optimal dose and 10 pre-defined factors including age,
gender, baseline L-dopa dose, dopamine agonist use, duration of PD,
reported number of months with morning akinesia, OFF UPDRS
scores, OFF Hoehn & Yahr score, experience of adverse events and
average daily time to first morning ON at baseline.
Results: The full efficacy analysis dataset included 88 patients
and full safety dataset included 127 patients. Optimal apomorphine
doses were 2 mg (n525), 3 mg (n512), 4 mg (n535), 5 mg
(n512), or 6 mg (n54). Optimal dose was not predicted by any of
the analyzed factors with the exception of a longer history of morn-
ing akinesia, which was associated with higher doses (p<0.05).
 POSTER SESSION
Conclusions: Optimal individual apomorphine dose for the treat-
ment of morning akinesia could not be predicted by demographic
nor clinical features with the exception of a longer history of morn-
ing akinesia. As the onset of morning akinesia might be a surrogate
for onset of motor fluctuations, these results suggest that higher apo-
morphine doses might be required to achieve optimal effect in
patients with longer history of fluctuating L-dopa response.
284
Apomorphine improves early morning motor function: Analysis
of secondary endpoints in the AM-IMPAKT trial
F. Pagan, S. Isaacson, W. Ondo, M. Lew (Washington, DC, USA)
Objective: To report secondary efficacy outcomes from the AM-
IMPAKT study.
Background: Primary efficacy analyses of the AM-IMPAKT
study have shown that apomorphine (APO) subcutaneous injection
significantly reduces time-to-ON in PD patients experiencing delayed
onset of their morning L-dopa dose. Secondary efficacy measures
also showed improvements in early morning treated subjects.
Methods: Subjects completed a 7-day Baseline Period where they
recorded initial time to ON with their morning dose of L-dopa. After
starting trimethobenzamide antiemetic therapy, they were injected
with 0.2 mg of APO and titrated to an optimal dose (defined as
achieving within 15 minutes at least 90% of post-levodopa motor
UPDRS). Patients then self-injected APO each morning upon awak-
ening for a 7-day Treatment Period. Objective secondary efficacy
outcomes were change from the initial titration pre-APO value (i.e.
during OFF) to 15 minutes post optimum APO dose (i.e. during ON)
in: UPDRS Parts III (motor) score and modified Hoehn & Yahr
stage. Improvements in subjective, rater and patient-reported second-
ary efficacy outcomes were assessed by comparison of Baseline vs.
Treatment Period scores in EQ-5D-3L, CGI-S, and PGI-S scales.
Results: 127 subjects were enrolled and included in the safety
population. The full analysis set included 88 patients. Mean 6 SD
UPDRS motor scores significantly improved from 35.53 6 9.79 at
pre-initial dose to 17.32 6 8.81 at 15 minutes post-optimum APO
dose (treatment effect 18.22 6 8.80; p<0.0001). Modified Hoehn &
Yahr scores also significantly improved from 2.79 6 0.66 to
2.31 6 0.54 (treatment effect 0.48 6 0.58; p<0.0001). All patient-
reported, subjective measures improved.
Conclusions: APO subcutaneous injection significantly improved
morning motor function by both objective and subjective measures
in PD patients experiencing delayed onset of their morning levodopa
dose. APO is a viable option for PD patients with morning akinesia.
285
Objective monitoring of motor function using the tablet-based
mobile application (iMotor): A feasibility study and patient
satisfaction survey
S. Papapetropoulos, A. Espay, I. Tsoulos, E. Mendoza, A.
Stavrakoudis, G. Mitsi (Wellesley Hills, MA, USA)
Objective: To assess the feasibility of objective quantification of
motor function through a tablet-based application (iMotor). To evalu-
ate patient satisfaction following the use of the application.
Background: Easy to use Technology-enabled Objective Meas-
ures (TOMs) can supplement standard clinical care and research
methodologies by providing rich, reliable and sensitive datasets dur-
ing and between office visits.
Methods: We conducted an IRB-approved, single-center, cross-
sectional evaluation of iMotor. Frequency, variability, duration and
velocity were assessed during finger tapping and hand pronation/
supination movements in healthy volunteers (HVs) and PD subjects.
Standard demographics and clinical data/scales were collected in a
HIPPA-compliant database. Hardware usability, software perform-
ance, and communication protocols were assessed. A 10-item patient
S109
satisfaction questionnaire using a standard 0-to-4 Likert scale was
administered.
Results: Twenty subjects completed the study (HVs N=10 and
PD N=10). For PD subjects, the mean age was 68 (SD =7.3) years,
mean disease duration was 5.6 (SD=4.48) years and mean H&Y
score was 1.9 (range 1-2.5). The mean 2-target finger tapping veloc-
ity in PD subjects was 15.2 (SD 2.25) cm/sec. The analyses of all
tasks differed between those with PD and those without. There were
no major hardware, software and communication protocol issues
throughout the study. The database was complete without missing
data. Most patients reported that the tests were fast and easy to per-
form and that they were willing to continue using iMotor (tablet-
based mobile application) at home. Study participants were very
interested in comparing their results with those of other subjects.
Conclusions: Measuring PD-associated motor function impair-
ment via iMotor is feasible and associated with high rates of satisfac-
tion. The potential value of iMotor as a remote at-home monitoring
tool and its impact on patient care is currently being evaluated.
286
E-DUO Study: Use of levodopa-carbidopa intestinal gel in
Spanish advanced Parkinsons disease patients. Discontinuation
factors subgroup analyses
J.C. Parra, F. Grandas, J.M. Arbelo, P. Mir (Madrid, Spain)
Objective: To compare baseline characteristics between patients
with APD who continued with LCIG (contLCIG) and patients who
discontinued LCIG (discLCIG) in order to identify factors associated
with LCIG discontinuation.
Methods: APD patients from 18 Spanish sites who had ever been
treated with LCIG between January 2006 and December 2011 were
included in this non-interventional and retrospective study.
Results: At baseline demographic characteristics were similar in
both groups. 52.0% and 53.7% of the patients were male and the
mean age was 70.1 6 8.0 and 71.6 6 9.4 years in contLCIG (n5123)
and discLCIG (n554), respectively and there was no statistical dif-
ference in Hoehn and Yahr and UPDRS score, both in ON and OFF,
motor and non-motor symptoms and number of previous treatments.
PD median duration was 13.1 years in contLCIG (min-max: 3.3-
35.4) and 13.5 years in discLCIG (min-max: 1.8-42.7).
Most frequent reasons to start LCIG treatment were increase in
frequency and duration of OFF-time (contLCIG: 85.4%; discLCIG:
87.0%), and lack of response to oral treatment (contLCIG: 62.6%;
discLCIG: 64.8%).
The main reasons for LCIG discontinuation were those related to
the medication (24.6%), exitus (21.7%) and disease progression
(15.9%).
Multivariate regression analysis showed that, at baseline, both
OFF-time (p50.0360; OR=1.028; CI95%=1.002, 1.055) and ON-
time with dyskinesia (p50.0376; OR=1.032; CI95%=1.002, 1.064)
were associated with LCIG discontinuation.
Conclusions: At baseline there were no significant differences in
patients characteristics between groups. LCIG discontinuation was
associated with longer OFF-time and ON-time with dyskinesias at
baseline.
287
E-DUO Study: Use of levodopa-carbidopa intestinal gel in
Spanish advanced Parkinsons disease patients. Disease duration
sub-group analyses
J.C. Parra, F. Valldeoriola, I. Regidor, V. Puente (Madrid, Spain)
Objective: To compare the effectiveness (percentage of change
in daily ON, OFF and dyskinesia times) and tolerability of LCIG in
patients with Parkinsons disease (PD) duration 10 years and <10
years.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S110 POSTER SESSION
Methods: APD patients from 18 Spanish sites who had ever been
treated with LCIG between January 2006 and December 2011 were
included in this non-interventional and retrospective study.
Results: PD median duration was significantly different between groups
(<10 years: 7.7 (n551) vs 10 years: 16.0 years (n5125); p<0.0001). The
rest of baseline characteristics were similar between groups.
Main reasons to start LCIG treatment were OFF-time increase
(<10 years: 92.2%; 10 years: 83.2%) and a lack of response to
oral treatment (<10 years: 64.7%; 10 years: 63.2%).
In the follow-up there was a significant reduction in the OFF-
time (<10 years: baseline=52.3% and follow-up=14.3%; p<0.0001;
10 years: baseline=45.8% and follow-up=16.9%; p<0.0001) and a
significant increase in the ON-time without dyskinesia (<10 years:
baseline=16.9% and follow-up=59.4%; p<0.0001; 10 years: base-
line=23.4% and follow-up= 54.0%; p<0.0001).
There was a statistically significant difference between groups in
the reduction of daily OFF-time (<10 years: -38.0% vs 10 years: -
28.9%; p50.0213). The increase in the percentage of daily on-time
without dyskinesia did not reach statistical significance.
A 9.8% of the patients in the <10 years group presented at least
one serious adverse event versus a 19.2% of the patients in the 10
years (p50.1274).
Conclusions: In the follow-up the group of patients with <10
years of PD progression presented a higher reduction of the OFF-
time and less incidence of adverse events in comparison with the
group of patients with 10 years PD progression.
288
External validation of a simple clinical fall prediction tool in
Parkinsons disease
S.S. Paul, R.P. Duncan, J.T. Cavanaugh, G.M. Earhart, T.D. Ellis,
M.P. Ford, K.B. Foreman, A.L. Leddy, C.G. Canning, A. Thackeray,
L.E. Dibble (Salt Lake City, UT, USA)
Objective: To externally validate the utility of a simple clinical
fall prediction tool in people with Parkinsons disease (PD).
Background: Assessment of fall risk in a person with PD is a
critical yet often time consuming component of patient care.
Recently, a simple clinical prediction tool which included weighted
scores from only three risk factors: fall history in the previous year,
freezing of gait in the past month, and preferred gait speed <1.1 m/
s, was used to accurately predict future falls in a sample of people
with PD from Australia (Paul et al, Mov Disord 2013;28:655).
Methods: The clinical fall prediction tool was administered to
community-dwelling individuals with PD from the United States.
Falls were monitored prospectively for 6 months following baseline
assessment of risk factors. The area under the curve (AUC) was used
to determine the discriminative ability of the clinical prediction tool.
Results: The external validation sample included 171 people with
PD (mean age 67 [SD 9] years, mean PD duration 6 [SD 4] years,
74 [43%] females). The validation sample had a similar risk gradient
as the development sample. The tool accurately discriminated future
TABLE 1. Change scores for each outcome across trials, by group.
Parkinsons disease
Outcome
Trial 1 vs 2
(FTR)
Reaction time* (s) -0.03
Peak centre of pressure displacement (m) 0.01
Peak centre of pressure velocity (m/s) 0.01
Heel displacement coefficient of variation* (%) 2 -7
group x trial interaction, between group difference, *within group difference across trials, significant at Greenhouse-Geisser conservative
p<0.05. FTR: first trial response.
Movement Disorders, Vol. 30, Suppl. 1, 2015
fallers from non-fallers (area under the curve 5 0.83; 95% CI 0.76-
0.89), which was comparable to the results of the Australian study.
Conclusions: The results of this study validate the utility of the
fall prediction tool in a cohort of people with PD in the United
States. The high clinical utility of the tool allows clinicians to
quickly and accurately identify an individuals absolute risk of an
impending fall. As such, it may be used as a starting point for in-
depth examination of additional fall risk factors in order to facilitate
the rapid implementation of fall prevention strategies.
289
First trial response performance of an anticipatory postural task
in people with Parkinsons disease and healthy adults
S.S. Paul, M.E. Lester, N.L. Salant, K.B. Foreman, L.E. Dibble (Salt
Lake City, UT, USA)
Objective: To compare first and subsequent trial responses during
an anticipatory postural task in people with Parkinsons disease
(PD), neurologically healthy age-matched and young adult controls.
Background: Unexpected perturbations often initially result in
exaggerated corrective postural reactions, but response magnitude
tends to diminish with repeated perturbation. Previous research has
suggested that lack of a difference between the first trial response
(FTR) and subsequent responses to unexpected perturbations may
identify those most at risk of falling. However, evidence of FTR dif-
ferences during volitional postural challenges is lacking. Specifically,
little is known about FTR differences during anticipatory postural
control tasks and whether people with PD respond similarly to peo-
ple without neurological impairment.
Methods: People with PD, healthy older and young adults each
performed three trials of a rise-to-toes task. Changes in reaction time
(RT), reflecting movement preplanning; peak posterior displacement
of the centre of pressure, reflecting anticipatory postural adjustment;
peak centre of pressure velocity (COPv) and coefficient of variation
of the vertical heel displacement (CV), reflecting postural stability;
were examined.
Results: 11 people with PD (mean 69 6 8 years, Hoehn and Yahr
stages 1-3), 13 healthy older (mean 64 6 9 years) and 15 healthy
young adults (mean 26 6 2 years) participated. RT FTR was slower
in all groups (Table 1). CV FTR was larger in healthy adults while
people with PD showed delayed improvement in CV across trials.
COPv FTR was small in healthy young adults, large in healthy older
adults and unchanged in people with PD. COPv and RT were slower
in people with PD compared to controls.
Conclusions: During an anticipatory postural control task, the
motor preplanning FTR was not influenced by age or PD. In contrast,
FTR differences in postural stability were lacking in people with PD
but repeated exposure tended to improve performance, which may
reflect delayed motor learning. Between group disparities in FTR dif-
ferences for postural stability may reflect differing age-related strat-
egies to optimize performance efficiency as well as a bradykinesia-
Healthy older adults Healthy young adults
Trial 1 vs Trial 2 Trial 1 vs
Trial 2 vs 3 2 (FTR) vs 3 2 (FTR) Trial 2 vs 3
-0.04 -0.10 0 -0.07 0
-0.01 0 0 0 -0.01
-0.01 -0.13 -0.01 0.07 0.03
-9 1 -3 -1
 POSTER SESSION
related adaptive failure in PD. The FTR may not be sensitive to
changes in anticipatory postural adjustments.
290
The effects of vitamin D supplementation on balance, motor, and
neuropsychiatric function in Parkinsons disease (PD)
A.L. Peterson Hiller, B.M. Lobb, C. Murchison, J.F. Quinn
(Portland, OR, USA)
Objective: To evaluate the effects of four months of high dose
vitamin D supplement on motor and neuropsychiatric function in per-
sons with PD.
Background: In elderly fallers without PD vitamin D supplemen-
tation appears to reduce falls. In PD various studies have shown rela-
tionship between vitamin D levels and motor symptoms, cognition,
and mood.
Methods: This is a double blind, placebo controlled vitamin D
intervention study. Participants with PD, some degree of balance
impairment (one or greater on a pull test, one fall a month, or two
near falls a month), no significant cognitive deficits (Mini-Mental
Statue Exam of 25), and serum vitamin D levels between 20 and
40 ng/ml were randomized to receive 10,000 units of vitamin D3 a
day or a placebo. All participants received 1000mg of calcium car-
bonate daily. Persons with vitamin D less than 20ng/ml were auto-
matically enrolled in the active arm, but still kept blinded.
Assessments at the baseline and after 16 weeks of either vitamin D
or placebo included measures of falls, strength, balance, cognition,
PD severity, and quality of life.
Results: One hundred and one participants were screened for the
study. Thirty-one failed screening because of vitamin D lev-
el > 40ng/ml (16), tuberculosis positivity (3), history of renal stones
(4), or because of not meeting other eligbility criteria (9) . The
randomized cohort included 69 subjects, mean age (67.5, SD 5 8.0),
77.3% male, mean H&Y=2.4 (SD 5 0.4), mean baseline vitamin
D 5 27.8ng/ml (SD 5 7.9), and mean years since diagnosis 9.8
(SD 5 6.5). There were no significant relationships identified between
baseline vitamin D and collected measures. Drop-out was 13.3%,
with 4 because of adverse events and 6 for other reasons. An intent-
to-treat analysis will include all 69 randomized subjects and a per
protocol analysis will include the 59 completers. Clinical activity for
the study was completed in December 2014 and database cleaning is
currently underway. Unblinded analysis of outcomes will be avail-
able at the time of abstract presentation.
Conclusions: Looking cross-sectionally it does not appear vita-
min D levels correlated with motor or neuropsychiatric measures.
This is counter to some prior data. The analysis of the intervention
data, which will be available for the poster, is critical in knowing if
it is worthwhile to further investigate vitamin D as a potential ther-
apy in PD.
291
Improvement of the gait performance under dual-task condition
after mental practice in patients with Parkinsons disease: A
single-blind, randomised clinical trial
M.E.P. Piemonte, M. Pikel, F.A.S. Mendes, L. Maciel, A. Lopes (Sao
Paulo, Brazil)
Objective: To compare the effects of Mental Practice associated
with physical gait training and the physical gait training only on gait
performance under dual-task condition in PD patients.
Background: Mental practice (MP) is defined as the repeated use
of kinesthetic imagery (internal rehearsal of movements from a first-
person perspective without any overt physical movement) to improve
motor performance. The internal representation developed by MP is
likely based on motor and sensory estimation of planned movement
consequences by a top-down process, resulting in an internal forward
model. This kind of top-down process could be useful to compensate
S111
the deficiency in automatic control in PD patients because it depends
on more cortical control.
Methods: A blinded, randomized, controlled, longitudinal clinical
trial was conducted with 36 idiopathic PD patients, mean age of 74.4
years (S.D. 5 9.6), at stages 1-3 of the Hoehn and Yahr Classifica-
tion, asymptomatic for depression and dementia. The patients were
randomly divided into two groups: MP group (MPG) that performed
physical gait training intercalated with MP training and Control
Group (CG) that performed physical gait training only. The sequen-
ces of movements involved in the gait was summarized by six key
movements used to guide MP. The same key movements were used
to guide the physical training for CG. Blinded examiner assessed
gait performance under Single Task Condition (ST) and Dual-Task
condition (DT) before and 1, 7 and 14 days after the end of the train-
ing. All participants signed the HCFMUSP informed consent term.
Results: One 2X2X4 RM-ANOVA using as factor Conditions
(ST, DT), Groups (MPG and CG) and assessment time points (BT,
AT, 7dATand 14dAT) as repeated measures for gait speed showed a
significant interaction among all factors (p5.003,ES=.99). Tukey pos
hoc test showed a significant increase in gait speed in DT condition
for MPG only (p5.01, ES=.80).
Conclusions: MP associated with physical gait training can
strengthen the top-down control of gait, improving gait performance
under dual-task conditions in PD patients.
292
Improvement of the gait stability after cognitive strategy patients
with Parkinsons disease: A single-blind, randomised clinical
trial
M.E.P. Piemonte, F.A.S. Mendes, M. Pikel, A. Lopes, L. Maciel (Sao
Paulo, Brazil)
Objective: To verify the effects of Cognitive Strategy associated
with physical gait training on gait stability in PD patients.
Background: The reduction in dopamine levels in striate cortical
circuits caused by PD compromises the automatic motor control for
balance and gait. This compromises the gait stability increasing the
risk of falls and decreasing the independence in daily living activ-
ities. The search for novel strategies to attenuate gait disturbances in
PD poses a challenge to physiotherapists. Cognitive strategy (CS)
has been used to compensate the deficiency in automatic control.
However, few studies have investigated the CS effect on gait
stability.
Methods: A blinded, randomized, controlled, longitudinal clinical
trial was conducted with 36 idiopathic PD patients, with a mean age
of 71.5 years (S.D. 5 9,63), at stages 1- 3 of disease evolution
according to the Hoehn and Yahr Classification, asymptomatic for
depression and dementia, were randomly divided into two groups:
CS group (CSG) that performed physical gait training following the
Cognitive Cues and Control group (CG) that received only orienta-
tions about falls prevention. The sequences of movements involved
in gait was summarized by six key movements used as Cognitive
Cues to guide the CS training. Blinded examiner assessed gait stabil-
ity before (BT), immediately (AT), 7 days (7dAT) and 14 days
(14dAT) after the training through Stability in Gait Section (21-27
test)from Balance Evaluation Systems Test (BESTest). These tests
evaluate the ability to walk in seven differents conditions evolving
change in gait speed, head rotations, pivot turns, stepping over
obstacles and Timed Get Up&Go in single and dual-task condi-
tions. All participants signed the HCFMUSP informed consent term.
Results: One 2X4 RM-ANOVA using as factor Groups (CSG;
CG), and assessments (BT, AF, 7dAT, 14dAT) as repeated measures
for BESTest punctuation showed significant interaction between the
factors (p5.0001, ES=.90). Tukey pos-hoc test showed a significant
increase in punctuations after training for CSG only (p5.02,
ES=.90), which was remained after the end of training.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S112 POSTER SESSION
Conclusions: CS associated with physical gait training can
improve stability on gait minimizing the deficency in the automatic
motor control in the balance and gait.
293
Evaluation of opicapone on cardiac repolarization in a thorough
QT/QTc study
R. Pinto, M. Vaz-da-Silva, N. Lopes, A. Santos, T. Nunes, J.F.
Rocha, P. Soares-da-Silva (S. Mamede do Coronado, Portugal)
Objective: Investigate the effect of opicapone (OPC) on cardiac
repolarization in healthy adult volunteers.
Background: OPC is a novel once-daily potent and long-acting
peripheral COMT-inhibitor under investigation for Parkinsons
disease.
Methods: Single-centre, randomized, double-blind placebo-con-
trolled, open-label active-controlled, 4-period crossover study con-
ducted in 64 subjects. In each period, subjects received a single oral
dose of either 50mg-OPC, 800mg-OPC, placebo or 400mg moxiflox-
acin. A 24-hour, 12-lead Holter monitoring was performed on base-
line and after each single dose. The primary criterion was the
individual QT interval corrected for heart rate (QTcI) derived for
each subject from the regression model that best fitted the relation-
ship between the QT and RR intervals.
Results: The largest upper bounds of the 95% one-sided confi-
dence intervals (CI) for the placebo-corrected QTcI change from
baseline were 3.46ms for 50mg-OPC and 4.45ms for 800mg-OPC,
considerably below the 10ms threshold of regulatory concern. Moxi-
floxacin caused an increase in QTcI with a lower bound of the two-
sided 95% CI higher than 5ms for majority of time points, demon-
strating assay sensitivity.
Conclusions: At clinical and supra-therapeutic doses, opicapone
was not associated with QTc prolongation.
294
Cardiac safety of opicapone in patients with Parkinsons disease:
Analysis of the centralized phase III ECG dataset
R. Pinto, M. Vaz-da-Silva, N. Lopes, J. Ferreira, A. Lees, H. Gama,
A. Santos, C. Oliveira, T. Nunes, J.F. Rocha, P. Soares-da-Silva (S.
Mamede do Coronado, Portugal)
Objective: Evaluate the effects of opicapone (OPC) compared to
placebo on electrocardiographic parameters in patients with Parkin-
sons disease.
Background: OPC, a novel once-daily peripheral COMT-
inhibitor, has shown to be safe and effective in reducing OFF-time
in Parkinsons disease (PD) patients with motor fluctuations.
Methods: Standard 12-lead ECGs, recorded at baseline (in tripli-
cate) and endpoint using digital electrocardiographs ELI 250V R , from
two multicentre, double-blind, randomised, placebo- and active-
controlled studies (BIPARK I and II) were pooled and evaluated.
Changes from baseline were calculated for QT, QTcF, QTcB, PR,
QRS and HR. Outliers and morphological abnormalities were eval-
uated by categorical analyses.
Results: A total of 3060 ECGs from 772 subjects (243 in 25mg-
OPC, 266 in 50mg-OPC and 263 in placebo) were evaluated. There
were no statistically significant differences between OPC groups and
placebo for the changes from baseline in QT/QTc, PR and HR esti-
mates. The mean placebo-adjusted increases in QTcF/QTcB were <4
msec with both OPC doses, and all upper limits of the 1-sided 95%
confidence intervals (CI) were <10 msec. The observed slight
increase in QRS interval [1.6 msec (90% CI: 0.2, 3.0) and 0.9 msec
(90% CI: -0.5, 2.3) with 25mg- and 50mg-OPC, respectively] is not
clinically relevant. Few significant ECG abnormalities were
observed, and these were distributed similarly across placebo and
OPC groups.
Movement Disorders, Vol. 30, Suppl. 1, 2015
Conclusions: OPC was not associated with any relevant effects
on ECG intervals or morphology.
295
Global long-term registry on efficacy and safety of levodopa-
carbidopa intestinal gel in patients with advanced Parkinsons
disease in routine care (GLORIA) Interim results in a
subgroup of patients with dyskinesia at baseline
W. Poewe, K.R. Chaudhuri, L. Bergmann, A. Yegin, S. Dubow, A.
Antonini (Innsbruck, Austria)
Objective: Levodopa-carbidopa intestinal gel (LCIG) was eval-
uated for the treatment of dyskinesia in a subgroup of advanced Par-
kinsons disease (PD) patients with relevant dyskinesia.
Background: Oral levodopa therapy in advanced PD patients can
lead to motor fluctuations and dyskinesia which can be difficult to
treat and affect patients quality of life.
Methods: 316 patients with advanced PD were treated at 75 cen-
ters in 18 countries in this 24-month prospective, observational
study. A post-hoc subgroup analysis was conducted on safety and
efficacy data collected on/before 3rd January 2014 from patients
with 4 hours dyskinesia at baseline. Changes in dyskinesia were
measured from baseline to months 12 and 24 by Unified PD Rating
Scale (UPDRS) item #32 and PD Questionnaire (PDQ-8) total score.
Results: At baseline (n5316), 36% of patients had 4 hours dys-
kinesia, 28% had <4 hours dyskinesia and 35% had missing data.
The dyskinesia subgroup (4 hours, n5114) was 53% male and
98% white with a mean [SD] age of 64.9[9.2] years. After 12 and 24
months of LCIG, dyskinesia duration was reduced 2 hours in 69%
and 60%, respectively. The mean [SD] UPDRS item #32 score was:
at baseline (n5114)=2.3 [0.8], 12 months (n588)=1.2 [1.0] and 24
months (n522)=1.5 [1.1]; and mean [SD] change from baseline was:
12 months (n588)= -1.1 [1.3] (p<0.0001) and 24 months (n522)= -
0.9 [1.2] (p50.0018). The mean [SD] change from baseline of total
waking hours with dyskinesia was: 12 months (n586)= -3.0 [8.6]
(p50.0017) and 24 months (n520)= -3.0 [5.9] (p50.0339). The
mean [SD] change from baseline of percent of waking day with dys-
kinesia was: 12 months (n586)= -23.1 [27.2] (p<0.0001) and 24
months (n520)= -20.5 [34.8] (p50.0164). The mean [SD] change
from baseline PDQ-8 total score was: 12 months (n567)= -16.6
[24.2] (p<0.0001) and 24 months (n516)= -9.6 [22.8] (p50.1144).
The tolerability of LCIG in the dyskinesia subgroup was consistent
with the established safety profile from previous studies.
Conclusions: Advanced PD patients with dyskinesia at baseline
had a significant and long-term improvement in dyskinesia during
LCIG treatment.
296
Impact of LSVT LOUD and LSVT ARTIC on speech
intelligibility in Parkinsons disease
L.A. Ramig, E.S. Levy, C.M. Fox, A. Halpern, J. Spielman, G. Moya-
Gale, A. Goudarzi (New York, NY, USA)
Objective: This Randomized Control Trial (RCT) was designed
to evaluate the impact of voice treatment (LSVT LOUD) and speech
treatment (LSVT ARTIC), administered in the same intensive dos-
age, on speech intelligibility in Parkinsons disease (PD).
Background: Nearly 90% of individuals with PD suffer from the
voice and speech disorders such as reduced vocal loudness and
imprecise articulation, which contribute to frustration, embarrassment
and social isolation. These disorders, which have been associated
with inadequate activation of the speech musculature (hypokinesia)
as well as disorders of sensory feedback and internal cueing, histori-
cally have been unresponsive to traditional speech or medical treat-
ments. Foundational research by Ramig and colleagues has
documented significant short (immediate post-treatment) and long
(24 months post-treatment) impact of LSVT LOUD on a range of
 POSTER SESSION S113

characteristics of speech production, including vocal loudness (Sound

Pressure Level; SPL). This new RCT is the first to evaluate the
impact of two treatments (LSVT LOUD and LSVT ARTIC) on
speech intelligibility.
Methods: Spontaneous speech samples were collected from 57
individuals with PD. After stratification, patients were randomly
assigned to one of three groups: LSVT LOUD, LSVT ARTIC and
no treatment (NOTX). Both treatments were administered by expert
clinicians, in an intensive dosage of four 1-hour sessions per week
for 4 weeks. Multi-talker babble was added to both pre and immedi-
ately post-treatment samples at pre-treatment 0dB SNR. Measures of
speech intelligibility included two dependent variables: blinded lis-
tener (n516) orthographic transcription accuracy and intelligibility
ratings (1-9 scale) of randomized sentences.
Results: Transcription accuracy (.95 reliability) increased for
both treatment groups LSVT LOUD (43%; SDs pre/post 0.295/
0.320), LSVT ARTIC (13%; SDs pre/post 0.264/0.347); NOTX
decreased (13%; SDs pre/post 0.380/0.305). Median ratings of intelli-
gibility (.91 reliability) increased for both treatment groups LSVT
LOUD (4), LSVT ARTIC (1); NOTX decreased (1); Range 1-9 for
all conditions.
Conclusions: Speech intelligibility improved for both LSVT
LOUD and LSVT ARTIC, but not for NOTX. The magnitude of
improvement in speech intelligibility was greater following LSVT Fig. 1. (297).
LOUD than LSVT ARTIC.
and 4 points on an 11-point Likert pain scale were randomized 1:1
to rotigotine or placebo. Treatment was titrated over 1-7 weeks and
297 maintained at optimal/maximum dose (16 mg/24h) for 12 weeks.
A randomized controlled pilot study to evaluate the effect of Primary efficacy variable was change in pain severity (Likert pain
rotigotine on Parkinsons disease-associated pain scale). Secondary variables included responders (2 point reduction
on Likert pain scale), PDQ-8, HADS, and UPDRS II1III. This pilot
O. Rascol, T. Zesiewicz, K.R. Chaudhuri, M. Asgharnejad, E.
study was not powered to detect statistically significant treatment
Surmann, E. Dohin, S. Nilius, L. Bauer (Toulouse, France)
effects; statistical analyses were performed in an exploratory manner
Objective: This double-blind, placebo-controlled pilot study only.
investigated the effect of rotigotine transdermal patch on Parkinsons Results: Of 68 patients randomized, 8 patients (rotigotine: 5, pla-
disease (PD) associated chronic pain. cebo: 3) were excluded from the full analysis set. Patients (mean
Background: Pain is a common non-motor symptom of PD; [6SD] age: 65.9 [12.8] years) had advanced-PD with (48; 70.6%) or
however, its management is based on an empirical approach, with without (20; 29.4%) motor fluctuations. Mean (6SD) rotigotine
poor level of evidence. RECOVER, a double-blind, placebo-con- maintenance dose: 14.7 (5.1) mg/24h. Mean (6SD) baseline Likert
trolled study, suggested that rotigotine may improve pain in patients pain score: 6.0 (1.35) rotigotine and 6.2 (1.74) placebo. A numerical
with PD (exploratory outcome). This study is the first to prospec- improvement in pain severity was observed in favor of rotigotine
tively investigate the effect of a dopamine agonist on PD-associated (p50.172; Figure 1), and the number of responders was higher with
pain as primary outcome. rotigotine (18/30; 60.0%) vs placebo (14/30; 46.7%). There were
Methods: DOLORES (PD0004; NCT01744496) was originally also numerical improvements in secondary outcomes (Table 1). 22
designed as a large-scale study. It was converted into a pilot study, (62.9%) rotigotine and 20 (60.6%) placebo patients reported adverse
and results are reported here. Patients with advanced-stage PD expe- events.
riencing chronic pain associated with PD (dystonia, musculoskeletal, Conclusions: Numerical improvements were observed in favor of
central neuropathic, or other pains worsened by PD) for 3 months, rotigotine for primary and secondary outcomes. The results of this

TABLE 1. Secondary outcomes

Mean (6SD) Mean (6SD) change
baseline score from baseline LS mean [95% CI]
treatment
Placebo Rotigotine difference vs Exploratory
Full analysis set (n530) (n530) Placebo Rotigotine placebo, ANCOVA* p-value
PDQ-8 38.85 (18.73) 39.48 (20.87) -3.77 (13.93) (n529) -12.40 (19.25) (n530) -8.01 [-15.56, -0.46] 0.038
HADS-depression 8.2 (4.8) 6.9 (3.5) -1.7 (4.3) (n528) -1.9 (4.1) (n528) -1.02 [-2.76, 0.73] 0.247
subscore
HADS-anxiety 7.4 (4.0) 7.4 (3.9) -1.0 (3.2) (n528) -1.8 (3.7) (n528) -0.58 [-1.85, 0.70] 0.371
subscore
UPDRS II1III 46.4 (24.9) 49.6 (20.3) -5.1 (11.7) (n529) -8.3 (11.2) (n530) -2.82 [-8.76, 3.13] 0.346
*Analysis of covariance (ANCOVA) model with treatment and region as factors and baseline values as covariate. P-values are exploratory only,
and do not infer statistical significance. PDQ-8, Parkinsons disease Questionnaire; HADS, Hospital Anxiety and Depression Scale; UPDRS, Uni-
fied Parkinsons disease Rating Scale; CI, confidence interval; SD, standard deviation; LS, least squares

Movement Disorders, Vol. 30, Suppl. 1, 2015

S114 POSTER SESSION

pilot study suggest that rotigotine may improve PD-associated pain, PD duration ranged from 60.17 (SD 10.26) to 72.77 (SD 7.87) and
and warrant further investigation in a large-scale confirmatory 2.4 to 11.2 years, respectivelly. Most of the studies provided 2 thera-
study. pies sessions per week with 60 minutes each. Six studies provided
[figure1] data about therapy intensity with amount of weight lifted or speed of
movements. The majority of the studies were about dance therapy
(8) and hydrotherapy (6). Tai chi, dance therapy, water exercises and
298 virtual reality therapy improved balance, movement function, gait
Height and weight changes after deep brain stimulation in and decreased number of falls. Dance therapy and water exercises
patients with Parkinsons disease: Role of clinical subtypes also showed improvements on QoL. Robotic gait training, mental
D. Reyes, H. Abboud, G. Genc, A.G. Machado, S. Cooper, M. practice, aerobic training, boxing training, whole body vibration and
Nordic walking showed relatively low level evidence of their effects
Gostkowski, H.H. Fernandez (Weston, FL, USA)
on people with PD.
Objective: To study the effect of Parkinsons disease (PD) clini- Conclusions: There was emerging evidence that some alternative
cal subtype (tremor predominant versus akinetic-rigid) on weight and therapies may be a suitable adjunct to traditional therapy. More
height changes after Deep Brain Stimulation (DBS). studies with higher methodological quality are needed comparing
Background: DBS has been established as a superior therapeutic alternative therapies, ranging in both duration and frequency, in an
option for advanced Parkinsons disease. Increased body mass index effort to clarify the associated risks and benefits to people living
(BMI) after DBS has been repeatedly reported in literature. However, with PD.
little is known about the effect of PD clinical subtype weight and
height changes after DBS.
Methods: We reviewed the charts of PD patients who underwent
300
DBS implantation at our center between 2006 and 2011 with com-
plete charting. Data was extracted for BMI, weight and height at the Use of an online portal to facilitate clinical trial recruitment: A
pre-surgical period, at 1-year post surgery, and at the latest available preliminary analysis of Fox Trial Finder
follow up (LAF). C. Rocker, L. Cappelletti, C. Marshall, C.C. Meunier, D.W. Brooks,
Results: There was 130 patients in the dataset (70% male, mean T. Sherer, S. Chowdhury (New York, NY, USA)
age 631/-9.1, mean BMI 27.5 1/-5.2). Eighty-eight patients had
available data at 1-year post DBS or longer. Mean LAF was 4.361/- Objective: Characterize the research volunteers (with and without
1.64 years post-DBS. An increment in BMI by 1 Kg/m2 or more PD) registered on Fox Trial Finder (FTF) as of June 2014 to identify
was noticed in 35% and 41% of the patients after 1-year and at core attributes, including differences between the PD and control
LAF, respectively. Increased height (1 cm-or-more) was seen in 25% populations.
of patients at 1-year and 19% at LAF. At 1-year post-DBS, 37.5% of
patients with akinetic-rigid type increased in height by 1 cm (OR
4.2000, 95% CI 1.4429 to 12.2252, P 0.0085) and 27.5% increased
in height by 2 cm or more (Or 8.72, 95% CI 1.8029 to 42.2162, P
Demographic characteristics of the FTF population
0.0071). In the tremor-predominant group, only 12.5% had a 1 cm or
more increment in their height at 1-year and 4% at LAF. There was Individuals
no correlation between PD clinical subtypes and weight changes. Attribute with PD Controls
Conclusions: This study confirms BMI increase after DBS in PD
patients and reports a novel finding of increased height after DBS in Age
patients with the akinetic-rigid clinical subtype. This might be sec- Mean (Years) 62 51
ondary to improved rigid posture following DBS. Median (Years) 63 50
No response (# of 560 (3%) 170 (2%)
respondents, %)
299 Gender (# of
Alternative physical therapies for Movement Disorders in respondents,%)a
Parkinsons disease: A systematic review Male 10,489 (61%) 1,647 (26%)
Female 6,735 (39%) 4,706 (74%)
P.A. da Rocha, J. McClelland, M. Morris (Bundoora, Australia)
No response 2,019 665
Objective: To evaluate the effects of alternative physical thera- Ethnicity (# of respond-
pies aimed at improving mobility in PD. ents, %)b
Background: Worldwide there is a trend towards incorporating White or Caucasian 16,314 (84.8%) 6,039 (86.1%)
physical exercises to complement medical management of PD. In Hispanic or Latino 620 (3.2%) 287 (4.1%)
recent years, some alternative physical activities have been proposed Asian 416 (2.2%) 168 (2.4%)
for PD with the goal of optimizing mobility and at the same time American Indian or 287 (1.5%) 121 (1.7%)
being enjoyable, and enhancing quality of life, social inclusion and Alaska Native
wellbeing. The growth and popularity of these alternatives therapies Black or African 272 (1.4%) 81 (1.2%)
attempts to fill the gap left by conventional physical therapy, which American
does not always directly target wellbeing, enjoyment and social Native Hawaiian or 64 (0.3%) 20 (0.3%)
participation. Pacific Islander
Methods: We conducted a systematic review of alternative physi- No Response 1,635 (8.5%) 534 (7.6%)
cal therapies for PD using RCT, nonRCT and case series studies of Location (# of respond-
people diagnosed with PD, walkers with or without assistive devices, ents, %)c
in any duration of PD. Studies were searched on Medline, Embase, New York-Northern New 562 (2.9%) 416 (5.9%)
Cinahl, The Cochrane Library and Pedro, from May to December Jersey NY-NJd
2014. Changes on mobility, balance, gait, falls, ADL, QoL, Move- Los Angeles-Western 466 (2.4%) 160 (2.3%)
ment Disorders and disabilities were analysed. Suburbs, CAd
Results: 20 RCTs, 2 nonCRTs and 12 case series studies met the
inclusion criteria with 1210 participants in total. The mean age and

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION S115

TABLE Continued 2011 to facilitate connection between PD research teams and

volunteers.
Methods: Profiles of volunteers with and without PD were ana-
Demographic characteristics of the FTF population lyzed to explore trends in geography, demographics, family history
and, for those volunteers with PD, disease progression and treatment
Individuals history. Volunteers based in the United States were the focus of the
Attribute with PD Controls analysis.
Results: The database contained 26,261 US-based volunteers,
Chicago Northern Sub- 456 (2.4%) 249 (3.5%)
including 19,243 volunteers (73%) with PD and 7,018 (27%) controls
urbs, IL-WId
without PD. Volunteers with PD were older (median age 63 vs. 50
Phoenix-Mesa-Glendale, 330 (1.7%) 118 (1.7%)
years), more likely to be male (61% vs. 26%) and less likely to
AZd
report a family history of PD (12% vs. 48.6%). The average time
Atlanta-Sandy Springs- 301 (1.6%) 141 (2.0%)
since diagnosis for PD volunteers was 5.7 years and the average age
Marietta, GAd
at diagnosis was 58 years. The medications that volunteers with PD
Houston-Sugar Land- 291 (1.5%) 108 (1.5%)
most commonly reported taking at the time of the analysis were
Baytown, TXd
carbidopa-levodopa (45.2%) and rasagiline (19.7%).
Fairfax Co., VAd 273 (1.4%) 155 (2.2%)
Conclusions: Volunteers with and without PD have demonstrated
San Diego-Carlsbad-San 267 (1.4%) 92 (1.3%)
a high level of willingness to participate in PD research. PD studies
Marcos, CAd
can leverage innovative technology, like FTF, to reach volunteers
Philadelphia Western 265 (1.4%) 149 (2.1%)
with a variety of demographic backgrounds and health
Suburbs, PA
characteristics.
Dallas North Suburbs, 262 (1.4%) 88 (1.3%)
TXd
Denver-Aurora-Broom- 254 (1.3%) 79 (1.1%) 301
field, COd
Minneapolis-St. Paul- 243 (1.3%) 107 (1.5%) Interim results of outpatient levodopa-carbidopa intestinal gel
Bloomington, MN-WId titration in patients with advanced Parkinsons disease
Seattle Southern Suburbs, 236 (1.2%) 112 (1.6%) R.L. Rodriguez, M. Lobatz, J. Dubow, S. Eaton, C.M. Hall, K.
WAd Chatamra, J.A. Benesh (Gainesville, FL, USA)
Los Angeles SE Suburbs, 234 (1.2%) 56 (0.8%)
Objective: To assess the efficacy of levodopa-carbidopa intestinal
CA
gel (LCIG) on non-motor symptoms and the safety of conducting
Sacramento-Arden- 230 (1.2%) 70 (1.0%)
outpatient titration via percutaneous endoscopic gastrojejunostomy
Arcade-Roseville, CA
(PEG-J) in a new, ongoing multicenter study of LCIG in subjects
San Francisco Eastern 222 (1.2%) 101 (1.4%)
with advanced Parkinsons disease (PD).
Suburbs, CAd
Background: LCIG is continuously infused during waking hours
Riverside-San 221 (1.1%) 48 (0.7%)
(16 hours/day) to treat motor symptoms in advanced PD.1 Previously,
Bernardino-Ontario,
LCIG was titrated via nasojejunal (NJ) tube or PEG-J in the inpatient
CA
setting.2 The safety and methods for outpatient LCIG titration have
San Francisco Peninsula 203 (1.1%) 113 (1.6%)
not been previously reported.
Suburbs, CAd
Methods: In this ongoing, 60-week open-label study, LCIG
New York-Long Island, 202 (1.0%) 92 (1.3%)
titration was initiated as a monotherapy in the outpatient setting
NYd
within 5 days of the PEG-J procedure, and continued for up to 4
Northern Jersey Suburbs, 193 (1.0%) 58 (0.8%)
weeks. Investigators could admit subjects for observation for up
NJ
to 48 hours following PEG-J placement. Titration was considered
Family History of PD
complete when the dose was not adjusted for the following 7
(# of respondents, %)
days. The primary endpoint of this study was mean change from
Father 1,008 (5.2%) 1,845 (54.1%)
baseline to Week 12 on the Non-motor Symptom Scale (NMSS)
Mother 728 (3.8%) 1,148 (33.7%)
total score and will be reported separately. Titration data were
Sibling 537 (2.8%) 355 (10.4%)
collected by clinical nurse educators. Safety was assessed
Child 25 (0.1%) 63 (1.8%)
throughout the study. Although the abstract includes interim
a: Percentages are calculated based on the number of volunteers that data, the presentation will report titration data for the final
answered the question; the number of non-responders is included for enrollment of 39.
reference. b: Respondents are allowed to select multiple ethnicities; Results: As of October 2014, 34 advanced PD subjects with a
thus, percentages will not add to 100%. c: Note that this list includes mean (SD) age of 64.6 (10.4) years were enrolled. Post-PEG-J place-
ment, the mean (SD, range) number of hours until discharge was
only the top 20 core-based geographic areas (CBGAs) for volunteers
20.4 (14.6, 2- 50.3) with an average of 21.8 (32.8, 0139) hours until
with PD, representing 29.7% of the total sample of 19,243 volunteers titration initiation. On average, LCIG titration was completed in 5.7
with PD. Overall, there were 823 CBGAs reported by 19,243 volun- (6.1, 032) days (n527); in the first week, the mean time in an out-
teers with PD and 582 CBGAs reported for 7,018 controls. d: Indi- patient facility ranged from 3.5 to 7.7 hours/day (Table 1). The
cates a CBGA that was in the top 20 for both PD and control majority of patients had an AE within the first week of PEG-J place-
volunteers ment, with fewer in the following 3 weeks (Table 2). There were 2
(5.9%) patients with serious AEs, 1 (2.9%) who discontinued due to
an AE, and no deaths during the first 4 weeks (n534). The mean
(SD) starting levodopa dose was 1243.2 (485.8) mg/day (n533), and
Background: Despite the fact that a majority of individuals with the mean (SD) change to final prescribed dose was 395.9 (715.7)
Parkinsons disease (PD) report being willing to participate in clini- mg/day.
cal research, few patients ever do, leading to significant chal- Conclusions: These data support the idea that LCIG can be safely
lenges with clinical study recruitment. In an effort to expedite and effectively titrated in the outpatient setting.
1
PD research, The Michael J. Fox Foundation established FTF in Olanow et al. Lancet Neurol. 2014; 13(2):141-9.

Movement Disorders, Vol. 30, Suppl. 1, 2015

S116 POSTER SESSION

TABLE 1. Average Number of Hours of Titrating LCIG in an Outpatient Clinic in the First Seven Days of Infusion
Hours of titration on each day following
initiation of LCIG infusiona n (%)b Mean [SD] Median Minimum - Maximum
Day 1 30 (100) 6.4 [2.0] 7.0 3.0 - 11.5
Day 2 29 (96.7) 7.7 [3.5] 7.5 2.0 - 16.0
Day 3 18 (60.0) 4.5 [2.7] 4.0 1.0 - 10.0
Day 4 12 (40.0) 4.6 [4.1] 4.0 1.0 - 16.0
Day 5 11 (36.7) 4.6 [4.3] 3.0 1.0 - 16.0
Day 6 8 (26.7) 4.7 [4.7] 3.0 1.0 - 16.0
Day 7 3 (10.0) 3.5 [1.8] 3.0 2.0 - 5.5
a
Data were collected by clinical nurse educators, N=30. bn of subjects who had an office visit on that day.

TABLE 2. Incidence of Adverse Events Post-PEG-J Placement in Outpatients during the First Four Weeks
Following PEG-J Placement, n (%) patientsa

Week 1 Week 2 Week 3 Week 4 Weeks 1-4

Any adverse event (AE) 20 (58.8) 6 (17.6) 0 5 (14.7) 23 (67.6)
AEs Occurring in  2 patients:
Procedural pain 13 (38.2) 0 0 0 13 (38.2)
Anxiety 5 (14.7) 0 0 0 5 (14.7)
Flatulence 4 (11.8) 0 0 0 4 (11.8)
Catheter site pain 3 (8.8) 0 0 0 3 (8.8)
Postoperative wound infection 3 (8.8) 0 0 0 3 (8.8)
Catheter site infection 0 2 (5.9) 0 1 (2.9) 2 (5.9)
Constipation 2 (5.9) 0 0 0 2 (5.9)
Dry mouth 2 (5.9) 0 0 0 2 (5.9)
Fall 0 1 (2.9) 0 1 (2.9) 2 (5.9)
Procedural site reaction 0 1 (2.9) 0 1 (2.9) 2 (5.9)
Urinary tract infection 1 (2.9) 1 (2.9) 0 0 2 (5.9)
a
N=34; bMedDRA preferred terms

2
Fernandez et al. Mov Disord. 2014 Dec 24.
302
Updated long-term safety from ongoing phase 3 trials of
levodopa-carbidopa intestinal gel in patients with advanced
Parkinsons disease
R.L. Rodriguez, N. Schmulewitz, D. Stein, W.Z. Robieson, C.M. Hall,
S. Eaton, K. Chatamra, J.A. Benesh, A.J. Espay (Gainesville, FL,
USA)
Objective: To assess the long-term safety of levodopa-carbidopa
intestinal gel (LCIG) in advanced Parkinsons disease (PD) patients.
Background: LCIG is a long-term treatment option for advanced
PD patients whose motor fluctuations cannot be controlled by oral
medication. The LCIG system administers continuous levodopa infu-
sion via percutaneous endoscopic gastrojejunostomy (PEG-J) and
reduces motor fluctuations as shown in multiple studies.1
Methods: Cumulative adverse events (AEs) from four ongoing
phase 3 studies through 31 March 2014 were integrated and summar-
ized using two datasets. Open-label (N=412), comprised of data
from all patients who received open-label LCIG treatment, was used
to present all safety except that related to the device/procedure (D/
P). All PEG-J (N=395), included data from patients who had PEG-
J placement and was used to present safety related to the D/P.
Results: Exposure to LCIG at cutoff averaged 854 (SD=564)
days. 94% (387) of patients had a treatment-emergent AE of any
kind. 76% (300) reported a D/P-associated AE, most commonly
complication of device insertion (41%), abdominal pain (36%), pro-
cedural pain (27%), and postoperative wound infection (26%). 92%
(379) reported a non-D/P associated AE, most commonly
insomnia (23%), fall (23%), nausea (20%), and constipation (20%).
D/P-associated serious AEs (SAEs) were reported by 17% (68) of
patients, and non-D/P associated SAEs were reported by 42% (171).
Over the 963 total patient years of exposure, 18% (72) discontinued
participation due to an AE, most commonly: complication of device
insertion (2.4%), death (1.2%), abdominal pain (1.0%), and pneumo-
nia (1.0%). There were 34 deaths (8.3%) due to an AE: 2 were con-
sidered possibly related to the treatment system and 32 unrelated or
unlikely related.
Conclusions: The majority of the D/P-associated AEs are known
complications of PEG-J, and most of the non-D/P associated AEs are
frequently associated with levodopa, PD, or the elderly. Discontinua-
tion due to AE was low compared to PD trials of much shorter dura-
tion.2 This cumulative update of the largest, longest-term safety
dataset for LCIG should be considered when evaluating benefit/risk
associated with this treatment.
1
Olanow et al. Lancet Neurol. 2014;13:141-9 & Fernandez et al.
Mov. Disord. 2014 Dec 24.
2
Stocchi et al. Mov. Disord. 2013;38:1838-46 & Pahwa et al.
Park. Rel. Disord. 2014;20:142-8.
303
Responder analyses of droxidopa in patients with symptomatic
neurogenic orthostatic hypotension
G.J. Rowse, L.A. Hewitt, A. Shields, R. Freeman, H. Kaufmann
(Deerfield, IL, USA)

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION S117

Objective: To evaluate the distribution of symptom (dizziness/

lightheadedness) improvement with droxidopa in patients with symp-
tomatic neurogenic orthostatic hypotension (NOH) and to estimate
the point at which a change in Item 1 of the Orthostatic Hypotension
Symptom Assessment (OHSA; dizziness/lightheadedness) score
becomes clinically meaningful (ie, a responder definition).
Background: Symptomatic NOH results from an inadequate
release of norepinephrine (NE) upon standing. The cardinal symptom
is dizziness/lightheadedness resulting from cerebral hypoperfusion.
Droxidopa is an NE prodrug that is FDA approved to treat sympto-
matic NOH caused by primary autonomic failure (Parkinsons dis-
ease, multiple system atrophy, and pure autonomic failure),
dopamine b-hydroxylase deficiency, and nondiabetic autonomic
neuropathy.
Methods: Analyses were performed on results of OHSA Item 1
from two, phase 3 trials: NOH301 and NOH306. In each trial
patients had 2 weeks of droxidopa titration followed by 1 week
of double-blind treatment. The responder definition of OHSA Item 1
was estimated using anchor-based methods employing the patient-
reported Clinical Global Impression-Severity (CGI-S) and Item 1.12
of The Movement Disorder Society-Unified Parkinsons disease Rat-
ing Scale and distribution-based methods (1/2 SD; SEM).
Results: Significantly higher proportions of droxidopa- vs
placebo-treated patients had improvements of 1 to 4 units on
OHSA Item 1 after 1 week in both studies. OHSA Item 1 scores cor-
related with improvement in CGI-S (NOH301: r=0.54, P<0.0001;
NOH306: r=0.51, P<0.0001) indicating that patients who reported
global improvement in their NOH also reported reduced dizziness/
lightheadedness in both studies; those with no change or worsening
of CGI-S scores had little to no change in OHSA Item 1 score.
Using anchor- and distribution-based methods, the point at which a
change in OHSA Item 1 scores becomes clinically meaningful
ranged from 22.18 to 22.48 and 21.09 to 21.59 (on an 11-point
scale), respectively.
Conclusions: A higher proportion of droxidopa- vs placebo-
treated patients experienced NOH symptom improvement above the
responder definition thresholds. The responder analyses support the
robustness of the data and indicate that droxidopa provides clinically
meaningful benefits to patients with symptomatic NOH.
304
Examining dopaminergic and clinical differences between
habitual exercisers and sedentary individuals with Parkinsons
disease
M.A. Sacheli, D.K. Murray, N. Vafai, K. Dinelle, N. Heffernan, J.
McKenzie, S. Appel-Cresswell, M. Schulzer, V. Sossi, A.J. Stoessl
(Vancouver, BC, Canada)
Fig. 1. (304).
Objective: To examine differences in dopamine (DA) release and
assess clinical differences between Parkinsons disease (PD) patients
who exercise regularly (habitual exercisers) and those who are
sedentary.
Background: Exercise is used as an adjunct therapy for PD, but
the mechanisms of benefit are poorly understood. It is suggested that
exercise may improve motor function through increased DA release
and may also enhance DA transmission via upregulation of DA D2
receptors.
Methods: Eighteen subjects with mild to moderate PD were allo-
cated into habitual or sedentary groups based on their amount of
exercise. Maximal oxygen uptake (VO2 max) was recorded in all
subjects to confirm cohort allocation. Two [11C]Raclopride PET
scans separated by 30min of cycling were conducted. The baseline
scan was compared to the post exercise scan to determine the change
in binding potential (DBPND), a measure of DA release, in 8 ROIs;
caudate and anterior, middle and posterior putamen for each brain
hemisphere. One subject from each cohort was excluded due to scan-
ning complications. Motor assessments (UPDRS III; Purdue peg-
board; finger tapping; and Timed-up-and-go, TUG) and non-motor
assessments (Montreal Cognitive Assessment; Beck Depression
Inventory; Starkstein Apathy Scale, SAS; and reaction time) were
compared between the two groups. A 2x2 (group x hemisphere)
ANCOVA with the baseline scan BPND used as a covariate was
conducted (age was also considered as a covariate, but it was not
significant). Motor and non-motor clinical measures were assessed
with independent t-tests.
Results: There was no difference in BPND at baseline between
the groups. A group by hemisphere interaction (F(1, 12)=5.6804,
p<.05) for DBPND was found in caudate. Fishers LSD Post-Hoc
revealed a significant difference between habitual and sedentary
(p<0.05) in the worse hemisphere and a trend (p50.053) in the bet-
ter hemisphere. [figure1] In both hemispheres of caudate habitual
exercisers had greater DA release compared to sedentary subjects.

TABLE 1. Patient demographics, mean (standard deviation)

Habitual Sedentary p value
Years since Diagnosis 5.63 (4.57) 5.14 (2.04) 0.8012
Age 62.78 (5.97) 68.89 (4.78) 0.0292*
Gender 9M 5 M, 4 F
UPDRS III (OFF) 19.25 (10.08) 26.00 (15.67) 0.3148
UPDRS III (ON) 16.22 (11.14) 23.33 (13.73) 0.2452
VO2 max 36.53 (5.94) 16.83 (3.24) 0.0000*
Baseline exercise participation counts/week 15.63 (6.50) 3.07 (3.72) 0.0001*
Baseline exercise participation minutes/week 516.72 (285.55) 104.26 (63.17) 0.0006*
UPDRS III, Unified Parkinsons disease Rating Scale motor section OFF (after 12 hour withdrawal from dopaminergic medication), ON (peak
dose); VO2 max, maximal oxygen consumption during cycling; Baseline exercise participation counts/week, the average amount of exercises
done for more than 20 minutes multiplied by intensity, x1 for mild, x2 for moderate and x3 for vigorous exercise; Baseline exercise participation
minutes/week, duration of exercise activities recorded in minutes multiplied by the counts per week. Subjects who exceed 4 counts of participa-
tion and 120 minutes of exercise per week are considered a habitual exerciser.

Movement Disorders, Vol. 30, Suppl. 1, 2015

S118 POSTER SESSION
Fig. 2. (304).
Additionally, habitual exercisers had lower scores (less apathy) on
the SAS (p<0.05) and were faster on finger tapping (right hand
p<0.01, left hand p<0.05) and the TUG (p<0.05). [figure2]
Conclusions: These findings suggest habitual exercise contributes
to relative preservation of motor and non-motor function, which may
in part be mediated by increased DA release.
305
Adenosine A2A receptor antagonist istradefylline can be more
beneficial in Parkinsons disease patients of advanced stage
without troublesome dyskinesia
H. Saiki, S. Matsumoto (Osaka, Japan)
Objective: To examine the effect of adenosine A2A receptor
antagonist istradefylline in motor and non-motor symptoms of
advanced Parkinsons disease (PD) patients.
Background: Istradefylline is a first-in-class adenosine A2A
receptor antagonist antiParkinsonian agent and has been marketed in
Japan since 2013, reported effective in improving off symptoms.
However, detailed effect against motor and non-motor symptoms in
advanced PD patients is not fully revealed.
Methods: 11 patients (six females and five males, averaged age
59.3 y.o., and averaged disease duration 12.5 years) attended this
study. Istradefylline was added on 20mg daily initially, then
increased to 40mg daily after 4weeks. Fluctuations were evaluated
patients diary. Motor and non-motor symptoms were evaluated with
MDS-UPDRS, apathy scale, Beck depression inventory II (BDI-II),
revised version of Parkinsons disease sleep scale(PDSS-2), Epworth
sleepiness Scale (ESS), The Parkinsons disease Questionnaire
(PDQ-39). The evaluations were scheduled before istradefylline
administration and after 4weeks administration of 40mg daily.
Results: Averaged off time decreased 1.4 hours after 40mg
administration of istradefylline without increasing of on time with
troublesome dyskinesia. Averaged MDS-UPDRS part III score was
decreased 32.0 to 27.5. However, there was no meaningful change in
scores of AS, BDI-II, PDSS-2, ESS, summary index of PDQ-39.
Movement Disorders, Vol. 30, Suppl. 1, 2015
Five patients discontinued istradefylline after the evaluation.
Non-motor scores of continued six patients showed tendency of
improvement. In contrast, those of discontinued group showed tend-
ency of worsening though improvement of MDS-UPDRS part III
was greater than continued patients. Discontinued patients had trou-
blesome dyskinesia initially, and off dyskinesia increased after
istradefylline administration. Continued patients had no troublesome
dyskinesia initially, and off dyskinesia decreased after istradefyl-
line administration.
Conclusions: It is considered that advance PD patients without
troublesome dyskinesia can be more beneficial by treatment with
istradefylline.
306
Amantadine vs rimantadine in Parkinsonian disorders: A
retrospective comparative tolerability study
B. Saminejad, K. Gannon, M. Zorn, D.R. Shprecher (Salt Lake City,
UT, USA)
Objective: This retrospective chart review study was aimed to
evaluate the comparative tolerability of rimantadine vs amantadine
for motor symptoms of Parkinsonian disorders.
Background: Amantadine is widely used to treat freezing of gait
(FOG,) dyskinesia and other motor symptoms of Parkinsons disease
(PD) and atypical Parkinsonian disorders. Rimantadine is a closely
related compound with fewer anticholinergic properties that could be
a better tolerated choice.
Methods: Fourteen patients were identified through chart review
with PD or progressive supranuclear palsy (PSP) who took amanta-
dine and then were switched to rimantadine due to side effects. Each
record was reviewed to investigate the reason amantadine was started
and why was the medication stopped/switched to rimantadine.
Results: The average age of our patients was 67.8 years. Out of
the 14 patients 13 had diagnosis of PD, one PSP. Amantadine was
switched to rimantadine in three patients due to insomnia, two
patients due to blurry vision, two due to orthostatic hypotension, two
due to worsening of cognitive impairment, one due to psychosis, two
 POSTER SESSION S119

Changes of diary and clinical scores; continued and discontinued patients

continued patients discontinued patients

pre D pre D
Age (years) 55.7 - 63.6 -
PD duration (years) 12.8 - 12.2 -
Levedopa equivalent dose at baseline (mg) 1013.5 - 1009.5 -
Off (hours) 5.8 -1.1 7.7 -1.8
On without troublesome dyskinesia (hours) 11.4 0.9 9.4 2.0
On with troublesome dyskinesia (hours) 0.0 0.0 0.6 0.0
Off with dyskinesia (hours) 0.9 -0.9 1.5 1.0
MDS-UPDRS part I 11.3 1.3 11.0 1.8
MDS-UPDRS part II 14.8 1.5 19.8 1.4
MDS-UPDRS part III 28.3 -0.8 36.4 -8.8
MDS-UPDRS part IV 5.0 0.5 10.0 1.2
Beck depression inventory II 17.7 -1.8 17.6 4.0
Epworth sleepiness scale 10.8 -1.0 9.4 3.4
Revised version of Parkinsons disease sleep scale 17.5 0.5 20.4 0.6
Apathy scale 15.5 -2.0 14.7 1.3
The Parkinsons disease questionnaire summary index 28.4 -5.8 28.9 12.3
D is difference between pre and post administration of istradefylline 40mg.

due to allergic reaction and two due to livedo reticularis. Rimanta-
dine was tolerated in 80% of these patients, and had to be discontin-
ued in 3 patients (20% of our patients that were studied) . One
patient developed psychosis and two developed dizziness. Rimanta-
dine was stopped in two patients due to lack of benefit. In the rest of
the patients rimantadine was tolerated without any side effects. Thus
far, eight patients have had documented improvement in their symp-
toms on rimantadine. Average duration of treatment thus far has
been 6.62 months (range between 2 to 15 months).
Conclusions: Rimantadine can be used in patients who develop
side effects when taking amantadine. Further tolerability/efficacy trial
on larger patient population needs to be done to have a larger sample
of patients.
between 63.7% to 72.1% for OPC groups vs. 50.9% for placebo and
52.5% for ENT. The improvement tendency was significant for both
25mg-OPC (p50.0055; p50.0370) and 50mg-OPC (p50.0008;
p50.0091) compared to placebo and ENT, respectively. The proportion
of patients assessed by investigators (IGAC) as having improved
ranged between 60.3% to 73.0% for OPC groups vs. 49.9% for placebo
and 50.9% for ENT. The improvement tendency was significant for
50mg-OPC (p50.0005 and p50.0070 vs. placebo and ENT, respec-
tively). No tendency was apparent for ENT when compared to placebo.
Conclusions: OPC was associated with favourable ratings in
patients and clinicians global impressions of change, in contrast to
essentially no difference for ENT compared to placebo in either of
these assessments.

307
Opicapone as adjunctive therapy to levodopa in patients with
Parkinsons disease and motor fluctuations: Global impressions
of change compared to placebo and entacapone
A. Santos, J. Ferreira, A. Lees, R. Pinto, N. Lopes, T. Nunes, J.F.
Rocha, P. Soares-da-Silva (S. Mamede do Coronado, Portugal)
Objective: Evaluate the subjects and investigators global assess-
ments of change in overall condition after opicapone (OPC) treat-
ment compared to placebo and entacapone (ENT).
Background: OPC, a novel once-daily peripheral COMT inhibi-
tor, has shown to be safe and effective in reducing OFF-time in Par-
kinsons disease (PD) patients with motor fluctuations. The subjects
and investigators global assessment of change (SGAC and IGAC)
are commonly used instruments in clinical trials that provide means
for evaluating perceptions about the change in overall condition with
treatment.
Methods: Multinational, multicentre, double-blind, 14 to 15-
week, placebo- and active-controlled study (BIPARK I). SGAC and
IGAC were secondary efficacy endpoints. The SGAC and IGAC was
performed in comparison to prior enrollment in the study (very
much improved to very much worse). Both were analysed with a
non-parametric van Elterens test stratified by region.
Results: The analysis set included 590 patients, placebo (N=120),
5mg-OPC (N=119), 25mg-OPC (N=116), 50mg-OPC (N=115) and
ENT (N=120). For SGAC ratings, the proportion of patients report-
ing to have minimally, much or very much improved ranged
308
Identifying potential best practices for treating Parkinsons
disease: A mixed methods approach
P. Schmidt, F. Cubillos, T. Simuni, C. Marras, M. Guttman, M.
Rafferty, K.A. Sabadosa, E.C. Nelson (Miami, FL, USA)
Objective: To identify specific care processes (potential best
practices or PBPs) for treating Parkinsons disease (PD) patients that
may be associated with better treatment outcomes for subsequent
prospective testing of their effects on PD patients.
Background: PD is a complex disease with diverse and variable
combinations of symptoms that usually requires multi-faceted treat-
ments that evolve over time to mitigate the effects of disease pro-
gression and co-morbidities. Unfortunately, the evidence base on the
relative efficacy of interventional approaches targeting different
symptoms across the range of patient demographics, phenotypes, and
disease stages is not well developed.
Methods: An interdisciplinary research team conducted a mixed
methods study to identify specific care processes that might be con-
sidered potential best practices (PBPs). First, we used multivariate
analyses to identify centers that appeared to have superior outcomes
across six outcome domains: mobility, cognitive status, health related
quality of life, falls, hospital admissions and caregiver burden. Case-
mix adjusted outcomes across 20 centers caring for over 7000 PD
patients were analyzed; the results showed that two centers had sig-
nificantly better outcomes. Second, we conducted site visits to these
two centers to gather qualitative data to determine PBPs that might be

Movement Disorders, Vol. 30, Suppl. 1, 2015

S120 POSTER SESSION
associated with better outcomes. Qualitative data on care processes
were based on direct observations and on interviews of interdiscipli-
nary center staff (n551), PD patients and family caregivers (N=34).
Third, we used a modified Delphi process to identify several PBPs.
Results: The quantitative results showed that one center had sig-
nificantly better outcomes on cognitive status, hospital admissions,
and quality of life and another center had significantly better out-
comes for caregiver burden and mobility. The qualitative results sug-
gested PBPs related to approaches to physical therapy and exercise,
mental health care, palliative care, and caregiver support.
Conclusions: Our data suggest that some centers appear to be
attaining superior outcomes for PD patients and that these outcomes
may be associated with specific care processes that could be tested
prospectively to turn potential best practices into evidence-based care
recommendations.
309
The analysis of the use of kinemetric devices to predict
outcomes: Results from NPF-QII
P. Schmidt, J. Nutt, M. Guttman, C. Marras, T. Simuni, F. Cubillos,
D. Tarsy, K.E. Friedl, E.C. Nelson, B.R. Bloem, M.S. Okun (Miami,
FL, USA)
Objective: To quantify the contribution of objective kinematic
measurement to understanding patient status in Parkinsons disease.
Background: With growth of commercial activity monitors,
patients and clinicians are increasingly interested in understanding how
motion tracking can be employed to better understand patient status.
Methods: Data was collected on a subset of 168 subjects in the
longitudinal National Parkinsons Foundation Quality Improvement
Initiative (NPF-QII) using commercial six-axis kinematic sensors
(Opals by APDM). The subject performed a task consisting of rising
from a chair, walking 7 meters, turning, returning to the chair, and
sitting back down (ITUG) with the sensors attached to each ankle
and at the waist. APDMs standard kinemetric outcomes were com-
puted, including assessments of straight-line gait and turn phases,
and these measures were compared with clinical and patient reported
outcomes including demographics,motor and cognitive evaluations,
and health-related quality of life (PDQ-39).
Results: The 30 metrics computed from the ITUG were well cor-
related with each other and with the manually timed TUG test (con-
ducted separately) within subjects, with only 8 of the 30 ITUG
measures not significantly predicted by the TUG (p < 0.05; R2 for
correlations between 0.23 and 0.73). Comparing the ITUG results
with five demographic, five treatment, and seven outcome variables,
individual ITUG measures were correlated with (all p < 0.05): TUG
(R2=0.73), disease duration (0.40), falls (0.39), age (0.31), use of a
dopamine agonist (0.28), physical and occupational therapy (0.27),
motor fluctuations (0.26), Hoehn and Yahr stage (0.26), comorbid-
ities (0.25) and total number of medication classes (0.23). The most
valuable measures for predicting clinical parameters were cadence
and gait cycle time, which correlated with disease duration, use of a
dopamine agonist, occupational therapy, TUG, and falls. Least valua-
ble were metrics related to the steps taken in the turn (number, fre-
quency), stance and double stance percentages, and swing velocity.
None of the ITUG measures significantly correlated with either the
cognitive evaluation or PDQ-39 results.
Conclusions: ITUG measures could provide valuable insight into
motor aspects of PD, including fall risk and benefits from interventions.
310
Big data in Parkinsons: Status of NPF-QII after five years
P. Schmidt, F. Cubillos, T. Simuni, C. Marras, M. Guttman, E.C.
Nelson (Miami, FL, USA)
Objective: To describe the status and recent findings from the
National Parkinsons Foundation launched the Quality Improvement
Movement Disorders, Vol. 30, Suppl. 1, 2015
Initiative (NPF-QII), a 7,500 subject observational clinical study con-
ducted at 21 expert clinics in 4 countries.
Background: In 2009, NPF launched NPF-QII with the twin
aims of (1) analyzing Parkinsons disease in the context of expert
care and (2) identifying, evaluating, and disseminating best practices
in Parkinsons care.
Methods: At participating expert clinics, a modified sequential
recruitment process has been employed to recruit subjects into the
study. The study is based on a simple standardized data set integrating
demographics; validated surveys and evaluations for health related
quality of life (PDQ-39), caregiver strain (MCSI), mobility (timed up-
and-go), disease severity (Hoehn and Yahr stage); a subset of the
MoCA evaluation for cognition; and an evaluation of living situation,
comorbidities, medications and treatment options, and utilization (hos-
pitalizations). Outcome analysis has focused on six key areas: mobil-
ity, cognition, HRQL, utilization, caregiver strain, and falls.
Results: As of 1/1/2015, 7,717 subjects have been recruited into
the study. Over the 66 months of the study, 17,850 evaluations have
been completed. Over 1872 (24%) subjects have withdrawn, with
1,116 (60% of withdrawals) due to changing the site of care, and
868 subjects have died. Currently, 20 centers are actively following
patients, with a mean of 367 subjects per center (SD: 172). At
recruitment, subjects were on average 67.1 years old (SD: 10.0) and
7.0 years since diagnosis (SD: 5.9) with 783 (10%) subjects recruited
less than one year since diagnosis. Median follow-up is 1.1 years,
with follow-up data collected on 4,874 (63%) subjects. A study of
kinemetric devices conducted within the study population has been
conducted and the results presented elsewhere and retrospective anal-
yses of the dataset have been conducted on diverse topics.
Conclusions: This study has demonstrated the value of prospective,
systematic collection of clinical data based on a simple minimal data
set that may be supplemented in sub-studies. Because of its size and
structure, the over-all dataset is well suited to the analysis methods
associated with very large sample size data sets termed big data.
311
Engaging people with Parkinsons in determining and defining
research priorities: The PDF community choice research award
K. Schroeder, B.A. Vernaleo, M. Barry, D. Blomquist, D. Cook, C.
Evers, J.C. Beck, V.L. Todaro (New York, NY, USA)
Objective: To understand how engaging people with Parkinsons
disease (PD) and their care partners in determining and defining
research priorities can help address the unmet needs of patients.
Background: The Parkinsons disease Foundation (PDF)
launched the Community Choice Research Award (CCRA) in 2013.
The purpose of this award is to fund a one and a half day dialog
among scientific and lay leaders on a research priority that is an
unmet need as identified by patients. In 2014, PDF funded two
CCRAs and gathered leaders in the field of PD, specialists from
related areas and people with PD to move the field forward by
assessing the understanding and treatment of two patient-identified
symptoms that are under-researched.
Methods: A questionnaire was administered to people with PD
and care partners via the PDF website and in-person via electronic
tablet at the 2013 World Parkinsons Congress to determine research
priorities. A survey was administered to researchers and clinicians
who attended the research priority meetings to determine their opin-
ions on patient involvement.
Results: A total of 304 people with PD and care partners com-
pleted the survey. Responses were wide-ranging and fatigue and gas-
trointestinal dysfunction were selected by PDF reviewers as topics to
be funded. These research areas are not well managed with current
therapies, lack a substantial body of research in current literature
regarding etiology or treatment, and are particularly disabling aspects
of PD that lead to reduced quality of life.
Two conferences were held to discuss the issues surrounding
these research areas. The researcher and clinician experts attending
 POSTER SESSION
the meetings were surveyed (n519) and analysis indicates that 95%
of those responding thought that patient input enriched the meeting
dialog; 84% thought that patient input influenced the outcome of the
meeting; 95% felt that there is a role for patients in next steps
related to the meeting outcomes; and 68% were more inclined to
include patients in future scientific conversations.
Conclusions: Engaging people with PD and their care partners in
determining research priorities can lead to identifying unmet needs
that warrant attention by researchers. Researchers who collaborate
with patients on defining research priorities find that it adds value,
influences outcomes, and increases the likelihood of patients involve-
ment in future scientific conversations.
312
The profile of the hospitalized and re-hospitalized Parkinsons
disease patient: 5 year data from the National Parkinsons
Foundation
L. Shahgholi, S. De Jesus, S. Wu, Q. Pei, A. Hassan, P. Schmidt, M.
Okun (Gainesville, FL, USA)
Objective: To identify the prevalence and risk factors for re-
hospital encounters (Emergency room visit or hospitalization) among
people with PD.
Background: Parkinsons disease (PD) patients are at higher risk
of hospital encounters (emergency room visits and admissions) when
compared to the general population. However, the prevalence of hos-
pital encounters overtime remains unknown. This study aimed to
determine the rate of hospital encounters over 5 years, to create a
profile of these patients, and to identify associated and potentially
modifiable factors.
Methods: Data was analyzed for 7,507 PD participants enrolled
in the prospective International Multicenter National Parkinsons
Foundation study (20 sites). Follow up data for years 2-5 were avail-
able for 4,680, 2,755, 1,429, and 416 participants, respectively. This
data was analyzed to create a profile, and to better understand the
nature of longitudinal hospital encounters.
Results: The cohort had a mean age of 66.5 6 9.9, disease dura-
tion of 8.9 6 6.4, and PDQ-39 summary index of 25.2 6 15.9. The
rate of hospital encounters was 25.6%, 32.8%, 34.9%, 34 .2%,and
38.5% for years 1-5, respectively. The significant factors (p < 0.05)
associated with hospital encounters included the number of co-
morbidities (OR 1.297), Timed Up and Go Test (OR 1.206), Multi-
dimensional caregiver strain index (MCSI) (OR 1.17 per standard
deviation), presence of deep brain stimulation (OR 1.868), levodopa
usage (OR 1.692) and utilization of physical therapy (OR 1.472).
Among the PD participants who had a first year hospital encounter,
the longitudinal analysis revealed the rate of repeat encounters was
elevated in each of the following four years (48.1%, 45.6%, 46.9%
and 50.0%). Rate of and time to repeat encounters were significantly
correlated with MCSI, living situation, severity of disease (H&Y
staging and PDQ39 summary index), and number of co-morbidities.
Conclusions: PD patients have a high risk for hospitalization and
this risk increases in subsequent years. The co-morbidities, disease
stage, mobility, prior DBS, levodopa usage, and MCSI were identi-
fied as risk factors associated with hospitalization or re-
hospitalization.
313
Withdrawn by Author
314
Predictive factors of placebo effect in Parkinsons disease: A
meta-analysis
C.W. Shin, S.K. Hahn, B.J. Park, J.M. Kim, E.O. Park, B.S. Jeon
(Seoul, Korea)
S121
Objective: To examine predictive factors of placebo effect and
time-placebo effect correlations using both the year of study publica-
tion (YSP) and the year of study initiation (YSI) in randomized
double-blind placebo-controlled trials in Parkinsons disease (PD).
Background: Several factors have been reported to be related
with the placebo effect in PD. The temporal correlation of nocebo
effect in patients on placebo was reported in a meta-analysis in PD.
Till now, there have been no studies assessing predictive factors
affecting placebo effect and time-placebo effect correlation in PD
with a systematic meta-analytic approach.
Methods: We searched PUBMED, EMBASE, and CENTRAL
databases (to November 2014) and reviewed reference lists of
included studies. Eligible studies for the meta-analysis were selected
by inclusion criteria. Two reviewers extracted data on study charac-
teristics, participants characteristics in placebo group, and outcomes.
The pooled mean change of Unified Parkinsons disease Rating Scale
(UPDRS) part III (motor subscale) score from baseline to primary
end point of placebo treated group in individual studies was calcu-
lated using a random effects model. The impacts of predictive factors
were assessed using linear meta-regression models. Significant pre-
dictors were entered in the multivariate meta-regression model.
Results: Thirty eight studies (comprising 4,850 participants on
placebo) were included in the meta-analysis. The pooled mean
change in the UPDRS part III score from baseline to primary end
point was -1.348 (95% confidence interval [-2.134, -0.563],
p 5 0.001, I2 5 93.4%). Duration of treatment (b = 0.09, p = 0.002,
N [Number of studies] 5 38), use of concomitant levodopa (b = -
1.79, p = 0.013, N 5 38), and the baseline UPDRS part III score (b
= -0.30, p  0.001, N 5 32) were significant predictors in univariate
meta-regression analyses. More recently published (b 5 -0.03,
p 5 0.566, N 5 38) or conducted (b 5 -0.17, p 5 0.120, N 5 26) stud-
ies showed tendencies to higher placebo effect. Duration of treat-
ment (b 5 0.07, p 5 0.013) and the baseline UPDRS part III score
(b 5 -0.29, p 5 0.001) were statistically significant in the multivar-
iate meta-regression analysis.
Conclusions: Duration of treatment and the baseline UPDRS part
III score were the independent predictors of the magnitude of pla-
cebo effect in randomized controlled trials in PD.
315
Resistance training with instability is more effective than
conventional resistance training for patients with Parkinsons
disease
C. Silva-Batista, D.M. Corcos, H. Kanegusuku, L.T.B. Gobbi, E.
Mattos, M.T. de Mello, M.E.P. Piemonte, C. Forjaz, H. Roschel, V.
Tricoli, C. Ugrinowitsch (S~
ao Paulo, Brazil)
Objective: To compare the effects of conventional resistance
training (RT) and resistance training with instability (RTI) in the
signs, quality of life, neuromuscular and physical function variables
on patients with Parkinsons disease (pPD).
Background: PD is characterized by motor and non-motor signs.
These signs negatively affect physical function, quality of life, and
neuromuscular parameters. RT is a usual strategy to counteract the
decline in neuromuscular and physical function parameters. How-
ever, the addition of instability to RT (RTI) may enhance not only
neuromuscular and physical function variables but also PD signs.
Methods: Thirty-nine pPD in moderate stages of the disease
(tested and trained in the clinically on state) were equally distrib-
uted into three groups: control group (CG), RT group (RTG), and
RTI group (RTIG).
Experimental groups underwent 12 weeks of training and CG did
not perform any exercise training. RTG performed hypertrophy-
oriented training (squat, pull down, leg press, chest press and plantar
flexion) and RTIG performed the same exercises but combined with
instability devices (i.e., bosu, dyna disk, balance disk, Swiss ball)
twice week. Motor signs (UPDRS-III), non-motor signs (MoCA),
activities of daily living (UPDRS-II), quality of life (PDQ-39), timed
Movement Disorders, Vol. 30, Suppl. 1, 2015
Fig. 1. (315).

Fig. 2. (315).
 POSTER SESSION
TABLE 1. Characteristics of the patients with Parkinsons disease (n 5 39) by group. Mean6SD.
Characteristics CG
Demographic
Men/women (number of patients) 8/5
Age (years) 64.2 6 8.3
Educational level (years) 8.7 6 2.1
Anthropometrical
Body weight (kg) 69.2 6 11.4
Body height (cm) 1.69 6 0.1
Clinical
Mini-Mental State Examination (score) 28.5 6 1.8
Beck Depression Inventory (score) 5.2 6 1.3
Years since diagnosis (years) 10.7 6 6.1
UPDRS-II (score) 22.9 6 4.8
UPDRS-III (score) 40.9 6 8.5
Hoehn and Yahr staging scale (a.u) 2.5 6 0.4
L-Dopa equivalent units (mg/day) 478.5 6 253.6
CG 5 control group, RTG 5 resistance training group, RTIG 5 resistance training with instability group, UPDRS-II and III 5 Unified Parkinsons
disease Rating Scale part II and III daily live activities and motor subscale, respectively.
up and go (TUG), balance evaluation systems test (BEST), leg press
one repetition maximum (1RM), rate of torque development (RTD)
of knee-extensor muscles, presynaptic inhibition (PSI) and disynaptic
reciprocal inhibition (RI) of the soleus muscle of the most affected
leg were compared before and after the training period.
Results: Clinical (UPDRS-II and III, PDQ-39 and MoCA) [fig-
ure1] and physical function (TUG and BEST) variables improved
only after RTI (p < .001). Neuromuscular variables, such as 1RM
and PSI increased after both RT (p < .002) and RTI (p < .002), while
RTD and RI increased only after RTI (p < .001) [figure2].
Conclusions: Our data suggest that RTI is more effective than
RT for pPD because it improves quality of life, neuromuscular and
physical function parameters in short time of intervention, thus alle-
viating the PD-related signs. Financial support: FAPESP: 2011/
04242-3, 2012/03056-4 and 2013/04970-4.
316
Biomarkers of pioglitazone effects in Parkinsons disease
D.K. Simon, T. Simuni, J.J. Elm, J. Clark, A.K. Graebner, D.J.
Babcock, L. Baker, B. Dunlop, M.E. Emborg, C. Kamp, J.C.
Morgan, G.W. Ross, S. Sharma, B. Ravina, On Behalf of the NET-
PD Investigators (Boston, MA, USA)
Objective: To assess the relationship of peripheral biomarkers
with pioglitazone treatment and disease progression.
Background: Multiple mechanisms are thought to contribute to
the pathogenesis of Parkinsons disease (PD), including mitochon-
drial dysfunction, oxidative stress, and inflammation. Pioglitazone is
an oral hypoglycemic agent that enhances mitochondrial energy
metabolism, in part by upregulating activity of peroxisome
proliferator-activated receptor gamma (PPAR) coactivator 1-alpha
(PGC-1a), a transcriptional coactivator that controls mitochondrial
biogenesis. Pioglitazone also has both antioxidant and anti-
inflammatory activity, and is neuroprotective against MPTP in mice
and in non-human primates. Pioglitazone therefore was selected for
testing in a double-blind, placebo-controlled phase 2 futility trial to
determine if it has the potential to slow the progression of early PD.
A biomarker substudy was conducted as a part of the trial.
Methods: A total of 210 early-stage PD patients were random-
ized to receive either 45mg pioglitazone, 15mg pioglitazone or pla-
cebo and were followed up for 44 weeks in the parent trial. Blood
and urine samples for the biomarker substudy were collected at base-
line, 16 weeks, and 44 weeks. Biomarkers included levels of expres-
sion in peripheral leukocytes of PGC-1a and its target genes, plasma
levels of interleukin 6 (IL-6) as a marker of inflammation, and levels
S123
RTG RTIG
9/4 9/4
64.1 6 9.1 64.2 6 10.6
8.5 6 2.5 8.1 6 3.1
70.8 6 10.1 71.3 6 8.2
1.68 6 0.2 1.69 6 0.2
28.5 6 1.9 28.8 6 1.7
5.5 6 3.1 5.0 6 1.9
9.6 6 3.9 10.5 6 4.1
24.7 6 12.1 24.1 6 7.5
41.1 6 13.1 42.2 6 7.6
2.5 6 0.5 2.5 6 0.4
391.5 6 236.5 400.1 6 202.9
of urine 8-hydroxydeoxyguanosine (8OHdG) as a marker of oxida-
tive damage to DNA.
Results: Baseline levels of these biomarkers were not associated
with the rate of progression of PD as measured by the change in
total Unified PD Rating Scale (UPDRS) at 44 weeks. Pioglitazone
treatment was not associated with changes from baseline in levels of
the biomarkers. The magnitude of the change in the biomarkers dur-
ing the study did not significantly correlate with rate of progression
of PD.
Conclusions: Levels of expression PGC-1a and its target genes
in peripheral leukocytes, IL-6 in plasma and 8OHdG in urine were
not associated with the rate of PD progression and were not affected
by pioglitazone. Other agents that more effectively target these
mechanisms remain of potential interest as disease modifying thera-
pies in PD.
317
Can we reliably establish Parkinsons disease subtypes in de
novo patients: Follow up results from the PPMI study
T. Simuni, C.J. Caspell-Garcia, C. Coffey, S. Lasch, D. Jennings, C.
Tanner, K. Kieburtz, K. Marek, For the PPMI Investigators (Chi-
cago, IL, USA)
Objective: To determine the frequency and stability over time of
the sub group characterization of the tremor dominant (TD) versus
postural instability gait disorder dominant (PIGD) Parkinsons dis-
ease (PD) in de novo patients.
Background: While the unifying feature of PD is Lewy body
pathology, there is a substantial body of literature on the clinical sub
classification of PD, specifically into TD versus PIGD subtype. The
former has been shown to be associated with the slower progression
and less accumulation of disability. However, there is limited data
on the stability of this classification especially in early disease.
Methods: Parkinsons Progression Markers Initiative (PPMI) is
an international study of de novo, untreated (at enrollment) PD par-
ticipants and healthy controls (HCs). At baseline, participants were
assessed with a wide range of motor and non-motor scales including
The Movement Disorder Society-Unified Parkinsons disease Rating
Scale (MDS-UPDRS). TD versus PIGD subtype was defined based
on the formula published by Stebbins et al(Stebbins, Goetz et al.
2013). Subtype classification was repeated at each study visit. We
have previously reported pilot data, this analysis includes the data on
subtype characterization for the full PPMI cohort.
Results: 423 PD patients were recruited into the study. 381 par-
ticipants had data on subtype classification at year 1 and were
Movement Disorders, Vol. 30, Suppl. 1, 2015
S124 POSTER SESSION
included in the analysis. 266 were classified as TD at baseline. Of
these at 12 months, 215 (81%) remained TD; 21 (8%) shifted to
Indeterminate and 30 (11%) to PIGD. 72 were classified as PIGD
at baseline. Of these at 12 months, 47 (65%) remained PIGD, 18
(25%) were classified as TD and 7 (10%) as Indeterminate. These
changes were not affected by the start of dopaminergic treatment.
Conclusions: Clinical classification of PD into TD versus PIGD
subtype is subject to substantial variability over first year in PD de
novo cohort. PIGD subjects at baseline seem about twice as likely to
have their status change at 12 months versus those classified as TD.
Dopaminergic therapy does not have an impact on the change of the
PD subtype. This instability has to be taken into consideration spe-
cifically when establishing correlations with the biomarkers and for
long term prognostication.
318
STEADY-PD III. A phase 3 study of isradipine as a disease
modifying agent in patients with early Parkinsons disease. Study
design and status update
T. Simuni, K.M. Biglan, D. Oakes, K. Helles, B.L. Greco, W.R.
Galpern, On Behalf of the STEADY PD III Investigators and
Parkinson Study Group (Chicago, IL, USA)
Objective: To evaluate the efficacy of isradipine 10 mg daily on
Parkinsons disease (PD) disability.
Background: Isradipine, a dihydropyridine calcium channel
antagonist with excellent penetration of the blood brain barrier, has
been shown to be neuroprotective in in vitro/in vivo models of Par-
kinsonism. Epidemiological data also points to a reduced risk of PD
with chronic use of dihydropyridines. Our recently completed Phase
II study found that isradipine 10 mg daily is safe and well tolerated
in participants with early PD. Finally, this dosage of Isradipine
achieves serum concentrations within the range found to be neuro-
protective in animal models of PD.
Methods: The study is as a 36 month, Phase 3, parallel group, placebo-
controlled study of the efficacy of isradipine 10mg daily versus placebo on
the progression of PD disability in 336 participants with early PD as meas-
ured by the change in the Unified Parkinsons disease Rating Scale
(UPDRS) Part I-III score over 36 months. Secondary outcome measures
include a number of clinically meaningful and widely accepted measures
of progression of disability in early PD including:1) Time to initiation and
utilization of dopaminergic therapy; 2) Time to onset of motor complica-
tions; 3) Change in non-motor disability. Exploratory measures will include
global measures of functional disability, quality of life, change in the
ambulatory capacity (sum of 5 UPDRS items: falling, freezing, walking,
gait, postural stability), cognitive function and pharmacokinetic analysis.
Results: The study was funded by NINDS and is being conducted
at 58 Parkinsons Study Group sites in US and Canada. Recruitment
began in November 2014 and remains ongoing.
Conclusions: This study represents a unique opportunity to evalu-
ate the potential impact of a novel therapy to slow progression of
PD disability and provide clinically meaningful benefits. If isradipine
is found to be effective in slowing PD progression, the study design
reflecting real life scenario and availability of low cost generic
isradipine would facilitate the translation of the study results into a
meaningful clinical application.
319
One year longitudinal change in the MDS-UPDRS scores in de
novo Parkinsons disease patients: Results from the PPMI study
T. Simuni, C. Caspell-Garcia, C. Coffey, S. Lasch, D. Jennings, C.
Tanner, K. Kieburtz, K. Marek, For the PPMI Investigators (Chi-
cago, IL, USA)
Objective: To determine the longitudinal change in The Move-
ment Disorder Society Unified Parkinsons disease Rating Scale
(MDS-UPDRS) in the de novo Parkinsons disease (PD) patients.
Movement Disorders, Vol. 30, Suppl. 1, 2015
Background: MDS-UPDRS is a validated revised version of
UPDRS that is increasingly used in clinical practice. One current
barrier to increased utilization of the MDS-UPDRS as the primary
outcome in clinical trials is lack of the longitudinal data on the rate
of change specifically in de novo population.
Methods: Parkinsons Progression Markers Initiative (PPMI) is
an international study of de novo, untreated (at enrollment) DATscan
positive PD participants and healthy controls (HCs). At baseline and
every visit participants are assessed with a wide range of motor and
non-motor scales including the MDS-UPDRS. Once participants start
dopaminergic therapy (DT), MDS-UPDRS is assessed in the defined
OFF medications state (12 hours post last dose of DT) and ON state
(approximately an hour after the last dose of DT). We report analysis
of the MDS- UPDRS change over 1 year.
Results: 423 PD patients were recruited into the study. 382 par-
ticipants had MDS-UPDRS data at year 1 and were included in the
analysis. MDS-UPDRS Part I-III at baseline was 32.4 (SD 13.1)
(Min, Max 7-72) with the annual change of 6.8 (12.1)(p<,0001). 177
(46%) of subjects did not require DT by year 1, their baseline MDS-
UPDRS was 29.4 with the annual change of 8.9 (10.3)) (p<,0001).
206 (54%) of subjects were started on DT by year 1, their baseline
MDS-UPDRS was 36.5 with the annual change (OFF scores) of 5.0
(13.2)) (p<,0001). Subjects who required DT had higher baseline
MDS-UPDRS scores (p50.0006) but less annual change (p50014).
Conclusions: This is the largest dataset to report longitudinal
change of MDS-UPDRS in de novo PD patients. This data can be
used for the power calculations and sample size estimate for the
interventional studies in de novo PD population. Smaller annual
change in the treated PD subset likely reflects long duration effect of
DT which means that defined medications OFF state might not be
a reliable measure of the baseline deficit in the early PD population
frequently treated with long acting DT.
320
Effects of exercise on mobility, cognition and locomotor circuit
connectivity in Parkinsonism
K. Smulders, L. King, M. Mancini, D.S. Peterson, P. Carlson-Kuhta,
M. Fleming, H. Schlueter, B.W. Fling, J.G. Nutt, F.B. Horak (Port-
land, OR, USA)
Objective: 1) To determine the effectiveness of a cognitively
challenging Agility Boot Camp (C-ABC) exercise program on mobil-
ity, cognition, and brain connectivity and 2) to determine whether
baseline mobility and cognitive deficits, and the integrity of locomo-
tor brain circuitry predict responsiveness to exercise in patients with
Parkinsons disease (PD) and Frontal Gait disorders (FGD).
Background: Parkinsonian gait and balance impairments have
been associated with cognitive deficits. Hence, it may be helpful to
integrate cognitive challenges into mobility training. We present a
study design to evaluate a novel, cognitively-challenging mobility
rehabilitation program in patients with PD and in patients with FGD.
Methods: One-hundred-twenty patients with PD or FGD will par-
ticipate in this randomized, cross-over design study. The C-ABC
intervention will consist of 90-min group exercise sessions, 3 days
per week for 6 weeks. Exercises include mobility skills such as fast
walking in different directions, boxing, lunging, and navigating an
agility course, focused on a variety of postural domains. Cognitive
challenge is added by memorizing sequences, dual tasking and inhib-
iting actions. The education control program will consist of 90-min
chronic disease self-management program in a group setting, once a
week for 6 weeks, and 5x30 minutes of active relaxation with audio-
tape at home for 6 weeks. Hence, each program consists of 240
minutes of activities every week. The primary outcome measure is
dynamic balance using the Mini-BESTest. Secondary outcome meas-
ures of objective mobility, cognition and locomotor functional con-
nectivity are detailed in Figure 1. Pre- and post-testing will occur
before and after each phase of the cross-over interventions.
 POSTER SESSION
Fig. 1. (320).
Results: The first group of subjects has completed the study.
Nine subjects with PD and one FGD patient were enrolled in the
study, 2 subjects dropped out because of injury (n51) and inability
to participate in a group setting (n51). Preliminary results will be
presented at the congress.
Conclusions: We hypothesize that mobility, cognitive, and loco-
motor circuit impairments will improve after the C-ABC program
but not after the control intervention. We also hypothesize that FGD
patients with freezing of gait, executive dysfunction and reduced
white matter tracks between the penduncular-pontine nucleus (PPN)
and frontal cortex will be poor rehabilitation candidates.
[figure1]
321
Safety and clinical effects of NTCELLV R [immunoprotected
(alginate-encapsulated) porcine choroid plexus cells for
xenotransplantation] in patients with Parkinsons disease (PD):
26 weeks follow-up
B.J. Snow, K.M. Taylor, J.A. Stoessl, A. Bok, M. Simpson, D.
McAuley, L. Macdonald, K.J. Durbin, J. Lee, H. Lin, V. Sossi, K.
Dinelle, J. McKenzie (Auckland, New Zealand)
Objective: To assess (1) the safety of xenotransplantation of
NTCELL by monitoring the occurrence of adverse events, including
clinical and laboratory evidence of Porcine Endogenous Retrovirus
(PERV) in implant recipients and their partners and (2) the clinical
effects of NTCELL on brain metabolism as demonstrated on PET,
and on the clinical features of Parkinsons disease (PD) using clinical
measures including the Unified PD Rating Scale (UPDRS), in
patients with PD, 26 weeks after receiving an implant of NTCELL
into the brain.
Background: NTCELL comprises neonatal porcine choroid
plexus (CP) cells encapsulated in alginate microcapsules to protect
them from immune rejection. The capsules are a source of multiple
growth factors that enhance neuronal survival in vitro. NTCELL
implanted into brains of rats without immunosuppression survives
rejection for over a year. NTCELL implantation into the brains of
non-human primates with MPTP-induced Parkinsons-like lesions,
produces improved neurological function and histological changes
consistent with amelioration of the lesion. These studies have also
demonstrated the absence PERV transmission. NTCELL has the
potential to deliver biological neural agents for the treatment of PD
which cannot be achieved by conventional treatment.
Methods: We conducted an open administration of NTCELL via
unilateral implantation into the putamen in four patients with PD.
Changes in dopa brain metabolism on PET and changes in clinical
features and the course of PD were evaluated up to 26 weeks post-
S125
implant. Laboratory tests including haematology, biochemistry, and
PERV were performed at intervals throughout this period. All
adverse events were recorded.
Results: The mean age was 62.5 (SD 4.4) years and mean disease
duration was 12.8 (SD 6.8) years. NTCELL was well tolerated.
There was no evidence of PERV in implant recipients or their part-
ners. MRI showed no evidence for inflammation. Efficacy data will
be available by the time of presentation.
Conclusions: Our data suggest xenotransplantation of NTCELL
in patients with PD is safe and well tolerated. On the basis of these
data, a further clinical trial of NTCELL in a larger number of
patients with PD is warranted.
322
BDNF rs6265 met allele confers suboptimal response to
medication in early Parkinsons disease subjects
C.E. Sortwell, M.L. Hacker, P.E. Konrad, T.L. Davis, J.S. Neimat, L.
Wang, Y. Song, Z.R. Mattingly, A. Cole-Strauss, J.W. Lipton, D.
Charles (Grand Rapids, MI, USA)
Objective: To determine whether the single nucleotide polymor-
phism (SNP) in the brain derived neurotrophic factor (BDNF) gene
(rs6265) confers a differential treatment response to either optimized
drug therapy (ODT) or subthalamic nucleus deep brain stimulation
(STN DBS) in early stage Parkinsons disease (PD) subjects.
Background: The efficacy of oral levodopa and STN DBS in
treating PD motor symptoms is highly variable and may be influ-
enced by subject genotype. The BDNF rs6265 SNP is relatively
common (prevalence of 40.6%) with the met allele disrupting pack-
aging and release of activity-dependent BDNF. Both chronic levo-
dopa administration and STN DBS can induce changes in BDNF
levels raising questions regarding the importance of BDNF in patient
response to anti-Parkinsonian therapies.
Methods: We genotyped DBS and ODT subjects enrolled in the
Vanderbilt DBS in Early Stage PD clinical trial (NCT00282152).
Subjects were followed for a period of 24 months. Assessments
included UPDRS and PDQ-39.
Results: Five of 15 subjects (33%) in the DBS treatment arm and
6 of 13 subjects (46%) in the ODT treatment arm possessed either
the heterozygous major allele (val/met) or the homozygous minor
allele (met/met) of the BDNF rs6265 SNP. At baseline, all clinical
endpoints were statistically similar across BDNF genotype (p>0.05).
Met allele subjects in the ODT treatment arm exhibited significantly
higher ON total UPDRS at 18 (p50.017) and 24 months (p50.019),
and significantly higher PDQ-39 scores at 12 (p50.033) and 24
months (p50.018, compared to ODT subjects with the more com-
mon BDNF SNP variant (val/val). Met allele subjects demonstrated a
Movement Disorders, Vol. 30, Suppl. 1, 2015
S126 POSTER SESSION
response to ODT at baseline (change in UPDRS part III from OFF
to ON) that was nonexistent after 24 months. In contrast, no signifi-
cant differences were observed due to met allele status in subjects
receiving DBS at any time point with any clinical metric (p>0.05).
Conclusions: Possession of the BDNF rs6265 met allele confers
suboptimal efficacy for antiParkinsonian medication and suggests
that these patients may experience superior therapeutic benefit from
STN DBS. Validation in larger cohorts of early PD subjects treated
with either DBS or ODT is warranted to determine whether BDNF
rs6265 SNP genotype should be used as a guide to inform optimal
personalized patient care for the medical vs. surgical management of
PD.
323
The addition of a cognitive task influences the performance of
static balance and upper limb dexterity tasks in Parkinsons
disease
C.O. Souza, A.F. Barbosa, M.C. Voos, H.F. Chien, J. Chen, D.V.
Francato, E.T. Fonoff, E.R. Barbosa (Sao Paulo, Brazil)
Objective: To evaluate the impact of adding a cognitive task on
two distinct motor tasks involving static balance and dexterity.
Background: In cognitive-motor tasks, healthy elderly tend to
prioritize the motor task and show loss of cognitive performance.
This has been particularly described in balance activities, when they
prioritize the motor component to prevent falls. Parkinsons disease
(PD) patients may show poorer motor than cognitive performance in
postural dual-tasks. It is not clear whether this attentional strategy
would also be observed in dexterity tasks.
Methods: Forty PD patients (HY 2-3) and 25 healthy controls
were evaluated (all with score 24 on MMSE). The timed perform-
ance on Trail Making Test (TMT) was used for dexterity assessment.
Part A provided the result of motor performance. Part B provided
the cognitive-motor score and delta TMT was considered as the cog-
nitive task. One-minute static posturography measured the trajectory
standard deviation in the anteroposterior axis in single-task (ST,
motor score) and dual-task (DT, cognitive-motor score), when volun-
teers named as many animals as possible. Cognitive performance
was assessed on sitting position, with the enumeration of words start-
ing with F. ANOVAs compared both groups and conditions: Part A
(motor) vs. Part B (cognitive-motor); delta TMT (cognitive) vs. Part
B (cognitive-motor); ST sway (motor) vs. DT sway (cognitive-motor)
and fluency-sitting (cognitive) vs. standing (cognitive-motor). We
hypothezised that the interaction between any of these conditions
would show that the groups had adopted different strategies.
Results: On the dexterity task, PD group had higher times on
Part A and Part B (p50.05). An interaction groups vs. tasks was
Fig. 1. (323).
Movement Disorders, Vol. 30, Suppl. 1, 2015
Fig. 2. (323).
found (p<0.01) because PD subjects showed higher times on the
cognitive-motor condition (Part B).[figure1] On the balance task, ST
and DT interacted (p50.02) because the PD group showed higher
body sway on ST.[figure2] No differences on verbal fluency sitting
vs. standing were found.
[figure1]
Conclusions: Our results show that adding a cognitive task to
upper limb dexterity and static balance tasks lead to different strat-
egies between healthy and PD volunteers. In the dexterity task, PD
subjects prioritized the cognitive task. In the static balance, they
showed higher body sway in both ST and DT and the addition of the
cognitive task did not change this strategy.
324
Insights in nocturnal hypokinesia in Parkinsons disease:
Quantitative data analysis derived from multisite wearable
sensors
J. Sringean, P. Taechalertpaisarn, C. Thanawattano, R. Bhidayasiri
(Bangkok, Thailand)
Objective: To quantitatively monitor nocturnal movements of PD
patients and compare with their spouses by multisite accelerometers.
Background: Nocturnal hypokinesia can cause serious problem-
s,including pain,bedsore,asphyxia.Since it is difficult to accurately
report nighttime problems,wearable sensors can play a significant
role in the quantification of it in PD patients assisting physicians to
evaluation.
Methods: Subjects were PD patients who met the criteria diagno-
sis of the UKPDSBB and their spouses whose age difference were
less than 10 yrs.Participants were excluded if they were bed ridden,-
other neurological diseases,bone/joint diseases that may impair their
nighttime mobility.Demographic data,NADCS and MPDSS were
recorded.Multisite accelerometers were worn at both wrists,ankles,-
torso by patients and spouses,figure1.The duration of monitoring was
8 hrs.Body turn was defined by change of 15 degrees from previous
position of axis Y and sustained at least 5 minutes (1).Paired t-test
and Pearsons correlation were used.
Results: Nineteen patients(14males,5females) and their spouses
participated in the study.Demographic data,nocturnal parameters
were shown in table 1,2.We found the statistical significant differ-
ence in the number of body turn,degree of body turn,velocity,acceler-
ation,number of nocturia between patients and their
spouses.Significant moderate correlations were observed between
H&Ystaging and cramp score of NADCS,and total NADCS,the dura-
tion of disease and total NADCS,the mean time of body turn and
 POSTER SESSION S127

subscore of UPDRS section III(No.22-31,axial symptoms),and

MPDSS subscore(No.9),the average degree of body turn and MPDSS
subscore(No.3).

Demographic data of nineteen PD patients

Age at onset (years) 54.53 (9.95)

Duration of disease (years) 10.05 (5.23)

Hoehn & Yahr 2.53 (0.42)
UPDRS III 23.26 (8.20)
History of nocturnal hypokinesia 11/19 (57.9%)
Total LED (mg) 917.37 (464.71)
Nocturnal akinesia score 1.74 (1.18)
Nocturnal dystonia score 0.55 (0.85)
Fig. 1. (324).
Nocturnal cramp score 0.79 (0.95)
Total NADCS 3.05 (2.25)
Total MPDSS 142.89 (28.96)
determine the effect of service improvements on in-patient care and
NADCS: Nocturnal Akinesia Dystonia Cramp Score, MPDSS:
length of stay.
Modified Parkinsons disease Sleep Scale
Background: Hospital admissions for people with PD are poten-
tially catastrophic: the majority are emergencies and PD is adversely
affected by acute illness and hospital stay1. Ensuring medication
regimes continue uninterrupted is crucial, as any disruption can pro-
long in-patient stay. On evaluation of in-patient PD care at our hos-
pital in 2010, we found many areas needing improvement,
Nocturnal parameters of PD patients compared with their particularly medicines management. Following this, our in-patient
spouses. service was improved: we established a pathway for people with PD
Mean (SD) Patient Spouse p value* requiring admission and elective surgery, a PD cohort ward with a
dedicated interdisciplinary team, including hospital PD specialist
Age (years) 64.63 (7.95) 64.32 (8.46) 0.833 nurses, and a daily PD outreach ward round for patients on other
Weight (kg) 61.13 (13.84) 62.63 (10.86) 0.727 wards. To improve hospital staff awareness, we run quarterly Parkin-
BMI (kg/m2) 2.27 (3.65) 2.48 (4.14) 0.111 sons Awareness Courses.
Number of body 6.16 (4.88) 10.63 (7.34) 0.048 Reference:
turn (times) 1. Gerlach OHH, Winogrodzka A, Wim EJ. Clinical problems in
Mean time change of 15.4 (11.8) 17.2 (19.7) 0.536 the hospitalised Parkinsons disease patient: systematic review. Mov
body turn (sec) Dis 2011; 26 (2): 197-208
Average degree of change 56.84 (21.75) 76.65 (15.98) 0.007 Methods: We carried out an observational audit using medical
of body turn (degree) notes and medication chart review of 30 consecutive in-patients with
Velocity (radiance/sec) 0.10 (0.06) 0.15 (0.05) 0.011 PD. Patients also completed a questionnaire about their in-patient PD
Acceleration (radiance/sec2) 0.08 (0.04) 0.19 (0.04) < 0.001 care.
Number of getting up at night 1.84 (1.21) 1.21 (1.08) 0.030 Results: Six patients were admitted electively and 24 as emergen-
(Nocturia, times) cies - 12 were PD related. 23% were admitted to the PD ward, whilst
Duration of sleep (min) 498.21 (81.33) 453.21 (70.02) 0.063 20% were under surgical care and the remainder under other medical
specialities. Results were compared with the same audit conducted in
* Paired t- test, statistical significance if p  0.05. 2010.
Twenty-one patients returned the survey.
Conclusions: Our audit found that the interdisciplinary interven-
Conclusions: Our study has demonstrated the utility of wearable tions undertaken have improved all aspects of in-patient management
sensors for monitoring nocturnal movements in PD patients.The find- of PD, regardless of whether the patient was on a PD or non-PD
ings indicated that PD patients significantly had fewer turns,turn ward. With greater staff awareness and regular input, we have
slower, and turn in a smaller degree compared to their matched spou- ensured that PD medicines management is strictly followed and
ses.The severity of nocturnal movements also correlated with axial
symptom indicated by UPDRSIII and the sleep quality.Our data pro-
vides the object evidence of nocturnal mobility problems in PD
Results: Medicines management standards
patients, raising the awareness of nighttime problems in PD and
focus of intervention to improve patients quality of life. 2010 audit 2014 audit
Medicines Management Standards (30 patients) (30 patients)
325
Medicines reconciled within 24 hours 40% 81%
In-patient management of Parkinsons disease (PD): Service Medicines accurately charted 73% 97%
evaluation of a dedicated unit one year on Delayed first dose of PD medications 60% 3%
M.P. Sritharan, S.J. Jackson, A. Goff, S. Andrew, S. Moore, J. Received contra-indicated medications 20% 10%
Maguire (Bristol, United Kingdom) Assessed for self-administration 35% 65%
Other Outcomes
Objective: To: (1) identify if our service met UK standards for Length of stay 24 days 12 days
medicines management in PD: accurate medication prescription, 30 day re-admission rate 13% 13%
medications received on time, patients assessed for self-medication
and staff awareness of the importance of medication timing; (2) Twenty-one patients returned the survey.

Movement Disorders, Vol. 30, Suppl. 1, 2015

S128 POSTER SESSION

and treating patients at risk of osteoporotic fracture, however there

Results: Patient Survey on In-patient PD management are two validated tools for quantifying risk in UK patients:
QfractureVR 2 and the Fracture Risk Assessment Tool (FRAXV R ).
2010 audit 2014 audit Refs:
In-patient questionnaire (25 responses) (21 responses) 1.van den Bos F, Speelman AD, van Nimwegen M et al. BMD
and Vitamin D status in Parkinsons disease patients. J Neurol 2013;
Did you receive Always/mostly - 18 Always - 9; 260:754-760
your medications Mostly - 10; 2.Hippisley-Cox J, Coupland C. Derivation and validation of
at the usual time? Sometimes - 2; updated QFracture algorithm to predict risk of osteoporotic fracture
Never - 0 in primary care in the United Kingdom: prospective open cohort
Did your admission Yes - 9; No - 16 Yes - 4; No - 17 study. BMJ 2013; 344: e3427
cause deterioration Methods: Fracture risk in consecutive patients with IPD attending
in your PD? follow-up was assessed using QfractureV R and FRAXV R . Based on
Did you feel confident 60% 86% treatment thresholds, patients at risk were offered either a dual-
that staff caring for energy x-ray absorbtiometry (DXA) scan or bone protection therapy.
you knew enough Results: Seventy-seven patients with IPD, mean age 73 years
about PD? (SD 9.1), mean disease duration 9.87 years (SD 6.3) and mean modi-
Were you satisfied 75% 86% fied Hoehn-Yahr of 2.29 (SD 0.61) were assessed. 19 had sustained
with the management a prior osteoporotic fracture, only 7 were on secondary preventative
of your PD in hospital? therapy, whilst 18 were on supplemental calcium and Vitamin D.
QfractureVR identified 39% and 68% of patients at risk of major
medication regimes adhered to, with a reduction in length of stay. osteoporotic fracture and fractured neck of femur at 10 years, respec-
Patients responses reflected improvements in PD awareness and tively. 34 patients underwent a DXA: 38% had osteoporosis, 56%
management. Our improvements have highlighted means in which osteopaenia and 2 patients had normal BMD. Hoehn-Yahr stage 3-4
in-patient care of PD can be enhanced. was associated with higher likelihood of meeting treatment threshold
than stage 1-1.5 (p50.14).
Conclusions: Osteoporosis risk increases with IPD disease dura-
326 tion and disability and should be assessed early. Assessment with a
Assessing the burden of osteoporosis in a population of patients combination of scoring tools allows rationalisation of primary bone
with idiopathic Parkinsons disease protection.
M.P. Sritharan, S.J. Jackson (Exeter, United Kingdom)
Objective: To quantify the burden of predicted fracture risk in a
population of patients with idiopathic Parkinsons disease (IPD) 327
under follow-up and evaluate the number of patients meeting treat- Effects of levodopa-carbidopa intestinal gel on non-motor
ment threshold when assessed using QfractureV R and Fracture Risk
symptoms and safety of outpatient titration: A new phase 3 study
Assessment Tool (FRAXV R ).
in patients with advanced Parkinsons disease
Background: Patients with IPD have lower Vitamin D and bone
D.G. Standaert, J.T. Slevin, C. Hall, J. Dubow, S. Eaton, K.
mineral density (BMD) compared to age-matched healthy controls1. Chatamra, J.A. Benesh (Birmingham, AL, USA)
Additionally, poor mobility, low body weight and increased bone
turnover, results in a higher incidence of osteopaenia and osteoporo- Objective: To assess the efficacy of levodopa-carbidopa intestinal
sis. As patients with IPD have an increased falls risk with poorer gel (LCIG) on non-motor symptoms (NMS) and the safety of titrat-
outcome from fractures, it is important to proactively screen patients ing LCIG in the outpatient setting in a new, ongoing multicenter
for fracture risk. There are no IPD-specific standards for identifying study of LCIG in patients with advanced Parkinsons disease (PD).

TABLE 1. Baseline Mean and Mean Change from Baseline to Week 12 on the Non-Motor Symptom Scale Total Score and
Domains
At Week 12 (n523)
At Baseline (n534)
LS Mean [SE] Change
Data as of October 2014 Mean (SD) from Baselinea P-value
NMSS total score 49.1 (37.6) -22.2 [4.1] <0.001
NMSS domains:
Cardiovascular 1.3 (1.8) 0.0 [0.5] ns
Sleep/Fatigue 12.1 (9.3) -6.5 [1.4] <0.001
Mood/Cognition 4.0 (6.4) -1.5 [1.5] ns
Perceptual problems/Hallucinations 1.9 (3.9) -0.2 [0.6] ns
Attention/Memory 4.8 (6.8) -2.1 [0.9] 0.020
Gastrointestinal tract 5.5 (6.3) -2.9 [0.7] <0.001
Urinary 7.9 (8.2) -2.4 [1.2] ns
Sexual function 2.4 (3.4) -2.5 [0.5] <0.001
Miscellaneous 9.1 (9.6) -4.1 [1.3] 0.002
a NMSS total score and NMSS domains were analyzed by a mixed-effect model for repeated measures using factors of study site, visit, and base-
line and the baseline-by-visit interaction. NMSS 5 non-motor symptom scales; SD 5 standard deviation; LS 5 least squares; SE 5 standard error;
ns 5 not significant
[figure1]

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION S129

TABLE 2:. Adverse Events Occurring in More Than Three Conclusions: LCIG treatment led to reductions in NMS burden
Patients in advanced PD patients, notably improving their sleep and gastroin-
testinal symptoms. The safety profile of LCIG when titrated in an
AEs occurring in  3 patients (N=34): n patients (%) outpatient titration setting was consistent with previous inpatient
titration studies.1
1
Procedural Pain 15 (44.1) Olanow et al. Lancet Neurol. 2014; 13(2):141-9.
2
Anxiety 6 (17.6) Chaudhuri et al. Mov Disord. 2007; 22(13):1901-11.
Fall 5 (14.7)
Catheter site infection 4 (11.8)
Catheter site pain 4 (11.8) 328
Flatulence 4 (11.8) HVA CSF levels in Parkinsons disease patients after levodopa
Postoperative would infection 4 (11.8) challenge: A new diagnostic tool?
Procedural site reaction 4 (11.8)
A. Stefani, S. Galati, C. Liguori, E. Olivola, M. Pierantozzi (Rome,
Constipation 3 (8.8)
Italy)
Urinary tract Infection 3 (8.8)
Weight decreased 3 (8.8) Objective: To verify, through chromatographic approach, the
CSF concentration of dopamine (DA) and its major metabolites in a
cohort of non-fluctuating Parkinsons disease patients.
Background: In Parkinsons disease (PD), stage biomarkers are
elusive and clinical trials obey to mere clinical assessments. An
unmet need is to define reliable biochemical parameters capable to
recognize disease-modifying therapies.
Methods: Here, we tested, through high performance liquid cro-
matography, if the cerebrospinal fluid (CSF) concentration of DA,
3,4-dihydroxyphenylacetic acid (DOPAC) and homovanilic acid
(HVA) correlate with motor performance in a group of non-
fluctuating PD patients. The studied population included 21 patients
with 1-2 Hoehn & Yahr disease stage (under rasagiline plus levo-
dopa and/or dopamine agonists). CSF samples were acquired, after 2
days of washout, via lumbar puncture, 130 min after a challenging
test with submaximal levodopa dose (200 mg), when administered
levodopa reaches a concentration plateau. Analysis was performed in
all patients (n 5 19) manifesting > 30% motor amelioration). The
chromatographic method here utilized (Alexys monoamine analyzer-
Decade II) is optimised for small sample volumes with a detection
Fig. 1. (327). limit below 50 pmol/L for the biogenic amines.
Results: Patients mean CSF concentration of DA, HVA and
DOPAC, following 200/50 mg (LD/carbidopa) were, respectively (in
nM/L), 2,03 (11,83); 11,91 (110,7) and 0,44 (10,38).
In these challenged PD patients, the DA metabolic products
Background: Previous reports have demonstrated that LCIG, showed an increase in parallel with the motor impairment: HVA con-
administered via percutaneous gastrojejunostomy (PEG-J) and centration correlated with pre-testing UPDRS-III scores (R 5 0.61).
titrated in the inpatient setting, reduced motor fluctuations in HVA and DOPAC concentrations correlated to each other
advanced PD patients.1 The effect of LCIG on NMS, which greatly (R 5 0,56), despite rather different kinetics.
impact patients quality of life, and safety of outpatient titration have Conclusions: These pilot observations suggest that early subtle
not been reported. alterations of the DA machinery occur even before the advanced PD
Methods: In this 60-week, open-label Phase 3 study, patients stages characterized by fluctuations and dyskinesia (as already shown
underwent LCIG titration in an outpatient setting within 5 days of by Lunardi et al, 2011). The indexing of CSF HVA concentration,
PEG-J placement. At the optimized dose, LCIG was administered when its correlation with disease progression would be confirmed in
during 16 waking hours as a monotherapy. The primary efficacy longitudinal follow-up, might represent a reliable biomarker for mon-
measure was mean change from baseline to Week 12 for the non- itoring the effectiveness of pharmacological agents with neuro-
motor symptom scale (NMSS) total score2; additional measures protective ambitions.
included NMSS domain scores, and normalized off time and on
time without troublesome dyskinesia (TSD). Safety was assessed
throughout the study. Although the abstract includes interim data, the 329
presentation will contain the primary efficacy endpoint with the final ADS-5102 increased ON time without troublesome dyskinesia
enrollment of 39. throughout waking hours in the EASED study
Results: As of October 2014, 34 of the 52 screened advanced PD M.J. Stempien, R. Pahwa, C.M. Tanner, K. Sethi, A.E. Ruby, J.T.
patients were enrolled with a mean (SD) age of 64.6 (10.4) years
Nguyen, N.L. McClure, R.A. Hauser (Emeryville, CA, USA)
and mean (SD) starting LCIG dose of 1243.2 (485.8) mg/day
(n533). The mean NMSS total score and 5 of the NMSS domain Objective: Characterize the 24-hour time course of troublesome
scores of LCIG-treated patients were reduced at Week 12 compared levodopa-induced dyskinesia (LID) and other PD states by an analy-
to baseline (Table 1). There were improvements in normalized off sis of PD diary data at baseline and after 8 weeks of treatment with
time and on time without TSD (Figure 1). There were 26 (76.5%) ADS-5102 (amantadine extended release capsules) or placebo in the
patients with AEs and 5 (14.7%) with serious AEs; the most fre- EASED study.
quently reported AE was procedural pain (44.1%)(Table 2). Three Background: ADS-5102 is administered once daily at bedtime,
(8.8%) patients discontinued due to an AE. One (2.9%) 70 year-old with the maximum concentration achieved in 12-14 hours. This
male died of congestive heart failure on Day 179, which was deemed results in sustained concentrations throughout the day, when patients
unrelated to the therapeutic system. are active and LID can be troublesome. There is a gradual decline to

Movement Disorders, Vol. 30, Suppl. 1, 2015

S130 POSTER SESSION
Fig. 1. (329).
lower amantadine concentrations during the evening, to reduce the
potential for sleep-related side effects. A randomized, placebo-
controlled multicenter study was conducted in the US (NCT
01397422). PD patients with troublesome LID were randomized to
placebo or to 1 of 3 dose levels of ADS-5102. As previously
reported, ADS-5102 significantly reduced LID as measured by
change in UDysRS total score over 8 weeks vs. placebo (primary
endpoint, p50.005 for the 340 mg dose group, MITT analysis). The
study also included home diaries to measure motor fluctuations over
a 24 hour period, which can be useful supplements to in-office
assessments.
Methods: Study subjects completed PD home diaries indicating
time spent asleep, OFF, ON without dyskinesia, ON with non-
troublesome dyskinesia and ON with troublesome dyskinesia. A post
hoc analysis was conducted using a pre-defined per protocol popula-
tion comparing the pooled ADS-5102 treated subjects (all doses) vs.
placebo for the percent of subjects experiencing each PD state over
24 hours in half hour intervals.
Results: 63 of 83 randomized subjects were included in this diary
analysis. Baseline diary data showed that troublesome dyskinesia and
OFF time can occur throughout waking hours and that PD patients
report OFF time most often during early morning hours. A compari-
son of the placebo vs. the pooled ADS-5102 groups showed that
after 8 weeks of treatment, unlike for the placebo group, ON without
troublesome dyskinesia was clearly the predominant PD state during
waking hours for the ADS-5102 group. Duration of sleep was not
affected.
[figure1]
Conclusions: This analysis confirms that PD patients can experi-
ence troublesome LID and OFF time throughout the day. ADS-5102
increases ON time without troublesome LID throughout waking
hours. Patient-completed home diaries provide additional support to
in-office determined outcomes based on the UDysRS.
330
Withdrawn by Author
331
Single oral treatment with the 5-HT1A/B agonist, eltoprazine,
counteracts L-dopa-induced dyskinesias in Parkinsons disease: A
phase I/IIA, double-blind, randomized, placebo-controlled, dose-
finding study
P. Svenningsson, C. Rosenblad, K. af Edholm Arvidsson, K.
Wictorin, C. Keywood, B. Shankar, D.A. Lowe, A. Bj orklund, H.
Widner (Stockholm, Sweden)
Movement Disorders, Vol. 30, Suppl. 1, 2015
Objective: To evaluate effects of eltoprazine, a 5-HT1A/B recep-
tor agonist, on L-dopa-induced-dyskinesias (LIDs) and therapeutic L-
dopa responses in Parkinsos disease (PD) patients.
Background: In advanced stages of PD, serotonergic terminals
take up L-dopa and convert it to dopamine. Abnormally released
dopamine may participate in the development of LIDs. Simultaneous
activation of 5-HT1A and 5-HT1B receptors effectively blocks LIDs
in animal models of dopamine depletion, justifying a clinical study
with eltoprazine against LIDs in PD patients.
Methods: This was a double-blind, randomized, placebo-
controlled and dose-finding phase I/IIa study. Single oral treatment
with placebo or eltoprazine, at 2.5, 5, and 7.5 mg, was tested in com-
bination with a suprathreshold dose of L-dopa (levodopa and carbi-
dopa) in PD patients with LIDs. A Wilcoxon Signed Ranked Test
was used to compare each eltoprazine dose to paired randomized pla-
cebo on primary efficacy variables; area under the curve scores on
Clinical Dyskinesia Rating Scale (CDRS) for three hrs post dose
(AUC0 3) and maximum change of Unified PD Rating Scale
(UPDRS) partIII for three hrs post dose. Secondary objectives
included effects on maximum CDRS, Rush Dyskinesia Rating Scale
(RDRS) AUC0-3, mood parameters along with the pharmacokinetics,
safety and tolerability. A mixed model, repeated measures was used
for post hoc analyses of the CDRS AUC0-3 and peak CDRS.
Results: Serum concentrations of eltoprazine increased in a dose-
proportional manner. Following levodopa challenge, eltoprazine
5 mg, caused a significant reduction of LIDs on CDRS AUC0-3 (-
1.02(1.49); p50.004)); RDRS AUC0-3 (-0.15(0.23);p=0.003)); and
maximum CDRS (-1.14(1.59);p=0.005)). The post hoc analysis con-
firmed these results and also showed a significant effect of eltopra-
zine 7.5 mg on peak dose dyskinesia. UPDRS partIII scores did not
differ between the placebo and eltoprazine treatments. The most fre-
quent adverse effects after eltoprazine were nausea and dizziness.
Conclusions: Single dose, oral treatment with eltoprazine has
beneficial antidyskinetic effects without altering normal motor
responses to L-dopa. All doses of eltoprazine were well tolerated,
with no major adverse-effects. The data support further clinical stud-
ies with chronic oral eltoprazine to treat LIDs.
332
Problems and potential solutions in using intraduodenal
levodopa/carbidopa infusion therapy
A. Tautscher-Basnett, V. Tomantschger, M. Freimueller (Hermagor,
Austria)
 POSTER SESSION
TABLE 1. Problems & Solutions
Peritonitis
Painful inflammation at stoma
Secretion and formation of hypertrophic
granulation tissue
Dislocation of tube
Broken tube
Pump failure
Broken connectors
Unexplainable alarm
Faulty cassette
Problems with order or delivery of medication
Disappointment with effects
Daily routine too elaborate
(*)These items resulted in an interdisciplinary workshop to improve quality of services.
Objective: To describe our experiences with Levodopa/Carbidopa
intraduodenal gel therapy (LCIG) in advanced Parkinsons disease
(APD) focussing on problems encountered and solutions used.
Background: LCIG is one of the recognised therapy options in
managing motor and increasingly also non-motor symptoms of APD.
Methods: Between 10/2006 and 12/2014 we switched 55 PD
patients (64% male, 36% female) from oral and/or deep brain stimu-
lation to LCIG therapy. Average age: 71.6 yrs (range 49-83); average
time since diagnosis: 13,7 yrs (range 3-40). We conducted two sur-
veys (2009 and 2014) on problems encountered by patients and their
carers. Inclusion criteria were a minimum of 6 months with LCIG.
We identified 10 technical, organisational or health-related problems.
In addition, some clients felt disappointed with the effects of LCIG
and some found the daily routine too elaborate.
Results: Our solutions for the 12 problems are summarised in
table 1.
Conclusions: LCIG is a method of delivering therapy to patients
with APD which is not without problems. However, if managed
Fig. 1. (333).
S131
Antibiotics (*)
Investigate and treat cause of problem (*); consider removal of tube
Tighten internal retention plate (dont twist tube); Eosin 0,15 solution;
Silver nitrate pen
Setting new tube (*)
Setting new tube (*)
Oral emergency medication until replacement of pump (*)
Specialist nurse changes connectors during home visit
Checking tube; switching off and on, telephone help; training
Replacement
Guidelines on: medical prescription, approval of prescription, ordering
medication through chemist
Increased information, goals and expectations agreed in writing
Increased information and training, ensuring social network is functioning
interdisciplinary and if appropriate support is given to patients and
their carers, these problems can be overcome and nevertheless lead
to client satisfaction. Still, 20% decided to discontinue with LCIG
therapy, mainly due to effects not living up to expectations or chal-
lenging routine care.
333
Impact of 6-month earlier initiation of rotigotine on long-term
outcome: Post-hoc analysis of patients with early Parkinsons
disease
L. Timmermann, M. Asgharnejad, B. Boroojerdi, E. Dohin, F.
Woltering, L.W. Elmer (Cologne, Germany)
Objective: To investigate the benefit of 6-month earlier initiation
of treatment with rotigotine transdermal patch in patients with early
Parkinsons disease (ePD).
Movement Disorders, Vol. 30, Suppl. 1, 2015
S132 POSTER SESSION
TABLE 1. Demographic and baseline characteristics for
ePD patients at HY stage 1-2 (DB baseline)
6-month earlier
rotigotine* Rotigotine**
Efficacy set (n5221) (n5125)
Age, mean 6 SD, years 60.9 6 9.7 63.0 6 10.3
Male, n (%) 150 (67.9) 83 (66.4)
Caucasian 214 (96.8) 121 (96.8)
Time since PD diagnosis, 1.4 6 1.4 1.3 6 1.3
mean 6 SD, years
HY stage 1, n (%) 67 (30.3) 38 (30.4)
HY stage 2, n (%) 154 (69.7) 87 (69.6)
Patients defined as having at least one UPDRS II1III assessment at
baseline, at the start of open-label maintenance period, and at least
one UPDRS II1III assessment in the open-label maintenance period.
* 6-month earlier rotigotine: patients received rotigotine during
preceding 6-month DB study, and rotigotine in open-label extension;
** Rotigotine: patients received placebo during preceding 6-month
DB study, and rotigotine in open-label extension (i.e. initiation of
rotigotine started in open-label study).
Background: The benefit of treating ePD patients with rotigotine
has been demonstrated over the short- and long-term. SP702
(NCT00594165) and SP716 (NCT00599196) were long-term, open-
label extensions of two double-blind (DB), placebo-controlled studies
of 6-month maintenance; rotigotine was well tolerated for up to 6
years, and demonstrated sustained efficacy (UPDRS II1III below
DB baseline) for 2 years in SP702 and 4 years in SP716. While
there are no established disease-modifying/neuroprotective therapies,
timing of therapy initiation is of clinical importance and earlier ini-
tiation has been shown to improve quality of life [1]. As initiation of
medication may be considered when patients experience functional
impairment or social embarrassment from symptoms [2], we investi-
gated the effect of 6-month earlier initiation of rotigotine in ePD
patients with mild symptom severity/disability, as defined by Hoehn
& Yahr (HY) scale.
Methods: In this post hoc analysis of pooled data from SP702
and SP716 and preceding DB studies, the effect of 6-month earlier
rotigotine initiation on UPDRS II1III is reported for patients at HY
1-2 at DB baseline. 6-month earlier rotigotine group: received roti-
gotine during DB study; rotigotine group: received placebo during
DB study.
Results: Demographic/baseline characteristics (Table 1). Rotigo-
tine/levodopa exposure (Table 2). Mean6SD UPDRS II1III at DB
baseline were similar between 6-month earlier rotigotine
(29.3 6 10.5) and rotigotine (27.8 6 10.1) groups. At start of open-
label rotigotine maintenance, mean change from DB baseline
UPDRS II1III were -8.5 6 10.6 in 6-month earlier rotigotine and -
7.7 6 9.0 in rotigotine. After this initial improvement, scores grad-
ually declined: it took 42 months for mean scores to return to DB
baseline in 6-month earlier rotigotine group, whereas it took 18
months in rotigotine group (Figure 1).
TABLE 2. Rotigotine and levodopa exposure over the course of the open-label studies
Efficacy set
Dose of rotigotine during open-label studies,
mean 6 SD, mg/24 h*
Number of patients who received concomitant
levodopa during open-label studies, n (%)
Dose of concomitant levodopa during open-label
studies, mean 6 SD, mg/day
Treatment with levodopa was not permitted during the DB studies. In the open-label studies, concomitant levodopa was allowed, if required,
after 1 month of open-label rotigotine maintenance. *Mean dose during open-label extension maintenance.
Movement Disorders, Vol. 30, Suppl. 1, 2015
Conclusions: In this post hoc analysis, 6-month earlier initiation
of rotigotine resulted in numerically slower return to baseline mean
UPDRS II1III scores; earlier initiation of rotigotine in ePD patients
at HY 1-2 may be associated with additional long-term benefit.
1. Grosset D, et al.JNNP.2007;78:465-9.
2. Connolly BS, Lang AE.JAMA.2014;311:1670-83.
[figure1]
334
Reasons and recommendations for stopping continuous
intraduodenal levodopa/carbidopa infusion therapy
V. Tomantschger, A. Tautscher-Basnett, M. Freimueller (Hermagor,
Austria)
Objective: To describe our experiences with Levodopa/Carbidopa
intraduodenal gel therapy (LCIG) in advanced Parkinsons disease
(APD) focussing on the reasons for the discontinuation of this
therapy.
Background: LCIG is one of the recognised therapy options in
managing the symptoms of APS. However, while recommendations
for starting with this therapy exist, there are no recommendations for
discontinuation.
Methods: Between 10/2006 and 12/2014 we switched 55 PD
patients (64% male, 36% female) from oral and/or deep brain stimu-
lation (DBS) to LCIG therapy. Average age: 71.6 yrs (range 49-83);
average time since diagnosis: 13,7 yrs (range 3-40). Of these 55
patients 13 patients stopped LCIG therapy, 8 of them died in the
course of time (total number of deaths: 25).
Results: The reasons for stopping LCIG therapy can be summar-
ised into four groups: a) routine care too difficult/dependency on
other people; b) effects too little or missing; c) unwanted side
effects; d) termination of therapy due to death. Of those that stopped
therapy two switched to Apomorphine pump, one went back onto
DBS only (instead of combination), the remainder went back to oral
medication.
The causes of death in this APD patient group were primarily
natural. However, 1 patient died of sudden cardiac death and 3
patients had cancer. 3 patients with very advanced symptoms of PD
survived for some considerable time due to the pre-existing PEG/J-
tube, here the question of dying in dignity had to be raised.
Conclusions: Continuous LCIG infusion is an effective method
of delivering therapy to patients with APD, however, the daily rou-
tine can be demanding on patients and carers. Reasons for discontin-
uing with LCIG therapy include the personal preference of patient
(carer), missing clinical effects, unwanted side effects and death.
End of life questions need to be raised. Should this therapy be
stopped when neither clinical effects on the symptoms of PD can be
observed nor any amelioration of burden of disease can be expected?
In agreement with patients, stopping LCIG therapy should be consid-
ered when patients develop severe dementia with behavioural disor-
ders, advanced malignancy or other serious medical conditions.
Ethical aspects must be considered in decision making and, in any
case, optimal oral treatment as well as support must be offered.
6-month earlier rotigotine (n5221) Rotigotine (n5125)
8.5 6 2.4 8.0 6 2.5
163 (74%) 91 (73%)
352.9 6 387.1 334.3 6 398.7
 POSTER SESSION S133

improved with OXN PR vs placebo at Week 16 (least squares mean

difference [95% CI] -0.6 [-1.26, 0.02] points, p50.058); nominal p
values indicated significant treatment benefits at Week 12 (-0.7
[-1.30, -0.11], p50.021), Week 8 (-0.7 [-1.22, -0.16], p50.011) and
Week 4 (-0.6 [-1.10, -0.11], p50.018).
24-h pain scores, double-blind treatment: [figure1]
Responder (Much improved or Very much improved) rates at
Week 16 (LOCF) were significantly higher with OXN PR vs placebo
for CGI-I (36.4% vs 26.7%, p50.019) and for PGI-I (37.5% vs 26.7%,
p50.022). NMS scale revealed OXN PR was not associated with wor-
sening of non-motor symptoms, including mood/cognition, perceptual
problems/hallucinations, sexual function and gastrointestinal function.
The overall incidence of adverse events (AEs; 65.2% vs 69.7%)
and treatment-related AEs (56.5% vs. 56.9%) was similar for OXN
PR vs placebo; specific AEs more frequent with OXN PR tended to
be mild/moderate.
Conclusions: This first study of OXN PR for severe PD-related
pain suggests OXN PR has analgesic efficacy in this setting, and sec-
Fig. 1. (335). ondary endpoints during double-blind treatment also support the ben-
eficial effects of OXN PR for pain relief in PD.

Non-Motor Symptom Assessment Scale in patients with PD-

related pain (LOCF; Full Analysis Population)
336
OXN PR (N=88) vs
Change in score: placebo (N=106) Least Squares Prognostic factors and symptoms in Parkinsons disease
Baseline to Week 16 mean difference (95% CI) P value Y.O. Trufanov (Kyiv, Ukraine)
Cardiovascular 20.1 (20.76, 0.65) 0.880 Objective: To analyze the prognostic factors and symptoms in
Sleep/fatigue 21.4 (22.95, 0.15) 0.077 Parkinsons disease (PD).
Mood/cognition 0.2 (22.06, 2.38) 0.887 Background: Despite all recent advances in symptomatic therapy
Perceptual problems/ 0.3 (20.01, 0.52) 0.059 PD continues to be a relentlessly progressive neurodegenerative dis-
hallucinations order [Poewe W., 2009]. In PD, the rate of clinical progression is
Attention/memory 0.1 (20.84, 0.98) 0.882 highly variable [Velseboer D.C. et al., 2013]. Knowledge of disease
Gastrointestinal function 0.3 (20.48, 1.17) 0.407 progression will play a key role, not only in providing useful clinical
Urinary 20.9 (22.09, 0.25) 0.123 information, but in assessing the benefit of neuroprotective interven-
Sexual function 20.2 (20.95, 0.54) 0.590 tions [Suchowersky O. et al., 2006].
Miscellaneous 20.2 (21.49, 1.15) 0.789 Methods: 230 consecutive patients with idiopathic PD (151 males
and 79 females, age range from 35 to 88) were questioned at time of
routine clinic visits.
Results: In our research, we studied more than 30 different motor
and non-motor PD symptoms and such potential PD prognostic fac-
335 tors as side of motor onset (dominant/non-dominant, right/left), hand-
Prolonged-release oxycodone/naloxone (OXN PR) is associated edness, gender, degree of motor asymmetry, age at disease onset,
with treatment benefits in patients with severe Parkinsons first syndrome at motor onset (bradykinesia or tremor), response to
disease (PD)-related pain: Results from a randomised, controlled dopaminergic therapy, disease progression in the first 3 years after
trial motor onset etc.
Conclusions: The reliable (p < 0.05) predictors of a favorable
C. Trenkwalder, P. Martinez-Martin, O. Rascol, M. Lomax, J. DeCe-
sare, M. Hopp, K.R. Chaudhuri (Kassel, Germany) course of Parkinsons disease include: PD onset on the non-dominant
side of the body, age at onset under 60 years, disease onset with
Objective: This randomised, double-blind study investigated the tremor, excellent or good response to dopaminergic therapy, slow
analgesic efficacy, safety and potential disease-related benefits of disease progression in the first 3 years after disease onset.
OXN PR vs placebo for severe PD-related pain. The reliable (p < 0.05) predictors of an unfavorable course of Par-
Background: Opioids effectively treat many types of moderate- kinsons disease include: PD onset on the dominant side of the body,
to-severe chronic pain, and OXN PR is demonstrated to provide age at onset after 60 years, disease onset with bradykinesia, poor
comparable analgesic efficacy and improved bowel function vs oxy- response to dopaminergic therapy, rapid disease progression in the
codone PR alone. However, there is little data on the use of opioids first 3 years after disease onset, and a number of disabling motor and
in patients with PD-related pain. non-motor symptoms.
Methods: Patients with PD (Hoehn & Yahr Stage IIIV), and The main prognostic symptoms of PD progression include: severe
average 24-h pain score 6 (11-point scale, defined below) were rand- bradykinesia and rigidity, severe disturbance of gait and severely
omised to OXN PR (N=93; titrated to 20/10 mg bid) or placebo stooped posture, moderate or severe intellectual impairment, severe
(N=109) for 16 weeks, followed by a 4-week extension phase (open- depression, marked impairment of speech, moderate or severe dyski-
label OXN PR). Primary endpoint was average 24-h pain score at nesia and clinical fluctuations. The main prognostic symptoms of PD
Week 16 (0 no pain to 10 pain as bad as you can imagine). Sec- progression also include such disabling symptoms as falling and pos-
ondary endpoints included Clinical Global Impression-Improvement tural instability, freezing when walking, swallowing difficulties, hal-
(CGI-I) and Patient Global impression-Improvement (PGI-I) scales, lucinations, confusions, urinary incontinence and retention.
Non-Motor Symptom (NMS) assessment scale, and safety. Handedness cannot be considered and taken into account as a
Results: Mean duration of patients PD-related pain was 3.4 prognostic factor of PD progression. There were no differences with
years. Mean 24-h pain score was numerically but not significantly respect to the rate of progression of PD between men and women.

Movement Disorders, Vol. 30, Suppl. 1, 2015

S134 POSTER SESSION

338
The rate of motor and non-motor symptoms in patients with Par-
Aerobic exercise increases the chemokine RANTES/CCL5 in
kinsons disease (n 5 230)
Parkinsons disease
Symptoms n % E.Y. Uc, M. Neal, V. Anantharam, D.J. Murry, K.C. Doerschug, T.R.
Thomsen, J.N. Kline, J.D. Dawson, W.G. Darling, A. Kanthasamy,
Motor Symptoms N.S. Narayanan (Iowa City, IA, USA)
Bradykinesia 230 100.0
Resting tremor 164 71.3 Objective: To determine the effects of aerobic exercise on
Action tremor 142 61.74 trophic factors and inflammatory markers in patients with Parkin-
Rigidity 227 98.7 sons disease (PD).
Postural instability 104 45.22 Background: Aerobic exercise improves motor function and cog-
Falling 71 30.87 nition in aging, dementia, and PD, and exerts neuroprotective effects
Disturbance of gait 191 83.04 in animal models of PD. Changes in trophic factors and inflamma-
Freezing 75 32.61 tory processes are thought to mediate the effects of aerobic exercise
Stooped posture 203 88.26 in PD, but evidence from human studies is limited.
Impairment of speech 152 66.09 Methods: Sixty non-demented, independently ambulatory patients
Dyskinesia 126 54.78 with PD (median Hoehn-Yahr stage II) enrolled in a 6-months Phase
Clinical fluctuations 103 44.78 I/II study. Patients walked at moderate aerobic intensity in commu-
Intellectual impairment 123 53.48 nity settings 45 minutes/session, three times per week. Blood sam-
Depression 84 36.52 ples were collected at baseline and after the intervention.
Hallucinations 31 13.48 Results: Forty-nine participants completed the intervention and
Confusion 22 9.57 showed significant improvements in aerobic fitness (VO2max) and
Sleep disturbances (insomnia or 136 59.13 various disease related measures as previously published (Uc et al.,
hypersomnolence) Neurology 2014;83:41325). We report that typical peripheral cyto-
Vivid dreaming 126 54.78 kines associated with Parkinsons disease, such as TGF-a, IL-1b, IL-
Swallowing difficulties 68 29.57 2 and IL-6, were unchanged. However, we find that RANTES (Regu-
Olfactory dysfunction 125 54.35 lated upon Activation, Normal T-cell Expressed and Secreted)/CCL5
Symptomatic orthostatic hypotension 88 38.26 (CC chemokine ligand 5), a chemotactic cytokine with a role in
Frequent urination related to Parkinsonism 88 38.26 recruiting T-cells, was significantly increased. Changes in aerobic fit-
Urinary urge incontinence related to 25 10.87 ness, gait speed, severity of Parkinsonism, fatigue, or mood did not
Parkinsonism correlate with changes in RANTES/CCL5.
Urinary retention related to Parkinsonism 16 6.96 Conclusions: These data provide evidence that this cytokine may
Constipation 121 52.61 be involved in Parkinsons disease, and may guide future investiga-
Salivation 85 36.96 tions into both the therapeutic value of aerobic exercise and future
biomarkers for neurodegenerative disease.

337
The rate of motor and non-motor symptoms in patient with
Parkinsons disease
Y.O. Trufanov (Kyiv, Ukraine)
Objective: To analyze the rate of motor and non-motor symp-
toms in patients with Parkinsons disease (PD).
Background: Around 1% of adults have PD, with a median time of
9 years between diagnosis and death [Clarke C.E., Moore A.P., 2007].
PD is a progressive neurological disorder characterized by a large num-
ber of motor and non-motor features that can impact on function to a
variable degree [Jankovic J., 2011]. PD causes substantial morbidity
and results in a shortened life span [Schapira A.H.V., 1999].
Methods: 230 consecutive patients with idiopathic PD (151 males
and 79 females, age range from 35 to 88) were questioned at time of
routine clinic visits.
The average age of PD patients was 67.91 6 0.72 years; the aver-
age duration of disease was 8.11 6 0.39 years.
Results: In our research, we studied the rate of motor and non-
motor symptoms in patients with PD.
Conclusions: Most of the motor Parkinsonian symptoms (brady-
kinesia, tremor, rigidity, disturbance of gait, impairment of speech,
stooped posture) were common complications of all stages of PD
(61.74% 100.0%).
Postural instability, freezing, falling, dyskinesia and clinical fluc-
tuations developed mainly at later stages of PD, and were observed
in 30.87% 54.78% PD patients.
Most often among non-motor symptoms of PD were observed
sleep disturbances (59.13% of all PD patients), vivid dreaming
(54.78%), intellectual impairment (53.48%), depression (36.52%),
olfactory dysfunction (54.35%), constipation (52.61%), orthostatic
hypotension (38.26%) and frequent urination (38.26%).
339
Motor and non motor symptoms of a cohort of young, early
onset Parkinsons disease patients enrolled in Transeuro: 3 year
follow up
N. Valle Guzman, R. Wijeyekoon, D. Daft, R. Barker (Cambridge,
United Kingdom)
Objective: To summarise the characteristics of a cohort of young,
early onset Parkinsons disease patients that have been followed up
for 3 years as part of the Transeuro study.
Background: The aim of Transeuro is to assess the safety and
efficacy of neural allo-transplantation with fetal ventral mesence-
phalic tissue in patients with Parkinsons disease, with the first trans-
plant taking place in the first months of 2015.
We here describe the characteristics of the patients enrolled in
Transeuro at the Cambridge Centre for Brain Repair that have been
followed up for up to 3 years. Some of these patients will receive a
cell transplant in 2015.
Methods: Patients enrolled in Transeuro are seen every 6 months,
and are evaluated with an extensive battery of motor, neuropsycho-
logical and quality of life assessments. We analysed this data up to
the 36 month follow up for all the patients enrolled at our centre,
which included UPDRS off & on medication, dyskinesia scales,
ACE-R and timed motor assessments.
Results: The mean age of diagnosis in our cohort was 51.7 years,
with a mean disease duration of 3.2 years at baseline. The average
UPDRS motor score off-medication at baseline was 28, with score of
20 on medication, at 36 months this was 37 off meds and 27 on
meds. These changes in motor functions are also reflected by
increased reaction times on 9 hole pegboard and timed walk, and
decrements in the number of taps on the 30 second tap test at follow
ups. 3 patients developed dyskinesias during the course of the trial.

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
Though some mild changes in cognition were observed at follow up,
cognitive functions remained stable, as did the non-motor symptoms.
Conclusions: Our aim was to summarise the characteristics of the
participants enrolled in Transeuro at our centre, that we have been
assessing every 6 months for nearly 3 years. The main changes were
seen UPDRS motor scores, timed motor assessments and dyskinesia
scores, whilst cognitive functions and non motor scores remained rel-
atively stable.
340
Long-term follow-up of the transcutaneous port (T-Port) in PD
patients with LCIG
T. van Laar, R. Nyman, M. Drent (Groningen, Netherlands)
Objective: To evaluate long-term safety and tolerability of the T-
PortVR in patients with advanced Parkinsons disease (PD) being
treated with levodopa-carbidopa intestinal gel (LCIG).
Background: LCIG is delivered to the jejunum by a catheter
inserted via percutaneous endoscopic gastrostomy (PEG-J). The
PEG-J is associated with many complications related to the stoma
and the tube. Some patients have been reluctant to try LCIG due to
the discomfort and unattractiveness of the PEG-J system. The T-
PortVR may offer patients a more attractive alternative. It permits an
easy detachment of the external tube, with only a small piercing
visible at the abdominal skin.
Methods: Open label prospective safety and tolerance study in
PD patients receiving LCIG. T-PortV R status was evaluated at 2
weeks, 3, and 6-months and thereafter until explantation or death.
All adverse device effects, reported spontaneously on general ques-
tioning or observed directly by the investigator, were recorded. At 6-
months the patients with prior PEG-J experience were asked which
system they preferred.
Results: In total 24 patients (15 males, mean age 61.8 years)
received a T-PortV R between May 2004 and Sep 2010. Postoperative
complications were similar to PEG placement (4 peritoneal irritation, 1
pocket pain). Eight patients had prior experience with the PEG-J and all
of them preferred the T-PortV R . At data cut-off the total device experi-
ence was 83.6 years and average survival time of the T-PortV R was 3.6
(range 1.1 - 5.2) years. Six ports were still in use and 2 patients died
due to non-device related reasons. 16 ports were explanted due to14
inflammatory stoma reactions, 1 infection, and 1 tilting of the port. At
the time of the study the T-PortV R was not available outside the study
so the explanted ports were replaced with PEG-J tubes without compli-
cations. Only two device malfunctions occurred of which both were
corrected in outpatient setting. No tube kinking, dislocation or blockage
occurred. The number of adverse device effects proved to be signifi-
cantly lower as compared to the PEG-J data from the literature.
Conclusions: The T-PortV R is safe and well tolerated. The most
important adverse effects are inflammatory reactions around the
stoma. T-port was explanted after a mean period of 3.6 yrs. Proper
cleaning and local treatment of the stoma site around the T-PortV R is
essential to prolong longevity.
341
Dance exercise is an effective alternative to multimodal physical
therapy to improve balance in Parkinsons disease
V.G. VanderHorst, D. Harrier, A. Snyder, A. Silver, L. Kraics, J.
Miller, C. Pierce, A. Worley, K. Shillue, N. Goodman, D.K. Simon,
L. Shih, D. Tarsy (Boston, MA, USA)
Objective: To test the hypothesis that dance exercise is as effec-
tive as multimodal physical therapy for improving balance in patients
with Parkinsons disease (PD).
Background: Problems with balance are common in PD. Multi-
modal physical therapy (PT), which includes flexibility, balance,
strength and endurance exercises, has been the gold standard to
improve mobility in PD. Alternative forms of exercise have become
S135
popular, but it remains unclear what types of exercise are effective for
which symptoms, and which forms carry the best long term effects.
Methods: We recruited 22 subjects with PD and balance prob-
lems (Berg Balance Scale BBS <=48); 10/11 completed a dance and
8/11 a PT program. Both groups were similar in disease duration and
H&Y score. Both programs consisted of 8 group sessions of 1 hour/
week and subjects were encouraged to perform home exercises. Bal-
ance as assessed with the BBS was the primary outcome measure.
Secondary outcome measures included functional reach test, Timed
Up and Go, 6 minute walk, UPDRS-III, PDQ-39, GDS-15, trail mak-
ing and MMSE. These tests were performed 1 week prior to and 1, 9
and 24 weeks following completion of the 8 week program. Motor
assessments were performed by a physical therapist who was blinded
to the treatment.
Results: Ordinary one-way ANOVA with Bonferronis multiple
comparisons test showed significant improvements in BBS from base-
line. Post-analysis demonstrated improvements at each of the time
points within both groups, but no significant difference between treat-
ment groups. Of the secondary outcome measures, functional reach,
but none of the other measures also improved in both groups. Further
within group analysis using repeated measures one-way ANOVA dem-
onstrated a small improvement of the 6 minute walk and Timed Up
and Go in the PT group but not the dance group, whereas UPDRS-III
scores had worsened significantly at 17 and 33 weeks in the dance
group, but not the PT group. Non-motor outcomes were not signifi-
cantly different between or within groups across time points.
Conclusions: Dance and PT each significantly improve balance,
suggesting that dance exercise is a useful alternative to PT in PD
patients with balance problems. The effects last well beyond the
intervention in both exercise formats. However, the improvement in
balance does not translate to increased gait speed, for which PT is a
more effective intervention.
342
NLX-112, a novel candidate for the treatment of L-DOPA-
induced dyskinesia: Behavioral and neurochemical profile in rat
M. Varney, H. Iderberg, A. Cenci, A. McCreary, A. Newman-
Tancredi (Dana Point, CA, USA)
Objective: To investigate the effect of NLX-112, a selective and
fully efficacious serotonin 5-HT1A receptor agonist, on behavioral
and neurochemical endpoints in a rat model of PD and L-DOPA-
induced Abnormal Involuntary Movements (AIMs).
Background: Prolonged treatment of PD patients with L-DOPA
results in the generation of dyskinesia. This is associated with false
neurotransmitter conversion of L-DOPA to dopamine by 5-HT neu-
rons projecting to the striatum. Inhibiting these neurons by targeting
5-HT1A receptors is an attractive therapeutic strategy, but previous
5-HT1A agonists have yielded disappointing efficacy, likely because
of low intrinsic activity at the 5-HT1A receptor and poor selectivity
against other receptor types.
Methods: We evaluated the effects of NLX-112 in hemiParkinso-
nian rats (unilateral 6-OHDA lesion) on behavioral and neurochemi-
cal readouts that included locomotor activity, motor coordination and
akinesia, LID and in vivo microdialysis.
Results: NLX-112 (0.16 mg/kg i.p.) potently abolished L-DOPA-
induced AIMs in hemiParkinsonian rats, an effect that was reversed
by the selective 5-HT1A antagonist, WAY100635. In microdialysis
experiments, NLX-112 profoundly decreased striatal 5-HT levels,
indicative of inhibition of 5-HT neuron activity. NLX-112 also
blunted the L-DOPA-induced surge in dopamine levels on the
lesioned side of the rat brain, an action that likely underlies its anti-
dyskinetic effects.
NLX-112 (0.16 mg/kg i.p.) also induced ipsilateral rotations in
hemiParkinsonian rats, suggesting that it had a motor facilitation
effects on the non-lesioned side of the brain. The rotations induced by
NLX-112 were abolished by WAY100635. In tests of potential side-
effects, NLX-112 (0.01-0.16 mg/kg) did not impair the capacity of L-
Movement Disorders, Vol. 30, Suppl. 1, 2015
S136 POSTER SESSION
DOPA to rescue fore-paw ataxia in the cylinder test, but decreased
rotarod performance, probably due to induction of flat body posture
(FBP) and fore-paw treading (FPT), which are typical of 5-HT1A ago-
nists upon acute administration. However, when NLX-112 was admin-
istered repeatedly, tachyphylaxis to FBP and FPT was observed,
whereas efficacy against L-DOPA-induced AIMs was maintained.
Conclusions: Taken together, these observations suggest that
NLX-112 could exhibit a robust anti-LID activity without impairing
the therapeutic properties of L-DOPA. These results support the eval-
uation of NLX-112 in PD subjects that exhibit LID.
343
Efficacy of transdermal nicotine, in advanced Parkinsons
disease. A controlled open-label study in 40 patients randomised
in two parallel groups
G. Villafane, E. Itti, C. Straczek, M. Quere-Carne, D. Schmitz, Nico-
park2 Study Team (Cr eteil, France)
Objective: To assess safety and efficacy of Transdermal Nicoti-
notherapy (TN) on motor symptoms and neuroprotection in Parkin-
sons disease (PD) patients.
Background: Use of transdermal nicotine in PD was suggested
by epidemiological and case-controlled studies that demonstrated a
low prevalence of smokers among PD patients. Given a growing
body of evidence implicating nicotine as an active drug that stimu-
lates nicotinic acetylcholine receptors, it became relevant to investi-
gate therapeutic significance of TN as a novel alternative to
dopaminergic treatments.
Methods: We carried-out a controlled, open-label randomized
study in 40 completed advanced PD patients, 65% males and 35%
females, mean age 57.4 67.3 years, As required by inclusion criteria
patients were non-smoker, presenting motor fluctuations, Levodopa
(LD) responder. (LD) dose at inclusion was 450 mg/d [400-600mg/d].
Patients regularly monitored during 50 weeks were distributed in 2 par-
allel groups: TN versus Best Medical Management (BMM). TN dose
was increased up to 90 mg/d or to maximal tolerated dose stable for
28 weeks, and afterwards gradually back to zero. According to investi-
gators opinion, LD could be decreased since week 7. Primary endpoint
was the improvement of UPDRS III motor score in defined OFF
conditions at end of stable phase. Among secondary endpoints we
assessed evolution of UPDRS III motor score ON, improvement of
cognitive function and quality of life (PDQ39). Patients underwent
DaTSCAN imaging before inclusion and at 1 year. Safety was assessed
by Adverse Events (AE), vital signs and 12-lead electrocardiography.
Results: Efficacy: Median delta UPDRS III motor score OFF
between W-1 and W50 was 0 in the BMM group versus -20 in the
TN group (P=0.001).
Statistical parametric maps of the difference between pre & post-
therapy imaging revealed an expected reduction of DaTSCAN uptake
in the BMM group while a relative stability, and even a slight
improvement was found in the TN group.
Safety: 6 patients tolerated the maximum TN daily dose of
90 mg and 1 patient withdrew from study. 8 patients reported 10
SAE which 5 are emergent.
Conclusions: Based on these encouraging data a double-blind
randomized study versus placebo in a larger cohort of patients could
be considered.
344
Rectal levodopa administration, nonsense or not?
J.M.J. Vogelzang, M. Luinstra, W.A.W.F. Rutgers (Groningen,
Netherlands)
Objective: The aim of this report is to discuss whether or not
there is rectal absorption of levodopa.
Background: In situations where oral intake of levodopa formu-
lations is not possible, the treatment options of Parkinsons disease
Movement Disorders, Vol. 30, Suppl. 1, 2015
patients are limited. Literature describes no or low rectal absorption
of levodopa.
Methods: A patient with an ileus was unable to take oral medica-
tion. After consultation with the neurologist and the pharmacist, the
surgeon decided to start with a rectal formulation of levodopa/carbi-
dopa (100/25mg) once daily. On day 3 of the therapy, one hour after
administration of the rectal formulation of levodopa/carbidopa a
blood sample was drawn.
Results: The levodopa concentration was 17 nmol/l. Compared to
levodopa concentrations described in the literature (1400-12000
nmol/l) the concentration is very low. Levodopa is well absorbed in
the small intestine by a specific amino acid transport system. If this
system is present in the rectum is not known, which would be a pos-
sible explanation for the low levodopa concentration. An additional
explanation for the low concentration of levodopa is the poor rectal
absorption of carbidopa, leading to a higher breakdown of levodopa
peripheral.
Conclusions: We found a levodopa concentration of 17 nmol/l.
Further research is needed to confirm the optimal rectal dosage.
345
Rivastigmine for mild cognitive impairment in Parkinsons
disease: A placebo-controlled study
D. Weintraub, E. Mamikonyan, S.X. Xie, E. Melvin (Philadelphia,
PA, USA)
Objective: The objective of this study was to determine the effi-
cacy and tolerability of rivastigmine for PD-MCI.
Background: Mild cognitive impairment (MCI) in Parkinsons
disease (PD) is associated with subtle functional impairment and
worse quality of life.
Methods: Patients with PD-MCI (n528) were enrolled in a 24-
week, randomized, double-blind, placebo-controlled, crossover single
site study of the rivastigmine transdermal patch. The primary out-
come measure was the Alzheimers Disease Cooperative Study- Clin-
ical Global Impression of Change (ADCS-CGIC). Secondary
outcomes included the Montreal Cognitive Assessment (MoCA),
Dementia Rating Scale-2 (DRS), Neurotrax computerized cognitive
battery, the Everyday Cognition Battery (ECB), and the Parkinsons
disease Questionnaire (PDQ-8).
Results: Twenty-six participants (92.9%) completed both study
phase assessments and 23 (82.1%) completed both phases on study
medication. The CGIC response rate demonstrated a trend effect in
favor of rivastigmine (regression coefficient for interaction term in
linear mixed-effects model 5 0.44, F[df] 5 3.01 [1, 24], p50.096).
For secondary outcomes, there was a significant rivastigmine effect
on the ECB (regression coefficient 5 -2.41, F[df] 5 5.81 [1, 22.05],
p50.03), but no treatment effect on any cognitive measures. There
were also trend effects in favor of rivastigmine on the PDQ-8
(regression coefficient 5 4.55, F[df] 5 3.93 [1, 14. 79], p50.09) and
the State Anxiety Inventory (regression coefficient 5 -1.24,
F[df] 5 3.17 [1, 33], p50.08).
Conclusions: Rivastigmine in PD-MCI showed a trend effect for
improvements on a global rating of cognition, disease-related health
status, and anxiety severity, and significant improvement on a
performance-based measure of cognitive abilities.
346
Contribution of a pharmacist to the multidisciplinary
consultation on Parkinsons short-stay ward
L. Wijma-Vos (Groningen, Netherlands)
Objective: Determination of the contribution of a pharmacist to
the multidisciplinary team of the Groningen Parkinsons Short Stay
(GPSS) ward.
Background: Since 2001, nursing home Maartenshof in Gro-
ningen (the Netherlands) offers a multidisciplinary rehabilitation
 POSTER SESSION
pathway for Parkinsons disease (PD) patients: the Groningen
Parkinson-short-stay (GPSS) treatment. Patients at an advanced stage
of disease, whos home situation is jammed, can be admitted here
for up to 6 weeks. The treatment is an alternative to final nursing
home admission. The treatment goals are evaluated weekly in a mul-
tidisciplinary consultation (MDC) consisting of a neurologist, a phy-
sician, a physiotherapist, a social worker etc. An important treatment
goal is optimisation of both the Parkinsons and non Parkinsons We
studied the contribution of a pharmacist to the MDC.
Methods: During a 12 weeks time period, a pharmacist attended
the MDC. The pharmacist therefore performed a pharmaceutical
analysis of the medication of the inpatients, by using the STOPP
(Screening Tool of Older Peoples potentially inappropriate Prescrip-
tions criteria) and START (Screening Tool to Alert doctors to the
Right Treatment) criteria. The proposed interventions were discussed
with the other MDC attendees. Actions that occurred from the dis-
cussion were executed by the attending physician and evaluated at
the next MDC.
Results: The medication of 22 patients was assessed and the
pharmacist proposed on average 2.3 interventions per patient. In
almost half the cases (48%) the pharmacist signalled overtreatment.
The other half of the advices predominantly consisted of avoiding
undertreatment (18%), improving the ease of use (10%) and dose
adjustments (12%). Most implemented advices were stopping medi-
cation (29%) and dosage reduction (16%).
Conclusions: A substantial part of the given advices was not
implemented due to several, sometimes unknown reasons. Follow up
of the proposals was not optimal. Nevertheless the contribution of a
pharmacist is considered useful by all attendants because of the phar-
macists professional overview of the entire medication profile, while
other professionals tend to focus mainly on the PD medication. Since
patients stay at least 4 weeks at the GPSS, weekly presence of a
pharmacist is not required. Monthly presence is sufficient to discuss
all inpatients at least once during their stay at the ward.
347
Patient and provider perception of video telehealth in
Parkinsons disease (PD)
J.R. Wilkinson, D. Korom-Djakovic, M. Spindler, J. Morley, J. Duda
(Philadelphia, PA, USA)
Objective: To identify barriers and facilitators of using video tel-
ehealth by qualitatively examining patients and providers percep-
tions of this modality.
Background: Access to specialty care remains an obstacle for
PD patients and their families due to disease-related disability,
resource limitations and other burdens of travel. Both in-home and
facility-to-facility video telehealth programs have emerged as
patient-centered approaches to reduce these burdens and increase
access to care. Quantitative studies support the feasibility and poten-
TABLE 1. Change from baseline to EoM in UPDRS II1III total score, and UPDRS II and III subscores
Mean (6SD) baseline Mean (6SD) change
score from baseline to EoM
Full analysis set,
last observation Placebo Rotigotine Placebo
carried forward (n5121) (n5123) (n5121)
UPDRS II1III (Pri- 32.7 (12.4) 32.0 (13.8) -0.2 (9.9)
mary outcome)
UPDRS II (Second- 9.3 (4.0) 9.2 (4.7) 0.1 (3.4)
ary outcome)
UPDRS III (Second- 23.3 (9.4) 22.8 (10.2) -0.3 (7.4)
ary outcome)
*Analysis of covariance (ANCOVA) model with treatment and region as factors and baseline values as covariate. Two-sided p-values presented.
CI, confidence interval; SD, standard deviation; LS, least squares
S137
tial benefits of telehealth in PD. However, formal qualitative studies
focused on patients and providers perception of this innovation
have not been undertaken. Qualitative data will add value to this
emerging field by informing future research hypotheses and clinical
program development.
Methods: PD patients and providers who had participated in a
12-month randomized clinical trial of video telehealth were recruited
for this qualitative study. Semi-structured interviews were completed
to explore and describe the participants and providers experiences
with telehealth, as well as perceived advantages and disadvantages
compared with in-person visits. Using qualitative data analysis soft-
ware, content analysis and thematic coding, categories of codes that
captured their responses were generated.
Results: 14 PD patients and six providers were interviewed. Both
providers and patients expressed generally positive views of tele-
health. Providers stated that initial concerns regarding telehealth,
such as lack of full exam and using new equipment did not come to
fruition. All providers viewed telehealth as a valuable, viable and
sustainable option for PD patient care. Decreased travel burden, con-
venience of telehealth and increased access to care were the most
frequently cited advantages by both providers and patients. Draw-
backs largely related to technical issues, such as poor video quality
or signal interruptions. Despite these disadvantages, all patients and
providers saw telehealth as a worthwhile alternative to in-person vis-
its and similar in quality-of-care.
Conclusions: Providers and PD patients using video telehealth
programs in a clinical trial reported an overall positive experience
and high-level of acceptability. This qualitative analysis provides val-
uable information to drive future studies and clinical programs.
348
Withdrawn by Author
349
Efficacy and safety of rotigotine transdermal patch in Chinese
patients with early-stage Parkinsons disease: A randomized,
double-blind, placebo-controlled study
Z. Zhang, M. Asgharnejad, X. Du, E. Surmann, L. Bauer (Beijing,
Peoples Republic of China)
Objective: This multicenter, double-blind, placebo-controlled,
phase III study conducted in China (SP0914; NCT01646268) investi-
gated the efficacy and safety of rotigotine transdermal patch in Chi-
nese patients with early-stage Parkinsons disease (PD).
Background: Two 6-month phase III pivotal studies conducted in
North America (SP512) and Europe, Australia, New Zealand, Israel,
and South Africa (SP513), have shown rotigotine (8 mg/24h) to be
an efficacious and well tolerated therapy in patients with early-stage
PD. Rotigotine significantly decreased Unified Parkinsons disease
LS mean [95% CI] p-value (ANCOVA
Rotigotine treatment difference treatment
(n5123) vs placebo difference)*
-4.9 (9.9) -4.82 [-7.18, -2.45] <0.0001
-1.4 (3.6) -1.53 [-2.29, -0.77] <0.0001
-3.4 (7.3) -3.27 [-5.07, -1.48] 0.0004
Movement Disorders, Vol. 30, Suppl. 1, 2015
S138 POSTER SESSION
TABLE 2. AEs occurring in 5% of patients in any treat-
ment group; safety set
Placebo Rotigotine
Preferred term* (n5123), n (%) (n5124), n (%)
Any AE 63 (51.2) 71 (57.3)
Nausea 4 (3.3) 11 (8.9)
Dizziness 7 (5.7) 10 (8.1)
Pruritus 5 (4.1) 10 (8.1)
Somnolence 4 (3.3) 10 (8.1)
Erythema 2 (1.6) 8 (6.5)
Vomiting 2 (1.6) 7 (5.6)
*MedDRA Version 16.1. Data are number (%) of patients reporting
at least one AE.
Rating Scale (UPDRS) II1III total score compared with placebo, and
resulted in a significantly greater number of UPDRS II1III responders
(20% improvement). In these studies >95% patients were Caucasian.
Methods: Chinese patients with early-stage PD were randomized
1:1 to receive transdermally delivered rotigotine or placebo, titrated
over 1-4 weeks, and maintained at optimal/maximum dose (8 mg/
24 h) for 24 weeks. Primary efficacy variable: change in UPDRS
II1III total score from baseline to end of maintenance (EoM). Sec-
ondary variables: change in UPDRS II (activities of daily living),
UPDRS III (motor), and UPDRS II1III responder rates (20%
decrease in UPDRS II1III). Safety outcomes included incidence of
adverse events (AEs) and discontinuations due to AEs.
Results: Of 247 patients randomized, 220 (89.1%) completed the
study (113/124 [91.1%] in the rotigotine group, and 107/123 [87.0%]
in the placebo group). All patients were Chinese (150 [60.7%] male;
mean [6SD] age: 59.4 [10.2] years), with mean (6SD) PD duration
of 1.01 (1.22) years. Rotigotine significantly decreased UPDRS
II1III total score vs placebo (p<0.0001; Table 1). UPDRS II and
UPDRS III subscores were also decreased with rotigotine vs placebo
(Table 1). The 20% responder rates were higher with rotigotine (52
[42.3%]) vs placebo (27 [22.3%]). Most common AEs are shown in
Table 2. A total of 13 (5.3%) patients discontinued due to AEs (roti-
gotine: 6 [4.8%], placebo: 7 [5.7%]).
Conclusions: Rotigotine transdermal patch was efficacious in
Chinese patients with early-stage PD, resulting in significant benefits
in control of activities of daily living and motor function. Rotigotine
was generally well tolerated and AEs were similar to those reported
in the pivotal studies of Caucasian patients.
350
Rhythmic cueing with the Google glass for patients with
Parkinsons disease
Y. Zhao, T. Heida, J.H. Nonnekes, R.J.A. van Wezel (Enschede,
Netherlands)
Objective: To develop and test applications for rhythmic cueing
in the Google Glass to improve gait in patients with Parkinsons dis-
ease (PD).
Background: Smartglasses, a type of wearable computer that
possesses the features of a smart phone but can be worn like conven-
tional glasses, offer new possibilities for therapy and continuous
monitoring during activities of daily living. In particular, smart-
glasses like the Google Glass can provide visual and auditory cues
that have long been used to improve gait disturbances in people with
PD. Using motion and feature tracking, smartglasses can personalize
cues based on the state of the user and/or the user environment.
Methods: To approach the design of cueing applications (app) for
smartglasses in a user-centered way, we conducted an online survey in
the Netherlands on the attitudes, needs, and preferences of people with
PD with respect to this new technology. We then developed a mobile
Movement Disorders, Vol. 30, Suppl. 1, 2015
app for the Google Glass, using visual (e.g. flashing square and optical
flow) and auditory (e.g. metro-nome) cues to modulate gait. In a pilot
study with 10 patients with PD, the effectiveness of the app was tested
to investigate 1) the feasibility of using the Google Glass as a cueing
device and 2) which cueing modalities (e.g. audio, visual, or optic
flow) were most effective in improving gait. The subjects were asked
to navigate obstacle courses that simulate real life situations, including
those known to induce freezing of gait (FOG). The temporal fre-
quency of the cues were specified by the user according to their pre-
ferred walking speed. Various kinematic parameters were measured.
Results: The respondents of the survey were overall very enthusiastic
about smartglasses potential to help them self-manage their motor
symptoms. Preliminary results with the custom cueing app for the Goo-
gle Glass showed that temporal variability in gait and the frequency of
FOG was reduced. Gait velocity and stride length need not necessarily
be increased to improve the quality of gait. Consequently, patients
gained more confidence in walking. In descending order, patients pre-
ferred the use of the metronome, followed by visual cues and optic flow.
Conclusions: Patients with PD were generally positive about the
prospect of using smartglasses to facilitate activities of daily living.
Smartglasses like the Google Glass have potential as a rhythmic cue-
ing device.
Choreas (non-Huntingtons disease)
351
New onset progressive chorea with elevated striational Ab titers
J.P. Battista, W. Tse (New York, NY, USA)
Objective: Introduction: There are numerous paraneoplastic,
parainfectious and autoimmune processes described in association
with rapid onset chorea in adults. Striational antibodies, which are
commonly part of a paraneplastic panel, act on skeletal muscle and
are most commonly seen in myasthenia gravis. In this case, a patient
with chorea exhibited elevated levels of striational Ab, which has
not been described before.
Case description: A 77-year-old man with a history of mild cogni-
tive impairment, diabetes, high cholesterol, and aortic valve replace-
ment on anticoagulation had presented to clinic initially with 5 weeks
of rapid onset generalized progressive choreiform movements. The
patient was at his baseline mental status. There was no family history
of similar movements. Over one month, his movements became more
severe with some resultant dysphagia and weight loss and was admitted
for evaluation. A serum paraneoplastic panel resulted positive for stria-
tional ab with an elevated titer of 1:30720. During the admission, he
had an MRI of the brain w/wo gadolinium, CT of the chest, abdomen,
and pelvis, and lumbar puncture prior to administration of 5 days of
intravenous immunoglobulin. Inpatient workup for neoplasm and CSF
paraneoplastic panel (not including striational ab) were negative. There
was a mild elevation in CSF protein (66), 14-3-3 (4.0), and serum
ANA, Ach-R antibody and MuSK antibody were negative. The patient
reported a decrease in dysphagia and mild reduction in the severity of
his truncal and axial chorea after treatment with IVIG. Six days after
discharge, his symptoms had improved further, only receiving one dose
of risperidone 0.5mg 3 days prior. Two weeks after the outpatient visit,
the patients movements worsened and he was started on quetiapine to
which the patient had an adverse reaction (rash) and was switched to
risperidone 0.25mg twice a day with better control of his chorea.
Discussion: This case illustrates a presentation of rapidly progres-
sive chorea with a workup positive only for a highly elevated stria-
tional antibody titer. This antibody is most commonly seen in
myasthenia gravis, but the patient had a negative serologic workup
for myasthenia and had no clinical findings to suggest that diagnosis.
An elevated striational antibody has not been previously reported in
a case of chorea, and we suggest it may be considered as part of the
medical workup for causes of chorea.
 POSTER SESSION
352
Chorea as presenting clinical feature in a patient with cryopyrin-
associated periodic syndrome (CAPS)
C. Blahak, C.J. Schwarzbach, W.H. Schmitt, H. Baezner, K. Szabo,
M.G. Hennerici (Mannheim, Germany)
Objective: To describe the case of a female patient with chorea
as the presenting clinical feature of Cryopyrin-associated periodic
syndrome (CAPS).
Background: Cryopyrin-associated periodic syndrome (CAPS) is
a rare but well treatable monogenetic autoinflammatory disease char-
acterized by elevated interleukin (IL)-1 levels. It comprises a spec-
trum of phenotypes of varying severity with in some cases also
neurological manifestations.
Methods: Case Report.
Results: The 38-year-old female first presented in 2008 with
slowly progressive involuntary choreiform movements of the hands
and feet for about 14 years. Past medical history included inherited
deafness, rush, arthralgia, lymph node swelling and history of myocar-
ditis, family history was positive for inherited deafness and chronic
kidney failure. Neurological examination revealed intermittent darting
movements of the tongue as well as pronounced bilateral chorea of
the hands and feet with irregular non-rhythmic movements of the fin-
gers. Cerebrospinal fluid (CSF) examination showed mild pleocytosis
and elevated total protein with positive oligoclonal bands, blood
examination revealed markedly elevated anticardiolipin IgG and serum
amyloid A (SAA) levels. Genetic testing for Huntingtons disease as
well as Huntingtons disease-like 1&2 was negative. Cerebral MRI
showed extensive white matter changes with gadolinium enhancement
of two lesions, suspicious for inflammatory CNS disease.
An additional progressive chronic kidney failure in the course of
the disease in synopsis with family history and SAA elevation led to
genetic testing, which revealed a rare missense mutation of the
NLPR3 gene (p.Tyr859Cys) in exon 6 associated to the neonatal-
onset multisystem inflammatory disease (NOMID) phenotyp of
CAPS. While conventional immunosuppressive therapy with prednis-
olone and hydroxychloroquine proved to be insufficient, neurological
symptoms as well as inflammatory CNS lesions almost completely
disappeared following interleukin (IL)-1 blockage with anakinra.
Conclusions: This case report is to our knowledge the first
description of considerable chorea associated with antiphospholipid
antibody syndrome as leading clinical presentation of CAPS in a
patient with a rare missense mutation of the NLPR3 gene, adding
new neurological aspects to the broad range of phenotypes associated
with this disease.
353
Neurologic and systemic variability in benign hereditary chorea
due to NKX2-1 mutations
E.A. Coon, M. Milone, Z. Niu, M.C. Patterson, J.E. Ahlskog
(Rochester, MN, USA)
Objective: To describe phenotypic variability in a family with
benign hereditary chorea and expand the systemic manifestations
associated with NKX2-1 mutations.
Background: Benign hereditary chorea is characterized by child-
hood onset of non-progressive chorea often caused by mutations in
the NKX2-1 gene. Systemic manifestations may include thyroid and
pulmonary dysfunction known as brain-lung-thyroid syndrome
however, immune system and muscle involvement have not been
reported in this disorder.
Methods: Whole exome sequencing was performed on the pro-
band of a family with 2 members affected with childhood-onset cho-
rea; NKX2-1 targeted Sanger sequencing was performed on the
proband and family members. Clinical and laboratory data, including
thyroid, pulmonary function and muscle biopsy results were reviewed.
Results: The proband and the affected child harbor a novel hetero-
zygous likely pathogenic mutation in exon 3 of the NKX2-1 gene (c.
S139
727C>T; p.R243C), which affects a highly conserved arginine in the
homeobox domain and is predicted to be deleterious. The unaffected
child and probands mother do not carry the mutation. The proband
was born preterm requiring ICU care for respiratory distress. Since
birth, she was hypotonic with involuntary jerky movements. Motor
development was delayed and she required leg braces however was
cognitively normal. Examination revealed mild chorea with superim-
posed myoclonus. In her 20s, she was diagnosed with IgA nephropa-
thy and Henoch-Sch onlein purpura. She developed intermittent low-
grade fevers and lymphadenopathy followed by recurrent aseptic men-
ingitis (CSF white blood cell counts ranging from 5 to 135 cells). The
probands child was born at term with choreiform movements noted
at 2 months. Motor development was delayed and she also required
leg braces; cognitive and language skills were preserved. Neurologic
examination revealed hypotonia with nearly constant choreiform
movements. Laboratory evaluation revealed hypothyroidism and mild
tetrahydrofolate deficiency. Muscle biopsy showed no histological
signs of mitochondrial myopathy but deficiency of mitochondrial
chain complexes I, III and IV in the affected child.
Conclusions: Benign hereditary chorea can have intrafamilial
phenotypic variability with regards to neurologic and systemic mani-
festations. We report recurrent aseptic meningitis and mitochondrial
complex deficiencies in symptomatic NKX2-1 mutation carriers.
354
HIV seroconversion-associated chorea
M.V. Della Coletta, R.A.P. Souza (Manaus, Brazil)
Objective: to describe a case of chorea as the first manifestation
of HIV Seroconversion.
Background: There are diverse forms of HIV seroconversion pre-
sentations, and neurological manifestations like headache, meningitis
and encephalitis are the most common forms. Among infectious
agents, HIV and opportunistic infections are the leading reported
causes of chorea. In the vast majority of patients, hyperkinesias
result from lesions caused by opportunistic infections, particularly
toxoplasmosis, which damage the basal ganglia connections.
Movement Disorders are most commonly reported associated
with opportunistic infections or encephalitis and rarely as first mani-
festations of HIV-seroconversion.
Results: Patient R.R.S., 23 years old, natural from Tabatinga,
Amazonas State, Brazil. The patient was sexually exposed on June
6th 2013 to an HIV-positive individual.
On June 11th 2013 the patient initiated post-exposure prophylaxis
with Zidovudine, Lamivudine and Lopinavir-R, following the plan
for 30 days.
On August 15th 2013 the patient presented left hemiparesis. The
patient sought a medical service where a CT scan revealed no lesions.
On August 23 2013 the patient presented a clinical picture with
choreic movements on the left side of the body. HIV serology was
performed, with negative results, cerebrospinal fluid was without
alterations, cranium MRI was without alterations.
Started on sodium valproate therapy until a dose of 1000mg a
day, under which control of the choreic movements was achieved.
Inflammatory tests including ANA, ANCA, anticardiolipin and
lupus anticoagulant were negative Genetic screening for Hunting-
tons Disease was negative.
On November 2013, the patient underwent a new screening for
HIV with positive results, and a viral load of millions of copies.
The patient interrupted the sodium valproate therapy. After one
month, choreic movements returned, after which sodium valproate ther-
apy was restarted and control was achieved on a dose of 1000mg a day.
Conclusions: HIV-associated Movement Disorders may be
related to opportunistic infections or by direct action on basal gan-
glia. The Movement Disorders most commonly associated to HIV
are hemichorea and hemibalism, followed by Parkinsonism. We
described this case, of which the manifestation of HIV seroconver-
sion infection was hemichorea.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S140 POSTER SESSION
355
A m.12242A>G MTTS2 (mt-tRNASer(AGY)) variant in a patient
with dystonia and choreoathetoid movements
R.J.B. Ellis, M. Bonello, N.A. Fletcher, S.A. Hardy, R.W. Taylor
(Liverpool, United Kingdom)
Objective: To report a case of choreoathetosis and dystonia asso-
ciated with a rare mitochondrial (mt-)tRNA variant.
Background: Mutations in mt-tRNA genes are important causes
of neurogenetic disease. Whilst there has been a previous report of a
mt-tRNASer(AGY) mutation causing deafness, retinal degeneration,
epilepsy and myopathy, Movement Disorders have not been associ-
ated with mutations in this gene.
Methods: Case report.
Results: We present the case of 26-year old female patient who
was referred to our centre for consideration of deep brain stimulation
and a diagnosis of athetoid cerebral palsy. She had a history of
motor developmental regression from age 21=2 years, prior to which
she was able to walk. She then became progressively disabled with
recurrent falls, involuntary movements and spasms resulting in her
becoming wheelchair-bound. She developed seizures at the age of 8
and these are well controlled on lamotrigine.
Examination revealed anarthria, severe generalised dystonia with
additional choreoathetoid movements affecting the arms, legs and
head. Her swallowing was also impaired.
DNA testing for Huntingtons disease, white cell enzymes, copper
and caeruloplasmin were negative and brain MRI scan was normal.
The patient underwent a muscle biopsy which demonstrated char-
acteristic features of mitochondrial disease including 10% cyto-
chrome c oxidase (COX)-deficient fibres. Sequencing the entire
mitochondrial genome (Ion Torrent PGM platform) revealed a rare
m.12242A>G MTTS2 (mt-tRNASer(AGY)) variant at near homo-
plasmic levels in patient muscle. This rare variant has a low allele
frequency in the population, is located within the T-stem of the mt-
tRNASer(AGY) molecule and is predicted to disrupt a Watson-Crick
base pair, with the potential to alter mt-tRNA secondary function
and impede function. Further functional testing is continuing.
Conclusions: We describe here a new phenotype associated with
mt-tRNA gene mutations. Movement Disorders are not an uncom-
mon component in mitochondrial syndromes. However it is impor-
tant to consider mitochondrial disorders in any unexplained,
progressive Movement Disorders, especially in the presence of other
syndromic features.
356
ADCY5 mutations can cause benign hereditary chorea
R. Erro, N.E. Mencacci, J. Hersheson, S. Wiethoff, B. Balint, C.
Ganos, M. Stamelou, N.P. Quinn, H. Houlden, N.W. Wood, K.P.
Bhatia (London, United Kingdom)
Objective: To determine the genetic contribution of ADCY5
mutations to Benign Hereditary Chorea (BHC) cases lacking muta-
tions in the TTF-1 gene.
Background: BHC defines a poorly delineated syndrome, charac-
terized by childhood onset of chorea, with little progression and
absence of other major neurological issues, including cognitive
decline. Mutations in the TTF-1 gene are detected in a number of
BHC families, but a genetic cause is not found in all cases. Recently
mutations in ADCY5 have been associated to Familial Dyskinesia
with Facial Myokymia (FDFM), an autosomal dominant Movement
Disorder characterized by early-onset, choreiform and dystonic dys-
kinesias, possibly associated with perioral and periorbital myokymia.
Methods: We studied 19 consecutive TTF-1 negative unrelated
cases (7 familial and 12 sporadic) with a clinical diagnosis of BHC.
Complete mutational analysis of ADCY5 was performed by whole-
exome sequencing or by direct Sanger sequencing.
Results: The previously described pathogenic mutation c.1252C>T;
p.R418W mutation of ADCY5 gene was identified in two cases (12.5%,
Movement Disorders, Vol. 30, Suppl. 1, 2015
1 familial and 1 sporadic). The mutation was inherited by the affected
father in the familial case and was de novo in the sporadic one. The
clinical phenotype of cases with ADCY5 mutations predominantly fea-
tured generalized chorea and dystonia, with significant intra-familial and
inter-familial phenotypic variability, but no facial myokimia. While
ADCY5 mutations might result in BHC-phenocopies at onset, the clini-
cal progression and the development of clear dystonic features might
allow the distinction from BHC related to mutations in the TTF-1 gene.
Conclusions: Our results show the association between patho-
genic ADCY5 mutations and familial and sporadic BHC syndrome.
Genetic analysis of ADCY5 should be therefore performed in cases
with early-onset benign choreiform Movement Disorder, even in
the absence of facial myokymia.
357
Acute onset hemichorea-hemiballism after treatment with
recanalization of middle cerebral artery
H. Kim, J.H. Jin, H.G. Roh, H.Y. Kim (Seoul, Korea)
Objective: Case report.
Background: Hemichorea-hemiballism (HC-HB) can result from
a variety of conditions, including cerebrovascular, metabolic, neuro-
degenerative, infectious, toxic, immunologic disorders, as well as
nonketotic hyperglycemia.
Methods: Here, we report a case with HC-HB occurred after
recanalization of middle cerebral artery (MCA).
Results: A 48 year-old man was presented to the emergency room
for left side weakness and dysarthria. The initial neurological examina-
tion revealed dysarthria, left lower facial weakness, drift of the left arm,
and sensory extinction. Brain computed tomography (CT) scan and mag-
netic resonance imaging (MRI) showed multifocal hyperacute infarctions
in the right MCA territory with large diffusion-perfusion mismatch area
and occlusion of the right MCA distal M1. He was given intravenous
rtPA therapy, followed by mechanical thrombectomy and thrombolysis
for the right MCA occlusion, and stenting for large floating thrombus in
right carotid artery. Recanalization of MCA was successful, however, he
developed HC-HB involving left arm and leg, left face and tongue dur-
ing intervention. Follow-up brain MRI confirmed no new lesion and
some areas with reversible DWI/ADC change in the right frontal white
matter, insula, and temporal opercular region compared to initial MRI.
His HC-HB completely disappeared after taking haloperidol, lorazepam,
and quetiapine, which was withdrawn on hospital day 4.
Conclusions: We assumed that hyperperfusion associated with
MCA recanalization played a central role in this case.
358
Network localization of hemichorea
S. Laganiere, A. Boes, L. Shih, M. Fox (Boston, MA, USA)
Objective: To determine whether neuroanatomically heterogene-
ous lesions causing hemichorea localize to a common functional
network.
Background: Brain lesions resulting in hemichorea have been
reported in a wide variety of locations including the cortex, basal
ganglia, thalamus and brainstem. Due to this heterogeneity, no single
neuroanatomical location can be considered necessary or sufficient
for this disorder. Interestingly, hemichorea associated with a hyper-
glycemic state demonstrates almost invariable involvement of the
posterior putamen. The discrepancy between the localization in these
two conditions remains unexplained.
Methods: We searched the literature for cases of stroke-induced
hemichorea with published neuroimaging findings. Brain lesion vol-
umes from each clinical scan were copied onto a reference brain in
atlas space. Each lesion volume was then used to seed a resting
state functional connectivity analysis utilizing data from a large
cohort of healthy subjects. This analysis identifies the network of
brain regions correlated with the lesion site in the healthy brain and
serves as a prediction of which regions are likely to be impacted by
 POSTER SESSION
the lesion in the patients brain. These network results were then
overlapped to find brain sites common to our set of lesions.
Results: Our literature search identified 29 lesions resulting in
hemichorea. Although lesions showed pronounced heterogeneity in
anatomical location, 26 of 29 lesions or 90% showed significant
functional connectivity specifically with the posterior putamen. A
control cohort of stroke lesions without hemichorea showed signifi-
cantly less connectivity to this area.
Conclusions: Our data suggest that strokes causing hemichorea,
while anatomically heterogeneous, almost all occur in areas with
functional connectivity to the posterior putamen. Such network local-
ization reconciles findings from stroke-induced hemichorea with sim-
ilar symptoms induced by hyperglycemia. These results highlight the
importance of the posterior putamen in hemichorea but also suggest
that specific Movement Disorder phenotypes may better localize to a
brain network than a single anatomical region.
359
Choreoballism arising from the involvement of the putamen: A
report of 18 cases and a systemic literature review
D. Lee, H.G. Woo, T.B. Ahn (Seoul, Korea)
Objective: In this study, we planned to investigate clinical and
neuroimaging features of choreoballisms involving the putamen.
Background: Vascular lesions can be associated with choreobal-
lism (vascular choeroballism, vCB). Both hyperglycemia and hypo-
glycemia are common etiologies of CB (glycemic CB, gCB). The
putamen is a commonly affected by gCB and vCB. No study was
done to compare the cases with gCB and vCB.
Methods: 1) To report our own cases with vCB and gCB, we retro-
spectively included patients with CBs based on our database. Those who
presented with CBs, with evidences of poor glycemic control or cerebro-
vascular events, and harbored responsible lesions including the putamen
were included. We summarized and described clinical and neuroimaging
data of our patients. 2) For further analysis, historical cases were collected
from the literature with the same inclusion criteria. Demographic, clinical
and neuroimaging data were extracted. Statistical analyses were done to
identify clinical and neuroimaging factors associated with clinical
outcomes.
Results: We included 18 cases (15 gCB and 3 vCB) from our hospital.
Total 266 cases (232 gCB and 34 vCB) including our own cases were ana-
lyzed. Chorea was more common as an initial manifestation than ballism.
CBs were persistent over 1 month in 91 cases. The protracted clinical
course over 1 month was more common in those with vCB. Additional
lesions outside the putamen were found in half the cases with gCB while
additional lesions were more common (73.5%) among those with vCB.
Age was a significant predictor for the prolongation of CBs over 1 month
[odd ratio (OR) 5 1.033, 95% confidence interval (C.I.) 5 1.008 1.059,
p 5 0.009]. Additional lesions outside the putamen was a significant factor
for CBs over prolonged clinical course over 12 months (OR=2.808, 95%
C.I. 5 1.269 6.212, p 5 0.011).
Conclusions: The putamen was frequently involved in CBs sec-
ondary to glycemic derangement or cerebrovascular events. Age and
extensive lesions including the putamen were important factors for
bad outcome in gCB and vCB.
360
Management of aceroplasminemia with a combination of
venesection, fresh frozen plasma and desferrioxamine
M. Narasimhan, S. Ramanathan, C. Turner, L. Ramon (Sydney,
Australia)
Objective: To demonstrate a role for venesection in
aceruloplasminemia.
Background: Neuronal brain iron accumulation disorders are a
rare group of inherited Movement Disorders with deposition of iron
in the brain. In two - aceruloplasminaemia and neuroferritinopathy-
S141
there is a link to iron metabolism, in others the mechanism of iron
deposition is unknown. Lack of ceruloplasmin interferes with iron
utilisation and causes iron deposition in the brain and other organs.
The gold standard of treatment has been chelation therapy, however
while it depletes peripheral iron, it is unclear whether brain iron
stores are affected.
Methods: Our patient was a 57 year old male who had been
diagnosed with aceruloplasminemia 13 years ago when aymptomatic
and was receiving desferrioxamine on a fortnightly basis. MRI
showed extensive iron deposition in the basal ganglia, cerebellum
and cortex. Five years ago he developed depression and aggression
and was being managed by a tertiary neuropsychiatric centre. Eight-
een months ago he developed right sided chorea which progressively
worsened with orofacial dyskinesias, truncal dystonia and ataxia, he
became wheelchair bound. Tetrabenazine, while effective, was asso-
ciated with side effects of insomnia and mood changes and was
withdrawn. He was initially treated with fresh frozen plasma and
oral zinc sulphate with some improvement but was readmitted with
worsening behaviour which stabilised on clonazepam and risperi-
done. Venesection was commenced under the aegis of haematology
in combination with FFP and chelation.
Results: A couple of months after commencing venesection there
was significant improvement in the Movement Disorder and psychi-
atric manifestations which has persisted 8 months later. He was man-
aged jointly by Neurology and Rehabilitation and gained
independent ambulation. Apart from a mild anaemia which is stable
he has tolerated venesection well with no side effects, his ferritin
levels have reduced significantly (figure 1). [figure1]
Conclusions: Aceruluplasminemia is a rare heredodegenerative
disorder with extensive brain iron deposition and complex neuro-
psychiatric features. While iron chelation is routinely used there is
no convincing evidence that it depletes brain iron stores. FFP has
been previously reported as being effective. We suggest the use of
venesection in combination with chelation and FFP based on its ben-
efit in our patient with no observed complications.
361
Optical coherence tomography in Huntingtons disease
V. Parisi, E. Gatto, S. Ochoa, D. Scocco, E. Fernandez Rey (Buenos
aires, Argentina)
Objective: To evaluate Retinal Nerve Fiber Layer (RNFL) thick-
ness measured by optical coherence tomography (OCT) in patients
with Huntingtons disease (HD).
Background: Optical coherence tomography (OCT) is a noninva-
sive procedure for analysis of retinal structure. Changes in the thick-
ness of the peripapillary retinal nerve fiber layer (RNFL) has been
identified and evaluated as marker of neurodegeneration in different
disorders such as Parkinsons disease or Alzheimer disease.
Fig. 1. (360).
Movement Disorders, Vol. 30, Suppl. 1, 2015
S142 POSTER SESSION
HD is an autosomal dominant neurodegenerative condition caused
by abnormal CAG expansion characterized by motor, behavioral and
cognitive symptoms. Experimental studies in animal models of HD
have shown an early and progressive retinal degeneration with photo-
receptor damage objectivable by OCT.
Methods: Consecutive HD patients with normal ophthalmologic
examination were prospectively analyzed using a Fourier domain
OCT (Heidelberg Engineering, OCT Spectralis plus). RNFL thick-
ness was assessed in temporal, nasal, inferior and superior quadrants
and automatically compared by the equipment with standardized con-
trols (SC). Demographic data was obtained.
Results: Nineteen eyes of 10 HD patients (6 women) underwent
OCT, mean age 41 years, median CAG repeat 44, mean disease
duration 5 years. OCT measurements of RNFL in 5 eyes from 4
patients showed borderline temporal RNFL thinning in HD patients
compared with SC.
Conclusions: To our best knowledge, this is the first study con-
ducted to explore retinal involvement in HD patients using OCT.
Besides the small sample size, a restricted RNFL thinning was seen
in some patients. A more extensive study is ongoing to assess if
OCT could be a potential and reliable biomarker in HD.
362
Clinical characteristics and genetic testing of a Huntingtin
mutation negative cohort
K.J. Peall, H.R. Morris, M. Wardle (Cardiff, United Kingdom)
Objective: To evaluate cases referred for Huntingtons disease
(HD) genetic testing with a subsequent negative genetic test. To deter-
mine: 1) their clinical characteristics, 2) nature of the progression of
their clinical symptoms, 3) any further genetic testing performed.
Background: HD is the most common form chorea with an iden-
tifiable genetic aetiology. However, there is increasing recognition of
HD-like syndromes with distinct genetic mutations.
Methods: Local genetics service database was used to identify
patients initially referred for HD genetic testing but with a subse-
quent negative test. Retrospective clinical information was collected
by use of a standard proforma and review of the clinical notes. The
genetics database was then used to identify which, if any, further
genetic tests were performed.
Results: Fifty consecutive cases, 14 with a positive family history
of a similar Movement Disorder, were identified. Mean age at
genetic testing was 55.4 years. Clinical characteristics included: cho-
rea (20%), cognitive decline (22%), Parkinsonism (10%), ataxia
(22%), seizures (2%), myoclonus (14%), dystonia (35%). Fifteen
cases (31%) had additional clinical features with tremor (6), mood
disturbance (4) and dysphagia (3) being most common. The clinical
course was graded as progressive (49%), static (31%) or improving
(8%), this information not being available in 7 cases. Twenty-two
cases (44%) went on to have further genetic testing with DRPLA
being most common (17/22) followed by testing of a spinocerebellar
ataxia panel (2, 3, 4, 6, 7, 17) (7/22) and DYT1 (5/22).
Conclusions: This cohort demonstrates a broad range of clinical
characteristics in those considered to have a HD-like phenotype but
with a negative HD genetic test. Less than 50% of this cohort were
considered for further genetic testing, with only 7 cases tested for
one or more of the HD like syndromes. Greater consideration should
be given to systematic testing of the HD like genetic disorders to
allow greater understanding of their genotype-phenotype relationship.
363
Pyramidal involvement in Huntingtons disease. Preliminary
report
A. Sanguinetti, E.M. Gatto, M. Cesarini, J. Etcheverry, V. Parisi, G.
Persi, L. Bevacqua, P. Lopez, A. Bertotti (Buenos Aires, Argentina)
Movement Disorders, Vol. 30, Suppl. 1, 2015
Objective: to describe clinical, structural (DTI tractography) and
electrophysiological pyramidal impairment in HD patients. Prelimi-
nary report.
Background: Clinical features of HD have been attributed to
subcortical basal ganglia circuits impairment, but there is increasing
evidence that the cerebral cortex and the loss of cortical pyramidal
neurons play a primary role in the pathobiology of HD. Moreover,
transcranial magnetic stimulation (TMS) has shown abnormal infor-
mation processing and decreased excitability in motor and sensory
cortices. Interestingly, these changes might occur early in HD and
explain the clinical heterogeneity.
Methods: Subjects with HD from our Institution were examined for
pyramidal signs. Additionally, DTI tractography and motor evoked
potentials (MEPs) elicited by TMS were performed. Demographic, epi-
demiological and clinical data were analyzed. The study was approved
by the Institutional Review Board. Non-parametric tests were used.
Results: 7 HD patients with pyramidal signs were evaluated,
mean age 47.14 years (range 23-62 years), mean age at onset 42.16
years (range 60-16), and mean disease duration of 7 years, (range 2-
13 years). Mean CAG repeats in expanded allele was 47 (range 42-
66). One patient had Juvenile HD. DTI was normal in 6/6 patients.
MEPs elicited by TMS were obtained in 4 patients. All cases
showed at least one of the following abnormalities; decreased MEP
amplitudes, increased latencies and/or central motor conduction
times, reduced cortical silent periods.
Conclusions: Present results add to previous experimental and
functional evidence that support a pyramidal involvement in HD sug-
gesting a possible cortical contribution to the variable HD pheno-
types and open new potential markers to be explored.
364
Non-rapid-eye movement and rapid-eye-movement parasomnia
with sleep breathing disorder, chorea and dementia associated
with antibodies to IgLON5: Case report
M.M. Simabukuro, L. Sabater, T. Adoni, R.G. Cury, M.S. Haddad,
C.H. Moreira, L. Oliveira, R.C. Alves, L.A. Soster, R.A. Nogueira, C.
Graig, R. Nitrini (S~
ao Paulo, Brazil)
Objective: To describe the clinical characteristics of a late onset
chorea related to a novel antibody IgLON5 and associated with sleep
dysfunction and dementia.
Background: IgLON5 is the most recent identified antigen within
category of neurologic disorders associated with antibodies against
cell-surface or synaptic proteins and establishes a new disease. It
was first described in 8 patients and differs from autoimmune
encephalitis described until this moment, because of it may have pro-
tracted course, the prominent symptom is sleep dysfunction, there is
little response to immunotherapy and neuropathological findings are
suggestive of neurodegenerative process. It is characterized by non-
REM and REM parasomnia with sleep breathing dysfunction, signs
of bulbar involvement, dysautonomia, chorea and dementia. IgG4
antibodies against IgLON5 is detected in serum and CSF, and all
patients whose HLA genotyping carried the same HLA alleles. Out-
standingly, neuropathology studies revealed tau deposition with pred-
ilection for tegmentum of brainstem and hypothalamus, without
other pathological changes seen in known tauopathies.
Methods: We describe the first case with IgG4 antibodies against
IgLON5 presented with inflammatory changes in CSF.
Results: A 71-year-old woman presented with snoring and exces-
sive daytime sleepiness six years earlier. A diagnosis of sleep obstruc-
tive apnea was made after a polissonography and CPAP was
indicated. Within one year, she evolved with chorea and progressive
dementia. On examination, she scored 20 points on mini-mental state
examination, chorea and subtle restriction of voluntary eye movement
in the vertical plane. Brain MRI and electroencephalogram showed no
remarkable findings. Cerebrospinal fluid disclosed mild pleocytosis
and elevated protein. Antibodies to IgLON5 were identified in serum
 POSTER SESSION S143

and CSF, and HLA genotyping resulted in HLA-DRB1*1001 and
HLA-DQB1*0501 alleles, also found in other patients.
Conclusions: Neurologic disorders associated with antibodies
against cell surface or synaptic proteins are continuously changing
paradigms. Better understanding how IgLON5 antibodies relate to
tau deposits may provide a unique model for assessing how autoim-
munity can trigger neurodegenerative processes. This is the first case
to show inflammatory changes in CSF, which favors the hypothesis
of an associated immune mechanism.
expert in Movement Disorders and referred to EMG laboratory for
confirmation of clinical opinion of OM.
Results: The mean age of patients was 84 (80-89), 3 of them
were men. They complained of gait difficulty, frequent spontaneous
falls and irregular tremulousness of the legs upon standing and 2
reported forgetfulness. Neurological examination revealed lower
body Parkinsonism in all. Inspection and palpation of the legs sug-
gested spontaneous bilateral contraction/relaxation especially of the

Myoclonus

365
Ortostatic myoclonus: Clinical and electrophysiological features
of four patients
H. Apaydin, B. Zeydan, A. Gunduz, G. Kiziltan, S. Ertan, M. Kiziltan
(Istanbul, Turkey)
Objective: Clinical features, electrophysiological findings and
treatment responses of 4 consecutive patients diagnosed with ortho-
static myoclonus (OM) was reported.
Background: OM, recently described as slowly progressive trem-
ulousness or unsteadiness upon standing, is usually seen in the
elderly with gait instability. It should be differentiated from ortho-
static tremor (OT) which is also a very rare condition. The electro-
myographic (EMG) evaluation of the leg muscles can be used to
differ the two conditions. Since patients with OM have difficulty in
explaining their atypical complaints, they are occasionally diagnosed
with functional Movement Disorder (FMD).
Methods: Patients admitted to our outpatient clinic with com- Fig. 2. (365).
plaint of unsteadiness due to tremulous legs were evaluated by an

Fig. 1. (365).

Movement Disorders, Vol. 30, Suppl. 1, 2015

S144 POSTER SESSION
gastrocnemius and anterior tibial muscles. One patient had vertical
gaze palsy. Nerve conduction studies and needle EMG were normal.
A surface multichannel EMG recording revealed myoclonic activity
during standing in the upright position. [figure1][figure2]The first
patient, diagnosed as vascular Parkinsonism, had dramatic response
to levodopa (LD). The second, diagnosed as progressive supranuclear
palsy, partially responded to LD. The third, diagnosed as Lewy body
dementia, remained unresponsive to LD. The last one was partially
ameliorated with high dose of pirasetam therapy.
Conclusions: OM is a very rare hyperkinetic disorder, usually
seen in conjunction with neurodegenerative diseases. The key point
in differentiation of OM and OT is the irregular and arrhythmic
bursts of short duration in EMG. Apart from detailed patient history,
the meticulous neurological examination with palpation of leg
muscles can help to exclude FMD. OM usually responds well to
treatment which lead significant improvement in quality of life.
Fig. 1. (366).
Movement Disorders, Vol. 30, Suppl. 1, 2015
366
Cortical myoclonus in neurocritical care unit in patients with
acute stroke and stroke like syndrome patients
N. Chaudhary, J.M.K. Murthy, S. Jaiswal, M. Reddy (Hyderabad,
India)
Objective: To study etiology of cortical myoclonus in neurocriti-
cal care unit presenting as stroke and stroke like syndrome.
Background: Myoclonus is sudden, involuntary jerking of a sin-
gle muscleor a group of muscles.Myoclonus is a rare symptom in
patients with stroke and mostly reported in posterior circulation stro-
kes,Focal cortical myoclonus almost always points to an underlining
lesion of the sensori-motor cortex, which produces hyperexcitabili-
ty(e.g.vascular,inflammatory, neoplastic).
Methods: Here we reviewed three patients with acute onset focal
neurological deficit suggestive of acute stroke and followed by focal
myoclonus, who are admitted in neurocritical care unit all three
 POSTER SESSION
Fig. 2. (366).
patients were undergone required neuroimaging,EEG, metabolic pro-
file, antiTPO antibodies.
Results: Case 1:This 39 years old Hypertensive male admitted
with recurrent irregular jerky movement in right upper limb involv-
ing distal 1 proximal arm suggestive of myoclonus.No facial twitch-
ing or loss of consciousness.His MRI DWI Suggestive of A tiny
focus of restricted diffusion in the right high parietal cortical region
His CT Brain angiogram shown 90% luminal narrowing of right ICA
along its entire course. His EEG was normal.He was found to have
hyper homocysteinemia.He remained asymptomatic after levetirace-
tam. [figure1]
Case 2:This70 years old male known case of coronary Artery dis-
ease on antiplatlets admitted with history of altered sensorium and
left sided weakness (grade 3/5) since 1 day.CT shown right Tempo-
parietal acute SDH .On second day of admission developed recurrent
abdominal jerking movements irregular suggestive of myoclonic
jerks.No oral facial or limb movements.He started on levetiracetam-
stopped abdominal movements, SDH drained.
Case3:10 year old male admitted with history of recent onset
recurrent generalized myoclonic jerks since 3 months, now came
with cortical blindness and left hemiparesis (4/5) he started having
recurrent focal movements of left UL and left face with superadded
irregular jerks suggestive of epilepsia partialis continua with myo-
clonic jerks (epileptic myoclonus), his myoclonic jerks were sensitive
to touch .he was on valproate and levetiracetam,He was homozy-
gous, his parents were heterozygous POLG gene mutation.[figure2]
Conclusions: Cortical myoclonus etiology is variable in presenta-
tion as acute stroke syndrome from genetic to acquired. Levetirace-
tam is very good drug for cortical myoclonus.
S145
367
Electrophysiological findings in Rasmussens encephalitis
A. Gunduz, M. E. Kiziltan, T. Coskun, S. Delil, N. Yeni, C. Ozkara
(Istanbul, Turkey)
Objective: We sought to demonstrate the electrophysiological
features in patients with Rasmussen encephalitis.
Background: Rasmussen encephalitis is a rare, inflammatory and
probably autoimmune disease presenting with epilepsia partialis con-
tinua which is generally in the form of myoclonic jerks and involves
upper extremity or head and upper extremity.
Methods: We performed continuous electrophysiological record-
ings of involuntary movement as well as recordings of startle
responses and long latency reflex in three patients with the diagnosis
of Rasmussen encephalitis.
Results: Positive and negative myocloni were recorded. Startle
responses were found to be suppressed. However, long latency
reflexes were high in amplitude and one patient even had C reflex.
Conclusions: Stimulus sensitive positive and negative cortical
myocloni are typical in epilepsia partialis continua of Rasmussen
encephalitis and degeneration of reticulospinal pathways may
develop in Rasmussen encephalitis.
368
Isolated lingual myoclonus as a presentation of celiac disease
D.C. Khandelwal, C.M. Sharma, B. Kumawat (Jaipur, India)
Movement Disorders, Vol. 30, Suppl. 1, 2015
S146 POSTER SESSION

Objective: To report a case of isolated lingual myoclonus as a scale (YBOCS-severity) and the YBOCS symptoms checklists, panic
presentation of celiac disease. disorder symptoms severity and 36 item health survey were assessed.
Background: Neurological disorders as a presentation of celiac Results: Clinical characteristics were not different between 11
disease is very rare. Isolated lingual myoclonus has been previously SGCE mutation positive (MP, 8 index patients and 3 family mem-
reported in the literature but not with celiac disease. bers from 2 index cases) and 8 negative group (MN) for age onset,
Methods: 59 years old gentleman was asymptomatic nine months family history, alcohol responsiveness and motor severity.
back until his wife noticed that there was some slurring of speech.
The patient didnt have difficulty in swallowing. There was no his-
tory of weight loss or diarrhea. Clinical examination revealed rhyth- Demographics and clinical characteristics of myoclonus dystonia
mic involuntary tongue movements.These movements were visible in with and without SGCE mutation
submental area even from outside. There were no associated involun-
SGCE(1) SGCE(-)
tary palatal movements. Patient could protrude and retract tongue but
lateral movements were severely restricted. Bulk of tongue was nor- Gender (% male/female) 55/45 25/75
mal and there were no twitchings. Floor of the mouth was raised Age 38(14.8) 45.7(10.3)
suggestive of enlarged sublingual salivary glands. Patient had lingual
Age at onset 9.9(6.7) 10.4(9.6)
dysarthria. Rest of neurological examination was normal.
Disease duration (yr) 28.6(15.4) 36.1(12.8)
Results: Electromyography (EMG) didnt revealed evidence of Family history (%) 75.0% 50.0%
denervation or renervation in tongue or any other limb muscles but Alcohol responsiveness 63.6% 75.0%
there were rhythmic EMG artefacts of about 4-5Hz. MRI neck with
Psychiatric symptoms by Total 54.5% Total 50.0%
contrast was done which revealed enhancement of left side of tongue
history
with adjacent floor of mouth, diffuse enlargement of bilateral parotid Depression 45.5% Depression 50.0%
and sublingual glands. Whole body FDG f18 PET showed increase Obsession 18.2% Anxiety 12.5%
uptake in the same regions. Immunofixation electrophoresis and
Alcohol disuse 9.1% Obsession 12.5%
immunological profile tests were normal. Histopathological examina-
Panic disorder 9.1% Phobia 12.5%
tion of right parotid gland revealed interlobule connective tissue BFMDRS score 10.2(8.8) 8.6(12.8)
oedema and infiltrates by few inflammatory cells.Serum tissue trans- UMRS score 53.2(26.4) 52.1(52.1)
glutaminase (tTG) IgA level was very high (>300U/ml) and anti
K-MMSE 28.8(1.1) 27.7(2.9)
endomysial antibodies were weakly positive. Serum vitamin B 12
level and serum methylmelonic acid levels were normal. Duodenal
biopsy was taken which revealed partial villous atrophy with crypt Data shown as mean(standard deviation)
hyperplasia, marked infiltration of lymphoplasmocytic cells in lamina
propria and increased intraepithelial lymphocytes. SGCE mutation rate was 50% in 8 index MP cases and 8 MN
Patient was diagnosed to have lingual myoclonus secondary to cases. Affected body part assessment for myoclonus dystonia showed
celiac disease and treated with gluten free diet. Serum anti tTG anti- more frequent truncal involvement for myoclonus compared to other
bodies level reduced to 28.6 U/ml after three months of follow up. body lesion in MP group.(p50.024).There was no significant differ-
Patient showed significant improvement in speech and lingual myo- ence between MP and MN group in quantitative psychiatric
clonic movements. assessments.
Conclusions: This case demonstrates that celiac disease can be
one of the potentially treatable causes of isolated lingual myoclonus.
Quantitative psychiatric assessments in myoclonus dystonia with
and without SGCE mutation
369
Questionnarie scores SGCE(1) SGCE(-) p-value
Psychiatric features may be clinical spectrum of myoclonus
dystonia syndrome regardless of SGCE gene mutation YBOCS 5.30(5.76) 2.88(3.60) 0.376
J.Y. Kim, W.W. Lee, H.J. Kim, B.S. Jeon (Seoul, Korea) AUDIT-K 3.6(6.57) 5.0(5.73) 0.188
Objective: (1) To compare the motor and psychatric features in PHQ-9 7.4(6.36) 4.88(5.89) 0.265
myoclonus dystonia with SCGE gene mutation to myoclonus dysto- Beck Depression Inventory 14.30(10.09) 9.63(8.40) 0.423
nia without SGCE gene mutation (2) To evaluate whether psychiatric Beck Anxiety Inventory 17.7(13.37) 14.13(9.63) 0.689
features found in myoclonus dystonia syndrome are related with Panic Disorder Severity Scale 3.0(4.22) 1.63(2.93) 0.686
SGCE mutation. Data shown as mean (standard deviation), Mann-Whitney U test
Background: Psychatric features such as depression, anxiety,
alcohol disuse or obsessive compulsive disorders have been fre-
quently reported in myoclonus dystonia patients with SGCE gene Physical and mental scores from SF-36 were similar between
mutation. However most studies had compared psychiatric features groups. Motor severity was not correlated with scores of psychiatric
in myoclonus dystonia patients with SGCE mutation and in patients questionnaires.
with other Movement Disorders. Approach for comparison of psychi- Conclusions: Our study suggest psychiatric features may be a
atric features in myoclonus dystonia patients with and without SGCE part of clinical spectrum of myoclonus dystonia syndrome regardless
mutation has been lacking. of SGCE mutation.
Methods: Patients who fulfilled the Grunewalds criteria of myo-
clonus dystonia syndrome were recruited. Symptomatic family mem-
bers of patients with SGCE gene mutation were invited. Secondary 370
causes of myoclonus and/or dystonia were exclude by history, brain Limbic encephalitis associated with antivoltage-gated potassium
MRI and laboratory tests including for DYT1 and Wilsons disease. channel complex antibodies mimicking Creutzfeldt-Jakob disease
Subjects underwent standardized interview and video recording for M.J. Liu, G. Chang (Phoenix, AZ, USA)
BFMDRS and UMRS. To quantify the psychiatric features, question-
naires including the patient health questionnaire-9, Beck depression Objective: VGKCC (anti-voltage-gated potassium channel com-
inventory, Beck anxiety inventory, alcohol use disorder identification plex) syndrome (LGI1 subtype), which mimicks Creutzfeldt-Jakob
test-Korean version(AUDIT-K), Yale Brown obsessive compulsive disease (CJD), has been reported with the recognition of epileptic

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
Movement Disorder; specifically, faciobrachial dystonic seizure, as a
clue to the diagnosis.
We report a case illustrating that the same LGI1 subtype may
present with myoclonic dystonia and choreoathetosis.
A 70-year old retired neuropathologist presented with 2 months of
progressive cognitive decline and myoclonus. Examination revealed
intermittent poor recall with occasional brief jerks. Despite poor mem-
ory, she was able to recall brief dystonic hand and leg posture lasting
seconds, and longer lasting episodic difficulty with stiff arms and
legs when she quickly moved, particularly upon standing after pro-
longed sitting. Her husband had to assist until the episodes eased, usu-
ally within a minute and there were no change of cognition during
these episodes. Carbamazepine was started and she had no further
spells of kinesogenic choreoathetosis, although brief spontaneous dys-
tonia and myoclonus persisted. Subsequent evaluation including brain
MRI and CSF examination were unrevealing. Continuous EEG moni-
toring showed no epileptiform activity. Following confirmation of
VGKCC syndrome (LGI1 subtype), she was treated with plasmapher-
esis and intravenous immunoglobulin with clinical stabilization. Ten
months after onset of her illness she has returned to her baseline while
being maintained on low dose prednisone and carbamazepine.
Although the clinical setting was concerning for CJD in this
retired neuropathologist presenting with subacute dementia and myo-
clonus, the presence of kinesogenic choreoathetosis, i.e. action-
induced segmental dystonic-athetoid like movement, is of interest.
Responsiveness to low dose carbamazepine reaffirms the previous
suggestion of basal ganglia epilepsy and further highlights the
range of Movement Disorder that may be seen.
Reference.
JY Yoo, LJ Hirsch. Potassium Channel Complex Antibodies
Mimicking Creutzfeldt-
Jakob Disease. JAMA Neurol. 2014;71(1):79-82.
371
An interesting case of post-infectious myoclonus secondary to
infection with cytomegalovirus
S. Padidam, D.E. Kremens (Philadelphia, PA, USA)
Objective: To report a case of myoclonus, ataxia and mild ence-
phalopathy without opsoclonus following a cytomegalovirus
infection.
Background: Although opsoclonus-myoclonus has been reported
as a post-infectious consequence of infection with cytomegalovirus
(CMV), reports of myoclonus without opsoclonus secondary to infec-
tion with CMV are exceedingly rare.
Results: A 44-year-old man was admitted to the hospital with an
acute onset of severe myoclonic jerking of his arms and legs, stutter-
ing speech loss of balance and mild confusion occurring 2 weeks
after an episode of fever, rash, fatigue, sinus pressure and headaches.
On admission, the patient was mildly confused and stated he did not
feel like himself. He was unable to stand or walk due to jerking
movements throughout his body. The myoclonus worsened with any
stimulus. The patient did not have opsoclonus, or nystagmus. An
MRI of the brain and lumbar puncture were unremarkable. A CAT
scan of his chest/abdomen/pelvis and testicular ultrasound did not
demonstrate any neoplasm and a serum paraneoplastic panel did not
detect any antibodies. EEG showed mild diffuse cerebral dysfunc-
tion. Acute EBV infection and Group A strep were excluded as the
patient was nonreactive for EBV IgM antibodies and had normal lab-
oratory values for ASO antibodies. The patient was diagnosed with
post-infectious myoclonus on the basis of reactive CMV IgM and
IgG and CMV Quantitative PCR of 384 copies/mL (normal 1:100).
Of note, the patient did have an elevated ANA titer (1:80); however
Rheumatology was consulted and they felt that this was likely sec-
ondary to the acute CMV infection. The patient was treated with
intravenous steroids and IVIG as well as clonazepam. His symptoms
improved and he was discharged to a rehabilitation facility. A month
after his original hospitalization, the patients symptoms reemerged
S147
and he was readmitted. The patient was given three days of IV ste-
roids and discharged with 60 mg of prednisone daily that was
tapered over several weeks. At six months follow up, he is off all
medications and his symptoms have essentially resolved although he
does still experience some very mild subjective balance difficulty not
elicited on exam.
Conclusions: CMV infection should be considered in patients
presenting with myoclonus following a nonspecific viral illness.
372
The efficacy of piracetam for management of cortical myoclonus:
A meta-analysis of randomized control clinical trials
A.R. Sanchez, R.C.M.L. Alemany (Pasig City, Philippines)
Objective: The main objective of this study is to determine the
efficacy of Piracetam versus placebo or in combination with existing
anticonvulsant treatment on cortical myoclonus.
Background: Myoclonus is clinically defined as rapid, shock-like
involuntary muscle contractions that may prove disabling and fatal.
One type that is commonly encountered in our clinical practice is
cortical myoclonus. Its treatment remains to be an important chal-
lenge. Piracetam is benefecial in several types of cortical myoclonus.
Its success as a monotherapy or in combination with other anticon-
vulsants has been reported in several case reports, open trials and in
two double-blind studies.
Methods: This study included randomized control clinical trials
on Piracetam for cortical myoclonus, involving patients of any
gender and age diagnosed with cortical myoclonus. The outcomes
used for analysis are the myoclonus rating indices such as, motor
impairment index, functional disability, global assessment by the
investigator, stimulus sensitivity, handwriting and visual analogue
scale. The studies are evaluated using the Review Manager 5.3
software.
Results: Databases and archives of the different online and non-
online registries were sought. The search yielded eight studies specific
for Piracetam 1 Cortical Myoclonus 1 Randomized-controlled
trials. A total of two trials were included in the final analysis. We
found significant and clinically relevant improvement in the mean
sum score of the myoclonus rating scale on both studies, particularly
in the functional disability index and visual analogue scale.
Conclusions: Anti-epileptic medications remain to be the most
commonly and widely used treatment in cortical myoclonus. This
type of myoclonus is usually diificult to control, with tendency for
attending physicians to use polytherapy. Various articles and studies
about Piracetam verify that it may be used as an alternative agent for
cortical myoclonus. In this meta-analysis, results showed that Pirace-
tam significantly manages cortical myoclonus of the patients with
good tolerability and minimal adverse effects. However, there is a
need to include for more clinical trials that have large sample size to
prove the efficacy of Piracetam in management of cortical myoclo-
nus. A head-to-head study with other anti-epileptic medications is
also recommended.
373
The prevalence of affected muscles and the associations between
the numbers of affected muscles and age of onset and duration
of disease in hemifacial spasm
K. Ukantapornpong, P. Chairangsaris (Bangkok, Thailand)
Objective: To determine (1) the clinical characteristics of hemifa-
cial spasm patients including the prevalence of affected muscles (2)
the association between duration of disease and the numbers of
affected muscles (3) the association between age of onset and the
numbers of affected muscles in patients with hemifacial spasm
(HFS).
Background: HFS is a Movement Disorder characterized by uni-
lateral episodic spasm of the muscles innervated by the ipsilateral
Movement Disorders, Vol. 30, Suppl. 1, 2015
S148 POSTER SESSION

facial nerve. HFS generally begins with clonic movements of orbicu-

laris oculi and spreads over the course of several years to other facial
muscles. There is little data on prevalence of affected muscles, and
the association between the numbers of affected muscles and dura-
tion of disease or age of onset in patients with HFS is still unclear.
Methods: We conducted a descriptive study of patients with HFS
at Phramongkutklao Hospital. The patients who did not expose to
botulinum toxin and clonazepam at least 12 weeks and 2 weeks
respectively were enrolled in the study. These patients were exam-
ined and observed for facial muscles twitching by a Movement Dis-
orders specialist. Baseline characteristics, prevalence of affected
muscles, the association between duration of disease and the num-
bers of affected muscles, and the association between age of onset
and the numbers of affected muscles were analysed.
Results: Sixty five HFS patients (17 men and 48 women) were
enrolled. The median age of onset was 56 years and the median dis-
ease duration was 6 years. Six percents of patients had bilateral
symptoms, 45% were right sided spasm, and 49% were left sided Fig. 1. (374).
spasm. The most common affected muscle was orbicularis oculi fol-
lowed by zygomaticus, platysma, risorious and orbicularis oris. Of
these patients, 26% affected with 1-2 muscles spasm whereas 46%,
22% and 6% affected with 3-4, 5-6 and more than 6 muscles spasm
respectively. There was no significant association between age of concordant to neurophysiology, but the other 6 cases (60%) differed
onset and the numbers of muscles spasm (P=0.461). The association in suspected origin of PHM.
between duration of disease and the numbers of affected muscles [figure1]
was also not significantly (P=0.15). Conclusions: Our data suggests an added value of analysis with
Conclusions: The majority of the numbers of muscles spasm in EEG/EMG, JLBA and coherence analysis above clinical examina-
patients with HFS was 3-4 muscles. Obicularis oculi was the most tion alone in clarifying anatomical origin of PHM. A better under-
common affected muscles. Furthermore, the numbers of affected standing of the anatomical origin might support prognosis and guide
muscles was not associated with age of onset or duration of disease. treatment. Further studies towards the relation with outcome are
required.
1. J.C. van Zijl, M. Beudel, H.J. vd Hoeven, F. Lange, M.A.J.
374 Tijssen, J.W.J. Elting. EEG Findings in Post Hypoxic Myoclonus.
The added value of neurophysiologic investigations in post- Journal of Intensive Care Medicine. Accepted for publication.
hypoxic myoclonus
J.C. van Zijl, M. Beudel, B.M. de Jong, J. van der Naalt, H.J. van
der Hoeven, F. Lange, W.M. van den Bergh, J.W.J. Elting, M.A.J. POSTER SESSION 3
Tijssen (Groningen, Netherlands) Tuesday, June 16, 2015
Objective: To evaluate the anatomical origin of post-hypoxic 12:3014:00
myoclonus (PHM) with advanced neurophysiologic investigations Grand Hall
and relate these to clinical presentation.
Background: PHM is a hyperkinetic Movement Disorder that
can occur after anoxic brain damage. Based on its clinical manifes-
tation PHM can be divided in generalized and (multi) focal PHM Parkinsons disease: Non-motor symptoms
of which the former is associated with a subcortical etiology and
very poor prognosis, and the latter with a cortical etiology and a
relatively better prognosis.1 However, these anatomic associations
are indirect and derived from conscious patients. To further investi- 375
gate the anatomical origin of generalized and (multi) focal PHM Safety and efficacy of transdermal rotigotine for the treatment of
we made a standardized videoprotocol and used advanced neuro- fatigue and quality of life (QOL) in patients with Parkinsons
physiologic investigations: EEG/EMG, jerk-locked back averaging disease
(JLBA) and coherence analyses to determine a cortical or a subcort- K. Abe, S. Kitamura, I. Yokoa, J. Ogura, M. Fjita, H. Yoshikawa
ical origin. (Nishinomiya, Japan)
Methods: 17 PHM cases were included (10 male, age m=53,
IQR=32). PHM was clinically classified in (i) generalized, (ii) (multi) Objective: To evaluate safety and efficacy of transdermal rotigo-
focal, (iii) both or (iv) uncertain. EEG/EMG, JLBA and coherence tine for the treatment of fatigue and quality of life (QOL) in patients
analyses were applied in each case. Significant corticomuscular with Parkinsons disease (PD).
coherence and a cortical discharge preceding the jerk were argu- Methods: This was a multi-sites study of 50 PD patients who
ments for a cortical origin. A muscle recruitment sequence starting met a Japanese PD diagnosis criteria. They received transdermal roti-
in brainstem innervated muscles, a cortical discharge following the gotine 4.5mg/day for 8 weeks. We added transdermal rotigotine on
jerk and no detectable cortical discharge in relation to the jerk were the previous anti-Parkinsons drugs.
arguments for a subcortical origin. Cinical signs were evaluated by Hoehn-Yahr (H-Y) stage, unified
Results: 5 patients were classified as (multi) focal (29%), 4 as Parkinsons disease rating scale (UPDRS), fatigue severity scale
generalized (24%), 1 as both (6%) and 7 as uncertain PHM (41%). (FSS), Euro quality of life (QOL).
After neurophysiologic analyses all 17 patients could be categorized, Results: The scores of FSS improved from 61.06 5.2
which is significantly more than the clinical assessment (p<0.05). (mean 6 SD) to 47.0 6 6.1 (P=0.035). The scores of QOL improved
This method scored 10 cortical (59%), 3 subcortical (18%) and 4 from 51.06 5.7 to 47.0 6 6.1 (P=0.025). There was no significant
both (23%) (figure 1). 4 of 10 (40%) clinical classified cases were improvement or worsening of the H-Y stages and UPDRS scores.

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
Conclusions: Our data demonstrate that, in a small sample size,
administration of transdermal rotigotine was associated with few side
effects and was modestly effective for the treatment of fatigue and
QOL in patients with PD.
376
Constipation preceding Parkinsons disease Systematic review
and meta-analysis
K.L. Adams-Carr, A. Schrag, S. Shribman, J.P. Bestwick, A. Lees,
A.J. Noyce (London, United Kingdom)
Objective: To systematically review and combine data reported
from different studies associating premorbid constipation with a later
diagnosis of Parkinsons disease (PD).
Background: The prodromes of PD comprise a variety of non-
motor symptoms. Patients with early non-motor features or clusters
of features may be the most appropriate subjects to identify and
recruit to future neuroprotective drug trials. Constipation is a well-
recognised non-motor feature of PD and has been reported to predate
PD in a number of observational studies, in some cases by over two
decades.
Methods: A systematic review and meta-analysis was carried out
following MOOSE criteria. A literature search was undertaken on 7
December 2014 using PubMed and the relevant search terms Parkin-
sons disease and Constipation. Articles were screened for suitabil- cohort
ity and included if they met the following inclusion criteria: (1)
observational studies with a cohort or case-control design; (2) cases
were patients with PD according to standard clinical criteria; (3) con-
trols were healthy or had no history of neurological disease; (4)
cohorts were representative of the general population; (5) constipa-
tion in controls was assessed over the same time period as for
patients; (6) original data were reported. Data were extracted and
combined using a fixed-effects model. Studies were included if they
assessed constipation by means of a structured questionnaire such as
NMS-Quest or it was coded in patient medical records. Studies that
used laxative use as a proxy for constipation were also included.
Heterogeneity was explored with the I2 statistic.
Results: Nine studies were included in the meta-analysis, with a
combined sample size of 753 429. Those with constipation had an
OR of 2.28 (95% confidence interval 2.10-2.46; p<0.001) for devel-
oping subsequent PD compared to those without constipation. Weak
evidence for heterogeneity was found (I2 38.9%, p50.11). Restrict-
ing analysis to studies assessing constipation greater than 10 years
prior to PD diagnosis gave a combined OR of 2.12 (95% confidence
interval 1.76-2.54; p<0.001).
Conclusions: This systematic review and meta-analysis demon-
strates that people with constipation are at a higher risk of develop-
ing PD compared to those without and this can predate PD diagnosis
by many years. This may have implications for our understanding of
the pathogenesis of the disease and for the planning of neuroprotec-
tive interventional trials.
377
Levodopa attenuates fatigue in reserpine-treated mice An
animal model of Parkinsons disease
A.S. Aguiar, Jr., D.L. Scheffer, R.D.S. Prediger, A.S. Latini
(Florian
opolis, Brazil)
Objective: There is a great demand for knowledge of perceived
exertion during physical activity. Decreased ability to work or exer-
cise until failure is known as fatigue, which has central and periph-
eral components, and is also a common symptom in neurology.
Background: In order to understand the mechanisms of fatigue,
it is important to distinguish symptoms of peripheral neuromuscular
fatigue from the symptoms of central fatigue Some evidence suggests
the role of increased serotonin/dopamine (5-HT/DA) ratio in the
S149
pathophysiology of this central fatigue. characteristic of basal ganglia
disorders, such as Parkinsons disease.
Methods: We depleted striatal DA in mice (Swiss, 10-12 weeks
age, 30-40 g) by systemic treatment with reserpine (1 mg/kg, i.p.),
an animal model of Parkinsonism.
Results: This increased the 5-HT/DA ratio in the striatum of ani-
mals. The reserpinized animals also showed fatigue intolerance in
the treadmill test, characterized by reduced mechanical work and
muscular recruitment. Levodopa (100 mg/kg, i.p) plus Benserazide
(50 mg/kg, i.p) partially reversed DA depletion reversed, Parkinson-
ism and fatigue tolerance. We consider that increased striatal 5-HT/
DA ratio played a crucial role in the development of central fatigue
because reserpine did not alter mitochondrial physiology and anat-
omy, and glucose uptake in muscle tissue.
Conclusions: The results suggest that striatal DA may be
involved in the development of central fatigue. Furthermore, the
effectiveness of levodopa suggests an important motor component of
this symptom in the Parkinsonism, which does not discard non-motor
components, such as motivation and attention.
378
Aspiration pneumonia in a hospitalized Parkinsons disease
L. Almeida, D. Martinez-Ramirez, K.W. Hageland, J.C. Giuni, C. Lit-
tle, J.P. Chapman, B. Ahmed, E. Monari, M. Troche, M.S. Okun
(Gainesville, FL, USA)
Objective: To determine the incidence of aspiration events in a
hospitalized Parkinsons disease (PD) cohort and to report the fre-
quency of swallow evaluations during hospitalization.
Background: Aspiration pneumonia is an important cause of
morbidity and mortality in PD. Clinical characteristics, such as gen-
der, age, disease duration, specific alterations in the swallowing
mechanism and decreased cough sensitivity, contribute to impaired
ability to effectively clear airways. These issues render patients more
prone to dysphagia and chronic, uncompensated aspiration events.
Additionally, PD patients often suffer clinical deterioration during
hospitalization and the potential relationship to aspiration events has
not been previously described.
Methods: A retrospective single center data/chart review of 212
PD patients who underwent 339 hospitalizations was performed from
January 2011 to March 2013. We describe demographic and clinical
characteristics, the reasons for hospitalization, and we examined
whether swallowing evaluations and aspiration precautions were
addressed.
Results: The cohort had a mean age of 74.1 6 10.1 years, disease
duration of 6 6 6.3 years and mean Hoehn and Yahr stage of
1.3 6 0.7. Of the 52 (15.3%) hospitalizations related to pulmonary
causes, 6 (11.5%) had aspiration pneumonia either at home or within
the first 48 hours of admission. Of the total cohort of 212 patients, 8
(2.3%) developed aspiration pneumonia during hospitalization, diag-
nosed by clinical history and radiological findings. Swallow evalua-
tions were conducted in 25% of the hospitalizations, and aspiration
precautions were initiated in 32%. Overall, 12.5% patients who were
diagnosed with in-hospital pneumonia had swallowing evaluations in
the hospital prior to the development of pneumonia.
Conclusions: Although aspiration pneumonia in our hospitalized
PD cohort occurred infrequently, which may be related to a rela-
tively short mean disease duration and low Hoehn and Yahr stage
in our population, preventive measures and precautions were not
routinely performed. These results bring to light the importance of
better screening and monitoring of swallowing problems in PD
patients during hospitalization. Despite the advances in dysphagia
research, the prompt access to these resources and management is
lacking.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S150 POSTER SESSION
379
Delineating non-motor symptoms in early Parkinsons disease
and first-degree relatives
F. Baig, M. Lawton, M. Rolinski, C. Ruffmann, K. Nithi, S.G. Evetts,
H.R. Fernandes, Y. Ben-Shlomo, M.T.M. Hu (Oxford, United Kingdom)
Objective: To delineate the prevalence, treatment and quality of
life of non-motor symptoms (NMS) in early Parkinsons disease
(PD), controls and first-degree relatives.
Background: NMS are an important prodromal feature of PD. How-
ever, their frequency, treatment rates and impact on health-related quality
of life (HRQoL) in the early motor phase is unclear. Rates of NMS in
enriched at-risk populations, such as first-degree PD relatives have not
been delineated. We assessed NMS in an early cohort of PD, first-degree
PD relatives and control subjects to address these questions.
Methods: 769 population-ascertained PD subjects within 3.5 years of
diagnosis, 98 first-degree PD relatives and 287 control subjects were
assessed. Validated severity questionnaires were employed to assess NMS
symptoms across the following domains: 1) neuropsychiatric 2) gastroin-
testinal 3) sleep 4) sensory 5) autonomic 6) sexual. Health related quality
of life (HRQoL) was assessed by the EQ-5D questionnaire. Functional sta-
tus was assessed by the Schwab and England Activities of Daily Living
scale. Management of REM sleep behaviour disorder, depression, consti-
pation, urinary symptoms and erectile dysfunction were also investigated.
Results: NMS were much more common in PD compared to con-
trol subjects. More than half of the PD cases had hyposmia, pain,
fatigue, sleep disturbance or urinary dysfunction. NMS were more
frequent in those with the postural instability gait difficulty compared
to tremor dominant phenotype (mean total number of NMS 7.8 vs
6.2, p<0.001). PD cases had worse HRQoL scores than controls (OR
4.1, p<0.001) with depression, anxiety and pain being stronger driv-
ers than MDS-UPDRS motor scores. NMS were rarely treated in rou-
tine clinical practice. First-degree PD relatives did not significantly
differ in NMS compared to controls.
Conclusions: Although more common in early PD, NMS are not
more commonly seen in first-degree relatives, suggesting their future
risk of PD is modest at best. Despite their major impact on HRQoL,
NMS are usually under-recognised and treated.
380
Safinamide significantly reduces pain treatments when given as
add-on therapy to levodopa in patients with Parkinsons disease
and fluctuations
P. Barone, C. Cattaneo, E. Bonizzoni, R. La Ferla, M. Sardina
(Baronissi, Salerno, Italy)
Objective: To investigate the effects of safinamide on concomi-
tant pain treatments and on the PDQ-39 scale items related to pain
in Parkinsonian patients with motor fluctuations, using pooled data
from studies 016 and SETTLE.
Background: Safinamide, a new drug with a dual mechanism of
action (dopaminergic and non-dopaminergic), has been studied as
add-on therapy in both early- and late-stage Parkinsons disease
(PD). In late-stage PD safinamide, given as add-on therapy to stable
doses of levodopa, was evaluated in two double-blind, placebo-con-
trolled, 6-months trials (016 and SETTLE), showing an increase in
ON time and a decrease in OFF time without increasing trouble- cular (2), sleep (5) and miscellaneous (4). The correlation of prevalence
some dyskinesia, with a high tolerability profile.
Methods: This post-hoc analysis of the pooled data from the piv-
otal Phase III trials 016 and SETTLE evaluated the effects of safina-
mide (100 mg/day oral tablets) vs. placebo on the reduction of
concomitant pain treatments and on the scores of the items 37-39 of
the Parkinsons disease Quality of life questionnaire PDQ-39 (meas-
uring pain in joints, body and muscles).
Results: Compared to placebo safinamide significantly reduced
on average the individual use of pain treatments of about 24%
(p50.0421) and significantly improved items 37 (p50.0009) and 39
(p50.0060) of the PDQ-39 scale.
Movement Disorders, Vol. 30, Suppl. 1, 2015
Conclusions: Safinamide, administered as add-on therapy in mid-
to late-stage fluctuating PD patients, contributed to reduce the number
of concomitant pain treatments and improved two out of three items of
the body pain domain of PDQ-39, the most widely used scale to mea-
sure both motor and non-motor PD symptoms; this may bring an addi-
tional positive impact on the quality of life of fluctuating PD patients.
381
Impulse control disorder and rapid eye movement sleep behavior
disorder in Parkinsons disease
S. Bayard, Y. Dauvilliers, H. Yu, M. Croisier Langenier, A. Rossignol,
M. Charif, C. Geny, V. Cochen De Cock (Montpellier, France)
Objective: To explore the association between rapid eye move-
ment (REM) sleep behavior disorder (RBD) and impulse control dis-
order in Parkinsons disease (PD).
Background: The relationship between ICD and RBD is still not
yet understood and the results from the current literature are contra-
dictory in PD.
Methods: Ninety-eight non-demented patients with PD underwent
one night of video-polysomnography recording. The diagnosis of
RBD was established according to clinical and polysomnographic
criteria. Impulse control disorders were determined by a gold stand-
ard, semi-structured diagnostic interview.
Results: Half of the patients (n549) reported clinical history of
RBD while polysomnographic diagnosis of RBD was confirmed in
31.6% of the patients (n531). At least one impulse control disorder
was identified in 21.4% of patients, 22.6% with RBD and 20.9% with-
out. Logistic regression controlling for potential confounders indicated
that both clinical RBD (OR=0.34, 95% CI=0.07-1.48, P=0.15) and pol-
ysomnographic confirmed RBD diagnoses (OR=0.1.28, 95% CI=0.31-
5.33, P=0.34) were not associated with impulse control disorder.
Conclusions: In PD, RBD is not associated with impulse control
disorder. The results of our study do not support the notion that
PSG-confirmed RBD and ICD share a common pathophysiology.
382
Assosciation of side of onset of motor symptoms to prevalence of
various domains of non-motor symptoms (NMS) in Parkinsons
disease (PD)
R.S. Boddepalli, T.S. Khan (Weston, FL, USA)
Objective: The study aims to compare the prevalence of various
domains of non-motor symptoms(NMS) in Parkinsons disease (PD)
patients with respect to their side of onset of motor symptoms.
Background: PD is the second most common neurodegenerative dis-
order affecting patients between the age group of 50 and 70 years old. PD
patients present with a wide range of Motor and Non-Motor symptoms.
Methods: We collected NMS data in patients diagnosed with PD
who attended the Movement Disorder clinic in Cleveland Clinic Florida
over the last 18 months. The side of onset of motor symptoms was docu-
mented for these patients. The standard self-administered NMS question-
naire was filled out for each patient. The questions are divided into
various domains; Gastro intestinal (7), Urinary (2), Pain (1), attention/
memory (2), Apathy (1), psychiatric (4), Sexual function (2), cardiovas-
of the various NMS domains to side of motor symptom onset is studied.
Results: 179 Patients with asymmetric symptoms were included
in the study; 103 males and 76 females. The mean 6 SD age was
69.03 6 9.99. 57 patients (31%) had right sided symptom onset and
52 patients (29%) had left sided symptom onset. The mean 6SD of
Non-Motor (NMS) in the study population with PD in both groups
were comparable. Patients with right sided symptom onset reported
significant difference (increased) in following domains of NMS; sleep
(p50.029), psychiatric (p50.058) and Miscellaneous (p50.029).
Conclusions: NMS related to sleep, psychiatric and miscellaneous
problems were more prevalent in right sided symptom onset PD patients.
 POSTER SESSION
383
Unmasking the face of Parkinsons disease: Immediate and 3
month followup from a randomized double-blind sham-
controlled behavioral intervention
D. Bowers, C. Sapienza, R. Rodriguez, H. Fernandez, M.S. Okun
(Gainesville, FL, USA)
Objective: To determine the efficacy of a behavioral intervention
for treatment of masked faces in Parkinsons disease (PD).
Background: A flat, expressionless masked face is one of the
hallmark features of Parkinsons disease and associated with negative
mis-attributions about mood and motivation by family members and
health care providers. Currently, there are no known treatments for the
masked face. In previous work, we used computer digitizing methods to
quantify PD facial expressions and found decreased amplitude and
slowing of facial movements that was only marginally improved with
dopaminergic medication. This study tested the hypothesis that a behav-
ioral intervention involving high intensity oral-facial strength training
would improve facial expressivity in PD patients.
Methods: Forty-two nondemented PD patients were randomly
assigned (1:1) to Target or Sham groups. Treatment consisted of
standard oral muscle strength training (MST), 5 days a week, 20
minutes/day for 4 weeks using a calibrated or sham handheld device.
Treatment and Sham were identical except for intensity of training
(i.e., 80% vs 5% MIP). All participants underwent computer analysis
of facial expressions before and after treatment. Primary outcomes
were changes in facial movement (entropy), timing parameters, and
subjective ratings by blinded judges.
Results: Baseline characteristics did not differ between the Treat-
ment and Sham groups. All participants were in their mid-60s, col-
lege-educated, 2/3 male, with mild-moderate disease severity (HY 2-
3). As predicted, the Treatment group exhibited significantly greater
improvement in facial expressivity, relative to Sham, as indexed by
entropy, expression rise time, and subjective ratings by blinded
judges. Positive treatment gains occurred both on and off dopa medi-
cations (Cohens D >1). These positive effects largely dissipated
after 3 months of no treatment.
Conclusions: Results indicate that a brief, daily behavioral exer-
cise intervention over 4 weeks can improve masked facies in Parkin-
sons disease. Consistent with the detraining literature, however,
these positive effects were not maintained after 3 months of no treat-
ment. Findings will be discussed in terms of 3 possible mechanisms
that underlie these changes.
384
Rotigotine objectively improves sleep in Parkinsons disease: A
pilot study with actigraphic recording
G. Calandra-Buonaura, P. Guaraldi, A. Doria, S. Nassetti, V.
Favoni, S. Cevoli, F. Provini, P. Cortelli (Bologna, Italy)
Objective: To objectively evaluate the effect of rotigotine on
sleep through actigraphic recording in Parkinsons disease (PD)
patients (pts) with self-reported sleep complaints (PD Sleep Scale-2,
PDSS-2 10).
Background: Sleep disturbances represent important predictors of
poor quality of life (QoL) in PD. Rotigotine transdermal patch, a
dopamine agonist used for treatment of motor symptoms in PD pts,
demonstrated to subjectively improve sleep disturbances. However
an objective evaluation of its effect on sleep is lacking.
Methods: Patients underwent wrist actigraphic recording for one
week at enrollment (T0) and while on rotigotine (T1) which was
titrated to the dose subjectively improving motor symptoms (4-8 mg
per day). We evaluated sleep efficiency (total sleep time/nocturnal
recording time, SE), activity mean and median (counts/min) and
wake minutes after sleep onset (WASO). We also assessed, by means
of scales and questionnaires, changes in cognitive performance (Mini
Mental State Examination), sleep disturbances and daytime sleepi-
ness (PDSS-2, Restless Legs Syndrome- RLS- criteria and Rating
S151
Scale, Epworth Sleepiness Scale), QoL and depression (PD
Questionnaire-39 and Beck Depression Inventory).
Results: 15 pts (12 males, mean age6SD 67 6 9 years, PD duration
5 6 3 years) were evaluated. During T1 compared to T0 a significant
improvement of self-reported sleep complaints and QoL was observed.
Cognitive performance, diurnal sleepiness and depression were unchanged.
Four pts reported RLS at T0 and a significant improvement in RLS symp-
toms at T1. Actigraphic recording did not show change in SE and WASO
at T1 compared to T0 while a reduction in activity mean and activity
median reaching significance only for activity mean (p 5 0.01 and
p 5 0.08) was observed. However, when considering only the ten pts who
presented pathological SE ( 85%) at T0, we observed a significant
improvement in SE (p 5 0.02) and a significant reduction in WASO
(p 5 0.01), activity mean (p 5 0.005) and activity median (p 5 0.04) at T1.
Conclusions: This pilot study suggests that rotigotine subjectively
improves sleep quality and QoL in PD pts with self-reported sleep
complaints and induces a significant reduction in nighttime activity,
which could contribute to compromise sleep. Further in pts with
reduced SE, rotigotine objectively improves all sleep parameters.
385
Sleep and sleepiness symptoms as predictors of cognitive decline
in early Parkinsons disease: Results from the PPMI study
L.M. Chahine, B. Tran, S. Xie, S. Christi, D. Abi, C. Linder, R.
Purri, T. Simuni, G. Murray, W. Daniel (Philadelphia, PA, USA)
Objective: To examine sleep/sleepiness symptoms as risk factors
for cognitive decline in early Parkinsons disease (PD).
Background: Cognitive dysfunction and decline are common in
PD, as are subjective nighttime sleep problems, dream enactment
behavior (DEB), and excessive daytime sleepiness (EDS). Predictors
of cognitive decline in PD have not been fully defined. As many
sleep problems are modifiable, examining them as risk-factors for
cognitive decline in PD may elucidate predictors and possible areas
for preventive or therapeutic intervention.
Methods: The Parkinsons Progression Markers Initiative (PPMI) is
an international multi-site prospective observational study of PD
patients untreated at enrollment. Sleep/sleepiness measures included
MDS-UPRDS item-1.7, Epworth Sleepiness Scale (ESS), and REM
sleep behaviour disorder questionnaire (RBDSQ). Global cognition was
assessed at baseline and annually with the Montreal Cognitive Assess-
ment (MoCA). Linear mixed effects models were used to examine the
relationship between baseline sleep/sleepiness symptoms (independent
variable, dichotomized) and rate of cognitive decline (change in MoCA
score, dependent variable). Age, gender, disease duration, years of edu-
cation, and baseline MoCA score were included as covariates.
Results: 423 PD participants completed baseline visits. Their mean
age was 61.7 years and 277 (65.48%) were male. 400, 270, and 104 par-
ticipants completed 1-year, 2-year, and 3-year follow-ups, respectively.
At baseline, nocturnal sleep problems occurred in 225 (53.19%), EDS
(ESS>9) in 66 (15.6%), and significant DEB (RBDSQ5) in 160
(37.83%). In multivariate analyses, predictors of future cognitive
decline included baseline DEB (b=-0.35, p50.003) and EDS (b=-0.37,
p50.014), but not nocturnal sleep problems (p50.70).
Conclusions: Dream enactment behavior and excessive daytime
sleepiness are independent predictors of longitudinal cognitive
decline in early PD. These results will have to be validated with fur-
ther longitudinal assessment of the cohort.
386
Fatigue in Parkinsons disease: The evidence of regional cerebral
glucose metabolism abnormalities
S.S. Cho, K. Aminian, S. Houle, A.E. Lang, M. Criaud, A.P. Strafella
(Toronto, ON, Canada)
Movement Disorders, Vol. 30, Suppl. 1, 2015
S152 POSTER SESSION
Objective: The aim of this study was to characterize the neural
substrate associated with a disabling non-motor symptom in Parkin-
sons disease (PD) represented by fatigue.
Background: Fatigue is a common and disabling non-motor
symptom of PD, affecting up to 70% of patients and related to dis-
ease progression, yet it has a vague basis and lacks definite clinical
intervention. PD patients with more severe fatigue are more seden-
tary and have worse quality of life compared with those with less
fatigue, hence improving our understanding about biological bases of
fatigue will help identifying new treatment methods.
Methods: Fifteen PD patients (mean age 63.1 6 7.8; 4 females)
were recruited and screened with the Montreal Cognitive Assessment
and the UPDRS W/Modified Hoehn-Yahr staging while off-
medication. Participants completed Fatigue Severity Scale and sleep
quality measurement questionnaires. [18F]FDG PET scans of 5 min
were acquired starting 40 min after injection of 4.8 MBq/kg FDG.
Image preprocessing and statistical analyses were carried out using
SPM 8. Statistical comparisons between groups were performed on a
voxel-by-voxel basis using t statistics. Statistical maps were set at a
voxel-level threshold of P<.005, uncorrected.
Results: PD with higher fatigue appeared to be reliant on
decreased regional glucose metabolism (rCMRglc) in anterior cingu-
late (ACC) and right insular along with superior temporal lobe which
are known to be part of the limbic system playing in important role
on emotional behavioral. We also found increased rCMRglc in
precuneus considered an important region within the default mode
network which may also play a suggestive role in altering behavior.
The relationship between rCMRglc and individual fatigue level
in PD were identified by correlation analysis. ROI analysis confirmed
the significant regional correlation of fatigue in right insular, superior
temporal lobe and bilateral precuneus. Several brain regions
that showed functional differences between PD with fatigue and
without fatigue exhibited good correlation with fatigue level in our
analysis.
Conclusions: PD patients with fatigue exhibited significant
changes of rCMRglc in those brain regions that have been suggested
to be the core node or hub of the default mode network. Our find-
ings indicate that these functional alterations may represent the neu-
robiological bases of this disabling non-motor symptom.
387
Olfaction and neuropsychiatric symptoms in early Parkinsons
disease
J.K. Choi, J.Y. Hong, M.K. Sunwoo, J.H. Ham, J.J. Lee, P.H. Lee,
Y.H. Sohn (Wonju, Korea)
Objective: Olfactory and emotional dysfunctions are very com-
mon in patients with Parkinsons disease (PD). Olfaction and emo-
tions share common neuroanatomical substrates. Therefore, in this
study, we evaluated the association between olfactory dysfunction
and neuropsychiatric manifestations in patients with PD.
Methods: PD patients who had been assessed for their olfactory
function and neuropsychiatric symptoms were included. A logistic
regression analysis was performed to evaluate the association
between low olfaction and different neuropsychiatric symptoms.
Results: The patients with low olfaction (cross cultural smell
identification test score  6) showed a higher prevalence of apathy
when compared with those with high olfaction, whereas the frequen-
cies of other neuropsychiatric symptoms were comparable between
the two groups. A multivariate logistic regression analysis revealed
that the presence of apathy/indifference (odds ration [OR] 5 2.859,
p 5 0.007), age 70 years or more (OR 5 2.281, p 5 0.009), and the
male gender (OR 5 1.916, p 5 0.030) were significantly associated
with low olfaction.
Conclusions: Our results demonstrate that apathy/indifference is
a unique neuropsychiatric symptom associated with olfactory dys-
function in PD. The findings also suggest that PD patients with low
olfaction have a high prevalence of apathy.
Movement Disorders, Vol. 30, Suppl. 1, 2015
388
Comparative patient satisfaction and efficacy of a Parkinsons
disease enrichment program (PEP)
T.K. Choudhury, M.K. York, C. Harris, K. Crist, B. Treece, T.
Satterwhite (Houston, TX, USA)
Objective: To evaluate the patient satisfaction and efficacy of a Par-
kinsons disease Enrichment Program (PEP) for improving cognitive and
psychiatric symptoms and quality of life in Parkinsons disease (PD).
Background: Available treatment options for PD are primarily geared
towards pharmacological and/or neurosurgical reduction or management
of motor symptoms. However, many patients also experience chronic non-
motor symptoms (NMS), including significant cognitive and psychiatric
changes. Currently, there is a gap in the literature regarding the efficacy of
pharmacological or nonpharmacological treatment options for these NMS.
Methods: Twenty independently functioning non-demented PD
patients participated in a five-week PEP, which is a broad-spectrum
social enrichment group. Each four-hour weekly session included con-
tent which addressed education, exercise, recreation and socialization/
support. PD participants received a pre-assessment, including cognitive
tests and questionnaires for depression, anxiety and quality of life
(QOL). After the completion of the program, participants completed
post-assessment batteries to measure changes in neurocognitive and
psychiatric status, as well as patient satisfaction regarding the program.
Results: The mean age of participants was 68.9 years, with a mean
education level of 16.6 years and a mean time since diagnosis of 6.3
years. Following the PEP program, significant improvements were
observed for semantic category switching and accuracy, as well as
delayed recall of a word list. No significant cognitive declines were
noted. After 5 weeks, participants reported a significant reduction in
symptoms of depression and in distress caused by their PD symptoms.
100% of participants reported overall high satisfaction with the program.
Conclusions: Positive participant feedback and short-term cogni-
tive and mood improvements suggest that further expansion of this
program for treatment of NMS may be beneficial in improving cog-
nitive and psychiatric status in PD patients. Follow-up data will be
collected after 6 months to measure for longer-term improvements in
cognition and emotional status. Additional PEPs will continue to be
evaluated to augment sample size and strengthen internal validity.
Future studies will compare the efficacy of PEPs to a best medical
therapy group and a cognitive rehabilitation intervention for PD.
389
Does the pattern of striatal dopamine depletion contribute non-
motor symptoms in Parkinsons disease?
S.J. Chung, J.J. Lee, J.H. Ham, P.H. Lee, Y.H. Sohn (Seoul, Korea)
Objective: To investigate whether the pattern of striatal dopa-
mine depletion contributes non-motor symptoms (NMS) in Parkin-
sons disease (PD).
Background: NMS has been recognized as a key determinant
factor for quality of life in PD, but the mechanism underlying NMS
in PD has not yet been elucidated well. In this study, we hypothe-
sized that PD patients with greater NMS might have a different pat-
tern of striatal dopamine depletion, particularly the areas other than
the posterior putamen, compared to those with less NMS.
Methods: We conducted a prospective survey of the degree of NMS
(using non-motor symptoms scale, NMSS) in 151 PD patients who had
been initially diagnosed at our hospital by dopamine transporter (DAT)
scanning, using a [18F] N-(3-Fluoropropyl)-2b-carbon ethoxy-3b-(4-iodo-
phenyl) nortropane (FP-CIT) PET scan (from March 2009 to June 2013).
Results: Patients with a higher NMSS score (above the median)
had an older age of PD onset (64.9 6 9.1 vs 61.5 6 10.1 years,
p 5 0.034), a higher initial UPDRS-motor score (assessed in drug-
naive state) (26.9 6 11.7 vs 20.9 6 10.3, p 5 0.003), and a greater
Beck depression inventory (BDI) score (14.7 6 8.1 vs 11.5 6 7.5,
p 5 0.013), compared to those with a lower score. However, DAT
activities in 6 striatal sub-regions and inter-sub-regional ratios were
 POSTER SESSION
comparable between the two groups. A general linear model showed
that patients with a higher NMSS score had significantly higher
UPDRS-motor score than those with a lower score after controlling
for onset age, gender, symptom duration, BDI score, and DAT activ-
ity in the posterior putamen (p 5 0.034).
Conclusions: This study demonstrates that the pattern of striatal
dopamine depletion does not contribute to the degree of NMS in
early PD, although some clinical features are different between the
patients with greater NMS and those with less NMS. This study also
suggests that patients with less NMS may have a benign course of
motor symptom progression, compared to those with more NMS.
390
Supine sleep and obstructive sleep apnea syndrome in
Parkinsons disease
V. Cochen De Cock, N. Benard-Serre, V. Driss, M. Charif, B. Car-
lander, D. Cugy, S. Bayard (Montpellier, France)
Objective: To explore the relationship between supine sleep and
sleep disordered breathing in patients with Parkinsons disease.
Background: Supine sleep is associated with increased obstruc-
tive sleep apnea (OSAS). Patients with Parkinsons disease complain
about difficulties turning around in their bed.
Methods: Fifteen consecutive patients with Parkinsons disease were
compared to 1) 15 age, sex, body mass index and Unified Parkinsons dis-
ease Rating Scale-III score matched patients with Parkinsons disease with-
out sleep disordered breathing and to 2) 11 age and sex-matched patients
with severe OSAS alone and 3) to 11 age and sex-matched healthy con-
trols. Outcomes were number of position changes during the night and per
hour of sleep and percentage of sleep time spent on the back.
Results: Patients with Parkinsons disease and severe OSAS spent
most of their sleep time in supine position (93 6 11%) while patients
with Parkinsons disease without OSAS (61 6 24%, p<0.001),
patients with isolated severe OSAS (50 6 28%, p<0.001) and con-
trols (40 6 21, p<0.001) stayed significantly less on their back.
Patients with Parkinsons disease and severe OSAS changed less fre-
quently their position in bed per hour of sleep (0.4 6 0.5) than
patients with Parkinsons disease without OSAS (1.1 6 0.8,
p50.002), patients with isolated OSAS (1.2 6 1.0, p50.006) and
controls (1.5 6 0.5, p<0.001) [figure1].
Conclusions: Severe OSAS in Parkinsons disease is associated
with a major reduction in the number of position changes and an
increased supine sleep during the night. In patients with Parkinsons
disease, alleviating the difficulties turning around in bed might
reduce supine sleep and improve sleep disordered breathing.
391
Excessive daytime sleepiness in Parkinsons disease: Subjective
and objective measures
V. Cochen De Cock, S. Bayard, I. Jaussent, M. Charif, B. Carlander,
C. Geni, Y. Dauviliers (Montpellier, France)
Fig. 1. (390).
S153
Objective: To explore the frequency and determinants of self
reported and objective sleepiness in Parkinsons disease.
Background: Excessive daytime sleepiness is a frequent com-
plaint in Parkinsons disease (PD), however the best measure to
explore sleepiness and its potential predictors remain unclear.
Methods: One hundred and thirty four consecutive patients with
PD, without selection bias for sleep complaint, underwent a semi-
structured clinical interview and a one night polysomnography followed
by a multiple sleep latency test (MSLT). Demographic characteristics,
medical history, PD course and severity, daytime sleepiness, depressive
and insomnia symptoms, treatment intake, pain, restless legs syndrome,
REM sleep behaviour disorder, and nighttime sleep measures were col-
lected. Self-reported daytime sleepiness was defined by an Epworth
Sleepiness Scale (ESS) score above 10. A mean sleep latency on
MSLT below 8 minutes defined objective daytime sleepiness.
Results: Of 134 patients with PD, 46.3% had subjective and only
13.4% had objective sleepiness with a weak negative correlation
between ESS and MSLT latency. A high body mass index (BMI)
was associated with both ESS and MSLT, a pain complaint with
ESS, and a higher apnea/hypopnea index with MSLT. However, no
associations were found between both objective and subjective sleep-
iness, and measures of motor disability, disease onset, medication
(type and dose), depression, insomnia, restless legs syndrome, REM
sleep behaviour disorder and nighttime sleep evaluation.
Conclusions: We found a high frequency of self-reported sleepiness
in PD, a finding which is however not confirmed by the gold standard
neurophysiological evaluation. Current treatment options for sleepiness
in PD are very limited; it thus remains to be determined whether decreas-
ing pain and BMI in association with the treatment of sleep apnea syn-
drome would decrease significantly daytime sleepiness in PD.
392
Pharmacological treatment for apathy in Parkinsons disease: A
systematic review
C.A. Cooper, N. Dahodwala (Philadelphia, PA, USA)
Objective: Since there are no approved treatments specific to
apathy in Parkinsons disease (PD), we reviewed the existing litera-
ture on pharmacological treatment of apathy to better inform clinical
practice and future directions for research.
Background: In patients with PD, the prevalence of apathy in
the absence of depression and dementia is estimated to be 12-17.4%.
These rates increase substantially when associated with either depres-
sion or dementia. Furthermore, apathy is associated with greater dis-
ability and caregiver burden.
Methods: We searched PubMed, PsycINFO, and the Cochrane
Library with the terms: apathy, treatment, and Parkinson. Results
were filtered for humans and English when available, and then
clinical trials and case reports separately. Search results were
reviewed and relevant abstracts and articles were included if apathy was
measured in a population of PD patients as either a primary or secondary
outcome, before and after pharmacological treatment. References of the
Movement Disorders, Vol. 30, Suppl. 1, 2015
S154 POSTER SESSION
included articles were reviewed and any titles that suggested that they
might meet our inclusion criteria were identified and reviewed as well.
Results: The search resulted in a total of 57 clinical trials and 13
case reports. After review of abstracts and articles, 10/57 clinical trials
and 1/13 case reports met the search criteria. Apathy was the primary
outcome in only 5/10 clinical trials. 5/10 trials showed a decrease in
apathy, and investigated the following drugs: levodopa, methylpheni-
date, rotigotine, amantadine, and rivastigmine. 4/5 of these drugs have
at least some dopaminergic effect. . There were mixed results for ace-
tylcholinesterase inhibitors with 1/3 trials showing a decrease in apa-
thy after treatment. Limitations of many of these studies included
small sample sizes, large drop-out rates, limited measures of apathy,
and confounding by co-morbid depression or dementia.
Conclusions: Few clinical trials have been published that are
designed to look at pharmacological treatment for apathy. There is
limited evidence that medications with dopaminergic effects may
improve apathy in addition to motor symptoms. Future studies of
pharmacological treatment for apathy may benefit from more stand-
ardized assessments of apathy to define study samples and endpoints.
393
Subthalamic stimulation lead coordinates correlate with non-
motor effects in Parkinsons disease
H. Dafsari, J.N. Petry-Schmelzer, T. Dembek, A. Rizos, A. Antonini,
P. Martinez-Martin, K.R. Chaudhuri, V. Visser-Vandewalle, L. Tim-
mermann, On Behalf of EUROPAR and the IPMDS Non Motor PD
Study Group (Cologne, Germany)
Objective: To study the influence of lead location in subthalamic
nucleus (STN) deep brain stimulation (DBS) on motor and non-
motor outcomes.
Background: DBS for patients with Parkinsons disease (PD)
improves motor and non-motor symptoms (NMS) with a consider-
able degree of inter-subject variance, possibly due to individual lead
locations. Although DBS targeting is performed visually, we
hypothesized that an atlas-based analytic approach could reveal a
correlation of lead locations with non-motor effects of DBS.
Methods: 20 patients with PD undergoing bilateral STN-DBS (40
hemispheres) were included in this ongoing study. UPDRS-II (activ-
ities of daily living), -III (motor impairment), and -IV (motor com-
plications) and NMS Scale (NMSS), which consists of nine domains
covering a wide range of NMS, were collected at preoperative base-
line (MedON) and 6 months follow-up (6MFU; MedON/StimON).
We used Wilcoxon signed-rank or t-tests, when parametric criteria
were fulfilled, to test for significant changes and corrected Type I
errors with the Bonferroni method. As we were interested in the
influence of DBS lead locations, post-hoc we analyzed Cartesian
coordinates of lead tips in respect to the anterior/posterior commis-
sure (AC-PC) line using fused postoperative CT/preoperative MRI
images computed with the OPTIVISE software. Left hemispheric
leads were mirrored to the right hemisphere. To analyze the relation-
ship between lead tips and change scores (baseline 6MFU) we
employed Spearman-correlations.
Results: All outcomes improved significantly from baseline to
6MFU (UPDRS-II: 14.65 vs. 10.60, p50.004, 27.7% improvement;
UPDRS-III: 28.05 vs. 19.42, p50.016, 30.8% improvement; UPDRS-IV:
Fig. 1. (393).
Movement Disorders, Vol. 30, Suppl. 1, 2015
6.65 vs. 4.00, p50.032, 39.9% improvement; NMSS: 58.70 vs. 38.65,
p50.040, 34.2% improvement). Mean (SD) lead tip positions in respect
to the AC for all axes were x: 10.91mm (1.28), y: -18.28mm (2.22), and
z: -6.04 (2.91). Table 1 shows significant correlations between lead loca-
tions and clinical outcomes; all other results were not significant.
[figure1]
Conclusions: The results of our cohort are in accordance with the
broad agreement that DBS outcomes highly depend on lead loca-
tions. This study might provide information for DBS lead positioning
in patients with clinically relevant NMS and may encourage further
studies including more complex models integrating stimulation
parameters to study motor and non-motor effects of DBS.
394
Dopamine dysregulation syndrome in patients with Parkinsons
disease in a rural based Movement Disorders clinic in Western
India
S.D. Desai (Anand, India)
Objective: To assess prevalence of dopamine dysregulation syn-
drome [DDS] and associated characteristics in patients with Parkin-
sons disease [PD] attending Movement Disorders clinic in rural
Western India.
Background: DDS is an important complication in patients with
PD. There is paucity of data on this phenomenon from rural areas of
India and world.
Methods: Case records of patients with PD attending Movement
Disorders Clinic of Shree Krishna hospital, Karamsad, Gujarat, India
between April 2010 to October 2014 were reviewed for presence of
DDS.DDS was diagnosed on the basis of criteria developed by
Pezella[2003] and Giovannoni [2000].
Results: Amongst 327 patients with PD examined [196 males],
DDS was present in 11 patients [7 males]. Mean age of patients was 51
[42-57]. Mean duration of PD was 7.4 years [4-11]. 9 of the 11 patients
had rigidity predominant form of PD. Mean LD dose taken by patients
was 2200[1800-4200]mg/day. 8 of the patients were from low eco-
nomic class. None of them took dopamine agonists though prescribed;
citing lack of effect, high cost,nausea and pedal edema as the reason
for default. 8 of the patients had dysthymia/depression, 5 had anxiety, 3
had hypomania. All patients reported having fear of developing Off
state leading to the behaviour of excess LD intake. The reason they got
hooked to LD was that they had suffered from early off or unpredict-
able off at the usual prescribed dose of LD and had found out that addi-
tional LD dose would improve them in those periods. They preferred
an On state with dyskinesia [which would enable them to do ADL]
rather than a rigid Off state making working diffiicult. None of the
patients reported hoarding or hiding medicines. None of the patients/
relatives were aware that the dyskinesias were due to excessive LD
use, rather they considered dyskinesias to be increased tremors related
to PD. In 4 patients relatives would give extra LD doses with a belief
to improve them. Associated punding was seen in 9 of 11 patients,
pathologic gambling in 2 patients, hypersexuality in 2 patients, compul-
sive eating and shopping in 1 patient each.
Conclusions: DDS is seen younger patients, of low economic
class, with rigidity predominant form, on LD therapy, with associ-
ated psychiatric symptom, in those who prefer On state even with
dyskinesia as compared to a rigid Off state.
395
Compulsive tobacco use in patients with Parkinsons disease on
dopamine agonist/levodopa therapy: Is it also an impulse control
disorder?
S.D. Desai (Anand, India)
Objective: To assess frequency and characteristics of excessive
tobacco use in patients with Parkinsons disease[PD] treated with
Dopamine agonists[DA] or Levodopa[LD].
 POSTER SESSION
Background: We found increased tobacco use in some of our
patients with PD after starting treatment. Amongst impulse control
disorders[ICD] in PD, compulsive tobacco use is not described in
literature.
Methods: Case records of all patients with PD attending Move-
ment Disorders clinic of Shree Krishna Hospital, a rural based medi-
cal teaching hospital in Karamsad, Gujarat in Western India were
reviewed to assess the presence of excessive/increased tobacco use
after starting therapy with DA/LD.
Results: Between April 2010 and Oct 1014, 327 patients with PD
were seen. Of these, 15 patients had increased tobacco use. 7 patients
developed tobacco use denovo after starting of LD/DA treatment. 8
patients had an increase in tobacco use by more than double com-
pared to baseline. Tobacco use was in the form of chewing paan
masala [oral form of tobacco with betelnut leaf extract] in 6 [3
naive, 3 old], bidi smoking in 6 [3 naive, 3 old smokers], cigarette
smoking in 3, [1 naive, 2 old smoker]. All of them reported having
issue with tobacco use, thinking a lot about tobacco use, having
excess desire to consume tobacco and getting distressed on not using
it; leading to difficulty in controlling tobacco use. These are all fea-
ture of ICD. Factors associated with tobacco use were male gender,
Fig. 1. (396).
S155
rigidity predominant PD, young onset PD, tobacco use by peers/in
the past, presence of dysthymia and constipation. This region of
Charotar is a hub of tobacco agriculture and business may also be
contributory factor. 10 of them were able to control tobacco use after
counselling, decreasing the LD/DA dose and use of nicotine chewing
gum and Escitalopram. Despite counselling, 6 patients were not will-
ing to stop tobacco use and declined deaddiction clinic consult.
Conclusions: Excessive/compulsive tobacco use should also be
considered amongst ICD in patients with PD especially in areas
where tobacco is freely available.
396
The non motor network in early Parkinsons disease: Is there
first network tightening followed by network loosening?
N.J. Diederich, N. Sauvageot, V. Pieri, G. Hipp, M. Vaillant
(Luxembourg-City, Luxembourg)
Objective: To explore the potential relationship between different
non motor (NM) symptoms in patients with early stage Parkinsons
disease (PD).
Movement Disorders, Vol. 30, Suppl. 1, 2015
S156 POSTER SESSION
Background: Various NM symptoms, all of different anatomical
origin, have been associated with early PD motor phase. However, it
is unknown if and how they are linked together.
Methods: Prospective study recruiting 64 medicated PD patients
(less than three years of disease duration) and 71 age-matched healthy
controls (HC). Assessed functions were clustered in eight non motor
domains (NMD): odour, colour discrimination, contrast sensitivity,
general cognition, psychomotor speed, executive function, mood,
sphincter function. The correlation coefficients between different
NMD were computed separately in PD patients and HC. Bootstrap
correlation coefficients were computed, followed by computation of
the averaged correlation coefficients and their 95% confidence inter-
vals (CI). Fourteen PD patients and 19 HC were available for a
follow-up study three years later.
Results: The mean age of PD patients was 64.2611.6 and of HC
64.7 6 8.6 yrs. 58% of PD patients and 37% of HC were male (p5
0.01). PD patients were taking 177.4 6 276.2 mg levodopa and
0.7 6 1.6 mg of dopamine agonists (expressed in pergolide equiva-
lents). At baseline PD patients performed less well than HC on all
NMD (all p <0.02). Out of 28 possible correlations between NMD,
11 were significant in PD patients and 7 in HC [figure1].The median
correlation level was higher in PD patients (0.21) than in HC (0.11).
At the follow-up exam tightening of the correlation network was lost
in PD patients, with the median of correlation values being now
equal in PD patients and HC.
Conclusions: In early PD patients reduced performances in various
non motor domains are highly connected, suggesting or strong influence
by a common cofactor, or parallel disease progression. In contrast, at a
later phase, the tight correlation network between NMD seems to be
lost, but this finding needs confirmation in a larger cohort.
397
Does movement impairments cause anxiety in Parkinsons
disease? A chicken or egg question
K.A. Ehgoetz Martens, C.G. Ellard, Q.J. Almeida (Waterloo, ON,
Canada)
Objective: The current study aimed to disentangle whether move-
ment impairments influence anxiety by contrasting walking versus
standing in virtual reality in both ON and OFF dopaminergic states.
Background: Anxiety is the most under-recognized non-motor
symptom of PD, yet it is unclear whether anxiety exacerbates the
motor impairment seen in PD, or vice versa. If anxiety drives the
motor impairment, then if PD are put in an anxiety-provoking envi-
Fig. 1. (397).
Movement Disorders, Vol. 30, Suppl. 1, 2015
ronment, no anxiety differences would be expected when required to
walk compared to standing. However, if movement is required to
elicit anxiety, then walking through an anxiety-provoking environ-
ment might lead to greater anxiety compared to standing. Thus, the
current study aimed to answer this chicken and egg question.
Methods: Seventeen participants with PD performed two tasks
(Stand vs. Walk) in two levels of anxious virtual environments: (i)
located on the ground (LOW), (ii) located above a deep pit (HIGH).
This protocol was completed in both ON and OFF states (to evaluate
the effect of exacerbating motor symptoms). Skin conductance (SCL)
and self-reported anxiety levels were collected.
Results: PD reported greater levels of anxiety and had higher
SCLs when walking compared to standing. The HIGH condition also
generated greater levels of anxiety compared to LOW especially
when required to walk. Dopaminergic replacement therapy signifi-
cantly reduced self-reported levels of anxiety during the experiment,
however it did not change SCLs.
[figure1]
Conclusions: Since PD had worse anxiety when walking com-
pared to standing, and this was exacerbated even further in the OFF
state, the current study provides evidence that movement impair-
ments can influence anxiety in PD. Thus, the study emphasizes the
importance of optimally treating movement impairments as a method
of reducing movement driven anxiety.
398
Intensive rehabilitation enhances lymphocytes BDNF-TrkB
signaling in patients with Parkinsons disease
C. Fontanesi, S. Kvint, G. Frazzitta, G. Pezzoli, A. Di Rocco, A.
Quartarone, H.Y. Wang, M.F. Ghilardi (New York, NY, USA)
Objective: Here we test the hypothesis that an exercise program
that improves motor function and slows down the progression of PD
can enhance brain-derived neurotrophic factor (BDNF) - tyrosine
receptor kinase B (TrkB) signaling in lymphocytes.
Background: Patients with Parkinsons disease (PD) show a
decreased long-term potentiation (LTP)-like plasticity, revealed by
both electrophysiological testing and diminished retention of motor
skills. We have previously found that a five-day treatment that
enhances cortical plasticity also facilitates BDNF-TrkB signaling and
increases activated TrkB and N-methyl-D-aspartate receptor
(NMDAR) association in both cortex and peripheral lymphocytes.
Methods: Sixteen patients with PD underwent a four-week Multi-
disciplinary Intensive Rehabilitation Treatment (MIRT), which
 POSTER SESSION
included aerobic training, physical and occupational therapy. Blood
was collected before as well as after two- and four-week MIRT.
Lymphocytes were isolated to examine BDNF-TrkB signaling
induced by incubation with 50 ng/ml recombinant human BDNF
(rhBDNF). TrkB signaling complexes, extracellular-signal-regulated
kinase 2 (ERK2) and protein kinase B (AKT1) were separately
immunoprecipitated; the content of the immunocomplexes were
determined by Western blotting.
Results: All patients showed clinical improvement after MIRT in
terms of motor performance, gait speed, and balance (all: p < 0.01).
Moreover, we found increases of BDNF-TrkB signaling in peripheral
lymphocytes at receptor, intracellular mediators and downstream lev-
els as well as of TrkB interaction with NMDAR. All components of
BDNF-TrkB signaling pathway were increased even after two weeks
of MIRT, except for Shc recruitment and TrkB-NMDAR association.
Four-week MIRT enhanced TrkB-NMDAR interaction, as indicated
by the increased association of obligatory NMDAR NR1 subunit
with TrkB.
Conclusions: The reduced severity of PD symptoms following
MIRT together with enhanced BDNF-TrkB signaling in lymphocytes
suggest that MIRT might increase the LTP-like plasticity mediated
by this pathway and that the immune system might be involved in
neurorestoration and recovery.
399
Olfaction and nonmotor symptoms (NMS) in subjects with scans
without evidence of dopaminergic deficit (SWEDDs)
M.E. Fullard, D. Weintraub, J.E. Duda, J.F. Morley (Philadelphia,
PA, USA)
Objective: To compare the characteristics of SWEDDs, de novo
Parkinsons disease (PD) subjects, and healthy controls (HC) in the
Parkinsons Progression Markers Initiative (PPMI) cohort.
Background: Approximately 10-15% of patients clinically diag-
nosed with early PD are found to be SWEDDs, the clinical pheno-
type of which is not well characterized.
Methods: Cross-sectional study of de novo PD subjects (N=428),
SWEDDs (N=65) and HC (N=200) in the PPMI cohort. Baseline
evaluation included olfactory testing with the University of Pennsyl-
vania Smell Identification Test (UPSIT) and motor and NMS assess-
ments. Group differences were examined using Fisher exact or v2
tests for categorical variables, Mann-Whitney U for continuous varia-
bles and partial correlations for associations between continuous vari-
ables, controlling for relevant covariates.
Results: The mean(SD) UPSIT score in the SWEDD group
(30.9(7.2)) was lower (reflecting worse olfaction) than HCs,
33.9(5.1), (p<0.001) and higher than the PD group at 22.2(8.3)
(p<0.001). When controlled for age and gender, 12/66(18.2%) of
SWEDDs exhibited severe olfactory impairment (OI, severe micro-
smia or anosmia), compared to 12/200(6.0%) (p50.005) of HCs and
268/428(62.6%) (p<0.001) of PD subjects. SWEDDs also had higher
rates of other NMS compared to HCs, including REM behavior sleep
disorder (RBD) symptoms (SWEDD 32.3%, HC 12.6%, p50.001),
depression (SWEDD 29.2%, HC 6.5%, p<0.001) and apathy
(SWEDD 21.2%, HC 5.1%, p<0.001). Rates of RBD (PD 25.5%,
p50.29) and apathy (PD 16.9%, p50.39) were similar between
SWEDDs and PD, while rates of depression (PD 13.8%, p50.003)
were higher in SWEDDs. Within the SWEDD group, OI subjects
had higher rates of depression (58.3% vs 23.1%, p50.03), and RBD
(58.3% vs. 26.9%, p50.048). There was a positive association
between UPSIT score and Montreal Cognitive Assessment (MOCA)
in SWEDDs (r=0.424, p50.001). UPDRS motor scores were similar
in SWEDDs with or without OI (16.6(10.7) vs 13.8(9.1)), (p50.39).
However, SWEDDs with the combination of RBD and OI had higher
bradykinesia scores 11.9(8.1) compared to those without 5.9(5.5),
(p50.02).
Conclusions: SWEDD subjects exhibit NMS more commonly
than HCs and often at frequencies similar to PD subjects. The clus-
S157
tering of OI with other NMS in SWEDDs may represent a distinct
clinical phenotype that can be further investigated as longitudinal
data from the PPMI accumulates.
400
Relationship between olfaction, motor and nonmotor symptoms
and dopamine transporter binding in de novo PD
M.E. Fullard, D. Weintraub, J.E. Duda, J.F. Morley (Philadelphia,
PA, USA)
Objective: To evaluate the relationship between baseline olfac-
tion and both cross-sectional and longitudinal motor symptoms, other
nonmotor symptoms (NMS), and dopamine transporter binding in
early Parkinsons disease (PD).
Background: Olfactory dysfunction is a common, easily meas-
ured feature in early PD, but its value as a predictive biomarker for
motor and NMS, and disease progression has not been explored in a
large, longitudinal cohort.
Methods: Parkinsons Progression Markers Initiative (PPMI) par-
ticipants underwent baseline olfactory testing, and baseline and serial
dopamine transporter (DAT) scans and motor and NMS assessments.
Group differences were examined using Fisher exact or v2 tests for
categorical variables, Mann-Whitney U test for continuous variables,
logistic regression for associations between categorical and continu-
ous variables, and partial correlations for associations between con-
tinuous variables, controlling for relevant covariates. Longitudinal
analysis was performed using linear mixed effects models.
Results: The sample sizes at each time point were: baseline (PD
=428, HC =200), year 1 (PD =361, HC =186) and year 2 (PD =234,
HC =137). PD patients had lower University of Pennsylvania Smell
Identification Test (UPSIT) scores than healthy controls [PD
22.2(8.3), HC 33.9(5.1), p<.001], reflecting worse olfactory function.
In PD participants, there was an inverse correlation between UPSIT
score and baseline UPDRS motor score (r= -0.12, p50.01), control-
ling for age and gender. Using logistic regression, the odds of base-
line RBD was higher as the UPSIT score decreased (reflecting worse
olfaction), (OR=0.97, p50.038). There was no significant correlation
between UPSIT score and depression, apathy or baseline cognitive
assessment (MoCA). In longitudinal analysis, there was no associa-
tion between baseline UPSIT score and UPDRS motor score progres-
sion. MoCA scores decreased by a mean of 0.5 points per year, and
there was an association between worse baseline olfaction and
decline in MoCA over time (b=0.027, p50.002). The annualized
decline in DAT binding was 7.8% per year, and lower UPSIT scores
(worse olfaction) were associated with faster decline (b50.0017,
p50.03).
Conclusions: Worse baseline olfactory function in de novo PD is
associated with worsening of cognitive measures and DAT deficit
over time and may be valuable as a predictor of clinical progression.
401
Prevalence and severity of non motor symptoms (NMS) of
Parkinsons disease (PD) in the elderly An Australian
perspective
S. Gangadharan, A. Withanage, C.P. Padmakumar, M. Rees, A.
Johnson (Newcastle, Australia)
Objective: To identify the prevalence and severity of NMS bur-
den in the patients with PD aged over 65 attending a suburban Aus-
tralian PD service.
Background: The burden of NMS is an important factor which
defines the disease related quality of life (QoL) in a PD patient.
Prevalence and burden of NMS varies widely among different patient
groups.
Methods: All patients aged over 65 years attending the PD clinic
at Rankin Park Centre, Newcastle, NSW, from January 2012-March
Movement Disorders, Vol. 30, Suppl. 1, 2015
S158 POSTER SESSION
2014 filled out the Non Motor Symptom Questionnaire (NMSQ).
Their disease burden was calculated using the Kings ISCIII grading.
Results:
Number of patients (n) 53
Mean age: 77 years
Male: Female 27:26
Nocturia 71%
Short term memory loss 67%
Low mood 60%
Difficulty concentrating 56%
Anxiety 52%
Constipation 47%
Sleep related disorders 45%
Based on the Kings ISCIII grading, 35% of patients had stage 3
(severe) burden, 34% had stage 2 (moderate) 24% had stage 1 (mild)
burden of NMS.
Conclusions: Our study shows 35% of PD patients over 65 years,
from suburban Australia had stage3 (severe) burden of NMS. Noctu-
ria, short-term memory loss and depressive features were the most
prevalent NMS.Severity of NMS burden equates to poor QoL
as shown by multiple studies. Streamlining the available resources
to manage the prevalent NMS will improve the QoL in patients
with PD.
402
The assessment of visuospatial functions in Parkinsons disease
patients without dementia
M. Gultekin, A. Ekinci, M. Mirza (Kayseri, Turkey)
Objective: The aim of this study was to evaluate visuospatial func-
tions in idiopathic Parkinsons disease (PD) patients without dementia.
Background: PD is the second most common neurodegenerative
disease. During PD, many disturbances occur in the cortico-basal
ganglia pathways and, due to these disturbances, visual perception
deficits are common in PD patients. Therefore, patients daily living
acvtivities are negatively affected by the disease.
Methods: Two groups were included in this study: Consecutive
PD patients without dementia and control subjects. Each of the
groups consisted of 30 patients. We used Addenbrookes cognitive
examination (ACE-R) to asses visuospatial functions in the groups.
We considered, in particular the score of that part of the ACE-R
which includes visuospatial abilities. This parts normal score is 16.
Results: The mean age of the patient group was 60.1 years and
that of the control group was 56.7 years. ACE-R mean score was
significantly lower in PD patients without dementia. The ACE-R
mean score of the patient group was found as 11.2 and that of the
control group was found as 14.6. The patient groups Mini-Mental
State Examination (MMSE) mean score was 26.5 and the control
groups MMSE mean score was 28.5.
Conclusions: Our findings were similar to those of previous stud-
ies and this situation was evaluated as the reflec:tion of impairment
of cortico-basal ganglia pathways in PD patients. Also, this result
indicates that reduced MMSE test score may not be strongly associ-
ated with visuospatial functions in PD.
403
The assessment of apathy symptoms in Parkinsons disease
patients without dementia
M. Gultekin, A. Ekinci, M. Mirza (Kayseri, Turkey)
Objective: The aim of this study was to evaluate apathy symp-
toms in idiopathic Parkinsons disease (PD) patients without
dementia.
Movement Disorders, Vol. 30, Suppl. 1, 2015
Background: The patients not only had motor symptoms: most
of them also had non- motor symptoms like depression, sleep disor-
ders, pain, apathy and other psychiatric disorders. The presence of
apathy in previous studies in PD patients has been reported with dif-
ferent results and varies from 7% to 70%. This variability originates
from the use of different criterias for determining apathy.
Methods: Two groups were included in this study: PD patients
without dementia and control subjects. Also, these groups had no
depression symptoms. Each of the groups consisted of 30 patients
who admitted consecutively. We used the Apathy Evaluation Scale
(AES) score for comparison between groups.
Results: The mean age of the patient group was 60.1 years and
that of the control group was 56.7 years. The AES test mean score
was significantly higher in PD patients without dementia. The AES
mean score of the patient group was found as 37.5 and that of the
control group was found as 29.3. We showed that PD patients have a
high apathy score without dementia and depression.
Conclusions: Apathy is a common condition in patients with PD
and is associated with a reduction in the performance of activities of
daily living. Thus every patient with PD should be questioned about
apathy symptoms before being prescribed treatment because there
are various treatment options.
404
Assessing postural stability in early stages of Parkinsons disease
H.D. Hambardzumyan, H.M. Manvelyan (Yerevan, Armenia)
Objective: The primary aim of this study was to examine the
suitability of different clinical assessment tests for the screening of
postural stability in early PD.
Background: Postural instability is an important symptom of Par-
kinsons disease (PD) that may cause problems in daily life. It is,
therefore, important to screen for this problem to identify those at
risk for falling and to reduce hazardous falls.
Methods: 24 people with idiopathic PD were assessed with com-
monly used clinical assessment tests, i.e. the Berg Balance Scale
(BBS), Timed Up and Go (TuG), Timed Up and Go-cognition (TuG-
cog), the Modified Figure of Eight (MFE), walking 30 meters at self-
paced and maximum speeds, together with disease severity rating,
self-reported fall history, the Falls Efficacy Scale-International (FES-
I) and the Freezing of Gait Questionnaire (FOG-Q). The Backstrand,
Dahlberg, and Liljenas Balance Scale (BDL), with more complex
balance demands, was also validated. Correlations between the dif-
ferent assessment tests, questionnaires, ratings of disease severity,
and fall history were calculated.
Results: Tests that included walking with a turning task were
more predictive of risk of fall and more highly correlated to the dis-
ease severity rating scales than were the other tests. The question-
naires FES-I and FOG-Q did not correspond to actual falls or to
disease severity.
Conclusions: To evaluate postural stability in early PD, we sug-
gest a battery of tests that includes the TuG, the TuGcog, and the
MFE. For evaluating exercise intervention in early PD the BDL is a
better test than the BBS.
405
Non-motor symptoms in Parkinsons disease: A correlation with
depression and quality of life
H.D. Hambardzumyan, H.M. Manvelyan (Yerevan, Armenia)
Objective: Aim of this study was to determine frequency and
severity of NMS in patients with PD. Moreover, we correlated NMS
scores with demographic data, quality of life, and depression.
Background: Non-motor symptoms (NMS) of Parkinsons dis-
ease (PD) are not well recognized in clinical practice, and are fre-
quently missed during routine.
 POSTER SESSION
Methods: 37 patients with PD participated in this study. NMS
severity was determined by using the Non-Motor Symptom assess-
ment scale for PD (NMSS; Chaudhuri KR, et al. Mov Disord.
2007;22(13):1901-11.) and selfcompleted NMS-Questionnaire for PD
(the NMSQuest; Chaudhuri KR, et al. Mov Disord. 2006;21(7):916-
23.). Quality of life was assessed by PDQ-8 questionnaire, and depres-
sion was scored by means of Beck Depression Inventory (BDI).
Results: Data from 37 consecutive patients, mean age 65.4 6 7.6
years, duration of disease 5.3 6 4.7 years, and all stages of PD were
collected. The mean NMSS score was 38.6 6 25.6 (range: 9-110).
The mean NMSQuest score was 10.7 6 4.5 (range: 2-22). We found
significant correlation between NMSS score and NMS-Quest score
(rho 0.72; p<0.0001), NMSQuest and duration of PD (rho=0.56,
p50.0007), NMS-Quest and BDI (rho 0.68; p<0.0001), NMSS and
BDI (rho 0.55; p50.0005), and PDQ-8 score and BDI (rho=0.51,
p50.0017) .
Conclusions: NMS are significantly frequent across all stages of
PD. This study proves the efficiency of screening questionnaire the
NMS-Quest, as well as of NMSS. Scores of both instruments highly
correlate. Moreover, NMS correlate with depression that correlates
with quality of life in PD. Our results stress the importance for
active detection of NMS in PD patients.
406
Characterize sleep related disorders in subtypes of Parkinsons
disease
S. Hanif, M.S. Bashir, T.M. Muhammad, J.A. Bajwa (Riyadh, Saudi
Arabia)
Objective: To describe sleep related disorders in Tremor Domi-
nant (TD) and Akinetic Rigid (AR) subtypes of Parkinsons disease
(PD) patients evaluated at Movement Disorders center, National
Neuroscience Institute, King Fahad Medical City, Riyadh, Saudi
Arabia.
Background: There is currently no data regarding sleep related
disorders in patients with TD-PD and AR-PD in Arab ancestry. Non
motor symptoms especially sleep related disturbances add significant
disease burden in PD patients.
Methods: We interviewed 36 patients. The questionnaires used
for interview consisted of demographic details, disease related
parameters (duration of PD, type of PD, number of drugs, duration
of sleep disturbance, effects of sleep disturbance on daily life, day-
time solemness). Standard Scales used were Parkinsons disease
sleep score (PDSS), Non Motor Symptoms assessment Score
(NMSS), Mini Mental State Examination (MMSE), Hoehn & Yahr
staging (H&Y) and modified Unified Parkinsons disease Rating
Motor Scale (UPDRS). The study protocol was approved by Institu-
tional Review Board (IRB).
Results: 36 patients among whom 23 were males and 13 were
females with mean age (6SD) of 61.8 6 8.02, were interviewed. 25
patients had TD-PD while 11 patients had AR-PD. Average disease
duration was 6.53 6 4.52 years in TD group and 3.33 6 2.78 years in
AR group. 83.3% patients reported sleep disturbances while remaining
16.7% denied any sleep disorder, 22% patients were found to injure
themselves during sleep (TD 11% vs AR 8.3%) while 30.6% injured
their sleeping partner (19% TD vs 8.3% AR), dreams with Rapid Eye
Movement Sleep Behavior Disorder (RBD) were described by 47.2%
patients (30.5%TD vs 16.6% AR) though dream content was described
in only in 33% (25% TD vs 8.3% AR). 33% patients reported daytime
solemnness (25% TD vs 8% AR), On PDSS nine patients (37%) had
moderate to severe sleep disturbance, (25% TD vs 12.5% AR).
Conclusions: Our data shows 83.3% of PD patients had sleep
related problems. Sleep related disturbances were more common in
TD-PD subtype although not statistically significant. Our findings are
limited given small sample size. Larger cohort and sleep studies are
required to further assess this preliminary data among TD-PD and
AR-PD in our Arab cohort.
S159
407
Use of the SpeechVive device improves communication in people
with Parkinsons disease
J.E. Huber, S. Snyder, C.E. Rountrey, C.L. Ludlow (West Lafayette,
IN, USA)
Objective: To examine the effectiveness of the SpeechVive device
for improving communication in persons with Parkinsons disease (PD).
Background: Speech impairments are common in PD and lead to
social isolation and reduced quality of life. Generalization of behav-
ioral speech therapy to everyday communication remains difficult for
many patients, possibly due to the sensory and cognitive problems
associated with PD. A potential solution is the SpeechVive device, a
wearable device that produces cocktail noise in one ear triggered by
the patients voice onset. This noise elicits the Lombard Effect, a
reflexive increase in the persons vocal intensity that does not inter-
fere with their ability to hear others speech.
Methods: Seventeen persons with PD wore the SpeechVive regu-
larly for 3 months. During pre- and post-testing, participants pro-
duced a variety of speech tasks first without and then with the
SpeechVive. Objective acoustic measurements determined if speech
changed over time with and without the device (p<0.01).
Results: Two measures improved pre- to post-testing without the
device; voice intensity in dB SPL increased during connected speech and
variability in fundamental frequency increased during sentence produc-
tion. While wearing the SpeechVive, both before and after treatment,
participants produced speech at higher vocal intensity and used longer
utterances. Based on means inspection, participants produced fewer revi-
sions, disfluencies, and filled pauses when wearing the SpeechVive.
Conclusions: Overall, wearing the SpeechVive resulted in
improved communication. Participants learned to use a higher vocal
intensity and better intonation patterns after treatment, even when
not wearing the SpeechVive. Some effects occurred with continued
use of the SpeechVive suggesting long-term use of the device may
be helpful to speech. Larger controlled trials are needed to determine
the level of benefit of such a device in PD and to determine what
patients are the best candidates for treatment.
408
Zero non-motor symptoms in a martial arts expert
L.J. Jaffe (San Diego, CA, USA)
Objective: To consider factors that might lead to the least non-
motor symptoms in Parkinsons disease.
Background: Identified to be at least as distressing as the motor
symptoms of PD, the non-motor symptoms of PD can be quantified
using the Non-Motor Symptoms Scale (NMSS.) This tool was devel-
oped in 2007 to quantify the number of some common distressing
non-motor symptoms for PD patients. Studies have shown that non-
motor symptoms can contribute to patients quality of life (QOL.)
Some reports show that tai chi and other forms of physical activity
have positive effects on diminishing PD symptoms, including non-
motor symptoms. Other reports did not support this positive effect. I
report on one patient whose NMSS remained zero for 3 years. He
happened to be a 9th degree karate master.
Methods: Pateint TS was diagnosed with IPD in 2011 at the age
of 56. He responded well to anti-PD medications early on but this
needed to be increased during the first year. The 30 item NMSS was
administered to the patient at the end of his first year and 2nd and
3rd year on anti-PD treatment.
Results: The patient continued to indicate no non-motor symp-
toms evolution in 1-3 years and he continued to maintain his busy
teaching, training, and work-out schedule over this time.
Conclusions: For this Martial Arts master, age 56, zero non-
motor symptoms evolved in 3 years of follow-up visits using the
NMSScale. Though the first few years after PD diagnosis is consid-
ered to be the honeymoon period with fairly good symptomatic
suppression in some people, it remains very unusual to remain free
Movement Disorders, Vol. 30, Suppl. 1, 2015
S160 POSTER SESSION
of any non-motor symptoms. It is possible that this was the case for
TS because he was a Martial Arts master and more investigations
into the potential benefits of martial arts and other physical activity
would likely lead to a better understanding of how to minimize non-
motor symptoms in Parkinsons disease.
409
Impulse control disorders and compulsive behaviors in
Parkinsons disease and control subjects
S. Jesus, C. Cortes, I. Huertas-Fernandez, M.T. Caceres-Redondo, F.
Carrillo, M. Bernal-Escudero, L. Vargas-Gonzalez, M. Carballo, P.
Mir (Seville, Spain)
Objective: Our objective was to analyze the existence of ICD
and CB in PD patients compared to control subjects and to assess
the clinical features in the PD group as well as the relationship
between these disorders and the dopaminergic treatment.
Background: The impulse control disorders (ICD) and compulsive
behaviors (CB) are included as non-motor symptoms in Parkinsons dis-
ease (PD) and they are closely influenced by the dopaminergic replace-
ment therapy.
Methods: We included 294 PD patients (132 males, 61.52 612.4
years) and 315 control subjects (132 males, 64.73 6 11.3 years). We
used the validated test QUIP-RS for screening and severity of ICD
Fig. 1. (410).
Movement Disorders, Vol. 30, Suppl. 1, 2015
and CB. We assessed the existence of both disorders at present and
in the past. We analyzed the clinical features and data related to the
treatment in the PD group. The statistical analysis used were Chi-
Square, T-student and Pearson correlation coefficient.
Results: The ICD and CB were more frequent in the PD group
(p<0.05). The disorders more prevalent were the hypersexuality, com-
pulsive eating and hobbism in both groups. In the PD group, patients
with ICD and CB showed a younger age at disease onset and an
increased rate of motor and non-motor fluctuations as well as cogni-
tive impairment. The dose of dopaminergic agonist was related to the
severity in compulsive buying disorder and dopamine dysregulation
syndrome. Rotigotine was the dopaminergic agonist associated to a
lower prevalence of ICD and CB.
Conclusions: The ICD and CB are more frequent in PD patients.
There are other clinical features related to the presence of these disorders.
The treatment influences in the apparition of ICD and CB being Rotigo-
tine the dopaminergic agonist linked to a lower prevalence of them.
410
An 8-year follow-up on the effect of subthalamic deep brain
stimulation on pain in Parkinsons disease
Y.J. Jung, H.J. Kim, B.S. Jeon, H. Park, W.W. Lee, S.H. Paek
(Seoul, Korea)
 POSTER SESSION S161

Objective: To evaluate the long-term effect of STN DBS on pain (p50.024)]. Comparison of the severity of PD by H&Y stage and
in PD following our previous studies about the beneficial effect on the quantitative CAIs failed to demonstrate the correlation except for
pain of three-month and two-year follow-ups after surgery. 30:15 ratio (P=0.034).
Background: Pain is a common and distressing feature in Parkin- Conclusions: CAIs can successfully demonstrate the cardiovascu-
sons disease (PD). Major indication of subthalamic deep brain stim- lar autonomic dysfunction and 30:15 ratio may be the optimal evalu-
ulation (STN DBS) is motor complication in advanced PD, however, ation method revealing the symptom severity in PD.
pain reduction after STN DBS has been noted.
Methods: Twenty-four patients who underwent STN DBS were
included. Pain was evaluated by asking patients about the quality 412
and severity of pain in each of their body parts. The assessments Increased energy expenditure may be reversed by dopaminergic
were performed preoperatively and eight years after surgery. Because medications in patients with Parkinsons disease
13 from the total 24 patients had additional two- year postoperative K. Kashihara, A. Hongo, H. Kagayama, K. Hasegawa (Okayama,
data, the serial change between the preoperative and the two- and Japan)
eight-year follow-ups after surgery was also evaluated.
Results: Sixteen of the 24 patients (66.7%) experienced off-state Objective: We studied the effect of dopaminergic medication on
pain at baseline. All off-state pain at baseline improved or disap- basic metabolism of PD patients.
peared at eight years after surgery. However, new pain developed in Background: Weight loss is a frequent complication of the
18 out of 24 patients (75%) patients during the eight-year follow-up patients with Parkinsons disease (PD). Weight loss induces malnutri-
period. The most prevalent type of newly developed pain was mus- tion which may result in infection and decubitus. The enhanced
culoskeletal. Although the number of body parts with pain increased, energy expenditure, decreased energy intake, or both have been pro-
the mean and median score at eight years after surgery were lower posed as the cause. Increased rigidity, tremor, and dyskinesia in PD
compared to baseline. may increase energy expenditure. Motor disturbance, dysphagia, gas-
[figure1] Effects of STN DBS on pain. trointestinal dysfunction may result in decreased energy intake.
The number of patients with off-state pain for each category of Dopamine replacement therapy also may affect weight loss through
pain and all pain for the total group (N=24) at baseline and 8 years affecting central nervous system, appetite, and/or glucose metabolism
after surgery (A) and subgroup (n513) at baseline, 2 and 8 years of patients.
after surgery (B). The numbers above the columns indicate the mean Methods: We measured the basic metabolism of patients with de
off-state pain score. novo PD (44 patients; 16 men, 28 women), as well as weight, height,
Conclusions: Pain in PD is improved by STN DBS, and the ben- appetite, and amount of daily calorie intake before, 3 and 12 months
eficial effect persists after a long-term follow-up of eight years. In after starting dopaminergic medications. Energy expenditure was
addition, new pain, especially the musculoskeletal type, developed in measured by use of Fitmate Pro (COSMED, Italy). In order to ana-
most of the patients, and it becomes a long-term troublesome lyze energy expenditure of patients, percentage of measured calorie
problem. relative to the estimated calorie for the age, sex, height and weight
of each individual determined by Harris-Benedict equation was
calculated.
411 Results: Mean (6SD) age of patients was 72.0 6 6.6 years old,
Evaluation of cardiovascular autonomic dysfunction in disease duration 17.7 6 37.7 months, and disease severity determined
Parkinsons disease by cardiovascular autonomic indexes by Hoehn & Yahr staging 1.8 6 0.5 at the time of starting
Y.J. Kang, T.K. Lee, J.H. Park, K.B. Sung (Bucheon-si, Korea)
Objective: The aim of this study is to investigate the usefulness
of the quantitative autonomic test and their correlation to the severity
of PD.
Background: Cardiovascular autonomic dysfunction is one of the
most frequent non-motor symptoms in Parkinsons disease (PD).
Several cardiovascular autonomic indexes (CAIs) using non-invasive
autonomic tests have been reported to represent the degree of auto-
nomic dysfunction in some neurodegenerative diseases. However,
quantitative assessment by physiologic autonomic function tests in
PD has not been fully evaluated yet.
Methods: Four parasympathetic and four sympathetic indexes
during cardiovascular autonomic tests by non-invasive beat-to-beat
blood pressure and heart rate monitoring were compared between
patients with PD (n520, age=69.70 6 10.388, Hoen&Yahr (H&Y)
stage=2.33 6 0.847) and age matched healthy controls (n520,
age=63.90 6 8.717). Parasympathetic indexes include expiration/
inspiration (E/I) ratio during deep breathing, valsalva ratio, 30:15
ratio during head tilt table test, BRSv (regression slope of heart
period over SBP during early phase 2) during valsalva maneuver.
Sympathetic indexes were pressure recovery time (PRT), sympathetic
index1 (BP fall during phase 2, SI1), SI3 (the difference in BP
between baseline and the end of phase 2) and BRSa (BP decrement
associated with phase 3 divided by the PRT) during valsalva maneu-
ver. To demonstrate the correlation of disease severity and the auto-
nomic abnormality, we also compared the H&Y stage and the
abnormalities of those CAIs.
Results: Several indexes of CAIs were significantly different
between PD and control groups [E/I ratio (p<0.001), 30:15 ratio
(p50.043), valsalva ratio (p<0.001), BRSa (p<0.001) and SI3 Fig. 1. (412).

Movement Disorders, Vol. 30, Suppl. 1, 2015

S162 POSTER SESSION

dopaminergic medication. Basic metabolic rates were decreased sig- tive marker of nighttime sleep in patients with Parkinsons disease
nificantly in 12 months after medication (Figure 1). Body mass index (PD).
did not change and calorie intake was increased significantly in 12 Background: Sleep disturbances as an important non-motor
months. There were positive correlations between energy expenditure symptom (NMS) in patients with PD are multifactorial and disturbed
ratio and amount of calorie intake. nighttime sleep can be expressed with excessive daytime sleepiness
Conclusions: Increased energy expenditure appears to be reversed (EDS). The PKG, a system consisting of algorithms operating on
after starting dopaminergic medication. Increased calorie intake also wrist worn accelerometry, can be used as an objective measure of
may compensate for the weight loss produced by PD pathology. different motor states. Furthermore, periods of immobility during
[figure1] daytime and nighttime can be measured by PKG and it is thought
that these periods represent episodes of sleep.
Methods: A total of 63 PD patients (43 male) were studied and
divided to a sleepy and non sleepy group based on Epworth Sleepi-
413 ness Scale (ESS). 33 patients have been evaluated as controls (PD-C,
Prevalence, severity and treatment rate of major non-motor ESS < 10) while 30 patients had EDS (PD-EDS, ESS > 10). The
Parkinsons disease symptoms according to social media groups were matched for age, gender and Hoehn and Yahr state.
platform PatientsLikeMe Data from 24-hour PKG recordings over six consecutive days are
compared with Hauser diaries and scales of motor state, sleep and
A. Killoran (Morgantown, USA)
health related quality of life (HRQoL).
Objective: To assess the prevalence, severity and treatment rate Results: Both patient groups are comparable in their motor disabil-
of major non-motor Parkinsons disease (PD) symptoms according to ity and depression as well as medication side effects were not con-
social media platform PatientsLikeMe. founders (hospital anxiety and depression scale (HADS) scores and
Background: PatientsLikeMe is a popular free online platform levodopa equivalent dose (LED) were not significant different between
that allows patients to document their diagnoses, symptoms and treat- the control and study group). Nighttime sleep markers such as the dura-
ments. In PD, non-motor symptoms negatively impact health-related tion of sleep and wake periods measured by PKG showed a significant
and perceived quality of life. Though increasingly recognized, it is correlation with the total score of the non motor symptoms question-
unclear if these non-motor symptoms are being clinically managed. naire (NMSQuest) (p50.002), single items of the NMSQuest, the total
Methods: An analysis was performed on data from PatientsLi- score of the Parkinsons disease sleep scale (PDSS) (p50.002) and a
keMe regarding PD patients reported symptoms and treatments. HRQoL scale (p50.002) in the PD-EDS group alone.
Results: PD was reported in 9,110 individuals (53% Males; 65% Conclusions: Our preliminary and pilot data suggests that the
60-plus years of age), with 8,895 claiming it as their primary condi- PKG may be a useful marker for assessment of nighttime sleep. Fur-
tion. Non-motor PD symptoms, their severity (rated as none, mild, ther studies with comparative nighttime polysomnographic studies
moderate or severe) and their respective treatments were documented would be useful.
by roughly half of the participants, depending on the particular
symptom. A summary of the findings are listed in Table 1. 415
Conclusions: Based on social media platform PatientsLikeMe,
relatively few PD patients are being treated for their non-motor The Biodex system: Sensitive for fall detection in Parkinsonism
symptoms, despite their high prevalence and severity. E. Lapointe, E. Lafleur Prudhomme, M. Panisset (Sherbrooke, QC,
Canada)
TABLE 1. Prevalence, severity and treatment rate of non- Objective: To evaluate the ability of the Biodex Balance System
motor Parkinsons disease symptoms according to SD (BBSSD) and of the Mini-BESTest to discriminate between Par-
PatientsLikeMe kinsonian fallers and non-fallers.
Background: The Mini-BESTest is a quick balance assessment
Moderate On that reliably identifies fallers among individuals with Parkinsons dis-
Participants Prevalence or treatment ease (PD). The BBSSD has been designed in part to assist in fall
Symptom (n) (%) severe (%) (%) risk screening. However, little is known about its usefulness in
patients with PD or Parkinsonian syndromes.
Fatigue 4,473 86.2 55.7 8.4 Methods: We retrospectively reviewed 39 different physiotherapy
Somnolence 4,348 71.2 43.2 1.6 evaluations in 36 patients with PD or Parkinsonian syndromes. The scores
Pain 2,601 70.2 52.2 9.8 of Mini-BESTest, BBSSD fall risk and modified clinical test of sensory
Memory 4,341 67.0 31.9 0.9 integration of balance (mCTSIB) were analyzed. mCTSIB was executed
problems on both a firm and unstable surface, with eyes opened and closed.
Insomnia 4,461 70.0 53.4 8.3 Results: There were 31 patients wtih PD, 2 with multiple system
Anxiety 4,435 65.3 42.0 8.9 atrophy-Parkinsonism, 3 with other Parkinsonism. Patients were sep-
Constipation 4,350 62.0 49.1 8.3 arated in two groups (fallers and non-fallers) based on history of at
Depression 4,350 60.9 41.1 18.6 least one fall within the prior year.
Sexual 4,293 56.2 31.0 0.2
dysfunction
Excess saliva 4,337 55.2 27.7 0.3 Patients characteristics
fallers non-fallers p
414
N 25 14 -
Sleep assessment in Parkinsons disease The use of Parkinsons Age 67.6 (9.8)* 58.3 (10.4)* 0.01
KinetiGraph Duration of disease 9 (6.7)* 7.3 (4.9)* ns**
L. Klingelhoefer, M. Horne, A. Rizos, A. Sauerbier, S. McGregor, D.
Trivedi, L. Perkins, K. Ray Chaudhuri (Dresden, Germany) *mean (standard deviation), **non significant

Objective: In this prospective controlled study we examine The between group difference showed a trend (p50.076) on the
whether the Parkinsons KinetiGraph (PKG) can be used as an objec- Mini-BESTest (mean total score, non fallers 22.9/32; fallers 18.9/

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
32). When looking at Mini-BESTest subcategories, fallers scored sig-
nificantly worse on the anticipatory transition section (mean 4 vs 5.2,
p5 0.017).
The Biodex mean fall risk was greater in fallers (1.54 vs 0.97,
p50.008), but both results fell in the normal expected range for age
according to the system normative data. The mCTSIB score, assessed
on a firm surface with eyes closed, was statistically higher in fallers
(2.08 vs 1.36, p50.014). There was a trend towards significance for
mCTSIB assessed on an unstable surface with eyes opened (1.66 vs
1.19, p50.058).
The Mini-BESTest total score correlated significantly only with
the mCTSIB performed on an unstable surface with eyes closed
(r 5 -0.682, p < 0.0001). However, correlations were found between
mCTSIB subtests and Mini-BESTest sections, as well as Biodex fall
risk and Mini-BESTests anticipatory transition section (r 5 -0.476,
p5 0.006).
Correlations between mCTSIB and MiniBESTest
mCTSIB subtest Mini-BESTest section significance
Eyes opened, unstable Sensory orientation r 5 -0.453, p50.020
Eyes closed, firm Anticipatory transitions r 5 -0.391, p50.05
Eyes closed, unstable Anticipatory transitions r 5 -0.519, p50.008
Eyes closed, unstable Postural responses r 5 -0.501, p50.01
Eyes closed, unstable Sensory orientation r 5 -0.61, p50.001
Eyes closed, unstable Dynamic gait r 5 -0.606, p50.001
Conclusions: In our study, Biodex fall risk and mCTSIB
appeared to be sensitive to falls in patients with Parkinsonism,
whereas the Mini-BESTest failed to differentiate the two groups.
However, these results need to be interpreted with caution as partici-
pants were not consecutive patients and the number of participants is
small. Also, Biodex tests normative data and cut-off scores need to
be determined.
416
REM sleep disorders in early onset Parkinsonism: Non-motor
symptoms and the functional predictors perspective in advanced
age
L.A. Leandro, H.G. Teive (Curitiba, Brazil)
Objective: To determine the prevalence, risk factors and func-
tional predictors associated with the disorder of REM sleep in early-
onset Parkinsonism.
Background: It is becoming increasingly clear that non-motor
manifestations of Parkinsons disease (PD), as REM sleep disorders
contribute to the reduction of functional capacity in PD. There are
concrete and specific evidence that many of these manifestations are
treatable and that appropriate therapy can have a signifi-cant way to
the day-to-day this population.
Methods: Cross-sectional study with a descriptive approach
which analyzed 19 patients with early-onset PD, over the age of 60,
stage II/III HY, with UPDRS III and Schwab England to assess the
functional level. To learn about sleep disorders REM was used
RBD1Q proposed the Postuma (2012).
Results: Of the 19 patients evaluated, 8 women and 11 men, we
found that 17 (89.47%) presented REM sleep disturbances through
RBD1Q. The UPDRS showed averages of 22 points in the activities
of daily living and motor exploring an average of 28.94. The main
risk factors were the duration of the disease and intolerance to medi-
cation. Advanced age and the duration of the disease appear as func-
tional predictors of dependency.
Conclusions: Sleep disorders REM found in patients as early
onset Parkinsons disease associated with non-motor symptoms and
risk factors directly interfere in day-to-day compromising their func-
tional performance and therefore their quality of life.
S163
417
Swallowing, voice and freezing of gait in patients with
Parkinsons disease Correlation between each other and
contribution to quality of life
S.Y. Lee, S.M. Cheon, J.W. Kim (Busan, Korea)
Objective: This study was done to find the correlation between
axial symptoms and the contribution to quality of life in PD.
Background: Axial symptoms of Parkinsons disease (PD) are
less responsive to treatment and can cause great limitation in daily
living of patients with PD.
Methods: Patients with PD were recruited from outpatient clinic.
Axial symptoms, which including speech, swallowing, and freezing
of gait, were evaluated by intensive interview with specific question-
naire (voice handicap index (VHI), swallowing quality of life scale
(SWAL-QoL), new freezing of gait (FoG) questionnaire (NFoGQ)).
Demographic and clinical characteristics of subjects were also eval-
uated and analyzed for correlation with those axial symptoms.
Results: Total 45patients with PD (age 68.9 6 5.8 years, Hoehn
and Yahr(HY) stage 2.46 0.5) were evaluated. Freezing of gait was
present in 23 patients and severity of FoQ was correlated with
SWAL-QoL score.The severity of swallowing difficulty was well
correlated with VHI. The severity of Parkinsonism was well corre-
lated with the severity of FoG, swallowing and speech disturbance.
All these threeaxial symptoms contributed to poor quality of life.
Conclusions: The axial symptoms of PD were accompanied
together and the severity of those symptoms was correlated with each
other.These axial symptoms wereassociated with poor quality of life.
418
The role of catastrophizing and non-motor symptoms in quality
of life of Parkinsons disease patients
S.F. Lerman, G. Bronner, N. Warman-Alaluf, O.S. Cohen, G. Yaha-
lom, S. Hassin-Baer (Tel Hashomer, Israel)
Objective: To explore the effects of non-motor symptoms
(NMS), the personality trait self-criticism and the coping style of cat-
astrophizing and their interaction on Parkinsons disease (PD)
patients health-related quality of life (HRQoL).
Background: PD is characterized by both motor and NMS,
which are important in the diagnosis of PD and have a negative
impact on patients functioning and HRQoL. Personality and coping
styles are also known to influence individuals ability to cope with
chronic medical conditions.
Methods: 105 individuals diagnosed with PD participated in the
study and completed questionnaires on NMS (NMS-questionnaire;
NMSQ, depression; BDI, anxiety; STAI, sleep-disturbances; PDSS,
pain; SF-MPQ, VAS, cognitive function;MoCA), personality (self-
criticism;DEQ-6), coping (catastrophizing;PCS) and disease specific
HRQoL (PDQ-39). Demographic variables and PD severity (motor-
UPDRS) were collected from patients medical records.
Results: NMS were prevalent in patients in the study, with
almost half reporting significant anxiety, pain and sleep disturbances.
All of the NMS, personality and catastrophizing were significantly
correlated with reduced HRQoL. Catastrophizing significantly corre-
lated with depression, anxiety, pain, sleep-disturbances, gender
(women more than men) and younger age. Younger patients were
also significantly more depressed, had higher levels of pain and
lower HRQoL. In a multiple regression analysis predicting HRQoL,
significant predictors were pain (b=.25, p<.05), sleep disturbances
(b=.28, p<.01), self-criticism (b=.21, p<.05) and catastrophizing
(b=.29, p <.05) after controlling for all the other study variables. A
significant interaction was found between gender and catastrophizing
(Figure 1) in which men were more sensitive than women to the neg-
ative effects of catastrophizing on their HRQoL (b=-.32, p <.05).
[figure1]
Conclusions: This is the first study to measure self-criticism and
catastrophizing in PD patients and to find their negative impact on
Movement Disorders, Vol. 30, Suppl. 1, 2015
S164 POSTER SESSION

DM subjects show more non-motor symptoms and significantly worse

in individual non-motor symptoms compared with PD-nDM subjects,
such as drowsiness, depression and sexual function changes.

420
Prevalence of non-motor fluctuations in Parkinsons disease
R. Llorens-Arenas, M. Rodriguez-Violante, A. Cervantes-Arriaga, D.
Pi~
na-Fuentes, M.I. Lopez-Belmonte, P. Escobar-Martinez (Mexico
City, Mexico)
Objective: To characterize and determine the prevalence of non-
motor fluctuations in PD.
Background: Non-motor symptoms in PD have been widely
Fig. 1. (418). studied, but their behavior during on and off periods is still
unknown. Similar to motor fluctuations, it is believed that non-motor
symptoms may vary depending on these periods. To date very few
studies have addressed this issue.
NMS and HRQoL. Our findings emphasize the important role of Methods: Fifty PD consecutive patients were recruited between
these factors in adjustment to this complex medical condition and June 23th and August 1rst 2014 at the Movement Disorders Clinic of
the need to identify patients at risk for poor HRQoL and emotional the National Institute of Neurology and Neurosurgery in Mexico
distress, especially men and younger patients. Therapeutic interven- City. Demographic data was collected. The presence of non-motor
tions designed to target self-criticism and catastrophizing should be symptoms was determined with MDS-UPDRS Part IA, and the
implemented in this population and tested for their effectiveness. severity and frequency of these symptoms were assessed with the
NMSS. The Non-Motor Fluctuations Questionnaire of the Spanish
Society of Neurology was applied to determine the pattern of these
419 features. Bivariate analysis was performed to determine correlations
between non-motor fluctuations and quality of life (measured by
Clinical analysis of the non-motor symptoms of Parkinsons PDQ8), Kings PD Pain Scale, the presence of motor fluctuations
patients with diabetes and the pharmacological treatment.
Y. Liu, C. Liu, J. Zhang, M. Wang, S. Chen, C. Zhao (Jinan, Results: Table 1 shows the mean scores of non-motor
Peoples Republic of China) symptoms.
Objective: Aim of our study was to investigate the different man- Pearsons chi-squared test did not show an association between
ifestations of the NMSs between PD-DM patients and PD-nDM (PD non-motor fluctuations and PDQ8 score, but pain fluctuation corre-
-no DM) patients. We performed a historical cohort study. lated with the nocturnal pain item in the Kings PD Pain Scale
Background: The causes of Parkinsons disease (PD) are not (p 5 0.015). Bivariate analysis did not show a correlation between
well known and the association between PD and Diabetes Mellitus the presence of motor fluctuations and any of the non-motor fluctua-
(DM) is not well studied. It has been reported that diabetes can tions, nor did the use of levodopa, dopamine agonist, MAO-B inhibi-
aggravate the motor symptoms of Parkinsons disease, such as mus- tor, COMT inhibitor or LEDD.
cle rigidity and gait abnormalities. However few reports mentioned
the effects of diabetes on the non motor symptoms.
Methods: We enrolled 200 Parkinsons patients who visited the
neurology clinic at QiLu Hospital from February 2013 to January
2014, and selected 30 PD patients with diabetes history, then each of TABLE 1. Non-motor symptoms according to MDS-UPDRS
whom was paired with one patient without diabetes history by sex IA and NMSS
and years of disease duration. We collected the basic information of
the 60 patients, including name, sex, age, duration of disease, H-Y Non-motor MDS-UPDRS IA
staging and medical dosage. We assessed the non motor symptoms symptom Mean 6 SD NMSS 6 SD
of the 60 patients using the NMSS. The score of each item was the
product of the severity(from 0 to 3) and frequency(from 1 to 4). We Cognitive impairment 0.84 6 0.87 NA
also scored each individual NMS as being present or absent in Depression 0.96 6 1.18 3.76 6 4.89
order to analyze the prevalence of each NMS. Statistical analysis: Apathy 0.30 6 0.76 2.26 6 4.16
SPSS 17.0 for Windows, Wilcoxon signed rank test, Paired t-test, X2 Hallucinations 0.28 6 0.73 0.32 6 1.33
test (fishers exact test), Wilcoxon signed rank test was used. The Anxiety 1.00 6 1.18 3.74 6 4.62
level of statistical significance was set at p<0.05. The p value was Pain NA 4.34 6 5.09
bilateral. Excessive sweating NA 2.72 6 4.37
Results: There is no difference of average H-Y staging in PD- Fatigue NA 2.84 6 4.08
DM group and PD-nDM group. The number of the NMSs of each Dopamine disregulation 0.20 6 0.64 NA
subject in the two groups is of significance(p50.011). The frequency syndrome
of the NMSs in the PD-DM group is significantly higher than the Mean MDS-UPDRS IA score was 3.58 6 3.28, and mean NMSS
control group in the following aspects: sleepiness(p50.011), percep-
score was 58.29 6 54.73. The most severe non-motor symptom was
tual problems and hallucinations (p50.037), gastrointestinal tract
pain, followed by anxiety and depression. 52% of patients (n 5 26)
symptoms (p50.024). The scores of the NMSS are significantly
higher than the control group in the following aspects: sleepiness had at least one non-motor symptom with a fluctuating pattern. The
(p50.001), depression (p50.016) and sexual function (p50.011). most common fluctuating symptom was hallucinations (66.7%), fol-
Conclusions: Diabetes mellitus is independently associated with lowed by pain and paresthesias (44.4% each). Complete fluctuation
more non-motor symptoms in patients with Parkinsons disease. PD- pattern is described in Table 2.

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 POSTER SESSION S165

TABLE 2:. Prevalence of non-motor fluctuations Objective: We evaluated the efficacy and the safety of a pro-
longed release oral formulation of oxycodone hydrochloride com-
Total patients bined with naloxone hydrochloride dehydrate, in a fixed ratio of 2:1
Total with a (OXN PR).
Non-motor patients fluctuating Prevalence Background: Pain is one of the most relevant and underestimated
symptom (%)* pattern (%) of fluctuation % non-motor symptoms affecting the quality of life of patients with
Parkinsons disease (PD). Although some pain symptoms can be
Depression 23 (46) 8 (16) 34.8
effectively treated by dopaminergic medication, a correct diagnosis
Apathy 14 (28) 5 (10) 35.7
of the different types and distribution of pain in PD is challenging,
Hallucinations 3 (6) 2 (4) 66.7
and accordingly, its treatment remains troublesome.
Anxiety 18 (36) 4 (8) 22.2
Methods: A total of 16 PD patients with history of pain with a
Paresthesias 27 (54) 12 (24) 44.4
minimum intensity of 4 on Number Rating Scale (NRS) were
Pain 27 (54) 12 (24) 44.4
observed for a period of 8 weeks and received OXN PR 5mg/2.5mg
Excessive 16 (32) 7 (14) 43.8
twice daily. The primary efficacy measure was the pain severity
sweating
assessed with NRS and Brief Pain Inventory (BPI). Secondary effi-
Fatigue 28 (56) 12 (24) 42.9
cacy measures the safety profile by recording the occurrence of side
*Non-motor symptoms at either on or off effects, Clinical Global Impression of Change (CGI-C), Parkinsons
disease Sleep Scale 2 (PDSS-2), Bowel Function Index (BFI).
Results: Patients who completed the study (14 out of 16) reported
Conclusions: Non-motor fluctuations occur in about half of PD a significant pain relief as observed by the significant reduction of
patients, and are independent of motor fluctuations and pharmacolog- NRS score and BPI. No adjustment of dopaminergic therapy was
ical treatment. The most common non-motor symptoms with a fluc- required in these patients. No significant changes were observed in
tuating pattern are hallucinations, pain, and paresthesias. Further bowel function and constipation symptoms as measured by the BFI
studies are warrant to confirm these results. during the 8-week period. Similarly PDSS-2 score did not modify
during the observation period, whereas CGI-C score showed an
improvement.
Conclusions: OXN PR was efficacious for the management of
421 pain symptoms of patients with PD. More importantly, patients did
Fatigue and cardiac sympathetic denervation in Parkinsons not experience significant side effects, such as constipation or seda-
disease tion. Our study provides evidence that opioids can be used to treat
C.C. Luca, D. Spengler, F. Nahab, A. Serafini, M. Georgiou, C. pain symptoms in PD patients.
Singer (Miami, FL, USA)
Objective: To evaluate the relationship between fatigue and car- 423
diac sympathetic denervation in patients with Parkinsons disease. Odour identification testing is a quick and accurate diagnostic
Background: Fatigue represents one of the least understood non- tool for Parkinsons disease
motor manifestations of Parkinsons disease (PD). Decreased cardiac
metaiodobenzylguanidine (MIBG) uptake was reported in PD P. Mahlknecht, K. Seppi, B. Pinter, E. Reiter, C. M uller, A.
patients previously. Cardiac sympathetic denervation seen in many Djamshidian, M. Nocker, G.K. Wenning, F. Krismer, J. Willeit, S.
patients with PD, has been proposed as a possible mechanism in Kiechl, W. Poewe, G. Gobel (Innsbruck, Austria)
fatigue. Objective: To assess the diagnostic value of smell identification
Methods: We recruited 10 PD patients with PD that have com- testing in distinguishing Parkinsons disease (PD) both from healthy
plained of fatigue. Fatigue was assessed using Fatigue Severity controls (HC) and from conditions with potential for false positive
Score (FSS). Epworth Sleepiness Scale (ESS), Geriatric Depression PD diagnosis like multiple system atrophy (MSA), progressive supra-
Scale (GDS) and UPDRS were also administered. To quantify car- nuclear palsy (PSP) and essential tremor (ET).
diac sympathetic denervation patients underwent SPECT scan with Background: Hyposmia is present in 75-90% of PD patients and
123
I-MIBG and heart-to-mediastinal uptake (H/M) ratios were may antedate the onset of classical motor symptoms by years. How-
calculated. ever, data on the diagnostic value of quick, cheap and reliable tools
Results: 10 PD patients were enrolled and 8 completed the study. to detect hyposmia in PD are limited.
The mean age was 60 years (7 male, 3 female) with an average Methods: Consecutively recruited patients with PD (n5134;
UPDRS score of 25.8500 6 8.4526. The fatigue scores FSS score mean age 68.0 6 8.8 years, 37.3% females), MSA (n523; 63.3 6 8.9
was 3.8570 6 1.7915. The mean early H/M ratio was years, 52.2% females), PSP (n523; 67.2 6 6.2 years, 30.4%
1.3775 6 0.1576. Using a linear regression model, we did not find a females), and ET (n529; 74.5 6 9.8 years, 58.6% females) diagnosed
significant correlation between the FSS score and the early H/M ratio according to current clinical diagnostic criteria and 343 HC
(r2 5 0.2597, F-statistic: 2.105 p-value: 0.1971). (68.0 6 9.7 years, 53.2% females) underwent olfactory testing with
Conclusions: In our small sample we have not seen a correlation the Sniffin Sticks 16-items identification test (SS-16) consisting of
between fatigue and cardiac denervation. Fatigue is subjective and reusable pen-like odour dispensing devices. The whole SS-16 as well
difficult to quantify. Larger studies are needed to better describe the sub-scores (i.e. reduced sets of the best-discriminating odours) were
correlation between fatigue and cardiac sympathetic denervation. used. The diagnostic accuracy to differentiate PD from (a) HC and
Study was sponsored by GE Healthcare. from (b) its differential diagnoses (i.e. MSA, PSP and ET) was
assessed with receiver operating characteristic curve analyses and is
reported in areas under the curve (AUC).
422 Results: PD patients scored significantly lower on the SS-16
(6.8 6 3.1) compared to HC (12.8 6 2.7) and to MSA (11.7 6 2.1),
Efficacy and safety profile of prolonged release oxycodone in PSP (11.0 6 2.6), and ET (12.6 6 3.7) patients (all Bonferroni-
combination with naloxone (OXN PR) in Parkinsons disease corrected p-values <0.001). The AUCs of the entire SS-16 in dis-
patients with chronic pain criminating PD patients from HC and from its differential diagnoses
G. Madeo, T. Schirinzi, M. Pierantozzi, A. Stefani, S. Natoli, A. were 0.93 (95%CI, 0.900.95) and 0.90 (95%CI, 0.850.94), respec-
Pisani (Rome, Italy) tively. With sub-scores of the top-five discriminating odours, the

Movement Disorders, Vol. 30, Suppl. 1, 2015

S166 POSTER SESSION
AUCs were 0.89 (95%CI, 0.860.93) and 0.89 (95%CI, 0.850.93);
and of the top-three discriminating odours, the AUCs were 0.86
(95%CI, 0.820.90) and 0.84 (95%CI, 0.790.89). Repeating the
analyses with early-stage PD patients (<3 years disease duration)
only, the results remained largely unchanged.
Conclusions: Odour identification testing provides excellent diag-
nostic accuracy in the distinction of PD from HC and from its fre-
quent diagnostic mimickers. Reduced sets of odours could be used as
an easy and quick tool in the workup of patients presenting with Par-
kinsonism and might also serve for PD risk indication within the
elderly population.
424
Clinical features and varieties of non motor fluctuations in
Parkinsons disease
N. Mansurova, A. Prokhorova (Tashkent, Uzbekistan)
Objective: To investigate the clinical features and varieties of
non-motor fluctuations in Parkinsons disease.
Background: While levodopa remains the most effective drug for
the symptomatic treatment of PD, its chronic use is complicated by
the development of motor and non-motor fluctuations and
dyskinesias.
Methods: There are 322 patients with Parkinsons disease (PD).
171 of them have motor fluctuations (MF) and non-motor fluctua-
tions (NMF), whereas 151 have only motor fluctuation.We separated
patients into 3 categories: psychiatric, autonomy and sensory. Face
to face interviews and evaluations were performed for clinical infor-
mation. We used the following scales for the evaluation: wearing off
questionnares 19, UPDRS 3. Hoehn nd Yahr stage.
Results: According to gender distribution 176 paetients are
female (54%) and 146 are male (46%). Mean disease duration of PD
is 6.6 6 5,0 Years(1,0-46,0), Average age at assessment is 70.8 6 8.4
Years (38,0-89,3), by H&Y stage 2.6 6 0.9 (1-5), Age at onset of PD
draw up 64.2 6 10.1 Years (28,0-84,3). In PD patients were found
out that the incidence of dementia was 15%, the incidence of both
dementia and depression was 11% and the incidence of both demen-
tia and psychosis was 9% . Failure of particular ANS component
produces characteristic clinical manifestations: orthostatic intolerance
was 20%, thermoregulatory dysfunction was 34%, impairement of
gastric motility was 70% and bladder dysfunction was 57%. Noctur-
nal sleep disturbances was registered at 60%. Number of patients
with non-motor symptoms are 80%,non-motor-symptoms and motor
symptoms-79%, both motor fluctuation and non motor fluctuation-
40% and with only non motor fluctuations are 7%. Comparisons of
all variables between patients with only MF and those with both MF
and NMF showed that patients with both MF and NMF had more
severe motor symptoms, (assesed by H&Y stage, UPRDS part 3, and
the number of motor symptoms on the WO)Q 19, more NMS and a
higher Levodopa daily dose. There were no significant differences in
age, age at PD onset, and PD disease duration between two group.
49% patients with psychiatric symptoms, 45% with sensory and 32%
autonomic symptoms showed a fluctuation.
Conclusions: The frequency of NMS was 80% and for NMF
40%. Patients with NMF and MF exhibited more severe MS, more
NMS and higher levodopa daily dose. Patients with psychiatric and
sensory symptoms showed significantly higher fluctuation rates.
425
Changes in retinal morphology and visual field in early
Parkinsons disease
C.J. Mao, L. Ling Li, X.Y. Ji, J. Jing Wei, J. Jing Chen, S. Sha-Sha
Guo, Y. Yi Chen, S.J. Li, C.F. Liu (Suzhou, Peoples Republic of
China)
Objective: To investigated changes in retinal morphology and
visual field in early PD patients and control individuals.
Movement Disorders, Vol. 30, Suppl. 1, 2015
Background: Visual symptoms are common non-motor symp-
toms of idiopathic PD. However, the biological basis of visual
impairments in PD patients is not well understood.
Methods: Peripapillary retinal nerve fiber layer thickness, macu-
lar thickness and volume, and foveal thickness were measured using
optical coherence tomography, and mean deviation of visual field
was measured using an automatic visual field analyzer. PD patients
were in an ON period during ophthalmic evaluation, and their clin-
ical characteristics were evaluated using the Unified Parkinsons dis-
ease Rating Scale (UPDRS) and Hoehn & Yahr (H&Y) scale during
an OFF period.
Results: Compared with control individuals, PD patients showed a
decrease in retinal nerve fiber layer thickness on average and in spe-
cific regions (i.e., inferior and superior quadrants; 5-, 7-, 10- and 11-
oclock positions). Mean total macular thickness and volume was also
significantly decreased in PD patients compared with control individu-
als, but there was no difference between groups in foveal thickness.
Mean deviation of visual field scores were significantly lower in PD
patients than in control individuals. Average retinal nerve fiber layer
thickness was negatively correlated with PD duration and H&Y stage,
macular thickness and volume were negatively correlated with UPDRS
motor score and H&Y stage, and mean deviation of visual field score
was positively correlated with PD duration and H&Y stage.
Conclusions: Our results show that patients with early PD exhibit
retinal dysmorphology and visual field defect.
426
The clinical analysis of sleep disorders in patients with
Parkinsons disease and the study of them by polysomnogram
Z. Mao, S. Ji, Q. Yang, H. Ye, Z. Xue (Wuhan, Peoples Republic of
China)
Objective: Using polysomnography to analyze sleep characteris-
tics, to evaluate sleep quality and to study the characteristics of night
and daytime sleep disorder in patients with Parkinsons disease (PD),
exploring potential factors related to them .
Background: Sleep disorder is the most common non-motor
symptom in PD, seriously affecting the quality of life, but people
have little knowledge of this .
Methods: (1) Using UPDRS-III,Hoehn-Yahr (HY),Pittsburgh
Sleep Quality Index (PSQI),Epworth Sleepiness Scale(ESS), Hamil-
ton depression Scale (HAMD) and medication questionnaire to eval-
uate disease duration,severity,extent of depression,dopaminergic drug
usage,sleep states of 200 patients with PD, meanwhile the correlation
between sleep disorder and duration of disease, severity and drug
usage was analyzed.
(2)50 clinically diagnosed PD patients and 45 age- and sex-
matched control patients with no significant central nervous system
diseases were monitored by polysomnography, then the sleep structure,
process parameters, and abnormal sleep behaviors were compared.
Results: 1)144 in 200 of PD patients were of poor sleep, the inci-
dence was 72%. Of which 105 cases were difficulty in falling asleep
(52.5%), 99 cases had sleep fragmentation (49.5%), 45 cases had
excessive daytime sleepiness(EDS) (22.5%).
2)Multiple linear regression analysis showed PSQI total score was
correlated with UPDRS-III score, HY score, HAMA score, average
daily levodopa dose and age, but not with gender, duration of disease.
3)The PSG monitoring found, the prevalence of sleep fragmentation,
sleep rapid eye movement behavior disorder (RBD), EDS in PD group
were higher (P <0.05), but respiratory sleep disturbance index between
the two groups was no significant difference;Sleep efficiency, percentage
of N2, REM sleep in PD group were significantly lower than that in the
control group (P <0.05), while the awareness index in PD group was
significantly higher than that in the control group (P <0.05) .
Conclusions: PD patients have poor quality of sleep, complicated
by the high incidence of sleep disorder.Sleep disorder is needed to
be defined as one of the basic symptoms of PD to be clinically
recognized.
 POSTER SESSION
427
The contribution of the insula in Parkinsons disease: A
quantitative meta-analysis study
M. Marion, L. Christopher, P. Boulinguez, B. Ballanger, A.E. Lang,
S.S. Cho, A.P. Strafella (Toronto, ON, Canada)
Objective: To investigate the functional organization of the insu-
lar cortex and its role in Parkinsonian features, a quantitative meta-
analysis (MA) method (activation likelihood estimation, ALE) was
performed on neuroimaging studies.
Background: The insula region is known to be an integrating
hub interacting with multiple brain networks involved in cognitive,
affective, sensory and autonomic processes. There is growing evi-
dence that this region may have an important role in non-motor
symptoms in Parkinsons disease (PD). Until now, no studies have
directly investigated what is the contribution of the insula in PD.
Using a quantitative MA method, we assessed the functional organi-
zation of the insular cortex and its role in Parkinsonian features.
Methods: Total 102 insular foci were selected from 89 published
experiments comprising five functional categories; cognition (28
studies), affective and behavioral symptoms (17 studies), bodily
awareness and autonomic functions (7 studies), sensorimotor function
(20 studies) and anatomical or functional changes not specific to any
previous function (17 studies). We applied ALE technique, a quanti-
tativeMA method that highlights brain regions that are activated reli-
ably across studies, to calculate the topographic convergence of the
coordinates using Ginger ALE (http://brainmap.org/ale). The statisti-
cal significance was set at a family-wise error corrected threshold of
p50.05 with extended threshold of 10 voxels.
Results: The ALE-MA across all included published studies
revealed three clusters in the insula that showed main changes in
PD: right anterior insula (MNI: x 5 38, y 5 16, z 5 -2; ALE
Fig. 1. (427).
S167
value=0.049), left insula (-36, 18, -8; ALE value=0.034), and right
dorsal posterior insula (40, -16, 2; ALE value=0.024).
Specific changes in cognitive domain were found in the left and
right anterior insula (-34, 20, -8; ALE value=0.029; 38, 14, -4; ALE
value=0.025, respectively) and in the left posterior insula (-40, -10, 4;
ALE value=0.018). The left mid-insula, on the other hand, showed spe-
cific sensorimotor function changes (-42, 6, -8; ALE value=0.018).
[figure1]
Conclusions: The insula has been under-recognized as a key
region involved in the pathogenesis of PD features. In our MA, we
identified different insular sub-regions associated with PD clinical
features. These functional abnormalities can shed new light in under-
standing the impairment of non-motor function in PD.
428
Heart rate variability by passive leg raising test in patients with
Parkinsons disease and multiple system atrophy in early stages
V.A. Martnez Villota, J.D. Triana, W. William Fern andez Escobar
(Pasto, Colombia)
Objective: to determine the presence of autonomic disfunction,
by testing heart rate variabiityin patients with Parkinsons disease
and multiple system atrophy in rest and by passive legs raising test.
Background: the differential diagnosis between Parkinsons dis-
ease and multiple system atrophy is a challenge especially in early
stages. therefore, the presence of early autonomic disfunction may be
a differential diagnostic tool by a reliable and easily available instru-
ment. Previous studies have shown alterations in heart rate variability
in Parkinsons disease and multiple system atrophy but has not been
comparatively evaluated these two disease from early stages.
Methods: On the movements disorders unit of the Universidad
Nacional de Colombia, we studied the heart rate variability on rest
Movement Disorders, Vol. 30, Suppl. 1, 2015
S168 POSTER SESSION

for 5 minutes and passive legs raising test for 5 minutes, in 25 patients
with Parkinsons disease and 10 with multiple system atrophy, with less
than 5 years of evolution, that meet international diagnostic criteria. The
patients with cardiac disorders and medications that affect heart rate var-
ibaility, was excluyed. . The heart rate variability was recorded using a
Polar heart rate monitor RS 800, the data were transferred to the Polar
ProTrainer 5 Software and then, were analyzed in the Finnish Kubios
HRV 2.1 Software program. The results were analized by Wilcoxon-
Mann-Whitney and bootstrapping methods. [figure1]
Results: In rest, multiple system atrophy had a decrease in LFun,
and LF/HF, and increased HFun versus Parkinsons s disease, con-
sistent with decreased activity of the sympathetic nervous system
and parasympathetic predominance.

Hear rate variability in rest Fig. 1. (428).

MSA PD AMS vs PD. p

LF un 42,9 66,7 0,025 2013. The sample included subjects from the UF site of the NPF
HF un 57,12 33,3 0,025 Quality Improvement Initiative (NPF-QII) and the UF GAITRite
LF/HF 0,75 2,0 0,025 database. To investigate the association between the use of psycho-
tropic drugs and falling, a Student T- test was performed, and an
MSA multiple system atrophy, PD Parkinso
ns disease, LF un low ANOVA pairwise comparison was conducted to understand whether
frecuency normatized unit, HF un high freuency normatized falls were different across classes and combinations of psychotropic
unit, LF/HF ratio between Lf and HF, p valor Wilcoxon-Mann- drugs. The UF IRB approved this study.
Whitney Results: Six hundred and forty-seven subjects were included in
the final analysis [table 1], and 40.7% (258/647) had a positive his-
tory of falling in the previous year.
In multiple system atrophy with passive elevation of the lower
limbs test, we found a significant increase in LFms2 and LFun with
HFun decline and the corresponding increase in LF/HF, may be
Demographic, clinical characteristics, and treatment of study
related to alteration in the parasympathetic response.
population.
On psychotropics No-psychotropics
Analysis for difference: rest- passive legs raising (n5433) (n5214) P
LFun p HFun p LF/HF p Male, n (%) 296 (68.4) 144 (67.3) .78
Age, y 68.5 (SD 10.4) 68.6 (SD 10.3) .92
MSA -5,70 0,0017 5,70 0,0015 -0,23 0,0015 Disease duration, y 11.1 (SD 6.1) 9.3 (SD 5.9) <0.001
PD 4,7 0,2 -1,7 0,42 0,42 0,4 UPDRS III on meds 29.8 (SD 12.4) 25.7 (SD 10.1) <0.001
Hoen & Yahr 2.6 (SD 0.9) 2.4 (0.7) <0.001
MSA multiple system atrophy, PD Parkinso ns disease, LFun Low
Levodopa, n (%) 414 (95.6) 184 (86) <0.001
frecuency normatized unit, HF high frecuency normatized unit,
Fall history, no. (%) 208 (48) 55 (25.8) <0.001
LF/HF ratio, p valor by bootstrap of median of valors.

Conclusions: The abnormality found in heart rate variability in

multiple system atrophy confirms sympathetic and parasympathetic
autonomic dysfunction, from early stages at rest and was able to dif-
ferentiate it of Parkinsons disease and controls. the test of passive
elevation of the lower limbs showed to be useful for the evaluation
of cardiovascular dysfunction in testing heart rate variability, but fur-
ther studies are required for their standardization.
429
Combining antipsychotics and antidepressants increase falls in
Parkinsons disease
D. Martinez-Ramirez, J.C. Giugni, L. Almeida, B. Ahmed, V. Rundle-
Gonzalez, A.R. Bona, E. Monari, C.J. Hass, M.S. Okun (Gainesville,
FL, USA)
Objective: To determine the association between psychotropic
drugs and falls in PD patients.
Background: Parkinsons disease (PD) patients have a 60% risk
of falls and these falls may lead to serious complications. Falls are a
major reason for hospitalization, they impact health-related quality of
life, and result in important social and economical consequences for
patient and families.
Methods: A retrospective, cohort, and descriptive multiple-source
study was conducted during the period of January 2013 to November
The most common psychotropics used were antidepressants
(22%), benzodiazepines (17%), and the combination of these two
drugs (16%). Subjects with the highest fall rate were those on, 1.
antidepressants with antipsychotics (2.4 6.4), 2. only antipsychotics
(1.7 6.3), 3. antidepressants with cognitive enhancers and benzodia-
zepines (1.5 6.2), 4. antipsychotics with cognitive enhancers and
benzodiazepines (1.5 6.8), and 5. antipsychotics with benzodiaze-
pines (1.5 6.6), as shown in figure 1.[figure1]
Conclusions: Psychotropic drugs increase the rate of falling in
advanced PD patients. It is important to strictly implement fall pre-
vention measures and to provide rehabilitation services in this group
of high risk subjects. Future studies will be necessary to uncover the
mechanisms underlying the detrimental effects of these drugs.
430
Fatigue is associated with performance on a demanding finger
motor task in Parkinsons disease
D. Martino, T. Tamburini, P. Zis, E. Pelosin, A. Sauerbier, G.
Abbruzzese, K. Ray-Chaudhuri, L. Avanzino (London, United
Kingdom)
Objective: To compare Parkinsons disease (PD) patients with
and without fatigue (PD1F, PD-F) on a demanding finger motor

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
Fig. 1. (429).
task (DMFT) designed to capture the dual (cognitive-motor) nature
of central fatigue.1,2
Background: Central fatigue occurs in 33%-58% of PD patients,
contributing substantially to quality of life impairment. The depend-
ency of fatigue in PD on central mechanisms is suggested by motor
cortex excitability and functional imaging studies. However, investi-
gation of attention-demanding repetitive motor tasks in this condition
is limited.
Methods: Forty-two right-handed non-demented patients with
PD were consecutively enrolled, divided into 21 PD1F and 21
PD-F (screened using the Parkinsons Fatigue Scale-16 scale, and
age- and gender-matched). Wearing a sensor-engineered glove
(Glove Analyzer System) on their dominant hand, patients per-
formed sequential opposition digital movements following an
acoustic cue paced at 2 Hz for 5 min (5min-SEQ), and for an
additional minute (1min-SEQ) following a 2-minute rest period.
Kinematic measures on the DMFT (movement time, contact time,
movement rate, and percentage of correct sequences) and clinical
scores of bradykinesia, depression and sleep impairment were
obtained in all participants.
Results: PD1F patients showed significantly increased move-
ment time (expressed as inter-tapping interval) and decreased
movement rate at MIN3 (p50.001 for both time and rate) and
MIN5 of the 5min-SEQ (p50.003 and p50.04, respectively) with
full recovery after the 1min-SEQ; PD-F patients maintained stable
movement time and rate throughout all the sequences. Deteriora-
tion and recovery indices of movement time differed significantly
between the two groups. PD1F patients performed also a lower
number of correct sequences than PD-F stably throughout the
whole DMFT. Bradykinesia, depression and sleep disruption
scores did not correlate significantly with any of the DMFT
measures.
Conclusions: Performance on a repetitive motor task requiring
sustained attention differs significantly between PD patients with and
without fatigue. This task could be explored as behavioural measure
of central fatigue in PD in future research.
References:
1 Avanzino L et al., Neuroscience. 2011 Feb 3;174:84-90. 2Bon-
zano L et al., Neuroimage. 2013 Jan 15;65:257-66.
S169
431
Elevated salivary DJ-1 in Parkinsons disease is associated with
altered salivary secretion
J.M. Masters, A.J. Noyce, G. Giovannoni, T.T. Warner, G.B. Proctor
(Herts, United Kingdom)
Objective: To investigate the composition of saliva in patients
with Parkinsons disease (PD) and understand more about how auto-
nomic dysfunction affects salivary secretion.
Background: Previous studies have shown changes in the compo-
sition and secretion of saliva in patients with PD, including an
increase in salivary DJ-1 concentration. Symptoms such as sialor-
rhoea, dry mouth and increased viscosity of saliva point towards
altered saliva gland function. Autonomic dysfunction is a known fea-
ture of PD and could contribute to abnormal saliva composition and
secretion.
Methods: In this pilot study, characterisation of unstimulated
whole mouth saliva collected from 16 patients with PD and 22 age-
matched controls was performed. Salivary DJ-1 concentrations were
measured with quantitative immunoblotting; total protein concentra-
tion with a BCA assay; amylase with an amylase activity assay; and
mucin concentrations with periodic-acid Schiff stained SDS gels.
Results: Salivary flow rate was not significantly different between
patients and controls. Patient saliva showed increases in DJ-1 con-
centration (0.97 vs 0.57 mg/ml, p50.005), and total protein concen-
tration (10.1 vs 5.2 mg/ml, p 5 0.003) but differences in salivary DJ-
1 became non-significant after adjusting for total protein concentra-
tion. In patients, adjusted DJ-1 levels correlated with disease severity
measured with the Unified Parkinsons disease Rating Scale
(p 5 0.02). Concentrations of amylase, but not mucins, were elevated
in the saliva of patients (0.127 vs 0.061 units/ml, p <0.001), and
correlated positively with both total protein (p <0.001) and DJ-1
concentration (p 5 0.013); suggesting that the major salivary glands
are the source of additional DJ-1 and protein in patient saliva.
Conclusions: This preliminary study suggests that the saliva of
patients with PD is different in composition to that of healthy age-
matched controls, which supports the notion that saliva may be a
good candidate for biomarker discovery in PD. Furthermore, altered
Movement Disorders, Vol. 30, Suppl. 1, 2015
S170 POSTER SESSION
protein secretion may be a manifestation of autonomic dysfunction
in PD.
432
The effect of sleep and wakefulness disorders on cognitive
function in Parkinsons disease
R.J. Matmurodov, O.E.U. Turgunkhujaev, K.M. Khalimova, U.S.
Ergashev (Tashkent, Uzbekistan)
Objective: To clarify clinical features of sleep disorders in
patients with Parkinsons disease (PD) and their effect on cognitive
function and emotional-personal sphere.
Background: Cognitive disorders in PD depands not only on
motor symptomps, but also on sleep disorders.
Methods: The study involved 62 patients with PD (33 men and
29 women) mean age 47.8 1 7.1 years. The control group consisted
of 20 patients without Parkinsonism matching by age and sex. The
diagnosis of PD was established by criteria A.Hughes. Patients
underwent an extended neuropsychological study with qualitative
and quantitative analysis. To determine cognitive disorders, we used
neuropsychological tests.
Results: 49 patients (79,3%) had sleep disorders. In the structure
of sleep disorders: 29 (59.2%) patients had insomnia and 11 (22.4%)
patients - parasomnia and 9 (18.4%) - hypersomnia. In a control
group, numbers were 4.5 times less. The analysis showed that the
structure of sleep disorders correlates with the form of PD. So,
insomnia is more rapidly met in akinetic-rigid form (55.5%), whereas
hypersomnia is presented in mixed form. Patients with insomnia
present 35% of predement cognitive impairment and 34% of demen-
tia (66.7% of mild degree dementia and 33.3% moderate dementia
severity). Whereas, in patients with hypersomnia 35% of predement
cognitive impairment, 60% of dementia (54.6% and 45.4%) were
observed. Among patients with permanent drowsiness 32.4% of pre-
dement cognitive impairment and 58.4% of dementia (44.8% and
55.2%) were diagnosed. Dementia (65.4%) was observed more in
patients with sudden sleep (42,8% and 57.2%).
Conclusions: sleep and wakefulness disorders depend not only on
the severity of motor symptoms, but also depend on the emotional
and cognitive state.
433
Quality of life in PD correlates with arising from chair, gait and
postural stability
A. Mentreddi, N. Patel, I. Bernstein, K. Pravin, S.M. McClintock,
C.M. Cullum, M.M. Husain, R.B. Dewey (Dallas, TX, USA)
Fig. 1. (434).
Movement Disorders, Vol. 30, Suppl. 1, 2015
Objective: To define the minimum number of items from the
UPDRS motor score which best correlates with quality of life in PD.
Background: There is existing literature linking axial subscores
of the UPDRS part III to quality of life, but it is unknown which
published subscore, or if some other set of motor items, performs
best for this purpose. This is important, because clinicians should
carefully monitor and direct treatments toward those disease features
that are most relevant to quality of life. We used UPDRS (version 3)
motor scores and Parkinsons disease Questionnaire (PDQ-39) data
obtained in a cohort of non-demented PD subjects to address this
question.
Methods: Four axial subscores were evaluated using Pearson
correlation coefficients with PDQ-39 index score and mobility
domain score: Vassar axial subscore (sum of speech (a), facial
expression (b), arising from chair (c), posture (d), gait (e), postural
instability (f), and body bradykinesia (g)), Schrag subscore (items
c1d1e1f only), a1b only, and c1d1e1f1g only. We also
included a tremor subscore (calculated by summing tremor scores
from each body part) in our analysis. We then ran correlations of
the individual items a-g with the PDQ-39 mobility score, ranked
them in descending order of correlation, and serially created sum
scores by dropping the least correlated item until a sum score with
a minimal number of items was identified which correlated with the
PDQ-39 mobility subscore.
Results: 124 PD subjects (mean age=65, mean UPDRS motor
score=14.8) were evaluated. The correlation coefficients (r) of each
subscore with PDQ-39 index and mobility score were: Vassar 0.55
and 0.67, Schrag 0.52 and 0.68, a1b 0.41 and 0.38, and
c1d1e1f1g 0.52 and 0.68 respectively. All four correlated signifi-
cantly with p<0.0001 with both the index and mobility score of the
PDQ-39. The tremor subscore was not correlated with quality of life.
By dropping the least correlated individual items we identified a sub-
score consisting only of c1e1f with r=0.71, p<0.0001 in relation to
the PDQ-39 mobility score.
Conclusions: Our study shows that subject performance on aris-
ing from chair, gait and postural stability are together (when
summed) closely correlated with quality of life in PD. These items,
at a minimum, should be carefully evaluated at patient visits and
treatments directed at improving performance in these critical areas.
434
Inner retinal layer thickness of the fovea depends on
dopaminergic medications in Parkinsons disease
S. Miri, S. Glazman, Y. Ding, S. Slotnick, E.M. Shrier, A. Joh, I.
Bodis-Wollner (Brooklyn, NY, USA)
 POSTER SESSION S171

Objective: To evaluate the relationship between dopaminergic

medications and inner retinal layer (IRL) thickness in Parkinsons
disease (PD) patients.
Background: IRL in the fovea is thinned in patients with PD.
Methods: In this retrospective, multicenter, cross-sectional study,
the data of 104 PD subjects (191 eyes) were reviewed. All patients
had full neurological and ophthalmological examinations and macu-
lar OCT scans. Subjects were classified according to their medication
history into four groups: 52 subjects (50%) were on levodopa; 14
subjects (13.5%) were on DA agonists; 22 subjects (21.2%) were on
combination therapy of levodopa and DA agonists; and 16 subjects
(15.4%) were on adjunct therapy (Amantadine/Selegiline) or were
untreated. IRL thickness was compared between these groups. Sec-
ondary study variables include age, ethnicity, gender, disease dura-
tion and stage (Hoehn and Yahr score), Unified Parkinsons disease
Rating Scale (UPDRS) motor score. Statistical analysis was per-
formed using SPSS 21.0 (Chicago, IL). P values P<0.05 were con-
sidered statistically significant.
Results: There was no significant difference between the three
treatment groups in terms of age (mean 67.2 6 8.3 years), gender,
ethnicity, PD duration (mean 5.6 6 4.4 years), stage (mean
2.4 6 0.4), and UPDRS motor score (mean 28.0 6 6.0). IRL thick-
ness measures was not different among the 3 treatment groups
(ANOVA, P0.05). Comparison of the Levodopa and the DA agonist
groups revealed a significantly thicker retina in the Levodopa group Fig. 1. (435).
at 0.5 0.75 mm from the foveola in the superior quadrant.
Although the Adjunct/untreated group had earlier stages of the dis-
ease (1.8 6 0.3, P=0.0001) with lower UPDRS score (20.5 6 5.5,
P=0.0001) and shorter disease duration (1.4 6 1.1 years, P=0.0001), to 3.3 6 0.8, p<0.01). However, the number of patients whose
they had a significantly thinner retina at radial distances of 0.25- SHAPS-J score was improved below cutoff level was only one. No
1 mm from the foveola. [figure1] serious adverse effect was not observed in all patients. [figure1]
Conclusions: There is a difference in thickness between levodopa Conclusions: This results suggest istradefylline may ameliorate
and dopamine agonists treated patients. This difference is evident at anhedonia in patients with PD without serious adverse effect. Further
the distance of 0.5 and 0.75 mm from the foveola. Untreated patients study is needed to confirm this effect in the future.
had thinner retina at radial distances of 0.25-1 mm from the foveola,
where dopaminergic amacrines are located in the human foveal
region. 436
Pattern of non motor symptoms (NMS) among subtypes of
Parkinsons disease in Arab ancestry
435
S. Nahrir, M.N. AlMotiri, Z.G. AlJohani, G.A. Alhifthi, T.M. Alayan,
The effect of istradefylline for anhedonia in Parkinsons disease J.A. Bajwa (Riyadh, Saudi Arabia)
H. Nagayama, M. Mishina, K. Kimura (Bunkyo-Ku, Japan)
Objective: To describe Non Motor Symptoms (NMS) in Tremor
Objective: In this study, we examined the effectiveness of istra- Dominant (TD) and Akinetic Rigid (AR) subtypes of Parkinsons
defylline, that is only clinically available adenosine A2A receptor disease (PD) before and after diagnosis in Arabs.
antagonist, for anhedonia in Parkinsons disease (PD) patients Background: Parkinsons disease is the 2nd most common neuro-
detected by Japanese version of Snaith-Hamilton pleasure scale degenerative disorder that involves loss of not only dopaminergic but
(SHAPS-J). also non dopaminergic neurotransmitters. Patients develop various
Background: Recently, a lot of symptoms other than motor non motor symptoms prior to or alongside development of the cardi-
symptoms are indicated in PD, and these symptoms are called as nal motor symptoms of PD. As patients do not attribute NMS as rel-
non-motor symptoms (NMS). Depression is one of these NMSs. The evant as motor symptoms of PD, they commonly fail to report.
main condition of depression found in PD is inability to experience There is little known about NMS among PD cohort of Arab
pleasure or lack of motivation, and these are correspond to the terms ethnicity.
of anhedonia or apathy. The depression in PD is known to respond Methods: This was an observational cross sectional study on reg-
to not only the treatment of PD itself, but also pramipexle and selec- istered patients in Movement Disorders database at King Fahad Med-
tive serotonin reuptake inhibitor. However, in the experimental ical City, Riyadh, Saudi Arabia. Demographics and historical data
model, it was suggested that the adenosine A2A receptor antagonist were obtained from chart review, clinic visit assessment, while NMS
was effective to depression in PD, and its effectiveness was equally were evaluated through telephone interview using NM Questionnaire
to tricyclic antidepressants. (NMSQuest). Study was approved by IRB. Statistical Analysis was
Methods: We enrolled 6 PD patients with anhedonia. Anhedonia made through SPSS version 22.
was detected by SHAPS-J, and 3 points or more is considered as Results: 112 diagnosed PD patients were reviewed,73 (65%)
anhedonia. The mean of age (6 SD) was 65.9 6 16.0 years old, were TD, and 39 (34.8%) were AR. NMSQuest was responded by
mean modified Hoehn-Yahr stage was 2.7 6 0.8, mean disease dura- 51 (TD-27 (52%) and AR-24 (47%). In the sub-analysis of the
tion was 7.7 6 1.5 years and male/female prevalence was 2/4. In respondent group, the mean total pre-diagnosis NMSQuest score was
these patients, istradefylline (NouriastVR ) 20mg was administrated 2 for TD, 1.3 for AR, post-diagnosis 6.8 for TD, 9.3 for AR. The
once a day for 4 weeks, then we checked SHAPS-J again, and eval- symptoms commonly reported at pre-diagnosis were Depression(AR-
uated the effectiveness. 16%,TD-11%); Anxiety(AR-11%,TD-8.3%); Dementia (AR-
Results: SHAPS-J score significantly reduced after administration 12.5%,TD-11%); Insomnia(TD-22%,AR-8.3%), symptoms reported
of istradefylline in comparison with before administrating (5.2 6 0.7 at post-diagnosis were Depression(AR-41%,TD-33%); Hallucination

Movement Disorders, Vol. 30, Suppl. 1, 2015

S172 POSTER SESSION
(AR-37%,TD-3%); RLS(AR-33%,TD-26%); Insomnia(AR-37%,TD-
40%); Vivid Dream(AR-41%,TD-11%); Constipation(AR-62%,TD-
66%); Fatigue (AR-45%,TD-22%).
Among the total 112 patients, there was no statistical significance
between the subtypes pre clinical NMS. However, there were signifi-
cant differences in some of the NMS variables in post diagnosis phase
i.e. AR group had statistically significant higher Apathy(p- 0.036);
Anhedonia (p-0.03); Hallucination(p-0.001); Dementia(p-0.001); Con-
fusion(p-0.036); Vivid Dream(p-0.001); and Nocturia(p-0.005).
Conclusions: AR group appears to have significant higher trend
for NMS than TD patients post diagnosis. There is considerable lack
of PD education in the Arab world perhaps making reporting further
challenging. Lack of NMS recognition in pre-clinical phase needs
further research given our respondent sample size was limited.
437
Parkinsons disease duration: Non motor symptoms: Arab
ancestry The new dimension
S. Nahrir, Z.G. AlJohani, G.A. Alhifthi, M.N. AlMotiri, T.M. Alayan,
J.A. Bajwa (Riyadh, Saudi Arabia)
Objective: To determine correlation between duration of Parkin-
sons disease (PD) and development of Non Motor Symptoms
(NMS) in Arab ancestry.
Background: NMS are thought to result from extra-nigral pathol-
ogy predominantly, serotonergic and nor-adrenergic. Its manifesta-
tions vary with the progression of the disease leading to significant
morbidity. Pattern of NMS through the course PD among patients of
Arab origin is not yet known.
Methods: This was an observational cross-sectional study con-
ducted on PD patients enrolled in the Movement Disorders registry
at King Fahad Medical City, Riyadh Saudi Arabia. Chart review was
used to retrieve demographics, but NMS Questionnaire was utilized
through telephone conversation in obtaining NMS data. The study
was approved by IRB. The Statistical analysis was done on SPSS
version 22.
Results: A Total of 112 diagnosed PD patients were identified.
Disease duration was as follows: < 5 y (n 5 58); 5 10 y (n 5 32);
>10 y (n 5 14). Gender distribution: <5 y (M-38 (65.5%), F-20
(34.5%); 5-10 y (M 21 (65.6%), F-11 (34.4%); >10 y(M-21
(71.4%),F-4 (28.6%). NMSQuest was responded by only 51 patients.
The mean total NMS increased remarkably from first 5 y to next 5 y
of disease (6.1 to 10.72) but stabilized at >10 y duration to a value
of 10.75. Post diagnosis NMS showed statistically significant correla-
tion only for apathy (P-0.045) at >10 y and dysphagia (P-0.031) at
5-10 y. Non statistically significant but higher trend of symptoms
with increasing duration of disease was seen in depression, hallucina-
tion, RLS, RBD, vivid dreams, sleep breathing disorder, nocturia/fre-
quency, siallorrhea, and constipation.
Conclusions: Duration of disease has influence on the occurrence
of NMS in this Arab cohort. Lack of significant NMS reporting
at > 10 y could be related to overwhelming clinical effect of motor
symptoms in advanced PD. Further studies are required to determine
the correlation of PD duration and NMS symptoms to better under-
stand PD progression and address treatment through appropriate
guidelines tailored to meet needs of this unique cohort.
438
Early onset Parkinsons disease vs. late onset Parkinsons disease
Is there any difference in non motor symptoms among Arab
ancestry?
S. Nahrir, G.A. Alhifthi, M.N. AlMotiri, Z.G. AlJohani, T.M. Alayan,
J.A. Bajwa (Riyadh, Saudi Arabia)
Objective: To illustrate the heterogeneity in presentation of Non
Motor Symptoms(NMS) in early onset Parkinsons disease(EOPD)
and late onset Parkinsons disease(LOPD) among Arabs.
Movement Disorders, Vol. 30, Suppl. 1, 2015
Background: Arabs are distinct through their genetic make-up,
traditional practices of consanguinity, habitual well water drinking
and geographic location. A recent single center study identified
greater prevalence of EOPD among Arabs. NMS have also been
reported to vary between people of different ethnicity yet the pattern
of NMS among Arabs with early and late onset PD is unknown.
Methods: This is a single center cross-sectional observational
study performed on PD patients registered in the Movement Disorder
database of King Fahad Medical City, Riyadh, Saudi Arabia. Demo-
graphics and clinical data were obtained from chart review and clinic
assessment. EOPD was defined by age of onset at or before 50y.
NMS data were obtained through telephone interview with the
patient using NMS Questionnaire(NMSQuest).
Results: 112 diagnosed PD patients were included. EOPD:
34(30.4%) M 22(64%), F-12(35%), LOPD: 70(62%)- M 47(67%)
F 23(32%). There was statistically significant higher frequency of
NMS among LOPD at pre diagnosis for depression (P-0.035);
dementia(P-0.03); restless leg syndrome (P-0.016); insomnia(P-0.03);
and constipation(P-0.001) but none at post diagnosis. NMSQuest was
reported by only 51 patients. On subgroup analysis of the responders,
we found mean total NMS for EOPD at pre diagnosis 1.5, post diag-
nosis 8.3; for LOPD pre diagnosis 1.7; post diagnosis 7.5. However,
non-statistically significant higher trend of NMS was observed in
EOPD pre-diagnosis group for anxiety(20% vs 5.8%), dry eye
(13%vs2.9%); dysphagia (13%vs 5.8%), post-diagnosis group for apa-
thy (26%vs8.8%); illusion (13%vs2.9%); vivid dream (33%vs17%);
sleep breathing disorder (13%vs2.9%); fatigue (46%vs29%), whereas,
for LOPD at pre-diagnosis for urgency of micturition (14%vs0%);
and sialorrhoea (5.8%vs0%), and at post-diagnosis for anxiety
(23%vs6.6%); confusion (17%vs6.6%); delirium (11%vs0%); and
choking (23%vs13%).
Conclusions: EOPD and LOPD patients of Arab ethnicity appear
to have diverse NMS presentation. This paradigm of NMS presenta-
tion could be related to underlying disease specific differences influ-
enced by genetics and environment. Research into EOPD associated
risk factors and disease course will enable us to understand better.
439
Does impaired peripheral vasoconstrictor response predict
orthostatic hypotension in Parkinsons disease?
T. Nakamura, M. Suzuki, A. Okada, J. Suzuki, M. Hirayama, G.
Sobue (Nagoya City, Japan)
Objective: To predict the onset of orthostatic hypotension, we
investigated the clinical characteristics of Parkinsons disease (PD)
patients without orthostatic hypotension who showed an impaired
peripheral vasoconstrictor response during orthostatic stress.
Background: Impaired peripheral vasoconstrictor response during
orthostatic stress is considered a cardinal component of orthostatic
hypotension in patients with PD. Moreover, an impaired peripheral
vasoconstrictor response during orthostatic stress can be an important
predictive factor for future orthostatic hypotension in patients with-
out orthostatic hypotension.
Methods: We retrospectively evaluated 66 PD patients (age:
66.3 6 7.7 y, disease duration: 5.8 6 4.8 y) who showed no ortho-
static hypotension in a head-up tilt test. To avoid the influence of the
cardiac response to blood pressure during orthostatic stress, we eval-
uated patients with a heart-to-mediastinum ratio of less than 1.7 on
cardiac 123I-meta-iodobenzylguanidine delayed scintigraphic image.
Using impedance cardiography, we measured the total peripheral
resistance, heart rate, and systolic blood pressure during head-up tilt
testing. Impaired peripheral vasoconstriction was defined as a lower
total peripheral resistance at the fifth minute in the 60 position than
that in the 0 position.
Results: Twenty-seven patients (41%) showed an impaired
vasoconstrictor response. The decrease in systolic blood pressure
was greater inn this group than in the vasoconstrictor group
(-5.7 6 7.6mmHg vs. 0.9 6 10.8mmHg, p <0.01). Age, disease
 POSTER SESSION
duration, Hoehn-Yahr stage, the coefficient variance of R-R intervals,
and the baseline norepinephrine concentration as well as its change
during the head-up tilt did not differ between the groups. However,
systolic blood pressure changes during the norepinephrine infusion
test and phase II and IV of the Valsalva maneuver test were greater in
the impaired vasoconstrictor group than in the vasoconstrictor group.
Conclusions: We showed that a high prevalence of impaired
vasoconstrictor response occurs even in PD patients without ortho-
static hypotension. These patients showed an abnormal response on
vascular sympathetic autonomic tests, indicating that they are likely
to develop orthostatic hypotension and require further careful
observation.
440
Olfactory dysfunction in Parkinsons disease could be associated
with central cholinergic system
E. Oh, J.G. Lim, J. Park, J. Youn, J.S. Kim, W. Jang (Daejeon,
Korea)
Objective: To evaluate the association between olfaction and
central cholinergic system in Parkinsons disease, we investigated
central cholinergic dysfunction via the short latency afferent inhibi-
tion (SAI) with transcranial magnetic stimulation (TMS) associated
with severity of olfactory dysfunction.
Background: Although a relation between early PD and olfactory
dysfunction is well recognized, the mechanism of olfactory dysfunc-
tion remained unclear. Some studies showed that cholinergic deficit
could be associated with olfactory dysfunction. Therefore, we eval-
uated SAI to determine an association between olfactory dysfunction
and cholinergic system in early PD patients.
Methods: Total 56 PD patients and 14 controls were enrolled.
Olfaction was evaluated by the Korean version of the Sniffin stick
(KVSS) test. The subgroups in accordance with the TDI (the sum of
olfactory threshold score, odor discrimination score, odor identifica-
tion score) scores were divided by 15-30 for hyposmia, and 15 in
anosmia. Cognition test was used to Korean version of mini-mental
state examination (K-MMSE). TMS of the motor cortex correspond-
ing to hand was used to get a motor evoked potential (MEP) and
SAI. SAI was checked at medication on state and measured at hand
without tremor. The protocol of SAI was based on the methods of
Tokimura et al.
Results: There were no differences in age, disease duration, Uni-
fied Parkinsons disease Rating Scale (UPDRS) Part 3, Hoeh and
Yahr stage, Levodopa Equivalent Daily Dose and K-MMSE score
between the PD with hyposmia and anosmia group. But significant
difference were shown in odor threshold (p< 0.01), odor discrimina-
tion (p< 0.01), odor identification (p< 0.01) and TDI score (p<
0.01) between the two groups. The TMS parameters which continu-
ously measured with time, SAI (%):N20, N20 1 2ms, N20 1 4ms,
were showed definite difference in PD with hyposmia, PD with anos-
mia and control groups (p< 0.01). And except odor threshold score
(r=-0.28), odor discrimination (r=-0.50), odor identification (r=-0.57)
and TDI score (r=-0.61) showed a moderate negative correlation
with SAI (%) N20 1 2ms.
Conclusions: We observed that olfactory dysfunction was highly
correlated with SAI which reflect central cholinergic function in PD
patient. Considering that olfactory dysfunction could be predictors
for cognitive deterioration in PD patients, SAI might also be early
marker of cognitive dysfunction in PD patients.
441
Opicapone and non-motor symptoms in Parkinsons disease:
Results from a double-blind, randomized, placebo-controlled
study and open-label extension
C. Oliveira, A. Lees, J. Ferreira, N. Lopes, R. Costa, R. Pinto, T.
Nunes, J.F. Rocha, P. Soares-da-Silva (S. Mamede do Coronado,
Portugal)
S173
Objective: Evaluate the effect of opicapone (OPC) in non-motor
symptoms of Parkinsons disease (PD) in patients who enrolled the
BIPARK-II study.
Background: OPC, a novel once-daily peripheral COMT inhibi-
tor, has shown to be effective in reducing OFF-time in PD patients
with motor fluctuations when added to levodopa.
Methods: Multinational, multicentre, 14 to 15-week double-blind
(DB), placebo-controlled study evaluating 2 OPC doses (25mg or
50mg), followed by a 1-year open-label (OL) extension where all
patients received OPC. Subjects started OL extension with 25mg-
OPC irrespective of prior DB treatment. One week after, either OPC
(25mg or 50mg), levodopa or anti-PD drugs could be adjusted based
on individual response. The non-motor symptoms were assessed by
the Non-Motor Symptoms Scale (NMSS) at different time points,
including baseline, end of DB and end of OL. Statistical analysis at
DB endpoint were based on an ANCOVA model.
Results: At baseline the mean NMSS scores ranged between 36.7
for 50mg-OPC and 38.2 for 25mg-OPC and placebo. At the end of
the DB period, the NMSS total score slightly improved across OPC
and placebo groups, with no significant differences between them (-
2.02, -4.9 and -5.2 for 25mg-OPC, 50mg-OPC and placebo, respec-
tively). Numerical differences in favor of OPC were seen for the
sleep/fatigue domain. At the OL 1-year endpoint a mean improve-
ment of -4.2 in NMSS total score was still observed. No deteriora-
tion of any particular domain was observed.
Conclusions: OPC added to levodopa-based regimens was associ-
ated with minimal but generally positive effects on non-motor symp-
toms of PD. Importantly there was no worsening of dysautonomia,
hallucinations or cognitive dysfunction.
442
Heart rate variability during sleep stages to assess autonomic
function in patients with Parkinsons disease: A preliminary
polysomnographic study
D.B. Oropeza-Canto, M. Vel azquez-Vaquero, R. Flores-Morales, A.
Espinosa-Ceron (Puebla, Mexico)
Objective: To assess the association between Parkinsons disease
(PD) and the responses of cardiac autonomic control during sleep
stages through the measures of heart rate variability (HRV) using the
nocturnal polysomnography, and to investigate the relationship
between frequency-domain measures and clinical characteristics of
patients with PD.
Background: Cardiac physiology and autonomic dysfunction dur-
ing sleep in PD remains poorly explored, especially through the dif-
ferent stages of sleep. Frequency-domain and time-domain analysis
of HRV are an effective tool for studying heart rate changes during
these sleep stages. The understanding of the physiological conditions
that are modified during Parkinsons disease progression allows to
ultimately explain its mechanisms, and strategies design to treat
alterations and various pathological conditions in humans.
Methods: Eleven patients with a diagnosis of Parkinsons disease
were compared with ten healthy persons (Control Group).
Frequency-domain and time domain measures of HRV were studied
during wake and sleep stages (NREM1-2, SWS and REM) by an
overnight polysomnography. Spearman correlation was performed
between frequency-domain values and PD patients clinical
characteristics.
Results: A slight non-significant increase in the LF component in
patients with Parkinsons disease was observed. Significant differen-
ces were found between PD patients and controls for the spectral
components of HF, and heart rates (mean R-R). These differences
were restricted only to Slow Wave Sleep (SWS) stage. A significant
correlation between the HF component was found in wake with
respect to disease progression and between NREM1-2, SWS and
REM relative to the heart rate (mean R-R interval).
Conclusions: The differences found in the SWS stage for the HF
component and heart rate might be associated with the relationship
Movement Disorders, Vol. 30, Suppl. 1, 2015
S174 POSTER SESSION
between variations in SWS and variation in neuromodulatory sys-
tems. These systems may in turn have an impact on the autonomic
nervous system. The non-significant increase of the LF component in
patients with PD compared to the control is associated with the
inclusion of patients in mild to moderate stage in disease progression
and to the similarity between demographic and polysomnographic
data. The results of HRV analysis in different sleep stages confirmed
changes in autonomic activity in PD group.
443
Prevalence of non-motor symptoms in Parkinsons disease versus
age-matched healthy controls: A systematic review with meta-
analysis
G. Pagano, E.E. Tan, M. Tagliati (Campobasso, Italy)
Objective: To systematically identify non-motor symptoms
(NMS) prevalence as reported by studies comparing Parkinsons dis-
ease (PD) patients with healthy controls (HC).
Background: NMS of PD are a key determinant of health and
quality of life. Despite their impact, they are not well recognized and
their prevalence varies widely among studies.
Methods: MEDLINE, Web of Science, CENTRAL and Scopus
databases were searched up to September 2014. Pooled prevalence
rates were analyzed using a random effects model. The impact of
age, gender, disease duration, age at onset, H&Y stage, UPDRS III,
use of levodopa and use of DA was also examined.
Results: From 30208 references identified, 71 were assessed for
eligibility and 31 articles, presenting NMS prevalence rates based on
NMSQuest or NMSS, were included for a total of 8520 patients. 21/
30 NMS were significantly more prevalent in PD patients, including
dribbling of saliva (OR 7.40; p<0.0001), hallucinations (OR 6.25;
p< 0.0001), acting out dream (OR 4.3; p<0.0001), constipation (OR
3.98; p< 0.0001), taste/smelling (OR 3.84; p<0.0001), loss of inter-
est (OR 3.67; p<0.0001), anxiety (OR 3.35; p<0.0001), depression
(OR 3.28; p< 0.0001), intense vivid dream (OR 3.14; p< 0.0001),
sex difficulty (OR 2.62; p50.002), bowel emptying (OR 2.51; p<
0.0001), swallowing (OR 2.49; p< 0.0001), urgency (OR 2.32; p<
0.0001), falling (OR 2.21; p5 0.032), concentrating (OR 2.19;
p50.001), restless legs (OR 1.85; p< 0.0001), nocturia (OR 1.85;
p50.002), sex drive (OR 1.79; p50.001), weight (OR 1.74;
p50.025), memory problems (OR 1.48; p<0.01), sweating (OR 1.43;
p50.009). The prevalence of the other NMS (vomiting, bowel incon-
tinence, unexplained pains, dizziness, insomnia, daytime sleepiness,
double vision, leg edema and paranoid ideation) were similar
between PD and controls. The meta-analysis showed a high degree
of heterogeneity (I2 values ranging from 33 to 75%, with few excep-
tions). Age had an impact only on intense vivid dreams (v2 5 0.139;
p50.021). H&Y stage had an impact only on weight changes
(v2 5 1.71, p50.044). Gender, disease duration, age at onset,
UPDRS III, use of levodopa and use of DA had no impact on NMS.
Conclusions: Despite a significant clinical heterogeneity of NMS
prevalence among different studies, some NMS appear to be more
prevalent than others in PD. These results will provide direction for
future standards of care and research.
444
Course of cognitive and neuropsychiatric features in patients
with Parkinsons disease
H.K. Park, J.E. Kim (Goyang, Korea)
Objective: We aimed to investigate the course of cognitive and
neuropsychiatric features in PD.
Background: Parkinsons disease with dementia (PDD) develops
in up to 80% of patients with PD. PDD results in nursing home
admission, cincreased burden of caregivers, and increased mortality.
Additionally, mild cognitive impairment may develop in the early
stages of PD and is an important risk factor for PDD. However, the
Movement Disorders, Vol. 30, Suppl. 1, 2015
longitudinal course of cognitive impairment and behavioral changes
in PD is not fully understood.
Methods: We retrospectively reviewed the results of neuropsy-
chological tests in patients with PD. A total of 77 patients with PD
were enrolled. The neuropsychological tests included the Korean
Mini-Mental Status Exam (K-MMSE), the Montreal Cognitive
Assessment- Korean (MoCA-K), the Neuropsychiatric Inventory
questionnaire (NPI-Q), Clinical Dementia Rating scale (CDR) and
Geriatric Depression Scale (GDS). According to total score of the
MoCA, seventy-seven patients were classified into three groups; Nor-
mal cognition26, 21PD-MCI<26, PDD<21. To assess longitudi-
nal pattern, seven MoCA subdomains were analyzed.
Results: Ten patients with PD were classified as normal cogni-
tion, 23 were PD-MCI, and 44 were PDD. The average total scores
of baseline MoCA test in three groups were 27.2 6 1.2, 23.1 6 1.4,
and 13.0 6 5.2, respectively. PDD patients were less educated than
PD patients with normal cognition and MCI (p value=0.006). Two
subdomains including memory (p50.015) and language (p50.004)
deteriorated compared to the baseline results. Most common neuro-
psychiatric symptoms at baseline test were apathy (51.9%) and
depression (51.9%). Apathy (67.3%) was more common than depres-
sion (36.5%) in the follow-up test.
Conclusions: Our findings suggest that lower degree of education
may be associated with cognitive impairment in PD. In contrast to
the previous reports with an emphasis of frontal/executive impair-
ment, this study showed that decline in memory and language
domains are prominent. This finding may be associated with the floor
effect of frontal/executive dysfunction in PD. It is of note that apathy
was increasingly common as the cognitive impairment progressed.
This study can improve our understanding of cognitive impairment
in PD and may help to establish therapeutic strategies in PD patients
with cognitive impairment.
445
Orthostatic dizziness in Parkinsons disease is attributed to
impaired cerebral autoregulation: A trancranial doppler study
J. Park, W. Jang, J.S. Kim, J. Youn, E. Oh (Busan, Korea)
Objective: To evaluate the cerebral autoregulation in dizzy
patients with Parkinsons disease (PD) using transcranial Doppler
(TCD) monitoring during head-up tilt.
Background: Dizziness in PD is attributed to autonomic dysfunc-
tion or side effect of medication. Orthostatic hypotension (OH) is the
most common cause of orthostatic dizziness. However, cerebral
autoreuglation in PD with dizziness has not been investigated. We
postulated that impaired cerebral autoregulation might cause ortho-
static dizziness in PD before orthostatic hypotension.
Methods: Thirty-nine PD patients with orthostatic dizziness and
thirteen patients without dizziness were enrolled in our study. In
dizzy patients, twenty had OH and nineteen did not. We divided par-
ticipants into three groups; group 1: patients with dizziness and
OH(n520), group 2: patients with dizziness but did not have
O(n519); group 3: patients without dizziness (n513). All participant
performed transcranial Doppler monitoring and blood pressure moni-
toring for 10 minutes during head-up tilt. We calculated the change
of mean flow velocity (mFV) in middle cerebral artery within 3
minutes after head-up tilt for estimating cerebral autoregulation. We
compared the change of mFV and mean blood pressure among three
groups.
Results: Demographic features did not differ among groups. The
change of mFV did not differ between group 1 (16.35 6 8.04) and 2
(14.05 6 7.24), but group 3 (7.53 6 4.62) showed significantly lower
than group 1 and 2 (p<0.01). However, the changes of mean blood
pressure did not differ between group 2 (2.30 6 5.24) and 3
(1.60 6 4.71), but group 1 (7.62 6 9.51) showed significantly higher
than the other groups (p<0.01).
Conclusions: Our results suggest that cerebral autoregulation is
impaired in patients with dizziness in PD despite lack of OH.
 POSTER SESSION
Furthermore, we assumed that TCD monitoring during head-up tilt
might be useful tool for evaluating dizzy patients without OH in PD.
446
Emaciation and life prognosis in Parkinsons disease
K. Park, T. Oeda, A. Umemura, M. Kohsaka, S. Tomita, H.
Sugiyama, H. Sawada (Kyoto, Japan)
Objective: To investigate the association between emaciation and
life prognosis in Parkinsons disease (PD).
Background: Many PD patients tend to lose the body weight
during the clinical course of the disease. Furthermore, previous stud-
ies show that weight loss is more evident in female PD patients than
male. A large number of epidemiologic studies demonstrate the asso-
ciation between low BMI (body mass index) and risk of death in
elderly people. However, in PD patients, the impact of emaciation
on life prognosis remains unclear.
Methods: A cohort of 651 (271 male and 380 female) PD
patients were retrospectively followed for a mean observation time
of 1,173 days. Emaciation was defined as BMI <18.5 at study
enrollment. The primary outcome was the survival time from the
study enrollment to death. We conducted survival time analyses
between two groups according to clinical features (age, disease dura-
tion, H&Y stages, dementia, psychosis, wearing off, dyskinesia, and
BMI <18.5), and then estimated the association between emaciation
and life prognosis using Cox regression models.
Results: 79 (38 male and 41 female) patients died in the observa-
tion period and the crude death rate was 38 per 1,000 person-years.
The BMI was lower in females than in males (22.0 [3.4] versus 20.6
[3.7], mean [SD], p <0.001). Levodopa equivalent dose/body weight
was higher in females (7.25[5.9] vs 9.17[7.9], mean [SD],
p 5 0.001), and the prevalence of dyskinesia and wearing-off were
also significantly higher in females (p <0.001). The clinical factors
related with poor life prognosis were H&Y stage of 4-5, dementia,
psychosis, and emaciation in both males and females (log-rank test,
p <0.0001). In Cox proportional hazard models, the hazard ratio
(HR) of emaciation was 2.8 [95% confidence interval; 1.28-5.99] (p
<0.0001) in males (adjusted for age, disease duration, H&Y stages,
and dementia). In females emaciation was marginally but not signifi-
cantly associated with poor life prognosis (HR 1.9 [0.96-3.83],
p 5 0.067).
Conclusions: Though the prevalence of emaciation (BMI <18.5)
was higher in female than in male, the association of emaciation and
poor life prognosis was significant in male PD patients, suggesting
the difference of impact of emaciation on life prognosis between
males and females. In male PD patients, BMI <18.5 can predict
poor life prognosis.
Comparison of demographic factors, clinical features and outcome between two groups based on etiology of admission
Characteristic Directly PD related Group I (n-52)
Mean Age 64.56 1 9.14 (42 -85)
Gender (Male %) 34 (65.4)
Duration of disease (yrs) 3.771 2.55 (0.5-10)
Hoehn and Yahr stage 2.71 1 0.82
Duration of hospital stay (days) 6.38 1 5.53
ICU admission 3 (5.7%)
Complications 8 (15.4%)
Death 1(1.9%)
Previous admission 3 (5.7%)
During hospital course 42 (28.7%) patients required ICU admission of which 20 (13.7%) needed mechanical ventilation, 11 (55%) patients were
of group II and 7 (35%) were non-PD related. There were 16 (10.9%) deaths - 9 (56.2%) in group II, 5 (31.2%) non-PD related, 1 (6.3%) in
group I and in 1 patient (6.3%) cause for hospitalization was both direct and indirect PD related.
S175
447
E-DUO Study: Use of levodopa-carbidopa intestinal gel in
Spanish advanced Parkinsons disease patients. Non-motor
symptoms and clinical global impression subanalyses
J.C. Parra, D. Santos, M.J. Catal
an, I. Regidor (Madrid, Spain)
Objective: To analyze the evolution of non-motor symptoms
(NMS) and patients and neurologists clinical global impression
(CGI) in APD patients treated with levodopacarbidopa intestinal gel
(LCIG).
Methods: APD patients from 18 Spanish sites treated with LCIG
between January 2006 and December 2011 were included in this
observational, retrospective study.
Impression of change in 31 NMS (rated on a seven-point Likert
scale from strong worsening to great improvement) and patients (P-
GIC) and neurologists (C-GIC) global impression of change scores
were collected from a single evaluation at enrollment.
Results: 52.0% of the patients were male and mean age was
70.1 6 8.0 years (n5123). Mean number of NMS per patient was
22.3 6 5.5 and 64.5% of the patients presented more than 20 NMS.
After LCIG treatment, 121 patients reported a total number of 2702
NMS, of which 35.3% improved, 38.9% remained equal and 25.8%
worsen. NMS with greatest improvements were dizziness (59.7%),
fatigue (57.6%) and flat mood (56.0%).
Global improvement was reported by 86.8% (45.5% great
improvement) of patients and 88.6% (50.4% great improvement) of
physicians according to P-GIC and C-GIC scores, respectively. In
the efficacy index (CGI-E) a 77.7% of the patients had a marked or
moderate therapeutic effect without adverse events or with adverse
events that did not significantly interfere with patients functioning.
Conclusions: NMS are prevalent in APD and may improve after
LCIG treatment, as e.g. dizziness, fatigue and flat mood. Additional
studies are required to confirm these results. LCIG seems to have a
beneficial effect according to CGI of patients and neurologists.
448
An observational study of pattern of admission in Parkinsons
disease
B.S. Paul, G. Paul, G. Singh, S. Kaushal, U. Verma (Ludhiana,
India)
Objective: To analyze the causes and outcomes of hospital
admission in PD population so that preventive measures can be
developed and translated into reduction in admissions.
Background: Hospitalization rates of patients with PD are 1.45
times higher than for age matched controls. Reasons for hospital
admission may be directly or indirectly related to the degenerative
process or may not be related to Parkinsons disease.
Indirectly PD related Group II (n- 73) p value
70.931 9.32 (49-90) 0.0014
49 (67.1) 0.14
4.52 1 3.23 (0.5-14) 0.014
2.97 1 0.78 0.078
9.2 1 6.80 0.011
25 (33.8%) HS
20 (27.1%)
9 (12.1%)
11 (14.9%)
Movement Disorders, Vol. 30, Suppl. 1, 2015
S176 POSTER SESSION
Methods: We prospectively studied patients with the known diag-
nosis of PD admitted to a tertiary care teaching hospital for a period
of 3 years. Etiology for hospitalization was determined from history
and investigational data and based on this patients were divided into
Group I: directly disease related causes (motor & non-motor compli-
cations), Group II- indirectly disease related causes (falls, delirium,
infections etc.) and Non- PD related causes like myocardial infarc-
tion, cerebrovascular disease etc. Factors potentially affecting hospi-
tal admission and course were analyzed by comparing the two
groups. Paired t-test was used for categorical variables and chi
square was used for continuous variables.
Results: 146 patients of PD fulfilled our inclusion criteria. 125
admissions were related to PD out of which 52 (35.6%) belonged to
Group I and 73 (50%) belonged to Group II, however there was an
overlap of 9 patients in which there were both direct and indirect
cause of hospitalization and 31 (21.2%) were non-PD related.
Conclusions: Our study revealed that poor outcome in PD
patients is significantly associated with indirect disease related causes
for admission. There was significant association of age (p5 0.0014),
longer duration of hospital stay (9.22 1 6.80; p50.0001) and need
for ICU admission (p50.011) in PD patients which were admitted
with indirect (group II) cause as compared to direct (group I). Also
these patients had increased risk of repeated admissions, need for
mechanical ventilation, complications and mortality.
449
Real time imaging of stomach motility in patients with REM-
sleep behavior disorder and de novo Parkinsons disease
E.K. Paule, T. Hasemann, A. Hermsen, E. Sittig-Wiegand, D. Vadasz,
K. Eggert, S. Knake, W.H. Oertel (Mainz, Germany)
Objective: To non-invasively investigate the gastric motility
using MRI in de novo, drug-naive Parkinsons disease (de novo PD)
patients, patients with REM - sleep behavior disorder (RBD) and to
compare them to healthy controls (HCs).
Background: Gastrointestinal dysfunction is a frequently
observed and early non-motor symptom of de novo PD. There is
neuropathological evidence for early affection of the enteric system
by alpha-synuclein aggregopathy in PD. However it is unclear when
this affection starts. To address this question, we selected gastric
motility as an indicator for gastrointestinal (dys-)function and
focussed our investigation 1) on subjects with early motor manifesta-
tions of PD (de novo PD) and 2) on subjects suffering from RBD, a
prodromal stage of PD with a risk of > 80% for developing PD later
on. Data was compared with age- and gender matched healthy con-
trols (HC).
Methods: After having a standardized breakfast the subjects
underwent a gastric MRI using a triggered TruFiSp-Sequence (3
Tesla MRI, Siemens Tim TRIO, Siemens Medical Solutions, Erlan-
gen) to visualize the peristalsis of the gastric wall. MRI videos were
analyzed by measuring amplitudes, distances and durations of three
peristaltic waves (D). Based on these parameters we calculated the
gastric motility index (GMI) using the following formula:
Damplitude x Ddistance/Dtime. A mean GMI was given for each
patient.
Results: 21 de novo PD subjects, 19 RBD subjects and 21 HCs
were studied. Patients with de novo PD had significantly reduced
amplitudes (p < 0,001) and GMI (p 5 0,002) compared to healthy
controls confirming data from our pilot study (Unger et al. 2010). In
patients with RBD there was a trend towards a reduced amplitude
(p 5 0,071) of the peristaltic wave (PW) as well as to lower GMI
(p 5 0,131) when compared to healthy controls. There were no
clear differences of the PWs distances between the three study
groups.
Conclusions: Our study shows a disturbed gastric motility visual-
ized by real-time MRI in patients with de novo PD and - to a lesser
extent - in patients with likely prodromal PD, i.e. RBD. MRI seems
to be a promising method to investigate gastrointestinal dysfunction
Movement Disorders, Vol. 30, Suppl. 1, 2015
as an early non-motor symptom in patients with PD and maybe also
in patients at risk to develop PD.
450
Effect of acute non-oral dopaminergic (apomorphine and
levodopa) treatment on non-motor symptoms in Parkinsons
disease
L. Perkins, M. Politis, F. Niccolini, A. Sauerbier, R. Inniss, A.
Martin, D. Trivedi, K. Ray-Chaudhuri (London, United Kingdom)
Objective: To analyse the Non-motor symptoms (NMS) of Par-
kinsons disease (PD) using the NMS Scale (NMSS) in acute non-
oral dopaminergic response tests.
Background: Global and domain based aspects of NMS of PD
can be assessed using the NMSS and it is recognised that some
NMS could be dopaminergic in origin (Chaudhuri and Schapira,
2009). Previous studies have shown that some NMS are more sus-
ceptible to improvement with Apomorphine (Apo) and Intrajejunal
levodopa infusion (IJLI) (Martinez-Martin, Reddy et al, 2014).
Methods: In two separate ongoing studies NMS have been docu-
mented before and after a standard Apo challenge test and also after
IJLI pump (off and on) in a cohort of advanced PD undergoing Apo
or IJLI therapy. In the Apo arm, a modified NMSS addressing only
severity of NMS was used while in the IJLI group NMSS was used
as a whole.
In the Apo arm, assessments were performed at baseline (OFF)
and after 15 and 30 minutes post Apo, whilst in the IJLI group,
NMS were measured at 4, 7 and 10 hrs after pump was switched on.
Results: Apomorphine patients (age (mean 1/-SD), 66.51/-9,
disease duration 7.41/-5.9, HY range 3-4) showed a reduction in
NMS severity after challenge, specifically the sleep/fatigue (66.7%),
mood and anxiety (66.7%) domains were improved.
In the IJLI arm (age (mean 1/-SD) 56.71/-9.2, disease duration
16.31/-3.7, HY range 4-5) sleep and fatigue domain (38%), gastroin-
testinal (40.7%), urinary (45.5%) improved and this was sustained as
long as the infusion was continued at 4, 7 and 10 hrs.
Conclusions: Although not matched, these acute challenge based
studies suggest that the non-oral agonist (Apo) and non-oral levo-
dopa therapies can lead to improvements in NMS. This supports the-
ories of some NMS being of dopaminergic origin.
451
Dysarthria in Parkinsons disease: Lusophony vs. francophony
comparison (FraLusoPark)
S. Pinto, I. Guimar~ aes, R. Rothe-Neves, J. Sadat, R. Cardoso, A.T.
Britto, F. Viallet, J. Ferreira, F. Cardoso (Aix-en-Provence, France)
Objective: To evaluate the effects of (1) disease duration, (2)
medication, and (3) language-context (French vs. Portuguese) on
acoustic and prosodic parameters, intelligibility, and psychosocial
impact of dysarthric speech in Parkinsons disease (PD).
Background: Along disease progression, PD patients have to
deal with speech degradation dependent on the neurodegenerative
processes. Also, effects of pharmacological treatment on speech are
often erratic and highly dependent on the stage of the disease. In
addition, speech alterations modulate acoustic and prosodic parame-
ters with potentially different impacts depending on the language: for
example, French stress occurs systematically on the last syllable and
is generally linked to prosodic boundaries, whereas Portuguese stress
is flexible across syllables and contributes to semantics. Up to now,
very few studies have studied how such language-specific parameters
are affected in PD dysprosody.
Methods: PD patients are recruited in Aix-en-Provence, France
(n560), Lisbon, Portugal (n560) and Belo Horizonte, Brazil
(n560). Evaluations are performed both off and on pharmacological
treatment. Groups of healthy age-matched volunteers provide base-
line references. Motor function is assessed and performance on
 POSTER SESSION
various speech tasks are recorded, ranging from vowel/a/production
to spontaneous speech. Speech organs, psychosocial impact of
speech, quality of life and cognitive functions are also assessed.
Effects of medication on speech parameters are examined according
to disease duration as patients are assigned to 3 different subgroups
(A: < 5 years; B: 5-10 years; C: > 10 years).
Results: We expect that acoustic and prosodic markers in con-
trols differ significantly across languages, but are affected similarly
in PD patients due to dysprosody. The impact of speech impairment
on intelligibility and psychosocial state is expected to change with
the language spoken by the patients. As a consequence, the worst
impact should be observed in patients speaking the language with
higher prosodic modulations.
Conclusions: Our project provides an innovative and interdisci-
plinary approach to study non-motor aspects of PD speech accross
languages. This international project is pioneering and will have
important consequences on the management of speech impairment in
PD.
452
REM sleep behavior disorder and neuropathology in Parkinsons
disease
R.B. Postuma, C.H. Adler, J.G. Hentz, H.A. Shill, E. Driver-
Dunckley, M.N. Sabbagh, S.A. Jacobson, C.M. Belden, L.I. Sue, B.N.
Dugger, G. Serrano, T.G. Beach (Montreal, QC, Canada)
Objective: To compare autopsy findings between PD patients
with and without possible REM sleep behavior disorder (RBD).
Background: The presence of RBD in PD has been associated
with differences in clinical phenotype, including more cognitive
impairment, higher risk of dementia, more cardiovascular autonomic
loss, and more gait dysfunction. One explanation proposed for this
finding is that synuclein-mediated neurodegeneration in RBD-
associated PD is more diffuse throughout the brainstem and cortical
structures. However, this has remained a hypothesis only; no autopsy
studies have assessed patterns of synuclein deposition in PD patients
with vs. without RBD.
Methods: Participants with PD from a population-based autopsy
study were screened for RBD with the Mayo Sleep Questionnaire
(both informants and patients were screened). On autopsy examina-
tion, synuclein deposition in 10 cortical and subcortical regions was
quantified using a 0-4 point semiquantitative scale and compared
between those with and without possible RBD. Amyloid pathology,
tau pathology and white matter lesions were also quantified using
standard methodology and compared between groups.
Results: A total of 81 patients were included, 41 with and 40
without possible RBD. Age and disease duration were similar
between groups. Patients with RBD demonstrated more severe synu-
clein deposition in every brain region examined. The total semiquan-
titative Lewy body score (0-40 scale) was 29.5 in the RBD group
compared to 24.5 in the non-RBD group (p50.002). On a region-
specific analysis, the semiquantitative score was significantly greater
in 8 of the 10 regions examined (and the 2 non-significant areas had
point estimates towards increase in RBD patients). The increased
score in RBD patients was of similar magnitude in all regions, rang-
ing from 0.33 to 0.64 points on the 0-4 scale. White matter infarct
burden was slightly higher in those without RBD.
Conclusions: PD patients with possible RBD have greater density
and range of synuclein deposition on autopsy, suggesting a more dif-
fuse and synuclein-driven pathophysiology.
453
Non-motor symptom burden in Parkinsons disease: A
longitudinal study
K.M. Prakash, N.V. Nadkarni, W.K. Lye, L.M. Chew, M.H. Yong,
E.K. Tan (Singapore, Singapore)
S177
Objective: This study was aimed to establish the progression of
NMS burden and factors affecting it.
Background: Non-motor symptoms (NMS) are common among
patients with Parkinsons disease however little is known about their
progression in terms of severity or burden.
Methods: Parkinsons disease patients were prospectively
enrolled and follow-up for up to 18 months. Non-motor symptoms
scale (NMSS) was used to evaluate the burden of non-motor
symptoms.
Results: There was a significant reduction of total NMS burden
(from 25.0 to 17.0, p-value <0.001)) over the follow-up period. Sim-
ilarly all NMS domains except domains 2 (sleep/fatigue) and 3
(mood/cognition) showed significant reduction of scores. In the uni-
variate analysis, Hoehn & Yahr staging, disease duration, Schwab &
England Activities of Daily Living score and UPDRS motor scores
were individually predictive of change in total NMS burden. How-
ever, in the multivariable analysis only the latter two were signifi-
cantly predictive of change in the total NMS burden.
Conclusions: There was a significant reduction of total NMS bur-
den over the study period. The severity of motor and activity of daily
living impairments were the best predictors of NMS change.
454
Prevalence of wearing off symptoms among Parkinsons disease
patients at a tertiary hospital
P.A.A. Quitasol, C.L. Go (Manila, Philippines)
Objective: To determine (1)the prevalence of wearing off symp-
toms among PD, (2)the most common wearing off symptoms among
Filipinos and (3)the average duration when the wearing-off symp-
toms would manifest from the diagnosis of PD.
Background: Parkinsons disease (PD), a tetrad of hypo-, brady-
kinesia, resting tremors, postural instability, or instability. Aside
from the more recognizable motor features, neuropsychiatric symp-
toms are also experienced by patients. These include depression, apa-
thy, anxiety, psychosis, sleep disorders, and impulsive and
compulsive disorders. Long term treatment of PD with Levodopa is
complicated by the development of motor complications such as
end-of-dose wearing off phenomenon, on-off fluctuations.
Methods: This is a cross sectional study including patients diag-
nosed with Parkinsons disease (PD) seen at the OPD . The follow-
ing were noted: Name and age, gender, year the patient was
diagnosed with PD, current medication and dose including interval
between doses, year when Levodopa was started medication intake,
duration of disease. Patient who did not give consent will be
excluded from the study as well as patients with diagnoses other
than PD. Informed consent was obtained for all participants. The
patient was asked to answer a wearing off questionnaire. The preva-
lence of wearing off was determined using descriptive analysis.
Results: 35 patients were interviewed and the age ranged from
37 to 82 years old (mean= 60.46, SD=12.91). The number of
wearing-off symptoms experienced by the patients ranged from 3 to
14 motor (mean 7.4, SD=2.98). The most common motor symptoms
experienced by the patient is slowness of movement= 34 (97.1%)
followed by general stiffness =25 (71.4%) and weakness=24
(68.6%). The most common non-motor symptoms are mood
changes=18 (51.4%) followed by aching=15(42.9.%) and pain=14
(40.0%).
Conclusions: PD patients seen at the OPD are mostly evaluated
based on their motor symptom and their medications adjusted
accordingly. Wearing-off phenomenon is mostly under recognized by
physicians especially the non-motor symptoms. The wearing-off
Questionnaire card is a tool of easy administration for the identifica-
tion of wearing-off manifestations and takes less than 5 minutes to
complete. A better recognition of these symptoms, both motor and
non-motor may improve the patients quality of life since it will aid a
clinician identify the patient symptoms and therapeutic changes.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S178 POSTER SESSION
455
Impaired contrast sensitivity is associated with more severe
cognitive impairment and nigrostriatal denervation in
Parkinsons disease
A.J. Ridder, M.L.T.M. Muller, V. Kotagal, K.A. Frey, R.L. Albin, N.I.
Bohnen (Ann Arbor, MI, USA)
Objective: To explore whether impaired contrast sensitivity cor-
related with cognition and the nigrostriatal deficit in PD and if there
are any associations with cortical cholinergic activity.
Background: Dopaminergic degeneration affects both the nigro-
striatal projections and retinal inner plexiform cells. Retinal function
changes, such as impaired contrast sensitivity and color discrimina-
tion, occur in Parkinsons disease (PD). Previous studies have shown
associations between color discrimination deficits and worse cogni-
tive performance in PD.
Methods: PD subjects (n546; 15F/31M; mean age 66.1 6 8.0
(range 51-84), mean Hoehn and Yahr stage 2.5 6 0.6 (range 1-5),
mean duration 5.9 6 4.7 yr (range 0.5-20), mean MoCa score
25.6 6 3.4 (range 15-3-) underwent vesicular monoaminergic type 2
(VMAT2) (1)-/ -[11C]dihydrotetrabenazine (DTBZ) and acetylcho-
linesterase (AChE) [11C]PMP (DTBZ) PET imaging, neuropsycho-
logical assessment and contrast sensitivity testing using the Rabin
test. One DTBZ scan failed in a patient.
Results: Mean Rabin contrast sensitivity score was 1.37 6 0.35
(range 0.6-2.0), mean global cognitive z-score was -0.45 6 0.90
(range -2.81 - 0.96), mean cortical AChE hydrolysis rates was
0.0239 6 0.0030 (range 0.0182-0.0298), mean putamen and dorsal
caudate nucleus DTBZ binding were 1.83 6 0.25 (range 1.37-2.55)
and 1.95 6 0.41 (range 1.40-3.50), respectively. Bivariate analyses
showed significant correlation between Rabin contrast sensitivity
scores and global cognitive z-score (R=0.55, P<0.0001), dorsal cau-
date nucleus (R=0.34, P=0.02) but not with putaminal DTBZ binding
(R=0.20, ns) or cortical PMP hydrolysis (R=0.07, ns).
Global cognitive z-score correlated with cortical PMP hydrolysis
(R=0.37, P=0.01) but not with caudate nucleus DTBZ binding
(R=0.22, ns).
Cognitive domain z-score post hoc analysis demonstrated most
robust correlation between the Rabin contrast sensitivity scores and
executive functions (R=0.54, P=0.0001) followed by verbal learning
(R=0.46, P=0.0012), visuospatial (R=0.33, P=0.028) and attention z-
scores (R=0.32, P=0.033).
Conclusions: Although cognitive impairment makes a major con-
tribution to impaired contrast sensitivity in PD, the underlying patho-
physiology reflects dopaminergic rather than cholinergic denervation
changes. Findings may imply parallel denervation changes in nigro-
striatal and retinal dopaminergic nerve terminals.
456
Role of premotor symptoms on non-motor symptoms burden and
quality of life
M. Rodriguez-Violante, A. Cervantes-Arriaga, I. Estrada-Bellmann,
R. Leal-Ortega, R. Millan-Cepeda, H. Morales-Brice~ no, G. Neri-
Nani, R. Llorens-Arenas, H. Calderon-Fajardo, C. Zu~niga-Ramirez,
A. Jorge de Sarachaga (Mexico City, Mexico)
Objective: To assess the correlation between nonmotor symptoms
(NMS) time of onset and NMS burden (measured by the nonmotor
symptoms scale) and quality of life in patientes with Parkinsons
disease.
Background: Premotor symptoms in Parkinsons disease (PD)
have been widely described.
In the ONSET PD study, which involved 109 newly diagnosed
PD patients, results from a questionnaire of nonmotor symptoms
(NMS) were reported according to three different premotor periods
before motor onset: <2 years, 2-10 and >10 years. Although several
cluster were found, no correlation between these symptoms and the
Movement Disorders, Vol. 30, Suppl. 1, 2015
total NMS burden and motor severity were found using the MDS-
UPDRS parts I and II.
Methods: Consecutive subjects with PD were included. All sub-
jects were evaluated with a structured questionnaire to assess the
presence of NMS as well as it temporality in regards to motor symp-
toms onset. Additionally, the following scales were applied: Move-
ment Disorders Society - Unified Parkinsons disease Rating Scale
(MDS-UPDRS) parts I to IV, nonmotor sysmptoms scale (NMSS),
Parkinsons disease quality of life (PDQ-8). All evaluationes were
performed by a neurologist with expertise in Movement Disorders.
Results: A total of 556 patients were included (54.1% male).
Mean age was 63.3 6 12.1 years and mean disease duration was
7.5 6 6.2 years. Frequency of premotor NMS is shown in table I.
Frequency of nonmotor symptoms and
its relation with motor onset
Time before
Nonmotor symptom Frequency (%) motor onset (years)
Hyposmia 125 (22.5%) 4.5 6 11.7
Depression 201 (36.2% 4.8 6 11.2
Anxiety 191 (34.4%) 7 6 14.1
Constipation 180 (32.4%) 8.5 6 16.7
Impulse control 58 (10.4%) 9.2 6 13.1
disorder
Pain 6 (1.1%) 8.3 6 13.9
Sleep disorder 207 (37.2%) 6.5 6 13.3
In regards to impulse control disorders binge eating was the most
common (37.9%). Within the sleep disorders spectra, REM sleep
behavior disorder was the most frequent (56%). After excluding
patients with NMS onset after motor symptoms, the multivariate
analysis showed that only premotor depression predicted a higher
total NMS burden measured by the NMSS. (B=27.9 6 13, p50.04).
No premotor symptom predicted a worst MDS-UPDRS score,
although hyposmia and depression did associate with a higher MDS-
UPDRS part I score (B=4.1 6 1.7, p50.02 and B=5.1 6 1.8,
p50.007, respectively). Finally, none of the NMS were associated
with the quality of life assessed by the PDQ-8.
Conclusions: Premotor depression is associated with a higher
NMS burden in PD, although it does not seem to affect its motor
presentation. Whether longer premotor periods or different premotor
clusters influence these outcomes is still unclear. Further studies with
drug-nave patients and controls, like the ONSET PD, are needed to
confirm these findings.
457
Motor and non-motor features of Parkinsons disease in
idiopathic REM sleep behaviour disorder
M. Rolinski, M. Lawton, S. Evetts, F. Baig, C. Ruffmann, C.E.
Mackay, T. Quinnell, Z. Zaiwalla, Y. Ben-Shlomo, M.T.M. Hu
(Oxford, United Kingdom)
Objective: We endeavored to elucidate the motor and non-motor
characteristics of RBD, in comparison to healthy controls and
patients with early drug-nave PD, accounting for potential genetic
confounders.
Background: REM sleep behaviour disorder (RBD) is the most
specific clinical marker for prodromal Parkinsons disease (PD).
However, RBD may also be associated with genetic PD. Therefore,
the development of early Parkinsonian features in patients with RBD
may simply represent the enrichment for genetic risk factors for PD.
Methods: Fifty-seven patients with polysomnography-proven idi-
opathic RBD were recruited from the sleep disorders clinic at the
John Radcliffe Hospital, Oxford and Papworth Hospital, Cambridge,
England. Patients with secondary RBD, either due to medication use
 POSTER SESSION S179

or the presence of a clinically defined neurological disorder, were
excluded from the study. Seventy-four age and sex-matched healthy
controls and patients with drug-nave PD were recruited from the
Oxford Parkinsons disease Centre (OPDC) patient cohort.
All participants were screened for mutations in the glucocerebro-
sidase (GBA) and the leucine-rich repeat kinase 2 (LRRK2) genes,
and a positive family history. Motor characteristics were assessed
using the Unified Parkinsons disease Rating Scale-III, Purdue peg-
board and Flamingo balance test. Nonmotor assessment included
screening for cognitive impairment, hyposmia, autonomic features,
anxiety and depression.
Results: Only one RBD patient carried a mutation in the GBA
gene. RBD patients showed evidence of motor impairment and pos-
tural instability. Patients with RBD were more likely to experience
cognitive impairment (Odds ratio 1.58, 95% CI 1.10, 2.27), hypo-
smia (Odds ratio 2.86, 95% CI 1.92, 4.26), constipation (Odds ratio
1.83, 95% CI 1.27, 2.64) depression and anxiety, compared to con-
trols. Modest differences in nonmotor symptoms between the RBD
and drug-nave PD groups were not statistically significant.
Conclusions: RBD is associated with motor and non-motor
impairment often seen in early PD. These impairments in so-called
idiopathic RBD subjects may represent the prodromal stages of spo-
radic PD rather than common genetic pathways. Further studies are
needed to assess whether these baseline findings can be used to
model an individuals life-long risk of conversion from RBD to PD
or a related neurodegenerative disorder.
458
Symptom severity and pain intensity may be risks for post STN
DBS impulsivity in Parkinsons disease
A. Rothstein, B. Avery, A. Boyanpally, J. Hesse, R. Coghill, A.
Laxton, S. Tatter, M. Siddiqui, I. Haq (Winston Salem, NC, USA)
Objective: To test the effects of STN DBS on pain and impulsiv-
ity in Parkinsons disease (PD).
Background: Patients with PD treated with deep-brain stimula-
tion (DBS) of the subthalamic nucleus (STN) may be more

Demographics

Disease Duration Time From Implantation

Participant Age (years) Baseline UPDRS 3 UPDRS 3 Postop to Testing (years)
1 73 24 70 16 7
2 58 21 31 18 8
3 56 6 45 22 7
4 73 10 38 23 1
5 57 14 47 36 1
6 76 16 37 26 5
7 71 12 18 15 3

Results

Change in
conflict
difference Mean Mean
Conflict Conflict with Conflict Conflict Mean Mean
Difference Difference change Difference Difference high-conflict low-conflict
on-stim off-stim in DBS on-stim off-stim decision time decision time
UPDRS3 Motor R= 0.849 R=-0.606 R=0.887 R=0.583 R=0.780 R=0.743 R=0.729
Score p50.07 p50.28 p50.05* p50.30 p50.12 p50.15 p50.16
Pain Intensity R=-0.226 R=-0.103 R=-0.0703 R=-0.728 R=-0.0318 R=-0.477 R=-0.422
rating on-stim p50.71 p50.87 p50.91 p50.16 p50.60 p50.42 p50.48
Pain Unpleasantness R=-0.167 R=-0.089 R=-0.047 R=-0.879 R=-0.397 R=-0.537 R=-0.497
rating on-stim p50.79 p50.89 p50.91 p50.05* p50.51 p50.35 p50.40
Pain Intensity rating R=-0.298 R=0.133 R=-0.262 R=-0.766 R=-0.622 R=-0.725 R=-0.711
off-stim p50.63 p50.83 p50.67 p50.131 p50.26 p50.17 p50.18
Change in Pain Int R=-0.758 R=0.492 R=-0.762 R=0.817 R=-0.539 R=-0.633 R=-0.612
with change in p50.14 p50.4 p50.13 p50.09 p50.349 p50.25 p50.273
DBS state
Change in Pain Int R=0.315 R=-0.517 R=0.509 R=0.817 R=.941 R=0.901 R=0.967
with change in p50.61 p50.37 p50.38 p50.09 p50.02* p50.04* p50.007**
DBS state
Change in Pain Int R=0.190 R=-0.368 R=0.341 R=-0.540 R=-0.21 R=-0.335 R=-0.295
with change p50.76 p50.542 p50.57 p50.35 p50.74 p50.58 p50.629
in DBS state
* Correlation is significant at the 0.05 level (2-tailed). ** Correlation is significant at the 0.01 level (2-tailed). Conflict decision time is defined as
time spent deciding on a response during the Frank (2007) paradigm for either high-conflict (HC) or low-conflict (LC) pairings. Conflict differ-
ence is defined as (HC-LC). Decreased conflict difference is one index of increased impulsivity. Change in conflict difference with change in
DBS is defined as [Off stim (HC-LC)]-[On stim(HC-LC)].

Movement Disorders, Vol. 30, Suppl. 1, 2015

S180 POSTER SESSION
impulsive in their risk evaluations. Time taken to process high vs.
low conflict decisions is one index of impulsivity. The evaluation of
pain stimuli may involve parallel circuitry. We tested whether pain
sensitivity is altered by STN DBS in PD or related to impairment in
decision-making abilities. We hypothesized that patients who exhib-
ited greater changes in pain perception on stimulation would show
greater increases in impulsivity on stimulation.
Methods: We enrolled 7 patients with idiopathic PD and bilateral
STN DBS, implanted at least 3 months prior to enrollment. We
excluded those with brain lesions, neuropathies, or dementia. Sub-
jects underwent a 12 hour medication washout prior to testing. They
were counterbalanced to starting in an off or on-stimulation state.
Participants first completed test training during which they were
briefly exposed to noxious heat stimuli ranging from 35 C - 49 C.
Participants then completed a computerized decision-making para-
digm designed to measure differences in reaction time between high
conflict and low-conflict decisions (Frank et al., 2007). Noxious heat
stimuli, 49 C, 20s on/30s off) were administered to patients right
ventral forearm. Subjects rated the pain intensity and its unpleasant-
ness using a visual analogue scale. Patients DBS states were then
switched. After a 30-minute break, the protocol was repeated.
Results: We found a significant relationship between higher
UPDRS3 scores and DBS effect on conflict processing. We found a
significant relationship between increased DBS effect on pain inten-
sity and increased conflict difference. There was no relationship
between DBS state alone and conflict difference, pain intensity, or
unpleasantness.
Conclusions: Higher symptom burdens correlate with greater
DBS effects on conflict processing. PD patients with higher preoper-
ative symptom burdens may be more likely to have post-DBS impul-
sivity. Increased DBS effects on pain intensity correlated with
increased conflict difference. Patients for whom DBS affects pain
intensity may prove slower at conflict resolution. We could not con-
firm a direct DBS-conflict interaction (p50.3). More research is
needed to better elucidate these relationships.
459
Comparing speech function in persons with Parkinsons disease
in clinical and home environments
C.E. Rountrey, N.M. Borras, C.L. Ludlow (Harrisonburg, VA, USA)
Objective: To compare the effects of setting (home versus clinic)
in persons with Parkinsons disease (PD) and healthy controls (HC)
on measures of speech sound level intensity and intelligibility.
Background: PD is a neurodegenerative disease affecting speech
and voice for communication. Typical disorders include hypokinetic
dysarthria, marked by reduced speech intelligibility and intensity,
impairing communication. Clinical observations of speech in persons
with PD have suggested an apparent discrepancy in speech function
between clinical settings and other environments and the need to pre-
dict speech function outside the clinical setting.
Methods: Twenty total participants included 10 HC and 10 per-
sons with PD. Each participant was fitted with a wearable speech
recording device in the clinical environment while speech conversa-
tion and testing were recorded. Each subject wore the device to
record 15 hours over 2 days in their home environment. Ten utteran-
ces were randomly selected from recordings made in each environ-
ment. Sound pressure level (dB) of each utterance (removing pauses
>150ms) was measured after calibration with a sound pressure level
meter. Three listeners transcribed each utterance and mean percent
words intelligible was computed. Repeated ANOVAs comparing
measures in the clinic and home between groups and group by envi-
ronment interactions were conducted for mean SPL and mean intelli-
gibility scores. Clinical measures of disease duration, cognition,
depression, speech rate, background noise, and sentence length were
examined for relationship with home measures of intensity and
intelligibility.
Movement Disorders, Vol. 30, Suppl. 1, 2015
Results: The PD group had reduced percent intelligibility com-
pared to the HC in both environments (p50.03) with no differences
found between clinic and home. The groups did not differ in speech
intensity but both had reduced intensity in the clinic compared with
home environment (p50.001). This was partly due to increased
background noise levels in the home environment in both groups
(p50.001). Only disease duration predicted reduced speech intelligi-
bility in the PD group.
Conclusions: Only speech intelligibility was impaired in persons
with PD, was the same in both environments and decreased with dis-
ease duration. No reductions in intensity were found in the PD group
and differences in settings may relate to differences in background
noise levels.
460
Parkinsons disease: Markers of lower body mass index (BMI)
J.J.E. Rovers, S.S. Wu, B.R. Bloem, M.S. Okun, B. Post (Nijmegen,
Netherlands)
Objective: This study aims to identify possible markers of a
lower BMI in patients with Parkinsons disease (PD), with focus on
disease severity (Hoehn & Yahr stage, HY) and cognition (immedi-
ate word recall, verbal fluency, delayed word recall).
Background: PD is mainly known for its movement-related
symptoms, which are most obvious in patients at an early stage.
Later, PD has its effect more on non-motor aspects. For example,
patients with PD have a lower BMI than controls. The effect of these
weight problems in clinical PD care is unclear, but a low BMI is
generally associated with frailty, greater morbidity and higher mor-
tality. Identifying possible predictors of lower BMI can potentially
improve care for PD patients and help to prevent negative effects of
a declining BMI.
Methods: In collaboration with the National Parkinsons Founda-
tions Quality Improvement Initiative (NPF-QII) we conducted a
cross-sectional analysis on 7066 PD patients. Of these patients, 4165
had BMI data at both a first and second visit, with a year in between,
usable for longitudinal analysis by a BMI change analysis. Multiple
regression analyses were used to assess the association between BMI
at the first visit and HY stage and cognitive functions (word recall,
verbal fluency and delayed word recall). Multiple linear regression
and ordinal logistic regression were used to assess associations
between baseline covariates and important factors and BMI change.
Results: Immediate word recall score had a significant positive
correlation with the BMI at baseline (p50.011). The HY stage,
verbal fluency score and delayed word recall score were not related
to a declining BMI. The BMI change between first and second visits
was analyzed by multiple linear regression and resulted in a signifi-
cant positive association between delayed word recall score and BMI
change (p50.012). HY stage, immediate word recall and verbal flu-
ency did not have a significant association. Ordinal logistic regres-
sion was used to assess the important factors when BMI change
category was considered as a dependent variable. It showed that only
verbal fluency was included in the final model but it was still not a
significant factor (p50.065).
Conclusions: No significant correlation was found between BMI
change and cognitive function, and there was no correlation between
HY stage and BMI. Longer longitudinal follow-up may be needed to
uncover a potential relationship.
461
An evaluation of non-motor symptoms in Parkinsons disease
patients using 2 rating scales
A. Sanchez-Jord
an, D. Padilla-Carmona, U. Rodrguez-Ortiz, M.C.
Boll (Mexico City, Mexico)
Objective: The purpose of this study was to evaluate dysauto-
nomic symptoms in PD patients using 2 rating scales. The composite
 POSTER SESSION S181

autonomic symptoms scale (COMPASS) and the scale for outcomes Conclusions: Our data demonstrate a role of OH as a risk factor
in Parkinsons disease patients- autonomic (SCOPA- AUT). for falls in patients with idiopathic PD. Data also suggest that careful
Background: Autonomic dysfunction in Parkinsons disease (PD) monitoring of supine and orthostatic blood pressure in such patients
patients has been recognized since its original description in 1817. may be useful for detecting individuals with PD at risk of falls and
Dysautonomic symptoms vary and include cardiovascular, gastroin- may be a significant modifiable factor for falls prevention.
testinal, and urogenital manifestations, among others. Because of
time spent and the potential risk of invasive tests, clinical rating
scales represent an important ally during the evaluation of these 463
patients.
Methods: This study included 89 patients with the diagnosis of REM density in patients with early or late stage Parkinsons
PD. Dysautonomic symptoms were assessed with both scales, COM- disease. A polysomnography-based case-control study
PASS and SCOPA-AUT, clinical severity and stage of disease were L.A. Schroeder, O. Rufra, N. Sauvageot, F. Fays, V. Pieri, N.J.
evaluated with the Hoehn & Yahr classification, patients age and Diederich (Howald, Luxembourg)
time evolution of the disease.
Objective: To explore REM density in patients with idiopathic
Results: We evaluated 89 patients (47.2% female, 52.8% male)
Parkinsons disease (IPD).
with diagnosis of PD looking for dysautonomic symptoms. Among
Background: In IPD, disease-inherent degeneration of sleep regu-
them, 90% presented constipation and/or nicturia in some degree,
lation centres has been postulated and progressive sleep de-
while only 30% presented some degree of orthostatic dysfunction. We
structuring has been evidenced by polysomnography (PSG). Rapid
confronted the presence of orthostatic dysfunction in SCOPA-AUT vs
eye movements (REM) are the hallmark of REM sleep and thought
COMPASS and we observed significative concordance in the fainting
to be linked to the generation of ponto-geniculo-occipital (PGO)
evaluation (Kappa=0.467; p<0.001) between both scales, however,
waves. REM density (RD) measures the frequency of these eye
COMPASS showed more detailed information (12 postprandial faint-
movements; it increases over the course of the night and is greatest
ing, 19 while standing and 16 related to physical activity).
when sleep pressure is lowest. In depressive patients, increased RD
Conclusions: Both scales threw similar results and showed a
has been demonstrated during the first part of the night. RD has not
highly significative concordance. Dysautonomy didnt show associa-
yet been explored in IPD.
tion with Hoehn&Yahr stage, side of onset, evolution of the disease
Methods: Retrospective PSG study on 81 non-demented subjects:
or the patients age, which is why this analysis of dysautonomic
29 early IPD patients (disease duration 3 yrs; age: 65.7 1/-10.5
symptoms in PD didnt identify risk factors. As we can see, there is
yrs), 21 late IPD patients (disease duration >3 yrs; age: 66.8 1/-
a clear difference when we compare dysautonomic symptoms of Par-
12.5 yrs) and 31 healthy controls (age: 66.9 1/-8.7 yrs). REM was
kinsons disease patients vs multiple system atrophy. Particularly
defined as all REM episodes with >3 minutes of continuous REM
when comparing the 30% of orthostatic dysfunction in our sample,
sleep; RD was expressed as number of ocular movements/REM
against a 100% in multiple system atrophy patients. We also noticed
minute.
a failure in both scales when assesing sexual function, since most of
Results: RD was lower in patients with early or late IPD than in
the patients refused to answer that part of both scales, or referred not
healthy controls (see figure). The difference was most significant for
having any problem on that matter. There is an obvious need to
the 3rd REM episode comparing late stage IPD patients and controls
design an adequate instrument to assess the sexual domain in the
(p50.01). However, the total number of REM episodes was not dif-
dysautonomic dysfunction.
ferent between the different groups. RD was independent from gen-
der, age, sleep efficiency, sleep latency, duration of total sleep or
462 sleep phases NREM1/2, NREM3/4, REM. In IPD patients, but not in
controls, reduced sleep efficiency was linked with age (p50.005)
Orthostatic hypotension increases the risk of falls in idiopathic and increased sleep latency (p5<0.001).
Parkinsons disease patients Conclusions: REM density is progressively reduced in IPD
M. Sarchioto, M. Zibetti, S. Maule, V. Milazzo, E. Montanaro, A. patients. Considered to be a sign of persistent high sleep pressure,
Romagnolo, S. Angrisano, F. De Matteis, C.A. Artusi, A. Bernardini, reduced RD in IPD further explains excessive daytime sleepiness in
L. Lopiano (Turin, Italy)
Objective: To evaluate the correlation between falls and ortho-
static hypotension (OH) in patients with Parkinsons disease (PD).
Background: Falls are a relevant cause of injury and a major
health problem for people with PD. Symptomatic OH is believed to
contribute to cause falls in PD patients, but few study have assessed
it directly.
Methods: Thirty six consecutive patients diagnosed with idio-
pathic PD were recruited. Patients were asked for any falls in the
previous 12 months and followed up for the next 6 months. All
patient underwent autonomic cardiovascular function evaluation
using the Ewing battery. Also epidemiological, motor, pharmacologi-
cal and neuropsychological data were collected.
Results: The mean age was 63.7 (SD 9.6) years and the mean
disease duration was 6.5 (SD 3.5) years. A statistically significant
association was found between falls and OH (p50.04). Falls also
inversely correlated with the value of systolic blood pressure reduc-
tion measured at the 1st and 3rd minute during tilt test (p50.01 for
both conditions) and directly correlate with the systolic blood pres-
sure reduction between supine and 1st minute orthostatic measure-
ment (Dp) (p50.02). A multiple regression model taking into
account possible confounding variables of axial symptoms and cogni-
tive status (MoCA) showed that Dp remained a significant predictor
of falls (t 5 2.6, p50.01). Fig. 1. (463).

Movement Disorders, Vol. 30, Suppl. 1, 2015

S182 POSTER SESSION
these patients. This is possibly due to direct involvement by the dis-
ease process of the presumed REM generation site in the pontome-
sencephalic tegmentum. We propose RD as additional tool in
polysomnography-based sleep studies of IPD patients.
[figure1]
Figure: Distribution of REM densities in healthy controls (HC), in early
IPD patients (3 yrs duration) and in late IPD patients (>3 yrs duration).
464
Skin biopsy is useful for diagnostic tool of Lewy body disease
R. Sengoku, H. Sumikura, Y. Saito, Y. Nishina, S. Miyagawa, T. Komatsu,
M. Ikemura, Y. Saito, K. Kanemaru, S. Murayama (Tokyo, Japan)
Objective: To evaluate the method including staining and sites of
skin biopsy for Lewy body disease (LBD) cases.
Background: Although the Lewy body pathology appearing on
the skin of LBD patients are known, the best method for evaluation
of skin biopsy is still unknown.
Methods: Two LBD cases with autonomic symptom were evaluated.
One pure autonomic failure (PAF) patient and one Parkinsons disease
(PD) patient were examined head up tilt test and iodine starch staining
test. Case 1: 66-year-old male with PAF was performed skin biopsies
including two anhidorosis lesions that was around the umbilicus and two
lesions of medial thigh and two lesions of lateral thigh that was recognized
sweat. Case 2: 78-year-old female with PD was performed skin biopsies
including four anhidorosis lesions that was around the umbilicus and two
lesions of medial thigh and one lesion of medial upper arm and one lesion
of lateral thigh that was recognized sweat. After fixation the sections were
embedded in paraffin. All sections were stained with hematoxylin and
eosin. We immunostained all sections with anti-phosphorylated alpha syn-
uclein (monoclonal and polyclonal), anti-phosphorylated neurofilament,
and anti alpha synuclein by protease treatment.
Results: Case 1 showed that five lesions were positive for both anti-
phosphorylated alpha synuclein immunostaining. Case 2 showed that four
lesions were positive for monoclonal anti-phosphorylated alpha synuclein
immunostaining and three were positive for polyclonal anti-phosphorylated
alpha synuclein immunostaining. On the other hand, all sections of two
cases were positive for anti alpha synuclein by protease treatment.
Conclusions: The evaluation of skin biopsy for LBD is necessary
to assess with accurate staining the sampling site on carrying out the
sweat test.
465
Characterizing apathy and possible neural correlates in
Parkinsons disease
J.H. Shin, J.Y. Lee, A. Kim, S.A. Shin, Y.K. Kim (Seoul, Korea)
Objective: To characterize clinical features of apathy in a set of
consecutively enrolled PD patients who underwent thorough clinical
evaluations including cognitive function and to analyze possible neu-
ral correlates of apathy in a matched subgroup of patients without
dementia and depression.
Background: Apathy is defined as a loss of goal-directed behav-
ior, a discrete clinical manifestation distinct from dementia or
depression in Parkinsons disease (PD). Apathy is responsible for
patients quality of life, and it is often resistant to anti-Parkinsonian
drug therapy. The pathophysiological mechanism of apathy as well
as its neural correlates in PD has yet to be sufficiently investigated.
Methods: Data from a total of 117 patients with PD were ana-
lyzed. Apathy was evaluated using the Apathy scale, and cognition
was evaluated by neuropsychological tests composed of K-Mini-
mental status examination, Digit span test, phonological comprehen-
sion, repetition, Boston naming test, Seoul verbal learning test, Con-
trolled oral word association test (COWAT), Contrasting program,
Go-no-go test, and Rey figure copy test. In a subgroup of PD
patients matched for age, Hoehn & Yahr stage, and duration of PD
(10 non-apathetic and 12 apathetic), we conducted [18F]-fluorodeox-
Movement Disorders, Vol. 30, Suppl. 1, 2015
yglucose positron emission tomography scan and volumetric mag-
netic resonance imaging. Clinically significant depression and the
presence of dementia were pre-excluded in the analyses.
Results: Among the subjects, 50 were apathetic. Apathetic
patients had a lower ability in the Digit span test (forward, p50.007
and backward, p50.035), lower recall score in the Seoul verbal
learning test (p50.045) than non-apathetic patients did. Apathetic
patients also showed a tendency of low score in COWAT (p50.063).
In a matched group analysis, there was a significant gray matter atro-
phy in the precuneus and posterior cingulate area and a significant
hypometabolism in the corresponding regions in apathetic subjects
(p<0.001) which was also correlated with apathy scale.
Conclusions: Apathy in nondepressive and nondementic PD
patients was characterized by impaired working and verbal memory
function and slight impairment in verbal fluency. The possible neural
mechanism of that was suggested by the hypoactive precuneus and
posterior cingulate cortex. Larger scale longitudinal studies with mul-
timodal imaging analysis warrant to be conducted in the future.
466
Mood fluctuations in Parkinsons disease: Toward a better
understanding
C. Siri, N. Meucci, A. Colombo, E. Reali, B. Pozzi, G. Sacilotto, M.
Zini, G. Pezzoli (Milan, Italy)
Objective: We analyzed changes in affective dimensions before
and after a single levodopa administration in patients with PD.
Background: Long term treatment of Parkinsons disease (PD) is
associated to motor and non-motor fluctuations. While the former are
well characterised and, therefore, easier to recognize, psychological
non motor fluctuations are less familiar to clinicians and underesti-
mated by patients.
Methods: We evaluated 60 non demented PD patients, 30 with
motor fluctuations (MF) and 30 without (NMF) (means MF: age
63.4 6 8, PD duration 9.1 6 4 yy, M/F=15/15; means NMF age
61.3 6 9, PD duration 3.6 6 3 yy, M/F=15/15) while undergoing a
levodopa challenge. In OFF and ON we evaluated: motor (UPDRS
III) and general cognitive status (MMSE and CDT); mood state was
evaluated using POMS. We calculated the percentage of change in
POMS and in UPDRS III. Depression (BDI II), anxiety (HAM-A)
and impulsive-compulsive disorders (QUIP) were also assessed.
Results: MF and NMF group were comparable for clinical and
demographic variables except for significant longer disease duration
and higher UPDRS III scores in MF. In both groups, difference in
UPDRS III between ON and OFF was significant while we did not
find any change in cognitive assessment between the two conditions.
As concerns POMS, repeated measures ANOVA found a significant
effect of condition (OFF vs ON) but not of group nor interaction
(group x condition) in total score (p50.000) and in all factors
(T=tension, A=anger, D=depression, S=fatigue, V=vigor p<0.006)
except for factor confusion(C); even when considering disease
duration and age as covariates the results remained stable.
Motor and non-motor scales Scores in the two groups
MF NMF
UPDRS III OFF* 26.7 17.3
UPDRS III ON 13.9 10.0
POMS total score OFF 26.9 18.1
POMS total score ON 8.8 8.7
*Significant difference between groups. All OFF vs ON compari-
sons are significant.
Percentage of change in POMS and in its factors did not show
any correlation with change in UPDRS III scores; POMS total score
 POSTER SESSION S183

and T,D,A subscales changes significantly correlated (p<0.009) with
BDI II score while C subscale correlates with HAM-A score
(p50.004).
Conclusions: POMS is sensitive to changes in affect states
induced by levodopa administration. These changes are not related to
motor improvement induced by therapy and can be found both
patients with and without motor fluctuations. Mood fluctuations
induced by levodopa administration correlated with depressive symp-
toms and should be considered as a red flag for patients psycho-
logical distress.
467
Different cardiovascular modulation in Parkinsons disease
patients with tremor dominant subtype compared to those with
akinetic rigid dominant subtype
P. Solla, C. Cadeddu, A. Cannas, D. Fonti, G. Orofino, M. Deidda,
L. Cugusi, M. Meloni, G. Mercuro, F. Marrosu (Cagliari, Italy)
Objective: To investigate cardiovascular autonomic modulation
in PD patients with tremor dominant subtype (TDS) in comparison
to akinetic rigid dominant subtype (ARDS) subjects using Heart Rate
Variability (HRV) analysis.
Background: Parkinsons disease (PD) can present itself with dif-
ferent subtypes of motor impairment depending on the predominant
symptoms (tremor or rigidity/bradykinesia). Slower disease progres-
sion and less cognitive decline are observed in TDS patients, con-
firmed by neuro-imaging and pathologic findings which describe a
more favorable outcome in these patients compared to ARDS sub-
jects. Autonomic cardiovascular disorders have been associated with
variable manifestations in patients affected by PD, although the defi-
nite correlations with different subtypes of PD are not clear. In this
context, analysis of HRV represents a non-invasive and established
tool in assessing cardiovascular autonomic modulation.
Methods: Twenty-eight consecutive PD patients (17 with TDS
and 11 with ARDS) were enrolled and compared to 17 age and sex-
matched healthy controls. The following parameters were assessed:
standard deviation of RR intervals (SDNN), root mean square of the
successive differences of RR intervals (RMSSD), total power (TP),
low frequency power (LF), high frequency power (HF).
Results: It was found that LF values were significantly lower in
the ARDS than in the TDS group [LF 41.4 6 13.6 versus 55.5 6 11.6
(p< 0.007), indicating that the disease led to a more evident impair-
ment of the baroreflex modulation of the autonomic outflow medi-
ated by both sympathetic and parasympathetic systems in the first
class of patients.
Conclusions: These findings support the biological relevance of
clinical subtypes supporting the idea of a different pathophysiologi-
cal process between these subtypes. These differences are not only
important for a better classification between PD patients, but also
suggest that different subtypes may also result in different responses
to therapy or in the possible development of cardiovascular side
effects of dopaminergic drugs in these different populations.
468
Apathy in Movement Disorders: A cross-sectional study
M. Sousa, J. Ribeiro, I. Marques, F. Cunha, N. Can
ario, F. Moreira,
A. Freire, C. Janu
ario (Coimbra, Portugal)
Objective: To evaluate apathy frequency and correlate with
motor, cognitive and neuropsychiatric symptoms in a sample of PD
and HD patients at different stages.
Background: Apathy is one of the most frequent and disabling
neuropsychiatric symptoms in several neurodegenerative diseases,
such as Parkinsons (PD) and Huntington (HD) disease. PD and HD
are distinct neurodegenerative Movement Disorders, affecting mainly
the basal ganglia generally having different motor presentations.
Methods: We consecutively assess PD and HD patients recruited
from Movement Disorders and Neurogenetics units, respectively,
from a University Hospitalar centre. In all patients demographics,
clinical data, motor score (Unified Parkinsons disease rating scale
part III for PD; Unified Huntingtons Disease rating scale part I for
HD), cognition (Montreal Cognitive Assessment scale), depressive
symptoms (Beck Depression Inventory-II) and apathy (Apathy Evalu-
ation Scale) were collected. Patients with dementia and major
depression were excluded.
Results: Sixty patients were enrolled, 30 with PD and 30 with
HD. Apathy was present in 63.3% of PD patients and 53.3% of HD
patients. In PD patients, apathy was strongly correlated with motor
score, H&Y stage and depressive symptomatology, whereas in HD
patients, was related with age, disease duration, motor score and cog-
nitive impairment.
Conclusions: We found a similar prevalence of apathy in PD and
HD patients. The results of this study suggests that slightly different
pathways within prefrontal cortex basal ganglia circuits may be
involved in the development of apathy in both diseases.
469
Olfactory performance and resting state functional connectivity
in non-demented drug nave patients with Parkinsons disease
M.K. Sunwoo, J. Cha, J.H. Ham, S.K. Song, J.Y. Hong, J.M. Lee,
Y.H. Sohn, P.H. Lee (Seongnam, Korea)

Demographic characteristics of Parkinsons disease patients according to olfactory performance

PD-H (n523) PD-H (n523) PD-L (n523) p-value

Age (yr) 62.3 (9.17) 66.6 (8.1) 64.1 (11.01) NS
Gender (number of men, %) 11 (46.6%) 26 (47%) 12 (53.4%) NS
Education levels (yr) 12.2 (3.6) 10.1 (3.4) 10.2 (4.8) NS
Parkinsonism duration (mo.) 22.3 (14.5) 24.2 (35.9) 25.5 (18.9) NS
UPDRS motor score 20.1 (8.9) 9.2 (1.3) 23.8 (7.2) NS
CCSI 9.5 (0.7) 6.7 (1.0) 3.6 (0.6) 0.001
K-MMSE 28.0 (1.9) 26.9 (1.8) 27.0 (1.7) NS
BDI 13.8 (10.4) 9.9 (5.8) 16.3 (9.9) NS
Intracranial volume (mm3) 1,303,646.1 (112,177.7) 1,307,842.1 (118,093.6) 1,322,964.3 (120,074.6) NS
Cortical thickness (mm) 3.18 (0.15) 3.11 (0.16) 3.17 (0.13) NS
Values are expressed as mean (standard deviation). PD-H= Parkinsons disease with high CCSI score; PD-M=Parkinsons disease with middle
CCSI score; PD-L=Parkinsons disease with low CCSI score; CCSI=Cross-Cultural Smell Identification; K-MMSE=Korea version of the Mini-
Mental State Examination; BDI=Beck Depression Inventory; UPDRS=unified Parkinsons disease rating scale; NS 5 not significant.

Movement Disorders, Vol. 30, Suppl. 1, 2015

S184 POSTER SESSION

PD-H vs PD-M vs PD-H vs

PD-H PD-M PD-L p-value* PD-M** PD-L** PD-L**
Attention 7.1 (1.3) 7.0 (1.5) 6.6 (1.5) NS NS NS NS
Language and related function 31.4 (3.9) 28.7 (5.1) 28.2(3.7) 0.046 NS NS 0.059
Visuospatial function 16.7 (1.2) 16.3 (2.3) 14.8 (4.0) 0.038 NS NS 0.041
Verbal memory function 14.7 (3.4) 15.3 (2.5) 12.9 (3.3) 0.027 NS 0.028 NS
Visual memory function 16.0 (5.1) 15.7 (5.3) 13.1 (4.2) NS NS NS NS
Frontal executive function 49.9 (6.9) 47.2 (7.8) 40.3 (12.3) 0.004 NS 0.055 0.005
Values are expressed as mean of composite scores (standard deviation). PD-H= Parkinsons disease with high CCSI score; PD-M=Parkinsons
disease with middle CCSI score; PD-L=Parkinsons disease with low CCSI score; NS=not significant. *p-value from analyses of covariance.
**Bonferroni corrected p-values of the post hoc comparison test.

Objective: To evaluate (1) olfactory performance as a predictor
of cognitive impairment influences the functional connectivity within
key brain areas of patients with PD.
Background: Olfactory dysfunction, a salient non-motor feature
of Parkinsons disease (PD) occurring in at least 90% of PD patients,
is associated with ongoing cognitive decline. Resting-state networks
(RSN) offers the evaluation the status of functional systems within
the brain without externally goal-directed cognitive performance. We
investigated the pattern of resting state functional connectivity in
patients with PD according to olfactory performance to further eluci-
date olfactory-dependent cortical-subcortical functional networks.
Methods: A total of 110 non-demented drug-nave patients with
PD were subdivided into three groups of high score (PD-H, n523),
middle score (PD-M, n564), and low score (PD-L, n523) based on
olfactory performance. We performed the resting-state functional

Fig. 2. (469).

Fig. 1. (469).

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
connectivity with seed region of interest in the posterior cingulate
cortex (PCC) and caudate.
Results: An analysis of functional connectivity revealed that PD-
L patients exhibited a significant attenuation of cortical functional
connectivity with the PCC in the bilateral primary sensory areas,
right frontal areas, and right parietal areas compared to PD-H or PD-
M patients.
Meanwhile, PD-L patients exhibited a significant enhancement of
striato-cortical functional connectivity in the bilateral occipital areas
and right frontal areas compared to PD-H or PD-M patients. In the
voxel-wise correlation analysis, olfactory performance was positively
associated with cortical functional connectivity with the PCC in sim-
ilar areas of attenuated cortical connectivity in PD-L patients relative
to PD-H patients[figure1]. On the other hand, the cortical functional
connectivity with the caudate was negatively correlated with olfac-
tory performance in similar areas of increased connectivity in PD-L
patients relative to PD-H patients[figure2].
Conclusions: The present study demonstrated that resting state
functional connectivity exhibits a distinctive pattern depending on
olfactory performance, which might shed light on a meaningful rela-
tionship between olfactory impairment and cognitive dysfunction in
PD.
470
Sleep disturbances in Parkinsons disease and related disorders:
Using Parkinsons disease sleep scale-2
K. Suzuki, A. Numao, Y. Watanabe, H. Fujita, M. Miyamoto, T.
Miyamoto, S. Suzuki, H. Sakuta, T. Kadowaki, K. Hirata (Mibu,
Japan)
Objective: In this study, we evaluated nocturnal symptoms in
Parkinsons disease (PD)-related disorders such as PD, multiple sys-
tem atrophy (MSA) and progressive supranuclear palsy (PSP) using
PD Sleep Scale (PDSS)-2.
Background: Sleep disturbances are one of the important prob-
lems, affecting the quality of life of a significant number of patients
with PD and related disorders. However, thorough assessment for
nocturnal symptoms in PD-related disorders with the use of validated
tools has not been performed.
Methods: A total of 61 PD patients (69.21/-9.2 years), 14 MSA
patients (67.51/-6.2 years) and 9 PSP patients (73.11/-8.5 years)
were included in this study. PDSS-2 was administered to all patients.
Disease severity was rated by Hoehn and Yahr stage. All patients
were assessed by Unified PD rating scale (UPDRS) part III for motor
function. UMSA rating scale (UMSARS) part II was also performed
in MSA patients.
Results: PDSS-2 scores were 17.41/-11.7, 13.91/-9.2 and
16.71/-10.3 in PD, MSA and PSP patients, respectively. Poor
sleepers, defined as PDSS-2 15, were observed as follows: PD,
54.1%; MSA, 50.0% and; PSP, 66.7%. PDSS-2 scores correlated
positively with UPDRS part III score and UMSARS part II score in
patients with PD and MSA, respectively. In PSP, no correlation was
found between PDSS-2 and UPDRS part III scores.
Conclusions: In our study a great number of patients show sleep
disturbances as evaluated by PDSS-2. We suggest that PDSS-2 is a
useful screening tool for evaluating nocturnal symptoms in not only
PD but also its related disorders.
471
The impact of diabetes mellitus on non-motor symptoms in
patients with Parkinsons disease
E.E. Tan, G. Pagano, M. Tagliati (Los Angeles, CA, USA)
Objective: To evaluate the prevalence of non-motor symptoms
(NMS) in Parkinsons disease (PD) patients with and without diabe-
tes mellitus (DM).
S185
Background: The association between PD and DM has been
described in several experimental and clinical studies. DM has been
associated with more severe motor impairment and higher prevalence
of postural and gait instability. Little is known about the impact of
DM on NMS in PD patients.
Methods: We conducted a retrospective cohort study of 385 con-
secutive PD patients seen in the Movement Disorders clinic at
Cedars-Sinai Medical Center over a period of 4 years. All subjects
met the U.K. Brain Bank clinical diagnostic criteria for PD and the
American Diabetes Association criteria for DM. Demographic and
clinical data, including vitals, motor and NMS, dopaminergic medi-
cations, comorbidities and anti-diabetic medications were collected at
the initial consultation visit. v2 test was used for categorical varia-
bles and Mann Whitney U for continuous variables. A two-tailed sig-
nificance level of p < 0.05 was adopted.
Results: Thirty-three patients (8.6%) reported DM. All of them
were type II. Twenty-five patients were treated pharmacologically in
mono- or polytherapy (13 on metformin, 5 on DDP-4 inhibitors, 5
on sulfonylureas, 4 on thiazolidinediones, 1 on exenatide, 4 on insu-
lin). Eight patients were on diet modification alone. No differences
were found for age, gender and PD duration between patients with
and without DM. The number of NMS was significantly higher in
DM patients (11.3 6 3.6 vs. 9.6 6 3.9; p value 5 0.016). Among spe-
cific NMS, only nocturia (63.6%, O.R. 5 2.213 (1.056 - 4.638), p
value 5 0.043), dizziness (57.6%, O.R. 5 2.547 (1.234 - 5.257); p
value 5 0.013) and weight loss (48.5%, O.R. 5 2.573 (1.250 - 5.299);
p value 5 0.014) were significantly more prevalent in patients with
DM. Multivariate linear analysis showed that age (b 5 0.057, 95%
C.I. 0.023 0.091, p50.001), disease duration (b 5 0.182, 95% C.I.
0.117 0.246, p50.0001) and DM (b 5 1.603, 95% C.I. 0.280
2.927, p50.018) were independent predictors of NMS burden in PD
patients.
Conclusions: In patients with PD, DM type II is associated with
a higher burden of NMS, independently of age and disease duration.
In particular, nocturia, dizziness and weight loss were significantly
associated with DM in PD. Larger, prospective studies will need to
further explore the role of DM in PD clinical phenomenology.
472
Parkinsons sleep disorder
A.N. Taravari, F.R. Mexhiti (Skopje, Macedonia)
Objective: To evaluate sleep changes in patients with Parkinsons
disease.
Background: Parkinsons disease is a degenerative disorder of
the central nervous system. The most obvious symptoms are
movement-related; these include tremor, rigidity, bradykinesia and
difficulty with walking and gait. Later, thinking and behavioral prob-
lems may arise, with dementia, depression etc.
Methods: The research was conducted on 32 subjects, patients at
the University Clinic of Neurology with Parkinsons disease. From
all, 8 are men younger than 60 years, 13 men aged 60 years, 6
women younger than 60 years and 5 women older than 60 years. All
32 respondents answered all 15 questions from Parkinsons disease
Sleep Scale. The research also encompasses the typical symptoms of
Parkinsons disease: rigors, tremor, bradykinesia and postural
instability.
Results: The analysis of the average values of almost all of the
answers to the questions individually indicates that the situation is
worst in relation to question 8 and it is 4,19 6 4,03 and the best in
terms of question number 9 and it is 8,25 6 2,41. Also, results
showed the following: total 32 respondents - 20 presents rigors,
tremor is present in 20, bradykinesia is present in 32 and postural
reflexes loss is manifested in 20 patients.
Conclusions: The analysis showed no statistically significant dif-
ference (p> 0.05) of the total score for the PDSS compared to the
analyzed variables (gender, age, rigors, tremor, bradykinesia and pos-
tular instability).
Movement Disorders, Vol. 30, Suppl. 1, 2015
S186 POSTER SESSION
473
Hyposmia as a predictor of non-motor features in patients with
de novo Parkinsons disease
B.L. Tran, L.M. Chahine, J. Rick, M. Christi, D. Abigail, L. Carly,
P. Rachael (Philadelphia, PA, USA)
Objective: To evaluate hyposmia as a predictor of non-motor
symptoms in patients with early Parkinsons disease (PD).
Background: According to the Braak staging scheme for PD,
early pathological changes involve the lower brain stem and olfac-
tory bulb. Given that olfactory dysfunction (hyposmia) is one of the
most prevalent non-motor manifestations of PD, we sought to exam-
ine hyposmia as a predictor of non-motor features in a newly diag-
nosed PD cohort.
Methods: The Parkinsons Progression Markers Initiative (PPMI)
is a multi-site, prospective study which aims to identify biomarkers
in PD. Assessments include the Movement Disorders Society Unified
Parkinsons disease Rating Scale (MDS-UPDRS) Part I items on
cognitive impairment, hallucinations/psychosis, depressed mood, anx-
iety, and apathy. All participants completed the University of Penn-
sylvania Smell Identification test (UPSIT), a measure of olfaction.
Binary logistic regression was used to examine the relationship
between hyposmia and presence of nonmotor features (MDS-UPDRS
Part 1 items), controlling for baseline age, disease duration, gender,
and years of education.
Results: Individuals were categorized into four groups based on
baseline UPSIT score quartiles (range: 1-40). Compared to normos-
mics, those in the lowest quartile had 4 times the odds of reporting
cognitive difficulties (OR=4.15, 95%CI: 1.96-8.78, p<.05) and twice
the odds of reporting anxiety (OR=2.24, 95%CI: 1.21-4.15, p<.05).
Conclusions: Moderate to severe hyposmia is a significant pre-
dictor of self-reported cognitive difficulties and anxiety in an early
PD cohort. These findings have implications for earlier recognition
of non-motor PD-related manifestations and promote further study of
the impact of hyposmia in PD.
474
Transcranial magnetic stimulation increases overall cognition in
patients with Parkinsons disease
J. Trung, A. Hanganu, S. Jobert, B. Mejisa-Constain, A.L. Lafon-
taine, M.A. Bruneau, O. Monchi (Montreal, QC, Canada)
Objective: To assess whether transcranial magnetic stimulation
(TMS) applied over left dorsolateral prefrontal cortex (DLPFC) in
patients with Parkinsons disease (PD) might have an influence on
cognition (PD-MCI).
Background: Cognitive impairment affects up to 40% of PD
patients in the early phase of the disease and it has been shown that
up to 80% of PD patients will eventually develop dementia. Nagano-
Saito et al., 2014 reported reduced activity in the DLPFC and the
caudate nucleus when comparing PD-MCI to PD-non-MCI patients
at the same stage of the disease. Previously we observed using fMRI
that TMS using intermittent theta burst parameters over the DLPFC
results in increased activity and connectivity within the cognitive
cortico-striatal loop. Furthermore, Strafella et al. (2001) showed an
increased dopamine release in the caudate nucleus when applying
repetitive TMS over DLPFC.
Methods: For this study 30 idiopatic PD patients are being
recruited. We performed an intermittent theta burst TMS protocol
applied over the left DLPFC. 15 patients are receiving real TMS
while the other 15 are receiving sham TMS. We applied a complete
battery of neuropsychological assessment which included five cogni-
tive domains: attention, executive functions, language, memory and
visuospatial abilities, as well as clinical tests including the Montreal
Cognitive Assessment, the Beck Depression and Anxiety inventory,
and the apathy evaluation scale .The neuropsychological and clinical
assessment was performed at days 1, 8, 21 and 37. TMS was applied
Movement Disorders, Vol. 30, Suppl. 1, 2015
at days 2, 4, 7. Z scores were calculated for each domain as well as
for the overall cognitive performance.
Results: So far, in 11 patients receiving active TMS, significant
increase in the overall cognitive performance was observed when
applying the real TMS (p<0.05, two-tailed paired t-test). The real
stimulation improved mainly the executive and the visuospatial
domains. Depression scores also improved significantly after TMS,
though anxiety, and apathy did not show any significant differences.
The analysis for patients receiving sham stimulation is under way.
Conclusions: Our preliminary data suggests an overall increase in
cognition after applying the TMS over DLPFC in PD-MCI patients.
Further analysis will be performed to verify the reliability of our pre-
liminary results as well as to differentiate sham stimulation from the
real TMS effects.
475
Effect of saccadic movement impairment cognition in
Parkinsons disease
O.E.U. Turgunkhujaev, R.J. Matmurodov (Tashkent, Uzbekistan)
Objective: Study effect of saccade impairment on cognition in
PD.
Background: Parkinsons disease (PD) is known to be accompa-
nied by a variety of cognitive defects, which can be explained by
progressive destruction of the basal ganglia system.
Methods: Research involved 32 patients with PD (17 men and 15
women) mean age 49.5 1 5.7 years, with almost same level of educa-
tion. The control group was 12 patients without PD. The PD diagno-
sis was established by criteria A.Hughes. To determine cognition
disorders, special neuropsychological test-chart was used.
Results: Patients with PD require longer time to solve graphic
task (51.5 seconds), control group solved in 30.7. We did structural
analysis by forms of PD. In akinetic-rigid form time was 57.8,
tremor form 47.4, mixed form 49.3. Analysis by stage of PD
revealed: 1st stage 45.7, 2nd stage 51.3, 3rd stage - 57.5. So, the
severity of cognition impairment correlates with stage and form of
PD. Attention on visual information is highly dependent from oculo-
motor programming system. Saccadic movements are main motor
program in controlling eye focus on visual object that are controlled
by basal ganglia loop, so they become less rapid in initiating and
have delay in cancelling. This phenomenon influences in PD
patients attention strength, so they are not able to stay in focus on
visual objects, and are not able to get full information about compli-
cated objects. All in one ends with lowering of visual information
intake. This possibly may lead to physiological abnormalities like
depression and low memory.
476
Effect of single levodopa/carbidopa intake on heart rate
variability in Parkinsons disease
A.F. Vasilenko, M.V. Shestakova (Chelyabinsk, Russia)
Objective: To evaluate heart rate variability (HRV) after levo-
dopa/carbidopa intake in Parkinsons disease (PD).
Background: PD is associated with cardiac denervation. We
studied how HRV changes to levodopa/carbidopa intake in idiopathic
PD.
Methods: 23 PD patients on standard levodopa/carbidopa treat-
ment were included in this study. The group of patient was homoge-
nous: III stage of disease, LED varied in small limits.
Rhythmocardiogram recordings were performed before and after sin-
gle levodopa/carbidopa intake.
Results: In group with initial SDNN  15 ms (n515) after levo-
dopa/carbidopa intake reduction of high frequency waves was
observed with lowering of SDNN in most cases. Only in two patients
it accompanied with increasing of low frequency waves and SDNN
raised. In this group the reaction was sympathetic: tendency to
 POSTER SESSION
increase heart beating, diminishing of high frequency waves and in
some cases increasing of low frequency waves. Reduction of high
frequency waves without changes of low frequency waves mean that
sympathetic fibers degenerated. Therefore, SDNN change after levo-
dopa/carbidopa intake is due to the presence of sympathetic nerves.
SDNN rise in safety of fibers and diminish after lesion. In group
with initial SDNN <15 ms (n58) the effect of levodopa/carbidopa
intake was insignificant on HRV. In 2 cases levodopa/carbidopa
intake provoked dysfunction of sinus node and in 1 case - short
period of atrial fibrillation.
Conclusions: The influence of levodopa/carbidopa intake on the
HRV in PD patients was due to the initial heart rate. The sympa-
thetic effect of levodopa/carbidopa was observed in patients with rel-
atively kept autonomic regulation. In the case of peripheral
autonomic denervation at peak of dose period of levodopa/carbidopa
the decompensation of the sinus node dysfunction is possible.
477
A comprehensive approach to Parkinsons disease
C.P. Vaughan, A.E. Vandenberg, F.C. Goldstein, L.M. Trotti, A.P.
Hermida, M.L. Weeks, S.A. Factor (Atlanta, GA, USA)
Objective: Describe the impact of a two-day comprehensive care
clinic program for Parkinsons disease to identify non-motor
symptoms.
Background: According to the AAN quality standards for Parkin-
sons disease (PD), providing high quality care involves addressing
both motor and non-motor symptoms. Non-motor symptoms are
often missed during routine visits even though non-motor symptoms
have a more negative impact on quality of life than motor symptoms
as PD progresses.
Methods: The Emory PD Comprehensive Care Clinic (PD CCC)
provides interdisciplinary team-based assessment and treatment of
PD patients. Referrals to the clinic come from within the university
health system, community providers, and patient self-referrals
through word of mouth and support groups. The presence or absence
of non-motor symptoms is not a requirement for participation in the
PD CCC. During a 2-day evaluation, patients are evaluated by pro-
viders in sleep, psychiatry, medicine, speech and language therapy,
physical therapy, occupational therapy, social work, neuropsychol-
ogy, nursing, and Movement Disorders. Data were collected to
describe the PD CCC patients. A subgroup completed the PDQ-39 to
assess quality of life (QOL) at the initial evaluation and at 6 months.
Results: Ninety-five patients participated in the PD CCC (60%
men, 75% white, mean age 68 yrs (range 38-97), UPDRS part III
mean score 23.8 (range 3-72). Of these, 79% were diagnosed with a
psychiatric condition, 76% with cognitive dysfunction, 98% with a
sleep disorder, and 95% with autonomic dysfunction. Additionally,
86% received recommendations for rehabilitation therapy. At 6
months, among 12 patients who completed the PDQ-39, a significant
improvement in overall QOL (decrease in PDQ-39 score) was
detected (pre mean 0.220 6 0.107, post 0.166 6 0.129, p-value
0.050). Subset scores for mobility (pre mean 0.175 6 0.141, post
0.123 6 0.113, p-value 0.054) and ADL independence (pre mean
0.295 6 0.173, post 0.219 6 0.156, p-value 0.056) also improved.
Conclusions: The Emory PD CCC model is effective in detecting
non-motor conditions in PD patients. The positive impact on QOL
should be evaluated in comparison to usual care in a Movement Dis-
orders clinic.
478
Increased odds of bladder and bowel symptoms in early
Parkinsons disease compared to healthy controls
C.P. Vaughan, J.L. Juncos, A.D. Markland, K.L. Burgio, P.S. Goode,
T.M. Johnson II (Atlanta, GA, USA)
S187
Objective: Estimate the burden of bowel and bladder symptoms
in early Parkinsons disease (PD) compared to healthy controls (HC).
Background: Urinary and bowel symptoms are common non-
motor symptoms of PD, yet studies are limited describing the preva-
lence of these symptoms in a well-defined early PD cohort.
Methods: Data were obtained from the Michael J. Fox Parkin-
sons Progression Markers Initiative (PPMI), which represents an
observational cohort study to verify progression markers in PD. For
this analysis, participants with early PD (diagnosed within two years
of baseline through physical exam and a positive DAT scan) and
healthy controls were included. Prevalent bladder (urinary inconti-
nence (UI) and nighttime voiding) and bowel (constipation and fecal
incontinence (FI)) symptoms were defined as occurring at least some-
times when queried using the Scale for Outcomes in Parkinsons dis-
ease for Autonomic Symptoms (SCOPA-AUT). Bivariate
comparisons were performed using t-test or chi-square analysis as
appropriate. Multivariable logistic regression evaluated bladder and
bowel symptoms between PD and HC participants adjusted for age,
gender, and cognition as measured by the Montreal Cognitive
Assessment.
Results: The early PD cohort included n5423 participants and
the HC cohort included n5195 participants. The proportion of men
(65% vs. 64%) and the mean age (61.0 6 9.7 vs. 60.2 6 11.2 years)
was similar between both early PD and HC. The prevalences of UI
and constipation were higher among early PD vs. HC (UI: 26.7% vs.
8.2%, constipation: 32.4% vs. 11.8% p< 0.0001 for both). The prev-
alence of nighttime voiding was high among both groups, but not
significantly different (82.5% vs. 84.1%, p-value 0.62). FI was infre-
quent among both groups (4.3% vs. 3.6%, p-value 0.69). The odds
of reporting UI and constipation were both significantly higher in
early PD even after adjustment for potential confounders (UI: OR
4.62 95% CI (2.66, 8.37), constipation: 3.30 (2.01, 5.41) p< 0.0001
for both).
Conclusions: The PPMI study represents a well-defined early PD
cohort with a well-matched HC population and symptom question-
naires that have been validated in PD. These results highlight the
burden of bowel and bladder complaints in early PD, which may not
respond to treatments targeting motor symptoms of the disease, but
may respond well to other behavioral or pharmacologic treatments.
479
Patients with REM behavior disorder demonstrate degraded
contrast sensitivity visual acuity while patients with restless legs
syndrome do not
P.H. Vogt, E.M. Keasler, M.J. Khayata, W.H. Whitfield, J.M.
Sanchez, G. Barr, D. Huang, C. Maitland (Tallahassee, FL, USA)
Objective: To analyze contrast sensitivity visual acuity (CSVA)
in patients with REM Behavior Disorder (RBD) and Restless Legs
Syndrome (RLS).
Background: RBD is a sleep disorder that produces motor enact-
ment during REM sleep. RLS is a disorder characterized by the urge
to move ones legs when resting. Although pathophysiology is uncer-
tain, both Movement Disorders involve the dopaminergic system.
Studies demonstrate nigrostriatal dopamine deficiencies in RBD
patients. In RLS, the role of dopamine is evident in the effects of
dopamine agonists, which relieve RLS symptoms, and dopamine
antagonists, which aggravate or induce RLS symptoms. We previ-
ously reported CSVA deficits in early-stage Parkinsonism1, which is
characterized by cellular alpha-synuclein aggregation and death in
dopamine producing cells. We therefore speculated that CSVA might
be impaired in individuals with RBD and RLS. Since both conditions
occur with increased incidence in Parkinsons.
Methods: 19 RBD and 16 RLS patients versus 29 controls. Tests:
visual function questionnaire, SLOAN CSVA wall charts at 100%,
2.5%, and 1.25%, general ophthalmologic and neurological examina-
tions. Spectral Optical Coherence Tomography (OCT). Exclusion
Movement Disorders, Vol. 30, Suppl. 1, 2015
S188 POSTER SESSION
criteria: Visual acuity <20/40, co-morbid ophthalmologic patholo-
gies, and dementia. Results were submitted to independent-samples
t-test.
Results: A statistically significant difference in mean contrast
sensitivity between the RBD and control groups, with the RBD
group scoring lower than the aged matched control group by
6.379 6 3.06 [mean difference 6 standard error], t(45) 5 2.08,
p 5 .043. Within the RBD group, 10 patients were identified with
Parkinsonism and 9 showed neither symptoms nor signs of that con-
dition. The difference in contrast sensitivity between the PD and
non-PD RBD subjects was not significant. There was no significant
difference between the mean contrast sensitivity of the RLS and con-
trol groups.
Conclusions: CSVA is diminished in subjects with RBD but not
RLS. The insignificant difference in CSVA between PD and non-PD
RBD subjects requires a longitudinal study to evaluate the risk of
developing PD in the asymptomatic group.
1. Nowalk N M, J, Wally M, Salmasinia D, Maitland CG. Inves-
tigational Study on the Degree of Contrast Sensitivity Visual Acuity
Defects in Early Stages of Parkinsonism. American Academy of
Neurology; 2013; San Diego, CA.
480
Frequency and predictors of fatigue in Parkinsons disease in a
population-based cohort
E. Warrlich, E.J. Vollstedt, S. Tunc, C. Bibergeil, C. Kritzinger, J.
Graf, V. Tadic, C. Klein, M. Kasten (L
ubeck, Germany)
Objective: To investigate the frequency and contributing factors
of fatigue in Parkinsons disease (PD) in a population-based cohort.
Background: Fatigue is a frequent and disabling symptom in PD
patients, fatigue is often persistent and difficult to treat. However, it
is not only common in PD but also in other disorders. Towards
determinants of fatigue several studies haven been performed and
interesting associations identified but await specification and
confirmation.
Methods: Based on a screening of 10,000 inhabitants of Lue-
beck/Germany aged 50-79 years with 60% response rate, we selected
and examined 743 persons at baseline and assigned groups according
to presence of motor impairment (due to PD or other diseases). 468
persons participated in the one-year follow-up. The second-year fol-
low-up comprised 413 participants and consisted of mailed question-
naires including the Fatigue Severity Scale (FSS), the Beck
Depression Inventory (BDI), the Epworth Sleepiness Scale (ESS),
and the Unified Parkinsons disease Rating Scale (UPDRS). We here
present the second-year follow-up. Groups comprise healthy controls
(HC, n5 184, disease controls (DC, n5137), persons with mild Par-
kinsonian signs (MPS, n548), and PD patients (n544).
Results: The mean age of all participants was 65.9 6 7.8, ranging
from a mean of 64 years in the HC to 67 years in the DC and PD
groups (p<0.001). Sex distribution was balanced (49.4% male over-
all) in all subgroups except for the MPS group (64.6% male).
Fatigue defined as at least mild symptoms in the UPDRS-item
1.13 was most frequent in the PS (27.3%) and the DC group
(22.8%).
Mean score in the FSS was lowest in the HC (24.6 6 12.8) and
highest in the PS group (33.5 6 13.7) (p50.001). In logistic regres-
sion, BDI (OR 1.25 95%CI 1.2-1.3) and ESS (OR 1.2, 95% CI 1.1-
1.3) scores were associated with higher likelihood of fatigue,
whereas age, sex, and diagnosis were not associated with fatigue.
Conclusions: Overall, fatigue was more common in the PD than
in the HC group. However, in logistic regression, depression and
sleepiness scores were associated with presence of fatigue whereas
diagnostic status was not. This suggests the increased frequency of
fatigue to be influenced by depressive symptoms and sleep problems,
which opens therapeutical options to address fatigue.
Movement Disorders, Vol. 30, Suppl. 1, 2015
481
Olfactory function in Parkinsons disease and related disorders
Y. Watanabe, K. Suzuki, A. Numao, M. Miyamoto, T. Miyamoto, H.
Fujita, T. Kadowaki, K. Hashimoto, K. Hirata (Mibu, Japan)
Objective: In this study, we evaluated olfactory function in Par-
kinsons disease (PD) and related disorders such as PD, multiple sys-
tem atrophy (MSA) and progressive supranuclear palsy (PSP).
Background: Olfactory impairment is an early non-motor symp-
tom of PD, being present in a large number of PD patients. It has
also been reported the usefulness of olfactory function test in differ-
entiating PD from Parkinsonian syndrome.
Methods: A card-type odor identification test, Open Essence (OE)
(Wako, Japan) was administered to 92 PD patients (68.7 6 9.0 years),
30 MSA patients (68.2 6 8.1 years), 19 PSP patients (72.1 6 7.1
years) and 74 control subjects (61.5 6 11.5 years). The OE test con-
sists of 12 different odorants familiar to Japanese subjects. Disease
severity was assessed by Hoehn and Yahr stage. All patients were
evaluated by Unified PD rating scale (UPDRS) part III for motor
function. UMSA rating scale (UMSARS) part II was also performed
in MSA patients. Cognitive function was evaluated by Mini-Mental
State Examination (MMSE). Cardiac 123I-metaiodobenzylguanidine
(MIBG) scintigraphy was performed in PD, MSA and PSP patients.
Results: The OE scores were 4.0 6 2.3, 6.9 6 2.5, 5.0 6 2.2 and
7.9 6 2.1 in PD, MSA and PSP patients and controls, respectively.
PD patients had significantly impaired olfactory function compared
with control subjects and MSA patients. In PD patients, the OE
scores inversely correlated with age and disease severity and posi-
tively correlated with MMSE score and the delayed and early heart-
to-mediastinum (H/M) ratio of cardiac MIBG uptake. In control sub-
jects and MSA patients, an inverse correlation between OE scores
and age was observed.
Conclusions: MSA patients exhibited mild impairment of olfac-
tory function compared to PD and PSP patients. Clinical evaluation
of olfactory function may be useful in differentiation of PD and
related disorders.
482
Antipsychotic use in Parkinsons disease is associated with
increased mortality
D. Weintraub, C. Chiang, H.M. Kim, J. Wilkinson, C. Marras, B.
Stanislawski, E. Mamikonyan, H.C. Kales (Philadelphia, PA, USA)
Objective: To determine if antipsychotic (AP) use in Parkinsons
disease (PD) is associated with increased mortality.
Background: Over the disease course, 60% of PD patients expe-
rience psychosis, and 80% develop dementia. Use of APs in PD is
common, with 50% of patients diagnosed with psychosis receiving
treatment. AP use in patients with dementia in the general population
is associated with increased mortality and morbidity, but it is not
known if this risk extends to PD patients as well.
Methods: In this retrospective, matched, case-control cohort
study, Fiscal Year 1999-2010 national Veterans Affairs health system
administrative data was used to examine the risk associated with AP
use in a large cohort of idiopathic PD patients with stable recent
health. We compared 180-day mortality rates in those patients initiat-
ing an AP with matched non-AP users (matched on age (1- 2.5
years), gender, race, index year, presence of dementia, time from
dementia dx to index date (1- 180 days), time from PD dx to index
date (1- 180 days), delirium, hospitalization, 3-category Charlsons
Comorbidity Index, and new non-psych medications within 14 days
of AP prescription). Cox regression models accounting for matching
were run using both intent-to-treat (ITT) and exposure period only
analyses.
Results: There were 7,877 matched PD pairs. Considering all
APs as a group, users were more than twice as likely to die com-
pared with non-users during 180-day period after AP initiation on
both ITT and exposure analyses (ITT HR=2.35, 95% CI=2.08, 2.66,
 POSTER SESSION
p<0.001). The HR was higher for typical compared with atypical
APs (ITT HR=1.55, 95% CI=1.24, 1.92, p<0.001). Among atypical
APs, HRs in descending order of risk were olanzapine (HR=2.79,
95% CI=1.97, 3.96), risperidone (HR=2.46, 95% CI=1.94, 3.12) and
quetiapine (HR=2.16, 95% CI=1.88, 2.48), all p values <0.001.
Conclusions: AP use is associated with an increased mortality
risk in PD patients, after adjusting for measurable confounders
related to PD severity and comorbidity. This result highlights the
need to use this medication class cautiously in this population.
Future studies should examine causes of death in AP users to inform
clinical care, as well as the role for non-pharmacologic strategies in
managing psychosis in PD. In addition, new APs that do not increase
mortality in patients with neurodegenerative diseases need to be
developed.
483
Deep brain stimulation (DBS) in the external globus pallidus
(GPe) promotes sleep in a rodent model
J. Wu, M. Qiu, M. Chen, D. Nelson, J. Lu (Minneapolis, MN, USA)
Objective: To quantify the effects of DBS in GPe on sleep of
rodent.
Background: Parkinsons disease (PD) is one of the most recog-
nized of the basal ganglia disorders and is characterized by impacts
on movement as well as non motor functions including sleep. Basal
ganglia mechanisms may drive both movement and sleep impacts of
PD. Similarly therapies for movement symptoms in PD may also
modulate sleep in PD. For movement it is well established that the
loss of substantia nigra pars compact (SNc) dopamine signaling to
the basal ganglia produces motor symptoms including rigidity, brady-
kinesia and tremor. More recent work suggests that reduced SNc
dopamine may also interfere with sleep regulation. Specifically,
dopamine from SNc is thoughtto act upon D2 receptors among stria-
topalldial inputs resulting in a disinhibition of GPe promotion of
sleep. DBS targeted to the basal ganglia consistently demonstrates
effective treatment of PD motor symptoms with the two most popu-
lar surgical targets for therapy are internal GP (GPi) and the subtha-
lamic nucleus (STN). Interestingly, clinical studies suggest that DBS
in both targets have also been reported to improve insomnia in PD
patients.
The study described here quantifies the impacts of neurostimula-
tion on GPe using sleep measurements in an established rodent sleep
model. Specifically we tested the hypothesis that GPe stimulation
would be associated with changes in NREM and REM sleep in this
model.
Methods: We placed the stimulation electrode in the GP and
EEG/EMG electrodes in 6 rats. After two weeks, we recorded the
baseline sleep during the night and administrated DBS (100 uA and
180 Hz) during 19:00-23:00 in the next day.
Results: Compared to the baseline sleep during the same period
of prior day, DBS (180 Hz and 100 uA) in the GPe during 19:00-
23:00 significantly increased both NREM sleep and REM sleep by
70%. Transitions from wake to NREM and from NREM to REM
and NREM to wake were significantly increased. The EEG power
spectrum of NREM sleep by DBS was similar to that of the baseline.
However, the sleep latency was not affected by the DBS. We have
tested different frequency and current and found 180 Hz and 100 uA
was ideal stimulation without abnormal behavior. DBS with > 100
uA caused upper body twisted.
Conclusions: GPe DBS promotes both NREM and REM sleep
and may provide a clinical method to improve sleep in PD patients
with sleep disorders associated with PD.
484
Demographics and motor features on risk of Parkinsons disease
dementia: A meta-analysis
Y. Xu, H. Shang (Chengdu, Peoples Republic of China)
S189
Objective: To evaluate the association between demographics,
motor deficits of patients with Parkinsons disease (PD) and the risk
of developing Parkinsons disease dementia (PDD) through a meta-
analysis.
Background: Parkinsons disease (PD) is one of the most com-
mon neurodegenerative conditions with not only prominent motor
features, but non-motor signs and symptoms as well. Parkinsons dis-
ease dementia (PDD) is a critical non-motor symptom and an impor-
tant prognostic factor. No review has comprehensively assessed
predictive factors for later diagnosis of PDD.
Methods: A systemic search for studies on risk factors or predic-
tors of PDD in MEDLINE and EMBASE, between 1972 and October
2014, was conducted. Cohort studies that clearly defined PDD and
presented odd ratios or risk ratios were included in the meta-
analysis. Random effects model was used to calculate relative risks
(risk ratios) and their corresponding 95% confidence intervals.
Results: Among 36 studies that met the inclusion criteria, 12
studies provided sufficient data and were included in the analysis.
Later diagnosis of PDD was found to be associated with age at study
enrollment (relative risk [RR], 1.07; 95% confidence interval [CI],
1.05-1.10) and male sex (RR, 1.73; 95% CI, 1.33-2.25). Positive
association with PDD was also found in higher UPDRS motor scores
(RR, 1.04; 95% CI, 1.03-1.05). Age at onset, disease duration, educa-
tional level, UPDRS total scores, and Hoehn & Yahr stages did not
show a significant association with later diagnosis of PDD.
Conclusions: Older age, male sex and higher UPDRS motor
scores increases the risk for later PDD diagnosis. Further studies are
needed to confirm our negative finding on the association between
other motor features and PDD.
485
Is palmomental reflex an important clinical marker of REM
sleep behaviour disorder in patients with Parkinsons disease?
R. Yadav, R. Mahale, P.K. Pal (Bangalore, India)
Objective: To detect clinical characteristics of importance in dif-
ferentiating Parkinsons disease patients with and without Rapid Eye
Movement sleep behavior disorder (RBD).
Background: Palmomental reflex is one of the primitive reflexes
used by clinicians in the clinical examination to discriminate the var-
ious degenerative dementias. The importance of primitive reflexes in
patients with RBD is not known.
Methods: This was a prospective, questionnaire based study done
at National Institute of Mental Health and Neurosciences, Bangalore
after prior Institutional ethics committee approval. Patients with PD
were clinically examined and the presence of RBD was diagnosed
using the minimal criteria for diagnosis of RBD (International Classi-
fication of Sleep Disorders-1). RBD screening questionnaire based
on the minimal criteria was used. The bed-partners were also inter-
viewed with Mayo sleep questionnaire. Other scales included Unified
Parkinsons disease Rating Scale-part III (UPDRS-III), Hoehn &
Yahr Stage, Mini Mental Status Examination, Pittsburgh sleep qual-
ity index, Parkinsons disease Sleep Scale, Epworth Sleep Scale,
Hamilton anxiety rating scale and Hamilton depression rating scale.
Results: A total of 126 PD patients without RBD (mean age:
61.1 6 9.8 years) and 30 with RBD (mean age 54.1 6 11.1 years)
were enrolled. Patients with RBD had higher gait score (p<0.05),
higher HAM-A (p50.02), higher ESS score (p<0.001) as compared
to patients without RBD. Patients with RBD had a mean MMSE
score of 26.87 6 2.31 (range: 23-30) and in patients without RBD it
was 27.98 6 2.33 (range: 23-30). (p50.005). There was no difference
in features as olfactory dysfunction, rigidity score, blink rate, trem-
ors, stooped stance and postural instability in the two groups. How-
ever Palmomental reflex was present in 63.3% patient of RBD and
only 34.9% of the non RBD (p50.007).
Conclusions: PD patients with RBD have significantly higher
presence of Palmomental reflex which is a frontal release reflex. This
could be reflection of the impaired cognitive dysfunction in these
Movement Disorders, Vol. 30, Suppl. 1, 2015
S190 POSTER SESSION
patients. Larger studies are needed to see the sensitivity and specific-
ity of this sign in patients with RBD.
486
Parkinsons disease clinical study of sexual dysfunction
H. Ye, Z. Mao, S. Ji, Q. Yang, Z. Xue (WuHan, Peoples Republic of
China)
Objective: The survey between Parkinsons disease(PD) patients
and the same period in hospitalized non-Parkinsons patients aged
with sexual dysfunction, clinicians fully understand the incidence of
sexual dysfunction in PD patients, characteristics and the quality of
life(QOL), and explore its mechanism and related factors.
Background: Sexual dysfunction is one of non-motor symptoms
in patients with Parkinsons performance,clinicians were lack of the
definite concept of sexual function, patients take on more psycholog-
ical and domestic pressure.
Methods: Using UPDRS-IIIscores, Hoehn-Yahr scores (HY),
Mini Mental State Examination (MMSE), Hamilton Depression Rat-
ing Scale (HAMD), the International Index of Erectile Function
Table (IIEF-5), designing a comprehensive survey of sexual function
table and World Health Organization quality of Life summary table
(WHOQOL),120 cases of patients were valid questionnaires.All of
40 PD patients completed levodopa equivalent dose (LED) conver-
sion, and non-PD 80 matching, without significant central nervous
system disorders, of WHOQOL questionnaire scores were one-
sample t-test statistical comparisons. PD group for sexual dysfunc-
tion and the control were compared in gender, age, educational level,
time of onset, duration and HAMD,which analysis the difference and
correlation.
Results: The rate of sexual dysfunction in PD was 90%. 30% in
the presence of moderate or severe erectile dysfunction, there are
still more than 50% of the libido, 75% had tried intercourse, only
25% were able to complete, only 7.5% received a sexual gratifica-
tion. WHOQOL profile average score lower than non-PD patients
(P<0.05), especially in the physical, social relationship score lower
(P<0.01), QOL significantly decreased. 80% of PD patients with
psychological symptoms, 20% family problems exist. In gender,age,
educational level, time of onset, duration, UPDRS-III, HY scores and
LED no difference; investigation HAMD score (14.951/-9.12)
points, the control (10.961/-9.82) points, the difference between the
two groups was statistically significant (P<0.05),which by linear
regression analysis showed that this survey was of meaningful.
Conclusions: Sexual dysfunction prevalence of PD patients, over-
all QOL at a low level, PD suffer sexual dysfunction and UPDRS-III
score, HY score, HAMD score,gender and age were related. Health
care and social security departments should strengthen the focus on
sexual dysfunction in patients with PD-related issues.
487
Visual exploration in Parkinsons disease
D.F. Ye, N. Vanegas-Arroyave, P. Lauro, M. Hallett, C. Lungu
(Bethesda, MD, USA)
Objective: To examine visual exploration patterns in patients
with Parkinsons disease (PD) and healthy volunteers.
Background: PD patients exhibit a number of oculomotor and
visuospatial abnormalities, including decreased saccade amplitude,
increased fixation duration, and diminished visual scanning area.
Freezing of gait in PD is an important deficit, often induced by door-
ways and narrow spaces, and therefore may be strongly influenced
by visual information. Studying visual exploration patterns in PD
patients may uncover interventions that improve their ambulatory
function. In previous studies, subjects have explored visual stimuli
under primarily static conditions during seated computer assess-
ments. Our study examines visual exploration strategies in PD
patients in a dynamic setting during walking.
Movement Disorders, Vol. 30, Suppl. 1, 2015
Methods: Subjects were 17 PD patients without freezing of gait
in the OFF medication state and 17 age-matched healthy volunteers.
Subjects were asked to walk down a corridor through a doorframe
and return to the starting point after reaching the end of the hall.
Using the portable SensoMotoric Instruments (SMI) Eye Tracking
Glasses, we measured number of blinks and saccades, saccade ampli-
tude, fixation duration, and fixation location in the recorded visual
field. Fixation locations were mapped to 15 predetermined visual
areas of interest (AOIs) on reference images of the testing corridor.
Comparisons were made between groups after data normalization
using SPSS.
Results: As previously demonstrated, PD patients demonstrated
decreased blinking time and longer fixation durations. Compared to
the control group, PD patients fixated more on the ground (p50.036)
and the lower portion of the end of the corridor (p50.014). In con-
trast, the control group displayed significantly greater exploration of
the doorway (p50.029) as well as a tendency to fixate on the lateral
walls of the hallway.
Conclusions: We found significant differences in the visual
exploration patterns between PD patients and healthy volunteers. PD
patients tended to focus on the floor and other areas near ground
level, whereas healthy volunteers were more likely to explore their
surroundings. These differences could potentially play a role in the
gait manifestations of PD and lead to visually-guided therapy para-
digms. Additional studies to examine oculomotor and visual perform-
ance in PD patients with freezing of gait are ongoing.
488
Chronotype and sleep quality in Parkinsons disease
R. Zangaglia, B. Minafra, M. Terzaghi, C. Pacchetti, R. Manni
(Pavia, Italy)
Objective: Aim of this study is to define the quality of sleep and
chronotype of PD patients and the relationship between chronotype,
sleep disturbances and clinical features of PD.
Background: Nighttime sleep disturbances affect up to 90% of
Parkinsons disease (PD) patients.
The most common sleep disorders in PD include insomnia, REM
sleep behavior disorder, sleep apnea, and restless legs syndrome/peri-
odic limb Movement Disorder . Changes in circadian rhythmicity
have been associated with reduced nighttime sleep quality, daytime
alertness and cognitive performance.
Methods: 274 subjects with PD completed successfully the
Morningness Eveningness Questionnaire-short version (MEQ). Each
patient, with the help of the caregiver, was also subjected to a brief
semi-structured interview in order to investigate the nocturnal sleep
quality, the presence of hallucinations and confusional arousals.
Moreover, all the patients filled in the Epworth Sleepiness Scale
(ESS) and were evaluated with Mini Mental State Examination
(MMMSE) and UPDRS.
Results: From the MEQ analysis 129 subject resulted Morning
and 145 Intermediate oriented and only 3 subject Evening
oriented.
Morning oriented subject (age 70.5 68.6 years) presented a ESS
score 5.45 64.24 and MMSE 25.01 6 4.60.
Intermediated oriented subject (age 71.07 610.67 years) pre-
sented a ESS score 4.92 63.75 and MMSE 24.54 6 4.16.
The two groups did not differ significantly respect to age, dura-
tion of illness, motor impairment (UPDRS) and cognitive function
(MMSE).
Within the group of intermediate, 42% of the subjects had visual
hallucinations (21.1% compared to the subject of the morning ori-
ented, p 5 0.007); while 28% had confusional arousals (vs. 8 .2% of
subjects morning oriented, p 5 0.005).
Conclusions: The two groups did not show significant differences
concerning sleep quality: duration, continuity and quality of noctur-
nal sleep, daytime sleepiness, presence of respiratory disorders and
parasomnias.
 POSTER SESSION
These preliminary results suggest a possible association between
chronotype and presence of visual hallucinations and confusional
arousals in subjects with PD.
489
Depression and nighttime-sleep problems in Parkinsons disease
K. Zhu, J. Marinus, J.J. van Hilten (Leiden, Netherlands)
Objective: To unravel the interrelationship between depression
and night-time sleep problems (NSP) in patients with Parkinsons
disease (PD).
Background: Insomnia is a characteristic of depression and these
features are therefore inherently related. Interestingly, an earlier
study found that NSP are even associated with depressive symptoms
in PD patients who do not meet the criteria of depression (1). Since
depression and NSP are highly prevalent in PD and negatively affect
quality of life, unravelling the temporal relation between the two fea-
tures is important for understanding the pathology and targeting
interventions. This knowledge is not available since most previous
studies had a cross-sectional design, while longitudinal studies usu-
ally focussed on either depression or NSP.
1. Verbaan D, van Rooden SM. Visser M, Marinus J, van Hilten
JJ. Nighttime sleep problems and daytime sleepiness in Parkinsons
disease. Mov Disord 2008:23:3541.
Methods: Univariate and multivariate survival analyses were per-
formed to identify risk factors for developing depression or NSP in
PD. Depression was defined as a score of 15 on the Beck Depres-
sion Inventory (BDI), while NSP was defined as a score 7 on the
SCOPA-SLEEP. Analyses were performed using data of the
SCOPA-PROPARK cohort, a longitudinal study of over 400 PD
patients who have been examined annually over a period of five
years.
Results: 88 (31%) of the 272 patients without depression at base-
line developed depression during follow-up. Age, age at PD onset,
daily levodopa dose and excessive daytime sleepiness (EDS)
emerged as independent risk factors for depression in the multivari-
ate model; although presence of NSP was univariately related to the
development of depression, it was not an independent predictor. 99
(37%) of the 271 patients without NSP at baseline developed NSP
during follow-up. Univariate analyses identified the BDI score as the
only risk factor for developing NSP over time and therefore multi-
variate analyses for NSP were not run.
Conclusions: In this longitudinal study, we identified age, age at
onset, daily levodopa dose and EDS but not NSP - as independent
risk factors for developing depression in PD, whereas depression was
identified as the only factor that predicted future development of
NSP. Thus, while depression emerges as an independent risk factor
of future NSP, the presence of NSP does not predict future develop-
ment of depression.
Neurophysiology
490
Electromyographic patterns of vocal cords during wakefulness
and polysomnographic abnormalities in patients with multi-
systemic atrophy
E. Alfonsi, N. Pozzi, M. Terzaghi, P. Prunetti, E. Alvisi, M.
Calabrese, A. Montini, M. Fresia, L. Marchetta, R. Manni, C.
Pacchetti, A. Moglia (Pavia, Italy)
Objective: To evaluate relations between electromyographic/elet-
trokinesiographic (EMG/EKG) abnormalities of vocal cord (VC)
muscles recorded during wakefulness and polysomnography (PSG)
dysfunction in multisystem atrophy (MSA).
S191
Background: The relationship existing between PSG abnormal-
ities and EMG/EKG abnormalities of VC during wakefulness has
never been examined in patients with MSA.
Methods: We examined 16 patients with MSA (13 MSA-P and 3
MSA-C). The different parameters of the PSG of these patients were
correlated to EMG/EKG of the VC recorded during wakefulness.
Results: The presence of stridor was significantly related to tonic
EMG activity at rest of VC, and to electromyographic recording of
inspiratory tirage during wakefulness. In particular, inspiratory
tirage and tonic EMG activity in quiet breathing during wakeful-
ness correlated both to the number of nocturnal desaturation, as well
as to the presence of episodes of nocturnal apnea/hypopnea. Neuro-
genic alterations of MUAPs of VC abductor muscles were present in
a very limited number of patients (2/16 cases). In particular, these 2
patients had maximal respiratory abnormalities associated with stri-
dor during PSG and showed the highest severity of the diseases.
Conclusions: The EMG/EKG study of the VC in the waking state
could provide useful information on respiratory conditions of patients
with MSA. Neurogenic alterations of VC muscles are rarely observed
in these patients. These alterations, when present, may be in relation
to aspects of extreme severity of the disease, at least as regards
respiratory symptoms.
References:
Not paralysis, but dystonia causes stridor in multiple system atro-
phy. Merlo IM, Occhini A, Pacchetti C, Alfonsi E. Neurology. 2002
Feb 26;58(4):649-52.
Pathogenesis of laryngeal narrowing in patients with multiple sys-
tem atrophy. Isono S, Shiba K, Yamaguchi M, et al. J Physiol
2001;536:237-49.
491
Intracranial EEG reveals differences in auditory change
detection of thalamic and basal ganglia regions
A.K. Beck, G. L utjens, K. Schwabe, R. Dengler, J.K. Krauss, P.
Sandmann (Hannover, Germany)
Objective: To better understand the involvement of subcortical
structures in the detection of relevant stimuli, involuntary attention
and distractibility.
Background: Attentive monitoring of the environment is funda-
mental for efficient detection of relevant stimuli and is well investi-
gated for cortical regions. The P300 component is frequently used in
electroencephalographic (EEG) studies as a measure for attentional
and cognitive functions and is supposed to give further insight into
context-specific processes of subcortical structures.
Methods: In this ongoing study, simultaneous recordings of local
field potentials (LFPs) and event-related potentials (ERPs) from
intracranial and scalp EEG were obtained in 16 patients (mean
age=55.9 6 19.7 years) undergoing deep brain stimulation (DBS).
These patients were implanted bilaterally with quadripolar electrodes
in the subthalamic nucleus (STN; n56; PD), the thalamic ventral
intermediate nucleus (VIM; n56; essential tremor) or the globus pal-
lidus internus (GPi; n55; segmental dystonia, Tourette syndrome).
Within 5 days after surgery, they performed an auditory three-class
oddball paradigm with externalized DBS electrodes. Subcortical and
cortical ERPs were analyzed upon presentation of one frequent
standard stimulus (900Hz; 72%) and two infrequent stimuli (600Hz
and 1200Hz), either being a relevant (14%) or a distractor (14%)
stimulus. Stimuli were presented for 62ms with an interstimulus
interval of 800 to 1200ms. Patients were asked to press a button to
the relevant stimulus.
Results: Analysis reveals high accuracy in all patients
(84.45%614.6). Preliminary behavioral results show shortest
response times in STN patients when compared with GPi or Vim
patients. First EEG results show a P300 component over parietal
regions that was largest upon presentation of target stimuli compared
with distractor and standard stimuli. A similar P300-like component
was also found in LFPs suggesting stimulus-specific responses of
Movement Disorders, Vol. 30, Suppl. 1, 2015
S192 POSTER SESSION

subcortical structures. Here, STN showed shorter latencies and larger

amplitudes compared to GPi or Vim.
Conclusions: The P300 reflects attentional processes that require
stimulus detection and discrimination. The present results point to an
association between short response times and high LFP amplitudes
in the STN and suggest that the STN may play a pivotal role in
context-specific processes.

492
Prevalence of quantitaive sensory abnormalities and correlation
with autonomic disturbances in patients with idiopathic
Parkinsons disease and Parkinsons plus syndromes
R. Borgohain, R.M. Kandadai, M.K.V. Ch, A. Jabeen, M.A.
Kanikannan (Hyderabad, India)
Objective: To identify and assess the correlation between quanti-
tative sensory abnormalities and autonomic dysfunction in patients
with idiopathic Parkinsons disease (PD) and Parkinsons plus
syndromes.
Background: Autonomic disturbances are seen in Parkinsons
disease (PD) and Parkinsons plus syndromes. But the contribution
of peripheral component and presence of sensory abnormalities in
these syndromes are not clearly known. As the sensory deficits are
mild and are usually missed on routine nerve conduction studies a
more sensitive sensory examination may be helpful.
Methods: Thirty-nine patients attending Movement Disorders
clinic with diagnosis of PD, progressive supranuclear palsy (PSP) Fig. 2. (492).
and multiple system atrophy (MSA) were included in the study.
Patients with other causes of autonomic dysfunction were excluded.
Conclusions: CASE -IV picked up sensory abnormalities in more
Detailed history, neurological examination, electroneuromyogram,-
than 50% of PD patients and 40% of patients of MSA-P. Impaired
cardiovascular autonomic function testing (AFT) and computer
cold detection was the most common disorder. Autonomic dysfunc-
assisted sensory examination (CASE IV) studies were evaluated in
tion was also more common in MSA and PD compared to PSP.
all. CASE IV studied three modalities -vibration detection threshold
There was a significant correlation between the two abnormalities
(VDT), cold detection threshold (CDT) and heat pain (HP). A value
suggesting impairment in small fibres.
corresponding to greater than 95th percentile (based on normal age
and sex matched controls) were considered to be hypoaesthetic and
abnormal.
Results: Among 39 patients, PD were 15 (38.4%), PSP 12 493
(30.7%), MSA 12 (30.7%) . All had normal nerve conduction
Deep brain stimulation (DBS) rescue of gait freezing by
response. PD (53.3%) and MSA-P (41.6%) had significantly higher
patterned stimulation in select Parkinsons disease (PD) patients
abnormalities on CASE-IV compared to PSP patients (8.1%). Overall
36% of all patients had QST abnormalities.PD (53.3%) and MSA-P D.L. Caputo, D.P. Schneider, R.J. DiPaola, S.F. Danish, E.L.
(41.6%) had significantly higher abnormalities on CASE-IV com- Hargreaves (New Brunswick, NJ, USA)
pared to PSP patients (8.1%) [figure1] .Abnormalities in cold detec- Objective: To report that PD gait freezing in some patients can
tion threshold was maximum (25%), followed by vibration detection be ameliorated through the use of patterned stimulation implemented
threshold (20%) and hot pain (15%). AFT abnormalities were seen through cycling.
in 75% of MSA, 46% of PD and 33.3% of PSP patients [figure2]. Background: Cycling is the automatic and periodic subsecond
On comparison of QST and AFT, there was significant correlation deactivation of programmed stimulation parameters. No reports dur-
with Pearson correlation coefficient of 0.42. ing the last decade indicate symptom relief from cycling (Montgom-
ery, 2005; Kuncel et al., 2012; Brocker et al., 2013). Here we report
a symptom profile that permits cycling to benefit gait freezing in a
small series of DBS implanted PD patients.
Methods: We implemented cycling in an initial case to lessen a
DBS adverse speech effect that also inadvertently improved gait
freezing. We have now attempted to implement cycling in a total of
7 PD patients (GPi=3, STN=4) with similar symptom profiles. After
standard optimization of the sessions initial parameter group, we
used subsecond cycling resolution to generate patterned stimulation
in a parallel group using any On/Off proportions and durations found
to be clinically effective. The two DBS parameter groups were then
compared for parameters and benefit.
Results: For a single case in each DBS site, cycling failed to be
implemented, due to return of uncontrolled tremor in the STN, and
lack of benefit in the GPi. In both these cases, pre-cycling frequency
for tremor control was greater than 150Hz. Cycling was successfully
implemented for the reduction of DBS related speech adverse effect
Fig. 1. (492). and amelioration of gait freezing in 2 GPi and 3 STN implanted PD

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
patients. In all successful cases, pre-cycling frequency for tremor
control was 130Hz or less. Post-cycling compensatory parameter
increases for breakthrough tremor were required for frequency 3/5,
pulsewidth 3/5 and amplitude 5/5 cases. Optimal cycling On/Off pro-
portions for the STN were balanced (.3/.2s, .3/.2s, & .1/.1s) while
optimal proportions for the GPi were disproportionate (.2/.5s & .2/
.5s). Implementation of cycling was immediately detected by all 5
patients as a lessening, or dropping away, of the stimulation.
Symptomatic benefit was self-reported by the patients and ranked by
three non-blinded experts.
Conclusions: Previously, cycling benefit has been sought for car-
dinal symptoms (Kuncel et al., 2012; Brocker et al., 2013). Cycling
may provide benefit for non-traditional DBS responsive symptoms
due to its non-continuous/patterned nature.
494
Exercise intervention modulate corticostriatal glutamatergic
neurotransmission by increased D2DR and NMDAR1 expression
of striatum in PD model of rats
W. Chen, X. Liu, D. Qiao, L. Hou (Beijing, Peoples Republic of
China)
Objective: To assess effects of exercise to striatal ultrastructure
of the synapses, concentration of Glu and expression of D2DR and
NMDAR1 in PD rats, this paper investigates mechanisms of exercise
improving PD related corticostriatal glutamatergic neurotransmission.
Background: Parkinsons disease (PD) is a slowly progressive prev-
alent neurodegenerative disorder, which characterized by the degenera-
tion of dopaminergic neurons projecting to the striatum. In striatal
dendritic spines of medium spiny neurons (MSNs), DAergic terminals
from the substantia nigra pars compacta converge with glutamatergic ter-
minals. The deficiency of DA in striatum may lead to significant changes
in corticostriatal glutamatergic synaptic architecture, and functional
changes of basal ganglia. In many animal models of PD, exercise has
been shown to induce improvement of basal ganglia function and to pro-
duce beneficial effects on motor behavior. Accordingly, exercise
improve motor function of PD patients might associated with cortico-
striatal glutamatergic neurotransmission changes.
Methods: Male SD rats were randomly divided into Control
group, Control1Ex group, PD group, PD1Ex group with 18 rats in
each group. PD rats was established by injection of 6-OHDA in right
medial forebrain bundle. Control and Control1Ex groups rats
received same dose of saline. Postoperative 24 h of exercise group
rats were take 4 weeks of exercise intervention, exercise program for
11 m/min, 30 min/d, and 5 days/week. The TEM detected synaptic
ultrastructure in striatum, the levels of Glu in the striatum were
detected by HPLC, observe the striatal D2DR and NMDAR1 expres-
sion by immunohistochemical and western blot technique.
Results: Compared with PD, striatal proportion of perforated syn-
apses was significantly decreased in PD1Ex rats (P < 0.05), exercise
can decrease striatal Glu concentrations in PD rats (P < 0.05). Com-
pared with PD, striatal D2DR and NMDAR1 expression increased
significantly in PD1Ex rats (P<0.05, P<0.05).
Conclusions: Exercise intervention can effectively decrease corti-
costriatal neurotransmission of PD rat model, which may be medi-
ated by exercise enhanced efficacy of DA regulate corticostriatal
glutamatergic neurotransmission.
495
Impedance variability of the different deep brain stimulation
neural targets
Y.M. Fernandez, D.L. Caputo, D.P. Schneider, S.F. Danish, E.L.
Hargreaves (New Brunswick, NJ, USA)
Objective: To compare the impedances of Deep Brain Stimulation
(DBS) targets; the Subthalamic nucleus (STN), Globus Pallidus interna
(GPi), and Ventral intermediate nucleus of the thalamus (VIM).
S193
Background: Lettieri and colleagues (2014; European Journal of
Neurology), claim that DBS of the Globus Pallidus interna (GPi) for
Dystonia was more efficacious, during the last six months of the
postoperative management year under current mode then under volt-
age mode. An underlying explanation may be related to an increased
variability of the GPi tissue impedance, compared to other targets.
Methods: Impedances were obtained with the NVision8840 Cli-
nician Programmer, during 24 sessions from 23 individuals
implanted with Activa family neurostimulators for Movement Disor-
ders (6 bilateral STN for PD, 7 bilateral and 2 unilateral VIM for
ET, and 8 bilateral GPi, 6 for PD and 2 for Dystonia). Data from a
single STN and GPi leads were excluded due to out of range values.
Six impedance measurement sets were obtained approximately 1
minute apart, during a single programming session. The mean bipolar
values and associated standard deviations (SDs) of the six readings
were analyzed by Target, and Contact Spacing, while duration of
therapy served as a covariate.
Results: GPi mean impedance values were significantly higher
than both the STN and VIM F(2,258)=3.071; p5.048, which were
not different from each other. Mean impedance also related to dura-
tion of therapy F(1,258)=12.457; p<.0005 where lower values were
associated with longer durations, when used as a covariate target dif-
ferences became non-significant F(2,258)=2.540; p5.081. Mean
impedance also varied with Contact Spacing where higher values
were associated with greater spacing F(2,258)=17.580; p<.0005, but
did not interact with Target or duration of therapy. Analyses of the
SDs indicated that the VIM was associated significantly greater SDs
than both the STN and GPi F(2,258)=5.530; p<.0005, which were
not different from each other. Neither Contact Spacing or duration of
therapy related to impedance SDs.
Conclusions: Our finding of greater impedance variability for the
VIM target may account for the known difficulty in achieving thera-
peutic stability (Zhang et al., 2010, Journal of Neurosurgery). The
findings of Lettieri et al., (2014) may also not be unique to the GPi
and could apply across all implant targets.
496
Effects of texting while walking (dual tasking) on objective gait
parameters
H.V. Gupta, T. Virmani (Little Rock, AR, USA)
Objective: To evaluate the changes in baseline gait characteris-
tics with dual tasking.
Background: Cellular phones are frequently used in our daily
lives while engaged in other activities. Dual tasking (such as count-
ing backwards while walking) has been reported to change baseline
gait parameters in the elderly and in Parkinsons disease can lead to
loss of independence and falls. Here we chose to assess the effects
of texting on objective gait parameters, as it is a commonly per-
formed dual task.
Methods: Healthy subjects aged 18-80 years without history of
falls, lower extremity orthopedic procedures or chronic pain, were
included in this study after obtaining IRB approval. Subjects were
instructed to walk on a 20 by 4 foot pressure sensor mat (Zeno
Walkway, Protokinetics, Havertown, PA) with multiple repetitions,
at their normal gait speed and then while texting on a cellular phone.
The data was collected and analyzed using the PKMAS software
(Protokinetics) for standard gait characteristics. Statistical analysis
was performed using SPSS 22 (IBM).
Results: 22 subjects with a mean age of 44, were enrolled and ana-
lyzed. There was a statistically significant decrease in average stride
length (140.0 6 14.8 vs 127.4 6 15.1 cm, baseline vs. texting; p<0.001
paired t-test), single support percent (36.65 6 1.5 vs 35.6 6 1.5;
p<0.001) and velocity (135 6 22 vs 116 6 19 cm/s; p<0.001). There
was also a significant increase in the coefficient of variation for stride
length (4.0 6 3.1 vs 6.1 6 7.6 cm, p50.007 Wilcoxon), single support
percent (3.0 6 1.9 vs 4.5 6 3.3 cm; p50.001) and step time (3.6 6 2.1
vs 4.4 6 2.3 cm; p50.002). No falls occurred.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S194 POSTER SESSION
Conclusions: There was a significant increase in variability in
baseline gait parameters while texting on a cellular phone which
could predispose to gait instability or falls.
497
Gait cycle related modulation of electrophysiological activity in
the human subthalamic nucleus of patients with Parkinsons
disease
F.L. Hell, K. Boetzel, J.H. Mehrkens, S. Kammermeier, A. Plate, P.
Hathway (Munich, Germany)
Objective: Can specific gait cycle related electrophysiological
activity be observed in the human subthalamic nucleus of patients
with Parkinsons disease.
Background: PD patients with implanted DBS electrodes allow
for the investigation of basal ganglia activity during gait. Whereas
the overall spectral content of local field potentials (LFP) in the BG
is known to change with movement, it is unclear as to whether indi-
vidual steps cause a modulation of the BG-LFP.
Methods: We investigated the electric local field potentials of the
subthalamic nucleus of 13 patients with PD recorded from deep brain
stimulation electrodes during gait. Simultaneously, gait parameters
were recorded with inertial sensor units and the gait cycle was subse-
quently analyzed in parallel to the electrophysiological activity.
Electrophysiological recording was done with either BrainVision
Recorder software (v 1.2, BrainProducts GmbH) using the external-
ized deep brain stimulation electrode leads after implantation or the
implanted investigational ActivaV R PC1S neurostimulator device
(Medtronic Inc.). Spectral separation of the different frequency con-
tents were computed with the Discrete Stationary Wavelet Analysis
(Matlab) and the envelopes of the resulting waves were correlated
with step-cycle phases.
Results: In eight of thirteen patients a significant gait cycle spe-
cific modulation of electrophysiological activity could be seen,
regardless of recording equipment. In these subjects, oscillatory
activity in the theta (4-8 Hz), alpha (8-13) and beta (13-30Hz) bands
transistently increases at the end of the stance phase and decreases
again in the acceleration phase of the swing phase.
Conclusions: Detecting regular modulation of specific frequency
bands in the STN may lead to algorithms for detecting gait by
closed-loop stimulation devices. Further research will aim at defining
the factors which determine whether such activity is seen or not.
498
Rubber hand illusion induced changes in sensorimotor
integration in Parkinsons disease
R. Isayama, G. Jegatheeswaran, M. Vesia, B. Elahi, C.A. Gunraj, L.
Cardinali, A. Farne`, R. Chen (Toronto, ON, Canada)
Objective: To examine multi-modal sensory integration in
patients with Parkinsons disease using the Rubber Hand Illusion
(RHI) and its influence on sensorimotor integration.
Background: To successfully perform goal-directed actions, the
brain must integrate sensory information about the limb position
from multiple sources and then transform this information to appro-
priate neural motor commands. This neural process is altered in
patients with Parkinsons disease (PD). However, the underlying
mechanisms of sensorimotor integration in PD remain unclear.
Methods: Ten patients with PD and ten age-matched healthy con-
trols will be recruited. A rubber hand illusion (RHI) paradigm, in
which subjects viewed a rubber hand being stroked by a brush during
the application of synchronous (test condition) or asynchronous (con-
trol condition) brush strokes on their own unseen hand, was used to
examine multi-modal sensory integration. Sensorimotor integration
was assessed by measuring short (SAI) and long (LAI) latency sen-
sory afferent inhibition using an electrical stimulation to the index
finger followed by transcranial magnetic stimulation (TMS) to the
Movement Disorders, Vol. 30, Suppl. 1, 2015
primary motor cortex. The amplitudes of the conditioned motor
evoked potentials (MEPs) to the unconditioned (without sensory
stimulation) MEPs were measured before and immediately after the
synchronous or asynchronous conditions. PD patients were evaluated
either on or off medications on two separate days.
Results: Preliminary behavioral data indicated that both the ten
healthy controls and two patients with PD showed a greater degree
of RHI in synchronous than asynchronous condition. In healthy sub-
jects, SAI was disinhibited (ratios at baseline: 0.83 6 0.26, RHI:
0.98 6 0.29) in the RHI synchronous condition. LAI was unchanged
(baseline: 0.75 6 0.38, RHI: 0.78 6 0.33) by RHI. In PD, the prelimi-
nary results suggest SAI was disinhibited during RHI in both the on
and off medication conditions. In contrast, LAI was increased by
RHI in the off medication condition and interestingly LAI turned
into facilitation by RHI in the on medication condition.
Conclusions: Our preliminary data suggest that LAI is abnor-
mally modulated during RHI in PD patients and the effects depended
on the medication status.
499
Transcranial magnetic stimulation as an early marker to
differentiate between early Alzheimers disease and
frontotemporal dementia and its further utility for early
diagnosis and prognostication in corticobasal ganglia
degeneration- A pilot study
T.G. Issac, S.R. Chandra, B.C. Nagaraju, T. Issac (Bangalore, India)
Objective: To introduce a cost effective, reliable technique for
early differentiation in cortical dementias and diagnosis of cortico-
basal ganglia syndromes.
Background: Currently there is no available tool for early defi-
nite diagnosis of cortical and subcortical dementias. Since motor
pathways are harbored in the frontal lobe and modulatory inhibition
is the function of the parietal lobe, early prolongation of Central
motor conduction time(CMCT) hypothesized in FTD and impaired
cortical inhibition in AD and as there is asymmetry in CBGD both
MT and CMCT could be affected.
Methods: Inclusion criteria;1.FTD,AD and CBGD Patient-
s.2.HMSE(Indian version of MMSE) score>20 Exclusion:1.Seizure his-
tory 2.Pacemakers,aneurysm clips etc. Evaluated using single pulse figure
of eight coil and right first dorsal interossei muscle contraction. Motor
threshold (MT) estimated on dominant motor cortex by- 10 stimuli applied
and at least 5 complexes >50mcV elicited. Supramaximal stimuli applied
and latency calculated(T1).Second site over C7 (T2). CMCT is equal to
T1-T2. Then Silent period assessed by the period of EMG arrest from the
end of motor evoked potential while FDI is contracted.
Results: Out of the 12 patients, 8 (68%)had AD and 2 had FTD
and 2 had features of CBGD. Comparing AD and FTD groups, there
was significant difference in HMSE scores with AD patients scoring
less (<0.05),and also had lesser cortical inhibition as evidenced by
lower MT(p<0.05) compared to FTD group whereas CMCT was
prolonged in FTD compared to AD(p5 0.048). A trend of consis-
tently lower SP was also seen among the FTD patients. Extrapolating
the same information to patients with CBGD, in whom single pulse
TMS stimuli was applied on both cortices a combination of
decreased MT and prolonged CMCT was observed in the affected
hemispheres in the 2 CBGD patients assessed.
Conclusions: This could mean that using TMS, subtle cortical
changes in early dementias can be picked, identified and therapy ini-
tiated accordingly alongwith paving a better understanding of the
function of GABAnergic system in the frontal cortex.
500
Physiological changes in Parkinsons symptoms by slow wave
potential
B.B. Khodaie, A.A.A.A. Lotfinia, M.M. Ahmadi, M.M. Lotfinia
(Tehran, Iran)
 POSTER SESSION
Objective: Various electrical neuronal waves have been found in
brain. In this line, slow wave potentiation has gain wide interest in
neurological disorders. This new therapeutic strategy has been tested
in Alzheimer and some others.
Background: Enhancement of the Glutamate level in central
nerve system seems to could ameliorate PD symptoms and could
provide a new therapeutic strategy, which could use as a replacement
of current dopaminergic treatment. Cortical Spreading depression
(CSD) is a negative DC deflection trigger by various neurological
disorders and also electrical or chemical could trigger in brain. CSD
passed through the brain and change glutamate level in extracellular
space. It seems that CSD induction in brain could initiate a wave,
which may have therapeutic properties in some disease. In present
study we test CSD effect on locomotion hyperactivity in rat that was
injected by high dose of MK-801 as a NMDA blocker.
Methods: Animals (65-80 gr) were classified in three groups
including sham animals, MK-801 treated and CSD, and MK-801
treated. Surgery was performed in CSD groups rats and a cannula
was placed over somatosensory cortex fixed by dental cement and
the brain was stitched up and animal transfer to home cage for one
week recovery. On the day of experiment animals received MK-801
injection (3 mg/kg, intraperitoneally) and rats were free to show
locomotion hyperactivity and then KCl was injected in amount of 15
ml by Hamilton syringe over the somatosensory cortex. Locomotion
hyperactivity was tested in different groups and was recorded for fur-
ther analysis.
Results: Our data showed that MK-801 injection can induce
sever locomotion hyperactivity in rats, which was obviously
recorded. Rats had severe tremor and difficulties to walk. This
change was observed in all the body from head to leg. However,
induction of CSD through cortical cannula by increasing glutamate
release in extracellular space could significantly reduce locomotion
hyperactivity in MK-801 treated rats.
Conclusions: CSD as a wave of depolarization could change glu-
tamate level and help rats who suffer Movement Disorder and can
be test in similar disease such as Parkinsons disease. This could be
a new therapeutic strategy, however larger groups and under details
analysis need to confirm safety of CSD induction for PD. Repetitive
CSD may cause neural injuries and interval of its induction must be
monitor.
501
Propensity for heterosynaptic motor cortex plasticity in the de
novo state predicts early motor complications of L-DOPA
treatment in Parkinsons disease
A. Kishore, T. Popa, P. James, L. Yahia-Cherif, S. Pradeep, S.
Krishnan, S. Meunier (Trivandrum, India)
Objective: To test whether an impairment in the response of
motor cortex (M1) to paired associative stimulation (PAS) is a signa-
ture of the de novo state in PD and whether the status of good or
poorresponse is a risk factor for motor complications in Parkin-
sons disease (PD).
Background: The propensity of M1 for heterosynaptic plasticity
is variable in healthy volunteers but reported to be impaired in de
novo PD. Chronic levodopa treatment restores this function in those
with stable motor response but not in those with motor complica-
tions. There are no longitudinal studies examining the predictive
value of the propensity of M1 to respond to plasticity induction para-
digms in the de novo state and the future development of motor
fluctuations.
Methods: In 29 de novo PD patients and 26 age-matched healthy
volunteers (HV), motor cortex plasticity was tested using paired-
associative stimulation (PAS). All PD patients were tested in the
untreated and ON states (after 100mg L-DOPA). Eighteen PD
patients were tested with PAS after one year of dopaminergic treat-
ment and all 29 patients were followed up for motor complications
by 1 year and 3 years of treatment.
S195
Results: In the untreated state, there was no plastic response to
PAS (Non-responders) in 15 patients and 15 HV while it was pre-
served in the remaining (Responders). The changes were similar in
PD and HV (GLM, P =0.1). In de novo PD and HV, an acute L-
DOPA dosing restored the plastic response in Non-responders
(LMM, P<0.01) and had no effect in Responders (P=0.9). At 1 year,
the status of patients based on response to PAS remained unchanged
but acute L-DOPA dosing worsened ongoing M1 plasticity in Res-
ponders. Wearing off occurred by 1 year in 4 and by 3 years in 4
more. A higher propensity for plasticity in the de novo state and
motor scores after first dose of L-DOPA, predicted the occurrence of
wearing off at 3 years (logistic regression: UPDRS-ON
v2(1) 5 4.40, P=0.036 and OVERALL PAS-untreated v2(1) 5 4.86,
P=0 .026).
Conclusions: The propensity of M1 for heterosynaptic plasticity
is similar in de novo PD and age- matched healthy volunteers. Early
identification of Responders to PAS of the motor cortex may help to
target dopa-sparing treatment or continuous dopaminergic stimulation
in this group in order to prevent or delay the development of motor
fluctuations in them.
502
Timing accuracy of voluntary rhythmic hand movement in
essential tremor and Parkinsons disease
F. Luft, S. Sharifi, W. Mugge, A.C. Schouten, L.J. Bour, A.F. van
Rootselaar, C. Heida (Enschede, Netherlands)
Objective: Timing accuracy (TA), synchronization of a hand tap-
ping movement with a predefined frequency, is studied in patients
with Parkinsons disease (PD), Essential tremor (ET) and healthy
controls (HC) to determine differences in performance. TA of hand
movement is recorded at 2 and 4 Hz using a 3D-accelerometer
attached to the back of each hand.
Background: Movement Disorders often involve the basal gan-
glia and the cerebellum. Both are involved in preparation and execu-
tion of internally and externally triggered movements [1]. In PD
internally triggered movements can be severely disturbed. External
cues can enhance patients motor performance. In ET impairment of
rhythm generation and an increased variability of rhythmic hand
movement has been observed [2]. In both disorders the TA is dis-
turbed, even though the underlying pathophysiology in PD and in ET
is different. Therefore, the aim of this study is to determine the dif-
ferences in TA of rhythmic hand movements in ET and PD to get
more insight into the differences between these disorders.
Methods: 4 PD, 16 ET patients and 14 age-matched HC were
included. Subjects performed a tapping task at two different frequen-
cies. Movement of both hands was recorded using a 3D-
accelerometer. Data was segmented into 3 seconds epochs. The tap-
ping frequency was estimated for each epoch by the highest peak of
the power spectral density. TA was the ratio of tapping to metro-
nome frequency. Thus, a TA of 1 means these two are equal. Intra-
and intergroup differences were calculated using one-way ANOVA
and post-hoc t-test (p>0.05).
Results: Intragroup analysis revealed no differences in TA
between the 2 and 4 Hz task in the HC and ET group. In the PD
group TA was significantly lower in the 4 Hz compared to the 2 Hz
task. Intergroup analysis revealed no significant difference between
groups for the 2 Hz task. For the 4 Hz task the PD group had a sig-
nificantly lower TA than the other two groups. No difference was
found between HC and ET.
Conclusions: It can be concluded that patients with ET synchron-
ize tapping movements with an external cues more effectively than
PD patients. It should be considered to include a task with an exter-
nal cue into clinical evaluation when differentiating between Move-
ment Disorders. Imaging studies might give more insight into
underlying mechanisms.
[1] Purzner, J., et al., J Neurosci, 2007
[2] Avanzino, L., et al., Eur J Neurosci, 2009
Movement Disorders, Vol. 30, Suppl. 1, 2015
S196 POSTER SESSION
503
Intraoperative electrocorticography activity in the sensorimotor
cortex differentiates generalized dystonia, segmental dystonia,
and Parkinsons disease
S. Miocinovic, C. de Hemptinne, S. Qasim, J.L. Ostrem, P.A. Starr
(San Francisco, CA, USA)
Objective: To investigate electrophysiologic characteristics of
sensorimotor cortical activity in patients with dystonia, with and
without arm symptoms, and Parkinsons disease (PD) undergoing
deep brain stimulation (DBS) surgery.
Background: Dystonia and PD are disorders of the basal ganglia-
thalamo-cortical network. Previous work showed that there is
impaired movement-related beta desynchronization in the sensorimo-
tor cortex in primary dystonia, but it is not clear whether this is an
endophenotype or a correlate of dystonic symptoms in the homolo-
gous body part. We hypothesized that dystonia with and without arm
symptoms would have distinct physiological signatures in the motor
cortex.
Methods: We measured local field potential activity over the arm
area of the sensorimotor cortex using a temporary 6-electrode sub-
dural strip in patients undergoing DBS surgery. We computed signal
power in multiple frequency bands and phase amplitude coupling
(PAC) between beta and broadband gamma, both at rest and during
simple movement tasks.
Results: We report results from 22 primary dystonia (12 in the
noArm symptoms group, and 10 in the Arm symptoms group)
and 15 age-matched akinetic-rigid PD patients. At rest there was no
difference in mean log spectral alpha or beta power between the
three groups. During movement, noArm group had earlier beta
desynchronization with respect to EMG muscle activity compared to
PD and Arm groups. Arm group had the least amount of movement-
related desynchronization, and this was significantly different from
noArm group in the alpha, low beta and low gamma, and from PD
in the high beta band. These differences between dystonia groups
were only found over the primary motor cortex. PD had stronger
beta desynchronization than dystonia groups in the sensory cortex.
At rest, motor cortex PAC and broadband gamma trended toward
reduced values in the noArm group, whereas PD and the dystonia
Arm group had very similar PAC and broadband gamma.
Conclusions: Dystonia without arm involvement is physiologi-
cally distinct from dystonia with arm symptoms. Movement-related
modulation of oscillatory activity at different frequencies and cortical
locations was more distinguishing of the disorders than the absolute
power levels. Generalized dystonia and PD may have physiologic
overlap with respect to motor cortex synchronization and resting
state activity.
504
A.P.A.: How aging, Parkinsons disease and anticipatory postural
adjustments correlate
A. Plate, K. Klein, A. Singh, O. Pelykh, A. Klein, J. Illmberger, K.
Boetzel (Munich, Germany)
Objective: Analyzing step initiation of healthy controls (HC)
with regard to physiological changes that take place during aging.
We also examined stepping behavior of patients with Parkinsons
disease (PD), some of whom add. suffered from freezing (FZ). All
groups were investigated during self-initiated (SIS) and externally
elicited stepping (EES) initiation.
Background: Anticipatory postural adjustments (APA) prior step-
ping seem to have an impact on step initiation in patients with PD,
especially in PD patients with FZ. Often freezing patients use exter-
nal triggers in order to start their motion. Little is known about alter-
ations of stepping behavior that take place in healthy older people.
Methods: We examined original data consisting of the data sets
of 1594 steps (84 subjects, 8-10 steps in 2 conditions via a treadmill
system (engaged belt). Groups consisted of HC, subjects with PD
Movement Disorders, Vol. 30, Suppl. 1, 2015
and subjects with PD and FZ. Averaged data were two data sets per
person corresponding to 2 conditions (SIS&EES). Statistics were per-
formed on averaged data.
Results: Variables of the 1st step (length, velocity) and APA-
measures (duration, lat., ant-post) showed no significant correlation
with age. In general EES were longer, faster and had a shorter dura-
tion as compared to SIS. Regardless of the age of the subjects, the
1st step is longer and its velocity is higher in HC as compared to
FZ. There was no difference between HC/PD or PD/FZ. This pattern
was seen in almost all statistical tests: i.e. HC & FZ had sign. differ-
ent APA-duration (FZ: longer). The only difference between FZ &
PD was a longer duration of APA2 and the slower max velocity of
APA1 in FZ. Remarkably, the extent of the APA excursion in the
ant.-post. direction was not significantly different between the 3
groups.
Conclusions: The results of our study show no significant physio-
logical changes of stepping behavior during aging. Surprisingly,
APA does not seem to be much influenced by the length of the 1st
step or by age. In general EES are larger (on average 5%) than SIS
and show a clear difference in several APA parameters: APA are of
shorter duration in EES but the APA excursions are larger (both
directions). Concerning PD patients we found no differences between
the ant-post. APA of the 3 groups. Only the lat. APA was reduced in
the PD groups (sign. only between HC/FZ). In summary, APA seem
to be a stable parameter during aging and do not seem to explain the
FZ phenomenon.
505
Developing a technique-specific nomogram for temporal
discrimination threshold testing
V.F.M.L. Ramos, M. Villegas, A. Esquenazi, T. Wu, M. Hallett
(Bethesda, MD, USA)
Objective: To establish a nomogram for temporal discrimination
threshold testing.
Background: The temporal discrimination threshold (TDT) is the
shortest interstimulus interval at which a subject can perceive succes-
sive stimuli as separate. Previous studies show that TDT abnormal-
ities have high diagnostic sensitivity and specificity in dystonia, and
are noted to be a feature not only of the disease, but also for gene
mutations associated with dystonia. However, there is great variety
in technique, and there are no standard normal limits. Reproducibil-
ity data are scarce.
Methods: We studied TDT using the method of limits (three
ascending and three descending limits) in 100 healthy volunteers,
equally divided among males and females, across ten age groups,
from 18 to 79 years. The stimulation intensity for testing, using ring
electrodes at the proximal and distal interphalangeal creases of the
index finger, was set for each individual at 120% sensory threshold.
Participants were instructed to report whether two test stimuli
occurred simultaneously or sequentially. The mean over the six lim-
its was taken as the TDT.
Linear regression analysis was performed to examine the relation-
ship between age and the following three TDT test outcomes: mean
of left hand (L-mean), mean of right hand (R-mean), and mean of
two hands (LR-mean). L-mean (or R-mean) was the mean of three
ascending TDT and three descending TDT measures from left (or
right) hand LR-mean was the mean of R-mean and L-mean. Reliabil-
ity analysis based on intraclass correlation coefficient was conducted
to assess the measurement reproducibility of the TDT test.
Results: Linear regression analysis showed that age was signifi-
cantly related to L-mean, R-mean and LR-mean with R-square equal
to 0.08, 0.164 and 0.132, respectively. Reliability analysis indicated
that the three measures had fair-to-good reliability.
Conclusions: TDT is affected by age, and has fair-to-good repro-
ducibility using our technique.
 POSTER SESSION
506
PARK 2 gene mutation and pramipexole use during pregnancy:
Report of two cases
J.G. Santos, H.F. Chien, E.R. Barbosa (Sao Paulo, Brazil)
Objective: 1. To report of two cases of pregnancy in women
with a mutation in PARK2 gene, which confers a form recessive of
Parkinsons disease autosssomica and Early Onset. 2. Describe and
document as was the use of Pramipexole during both pregnancies.
Background: Both patients were diagnosed with early onset Par-
kinsons disease (EOPD). Moreover, their belongs to a large family
cluster with intricated intermarriage between cousins resulting in
many PD members due to Parkin mutation. The more young lady(1)
to get pregnant for the first time in april 2011 and as soon she got
pregnant again in March 2012. She could not tolerate selegiline or
biperiden and pramipexole was introduced before from gestation.
During both pregnancies the patient keep pramipexole, once your
symptoms worsened progressively despite our guydances. The
another lady currently be pregnant and keep pramipezole 0,125mg
eTID, and be reasonable well in fifth week of gestation.
Results: Delivery was in due time and the baby and mother were
dismissed from hospital well. Today both children are healthy and
acquiring the development milestones properly. In each case were in
agreement their families.
Conclusions: Genetic forms of Parkinsonism with EOPD
increases the chance of the affected woman to get pregnant. The
majority of drugs used for the treatment of PD are classified by the
Food and Drug Administration in category C. Nevertheless, most
studies in humans have shown the safe use of levodopa. Our patient
was treated with pramipexole and the Parkinsonian symptoms were
stable during gestation and the newborns were healthy. There are
few series in the literature with small number of patients to conclude
with certainty the influence of pregnancy on PD as well as the effect
of the antiParkinsonian drugs on the fetus. Women with EOPD need
to be instructed about the risks of the medication during gestation,
the drug regimen, andspecialized prenatal care for closer surveillance
of mother and fetal health.
507
Efficacy of high-frequency repetitive transcranial magnetic
stimulation on depression in Parkinsons disease
H.W. Shin, S.J. Chung, Y.H. Sohn (Seoul, Korea)
Objective: To investigate whether high-frequency repetitive
transcranial magnetic stimulation (rTMS) is effective on depression
in patients with Parkinsons disease (PD).
Background: Repetitive transcranial magnetic stimulation
(rTMS) has been approved as an effective treatment modality in
major depressive disorder patients who do not respond to antidepres-
sants. The number of clinical trials conducted for evaluating efficacy
of rTMS on depression in PD patients limited.
Methods: Eighteen depressed patients with Parkinsons disease
participated in this study. Subjects were randomized as a group of
receiving real-rTMS and another group of receiving sham-rTMS.
rTMS was applied over the dorsolateral prefrontal cortex. For 10
days, 600 stimulations a day were applied with an intensity of 90%
of the resting motor threshold of (RMT) with 5 Hz frequency.The
Unified Parkinsons disease Rating Scale (UPDRS) motor part (III),
Beck depression inventory (BDI), Montgomery-Asberg Depression
Rating Scale (MADRS) and the Hamilton Rating Scale (HRS) were
compared before rTMS, immediately after stimulation, and 4 weeks
after the last stimulation.
Results: Ten patients and 8 patients were randomized as groups
of real and sham-rTMS, respectively. The mean age, disease duration
and levodopa equivalent dosage of the patients were comparable
between two groups.
S197
Demographic characteristics of the patients
Real-stimulation Sham-stimulation
group group
Age (years, range) 69 (55-82) 69 (62-79)
Female sex ratio 5/10 5/8
Disease duration (M) 109.6 6 111.9 95.625 6 53.6
Dopamine equivalent 804.6 6 429.9 842.0 6 410.0
dosage (mg)
[Table1]
In real-rTMS group, repeated measures ANOVA analysis showed
that the BDI, MADRS and HRS after rTMS significantly decreased
compared to those before rTMS. The BDI was 30.0 6 5.7, 21.0 6 4.6
and 18.7 6 5.0 before, immediately after and 4 weeks after rTMS,
respectively (mean6standard deviation, p<0.05). The MADRS was
20.6 6 1.3, 9.7 6 4.3 and 12.3 6 3.2, and the HRS was 12.7 6 1.3,
6.5 6 1.3, and 5.8 6 1.5 before, immediately after and 4 weeks after
rTMS (mean6standard deviation, p<0.05). The UPDRS part III was
also significantly different at each visit (14.2 6 2.8, 9.0 6 2.9 and
10.8 6 3.1, mean6standard deviation, p<0.05). However, in the
sham-rTMS group, there was no difference of the BDI, MADRS,
HRS and the UPDRS part III at the drug-on stage between before
and after rTMS.
Conclusions: Our findings demonstrate that rTMS can reduce the
severity of depression as well as of motor symptoms at the drug-
on stage in PD patients. In addition, the efficacy of rTMS continues
for a long period of time. rTMS may be an option for treatment of
depression in PD patients.
508
LTD-like effect in human motor cortex with low frequency and
very short duration of paired associative stimulation
P. Srivanitchapoom, J.E. Park, N. Thirugnanasambandam, P.
Panyakaew, S. Pandey, T. Wu, M. Hallett (Bangkok, Thailand)
Objective: To investigate plasticity effects in human motor cor-
tex using low frequency and very short duration paired associative
stimulation (PAS).
Background: PAS has been used to investigate the synaptic plastic-
ity in human motor cortex. Classically, to create long-term depression
(LTD) or long-term potentiation (LTP) like effects in human motor cor-
tex, studies use low frequency with long duration of the stimulation of
PAS (1). High frequency of very short duration can create LTP-like
effect but have failed to create LTD-like effect (2). In exploring low
frequency with very short duration of PAS with inter-stimulus interval
of 10ms (PAS10ms) we have found an LTD-like effect.
Methods: Five groups of parameters including 1 minute stimula-
tion of 0.25 and 0.5Hz and 2 minutes stimulation of 0.2, 0.25 and
0.5Hz were investigated with PAS10ms. Six healthy volunteers (HVs)
were in each group. Right median nerve was stimulated at 200% of
sensory perception threshold over the wrist followed by transcranial
magnetic stimulation (TMS) at 80% of resting motor threshold over
the left motor cortex (M1). We obtained motor evoked potentials
(MEPs) from right abductor pollicis brevis muscle with approxi-
mately 1mV at baseline. We recorded MEP amplitude before and 1,
5, 10, 15, 20, 25 and 30 minutes after PAS.
Results: One-factor repeat measurement ANOVA showed that
only the group of 1 minute stimulation of 0.25Hz of PAS10ms showed
statistical significant inhibition (p50.023) whereas both 1 minute and
2 minutes stimulation of 0.5Hz tended to show facilitatory effect. Post-
hoc analysis of the group of 1 minute stimulation of 0.25Hz showed
that the LTD-like effect lasted for 20 minutes [figure1].
Conclusions: Low frequency with very short duration of the stim-
ulation of PAS10ms can create an LTD-like effect. This finding might
be useful for future research related to synaptic plasticity by reducing
Movement Disorders, Vol. 30, Suppl. 1, 2015
S198 POSTER SESSION
Fig. 1. (508).
duration of study and minimizing subject discomfort with less
stimulation.
509
Orbicularis oculi muscle activity during swallowing in
blepharopsm and Meigs syndrome patients
F. Tokucoglu, N. Gurgor, N. Razizadeh, S. Arici, C. Ertekin (Izmir,
Turkey)
Objective: The aim of the study is to evaluate essential blepharo-
spasm and Meigs syndrome cases if they may differ anyway from
normal subjects during water and lemon juice swallowing particu-
larly concerning synchronous activity of OC,OR and SM muscles
during swallowing.
Background: Oropharyngeal swallowing (OPS) is a complex
activity that requires coordination of muscle contraction and respira-
tory functions. Orbicularis oculi (OC) muscles are not known to be
involved during OPS. However electrophysiological studies clearly
showed their activity during OPS demonstrated by Ertekin et al 2013
in normal adult subjects.There is no study for the neurologic disor-
ders for instance in extrapyramidal disease.
Methods: Patients who had essential blepharospasm and Meigs
syndrome (MS) were included. They all had botulinum toxin injec-
tions previously. They were evaluated prior to botulinum toxin injec-
tion. OC, orbicularis oris (OR), submental muscle (SM) activity were
recorded with cup electrodes using EMG machine (Oxford Inst Syn-
ergy). These activities were time locked to respiratory activity which
was recorded with a nasal cannula. Muscle activities were rectified.
Each patient swallowed 5,10, 15, 20 ml water and fresh lemon juice
(LJ). Number of swallows and apnea periods, duration of apnea
period and SM muscle activity and presence of synchronous contrac-
tion of OC and SM muscles were recorded. Recordings were eval-
uated off line.
Results: Ten out of 13 consecutive patients and 21normal control
(NC)subjects were included.Four of the patients had MS. OC and
SM contracted synchronously in most of the blepharospasm patients
as in normal controls.In one patient OC muscle spasm activity
ceased during the swallowing which was continuous at rest. In some
patients LJ caused prolonged OC contractions with higher amplitude.
In normals apnea duration is well correlated with SM activity dura-
tion during 10ml water swallowing while that was the case for BP
patients 5,10,15 and 20 ml. There was no other significant difference
between two groups for water swallowing.LJ swallowing parameters
Movement Disorders, Vol. 30, Suppl. 1, 2015
of BP and Meig patients differed significantly from normal controls
and their own water swallows.
Conclusions: It could be said that in BP, OC muscle activity is
present during swallowing and it is synchronous with other swallow-
ing movements. In MS patients OC activity is also present but syn-
chronicity is not clear.
510
Comparison of GPi local field potential characteristics in patients
with Parkinsons disease, craniocervical dystonia, and
generalized dystonia
D.D. Wang, C. de Hemptinne, S. Qasim, S. Miocinvic, J.L. Ostrem,
P.A. Starr (San Francisco, CA, USA)
Objective: To test the hypothesis that resting state LFP character-
istics distinguish the Parkinsonian state from segmental and general-
ized dystonia.
Background: Implantation of DBS leads performed in the awake
state provides an opportunity to study network oscillations in Move-
ment Disorders. Prominent beta band oscillations have been observed
in Parkinsons disease (PD) in the STN and GPi, and proposed as
closed-loop signal controls for DBS therapy. The GPi is a less stud-
ied target than the STN and human basal ganglia physiology has
rarely been compared across different disease states.
Methods: Resting state GPi LFPs were recorded intraoperatively
from DBS electrodes in 14 PD patients, 3 craniocervical dystonia
patients, and 4 generalized dystonia patients in the awake state.
Alpha-beta power characteristics were calculated characterizing the
peak power band at those frequencies. Phase-amplitude interactions
(PAC) in both cortex and STN are increasingly recognized as poten-
tial disease biomarkers, we quantified the interaction between the
amplitude of high frequency activity and alpha-beta phase as previ-
ously described (Lopez-Azcarate 2010 and de Hemptinne 2013).
Results: GPi LFPs demonstrated similar frequencies for the
alpha-beta spectral peak, at 19.0 6 5.8 Hz for PD, 20.5 6 6.8 Hz for
craniocervical dystonia (c-dys), and 17.6 6 8.3 Hz for generalized
dystonia (g-dys) patients (p50.79). The amplitude of the log spectral
peak power was not significantly different; 0.9 6 0.40 for PD,
0.6 6 0.2 for c-dys, and 1.1 6 0.6 for g-dys (p50.38). For PAC anal-
ysis, 8 PD, 2 c-dys, and 3 g-dys patients showed coupling between
alpha-beta phase and the amplitude of a narrowband high frequency
oscillation (280-360Hz). Coupling of beta phase to broadband power,
 POSTER SESSION
as has been observed in the motor cortex in PD, was not found in
GPi.
Conclusions: Direct comparison of GPi LFPs in PD, craniocervi-
cal, and generalized dystonia shows that all patients have peak spec-
tral power in the beta band, casting doubt on the view that excessive
beta band power is a specific biomarker of the Parkinsonian state.
Cross frequency interactions between beta phase and high frequency
oscillations are also found in GPi and are not specific for disease
state. The study reveals potential similarities between abnormal neu-
ral network activity and synchronization in PD and dystonia.
511
Phase reorganization of thalamic oscillatory activity contributes
to the generation of the somatosensory evoked potentials in Vim
thalamus in Parkinsons disease and essential tremor patients
K. Watanabe, S. Sato, M. Futaba, Y. Okamura, M. Taniguchi (Tokyo,
Japan)
Objective: We investigated whether reorganization of background
thalamic oscillatory activity contributes to the generation of the
evoked potentials in Vim thalamus triggered by median nerve stimu-
lation in patients with Parkinsons disease and essential tremor.
Background: It has been long debated whether averaged electri-
cal responses result from stimulus-evoked brain events or stimulus-
induced changes in phase resetting of ongoing brain oscillatory activ-
ity within specific frequency bands.
Methods: We recorded median nerve stimulation-elicited somato-
sensory evoked potentials (SEPs) from the ventralis intermedius
(Vim) thalamus with semi-microelectrodes during stereotactic sur-
gery in 7 patients with Parkinsons disease (n53) and essential
tremor (n54). We here calculated the phase-locking factor (PLF) in
order to measure the phase correlation of ongoing local field poten-
tials (LFPs) oscillation across trials for given frequency bands in the
generation of the SEPs in Vim thalamus. This measure corresponds
to the inter-trial coherence, which indexes the degree of phase syn-
chronization of trials relative to stimulus presentation. The PLF mea-
sure takes values between 0 (absence of synchronization) and 1
(perfect synchronization) (Strogatz, 2000).
Results: In about two thirds of thalamic SEPs examined, we
found phase-locking of g frequency band comes first in temporal
order, and subsequently that of b band, and followed by phase-
locking of slower frequency band (u and a) of ongoing thalamic
LFP oscillation across trials. Transition across trials from uniform to
packed phase distribution revealed temporal phase reorganization of
given rhythms of thalamic LFP oscillation in relation to stimulation.
Conclusions: The identification of a phase-locking in each
rhythm of thalamic SEP trials reinforces the contribution of phase
resetting model for somatosensory information processing. This may
imply that phase resetting of each ongoing LFP rhythm in an appro-
priate temporal order at least partly participates in thalamic SEP for-
mation. Understanding characteristic transient responses of neuronal
populations to external stimulations may provide us with invaluable
clues for investigating how the central nervous system such as tha-
lamic nucleus reacts and adapts to the stimulus perturbations.
512
Sensorimotor integration in dopa-responsive dystonia in different
dopaminergic states
A. Weissbach, T. Baumer, N. Br
uggemann, V. Tadic, C. Klein, A.
Munchau (L
ubeck, Germany)
Objective: To examine sensorimotor integration in GCH1 muta-
tion carriers (MC) with dopa-responsive dystonia (DRD) and healthy
control subjects in different dopaminergic states using transcranial
magnetic stimulation (TMS).
Background: Movement Disorders including DRD have tradi-
tionally been regarded as disorders of impaired motor control. This
S199
Fig. 1. (512).
notion has recently been extended, given the discovery of several
non-motor features like a temporal discrimination deficit. This raises
the question of whether the sensory system is also involved in the
pathophysiology of DRD.
Methods: We assessed short-interval afferent inhibition (SAI)
after digital stimulation in fifteen GCH1 mutation positive DRD
patients at least 12 h after drug withdrawal (OFF state) and after
intake of 200 mg levodopa (On LD state). SAI was also tested in 20
healthy controls before and after receiving 200 mg levodopa. The
conditioning electrical pulse was applied at an interstimulus interval
(ISI) of 25 ms and an intensity of three times the individuals sen-
sory perception threshold. The test stimulus intensity was set to pro-
duce a motor-evoked potential of 0.5-1 mV.
Results: SAI was significantly influenced by the dopaminergic
state in DRD patients. ANOVA comparing groups in the two differ-
ent states (OFF and ON LD state) revealed an interaction of the fac-
tors GROUP x STATE (F(1,33) 5 7.09, p 5 0.012). We therefore
analysed the two different states separately with a post hoc t test and
found a significant group effect of the SAI in the ON LD state
(p 5 0.034), but not in the OFF state (p 5 0.44), as well as a signifi-
cant difference between the OFF and ON LD state for the DRD
group only (p 5 0.045) [figure1]
Conclusions: The attenuation of SAI in DRD may indicate an
adaptive cortical response of the sensorimotor system to compensate
for the functional consequences of the chronic dopamine deficit. One
could speculate that reduced inhibition of motor output by sensory
input might facilitate motor execution and thus help to compensate
motor symptoms.
513
Modulation of short-latency afferent inhibition (SAI) in
multisystem atrophy by low frequency (1-Hz) repetitive
transcranial magnetic stimulation (rTMS) of the cerebellum
F.G. Yildiz Sarikaya, E. Saka, B. Elibol, C.M. Temucin (Ankara,
Turkey)
Objective: To evaluate the effects of low frequency repetitive
TMS over cerebellum on SAI parameters in MSA-C patients and
healthy controls.
Background: Impaired cognitive functions in MSA were corre-
lated with SAI reduction response in recent studies, more evidently
in MSA-C subgroup. SAI study is a neurophysiological examination
that evaluates modulation of motor cortex excitability. Impact of the
cerebello-cortical pathways on this impaired modulation is not clear.
In this study we aimed to identify the role of cerebello-cortical path-
ways by inhibitory effect of low frequency (1-Hz) rTMS over the
cerebellum.
Methods: Eight MSA-C patients (range 45-69 years and 9
healthy controls (age 45-64 years) were included to this study. None
Movement Disorders, Vol. 30, Suppl. 1, 2015
S200 POSTER SESSION
of the subjects was under any cholinergic or anti cholinergic treat-
ment. Motor-evoked potentials (MEPs) were obtained in the contra-
lateral first dorsal interosseous (FDI) muscle by TMS. MEPs
amplitudes were obtained by TMS alone without peripheral nerve
stimulation (MEP control) and TMS with stimulation of contralateral
median nerve at wrist at 5 interstimulus intervals (ISI) (MEP test).
At each ISI MEP control values were expressed percentage of MEP
test values and called as SAI t1-t5. Also average of SAI values
1expressed as SAI mean. For rTMS, low frequency (1 Hz) rTMS of
600 pulses was performed over contralateral cerebellum. SAI values
were obtained before (pre-SAI) and within the 10 minutes following
rTMS (post-SAI). Pre-SAI and post-SAI response values were com-
pared by using multivariate analyses. Also we calculated pre-SAI/
post-SAI ratio.
Results: Pre-SAI values were significantly lower in MSA-C com-
pared control groups as previously found (p<0.009).These reductions
of SAI parameters in the patient group were significantly disappeared
after rTMS; post-SAI values were significantly increased in MSA-C
group compared with pre-SAI values (p<0,05); while in control
group there were no changes (p>0,05).
Conclusions: There is a significant improvement in SAI response
results after low frequency rTMS over the cerebellum in MSA-C
patients. rTMS, as a non-invasive neurophysiological method disinhi-
bits the inhibitory output of cerebellum on cortex. Impaired SAI and
its modulation after low frequency rTMS may be an electrophysio-
logical correlate of possible maladaptive cortical circuits in MSA-C.
514
Temporal patterning of spike-LFP synchronization in the
internal globus pallidus in Parkinsons disease
S.E. Zauber, S. Ratnadurai-Giridhara, R.M. Worth, T. Witt, L. Rub-
chinsky (Indianapolis, IN, USA)
Objective: To investigate the fine temporal structure of intermit-
tent synchronization between spiking neural units and local filed
potentials (LFP) in internal pallidum (GPi) in Parkinsons disease
(PD).
Background: Increased synchronization in the beta frequency
band, throughout cortico-basal ganglia-thalamic circuitry, is associ-
ated with hypokinetic symptoms of PD. However, the magnitude of
this increased synchrony is relatively low. We have previously stud-
ied the intermittent nature of beta-band synchronization between
spikes and LFP and its changes over time in the subthalamic nucleus
(STN) of PD (Park et al., 2010). The present study investigates simi-
lar properties of neural synchronization in GPi and compares them
with those of STN.
Methods: We recorded spiking units and LFPs in the GPi of five
patients with PD undergoing deep brain stimulation surgery (DBS).
The beta-band oscillatory activity in the time series of both single
spiking units and LFP was filtered, and we studied the phase locking
between the two resulting signals. We used time-series analysis tech-
niques (Park et al., 2010; Ahn et al., 2011) to study the temporal var-
iability of synchronous dynamics and compared it with the
variability of synchrony in STN.
Results: Synchronization between spiking activity and LFP in
GPi in PD is intermittent; episodes of synchrony are interrupted by
episodes of desynchronized activity. Short durations of desynchroni-
zation episodes prevail.i.e. the longer a desynchronization episode is,
the less likely it is to occur.
Conclusions: The observed similarity of fine temporal structure
of the beta-band synchrony between spikes and LFP in GPi and in
STN (in spite of the fact that these structures have different cells,
synapses, projections and local architecture) may suggest that both
structures are engaged in the same type of neural dynamics, pointing
to significance of inter-nuclei circuits in PD.
C Park, RM Worth, LL Rubchinsky (2010) Fine temporal struc-
ture of beta oscillations synchronization in subthalamic nucleus in
Parkinsons disease. J. Neurophysiol. 103:2707-2716.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S Ahn, C Park, LL Rubchinsky (2011) Detecting the temporal
structure of intermittent phase locking. Physical Review E, 84:
016201.
Therapy in Movement Disorders: Neurotoxin
515
Long-term efficacy of incobotulinumA toxin in treatment of
resistant dysphagia due to severe spasticity of upper oesophageal
sphinter. A case report
M. Basciani, F. Di Rienzo, D. Intiso (San Giovanni Rotondo, Italy)
Objective: Treatment of severe dysphagia due to spasticity of
upper oesophageal sphincter (UES) by high dose of botulinum toxin
A (BoNT-A). Description of a case.
Background: Dysphagia following UES spasticity is commonly
treated by BoNT-A at the dosage ranging from 2.5 to 120 IU and
from 60 to 300 IU of botulinum toxin A and abobotulinumtoxinA,
respectively (1). Nevertheless, subjects could not benefit from this
therapeutic strategy and could underwent to surgical intervention
consisting of cricopharyngeal muscle (CM) myotomy (2). A 50 years
old man with severe dysphagia and tetraparesis following encephali-
tis was treated by growing dosage of BoNT-A injected into crico-
pharyngeal muscle (CM) (10 IU of botulinum toxin a and 100 IU of
Xeomin, at two separated infiltration sessions) associated to pneu-
matic dilatation, unsuccessfully.
Methods: Oesophageal manometry (OM) and videofluoroscopy
(VS) before and after high BoNT-A dose were used to evaluate dys-
phagia. After informed consent, 200 IU of BoNT-A (Incobotulinum-
toxinA Xeomin) diluted at 25 ml/ml were injected into spastic CM
by endoscopic guidance. BoNT-A was injected in 3 equidistant
points along two perimeters of CM. Each site received 30, 30 and 40
IU of BoNT-A, respectively. Oesophageal pneumatic dilatation was
associated.
Results: Before BoNT-A treatment, VS showed no passage of
barium into the oesophagus due to UES spasticity (A). [figure1]
Severe spasticity of UES did not permit OM. After two weeks from
BoNTA injection, VS showed significant improvement of swallowing
consisting of good bolus transit into the oesophagus (B). Normal val-
ues were detected to OM. Subject experienced improvement of dys-
phagia for eight months. Mild local pain and paresis of right vocal
cord lasting two weeks were observed. A second BoNT-A injection
with same technique was performed, successfully. No side effect was
observed after the further BoNT-A injection.
Conclusions: High dose of 200 IU of BoNT-A (Xeomin) was
effective and safe in treating dysphagia due to severe spasticity of
UES that was resistant to common BoNT-A dosages. Mild side
effects were observed. The use of high BoNT-A dose should be con-
sidered before suggesting surgical procedures, whenever the common
therapeutic doses resulted ineffective.
Fig. 1. (515).
 POSTER SESSION
516
Botulinum toxin treatment: Experience in a public hospital from
Buenos Aires, Argentina
M.J. Casen, C. Christie, S.A. Rodrguez-Quiroga, M.L. Assante, V.
Daz Aragunde, M. Mancuso, T. Arakaki, N.S. Garretto (Ciudad
Autonoma de Buenos Aires, Argentina)
Objective: To present our experience in the use of BoNT-A in
the Movement Disorders Section in a public hospital from Buenos
Aires, Argentina.
Background: Botulinum Toxin Type A (BoNT-A) is used since
1989 for the treatment of different neurological conditions with a rel-
evant efficacy and safety profile. Clinical effects are often seen
within first week of injection, and the benefits usually last from 3-6
months.
Methods: We reviewed the medical records of 220 patients who
received BoNT-A between 1992 and 2014. We analyzed the diagno-
sis and time of evolution (TE), the maximum dose received (MD),
the treatment response and the adverse events (AE).
Results: Male: 34%, average age: 57.6 years [18-93], average
TE: 73.6 months.
Of the total number of patients, 53% had hemifacial spasm (HF),
18% blepharospasm (BE), 4% Meige syndrome, 12% cervical dysto-
nia (CD), 8% other dystonias and 5% other diagnoses.
In patients with HF a history of peripheral facial palsy was pres-
ent in 27%, and neurovascular compression was diagnosed in 13%.
Patients with CD showed torticollis in 26%, retrocollis in 11%,
laterocollis in 7%, and mixed patterns in 56%. Sialorrhea and spas-
ticity were the cause of prescription in 2 and 7 patients respectively.
The maximum dose used was 600U in a patient with spasticity,
100U in HF, 100U in BE, 300U in Meige syndromes patients and
500U in CD, and the average time between injections was 5.5
months.
Fig. 1. (517).
Fig. 2. (517).
S201
An effective response to the treatment was observed in 98%
patients.
Adverse events were presented in 25% of patients; the most com-
mon were palpebral ptosis and drooping lip corner in HF and BE/
Meige, and transient mild dysphagia in CD.
None of patient had allergy or resistance to BoNT-A.
Conclusions: BoNT-A is the gold standard in the treatment of
HF and dystonias; it is effective and safe. The keys for a good
response are: a correct selection of patient and an appropriate dose
and choice of the injection sites. A proper training of medical staff
and a suitable knowledge of anatomical structures are essential in
order to improve the results and avoid adverse events.
517
Botulinum toxin type A therapy for cervical dystonia - An
update of a Cochrane systematic review and meta-analysis
M. Castel~
ao, R. Marques, G. Duarte, F.B. Rodrigues, J.J. Ferreira,
P. Moore, J. Costa (Lisboa, Portugal)
Objective: To assess the effects of botulinum toxin type A for
cervical dystonia in adults.
Background: This is an update of a Cochrane review first pub-
lished in 2005 (Costa 2005). Cervical dystonia is a frequent and dis-
abling disorder characterized by painful involuntary sustained or
intermittent muscle contractions causing abnormal head movements
and postures. Botulinum toxin type A (BtA) is currently the treat-
ment of choice for cervical dystonia. Recently, several clinical stud-
ies have been conducted providing new data and addressing further
questions regarding the efficacy and safety of BtA treatments.
Methods: Search Methods: Cochrane Movement Disorders Group
trials register, Cochrane Central Register of Controlled Trials, MED-
LINE, EMBASE, as well as reference lists of articles and conference
Movement Disorders, Vol. 30, Suppl. 1, 2015
S202 POSTER SESSION
proceedings. Selection criteria: Parallel group, double-blinded,
randomized, placebo-controlled clinical trials of botulinum toxin type
A (BtA) in adult patients with cervical dystonia. Data collection:
Two independent authors assessed records, selected included studies,
extracted data and evaluated the risk of bias. Disagreements were
solved by consensus or by a third element.
Results: We included 7 studies (n 5 797; 64% [513] women) and
excluded 8 previously included studies. The included studies had an
overall medium methodological quality overall.
Treatment with one BtA injection was associated with an
improvement of 18% in the patients clinical status [figure1], reduc-
ing 8 points in TWSTRS-total score. There was a large clinical bene-
fit in the perspective of patients and physicians, with a moderate
reduction in pain intensity (SMD 0.50, CI 0.35 to 0.65, P < 0.00001)
and a NNT of 2 to 5. BtA-treated patients were 1.20 more likely to
report adverse events (RR 1.20, CI 1.04 to 1.37, P 5 0.01) [figure2],
from which neck weakness (18%) and dysphagia (14%) were the
most common (RR 3.50, CI 1.42 to 8.58, P 5 0.006; RR 3.34, CI
1.83 to 6.07, P < 0.0001). Time to retreatment ranged greatly
between studies (1 to 11 months).
Conclusions: All BtA formulations assessed in this review (botu-
linum toxin a, abobotulinum toxin A and incobotulinum toxin A) are
effective and well tolerated in the treatment of adults with cervical
dystonia. The main adverse events of treatment with BtA are neck
weakness and dysphagia, and are not commonly a reason for discon-
tinuation of treatment. The exact duration of clinical effect of BtA
remains uncertain.
518
A retrospective analysis of 73 patients switched from
onabotulinumtoxinA to incobotulinumtoxinA
D.R. Greeley (Spokane, WA, USA)
Objective: To test the hypothesis that onabotulinumtoxinA and
incobotulinumtoxinA are more clinically similar than not and to
evaluate why one may switch from one toxin to another.
Background: The four available botulinum products in the US
are unique but the clinical implications of the differences between
them has not been definitively established. Similarly, the reasons for
switching from one toxin to another are not well defined.
Methods: This was a single center, retrospective review of
patients switched from onabotulinumtoxinA to an equivalent or near-
equivalent dose of incobotulinumtoxinA over a one year injection
cycle per patient. Reasons for the switch and clinical experience
were reviewed and the financial implications of the switch were
evaluated.
Results: Seventy-three patients were identified who had been
switched from onabotulinumtoxinA to incobotulinumtoxinA. Fifty-
nine (81%) were female. Fifty-one of the total (70%) had cervical
dystonia, twelve (16%) had migraine, four (5%) had blepharospasm,
four (5%) had hemifacial spasm, one had task-specific dystonia and
one had axillary hyperhidrosis.
Sixty-one (84%) of the total patients switched received the exact
same dose of incobotulinumtoxinA, twelve (16%) received three per-
cent less (150u incobotulinumtoxinA instead of 155u onabotulinum-
toxinA) and no patient received more incobotulinumtoxinA than
onabotulinumtoxinA. No adverse drug reactions occurred.
Seventy-one (97%) of the total patients switched noted no clinical
difference after switching products. Two (3%) switched back to ona-
botulinumtoxinA at the next injection cycle one due to perceived
pain at time of injection and the other due to a perceived decrease in
efficacy.
The reason(s) to switch were multi-factorial in most patients but
included reduction in cost (98% of patients switched), ability to get
injections more frequently (64% of patients switched) and ability to
keep the product at room temperature (16% of patients switched).
Using incobotulinumtoxinA instead of onabotulinumtoxinA resulted
in significant cost savings.
Movement Disorders, Vol. 30, Suppl. 1, 2015
Conclusions: Switching from onabotulinumtoxinA to an equivalent
or near-equivalent dose of incobotulinumtoxinA did not result in a per-
ceivable clinical difference. Reduced cost is the most common reason
for the switch. Further studies are needed to confirm these results.
519
Real-world onabotulinumtoxinA treatment patterns in Movement
Disorder patients in a prospective, observational cohort study:
MOBILITYV R
M. Jog, M. Bhogal, G. Trentin (London, ON, Canada)
Objective: Characterize real-world onabotulinumtoxinA (ona-
botA) treatment patterns in Movement Disorder (MD) patients.
Background: OnabotA injections have become an important
treatment option for MD patients. Although guidelines are available,
treatment in actual practice often differs from existing recommenda-
tions. As such, it is important to understand real-world treatment pat-
terns to help optimize treatment paradigms and assess safety over
multiple treatment sessions; however, data on onabotA treatment in
clinical practice is limited.
Methods: This was a Canadian, multi-center, observational study
in patients initiating (nave) or continuing (maintenance) onabotA
treatment. Treatments were administered at the physicians discre-
tion. OnabotA treatment data was a secondary measure, collected at
baseline and each treatment visit (1-5) and summarized using
descriptive statistics. The safety cohort included patients who
received 1 onabotA treatment.
Results: 455 patients (blepharospasm [BSP, n583], cervical dys-
tonia [CD, n5250], hemifacial spasm [HFS, n5122]) between 17-91
years old were enrolled; majority were female (70%), Caucasian
(96%), and on maintenance treatment (75%). Mean onabotA doses
were 57-60U (BSP), 226-247U (CD), and 37-40U (HFS), across all
treatment visits; however, doses up to 700U (CD) were observed. In
nave patients, the average dose at the last injection was generally
higher than at baseline, whereas dosing remained relatively consist-
ent in maintenance patients. Mean time between treatments was 120-
134 days (BSP), 113-132 days (CD), and 121-145 days (HFS). Over-
all, nave patients were generally treated with lower doses at shorter
treatment intervals compared to maintenance. A total of 22
treatment-related adverse events (TRAEs) were reported in 3%
patients (n513: 4 BSP, 6 CD, 3 HFS). Serious TRAEs (n59) were
reported in 1% patients (n54: 1 BSP, 3 CD). Most commonly
reported TRAE was dysphagia (n55).
Conclusions: Data from MOBILITYV R demonstrates the variability
in onabotA treatments for MDs, likely due to the need for individual-
ized treatment and physician preferences. Treatment patterns suggest
that different approaches are often considered based on a patients
underlying disorder and treatment history with onabotA. Overall, data
continues to support the favorable safety profile of onabotA.
520
An experience of changing from onabotulinumtoxin-a to
abobotulinumtoxin-a in 64 patients with focal hyperkinesias
M. Kuzu, S.I. Gul, S. Tezcan, C.M. Akbostanci (Ankara, Turkey)
Objective: Due to a regulatory change in our country weve had
to change all patients botulinum toxin type from onabotulinumtoxin-
a (ONA) to abobotulinumtoxin-a (ABO). This gave us opportunity to
evaluate the safety and effectiveness of this switch.
Background: Debate continues concerning dose-conversion ratio
that should be used when switching products in clinical practice, as
well as comparative effectiveness and safety.
Methods: We included patients with at least two injection sessions
of abobotulinumtoxin-a. Out of 64 patients, 39 (60.9%) were cervical
dystonia, and 16 (25%) were hemifacial spasm.We did not use a spe-
cific ratio for the switch between toxin types, but we performed first
injection of ABO as declared in randomized controlled trials (plus
 POSTER SESSION S203

took care about the clinical properties of the individual patient, like if continue treatment (0.6g 6 0.6 and 1.6 6 2 respectively). Adverse
tremor is prominent we injected oblique muscles). Doses and injection events were difficulty chewing (1) and thick saliva (1), resolving
sites were altered in accordance with the effectiveness and side effects over 4-6 weeks.
of the first injection. Effectiveness was rated by a visual analog scale Conclusions: Incobotulinum Toxin A was safe but did not signifi-
of 0-100% (100% being asymptomatic). cantly improve subjective or objective measures of drooling, possibly
Results: Cervical dystonia: The last mean ONAdose was 169 U, due to the small sample, although possible trends were evident.
the first and second ABO doses were 720 and 643. Mean effective-
ness of the last ONA injection was 66%, and the first and second
522
ABO injections were 69% and 70% effective. Side effects were
detected in the last ONA injections in 5 patients, and for the first Botulinum toxins type A and B for cervical dystonia,
and second ABO injections they were detected in 14 and seven blepharospasm and hemifacial spasm An update of Cochrane
patients. Conversion ratio of toxins was 4,3 (range 2,3-5,7). Movement Disorders group systematic reviews
Hemifacial spasm: The last mean ONA dose was 29 U, the first F.B. Rodrigues, G. Duarte, R. Marques, M. Castel~
ao, J.J. Ferreira,
and second ABO doses were 136 and 131. Mean effectiveness of the P. Moore, J. Costa (Lisbon, Portugal)
last ONA injection was 78%, and the first and second ABO injec-
tions were 74% and 75% effective. Side effects were detected in the Objective: To assess the effects of botulinum toxin A (BtA) and
last ONA injections in 3 patients, and for the first and second ABO B (BtB) for cervical dystonia (CD), blepharospasm (BPS) and hemi-
injections they were detected in 7 and 1 patients. Conversion ratio of facial spasm (HFS) in adults.
toxins was 5,0 (3,2-9,1). Background: This is an update of seven Cochrane reviews first
All parameters of the last ONA and second ABO injections were published by Costa et al. from 2003 to 2005. CD, BPS and HFS are
similar. frequent and disabling disorders characterized by painful involuntary
Conclusions: When switched from botulinum toxin types, side sustained or intermittent muscle contractions causing abnormal
effect rates were high in the first session, but come down to similar movements. Botulinum toxin counteracts the release of acetylcholine
rates in the second session. Their effectiveness is similar. Switch causing local chemodenervation and inhibition of muscle contraction.
ratio (that gives similar effectiveness and side effect rates) is highly Methods: Search Methods: Cochrane Movement Disorders Group
variable (from 2 to 9). This may provide further evidence that there trials register, Cochrane Central Register of Controlled Trials, MED-
is no clinically meaningful dose-equivalency ratio. LINE, EMBASE, as well as reference lists of articles and conference
proceedings. Selection criteria: Double-blinded, randomized,
placebo-controlled clinical trials of BtA and BtB in adult patients
521 with CD, BPS, HFS. Data collection: two independent authors
assessed records, selected included studies, extracted data and eval-
Randomized double-blind placebo-controlled cross-over study of
uated the risk of bias. Disagreements were solved by consensus or
incobotulinum toxin A for troublesome drooling in Parkinsons
by a third element.
disease (PD)
Results: We included 31 studies (13: BtA vs BtA for CD, BPS
P. Narayanaswami, A. Tarulli, E. Raynor, S. Gautam, T. Geisbush, and HFS; 7: BtA vs placebo for CD (i.e. [figure1]); 6: BtA vs anti-
D. Tarsy (Boston, MA, USA) cholinergics for CD; 3: BtA vs BtB for CD; 4: BtB vs placebo for
Objective: To evaluate the safety and efficacy of salivary gland
injections of Incobotulinum Toxin A for drooling in patients with
PD.
Background: Safe and effective treatments for drooling in PD
are lacking. Studies have shown benefit from salivary gland injec-
tions of botulinum toxin; one small pilot study reported possible ben-
efit of Incobotulinum Toxin A.
Methods: Inclusion criteria: PD, normal cognition, no severe dys-
phagia. Exclusion criteria: current warfarin use, significant medical ill-
ness, history of myasthenia gravis/Lambert-Eaton syndrome, past
botulinum toxin use. Subjects were randomized to placebo/drug and
crossed over to the other treatment at the second injection. Incobotuli-
num Toxin A dose was 20 units to each parotid, 30 units to each sub-
mandibular gland (total 100 units). Study duration was 7-8 months,
with monthly evaluations. Outcome measures were saliva weight,
Drooling Severity and Frequency Scale (DSFS). After three evalua-
tions, subjects entered washout (1-2 months). The second injection
was performed at the 4 month visit if saliva weight was 6 0.5 standard
deviations (SD) of baseline, or at the 5 month visit.
Results: Nine of 10 subjects completed the study (6 male, 3
female; mean age/SD 68 6 0.92). Primary outcome was the differ-
ence in saliva weight between baseline and one month post-injection
in drug vs. placebo periods: mean reduction/SD 0.33g 6 0.95 (95%
CI: -0.31 to 0.97) favoring treatment. Secondary outcomes: DSFS
difference between baseline and one month post-injection in drug vs.
placebo periods: mean reduction/SD 0.22 61.9 (95% CI: -0.99 to
1.68) favoring treatment. DSFS decreased 2 points in 2/9 subjects
on drug vs. 1/9 on placebo. Saliva weight decreased  20% in 3/9
subjects on drug vs. 2/9 on placebo. Regression analysis of saliva
weight and DSFS over time showed a steeper slope in the treatment
period (-0.139 vs -0.035 and -0.11 vs. -0.06, p NS). In 6/9 subjects
who continued treatment post-trial there was greater decrease in
saliva weight (0.8g 6 0.8) and DSFS (0.5 61.6) vs. 3/9 who did not Fig. 1. (522).

Movement Disorders, Vol. 30, Suppl. 1, 2015

S204 POSTER SESSION
Fig. 2. (522).
CD; 2: BtA vs placebo for BPS; 1: BtA vs placebo HFS) and
excluded 19. The included studies had an overall medium methodo-
logical quality (i.e. [figure2]).
Meta-analysis was not always feasible. When achievable it showed
that intramuscular injection of BtA and BtB were associated with an
improvement in patients clinical status as assessed by disease-specific
validated scales, and by clinician- and patient-subjective assessments.
When comparing BtA or BtB with placebo adverse events were more
frequent in the treatment group. In regards to how BtA and BtB com-
pare, data showed no significant differences in efficacy or in adverse
events. It was not possible to estimate time to retreatment and seldom
was it possible to include immunogenicity data.
Conclusions: BtA and BtB formulations assessed in this review
are effective and well-tolerated in the treatment of adults with CD,
BPS and HFS. There is no current evidence to support a dose-
dependent clinical response. The exact duration of clinical effect
remains uncertain. The adverse events are frequent but are not com-
monly a reason for discontinuation of treatment.
523
Safety and efficacy of botulinum toxin injections for lower limb
spasticity management in children
M. Venkatesh, D. Ghosh (Strongsville, OH, USA)
Movement Disorders, Vol. 30, Suppl. 1, 2015
Objective: Though proven to be useful for spasticity based on a
few small studies, Food and Drug Administration has not approved
Botulinum toxin in children for spasticity. The current study was
planned to provide more data regarding safety and efficacy of Botuli-
num toxin in children with spasticity.
Background: The neuromuscular blocking activity of Botulinum
toxin has been utilized to treat muscle hyperactivity in dystonia or
spasticity. Considering the high efficacy and excellent safety profile,
Botulinum toxin is approved by FDA to treat spasticity and dystonia
in adults, not yet in children due to some safety concerns.
Methods: All patients < 21 years of age, at Cleveland Clinic
Pediatric Neurology Center between January 2006 and August 2011
who received Botulinum toxin injection in lower limbs for spasticity/
dystonia were included. The procedure was performed using EMG or
e-stim guidance after oral anxiolysis using Midazolam. Either Ona-
botulinumtoxinA or RimabotulinumtoxinB was used. Patient data
and efficacy assessment including Pain Score, Spasm Score, Modi-
fied Ashworth Scale (MAS), and time to walk 25 feet was collected.
Goals were set before the injection to determine Goal Attainment
Scale (-3 to 12). The assessments were done pre-injection, 6 weeks
post-injection, and then every 3-4 months preceding re-injection ses-
sion. Complications were recorded. Mann-Whitney test was used to
show the improvement in scores at different points in time.
Results: 159 children were included (86 male, 73 female); mean
age 9.41 6 5.55 yrs. Significant improvement in Pain Score
(p 5 0.03), Spasm Score (p50.0007), MAS (p5 0.001) was noted at
6 week post-injection; Goal Attainment Scale: 2 in 15/68; 0-1 in 52/
68. The time to walk 25 feet improved from 10.08 6 4.64 secs to
6.97 6 3.72 secs. On 5-year follow up while each patient received 1-
16 sessions of injections, the improved state was maintained. Only 1
child with spastic quadriplegic cerebral palsy developed transient
worsening of already existing weakness of the trunk muscles 10 days
after injection of the hip adductor muscles; she improved in 2 days
without any specific treatment.
Conclusions: This is a large series of Botulinum toxin injection
in children for lower limb spasticity. The injections were well toler-
ated, and were very effective and safe for spasticity and dystonia.
The improvement persisted even after repeated injections over a
period of 5 years.
524
Clinical utility of apraclonidine in ptosis
S. Wijemanne, J. Jankovic (Houston, TX, USA)
Objective: To report two clinical applications of apraclonidine in
patients with ptosis.
Background: Elevation of the eye lid results from a combined
action of two muscles namely, levator palpebrae superioris (inner-
vated by oculomotor nerve) and superior tarsal or M uller muscle
(innervated by sympathetic nerve). In Horners syndrome partial pto-
sis is due to interruption of the oculosympethetic nerve supply to the
M uller muscle. On the other hand, transient ptosis can also occur as
a complication following botulinum toxin injection to the eye lid due
to migration of botulinum toxin in to the levator palpebrae superioris
muscle. Apraclonidine, an a2-adrenergic agonist, is effective in treat-
ing ptosis in these two clinical situations.
Methods: Patient A, a 44 year old female, presents with insidious
onset painless right eye droop. On exam she had right eye partial
ptosis, miosis and dry skin around the eye.
Patient B, a 14 year old female with Tourette syndrome was
injected 15 units of botulinum toxin A to each upper eye lid for eye
blinking tics. A week later she presented with drooping of the right
eye lid. On exam she had right eye partial ptosis with normal papil-
lary exam and accommodation.
Two drops of apraclonidine 0.5% solution was instilled in to the
eye with the ptosis in each patient and was reexamined 20 minutes
later.
 POSTER SESSION
Results: There was complete resolution of partial ptosis in patient
A, which helped to confirm the diagnosis of Horners Syndrome. She
continued to use apraclonidine 2 to 3 times a day as a therapeutic
option with good effect. The workup to identify the etiology for the
Horners syndrome thus far has been negative. In patient B, there
was >50% improvement in the partial ptosis following the applica-
tion of apraclonidine. She continued to use apraclonidine 2-3 times a
day as a therapeutic option with good effect for the transient ptosis.
Conclusions: Apraclonidine is effective in correcting partial pto-
sis in Horners syndrome as well as transient ptosis following botuli-
num toxin injection.
Pediatric Movement Disorder
525
Neural and physiological changes following intensive voice
therapy in children with motor speech disorders secondary to
cerebral palsy
C.A. Boliek, R. Bakhtiari, A.J. Reed, B.J. Major, I. Cribben, H.H.M.
Gynane, A. Jaswal, D. Bremmekamp, C.M. Fox, B. Chouinard, J.
Cummine (Edmonton, AB, Canada)
Objective: To evaluate the contributions of the brains neural
developmental regulation and peripheral neuromuscular change in
response to a specific standardized intensive voice and speech treat-
ment in a group of children with motor speech disorders secondary
to cerebral palsy (CP).
Background: Previously we have applied an intensive voice
treatment protocol (Lee Silverman Voice Treatment, LSVT) that is
commensurate with activity-dependent neuroplasticity principles on
groups of children with dysarthria secondary to CP. Post-treatment
positive outcomes have been shown in respiratory and muscle physi-
ology, cortical white matter integrity, and acoustic correlates of
speech and voice. Advances in neuroimaging techniques offer a via-
ble method with which to interpret meaningful behavioural changes
following treatment.
Methods: Nine children having motor speech disorders and CP com-
pleted a full dose of LSVTV C LOUD (16 hours direct treatment in four
weeks, plus standardized practice) and a 12-week maintenance program.
Pre- post- and follow up testing involved speech breathing kinematics,
surface EMG of chest wall muscles, acoustic measures of voice and
speech, structural images (water diffusion tensor imaging, DTI) and
functional neuroimaging (fMRI) of overt speaking. Nine matched typi-
cally developing controls were tested at the same three time points.
Results: Preliminary analyses on speech breathing and chest wall
muscle activity indicated a positive change post-treatment and stability
or continued improvement following the maintenance program.
Changes in white matter integrity (DTI) for the corticospinal tract,
superior and inferior longitudinal fasciculi, and uncinate will be
reported. In addition, changes in number and strength of neural connec-
tions (fMRI) during speaking are described. General stability in physio-
logical and neuroimaging measures was observed in the control group.
Conclusions: Our preliminary analyses indicate potential neural
regulation and peripheral neuromuscular change in response to a spe-
cific standardized intensive voice and speech treatment in children with
motor speech disorders secondary to CP. These data provide some ini-
tial insight about therapy-induced brain activation, motor learning sta-
bility and motor skill acquisition in relation to cortical reorganization
and processes specific to voice and speech in children with CP.
526
Technology-enhanced maintenance practice following intensive
voice therapy (LSVT LOUD) in children with cerebral palsy and
dysarthria
C.M. Fox, C.A. Boliek (Denver, CO, USA)
S205
Objective: To evaluate the feasibility of using the LSVT Com-
panion System for practice during a 12 week maintenance phase post
LSVT LOUD in nine children with cerebral palsy (CP).
Background: Children with cerebral palsy (CP) have speech dis-
orders that negatively impact communication. Positive outcomes
immediately post-LSVT LOUD voice treatment in children with CP
have recently been reported, however maintenance of effects were
variable. Consistent practice post-treatment may be a key to main-
taining improvements over time. A recently developed computer pro-
gram, called the LSVT Companion, guides a client through
homework sessions while collecting data on sound pressure level
(SPL), frequency and duration. Use of such a system with children
with CP post LSVT LOUD may be a mechanism to make continued
post-treatment practice feasible as well as objectively quantify the
amount and quality of that practice.
Methods: Nine children with CP and dysarthria participated in
this study. Children ranged in age from 8Years; 7months to 15years;
8months; 3 females. Pre-treatment data collection included acoustic,
physiological, and neural imaging. The children completed 4 weeks
of LSVT LOUD therapy and repeated the data collection immedi-
ately post-treatment and at 12 weeks follow-up. During the 12 week
maintenance phase children completed daily homework practice uti-
lizing the LSVT Companion System allowing for quantitative data
regarding amount and quality of practice. Child and parent inter-
views regarding usability of the LSVT Companion System were also
completed.
Results: All nine children successfully completed LSVT LOUD.
Data from the 12-week maintenance phase indicated that increased
practice during this time period may have contributed to better main-
tenance of vocal SPL in sentences, except for one child. Parents and
children found the Companion usable to varying degrees and offered
suggestions for improving the system.
Conclusions: This is the first study to produce objective docu-
mentation of the amount and quality of practice during a speech
treatment maintenance phase in children with CP. The use of the
Companion motivated some children to continue their practice post
treatment. Alterations to the program are needed for more effective
use.
527
Successful treatment of juvenile Parkinsonism with bilateral
subthalamic deep brain stimulation in a 14-year-old girl
G. Genc, S. Ertan, H. Apaydin, A. Gunduz, C. Poyraz, H. Canaz, S.
Aydin (Istanbul, Turkey)
Objective: Case Report.
Background: DBSs impact on Juvenile Parkinsonism (JP) in
pediatric age group is unknown.
Methods: We present a JP case who was successfully treated
with bilateral subthalamic DBS surgery due to severe dyskinesias,
motor fluctuations, tremor and bradykinesia which have affected her
quality of life despite optimal medical therapy.
Results: A 14-year-old girl was admitted for evaluation in terms
of therapeutic options for her JP. Her complaints began at the age of
10 with left hand tremor, stooped posture, and dragging of the left
leg. Her family history was unremarkable. One year after the onset
of symptoms, she was diagnosed with JP in another tertiary referral
hospital. Then, she was put on levodopa treatment, and the dosage
was increased up to 50/500 mg carbidopa/levodopa daily in 6
divided doses. She was fully responsive to levodopa (LD), however,
in two years after the diagnosis she eventually developed severe
motor fluctuations with a drug response duration of only two hours,
and severe dyskinesias predominantly involving left extremities and
affecting nearly the whole on time period. Her neurologic exami-
nation revealed during off periods a total akinetic-rigid condition,
anarthria and also dystonic posturing and severe tremor on her
extremities with a UPDRS part III score of 48, whereas it was 7 dur-
ing on. Following a detailed pre-DBS evaluation, she underwent
Movement Disorders, Vol. 30, Suppl. 1, 2015
S206 POSTER SESSION
bilateral STN DBS surgery. One month after the surgery, she was
steadily treated with continuous bilateral monopolar stimulation
through contact 3 on the left electrode and contact 11 on the right
electrode (2.0 V; 130 Hz; 60 msec). With these settings, the dystonia,
bradykinesia and speech were markedly improved and the tremor
was resolved. She was able to arise from a chair and walk in normal
stride independently. Post-surgery UPDRS part III scores were mark-
edly improved (3 during onstimulation, on medication state with- were held.
out dyskinesias). In the first month after surgery, her daily LD
dosage was decreased by 50%.
Conclusions: To our knowledge, our case is the youngest case of
JP treated with DBS. Clearly the positive impact of DBS on JP in
pediatric age group that we observed in our case, will need to be
confirmed in a larger pediatric cohort and in a longer period of time,
but we can suggest DBS as a treatment option in severely disabled
and complicated JP cases.
528
Is there a genetic predisposition to functional/psychogenic
Movement Disorder?
T. Hedderly, M. Woods, P. Hindley, S. Robinson (London, United
Kingdom)
Objective: To highlight the need to recognise undiagnosed neuro-
logical or neurodevelopmental disorders in children presenting
acutely with a functional movements and explore the genetic role in
pathophysiology.
Background: Functional or psychogenic movements have been
conceptualized to be primarily related to psychological factors rather
than having a neurological or genetic basis. There has been recent
debate around terminology and the term non organic is widespread.
In our clinic (TANDeM) we have identified that children presenting
acutely with functional movements may have associated and unrec-
ognised neurological or developmental disorder ie Tourette syndrome
(TS) or autism spectrum. In addition, Children with recognised TS
can present with functional movements in a way that children with
epilepsy present with non epileptic attacks. Mechanisms are still
unknown and it is vital to define phenomenology to help inform
these.
Methods: The children have a full neurological assessment and
when appropriate neuropsychological and developmental profiling.
Targeted symptom management is given for specific difficulties
including social communication problems and tic disorders as well
as co-occurring anxiety, OCD and specific learning problems. There
has been no focused management for motor symptoms as these are
considered a possible secondary phenomenon despite appearing as
the presenting complaint. For the child and parent the movements
are described as well recognised neurological events that come from
the brain or mind and which respond well to psychological treat-
ments.The family history may include Tourettes, Autism or Anxiety
disorders and genetic investigations are requested if appropriate.
Results: One example is SH a 15 year old girl with functional
movements identified to have attention deficit and undiagnosed Tour-
ettes and OCD. A 15q14q15.1 array duplication was inherited from
her mother who herself suffered severe social anxiety, This anomaly
has been described in anxiety disorders.The movements stopped fol-
lowing cognitive behavioural intervention.
Conclusions: Children presenting with functional movements
need careful evaluation for an associated neurological or neurodeve-
lopmental disorder. Approaching these disorders within a bio-
psycho-social model seems to improve the management of all the
components of the disorder, The term non organic should be
avoided and we should further explore probable genetic influences.
529
What do we know about PANS.?
S.E. Munasipova, Z.A. Zalyalova (Kazan, Russia)
Movement Disorders, Vol. 30, Suppl. 1, 2015
Objective: The determine a clinical, epidemiological, laboratory
and neuroimaging criteria for patients with PANS (Pediatric Acute-
onset Neuropsychiatric Syndrome).
Methods: The clinical, epidemiological, extended immunological,
microbiological studies, MRI of brain to 57 patients with tics group
PANS, 12 patients with tics group non-PANS, 39 patients with
chronic diseases of upper respiratory tract and 20 healthy individuals
Results: PANS-syndrome occurs 2.5 times more frequently in
males. The presence of chronic foci of infection was not a predictor
of the development of the syndrome PANS. The group PANS
characterized by the Tourette syndrome (39%), OCD (obsessive
compulsive disorder) from mild to severe degree, ADHD (attention
deficit hyperactivity) with a predominance of hyperactivity. Morpho-
metrically PANS characterized by an increase in the size of the
corpus callosum (increase its maximal length, knee length, roller
width of the corpus callosum in a coronal section, p <0.05), reduc-
ing the size of the thalamus in the left hemisphere (p <0.05), flat-
tened shape globus pallidus in both hemispheres, the rounded shape
of the shell in the left hemisphere. Reduced level JgM (immunoglob-
ulin M), increased levels of CD8 1 lymphocytes and carrier of
BGSA (-b-hemolytic streptococcus group A) were found in patients
of PANS.
Conclusions: According to the clinical manifestations of patients
with PANS vary in severity and phenomenology of tics and behav-
ioral disorders. In males this syndrome occurs 2.5 times more fre-
quently. The presence of a chronic source of infection is not a
predictor of the development of PANS. The presence of carrier
BGSA, decreased level JgM and elevated levels of CD8 1 lympho-
cytes may play a key role in the development of PANS. Mor-
phometric differences are characterized by an increase in the size of
the corpus callosum, reduction in size of the thalamus in the left
hemisphere and the change in shape of the globus pallidus, shell.
530
BCAP31 mutation causing congenital dystonia and central
hypomyelination discovered using exome sequencing
P. Vittal, D.A. Hall, E. Berry-Kravis (Chicago, IL, USA)
Objective: To present two cases of congenital dystonia and cen-
tral hypomyelination discovered by exome sequencing.
Background: A mutation in BCAP31 was recently described in 3
families with strabismus, optic atrophy, deafness, congenital dysto-
nia, and central hypomyelination. Lack of BCAP31 protein function
disrupts endoplasmic reticulum (ER) metabolism, and causes disorga-
nization of Golgi. It impacts ER-to-Golgi crosstalk and results in
impaired protein trafficking.
Methods: Two male siblings (18 and 21 yo) presented with poor
head control and hypotonia at 2 months of age, strabismus and optic
pallor at 4 months of age, and choreoathetotic/dyskinetic movements
at 6-12 months of age that progressed to dystonia. Both had severe
motor and language delay, sensorineural hearing loss, facial dysmor-
phism and neither could walk. The mother had similar facial fea-
tures, but no neurological or cognitive problems. Both patients had
minimal response to levodopa, pimozide, trihexyphenidyl, clonidine,
baclofen, clonazepam, and tetrabenazine. Work up including inborn
error screen, urine, blood, CSF studies and electrophysiologic studies
were unremarkable. MRI brain revealed delayed myelination,
decreased gray/white matter in posterior occipital lobes, hypoplasia
of the superior cerebellar vermis and thinning of the corpus cal-
losum. Genetic work up including subtelomeric FISH, screening for
MERRF, MELAS, NARP, and Leighs mutations was negative. Non-
random X- inactivation in studies of maternal DNA suggested X
linked transmission.
Results: Exome sequencing was performed on the entire family.
Both patients were found to have a 6 base-pair deletion in BCAP31
at Xq28, and the mother and patients sister were carriers.
 POSTER SESSION
Conclusions: This report describes 2 patients in the same family
affected by a recently diagnosed X linked disorder characterized by
dystonia, deafness and central hypomyelination. This 6 base pair
deletion in the BCAP31 gene is expected to alter function of the pro-
tein. It highlights the clinical features of mutation in BCAP31 and
the utility of exome sequencing to obtain diagnosis.
531
Intense imagery movements (IIM): Neuropsychological case
series of a newly identified subgroup of motor stereotypies
M.L. Woods, S.J. Robinson, T.J. Hedderly (London, United
Kingdom)
Objective: The objectives are to report clinical features and pre-
liminary neuropsychological findings for children with Intense
Imagery Movements (IIMs), to inform clinical management and the-
oretical understanding.
Background: We have recently identified a new subgroup of
children who present with stereotyped movements in the context of
episodes of intense imagination, termed IIMs.
Methods: 10 children (9 boys and 1 girls) were identified via
teams with expertise in pediatric Movement Disorders. Neuropsycho-
logical assessments were conducted for four children (3 boys, 1 girl;
mean age 9 years 4 months) due to parental concerns regarding the
management of IIMs. Children were administered standardized tests
of IQ, memory, oral expression, attention and executive functioning.
Parents completed of a range of questionnaires.
Results: Stereotypies presented as paroxysmal complex move-
ments. Imagination themes included computer game, cartoons/movies
and fantasy. Engagement in acts of imagination preceded the move-
ments, which were not under volitional control. All children exhib-
ited discrepant intellectual profiles, with three functioning
predominantly in the superior rage and one in the borderline range.
All exhibited clinically significant impairments in processing speed
and attention, but strengths in memory or oral expression.
Conclusions: Children with IIMs appear to form a discrete ster-
eotypy subgroup, for whom cognitive skill development is uneven.
Good memory or verbal expression skills may underpin imaginary
abilities, whilst weaker attention and processing speed skills may
contribute to engagement in imaginary acts when bored, with move-
ments likely to serve the function of increasing sensory stimulation.
Children with IIMs are of relevance to clinical practice but also raise
interesting theoretical questions regarding the association between
neural networks underpinning cognition and motor functioning.
History
532
A historical review of Wilsons disease
F.M. Branco Germiniani, B.E. Scheffer, W.O. Arruda, H.A.G. Teive
(Curitiba, Brazil)
Objective: To make a brief review of the historical hallmarks of
Wilsons Disease worldwide, focusing on the Brazilian contributions.
Background: WD is one of the most important neurological dis-
orders due to metal deposition in the central nervous system, with a
rich history from discovery until successful treatment.
Results: First described as pseudosclerosis by Westphal in
1883, when he reported 2 patients with tremors, and by Gowers in
1888, who coined the term tetanoid chorea, WD would eventually
become notorious following the description by Samuel Alexander
Kinnier Wilson. Wilsons monograph on progressive lenticular
degeneration became the longest single article published on the
medical journal Brain, on March 1912, with 214 pages. Shorter ver-
sions were published in The Lancet and Revue Neurologique. His
S207
series comprised 4 original patients, 2 additional cases from the
registry of Londons national hospital and 6 other previously pub-
lished cases . The clinical and anatomical descriptions would remain
essentially unaltered even 102 years after his report. Wilson per-
formed all the anatomopathological studies himself and drew all the
figures of his monograph. Prior to Wilsons monograph, Kayser and
Fleischer independently reported the finding of a pigmented ring
around the cornea in patients with suspected multiple sclerosis,
which would later become one of the hallmarks in the clinical diag-
nosis of WD. As to the evolution of therapy, the use of copper che-
lating agents remained unsuccessful until the introduction by Walshe
in 1956 of Penicilamine, providing a means of long-term treatment.
In Brazil the first reported case of WD was made by Austregesilo
Filho in 1944, who highlighted tortion spasms as the main neurologi-
cal manifestation of his patient, suggesting it was a dystonic form of
WD. Cerebral abnormalities and hepatic cirrhosis on autopsy would
confirm the clinical diagnosis. In the sixties Horacio Martins Cane
contributed with laboratory techniques and specific tools for meas-
uring the metabolism and values of copper in different organic fluids
and participated in clinical studies that helped understand the pro-
gression of the disease. We also highlight the contribution of Egberto
Reis Barbosa with a large cohort of Brazilian patients in 2006.
Conclusions: WD is one of the main neurological disorders due
to abnormal metal deposition. We attempted to highlight some of its
historical hallmarks.
533
Catatonia: Historical perspective
R. Fekete (Valhalla, NY, USA)
Objective: The aim of the study is to present early ideas regard-
ing the definition and phenomenology of catatonia, which at the time
was referred to as katatonia.
Background: Kahlbaums seminal 1874 manuscript introduced
katatonia as a distinct disease entity. The word is derived from Greek
katatein^
o meaning to stretch tightly. Spannungs Irreesein (spastic/
tonic insanity) was an alternative name proposed by Kahlbaum. His
formulation was based on earlier classification work on vesania
typica (1863), a term which did not receive acceptance by succeed-
ing authors. Considerable controversy regarding whether katatonia is
a distinct disease or syndrome ensued.
Methods: Google books archive was queried using keywords
katatonia, melancholia attonita.
Results: 9 historical manuscripts (review articles and dictionary
entries) describing phenomenology and definition of katatonia were
retrieved (1887, 1889, 1890, 1892, 1894, 1895, 1897, 1902, 1904).
Conclusions: The idea of katatonia as an organic disease entity
was supported by Neisser, Koch, Kiernan (1882), and Spitzka
(1883). In contrast to the modern definition, Kahlbaums 1874 defini-
tion of katatonia consisted of phases that may have also included an
excited, hysterical, or hyperkinetic phase with spasmodic attacks
or convulsions (melancholia agitata) in addition to the cataleptic
phase. According to Meynert (1872) and Seglass (1890), catatonia is
a form of melancholia attonita while other contemporary authors
stated that melancholia attonita differed from katatonia by having
extended as opposed to brief periods of catalepsy. Bondurant (1894)
describes seeing both typical forms of katatonia and also a progres-
sion towards cataleptic features of other recognized psychiatric disor-
ders. Westphal (1878) disagreed with katatonia as a distinct
diagnosis.
534
XIX-XX Century art and dystonia
J.C. Martinez Castrillo, P.J. Garcia-Ruiz, J. Slawek, E.J. Sitek
(Madrid, Spain)
Movement Disorders, Vol. 30, Suppl. 1, 2015
S208 POSTER SESSION
Objective: To describe representations of dystonia in the Art of
the last two centuries.
Background: Dystonia has a recent History in Medicine. Focal
dystonia was described in XIX century by several classic authors
including Gowers, whilst generalized dystonia was described at the
turn of the century by Oppenheim, Flatau and W. Sterling. However,
it is possible to find precise descriptions of dystonia in Art, decades
and even centuries before the medical definition.
Methods: We have reviewed several depictions of abnormal pos-
tures in art (sculpture, painting and literature) over the last two cen-
turies that might represent descriptions of dystonia.
Results: We have found dramatic descriptions in modern Art,
such as painful cervical dystonia (Suffering from Brancusi), cervical
dystonia with sensory trick (Modigliani) and upper limb dystonia
(Wyspianski). Literature is also a source of precise pre-neurological
descriptions, especially during the XIX century. In David Copper-
field, Dickens depicts characters with generalized dystonia (Uriah
Heep); cervical dystonia (Mr Sharp) and even spasmodic dysphonia
(Mr Creakle).
Conclusions: Art is a source of Neurological information, and
that includes primary and secondary dystonia.
535
Need for improved bone mineral density screening in
Parkinsonism
M.S. Nicoletti, B. Hanna-Pladdy, J. Rowe, K. Holmes, L.M. Shulman,
S.G. Reich, R. von Coelln, M.J. Armstrong (Baltimore, MD, USA)
Objective: To investigate current osteoporosis screening patterns
in Parkinsonism patients.
Background: Parkinsonism patients are at high risk of falls and
fractures; both are associated with increased morbidity. Parkinsons
disease (PD) patients also have an increased osteoporosis risk. Lim-
ited evidence exists regarding bone mineral density (BMD) screening
patterns in Parkinsonism.
Methods: Consecutive English-speaking patients participating in
a longitudinal Parkinsonism database and presenting for follow-up
were approached for participation. Consenting subjects completed a
bone health questionnaire. Frequency of BMD testing recommenda-
tions was assessed and the relationship with age, gender, and fall his-
tory was analyzed using t-tests and logistic regression for continuous
variables and Chi square and Fishers exact tests for dichotomous
variables.
Results: 73 individuals participated (40% female), all with PD
except three with Parkinsonism. Average age was 66.0 (SD
10.3) years. Thirty-four (47%) reported that a physician recom-
mended screening; 33 had BMD testing performed (5 osteoporosis,
14 osteopenia, 14 normal). Female gender (p<0.001) but not age
was significantly associated with a higher likelihood of BMD test-
ing recommendations. Of the fourteen women 65 years for whom
screening is universally recommended, thirteen had it performed.
All women over 52 years (n522) except one had screening
(p<0.001 vs rest of cohort). Of the 16 patients with a fracture
since diagnosis (range 1-3 fractures), fourteen were recommended
to have BMD screening. Thirty-two patients (44%) reported at
least one fall in the past six months (range 1-100), but this was
not associated with increased screening recommendations
(p50.39). Of patients who fell in the last 6 months, 4/9 women
had received BMD screening recommendations and only 9/23 men
had received recommendations; of these, all four women and five
men already had fractures. Likelihood of BMD screening recom-
mendations was not associated with disease duration or UPDRS
motor or MoCA scores.
Conclusions: Less than half of Parkinsonism patients received
BMD screening recommendations. An opportunity exists to target
Parkinsonism patients with falls for increased BMD screening recom-
mendations, especially men, who are receiving recommendations
much less often but who are also at increased risk.
Movement Disorders, Vol. 30, Suppl. 1, 2015
POSTER SESSION 4
Tuesday, June 16, 2015
12:3014:00
Coronado Ballroom
Surgical Therapy: Parkinsons disease
536
Predictors of functional and quality of life outcomes in
Parkinsons patients after deep brain stimulation
H. Abboud, G. Genc, N. Thompson, S. Oravivattanakul, F. Alsallom,
D. Floden, A. Machado, M. Gostkowski, A. Ezzeldin, H. Maarouf,
O.Y. Mansour, H.H. Fernandez (Cleveland, OH, USA)
Objective: To evaluate predictors of intermediate and long-term
quality of life (QOL) and functional outcomes (6-months and 1-year
postoperative EQ5D and UPDRSII respectively) following DBS in
patients with Parkinsons disease (PD).
Background: While predictors of motor outcome after DBS in
PD patients are well-described, little is known about predictors of
functional and QOL outcomes after surgery.
Methods: PD patients who underwent DBS at our Center from
2006 to 2011 and had complete charting were evaluated. To deter-
mine predictors of post-operative outcomes, the changes in UPDRSII
and EQ5D questionnaires after surgery compared to before surgery
were analyzed using a logistic regression model. Secondary out-
comes included the Patient Global Impression Scale (PGIS), and the
Clinical Global Impression Scale (CGIS).
Results: We identified 130 patients [71% male, mean age:
63 6 9.1, mean PD duration: 10.7 6 5.1]. For functional and QOL
outcomes we identified 56 patients [73.2% male, mean age:
61.3 6 9.6, mean PD duration: 10.6 6 4.7] with available pre and
post-operative health status measures. Patients with postural instabil-
ity had 6-month UPDRS II scores that were, on average, 6.48 points
worse than patients without postural instability (P=0.0193). A similar
estimated effect of postural instability was found for 1-year UPDRS
II scores but statistical significance was not achieved (Estimated
Effect 5 6.45, P=0.0634). Patients with postural instability had 1-
year EQ-5D index scores that were, on average, 0.12 points lower
than patients who did not have postural instability (P 5 0.0191). For
every one-point increase in UPDRS on-state motor score, the 6-
month EQ-5D index worsened by 0.01 units (P 5 0.0050). Of
patients that had tremor, 84.0% were much or very much
improved on the CGIS, whereas 60.0% of patients without tremor
were much or very much improved (P 5 0.0075). Patients with-
out dyskinesia and patients without freezing were more likely to be
much or very much improved (P=0.038, P=0.031 respectively).
Conclusions: The presence of postural instability predicted worse
post-operative functional outcome at 6-months and worse QOL out-
come at 1-year, and higher preoperative UPDRS motor score pre-
dicted worse post-operative functional outcome at 6 months. Patients
with significant dyskinesia, freezing, and absence of tremor were less
likely rated as much or very much improved by clinicians.
537
Factors associated with postoperative confusion following deep
brain stimulation surgery for Parkinsons disease
H. Abboud, G. Genc, N. Thompson, S. Oravivattanakul, F. Alsallom,
D. Floden, A. Machado, M. Gostkowski, A. Ezzeldin, H. Maarouf,
O.Y. Mansour, H.H. Fernandez (Cleveland, OH, USA)
Objective: To evaluate predictors of immediate outcomes (i.e.
presence of postoperative confusion and prolonged hospitalization)
 POSTER SESSION
following deep brain stimulation surgery (DBS) in patients with Par-
kinsons disease (PD).
Background: While predictors of long-term motor outcome after
DBS in PD patients are well-described in literature, little is known
about predictors of immediate postoperative outcomes following
DBS surgery.
Methods: PD patients who underwent DBS surgery at our Center
from 2006 to 2011 with complete charting were analyzed. We com-
puted the proportion and percent of patients that had post-operative
confusion and that had a post-operative length of stay of more than
2 days. Fishers exact tests were performed to determine association
with categorical predictors and logistic regression models were cre-
ated for continuous predictors. For each model, we computed the
odds ratio along with 95% confidence intervals and tested whether
each odds ratio was significantly different from 1.
Results: We identified 130 patients [71% male, mean age:
63 6 9.1, mean PD duration: 10.7 6 5.1]. There was 7 cases of post-
operative confusion and 19 cases of postoperative hospitalization lon-
ger than 2 days. Of the 48 patients with tremors, none had post-
operative confusion, whereas 10.1% (7/69) of patients without trem-
ors had post-operative confusion (P=0.0425). Also, 10.2% (6/59) of
patients with postural instability had post-operative confusion while
1.6% (1/61) of patients without postural instability had post-
operative confusion (P=0.0575). For every one-unit increase in the
baseline UPDRS-on state motor score, the odds of having post-
operative confusion increased by 10% (P=0.0420). Finally, we had
previously reported an association between baseline attention impair-
ment and prolonged postoperative hospitalization in PD patients fol-
lowing DBS [Abboud h, et al. Impact of Mild Cognitive Impairment
on Outcome following Deep Brain Stimulation Surgery for Parkin-
sons disease. Parkinsons and Relat Disord (2015), doi: 10.1016/
j.parkreldis.2014.12.018]. No association was noted regarding the
age at disease onset, disease duration, presence of dyskinesia or
freezing, and baseline levodopa equivalent dose.
Conclusions: Absence of tremors, higher preoperative UPDRS
motor score, presence of postural instability, and attention impair-
ment were associated with acute post-operative confusion or pro-
longed hospitalization.
538
Postoperative deep brain stimulation (DBS) impedance
variability in Parkinsons disease (PD) patients implanted with
Vercise system
F. Alesch, R. Jain, L. Chen, T. Br ucke, F. Seijo, E. Suarez San
Martin, C. Haegelen, M. Verin, M. Maarouf, M.T. Barbe, S. Gill, A.
Whone, M. Porta, D. Servello, L. Timmerman (Vienna, Austria)
Objective: The VANTAGE study evaluates motor improvement
in moderate-to-severe Parkinsons disease (PD) following bilateral
subthalamic nucleus (STN) deep brain stimulation (DBS). Impedance
variability in subjects was collected to evaluate changes in imped-
ance following DBS.
Background: Most DBS systems use voltage-controlled systems
that deliver stimulation dependent on impedances. Modeling displays
an impedance change of 450X resulted in 50% reduction in volume
of tissue activated (Butson, et al. 2006) and such changes are
reported in animal studies (Steinke et al., MDS Congress 2013).
Impedance instability could be, in part, responsible for the need to
reprogram stimulators, postoperatively. A current-controlled DBS
system is expected to better control stimulation with changing impe-
dances. However, long-term data in human DBS subjects is limited,
and within-subject impedance variability is thought to be minimal.
Thus, impedance variability in 40 subjects with bilateral DBS
over a 52 week period is presented here.
Methods: Forty subjects with idiopathic Parkinsons disease (PD)
were implanted bilaterally with the current-controlled, CE-marked
Vercise DBS system in the subthalamic nucleus (STN). Subjects
devices were activated 2 18 days after implant. The impedances
S209
were measured during office visits at activation, 12, 21, 26, and 52
weeks post-implant.
Results: A trend of large changes in impedances was observed in
these subjects over the entire period evaluated. A high degree of
inter-patient variability was observed, with impedances ranging from
574 - 1512 ohms (X) at activation (n5 33, mean=844.8,
median=778), 919 - 1583 X at 12 weeks (n528, mean=1182.5,
median=1152), 907 - 1626 X at 21 weeks (n518, mean=1177.9,
median=1168), 809 - 1488X at 26 weeks (n526, mean=1164.3,
median=1158), and 746 - 1488 X at 52 weeks (n520, mean=1215.4,
median=1261). In addition, within-patient impedance variation on
individual contacts ranged from 135 (6.7%) to 4436 X (63.1%)
changes between office visits.
Conclusions: Impedances in DBS subjects vary between and
within subjects. This variability over time is similar to that previ-
ously reported in animal data. With data on long-term impedance
variability in human DBS subjects, this study demonstrates the
importance of current-controlled DBS systems that can control stimu-
lation despite impedance variability over time.
539
Usability and technical options of rechargeable pulse generators
F. Alesch, A. Amon (Vienna, Austria)
Objective: To compare usability, technical options including
error handling of the rechargeable pulse generators currently avail-
able on the CE market.
Background: Deep brain stimulation for Movement Disorders
has seen an increasing interest in rechargeable systems. The initial
concern that patients might not be able to manage the recharging
process is fading. In the present study we analyze if there are key
features that might improve the usability of these devices and thus
increase the general acceptance of rechargeable systems.
Methods: Three rechargeable pulse generators, ACTIVAV R RC
(A), BRIO TM (B), and VERSICE TM (V) were evaluated under test
bench like conditions and the interaction with both, human factors
(patient) and technical factors (external unit) were evaluated. In addi-
tion technical features were evaluated.
Results: The general concept of all three tested devices is similar,
the difference becomes obvious when it comes to handling. The
external charging part is made of two pieces with a wired connection
in A and B while it is single piece and thus wireless in V. The maxi-
mum implantation depth, a key factor for the recharging perform-
ance, varies between 1 cm (A) and 2 cm (B,V).
Reaction time in case of charging malfunction was between 48
seconds (A) and 1 second (V). Steps to initiate recharging were 2 in
B and V and 3 in A. Steps to relaunch an interrupted charging pro-
cess were 1 in A and 0 in B and V.
Longevity, a factor influencing repeated surgery, is 9 years (auto-
matic shut off) in A and theoretically unlimited in B and V.
Conclusions: Whereas the size and the general surgical handling
of these devices are very similar, they significantly differ when it
comes to usability and technical features. Design aspects might com-
plicate the handling of a rechargeable system and negatively impact
acceptance by patients.
540
Effects of STN-DBS on diphasic dyskinesia patients with
Parkinsons disease
A. Altinkaya, M. Fraraccio, C. Lepage, T.T.M. Pham, E. Lafleur-
Prudhomme, A.F. Sadikot, N. Jodoin, M. Panisset (Montreal, QC,
Canada)
Objective: To compare the effects of deep brain stimulation of
the subthalamic nucleus (STN-DBS) in patients with Parkinsons dis-
ease (PD) with or without diphasic dyskinesia (DID).
Movement Disorders, Vol. 30, Suppl. 1, 2015
S210 POSTER SESSION

TABLE 1. Demographic Information
DID non-DID
n 4 15
age 56 6 9.5 57 6 8.4
disease duration(years) 7 6 1.8 11 6 5
operation side 1 patient R, 1 patient R,
3 patients B 1 patient L,
13 patients B
Background: STN DBS is an effective treatment on Parkinsonian
motor symptoms and levodopa-related complications. There are sev-
eral studies about the effect of STN-DBS on the LID (Levodopa
induced dyskinesias) and most of them are focused on the peak-dose
dyskinesias. There is no report which is comparing the effects of the
STN DBS on the DID patients and non-DID patients in PD.
Methods: Consecutive patients were evaluated using the Unified
Parkinsons disease rating scale (UPDRS), CAPIT timed tests
(CAPIT-TT), Tremor Rating Scale (TRS), Timed Up and Go (TUG),
10 Meter Walk Test (10MWT), 6 Minutes Walking Test (6MWT),
5X Sit-to-Stand Test (5XSST), MiniBEST, Montreal Cognitive
Assessment (MoCA), semantic word fluency, Epworth Sleepiness
Scale, Pittsburg Sleepiness Questionnaire (PSQI), Hospital Anxiety
and Depression Scale (HADS/A and HADS/D), Parkinsons disease
Fatigue Scale (PDFS), Zarit Caregiver Burden and Patients Global
Impression of Change (PGIC). We considered here only the OFF
motor evaluations. The Mann-Whitney U test was performed with 2-
sided p values and 0.05 significance level.
Results: Four DID patients and 15 non-DID patients were eval-
uated pre- and 7 to 15 months post-surgically. The demographic
information is summarized in Table 1. UPDRS I and word fluency
tests showed significant between group difference. The results are
summarized in Table 2.
Conclusions: Our data shows that, even though there is no
between group difference in disease severity, PD patients with DID
seek surgery earlier in the disease evolution. STN DBS appears as
effective in DID as in non-DID in suppressing dyskinesia. Patients
without DID had more tremor and show a good response to surgery.
Although there were no between group difference on the MoCA
scores pre- and post-surgically, patients with DID worsened signifi-
cantly compared to patients without DID on UPDRS I especially for
thought disorder and motivation and word fluency. This suggest that
patients with DID may be different in their response to STN DBS.
This will need to be explored further with groups matched on disease
duration.
541
Long-term outcomes of subthalamic deep brain stimulation in
monogenic Parkinsons disease
C.C. Aquino, N.P. Visanji, I. Beaulieu-Boire, Y.Y. Poon, A. Valencia,
M. Fallis, R. Munhoz, S. Kalia, M. Hodaie, A. Lozano, H.B. Ferraz,
E. Rogaeva, E. Moro, A.E. Lang, A. Fasano (Toronto, ON, Canada)
Objective: To evaluate long-term outcome of subthalamic deep
brain stimulation (STN-DBS) in monogenic Parkinsons disease
(PD). We hypothesise that genetic variation may underlie heteroge-
neity in surgical response to STN-DBS in PD.
Background: STN-DBS outcome is variable in terms of motor
improvement and development of complications. Mutations in genes
linked to PD play a role in phenotypic heterogeneity, including
response to treatment, and these patients are enriched within the sur-
gical population due to early disease onset. Previous studies in a
small number of subjects suggested that Parkin or PINK1 patients
have a promising short-term outcome limited by axial symptoms.

TABLE 2. Motor and Non-motor Significant Results

DID non-DID

pre-op post-op pre-op post-op p value

UPDRS total 60.25 6 12.68 37.75 6 14.05 68.92 6 12 50.83 6 15.17 n.s
UPDRS I 260 4.5 6 1.73 1.54 6 1.27 1.83 6 1.53 0.056
UPDRS II 18.5 6 7.41 14.5 6 8.26 20.38 6 5.12 16.17 6 6.72 n.s
UPDRS III 39.75 6 8.05 18.75 6 9.7 46.62 6 10.7 32.83 6 10.1 n.s
UPDRS IV (duration of dyskinesias) 0.75 6 1.5 060 0.23 6 0.83 0.08 6 0.28 n.s
UPDRS I (tought disorder) 060 160 060 061 0.03
UPDRS I (motivation) 161 360 060 161 0.055
CAPIT-TT Pro/Sup L and R together 36 6 7 24 6 4 37 6 13 36 6 12 n.s
CAPIT-TT 2 Pt. Touch L and R together 26 6 5 24 6 8 24 6 8 24 6 10 n.s
CAPIT-TT Finger dexterity L and R 39 6 4 52 6 18 40 6 18 52 6 36 n.s
CAPIT-TT 23 foot TUG (sec) 20.94 6 8.91 11.63 6 4.54 17.82 6 5.15 22.59 6 25.75 n.s
TRS Total 20 6 17.33 5.75 6 1.89 35.69 6 16.32 12.5 6 8.3 n.s
A-iD 5X (sec) 18.12 6 5.52 16.01 6 1.52 14.28 6 4.48 17.31 6 8.84 n.s
A-iD nb/30s 9.75 6 3.59 10.25 6 0.96 12.64 6 5.06 11.82 6 3.45 n.s
MoCA 28.5 6 1.29 26.5 6 4.04 27.2 6 2.04 26.86 6 2.32 n.s
Fluency lexical P1R 27 6 1 28 6 1 27 6 11 28 6 10 n.s
Fluency Semantic 33.75 6 6.95 26.67 6 5.03 59.27 6 6.87 28.73 6 7.82 0.013
Epworth Scale 767 6.75 6 4.5 7.72 6 5.44 7.33 6 5.3 n.s
Zarit Scale 24.66 6 10.5 27.66 6 8.14 19 6 15.42 18.91 6 21.24 n.s
PSQI 8 6 4.58 10.75 6 5.37 7.92 6 4.23 8.6 6 5.75 n.s
Mood Scale 4.33 6 3.78 5 6 3.16 4.13 6 3.13 3.8 6 2.88 n.s
PDQ-39 54 6 40.14 60.5 6 24.9 52.4 6 18.77 42.16 6 27.3 n.s
HADS/A 6.66 6 1.15 6.25 6 4.57 6.42 6 4.14 5.93 6 3.05 n.s
HADS/D 5.33 6 1.52 6 6 4.32 4.78 6 2.32 4.46 6 3.31 n.s
PDFS 53 6 20.88 50.33 6 4.93 49.78 6 17.75 44.6 6 14.52 n.s
PGIC 1 (bigger the number is better) - 5 6 2.5 - 5 6 1.4 -
PGIC 2 (smaller the number is better) - 4 6 4.1 - 3 6 1.8 -

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
Additionally patients with Parkin undergo surgery later, whereas
GBA patients undergo surgery earlier and have poorer cognitive
outcomes.
Methods: From a total of 514 individuals with PD and STN-
DBS, 96 had genetic testing, 18 tested positive for monogenic PD
and 11 consented to participate (2 for LRRK2, 7 for Parkin, and 2
for GBA). A retrospective chart review was performed on these indi-
viduals (PD onset: 37 years (range 24-45), disease duration at sur-
gery: 13 years (range 6-24), follow-up duration: 14 years (range 1-
21). 3 had previous pallidotomy. Pre and postoperative clinical infor-
mation was used to perform a comprehensive outcome assessment
based on a wide range of motor and non-motor outcomes.
Results: At last follow-up stimulation afforded 25% improve-
ment, levodopa 36% improvement and in combination 50%
improvement was achieved. Axial symptoms developed at long term
follow-up. 3 patients underwent further surgical procedures to
address dyskinesia. Neuropsychiatric symptoms were frequent at 1
year-follow-up, whereas apathy was observed longer-term.
Conclusions: The long-term outcome of monogenic PD after
STN-DBS does not differ from that reported in larger series includ-
ing non-monogenic forms. Interestingly, we found evidence for a
long-term synergic effect of levodopa and stimulation. Increased
understanding of the influence of genetic factors on long-term
response to STN-DBS may inform future patient and target selection
for DBS improving surgical outcome.
542
Parkinsonism-hyperpyrexia syndrome due to deep brain
stimulation withdrawal: Case report
C.A. Artusi, M. Zibetti, A. Merola, A. Romagnolo, F. Dematteis,
M.G. Rizzone, M. Lanotte, L. Lopiano (Turin, Italy)
Objective: To report on a Parkinsonian patient treated with sub-
thalamic nucleus deep brain stimulation (STN-DBS) who developed
Parkinsonism-hyperpyrexia syndrome (PHS) after battery depletion,
despite the assumption of dopaminergic therapy.
Background: PHS is a life-threatening disorder similar to
neuroleptic-malignant syndrome, usually associated to the abrupt
withdrawal of levodopa in Parkinsonian patients. Few anecdotal
cases of PHS following STN-DBS abrupt interruption have been
reported in literature, suggesting that the electrical stimulation with-
drawal might induce the same complications of the acute dopaminer-
gic drug discontinuation.
Methods: A case of PHS related to DBS abrupt discontinuation
is reported, describing clinical assessment, laboratory tests and thera-
pies administered.
Results: A 63-year-old man, with a 13-year history of Parkin-
sons disease and treated with bilateral STN-DBS and oral dopami-
nergic therapy, was hospitalized for the internal pulse generator
(IPG) battery depletion.
Despite the dosage of dopaminergic drugs was increased to com-
pensate the IPG switching off, the patient reported severe axial and
limb rigidity, upper limb tremor and anxiety and developed speaking
and swallowing difficulties. At admission, he showed dyspnea and
tachycardia, high blood pressure and fever. The body temperature
was 38 Celsius and blood tests demonstrated a significant increase
of CK (2.820U/L) and mild leukocytosis (10.000/lL); serum creati-
nine was 0.93 mg/dL and C-reactive protein 50.1 mg/L. Intravenous
hydration, clonazepam, paracetamol and higher levodopa dose (from
900 mg to 1300 mg) were administered with partial relief of symp-
toms and improvement of vital parameters. Two days after hospitali-
zation, IPG replacement was performed and the stimulation switched
on using the former parameter setting, causing a prompt and com-
plete relief of symptoms: tremor and rigidity disappeared and the
patient returned to his previous autonomy.
Conclusions: PHS should be considered as a possible, severe pre-
sentation of the sudden STN-DBS device switch off. The increase of
dopaminergic drugs could be ineffective, due to the levodopa-
S211
response modification occurring in DBS treated patients. The prompt
replacement of IPG must be considered as an emergency in STN-
DBS Parkinsonian patients presenting with symptoms of PHS.
543
Subthalamic nucleus deep brain stimulation (STN-DBS) reduces
freezing of gait in Parkinsons disease in the VANTAGE
prospective, multi-center trial
M.T. Barbe, C. Stummer, N. Van Dyck, R. Jain, L. Chen, T. Br ucke,
F. Seijo, E. Suarez San Martin, C. Haegelen, M. Verin, M. Amarell,
S. Gill, A. Whone, M. Porta, D. Servello, F. Alesch, B.R. Bloem, L.
Timmermann (Cologne, Germany)
Objective: This study assesses the effects of subthalamic nucleus
deep brain stimulation (STN-DBS) on freezing of gait (FOG) in Par-
kinsons disease (PD) subjects participating in the VANTAGE clini-
cal trial.
Background: Deep Brain Stimulation (DBS) is effective for PD
symptom relief; however, improvement of freezing of gait (FOG)
remains under debate. Some studies indicate STN-DBS alleviates
FOG, while others suggest an association of STN-DBS with worsen-
ing of gait and balance or even induction of FOG. The VANTAGE
study assesses motor improvement in moderate-to-severe PD follow-
ing bilateral STN-DBS using a new, implantable, rechargeable,
multiple-source, 8-contact, constant-current, CE-marked DBS System
(Vercise). We report the effects of STN-DBS on FOG in this cohort
of PD subjects.
Methods: VANTAGE is a monitored, prospective, multi-center,
non-randomized, open-label interventional trial, sponsored by Boston
Scientific Corporation. FOG was characterized with UPDRS-II item
14, the freezing of gait questionnaire (FOGQ) and a walking test
known to provoke FOG pre- and post- surgery. Data collection
included FOGQ at Baseline and 26 weeks post-implantation, and the
walking test at Baseline, 12, 26, and 52 weeks post-implantation.
The walking test was videotaped and rated remotely by an independ-
ent rater (CS), blinded to the subjects implantation status.
Results: Thirty-eight subjects, of the forty implanted, were ana-
lyzed with FOGQ data. The FOGQ showed significant improvement
at 26 week follow up versus baseline derived from UPDRS-III item
29 and UPDRS II item 14. FOGQ (item 3) data at 26 weeks versus
baseline indicated 12 freezers remained freezers, 15 freezers turned
to non-freezers, 10 non-freezers remained non-freezers, and one non-
freezer turned to a freezer. The walking test was performed by 29 of
38 subjects at baseline during medication off. Thirteen subjects
showed FOG-episodes off medication at baseline and improved after
L-Dopa intake. Postoperatively, the total walking time, FOG episode
occurrences, and total time spent frozen were reduced at week 12,
26, and 52 compared to baseline during medication off.
Conclusions: FOGQ and walking test data demonstrate that STN-
DBS can reduce FOG occurrence and severity at 26 weeks postoper-
atively with constant effects at week 52. Follow-up data will help to
understand if improvement on FOG persists long term.
544
Placement accuracy of deep brain stimulation electrodes
implanted by frameless system - NexframeVC
J. Bardon, D. Krahulik, P. Otruba, M. Nevrly, M. Vaverka, P.
Kanovsky (Olomouc, Czech Republic)
Objective: The object of the study was to evaluate the placement
accuracy of the deep brain stimulation (DBS) electrodes using the
frameless navigation NexFrameV C in our department.
Background: Methods for targeting the subthalamic nucleus
(STN) in case of Parkinsons disease (PD), ventral intermediate tha-
lamic nucleus (ViM) in case of essential tremor (ET) and globus pal-
lidus internus (GPi) in case of dystonia, differ in using direct
visualization of preoperative magnetic resonance scans, in using
Movement Disorders, Vol. 30, Suppl. 1, 2015
S212 POSTER SESSION

intraoperative microelectrode recording or in anatomical target coor-

dinates. A frame based stereotaxy or a frameless stereotactic system
(NexFrameV C ) are used during the electrodes placement. Accurate

placement of an electrode is necessary for the correct function of the

deep brain stimulation.
Methods: Coordinates of the planned target point according to
anterior and posterior commissural points are found using preopera-
tive MRI of the brain and are usually modified intraoperatively
according to microrecording and clinical examination. Coordinates of
the real position of the electrode are detected using the fusion of pre-
operative MRI with postoperative CT. To determine the placement
accuracy of the electrodes, the vector error and the lateral, anteropos-
terior and vertical errors were calculated.
Results: 49 DBS electrodes were implanted using NexFrameV C

system to 25 patients diagnosed with PD, ET or dystonia (mean age

61.6 6 8.7) between June 2013 and September 2014. The mean vec-
tor error was 2.43 6 1.32 mm, the mean lateral error was
1.19 6 0.81 mm, the mean anteroposterior error was 1.35 6 0.99 mm
and the mean vertical error was 1.20 6 1.18 mm. All results were
compared to the results of other authors studies.
Conclusions: Results of our study show that using the frameless
system NexFrameV C in our department provides sufficient placement

accuracy of electrodes needed for successful treatment using the

DBS.

545
Effects of low and high frequency STN DBS on beta oscillations
and movement using synchronized neural and kinematic
recordings in freely moving Parkinsons disease subjects
Z. Blumenfeld, T.E. Prieto, M. Miller Koop, A. Velisar, E.J. Quinn,
M.H. Trager, C. Kilbane, J.M. Henderson, H. Bronte-Stewart (Stan-
ford, CA, USA)
Objective: To determine the effects of 20, 60 and 140 Hz DBS
on synchronous recordings of both STN local field potentials (LFPs)
and/or upper extremity movement velocity in Parkinsons disease
(PD) subjects.
Background: High frequency (HF) STN DBS attenuates rest
STN LFP power in the 13 30 Hz (beta) band and improves PD
motor signs. 20 and 60 Hz STN DBS have not been shown to
improve bradykinesia; their effects on STN LFPs are unknown.
Hypothesis: 140 Hz (HF) DBS will improve limb bradykinesia AND
attenuate beta band power but 20 and/or 60 Hz DBS will not
improve bradykinesia or attenuate beta band power.
Methods: Nine PD subjects (sixteen sides) off-medication  1
month after surgery performed a thirty second repetitive wrist
flexion-extension task without DBS (baseline) and during randomized
presentations of 60 or 140 Hz DBS (2V or 3V); eleven sides also
received 20 Hz DBS. In ten sides, STN LFPs were synchronously
recorded from the DBS lead (model 3389, Medtronic, Inc.) via
telemetry using the investigational ActivaV R PC1S system (Med-
tronic, Inc.; FDA-, IDE-, and IRB-approved). Hand angular velocity
was recorded using solid-state gyroscopic sensors and acquired using
Spike software. Extracted metrics: root mean square velocity (Vrms);
coefficient of variation of velocity (CVvel), and of frequency
(CVfreq).
Results: 140 and 60 Hz DBS increased Vrms compared to base-
line (P < 0.05) while attenuating LFP beta band power (P < 0.001
(rest) and P < 0.05 (movement)). CVvel decreased (more regular)
during 60 Hz DBS (P < 0.05), while CVfreq decreased (more rhyth-
mic) during 140 Hz DBS (P < 0.05). During movement, baseline
beta band (15-28 Hz) and peak power decreased (P < 0.05 and
P < 0.001, respectively) and the peak frequency increased (P < 0.01).
20 Hz DBS improved Vrms (P < 0.05), but there was no improve-
ment in regularity (CVvel) or rhythmicity (CVfreq). [figure1]
Conclusions: Both 60 and 140 Hz STN DBS improved bradyki-
nesia while attenuating rest and movement-related STN beta oscilla-
tions; each improved one aspect of rhythmicity or regularity. 20 Hz
Fig. 1. (545).
DBS improved bradykinesia, and baseline movement attenuated
baseline rest beta power. This is the first study to show concurrent
attenuation of beta oscillations and improvement in bradykinesia dur-
ing low and high frequency DBS.
546
Unilateral subthalamic nucleus deep brain stimulation for on-
state freezing of gait in Parkinsons disease
P.R. Chand, R.D. Bucholz (St. Louis, MO, USA)
Objective: To describe the successful treatment of on-state freez-
ing of gait in Parkinsons disease by unilateral subthalamic nucle-
us(STN) deep brain stimulation (DBS).
Background: Freezing of gait (FOG), an impairment of gait ini-
tiation or the ability to continue moving forward is a common and
disabling symptom of Parkinsons disease (PD). FOG is a complex
phenomenon and may or not be Levodopa responsive. FOG that
occurs after Levodopa intake in the on-state is a rare phenomenon
and the pathophysiology is unclear. Reductions in Levodopa may
help FOG but may worsen other PD symptoms. DBS typically
improves Levodopa responsive PD symptoms and the response of
on-state FOG to DBS is not known. We report the outcome of uni-
lateral STN DBS in a PD patient with on-state FOG.
Methods: A 68 years old Caucasian male had a 8 year history of
tremor, rigidity of the left hemibody that later became bilateral. He
was diagnosed as PD and treated with Carbidopa Levodopa (CD/LD)
25/250 mg 2 tablets qid, Pramipexole 4.5 mg/d with improvement in
his symptoms. About 6 years after the onset of PD he started to
develop freezing of gait (FOG) and falling in the on state after tak-
ing CD/LD.
Initial evaluation in the off state revealed moderate asymmetric
left > right bradykinesia and rigidity. In the on state after 2.5 tablets
of CD/LD 25/250 mg he had improved rigidity, bradykinesia but had
severe freezing of gait with inability to walk. Reduction of CD/LD

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
25/250 mg to 1 tablet qid reduced the symptom of FOG slightly but
he continued to experience on-state FOG and falls. Gait training, vis-
ual cues, trials of Rasagiline and later Selegiline did not improve on-
state FOG.
Results: He underwent right STN DBS for his predominant left
sided symptoms. A month after DBS he was programmed to a
monopolar setting with significant improvement in on-state FOG
without further reduction of CD/LD. Higher current settings tended
to worsen on-state FOG and the optimal settings were at 1 Volt 60
pw 130 Hz. Subsequent reprogramming sessions continued to pro-
vide ongoing benefit for on-state FOG.
Conclusions: Our results support the efficacy of unilateral STN
DBS for on-state FOG in PD. The therapeutic response was seen
with an optimal setting of stimulation parameters.
547
Benefits of subthalamic stimulation for elderly Parkinsonean
patients over age 70 years
S.M. Chiou, M.K. Lu, C.H. Tsai (Taichung, Taiwan)
Objective: Present study investigated the age impacts in out-
comes of deep brain stimulation (DBS) at the subthalamic nucleus
(STN) particularly focused on the elderly patients with Parkinsons
disease (PD).
Background: The STN-DBS is an accepted treatment for
advanced PD. However, there is general reluctance to consider this
therapy for patients aged 70 years or older with limited supporting
evidence.
Methods: Seventy-two consecutive patients were divided into
younger and elderly (n516, cutoff age=70 years) groups. Both
groups were comparable in preoperative clinical severity, except the
elderly exhibited inferior levodopa (LD) response (P<0.05) than the
younger. Improvements in drug-off/DBS-on Unified PD Rating
Scale (UPDRS) scores and reduction in daily LD-equivalent dose
(LED) after 6-month were evaluated relative to the presurgical
drug-off baseline. Preoperative factors predictive of favorable surgi-
cal outcomes were analyzed using multivariate linear regression
model.
Results: After DBS therapy, elderly patients exhibited clinical
improvements particularly in the tremor and the LD-induced dyski-
nesia. Improvement of axial dysfunction and reduction of daily LED
needs indicated no intergroup difference. The overall improvements
in UPDRS scores were suboptimal in elderly group, correlated to
their preoperative inferior LD responses. Elderly patients could
achieve better surgical outcomes if they presented dominantly with
akinesia before surgery (P<0.001, Adjusted R2=0.657).
Conclusions: STN-DBS therapy is also beneficial to some elderly
PD patients over age 70 years. Tremor, axial dysfunctions or dyski-
nesia are the main indications for the elderly; however, its clinical
effectiveness was relatively inferior to that in younger patients.
548
Interventional MRI (iMRI) guided DBS: Factors affecting lead
placement accuracy
R.R. Coleman, J.L. Ostrem, P.A. Starr, A.J. Martin, S.E. Qasim, N.
Ziman, P.S. Larson (San Francisco, CA, USA)
Objective: To quantify target coordinates as well as lead place-
ment error with DBS using an iMRI system and to qualify the rea-
sons for outliers.
Background: iMRI DBS allows for real-time image-guided
placement of leads under general anesthesia. As microelectrode
recording and macrostimulation are not used, lead placement relies
solely on direct targeting. The ClearPoint system (software and sur-
gical platform for iMRI DBS) is commercially available. Published
data on its real-world application accuracy are limited.
S213
Methods: Data were prospectively collected from a consecutive
series of iMRI DBS implantations using ClearPoint in a 1.5T MRI at
UCSF from 8/2010 to 11/2013, regardless of indication or target.
Lead location was obtained with T2 images from the post-
implantation scan. Lead placement error (radial error) was the vector
difference between the intended target and the actual location of the
DBS guidance sheath/stylet in the axial plane used for target selec-
tion. Leads with error greater than twice the SD of the mean were
identified and were subject to a review of records and imaging to
identify the cause of increased error.
Results: 134 leads were implanted in 79 patients. 69 leads were
implanted in the STN, 61 in the GPi, and 4 in the thalamus. Mean
target coordinates (1/- SD) in relationship to the MCP were X=11.9
1/- 0.8 mm, Y=-3.0 1/- 0.8 mm, and Z=-4.1 1/- 0.4 mm for the
STN and X=20.6 1/- 2.2 mm, Y=3.4 1/- 1.8 mm, and Z=0.0 1/-
0.9 mm for the GPi. The mean radial error for all targets was 0.6
1/- 0.3 mm. Radial error did not differ significantly between STN
and GPi. 5 leads with radial error greater than two SD above the
mean were identified with a maximum error of 1.8 mm. Increased
lead placement error was attributed to deflection of the lead by the
gyral edge at the entry point of the brain(1), by the dura(1), by T2
periventricular white matter pathology(1), and by proximity to the
ventricular wall(1). One case was associated with error of unclear
etiology.
Conclusions: iMRI placement of DBS leads with the ClearPoint
system is accurate and precise. Identifiable reasons for increased
lead placement error were technical and may be avoided with care-
ful dural incision and planning to avoid gyral edges, proximity to
ventricles, and white matter pathology. The heterogeneity of target
coordinates suggests variability in the anatomy of basal ganglia
structures between patients and supports the importance of direct
targeting.
549
Subthalamic deep brain stimulation modulates small fiber-
dependent sensory threshold in Parkinsons disease
R.G. Cury, R. Galhardoni, E.T. Fonoff, M.G. dos Santos Ghilardi,
M. Myczkowski, M.A. Marcolin, E.R. Barbosa, M.J. Teixeira, D.
Ciampi de Andrade (S~
ao Paulo, Brazil)
Objective: The aim of our study was to prospectively evaluate
the changes in painful and nonpainful sensory thresholds brought
about by STN-DBS in PD patients compared to matched healthy
controls. In addition, we studied the relationship between sensory
changes and the improvement in motor symptoms and pain under
STN-DBS.
Background: Nonmotor symptoms (NMS) such pain are thought
to be present from the early stages of the PD and are often more dis-
abling than motor symptoms. Pain has a prevalence of 40-85% of
PD patients and is associated with significant reduction in quality of
life. STN-DBS is an effective treatment for the motor symptoms of
PD. It has been shown that STN DBS could produce significant pain
relief in more than 80% of PD patients. Despite these results, the
mechanisms implicated in the possible analgesic effect of STN-DBS
remain speculative.
Methods: We have prospectively evaluated 37 patients with PD
before and one year after STN-DBS and 35 healthy subjects. We
evaluated the cold and warm limen (pain - detection thresholds)
using a quantitative sensory testing (QST) before surgery during off-
medication condition and 01 year after surgery during on-stimulation
condition. The Hoehn&Yahr scale, UPDRS III, Visual Analogic
Scale and SF-36 quality of life scale were recorded.
Results: The mean age was 57 6 10 and Hoehn&Yahr off-
medication score was 2.80 6 0.64. Before surgery UPDRS-III scores
were 19.7 6 8.2 and 43.5 6 12.5 in on and off medication conditions,
respectively. There was a significant improvement in pain after sur-
gery (78% to 29%; p<0.005), intensity of pain (VAS=5.96 6 2.84 to
1.64 6 2.48, p50.001) and quality of life (SF-36
Movement Disorders, Vol. 30, Suppl. 1, 2015
S214 POSTER SESSION

Quantitative sensory testing in PD patients before (off-medication) and after surgery (on-stim and off- med).

off-med vs off-med vs
Baseline After surgery Helthy controls, off-med/on-stim, off-med/on-stim
QST (off-med) (off-med/on-stim) Subjects P values P values vs controls, P values
Cold limen 9.64 6 7.04 15.40 6 8.27 12.03 6 5.94 0.043* <0.0005** 0.039
Warm limen 6.47 6 4.17 8.43 6 4.84 9.60 6 5.16 0.003** 0.009* 0.370
Mechanic limen 9.62 6 3.39 10.88 6 3.64 12 6 3.02 <0.0005** 0.048 0.168
SuH (/100) 45.08 6 27.23 53.21 6 26.88 38.12 6 26.58 0.130 0.061 0.01*
InC (/100) 46.95 6 27.94 52.05 6 26.92 36.37 6 22.84 0.71 0.210 0.046*
VDT (lm) 2.71 6 1.22 2.67 6 1.60 1.4 6 0.6 <.0005** 0.905 <0.0005**
The values are presented as 6mean. Significance set at P < .05* and at P < .0055** for Bonferroni correction for multiple comparisons.
QST 5 Quantitative somatosensory testing; VDT 5 vibration detection threshold; SuH 5 pain rating to suprathreshold heat stimulation; InC 5 pain
rating to infrathreshold cold stimulation.

Influence of the presence of pain before and after deep brain stimulation of the subthalamic nucleus and QST values

Group A pain before Group B Pain Group C AxB, AxC, BxC,

QST only 5 18 before/after 5 11 No pain 5 8 P Value P Value P Value
Before surgery
Cold limen 9.90 6 7.43 10.24 6 6.67 8.28 6 6.84 0.741 0.440 0.308
Warm limen 6.60 6 4.61 5.95 6 3.30 6.88 6 4.36 0.800 0.730 0.439
Mechanic limen 9.00 6 3.93 10.23 6 8.1 10.20 6 3.29 0.103 0.246 0.727
SuH (/100) 31.38 6 23.62 50.04 6 19.07 41.06 6 26.38 0.001** 0.161 0.156
InC (/100) 39.48 6 28.37 59.04 6 23.93 46.46 6 28.00 0.001** 0.376 0.138
VDT (lm) 1.83 6 1.15 1.66 6 1.40 1.28 6 1.06 0.366 0.071 0.323
After surgery
Cold limen 17.46 6 9.34 14.55 6 7.22 11.93 6 5.67 0.138 0.021* 0.181
Warm limen 9.20 6 5.17 7.16 6 4.80 8.36 6 3.97 0.100 0.500 0.370
Mechanic limen 10.75 6 3.46 10.77 6 4.12 11.33 6 3.51 0.796 0.729 0.867
SuH (/100) 46.10 6 25.67 49.42 6 25.04 50.06 6 21.66 0.642 0.640 0.797
InC (/100) 49.79 6 27.44 53.84 6 28.01 54.68 6 25.43 0.584 0.475 0.942
VDT (lm) 3.14 6 2.71 2.22 6 2.12 2.25 6 1.31 0.290 0.699 0.356
The values are presented as 6mean. Significance set at P < .05* and at P < .0055** for Bonferroni correction for multiple comparisons.
QST 5 Quantitative somatosensory testing; VDT 5 vibration detection threshold; SuH 5 pain rating to suprathreshold heat stimulation; InC 5 pain
rating to infrathreshold cold stimulation.

before=368.97 6 153.52; after=562.72 6 137.56;p<0.001). The warm Background: Although Deep brain stimulation (DBS) is the main
and cold limen increased after surgery (p<0.05). surgical procedure proposed for patients with advanced Parkinsons
There was no difference between groups with or without pain in disease (PD), gait disturbances such as freezing of gait and apraxia
QST results.
There was no correlation between changes in sensory thresholds
and motor or quality of life improvements after surgery.
Conclusions: This study showed that STN-DBS was associated
with a significant relief of ongoing pain and changes in cutaneous
sensory thresholds, mostly thermal innocuous and noxious ones. In
particular, the modulation of the thresholds was not related to motor
improvement. These data will add to the growing knowledge on the
mechanisms of action of STN-DBS on NMS in PD.

550
Motor cortex stimulation for gait disorders in advanced
Parkinsons disease
E.U. da Silva, L.A. Nilton, Jr., J.C.E. Veiga, J.M.d.A. Silva, H.C. de
Souza (Sao Paulo, Brazil)
Objective: We report the benefit of Motor Cortex Stimulation
(MCS) in four patients with minor appendicular symptoms and
severe gait and balance disorder. Fig. 1. (550).

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
Fig. 2. (550).
remains challenging. Gait disturbances such as freezing of gait
(FOG) and apraxia are generally resistant to conventional drug and
non-drug treatment, can generate a loss of autonomy and traumatic
complications. Recently, researches have been directed toward these
devastating symptoms. Traditional subthalamus or pallidal internal
stimulation have been proved worthless and pedunculopontinous
nucleus stimulation, proposed as a new potential target, still havent
been widely accepted for its risks and lack of predictors. Few
reports suggested improvement of bradykinesia and gait after motor
cortex stimulation. Lately, the possibility of cortex modulation with
transcranial magnetic stimulation and transcranial direct cortex stim-
ulation (tDCS) have leaded to new perspectives and non-invasive
approaches. Many authors reported changes in gait and motor skills
after these modalities, always with short responses. We report the
benefit MCS in 4 patients who presented improvement after MCS.
Methods: In this open study, we selected 4 PD patients, who pre-
sented motor fluctuations, severe gait disturbances, insufficient
improvement after levodopa trial (<30%), and good response to TDCS.
A stereotactic surgical 4 electrode lead implantation over the left Motor.
Outcome measures included: medication dosage change, improve-
ment of gait considered: as remission of FOG, steps larger than a foot,
5 m walking time, and improve in postural stability and balance.
Results: All patients showed expressive gait changes. The mini-
mum follow-up was four months and the maximum eighteen months.
The parameters with greater improvement were postural stability and
the walking time. During this period several increases in delivered
therapy were needed in order to maintain walking independence. No
reduction of mean daily medication intake was obtained.
[Figure1]
[Figure2]
Conclusions: This study suggests that MCS improves gait distur-
bances in PD and could be considered as an alternative approach in
selected and refractory patients. Randomized studies with larger sam-
ple are needed.
551
Interest of microrecording for STN DBS
T. Danaila, G. Polo, P. Mertens, E. Broussolle, S. Thobois (Bron,
France)
Objective: To measure the importance of microelectrode map-
ping and macrostimulation in the final choice of trajectory in patients
with idiopathic PD undergoing bilateral STN stimulation.
S215
Background: STN stimulation was shown to improve motor symp-
toms in patients with advanced PD not adequately controlled by medica-
tion. In our centre the combination of presurgical image-based targeting,
microelectrode mapping and macrostimulation is used. However the
weight of each approach to finally select the placement of the electrode
within the STN area has never been estimated to our knowledge.
Methods: We collected data from 115 PD patients who under-
went bilateral STN DBS in our centre between 1999 and 2006. A
clinical evaluation was performed one week before the surgery and
one year after the surgery. STN was located by MRI and ventricu-
lography or by MRI and stereotactic CT scan. Leads implantation
was performed under local anesthesia, guided by microelectrode
mapping and macrostimulation in order to determine the best trajec-
tory among the three tested on average for each side.
Results: Patients had a mean off-medication UPDRS-III score of 41.9
(1/-12.7) and a mean on-medication UPDRS III score of 9.6 (1/- 6.9). A
best quality of microelectrode mapping led us to change the trajectory ini-
tially planned by anatomical approach on the right side in 59 patients
(51,3%) and in 66 patients (57.3%) on the left side. Electrophysiology
was fully concordant with presurgical image-based in 35 patients (30.4%).
Then, macrostimulation was performed and led to further change of the
selected trajectory in 4.3% of the cases . Using this 3 stages approach clin-
ical results were good with a reduction of the total UPDRS motor score of
58.7% (off-medication) by STn stimulation alone at 1 year. No difference
was noted for the UPDRS III scores between the preoperative on-
medication condition and the postoperative on-medication/on-stimulation
conditions at 1 year (>0.05). Serious side effects consisted in material
infection (3 patients) and intracerebral hemorrhage (2 patients).
Conclusions: In our hands, these data suggest the importance of
microelectrode mapping to determine the best electrode placement for
STN DBS in PD. However comparing different implantation strategies
(i.e with or without anesthesia, with or without electrophysiology. . .)
will require randomized studies comparing these different techniques
performed ideally by same neurosurgeons and in same surgical centres.
552
Defining neural connectivity variables mediating successful
clinical outcomes in deep brain stimulation for Movement
Disorders
G.A. de Erausquin, K. Vyas, E. Sanchez, L. Alba-Ferrara, D. Smith,
F. Vale, T. Malapira, T. Zesiewicz (Tampa, FL, USA)
Objective: DBS surgery for idiopathic PD is an established treat-
ment. However, a significant limitation to efficacy is that in spite of
Movement Disorders, Vol. 30, Suppl. 1, 2015
S216 POSTER SESSION
standardized procedures for direct and indirect targeting, a number
of patients fail to benefit as expected or suffer treatment-limiting
side effects in an unpredictable fashion. We study the anatomical
and functional connectivity of active DBS contacts to correlate it
with clinical outcomes with the goal of establishing better predictors
of clinical improvement and side effects from individual contacts.
Background: Despite positive long term effects, prediction of ther-
apeutic response to DBS for PD with motor remains largely empirical.
Given the complexity of the fiber pathways involved in PD, it is likely
that better anatomical and functional understanding of circuits engaged
by active DBS contacts can achieve better clinical benefit.
Methods: We collected data from 20 patients who underwent DBS
surgery for PD. Preoperative MRI images were merged with postopera-
tive CT images to locate the DBS contacts. ROI tracing involving
active DBS lead contacts was performed. Tractography was used to vis-
ualize fiber tracts. DBS-ERP were then obtained from each monopolar
configuration and source analysis was performed with SLORETA. We
recorded time locked fNIRS signals bilaterally over the frontal and pre-
frontal lobes for optical detection. Connectivity measures were corre-
lated with clinical outcome from DBS and programming data.
Results: Tractography demonstrated all STN DBS subjects shared
pathways from their activated optimal contact to 1)Primary Motor
Cortex 2)Supplementary Motor Area 3) Cerebellum. Involvement of
White matter tracts connecting to the cerebellum seem to decrease
the efficacy of tremor and rigidity and tracts connecting to PMC
seem to result in optimal reduction of bradykinesia. Source analysis
of DBS generated ERPs revealed most the cortical sources in frontal
and parietal cortex which interestingly correlated with the coherence
analysis during activation of individual DBS contacts.
Conclusions: Our method of combining imaging data, tractogra-
phy, electrophysiology to study connectivity variables correlated
with clinical data suggests a novel approach to improve DBS out-
comes in Movement Disorders. Moreover, description of neural path-
ways linked to therapeutic benefit may provide ways to improve
surgical target selection.
553
To test the effect of deep brain stimulation (DBS) frequencies on
gait abnormalities in Parkinsons disease (PD)
A. Deep, R. Dhall, A. Lieberman, N. Krishnamurthi (Phoenix, AZ,
USA)
Objective: To test the effect of deep brain stimulation (DBS) fre-
quencies on gait abnormalities in Parkinsons disease (PD).
Background: Gait abnormalities are major contributor to falls in
PD patients they usually, do not respond well to pharmacological
treatment. Recent studies indicate that low-frequency stimulation of
subthalamic nucleus (STN) or globus pallidus internus (GPi) improve
gait in PD. In this study we quantitatively studied the effect of low
(LF-30 Hz), intermediate (IF-80 Hz) and high frequency (HF-clini-
cally determined) DBS of STN and GPi.
Methods: We tested 10 patients. Subjects were first tested in their
usual HF DBS setting. They were reevaluated twice at IF, and LF
conditions in medication-off state after random selection of the
sequence of IF and LF conditions. A minimum of 30-minute wait
period was allowed before evaluation after changing stimulation
frequency.
Results: Stride length improved in 5 patients on IF, 4 patients on
HF and 1 patient on LF stimulation. Double support duration
improved in 4 patients on IF, 3 patients on HF and 3 patients on LF
stimulation. Cadence improved in 4 patients on IF, 3patients on HF
and 3 patients on LF stimulation. Gait stride velocity improved in 4
patients on IF, 4 patients on HF and 2 patients on LF stimulation.
Conclusions: Stride length, double support duration, and cadence
improved in more number of patients on IF DBS stimulation than
other frequency conditions. The preliminary data indicates that IF
DBS can improve gait in PD and can be confirmed by including
more patients.
Movement Disorders, Vol. 30, Suppl. 1, 2015
554
Vercise DBS registry: Outcomes of a prospective, multi-center
international registry for Parkinsons disease
G. Deuschl, R. Jain, S. Lin, N. Van Dyck, A. Kuhn, G.H. Schneider,
C. van Riesen, H. Mehdorn, A. Schnitzler, L. Timmerman, V. Visser-
Vandewalle, E. Suarez San Martin, I. Regidor, P. Eldridge, M. Cav-
allo, M. Sensi, J. Vesper (Kiel, Germany)
Objective: The Vercise DBS Registry compiles the effectiveness
and safety related real-world outcomes of the use of Boston Scien-
tific Corporations CE-marked Vercise System for Deep Brain Stimu-
lation (DBS) in the treatment of levodopa-responsive Parkinsons
disease (PD).
Background: The use of Deep Brain Stimulation (DBS) as an
effective strategy to reduce the motor complications of subjects with
Parkinsons disease (PD) has been substantiated by randomized con-
trolled trials (Scheupbach et al., 2013). Motor improvement follow-
ing DBS has also been previously shown to be sustained for up to
10 years (Castrioto et al. 2011). Therefore, an in depth evaluation of
a wide range of clinical endpoints that demonstrate improvement in
disease symptoms and overall quality of life will represent a poten-
tially compelling resource for clinicians to better understand how
best to manage symptoms of PD using DBS.
Methods: Vercise DBS Registry is a prospective, on-label, multi-
center international registry sponsored by Boston Scientific Corpora-
tion. The Vercise system is a multiple-source constant-current based
DBS system with a rechargeable battery. Subjects will be followed
up at 3, 6, 12 months and up to 3 years post implantation where their
overall improvement in quality of life and PD motor symptoms with
use of Vercise DBS system will be evaluated. Clinical endpoints will
be evaluated at baseline and during study follow up and include the
following: Unified Parkinsons disease Rating Scale (UPDRS), MDS-
UPDRS, Parkinsons disease Questionnaire (PDQ-39), and Global
Impression of Change. Adverse events are also collected.
Results: This accompanying report provides the safety and effec-
tiveness outcomes of the first cohort of subjects (n 5 20) with the
use of Vercise DBS System at 6 months post-implantation as com-
pared with baseline.
Conclusions: The Vercise DBS registry represents the first com-
prehensive, large scale collection of real-world outcomes using the
Vercise DBS System in the management of PD symptoms and
includes evaluation of the following: safety, effectiveness, program-
ming parameters and economic value. This endeavor therefore can
significantly increase the understanding of subject outcomes when
acting to control the symptoms of Parkinsons disease.
555
Effects of STN versus GPi deep brain stimulation on impulse
control disorders
M.G. dos Santos Ghilardi, A.M.N. Coutinho, R.G. Cury, E.R.
Barbosa, M.J. Teixeira, E. Etchebehere, E.T. Fonoff (S~
ao Paulo,
Brazil)
Objective: Determine the incidence of impulse control disorders
(ICDs) in patients with advanced Parkinsons disease undergoing pal-
lidal versus subthalamic DBS.
Background: The occurrence of ICDs is being increasingly
reported in patients with PD. It is described as the failure to resist an
impulse, drive, or urge to perform a harmful act, and it is usually
related to dopamine replacement therapy. ICDs encompass a group
of psychiatric dysfunctions including compulsive gambling, buying,
sexual, and eating behaviors, besides dopamine dysregulation syn-
drome and punding. The reports regarding the effects of DBS on
ICDs are scarce and controversial, and there is no comparative study
between the targets. Some evidence suggest that ICDs are associated
with reduced ventral striatal dopamine transporter availability.
99mTc-TRODAT is a pre-synaptic dopamine transporter SPECT
radiotracer, semi-quantitative analysis of 99mTc-TRODAT uptake
 POSTER SESSION S217

with the help of manually drawn volumetric regions of interest Objective: In this presentation, a case of especially the axial
(VOI) in SPECT/CT equipments could be a reliable way of evaluat- symptoms including Parkinsons disease (PD) was applied with bilat-
ing the uptake in the basal ganglia in response of DBS and its asso- eral Subthalamic Nucleus Deep Brain Stimulation (STN-DBS) and
ciation with ICD. We present preliminary data of a prospective him bizarre clinical course is presented.
study. Background: Our case has been disabled to walk and showed
Methods: Twelve patients (9 males; 3 females) with advanced difficulty in speech, involuntary movements spreading the neck and
PD were prospectively, randomly and blindly assigned to undergo face. His PD has been tried to overcome with surgical intervention.
either pallidal (6 patients) or subthalamic stimulation (6 patients). Methods: 54 year-old, right-handed man with inability to walk,
The primary outcome was the occurrence of ICDs pre and six difficulty in speech, was applied with involuntary movements. The
months after the surgical procedure, identified through the shortened initial side involved was right hand. In 2003, writing and walking
version of the Questionnaire for Impulsive-Compulsive Disorders in diffuculties began. PD was diagnosed.
Parkinsons disease (QUIP-S). Secondary outcomes included changes Results: Last 5 - 6 years, involuntary contractions of the body,
in motor function (UPDRS-III), Levodopa equivalent dose and head and neck, difficulty in initiating and stopping movements
99mTc-TRODAT SPECT/CT binding potential obtained for the cau- began; he had severe difficulties to continue daily life. There was
date nuclei (right and left) and the putamen (right and left). dystonic spasms on his neck, mouth and chin areas. Intensive treat-
Results: Between the twelve patients enrolled, 6 presented ICDs ment with L-dopa and dopamine agonists created dense dyskinesia
during the study. 4 patients preoperatively, among them 2 underwent and severe on-off periods in time. Most obvious symptoms were
pallidal and 2 subthalamic stimulation. Six months after the proce- stiffness while talking; it was emphasized as contractions in the
dure on the GPi group just 1 patient continued with ICDs, at the neck and jaw during speaking. Hoehn/Yahr staging of PD was stage
STN group 1 remained with ICD, 1 remitted and we had 2 de novo 4 and UPDRS score was 54. The MMSE scores, psychiatric evalua-
cases. There was no statistically significant difference between the tion, brain-cervical MRIs were normal.
occurrence of ICD pre- and postoperative (p 0,276) and among the Bilateral STN-DBS was therapeutic choice for this case. Most
targets (p 0,533). notable clinical improvements were in initiating/stopping movement,
cranio-cervical dystonia and in speech disorders. The UPDRS score
decreased to 21 and Hoehn and Yahr stage was 2.
Descriptive Data Conclusions: Nowadays, STN-DBS for PD improvement in the
overall table comes with an undisputed position. However, GPi is
N Mean Std. deviation
more prominent for dystonic etiology. In our case, there were
Age 12 49,5833 8,42570 marked improvements in slurred speech and neck movements. These
Disease duration 12 9,833 2,72475 findings showed STN-DBS approach can improve stuttering and
cranio-cervical dystonia.
UPDRS-III OFFmed pre- 12 43,5 6,89532
UPDRS-III ONmed pre- 12 12,1667 6,82020
UPDRS-III OFFmeONstim 12 23,7500 9,53582 557
UPDRS-III ONmedONstim 12 10,9167 6,00694
Levodopa equivalent dose pre- 12 1556 376,44968 Electrode lead induced white matter changes in patients treated
Levodopa equivalent dose post 12 960,25 533,31879 with deep brain stimulation
R. Erasmi, O. Granert, D. Zorenkov, O. Jansen, D. Falk, G.
Deuschl, K. Witt (Kiel, Germany)
Objective: To quantify the incidence and describe the character-
Conclusions: ICDs are prevalent among patients with PD. Further istics of MRI changes around deep brain stimulation (DBS) electro-
studies are necessary, especially to clarify their pathophysiology and des and leads in patients with DBS in a retrospective study.
relation to DBS. Background: DBS is an established treatment for Parkinsons
disease, tremor and dystonia. A small number of histopathologic
556 post-mortem case series suggest only mild gliotic changes around the
DBS electrode. However, we observed repeatedly on Magnetic reso-
The effects of subthalamic nucleus deep brain stimulation on nance imaging (MRI) white matter changes surrounding the electrode
axial motor impairment, cranio-cervical dystonia, stuttering in lead. There is no data available about the potential damage to brain
Parkinsons disease: Case report parenchyma through the implanted electrodes and leads.
H. Ekmekci, H. Kaptan (Konya, Turkey) [Figure1]

Results

GPi pre- GPi postoperative p STN pre- STN postoperative p

QUIP-S* 1,8 6 2,9 0,2 6 0,4 0,157 0,7 6 1,0 0,8 6 1 0,785
UPDRS-III OFFmed 44,8 6 8,6 24,5 6 10,9 0,028 42,2 6 5,2 23 6 9,0 0,028
Levodopa equivalent dose 1740 6 385,2 1183 6 564,6 0,046 1372 6 286,6 737,5 6 433,5 0,028
CN right** 0,74 6 0 0,45 6 0,1 0,180 0,4 6 0,1 0,7 6 0,5 0,465
CN left** 0,8 6 0,2 0,6 6 0,2 0,655 0,4 6 0,3 0,7 6 0,2 0,273
Putamen right** 0,2 6 0,1 0,3 6 0 0,317 0,6 6 0,6 0,5 6 0,3 0,715
Putamen left** 0,4 6 0,1 0,3 6 0,1 0,655 0,3 6 0,2 0,5 6 0,3 0,144
*sum of the answers yes ** 99mTc-TRODAT uptake in the basal ganglia was visually assessed (qualitative analysis) and the binding potential of
the radiotracer was calculates with a semi-quantitative method. The mean radioactive counts of each nucleus were assessed with a manually
drawn region of interest (ROI) and calculated with the following equation: Target area ROI occipital cortex mean counts/occipital cortex mean
counts. Binding potential was obtained for the caudate nuclei (right and left) and the putamen (right and left) of the patients with ICDs.

Movement Disorders, Vol. 30, Suppl. 1, 2015

S218 POSTER SESSION
Fig. 1. (557).
Methods: We retrospectively identified 32 patients that had
undergone postoperative and additional one or more MRI imaging
sessions in a time window from 3 months to 8 years after DBS sur-
gery. 21 of those patients suffered from Parkinso ns disease, 4 had
dystonia, 7 had tremor. All patients were implanted bilaterally, 20
into the subthalamic nucleus, 9 into thalamus, 3 into globus pallidus
internus. Complete MRI T2 sequences were analyzed in a semi-
standardized way by two raters blinded to the clinical data of the
patients using a lesion mapping procedure (MRIcron and SPM-and
Matlab-based software).
Results: 29 out of 32 analyzed patients showed new hyperintense
subcortical white matter lesions surrounding the DBS lead compared
to the postoperative scan after 35 months on average. Mean volume
of the lesions was 2.71 ml (1.27 ml on the right and 1.40 ml on the
left brain), ranging from 1.17 ml to 7.10 ml. Lesions were most pro-
nounced in subcortical white matter structures, while we did nt find
these changes around the electrode in the target area. There was a
significant correlation between lesion volume and time (from DBS
surgery to MRI, p<0.05) while there was no correlation with diagno-
sis or target region.
Conclusions: White matter changes around the lead of DBS elec-
trodes can be demonstrated with in-vivo MRI imaging. This is a fre-
quent finding. The changes are primarily located around the leads in
the subcortical white matter structures, seem to increase over time
but to be independent from underlying disease or target structure.
This is the first report of this finding but neither the mechanism, nor
the clinical relevance are known. They need to be assessed in a fur-
ther prospective study.
558
Patient expectations and outcome after DBS: 24-month results
N. Esnaashari, J.S. Hui, C. Liao, J. Liang, J. Hwu, S. Chen, M.A.
Liker, D.M. Togasaki (Los Angeles, CA, USA)
Objective: This study determined patients expectations preopera-
tively, evaluated their fulfillment postoperatively (24 months) and
correlated this with their self-rated motor improvement and with
clinical evaluations.
Background: The outcome of deep brain simulation (DBS) for
Parkinsons disease has been examined, but few studies have
assessed patient satisfaction and fulfillment of patients expectations.
The specific factors involved in patient satisfaction for the results of
DBS therapy are poorly understood.
Methods: Patients undergoing surgery completed a questionnaire
recording three goals for DBS. These goals were sorted into one of
thirteen categories (which had been formulated from initial observa-
tions). At 6, 12, 18, and 24 months after surgery patients completed
follow-up surveys. Clinicians assessed each patient before and at 6,
12, 18, and 24 months after DBS placement using the Clinical
Global Impression-Improvement (CGI-I) scale.
Results: Thirteen patients have 24-month data. All patients
reported improvement in their neurologic symptoms, but the extent
of improvement correlated poorly with CGI-I scores. Self-rated
Movement Disorders, Vol. 30, Suppl. 1, 2015
improvement in neurologic symptoms correlated much better with
how well preoperative expectations were fulfilled. Of the thirteen
goal categories, the three that correlated best with patient satisfaction
were (i) reducing medications; (ii) reducing dyskinesia; and (iii)
improving gait/balance.
Conclusions: At 24 months after DBS implantation, patients self-
rated improvement in neurologic status after DBS for Parkinsons dis-
ease more strongly correlated the degree of fulfillment of their initial
expectations than with physician-rated improvement (CGI-I).
559
A stimulating idea: Treating mixed essential tremor and
Parkinsons disease tremor with a novel DBS approach
R.A. Falconer, S.L. Rogers, C. Kalhorn, F. Pagan (Washington, DC,
USA)
Objective: This case series demonstrates an effective and novel
approach to treating combination Essential Tremor (ET) and Parkin-
sons disease (PD) tremor. One Deep Brain Stimulation lead was uti-
lized to simultaneously stimulate the Ventral Intermediate Nucleus of
the thalamus (VIM) for ET and the Subthalamic Nucleus (STN) for
PD, improving both conditions with one lead per side.
Background: Deep Brain Stimulation (DBS) is an established
treatment for many of the hallmark symptoms associated with both
ET and PD. With proper lead placement and device programming,
significant improvement can be gained in the tremor of ET and the
motor symptoms of PD. The majority of DBS implantations for ET
or PD have targeted separately the VIM of the thalamus for ET or
the STN for PD. Co-diagnosis of PD exists in approximately 20% of
patients with ET, validating the need for a treatment that would
improve both conditions. Prior studies have shown symptomatic con-
trol in DBS cases targeting the VIM and STN with two separate
leads, while other studies have shown control with DBS targeting of
the thalamus combined with STN lesioning. Currently, no case
reports exist that utilize one DBS lead implanted bilaterally spanning
both targets.
Methods: We present four cases of patients with mixed tremor
diagnosed with both ET and PD, where one DBS lead was inserted
bilaterally allowing stimulation of both the VIM nucleus of the thala-
mus and the STN below with the goal of improving control of both
syndromes.
Results: Bilateral insertion of DBS leads spanning both the VIM
nucleus of the thalamus and the STN improved the clinical symp-
toms of these four patients ET and PD.
Conclusions: This case series illustrates the effectiveness of
implanting one DBS lead bilaterally to simultaneously stimulate the
VIM and the STN to ET and PD symptoms, thus minimizing the
need for additional leads and procedures.
560
The neuroprotective potential of subthalamic nucleus deep brain
stimulation in an a-synuclein overexpression rat model of
Parkinsons disease
D.L. Fischer, F.P. Manfredsson, C.J. Kemp, M.F. Duffy, N.K.
Polinski, K. Steece-Collier, T.J. Collier, S.E. Gombash, D.J. Buhlin-
ger, C.E. Sortwell (Grand Rapids, MI, USA)
Objective: To investigate whether subthalamic nucleus deep
brain stimulation (STN DBS) can mitigate nigrostriatal degeneration
produced by a-synuclein-mediated neurotoxicity.
Background: DBS is the most common neurosurgical treatment
for the alleviation of Parkinsons disease (PD) motor symptoms.
Beyond symptomatic efficacy, our laboratory and others have dem-
onstrated that high-frequency STN DBS provides neuroprotection for
dopaminergic neurons of the substantia nigra (SN) in the 6-
hydroxydopamine (6-OHDA) rat model of PD. However, the evalua-
tion of neuroprotective strategies in neurotoxin models of PD is
 POSTER SESSION
limited, so here we test our hypothesis in an additional PD model,
overexpression of human wild type a-synuclein in which we have pre-
viously demonstrated progressive loss of nigral dopamine neurons.
Methods: Young-adult, male, Sprague-Dawley rats received two,
2.0 l l, unilateral, intranigral injections of recombinant adeno-
associated virus pseudotype 2/5 (rAAV2/5) expressing human wild
type a-synuclein. Rats were implanted ipsilaterally with an electrode
in the STN 18 days following vector injections. One cohort of rats
received continuous STN stimulation for four weeks (130 Hz, 60 ls,
amperage adjusted below the level of dyskinesia induction), whereas
control rats with implanted electrodes received no stimulation during
the same four-week interval. Forelimb akinesia was assessed at mul-
tiple time points throughout the experiment.
Results: Postmortem morphological assessments are ongoing and
will include verification of electrode placement, nigrostriatal a-
synuclein transduction and stereological quantification of tyrosine
hydroxylase immunoreactive SN neurons.
Conclusions: Our pending results will determine whether STN
DBS can ameliorate functional deficits or provide neuroprotection
from a-synuclein-mediated nigrostriatal degeneration.
Supported by Spectrum Health, the American Parkinsons disease
Association and the Morris K. Udall Center of Excellence for Parkin-
sons disease Research at Michigan State University.
561
Implementation of the 3D-atlas of the human brain for high
precision robot-guided and frame-based stereotactic implantation
of intracerebral deep brain electrodes
H. Forutan, M. Majtanik, C.P. Buehrle, H. Treuer, A. Gierich, J.K.
Mai (Duesseldorf, Germany)
Objective: The correct anatomical localization is fundamental for
optimal targeting in Deep Brain Stimulation (DBS). In this study we
tested the improvement in precision and efficacy of targeting by the
integration of 3D-application of the Atlas of the Human Brain
(3D-AHB) for robot-guided frame-based stereotactic implantation of
intracerebral DBS electrodes.
Background: MR-X-BrainV R provides a high fidelity generic
model of the human brain (3D-AHB) with meticulously segmented
structures of the brain (cortex with areal boundaries, major nuclei and
fiber tracts) and a software library that allows for automatic registra-
tion of the model to the individual patient brain. 3D-AHB transformed
into the patient brain supports the planning process by detailed identi-
fication of structures relevant for DBS (e.g. substructures of basal gan-
glia, thalamus, amygdala, basal nucleus of Meynert, hypothalamus).
3D-representation of target areas allows for simulation and computa-
tion of trajectories and optimization of contact positions. Since the
3D-AHB is registered in the MNI-space the planning process is
enriched by database information relevant to specific targets.
Methods: We have compared positions of the electrode in the
subthalamic nucleus in our standardized clinical setting with those
determined by the automatic targeting by means of the 3D-AHB. In
addition, we established the interoperability between the 3D-AHB
and the stereotactic planning robot software for DBS implantation.
TABLE 1. Demographic data
Baseline
Schooling time (years) 12 years
Age at disease onset (years) 47 years
Disease duration (years) 8 years
Levodopa improvement (%) 52,5%
Hoehn & Yahr stage
UPDRS total score
Unified Dyskinesia Scale
S219
Finally, we designed a framework for registration of multiple target
points on to the 3D construct of the AHB in MNI-space as a plat-
form for registry of intra- and extramural DBS-results.
Results: Results and Conclusions: The 3D-representation of target
areas yields improved structural accuracy of positioning of electrode
contacts and monitoring of DBS procedures. Inclusion of biochemical
information and of functional properties from database entries adds
value during the planning procedure but still requests assessment of
validity. Tractography or the relation with physiological parameters
like topography-related microelectrode recordings are to be evaluated.
562
Unilateral forel H1 stimulation for Parkinsons disease: A
possible option for axial motor symptoms
F.F. Godinho, M.O. Oliveira, C.D.M. Costa, R.G. Kauark, A.T.
Neves, P.R. Terzian, M.S.G. Rocha (Sao Paulo, Brazil)
Objective: To describe the motor, non-motor and neuropsycholog-
ical outcomes in one PD patient before and 6-months after FFDBS.
Background: We recently reported clinical improvements in 9
Parkinsons disease (PD) patients who underwent H1 Forels Field
campotomy1. These results, along with anatomical evidences, sup-
port us to test the feasibility of H1 Forels field electrical stimulation
(FF-DBS) to treat PD symptoms. Here, we present the first results of
unilateral FF-DBS in one patient with PD.
Methods: Case report: A 55 year-old female PD patient under-
went unilateral right FF-DBS. Motor evaluation included UPDRS,
Hoehn & Yahr, Berg balance, CAPSIT motor and gait tests, and
Dyskinesia scale. Non-motor evaluation included non-motor symp-
toms scale (NMS), fatigue severity scale (FSS), SCOPA, Neuro-
psychiatric and Beck Inventories. Neuropsychological evaluation
included all tests recommended by the Movement Disorders Society.
Gait was evaluated through clinical scales. The PDQ-39 scale esti-
mated quality of life. Surgery was performed using stereotactic
tomography and non-stereotactic MRI fusion, microelectrode record-
ings and macrostimulation.
Results: Results are shown in [table1].
Baseline and postoperative motor evaluations were performed in
OFF-medication, while Neuropsychological batteries were run in
ON-medication. Motor and gait features improved after surgery.
UPDRS part III improved 32,5%. Gait measures had an improvement
on walking time (55% on up to go test) and an important reduction
on freezing (71,5%).
There was improvement on balance (28,2%) and a significant
reduction on dyskinesias (69,7%). We observed 20% reduction on
ipsilateral bradykinesia. Mild effects on non-motor symptoms were
observed. There was no impact on neuropsychological functions.
Quality of life improved 31,6%.
Conclusions: Six-months evaluation after unilateral FF-DBS
showed a considerable improvement on all motor outcomes, includ-
ing axial symptoms. Noticeable reduction on freezing and dyskine-
sias was reported. This suggests that FF-DBS may be an interesting
option for PD patients who present disabling axial motor symptoms.
More detailed assessment by gait laboratory techniques is under
Postop - 6 months
follow-up DBS on Difference
3 2.5 - 0.5 points
68 46 - 32.4%
76 23 - 69.7%
Movement Disorders, Vol. 30, Suppl. 1, 2015
S220 POSTER SESSION
TABLE 2. Clinical data on bradykinesia and gait measures.
Postop
Baseline DBS on Difference
Walking time (seconds) 12 8 - 33.3%
Number of freezing 7 2 - 71.5%
Number of steps 17 9 - 47.1%
Worst upper limb 5 13 > 100%
movements
Better upper limb 6 17 > 100%
movements
Berg balance scale 39 50 1 28.2%
Up to Go Test 20 9 - 55%
investigation. Godinho F, Rocha MS, Terzian P, Moraes O, Cravo A.
Microelectrode-guided unilateral Forel H1 campotomy for Parkin-
sons disease: Short-term results of nine patients. Movement Disor-
ders Journal Vol 29(Suppl 1) p113, 2014.
563
Differential effects of subthalamic nucleus stimulation frequency
on speech intelligibility and verbal fluency in patients with
Parkinsons disease
T. Grover, D. Georgiev, R. Kaliola, L. Zrinzo, M. Hariz, T. Foltynie,
M. Jahanshahi, P. Limousin, J. Candelario, E. Tripoliti (London,
United Kingdom)
Objective: To examine how speech intelligibility, perceptual
speech characteristics and verbal fluency respond to different fre-
quencies of stimulation (60Hz, 80Hz, 110Hz, 130Hz and 200Hz), in
patients with Parkinsons disease (PD) treated with subthalamic
nucleus deep brain stimulation (STN DBS).
Background: STN-DBS is an established treatment for the pri-
mary symptoms of Parkinsons disease (Limousin et al, 1995).
Speech and verbal fluency can have a variable response to stimula-
tion (Tripoliti et al, 2014).
Methods: Fifteen patients (mean age: 57 years, SD=5.9) treated
with bilateral STN DBS for a mean of 8 6 3.3 years participated in
this double-blind study. A phonemic and semantic verbal fluency
task, a one-minute monologue and a standardised reading speech
intelligibility task were recorded and analysed perceptually. Frequen-
cies were randomly allocated. Patients were assessed following over-
night withdrawal of medication.
Results: Low frequency stimulation (60 and 80 Hz) significantly
improved the (overall) perceptual speech score of the reading speech
intelligibility task (p=.046) and in particular, the sub score of articu-
lation for both the reading speech intelligibility task (p=.001) and the
one minute monologue (p=.012). Verbal fluency was not significantly
altered by low frequency stimulation. There was no change of speech
intelligibility for the standardised reading task.
Conclusions: These results highlight the positive effects of lower
frequency stimulation on speech. Investigating the mechanism of
lower vs higher stimulation frequency could elucidate further the
role of basal ganglia on speech and motor control in PD.
564
Deep brain stimulation in early stage Parkinsons disease may
reduce the relative risk of worsening of both motor symptoms
and complications of therapy
M.L. Hacker, J.A. Tonascia, M. Turchan, A. Currie, L. Heusinkveld,
P.E. Konrad, T.L. Davis, J.S. Neimat, F.T. Phibbs, P. Hedera, L.
Wang, Y. Shi, D. Charles (Nashville, TN, USA)
Movement Disorders, Vol. 30, Suppl. 1, 2015
Objective: To evaluate continuous & patient-centered outcomes
of the Deep Brain Stimulation (DBS) in early stage Parkinsons dis-
ease (PD) pilot trial.
Background: The DBS in early stage PD pilot trial was con-
ducted to gather preliminary safety & tolerability data to inform the
design of a pivotal, phase III trial. In order to provide results that are
most meaningful patients, we conducted a post hoc analysis of con-
tinuous and patient-centered outcomes of the DBS in early PD pilot
data for subjects on medication 1-4 years.
Methods: The DBS in early stage PD pilot study was a prospec-
tive, randomized, parallel, single-blind clinical trial (clinicaltrials.gov
NCT00282152, FDA IDE#G050016)[1]. Clinically important worsen-
ing was defined as both a 3 point decline in UPDRS Part III On
(motor symptoms) and a 1 point worsening of UPDRS Part IV
(complications of therapy) after 2 years. Subjects were randomized
to DBS 1 medication (DBS n59) or optimal drug therapy (ODT
n511) and evaluated on & off therapy every 6 months for 2 years.
Results: DBS was better than ODT at every time point for con-
tinuous scores of Total UPDRS & UPDRS Part III On (24 month
differences: D9.85 P=0.035, D7.87 P=0.021, respectively). Total
UPDRS & UPDRS Part IV significantly worsened in the ODT group
after two years (19.68 P=0.002, 11.82 P=0.002, respectively), with
no significant change in the DBS group. A patient-centered outcome
was also defined & analyzed to determine the relative risk of clini-
cally meaningful worsening on two key PD outcomes: UPDRS Part
III On & Part IV. Fifty-five percent of ODT subjects (6/11) experi-
enced clinically important worsening of both Part III On and Part IV
after two years. Conversely, only 11% (1/9) of DBS subjects wors-
ened over 24 months representing an 82% reduction in the relative
risk of symptom worsening (95% CI 0.03-1.40; P=0.0703).
Conclusions: Results of the pilot trial of DBS in early PD sug-
gest subjects treated with ODT are five times more likely to experi-
ence clinically important worsening of both motor symptoms and
complications of therapy than those treated with DBS. The FDA has
approved (IDE#G050016) a prospective, multicenter, double-blind,
placebo-controlled, phase III, pivotal clinical trial (n5350) to deter-
mine if DBS in early stage PD is superior to standard medical
therapy.
Reference:
[1] Parkinsonism Relat Disord. 2014 Jul;20(7):731-7
565
Programming strategies for tremor resistant to standard DBS
settings: Constant current vs interleaving
S.L. Heath, S. Miocinovic, N.B. Galifianakis (San Francisco, CA,
USA)
Objective: To highlight the utility of constant current (CC) and
interleaved (IL) constant voltage deep brain stimulation (DBS) set-
tings to control refractory tremor in Parkinsons disease (PD) or
Essential Tremor (ET) patients.
Background: Current DBS generators allow the clinician pro-
grammer to use constant voltage or CC settings. In addition, inter-
leaving can be used to further refine the stimulation field. It has been
reported that CC delivers a stable therapy during post-operative
period when intracranial tissue impedances are rapidly changing.
Beyond this time period the clinical value of using constant current
has not been demonstrated.
Methods: Most PD or ET DBS patients were selected who had at
least two programming sessions for symptoms of refractory tremor,
defined as large amplitude, coarse tremor requiring more than the
basic monopolar or bipolar programming strategies. These patients
underwent additional programming to set up parameter groups that
they then tested in home environment over several days and self-
reported which group they preferred for tremor control. They could
choose from (a) single monopolar or bipolar CC or (b) IL single or
bipolar constant voltage groups or (c) standard settings. Patients
 POSTER SESSION
were not blinded and were able to adjust stimulation amplitude for
all groups.
Results: Of 32 DBS implanted refractory tremor patients, 16
patients found CC settings best controlled their tremor, while ten
patients preferred IL programming (using a second active contact
with a separately titrated voltage) and six patients received benefit
from standard programming strategies. Patients determined their
best settings and at the return clinic visit the subjectively chosen
best group was verified. CC settings were programmed slightly
lower than voltage settings due to stim-related side effects. The tar-
gets for this study were: GPi, STN, VIM or ZI.
Target and Programmed Settings
GPi STN VIM ZI
Constant Current 4 6 2 4
Interleaved Voltage 4 5 1 0
Standard Voltage 1 4 0 0
Conclusions: Tremor control can be challenging in some DBS
patients. For the majority of our tremor-dominant patients whose
tremor did not respond to simple programming techniques using CC
or IL proved successful to control their large amplitude tremor.
The neurophysiologic mechanisms of CC benefit on tremor con-
trol are unclear and deserve more study.
566
Computer-guided deep brain stimulation programming using
automated motion sensor-based functional mapping
D.A. Heldman, C.L. Pulliam, E. Urrea Mendoza, M. Gartner, J.P.
Giuffrida, E.B. Montgomery, F.J. Revilla (Cleveland, OH, USA)
Objective: To evaluate software for computer-guided functional
mapping based on objective motor assessments and intelligent algo-
rithms for navigating the deep brain stimulation (DBS) programming
parameter space to resolve an optimal set of programming
parameters.
Background: The clinical utility of DBS for the treatment of Par-
kinsons disease (PD) is well established; however, great outcome
disparity exists among recipients due to varied postoperative man-
agement, particularly concerning DBS programming optimization.
Many programmers have only a cursory understanding of electro-
physiology and lack the expertise and/or time required to determine
an optimal set of DBS parameters from thousands of possible
combinations.
Methods: Seven adults (5 male; 54-71 years) with recently
implanted DBS systems underwent initial post-operative program-
ming according to standard practice. Within three days of initial pro-
gramming, the participant returned to the clinic to undergo
computer-guided functional mapping and parameter selection. A
motion sensor was placed on the index finger of the participants
more affected hand. Software guided a monopolar survey during
which monopolar stimulation on each contact was iteratively
increased followed by an automated assessment of tremor, bradyki-
nesia, hypokinesia, and dysrhythmia. After completing assessments
at each setting, a parameter search algorithm output programming
parameters designed to maximize symptomatic benefits while mini-
mizing side effects and battery usage.
Results: Optimal programming parameters were chosen based on
average severity of four motor symptoms measured by the motion
sensor as described above. Settings chosen by the parameter space
search algorithm identified a therapeutic window and improved PD
motor symptoms by an average of 37.8% compared to off (p50.01),
which is similar to the benefit expected using traditional program-
ming techniques.
S221
Conclusions: Functional mapping software successfully guided a
monopolar survey with minimal clinician involvement and search
algorithms successfully identified optimal stimulation parameters that
significantly improved PD motor symptoms. This suggests that
computer-guided DBS programming based on automated functional
mapping is achievable and could extend expert programming strat-
egies to populations who do not have access to specialized DBS
centers.
567
Wearable sensors for quantifying deep brain stimulation washout
effects on gait in Parkinsons disease
D.A. Heldman, E.B. Brokaw, A.J. Espay, F.J. Revilla, D.E. Riley,
T.O. Mera, J.P. Giuffrida, B.L. Walter (Cleveland, OH, USA)
Objective: To evaluate gait changes in patients with Parkinsons
disease (PD) with and without deep brain stimulation (DBS) using
wearable movement sensors in order to assist DBS programming
efforts.
Background: Changes in DBS settings can have a delayed effect
on gait function, which makes it impractical to optimize for gait in
the clinic. Wearable movement sensors could be used to assess gait
impairment in patients homes hours after treatment adjustments are
made in the clinic.
Methods: Twenty-two adults (17 male, 5 female; age 45-72
years) with PD and implanted DBS systems wore motion sensors on
their ankles, feet, and thighs. Participants completed lower extremity
tasks from the motor subscale of the Unified Parkinsons disease Rat-
ing Scale (UPDRS) on and serially for up to three hours after turning
DBS off. Data recorded from the motion sensors were processed into
scores using previously validated algorithms. Changes over time in
clinician-driven UPDRS and sensor impairment measures were
evaluated.
Results: Clinician and motion sensor-based measurements were
not significantly different from each other and both captured impair-
ment changes after turning DBS off. Motion sensor-based gait scores
worsened significantly immediately after turning DBS off (p<0.05)
and remained significantly worse three hours after turning DBS off
as did clinician gait scores (p<0.01).
Conclusions: Wearable movement sensors are sensitive to gait
impairment changes and could be useful for remotely and accurately
quantifying gait impairment after clinic assessments. These data
could help clinicians optimize post-DBS gait-related outcomes and
aid in the development and evaluation of novel interventions for
individuals with PD.
568
Unilateral microelectrode mapping to guide bilateral deep brain
stimulation electrode implantation: A retrospective study of DBS
programming outcomes
T.M. Herrington, J. Simon, E.N. Eskandar (Boston, MA, USA)
Objective: To assess deep brain stimulation (DBS) programming
outcomes after bilateral electrode implantation with unilateral micro-
electrode mapping.
Background: Among DBS centers there is considerable variabili-
ty in the practice of intraoperative microelectrode recording (MER)
during DBS electrode placement. Some centers perform bilateral
multi-pass MER while others perform no MER at all. MER confirms
the borders of the target nucleus and helps identify the sensorimotor
subregions of the targets, but requires longer, awake surgeries and
probably increases the risk of intracranial hemorrhage. Our practice
is to perform imaging-based stereotactic planning followed by unilat-
eral MER on the initial side to confirm the targeting accuracy. The
second side is then implanted at the symmetric location, without
MER. Effective placement is confirmed intraoperatively with macro-
stimulation testing.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S222 POSTER SESSION
Methods: We retrospectively reviewed all cases of deep brain
stimulator electrode placement for Parkinsons disease performed at
our center by a single surgeon (E.E.) between 2007 and 2014
(n 5 135 cases). In 103 cases (53 STN, 50 GPi), bilateral electrode
implantation was performed with unilateral MER. We reviewed the
DBS programming outcomes of the 73 cases (37 STN, 36 GPi) fol-
lowed longitudinally at our center.
Results: Comparing the microelectrode mapped vs. unmapped
hemisphere, we observed no difference in DBS voltage, pulse width,
likelihood of non-monopolar stimulation, or distribution of active
contacts and no difference in the number of programming adjust-
ments required to reach stable stimulator settings. Intraoperatively,
for STN electrodes there was no difference in the rate of electrode
repositioning after macrostimulation testing, whereas for GPi electro-
des there was a trend towards repositioning more frequently for the
unmapped hemisphere (4/50 mapped, 9/50 unmapped, p 5 0.14, chi-
square test). We observed 2 asymptomatic and 1 symptomatic intra-
parenchymal hemorrhages in 103 cases, 2/3 in the mapped
hemisphere.
Conclusions: These results suggest that careful imaging-based
targeting paired with unilateral microelectrode mapping can achieve
safe and effective DBS electrode implantation. Limitations of this
study include the retrospective design and absence of detailed DBS
motor outcomes which were not available in our database.
569
Impact of advancing age on outcomes of deep brain stimulation
for Parkinsons disease
P.T. Hickey, M.R. Delong, K.T. Huang, J. Gallis, B. Parente, D.A.
Turner, S.P. Lad (Durham, NC, USA)
Objective: To evaluate the step-wise effect of increasing age on
short-term complications following Deep Brain Stimulation (DBS)
surgery.
Background: DBS is a well-established modality for the treat-
ment of advanced Parkinsons disease (PD). Although no specific
age cutoff has been defined, most clinical studies have excluded
patients of age >75 years. In this study, we evaluated the step-wise
impact of increasing age (in 5-year epochs) on short-term complica-
tions following DBS surgery. We hypothesized that increasing age
would be associated with an increase in postoperative complications.
Methods: A large, retrospective, cohort study was performed
using the Thomson Reuters MarketScanV R national database, examin-
ing 1757 patients who underwent DBS for PD from 2000-2009.
Within this database, all inpatient admissions, inpatient services, out-
patient services, outpatient pharmaceuticals, and enrollment tables in
the United States were examined. Primary outcome measures exam-
ined included hospital length of stay and aggregate and individual
complications within 90 days following surgery. Multivariate logistic
regression analysis was used to calculate complication odds ratios
for each 5 year age epoch after controlling for covariates.
Results: Overall, 132 (7.5%) of 1757 patients experienced at least
one complication within 90 days, including wound infections (3.6%),
pneumonia (2.3%), hemorrhage or hematoma (1.4%), or pulmonary
embolism (0.6%). After adjusting for covariates, increasing age rang-
ing from <50 up to 90 years of age, did not significantly impact
overall 90-day complication rates (OR 1.10 per 5-year increase; 95%
CI 0.96, 1.25; p 5 0.173). The two most common procedure-related
complications, hemorrhage and infection, did not significantly
increase with age (hemorrhage OR 0.83; 95% CI 0.63, 1.07;
p 5 0.144, infection OR 1.04; 95% CI 0.87, 1.24; p 5 0.693).
Conclusions: Among older PD patients (>75 years), who under-
went DBS, the 90-day complication risk and the risk of postoperative
hemorrhage or infection remained relatively stable, despite increasing
age. Our findings suggest that age alone should not be a primary
exclusion factor for determining candidacy for DBS. Instead, a clear
focus on patients with medication-refractory symptoms and difficult
Movement Disorders, Vol. 30, Suppl. 1, 2015
to control onoff fluctuations with preserved cognition may allow an
expansion of the traditional therapeutic window.
570
Interdisciplinary deep brain stimulation screening and the
relationship to unintended hospitalizations and quality of life
M. Higuchi, H. Morita, D. Bowers, H. Ward, L. Warren, M.
DeFranco, M.S. Troche, S. Kulkarni, E.H. Monari, D. Martinez-
Ramirez, K.D. Foote, Y. Tsuboi, M.S. Okun (Gainesville, FL, USA)
Objective: To investigate the impact of deep brain stimulation
(DBS) pre-operative interdisciplinary assessments on hospitalizations
and quality of life (QOL).
Background: DBS has been utilized successfully for many cases
of Parkinsons disease (PD). Although DBS is becoming a more
common management approach there are no standardized criteria for
selection of DBS candidates. Additionally, most expert centers utilize
an interdisciplinary or multidisciplinary screening model; however,
there are no data to support its use. We reviewed the outcomes of an
interdisciplinary model utilizing seven specialties to pre-operatively
evaluate potential DBS candidates.
Methods: The University of Florida (UF) INFORM database was
queried for PD patients who had DBS implantations performed at
UF between January 2011 and February 2013. Records were
reviewed to identify unintended hospitalizations, falls, and infections.
Minor and major concerns or reservations from each specialty were
well documented and were quantified. Clinical outcomes were
assessed through the use of the Parkinsons disease quality of life
questionnaire (PDQ-39), and the Unified Parkinsons disease Rating
Score (UPDRS) Part III.
Results: A total of 164 cases were evaluated for possible DBS
candidacy of which 133 subjects received interdisciplinary screening
and were approved for a DBS surgery (81.1%). There were 28 cases
(21.1%) who experienced unintended hospitalization within the first
12 months following the DBS. The patients identified during interdis-
ciplinary evaluation with major or minor concerns from any specialty
service had more unintended hospitalizations (92.9%) when com-
pared to those without concerns (7.1%). The majority of unintended
hospitalizations (82.1%) were not directly related to the DBS surgery
itself. When the preoperative concern shifted from major to
minor to no concerns, the rate of hospitalization decreased from
88.9% to 33.3% to 2.9%. A strong relationship was uncovered
between worsened PDQ-39 at 12 months and increased
hospitalization.
Conclusions: Unintended hospitalizations and reduced QOL
scores correlated with the results of interdisciplinary DBS evalua-
tions. The data suggest that detailed screenings by interdisciplinary
teams may be useful for more than just patient selection. These eval-
uations may help to stratify risk for post-operative hospitalization
and QOL outcomes.
571
A probabilistic atlas defining an optimal deep brain stimulation
site in Parkinsons disease based on long-term clinical outcome
A. Horn, R. Serrano Sandoval, T. Schmitz-H ubsch, E. Accolla, G.H.
Schneider, A.A. K
uhn (Berlin, Germany)
Objective: To optimize treatment outcome and better understand
the mechanism of action of DBS, patient specific DBS electrode
reconstructions were correlated with corresponding clinical
outcomes.
Background: Electrode placement is crucial to ensure efficacy in
DBS therapy. Based on postoperative MR or CT imaging, electrode
positions can be reconstructed and their position analyzed within the
subcortical volume of the brain. Moreover, stimulation settings can
be used to predict a volume of activated tissue (VAT) that simulates
the patient-specific effect of DBS therapy (Horn 2014).
 POSTER SESSION
Fig. 1. (571).
Methods: DBS electrode placements were reconstructed for sixteen
patients based on pre- and postoperative MR imaging. Using the long-
term stimulation parameters actually applied in the clinical setting, a
VAT was calculated at the active stimulation site of each electrode. The
volumes of intersection between the VAT and three separate atlases of
the STN were then calculated. In a second analysis, the VAT of each
patient was weighted with the respective clinical improvement and aver-
aged across the group of patients in standard stereotactic space.
Results: The volume of intersection between VAT and STN was
predictive for the long-term clinical outcome of patients (expressed
by improvements in UPDRS III motor score; figure 1, R=0.74;
p50.001). The best clinical improvement was reached in patients
with VAT lying within the postero-ventro-lateral portion of the STN,
which corresponds to its sensorimotor functional zone.
(figure 1)
In a second step, VAT were weighted by clinical improvement of
each patient and averaged across the group of patients, resulting in a
probabilistic atlas that defines the mean clinical motor improvement at
each coordinate covered by the group of VAT. This atlas also peaked
within the sensorimotor functional zone of the STN (figure 2).
(figure 2)
Conclusions: The results demonstrate that computer simulations
of patient specific DBS electrode placements are predictive for the
respective clinical patient outcome. Furthermore, the atlas established
in this study can be used to retrospectively analyze stimulation vol-
umes in STN DBS therapy more deliberately. Moreover, it may help
to set optimized DBS parameters prospectively based on modeled
VAT.
Fig. 2. (571).
S223
Horn, A., & K uhn, A. A. (2015). Lead-DBS: A toolbox for deep
brain stimulation electrode localizations and visualizations. Neuro-
Image, 107, 127135.
572
DBS experience at a tertiary care referral center
J. Jimenez-Shahed, J. Keller, C. Hunter, J. Jankovic (Houston, TX,
USA)
Objective: 1. Describe the characteristics of an active DBS
cohort at an academic, tertiary care center.
2. Identify trends in DBS care for patients with PD.
Background: The Parkinsons disease Center and Movement Dis-
orders Clinic has been involved in surgical treatment of Parkinsons
disease (PD) and other Movement Disorders and at the forefront of
DBS research since 1998. The role of DBS in treatment of Move-
ment Disorders is expanding. Novel imaging and neurophysiologic
techniques will optimize DBS placement.
Methods: A retrospective review was performed to characterize a
cohort of DBS patients followed or implanted at the PDCMDC since
2010.
Results: Since database implementation in 2010, 271 patients,
160 with PD, 58 with essential tremor (ET), 30 with dystonia, 11
with Tourette syndrome (TS), 7 with cerebellar outflow tremor, and
5 with other Movement Disorders, have been followed. Our pre-
operative assessment protocol includes a disease-specific motor eval-
uation, neuropsychological evaluation, and consensus team review.
Of 132 new implants, diagnoses include PD (n576, mean age 62yrs,
SD 8.9), ET (n526, mean age 64yrs, SD 10.1), dystonia (n518,
mean age 52yrs, SD 14.8), TS (n56, mean age 20yrs, SD 4.9), and
other (n56). Each year 21-30 new implants were performed. Among
new PD implants, 43 were in subthalamic nucleus (mean age 591/-
8.6yrs), 26 in globus pallidus interna (mean age 631/-8.7yrs), 4 in
ventral intermediate nucleus (mean age 671/-2.9yrs), and 3 other
(mean age 71 1/-10.1yrs). Additionally, 184 battery exchanges and
15 lead revisions were performed. Of all patients, 55 (20.3%) have
rechargeable batteries, of which 29 (52.7%) were placed at initial
implantation, and 16 in the last 4 years (10.6% of all new implants).
Conclusions: DBS for PD continues to represent the largest
group of patients (59%) in our cohort.
A comprehensive database with a well-characterized cohort is
critical for on-going monitoring of DBS patients and to facilitate
DBS-related research.
573
Optical neuromodulation of nigrostriatal pathway
T. Jo, G. Oyama, K. Yoshimi, S. Sato, T. Danjo, A. Uemura, Y.
Shimo, N. Hattori (Tokyo, Japan)
Movement Disorders, Vol. 30, Suppl. 1, 2015
S224 POSTER SESSION

Objective: To establish selective and controllable dopaminergic

modulation of nigrostriatal pathway utilizing optogenetics.
Background: Levodopa is the gold standard treatment for Parkin-
sons disease (PD). However, longterm levodopa use causes motor
fluctuation. Excess of dopaminergic stimulation may result in dyski-
nesia and impulse control disorder. Subthalamic nucleus (STN) deep
brain stimulation (DBS) is a therapeutic option for motor fluctuation,
although the neurophysiological mechanism of STN DBS remains
unclear. Whether high frequency stimulation of the STN induce stria-
tal dopamine release or not is under debate. Optogenetics is a new
technology to optically modulate the specific neuron activity by
introducing light-gated ion channels such as channelrhodopsin and
archaerhodopsin. Utilizing optical stimulation not only able to acti-
vate but also to suppress nigrostriatal pathway.
Methods: Channelrhodopsin-2 (ChR2) or archaerhodopsin (Arch) Fig. 1. (574).
were selectively expressed in the midbrain dopaminergic neurons of
tyrosine hydroxylase-cre mouse (courtesy gift from Dr. T. Dawson)
was taken and neurological examination performed in all. ICD was
using AAV vectors. Transient dopamine release was detected by
studied using Questionnaire for Impulsive-Compulsive Disorders In
fast-scan cyclic voltammetry (FSCV) on carbon fiber microelectrode
Parkinsons disease (QUIP-RS) which evaluated - pathological gam-
in the dorsal striatum. Electrical pulses were given to substantial
bling, sexual impulses, eating,buying, hobbying, punding and PD
nigra (SN) by conventional electrodes, and blue (432nm) or yellow
medication overuse.Student t test was used to asses the difference
(589nm) light were delivered to medial forebrain bundle (MFB) by
between discrete variables and chi-square test was used to identify
optial fibers.
differences between the proportions.
Results: Optical activation (blue ligth) of MFB evoked dopamine
Results: Among 50 PD patients 35 were men; mean age was
release as well as electrical stimulation (Figure 1 left). Optical sup-
55.0 610.7 years mean duration was 6.6 6 3.7 years mean Hoehn
pression (yellow light) of MFB significantly decreased dopamine
and Yahr score was 2.5 6 1.0. ICD was present in 64% of patients.
release (2 tailed t-test, p<0.01, Figure 1 right).
None of our patients gambled. Hobbying/punding was commonest
[Figure1]
ICD seen in 40% with avereage score of 4.3B67.4 followed by
Conclusions: We demonstrated that optical stimulation can sup-
hypersexuality(28%) eating (26%) PD medication overuse (22%)
press as well as induce dopaminergic release in striatum. Optical
and buying (10%). On comparing patients with and without ICDs,
stimulation enable neuron-specific and controllable neuromodulation
presence of dyskinesias (p50.002) and cognitive impairment
in nigrostriatal pathway.
(p50.004) was significantly more in patients with ICD. Bilateral
STN DBS was strongly associated with ICDs with an odds ratio
574 of 2.93 (95% CI 0.8 to 9.7) . On evaluating the ICDs in DBS and
non DBS patients, significantly higher prevalence of ICDs, and
Effect of bilateral STN DBS on impulse control disorders in
among them PD medication use and buying were seen in DBS
patients with idiopathic Parkinsons disease- A case control study
group compared with non DBS (p50.01,0.0004 & 0.03 respec-
R.M. Kandadai, S.K. Jogu, A. Jabeen, A.K. Puligopu, P. Ankati, tively) [figure1].
M.A. Kanikannan, R. Borgohain (Hyderabad, India) Conclusions: ICDs are a common feature in PD patients. Com-
Objective: To evaluate the prevalence of impulse control disorder- pared to the west our profile is different with hobbying/punding
s(ICD) in patients with idiopathic Parkinsons disease and compare the being the most common. STN DBS confers increased risk of devel-
ICDs in patients who have undergone bilateral subthalamic deep brain oping ICD.
stimulation (DBS) surgery to those on medical management.
Background: ICDs cause impairment of quality of life in PD
patients and are under recognized and under reported. They may be 575
intensified by dopamine agonists. The effect of DBS on ICDs are
still unclear. Pallidal stimulation is effective for complex cranio-cervical
Methods: We studied 50 patients with PD.25 patients had under- dystonia and an unappreciated advers effect as tensor sensation
gone DBS while 25 were on medical management. Detailed history H. Kaptan, H. Ekmekci (Konya, Turkey)

Fig. 1. (573).

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
Objective: In this presentation, a unique case of right sided torti-
collis in cranio cervical dystonia was applied with bilateral GPi
DBS and her peculiar clinical course is presented.
Background: Our case is a complex cervical dystonia that has
been complicated with surgical intervention and has been under the
cure of medical therapy.
Methods: A 40 years old woman who has been suffering from
right sided cranio-cervical dystonic symptoms and unwilling spas-
modic movements spreading toward shoulder and arm. Right sided
torticollis was overlapped with contralateral and slight dystonic Stre-
nocloidomastoid (SCM) muscle. Patient was operated twice in Plastic
and Reconstruction department on SCM first on right then on left
side after 9 years of period when the medical therapy was unrespon-
sive. The main problem could not be solved; for this reason several
times botulinum injections were tried.
Results: SCM hypertrophy and C6 7 paracentral protrusionin
MRI. In cerebral MRI, a small chronic infarction area at left nucleus
caudate nearside of frontal horn of lateral ventricle. Preoperative
Burke-Fahn-Marsden dystonia scale (BFMDRS) was 13. The patient
was applied with bilateral GPi DBS and discharged without any
complication at 3rd day. Postoperative BFMDRS was 8. At the
monthly control exam, she was very well with an acceptable
improvement of dysphagia, dysarthria and tongue movements. The
gain of BFMDS was 5 score, the most felt healing at dystonic cervi-
cal posture and global dystonia disability scale. In subacute period,
extension wire area a sensitivity feeling was encountered. This feel-
ing disappeared nocturnally. This new resulting table and new find-
ings will be discussed on behalf of surgical procedures, elongation of
wire or psychiatric reasons.
Conclusions: GPi DBS is still a good alternative approach for
such case aferomentioned above. Since in literature scanning, we
could find an unappreciated adverse effect as a painful tensor sensa-
tion as the second time.
576
Patient-centered outcomes of deep brain stimulation in
Parkinsons disease
J.A. Karl, B. Ouyang, L. Verhagen (Chicago, IL, USA)
Objective: To determine long-term patient-centered outcomes of
bilateral STN DBS in PD, emphasizing satisfaction, quality-of-life
and disability.
Background: STN DBS is effective for motor symptoms of PD
but long-term patient-centered outcomes are lacking.
Methods: We developed a survey to query satisfaction in patients
>5 years post-DBS, questioning expectations, satisfaction, decision
to undergo DBS, willingness to hypothetically undergo DBS again,
timing of DBS, and confidence in recommending DBS. Patients used
scores from 0-10, whereby 0 represented the most positive answer.
Rating scales that were completed pre-operatively, including the
PDQ-39 (quality-of-life, lower score better), UPDRS-I (behavior,
lower score better), UPDRS-II (disability, lower score better),
UPDRS-IV (complications of levodopa therapy, lower score better),
and S&E (disability, higher score better) were repeated at time of
survey. We will recruit a total of 100 consecutive patients in this
ongoing study. Current data were analyzed using simple comparison.
Regression analyses will be used with the future larger data set.
Answers were obtained from patients and their caregivers.
Results: 24 patients (mean6SD, 8.5 6 3 years post-DBS) com-
pleted this ongoing study thus far. Satisfaction was high with median
score (range) of 1.5/10 (0-8). Expectation was also high with median
score of 3/10 (0-10), with satisfaction exceeding expectation by
4.86%. Patients endorsed their decision to undergo DBS, score 0/10,
(0-10), would proceed with surgery again, 0/10 (0-10), would have
preferred DBS earlier, 3/10 (0-10) and would recommend DBS to
others, 0/10 (0-10). The difference in means (SD) between pre-
operative and time of survey PDQ-39 scores was 0.07(21.5). Mean
difference (SD) of UPDRS-I scores, UPDRS-II-OFF/ON scores, and
S225
UPDRS-IV scores was 1.3(2.3), -0.08(10)/8.7(8.5) and -4.8(3.8)
respectively. Mean difference (SD) of S&E-OFF/ON scores was -
0.08(0.32)/-0.21(0.25).
Conclusions: Preliminary results demonstrate that satisfaction
with DBS is maintained 8.5 6 3 years after surgery. In general,
patients would choose to have surgery again, at an earlier time, and
recommend DBS to others. Interestingly, quality-of-life was main-
tained despite increasing disability, however no firm conclusion can
be drawn due to the large variability in the current data.
577
Estimating the proportion of essential tremor and Parkinsons
disease patients referred for deep brain stimulation: Five-year
data from Columbia University Medical Center (2009-2014)
M. Kestenbaum, E.D. Louis (New York, NY, USA)
Objective: To estimate the proportion of essential tremor (ET)
and Parkinsons disease (PD) patients referred for deep brain stimu-
lation (DBS) surgery.
Background: DBS has become an important treatment for
patients with ET and PD. Surprisingly, there is no data on the actual
proportion of such patients referred for this procedure.
Methods: A search was conducted of the computerized billing
database of the Center for Parkinsons disease and Other Movement
Disorders, Columbia University Medical Center (CUMC) for patients
who received the diagnostic codes 333.1 (tremor) and/or 332.0 (PD)
in the period from January 1, 2009 to May 8, 2014. One-hundred
electronic charts were reviewed for each diagnostic code to validate
the ET and PD diagnoses. The proportion of patients who had been
followed by a doctor at the Center and who had undergone DBS for
these diagnoses was then estimated.
Results: One-hundred-eighty-six patients underwent DBS in this
time period; 105 were excluded because they were referred directly
from outside the Center for DBS evaluation. The remaining 81 (52
PD, 14 ET, 11 ET1PD, 4 other) were followed at the Center prior
to the DBS referral and surgery. The total number of patients who
received the diagnostic codes 333.1 and 332.0 was 1,198 and 5,191
respectively. The validity of the ET and PD diagnoses, based on
chart review, was 75% and 88%; hence the above values were
adjusted to 898 and 4,568. The proportion of ET patients referred for
DBS was 25/898 (2.78%, 95% confidence interval [CI] 5 1.84
4.14%) and for PD was 63/4,568 (1.38%, 95% CI 5 1.07 1.77%).
The difference was significant (p 5 0.002).
Conclusions: At our tertiary center, approximately 1-in-35 to 1-
in-72 ET or PD patients were referred for DBS surgery. In this sam-
ple, the proportion with ET was higher than that of PD.
578
The effect of subthalamic nucleus deep brain stimulation on
REM sleep behavior disorder
B. Kocer, S.S. Comoglu, H. Guven, A.S. Eren, S. Ferik (Ankara,
Turkey)
Objective: To evaluate the effect of subthalamic nucleus (STN)
deep brain stimulation (DBS) on REM sleep behavior disorder
(RBD) in patients with Parkinsons disease (PD).
Background: Sleep disorders and RBD are common in PD. STN
DBS may improve subjective and objective sleep measures, includ-
ing sleep efficiency and nocturnal mobility, as well as motor symp-
toms, while its effect on RBD is still unclear in patients with PD.
Methods: In this prospective study 85 patients diagnosed with
idiopathic PD (51 male, 60%) according the UK Brain Bank criteria
were evaluated with a semi-structured clinical interview for probable
RBD before and on the sixth month of STN DBS. The diagnosis of
probable RBD was based on the diagnostic criteria for parasomnias
provided in the International Classification of Sleep Disorders. The
severity of clinical symptoms were measured using Unified
Movement Disorders, Vol. 30, Suppl. 1, 2015
S226 POSTER SESSION
Parkinsons disease Rating Scale (UPDRS) II and III; and dopami-
nergic treatment dosage calculated as levodopa equivalent dose
(LED).
Results: The mean age was 54.92 6 9.65 and the mean disease
duration was 13.64 6 6.35 years. Forty- three (50.58%) and 34
(40%) patients were noted for having RBD before and after STN
DBS respectively. Six months after the stimulation 12 patients
reported improvement of their RBD (27.9%), while recently devel-
oped RBD was detected in 3 patients (7.14%). After STN DBS,
mean 55.83%; 58.9%; and 46.35% reduction was found on UPDRS
part II; III scores, and LED respectively. Among the patients with
RBD before STN DBS, %42 and %58.5 decrease in LED was found
in patient groups with and without RBD after the stimulation respec-
tively. We also found that mean 11.51% LED reduction in patients
with recently diagnosed RBD.
Conclusions: Our findings indicated that recently diagnosed RBD
or improvement of RBD both may be seen in PD patients after STN
DBS. However in our study the improvement of RBD in the early
period of the stimulation was more significant. Less decrease ratios
in the dopaminergic treatment dosage after the stimulation may be
the marker of more severe symptoms and extensive neurodegenera-
tion. Thus RBD may not well respond to the stimulation, additionally
de novo RBD may occur. Moreover the improvement of RBD after
the stimulation may be associated with the pathway regulates REM
sleep which was affected by the STN DBS.
579
Deep brain stimulation can preserve working abilities in
Parkinsons disease
N. Kov
acs, I. Bal
as, S. Komoly, T. Doczi, J. Janszky, Z. Aschermann,
A. Makkos, E. Bosny ak, G. Deli (P
ecs, Hungary)
Objective: Our investigation aimed to evaluate if DBS therapy
was able to preserve the working capabilities.
Background: There is a debate on the potential advantageous
effects of bilateral subthalamic deep brain stimulation (DBS) in the
treatment of Parkinsons disease with early fluctuations.
Methods: We reviewed the data of 40 young (<60 year-old) PD
patients who underwent DBS implantation at University of Pecs and
had an at least 2 years follow-up. Patients were categorized into two
groups based on their working capabilities at time of surgery:
Active job group (n520) and No job group (n520). Baseline
characteristics were comparable. Severity of motor symptoms
(UPDRS-3), quality of life (EQ-5D) and presence of active job were
evaluated preoperatively and 2 years postoperatively.
Results: Although similar (approximately 50%) improvement was
achieved in the severity of motor and major non-motor symptoms in
both groups, the postoperative quality of life was significantly better
in the Active job group (0.687 vs. 0.587, medians, p<0.05). Major-
ity (80%) of Active job group members were able to preserve their
Comparison of electrode location and threshold for side effects between first side and second side
First insertion side
Deviation of the electrodes in 3D space 1.1 6 1
Deviation of the electrodes in X axis 0.9 6 0.7
Deviation of the electrodes in Y axis 1.4 6 1
Deviation of the electrodes in Z axis 1.4 6 0.9
Threshold for any side effect (Volts)
Contact 0 (n567) 2.7 6 1.2
Contact 1 (n570) 3.1 6 1.1
Contact 2 (n561) 3.6 6 1
Contact 3 (n559) 4.1 6 1.2
Movement Disorders, Vol. 30, Suppl. 1, 2015
job 2 years after the operation. However, only a minimal portion
(5%) of the No job group members was able to return to the world
of active employees (p<0,01).
Conclusions: Although our study has several limitations, our
results fits well with the conclusions of EarlyStim study. In patients
with active job the appropriately early usage of DBS might help
preserve working abilities in a two-year time-frame and gain higher
improvement in quality of life.
580
The sequence of electrode placement affects outcomes after
subthalamic nucleus deep brain stimulation for Parkinsons
disease
V. Krishna, F. Sammartino, N.K.K. King, V. Bruno, C. Marras, S.
Kalia, M. Hodaie, A. Lozano, A. Fasano (Toronto, ON, Canada)
Objective: To explore the effects of sequence of electrode place-
ment on outcomes after deep brain stimulation (DBS).
Background: The deviation in electrode location and its effect
on outcomes after bilateral subthalamic nucleus (STN) DBS is
unknown.
Methods: We retrospectively analyzed clinical and radiographic
data on consecutive PD patients who underwent bilateral STN DBS
at our center. We only included patients with at least one-year fol-
low-up. Pre and post-operative images were fused using Framelink
(v 5, Medtronic Inc, Minneapolis, USA). Individual trajectories were
analyzed in X, Y & Z axes and the Euclidian distance between
intended target and actual electrode tip was calculated. Linear regres-
sion analysis was performed to analyze the predictors of postopera-
tive UPDRS-III. The covariates included were age, preoperative
UPDRS-III (OFF state), preoperative UPDRS-II (OFF state), levo-
dopa responsiveness and deviation (measured by mean absolute devi-
ation) of electrode location on both sides.
Results: We included 76 consecutive patients (mean age 58 6 7.2
years). After DBS, motor symptoms and fluctuations significantly
improved (60% reduction in UPDRS-III & 50% in UPDRS-IV) and
were paralleled by a 50% decrease in levodopa dose equivalent. The
second side electrode had significantly more deviation from intended
trajectory (deviation in the Z-axis, p50.04) and lower threshold for
side effects (contact 0, p<0.001 and contact 3 p50.004).
There was a trend towards higher overall 3D deviation on the
second side (p50.095) [figure1].
In the linear regression analysis, the significant predictors of out-
come were baseline UPDRS-II score (p50.010), levodopa respon-
siveness (p50.022) and deviation of electrode on the second side
(p50.018).
Conclusions: We observed a higher deviation for the electrode
implanted on the second side and it is a significant predictor of out-
come at 1 year. We propose that the electrode contralateral to the
Second insertion side P value
1.5 6 1.9 0.095
1.4 6 1.5 0.048
1.4 6 1 0.9
1.6 6 1.5 0.8
2.1 6 0.9 <0.001
2.9 6 0.9 0.22
3.4 6 0.9 0.27
3.7 6 1 0.004
 POSTER SESSION
Fig. 1. (580).
worst side should be implanted first. *VK and FS contributed equally
to this work.
581
The impact of the cause of death on neuropathological changes
due to deep brain stimulation
M. Kronenbuerger, K. Nolte, V.A. Coenen, J.M. Burgunder, J.
Krauss, J. Weis (Baltimore, MD, USA)
Objective: To assess the impact of the cause of death on neuro-
pathological changes around Deep Brain Stimulation electrodes.
Background: Astrogliosis and chronic inflammatory responses
along the Deep Brain Stimulation electrodes tract are the most com-
monly described tissue changes. However, the cause of death may
impact the tissue responses to the implanted electrodes.
Methods: Brains of 10 patients (with 8 Parkinsons disease and 2
with essential tremor) were systematically examined up to 7.5 years
after surgery. Six patients died from sepsis and 4 from acute cardio-
vascular events. The following characteristic histological aspects were
analyzed in a semi-quantitative fashion: extent of hyaline ensheath-
ment, astrogliosis, Rosenthal fibres, hemosiderin deposits, CD3 or CD
20 stained lymphocytes, granulocytes, MNGC, and macrophages.
Results: Patients who died in septicaemia showed a more severe
astrogliosis and giant cell reaction than patients who died from cardi-
ovascular events all (P < 0.05 as assessed by multilinear regression
analysis).
S227
Conclusions: The state of activation of the immune system
affects the degree of brain tissue reaction to the Deep Brain Stimula-
tion electrode. This may help to a better understanding of the tissue
changes due the Deep Brain Stimulation.
582
Parkinsons disease (PD) patient experience with deep brain
stimulation (DBS) surgery using asleep interventional MRI
(iMRI)-guided versus awake physiology-guided implantation
techniques
S.C. LaHue, J.L. Ostrem, N.B. Galifianakis, M. San Luciano, N.
Ziman, S. Wang, C. Racine, P.A. Starr, P.S. Larson, M. Katz (San
Francisco, CA, USA)
Objective: To assess PD patient experience with either asleep
DBS implantation guided by iMRI or awake DBS implantation
guided by intraoperative physiology.
Background: Traditional awake DBS may be poorly tolerated by
some patients. The iMRI technique was developed to obviate the
need for patients to be awake by using real-time image guidance to
place DBS leads under general anesthesia. We explored both asleep
iMRI and awake DBS surgical experiences to better understand
patient perspective with these techniques.
Methods: All English-speaking PD patients who underwent iMRI
DBS implantation, or a staged combination of iMRI and awake DBS
implantation, between 2010-2014, were invited to participate. Sub-
jects underwent a structured telephone survey exploring pre-
operative preferences as well as intra- and post-operative experien-
ces. At our Center, patients have both procedures explained and can
choose between them. Two visits are required for the iMRI proce-
dure, as the implantable pulse generator cannot be placed in the radi-
ology suite for logistical reasons, whereas all hardware implantation
for awake DBS can be completed in one day.
Results: 70 patients were screened and 44 patients (34M/10F)
completed the study [mean age: 64 6 7 years, mean duration of dis-
ease 12 6 5 years, mean baseline UPDRS-III off score: 41 6 11].
Reasons to prefer iMRI, in order of importance, included: ability to
be asleep during surgery, absence of awake stereotactic head-frame
placement, and ability to take PD medications on the day-of surgery.
Four patients would not have undergone DBS if the iMRI technique
was unavailable. Mean satisfaction score with iMRI DBS surgery
was 0.22 6 0.48 (0 5 very satisfied, 4 5 very unsatisfied).
Five patients underwent both iMRI and stereotactic DBS surgery
in a staged fashion. Three patients preferred iMRI due to pain during
frame placement and awake surgery. Reasons for preferring the
awake method included a desire for a consolidated surgery and his-
tory of complications related to iMRI surgery.
Conclusions: PD patients who underwent iMRI DBS surgery have
an overall positive experience. The decision to choose this technique is
driven by concerns about being uncomfortable during awake neurosur-
gery. Future studies should include a larger cohort of comparison cases.
583
Effects of randomized subthalamic nucleus deep brain
stimulation on gait in patients with Parkinsons disease
K.J. Lizarraga, J. Jagid, B. Gallo, C. Luca (Miami, FL, USA)
Objective: To identify the differential effects of unilateral subthala-
mic nucleus deep brain stimulation (STN-DBS) on gait kinematics in
patients with Parkinsons disease (PD) and associated gait dysfunction.
Background: STN-DBS improves motor symptoms in PD. How-
ever, unbalanced STN-DBS may worsen gait due to STN functional
asymmetry.
Methods: Twenty-two PD patients with gait impairment after
being treated with STN-DBS were tested in 4 randomly assigned
conditions: bilateral (BL-ON), right (R-ON), left (L-ON) and
Movement Disorders, Vol. 30, Suppl. 1, 2015
S228 POSTER SESSION
bilateral off (BL-OFF) stimulation. Gait kinematics were evaluated
in all conditions using wireless sensors.
Results: Without stimulation, mean MDS-UPDRS was 48.68 6 3.41
and PIGD (gait score) was 9.22 6 1.06. STN-DBS significantly
improved these scores to 24.09 6 2.76 and 6.27 6 0.94 (BL-ON). There
were no differences between R-ON and L-ON in terms of motor scores
(35.59 6 3.19 R-ON and 38.36 6 3.52 L-ON) or PIGD (7.4 6 0.94 R-
ON and 7.63 6 0.97 L-ON). During BL-OFF, mean walking stride length
was 0.95 6 0.06 m., velocity 0.85 6 0.07 m/s and turning time
4.89 6 0.6 sec. STN-DBS significantly improved stride length to
1.09 6 0.04 m., velocity to 0.96 6 0.05 m/s and turn time 4.13 6 0.5 sec.
R-ON improved stride length more than L-ON (1.06 6 0.04 vs.
1.01 6 0.05; p50.02). Similarly, velocity was better with R-ON
(0.93 6 0.05 m/s) than with L-ON (0.90 6 0.05 m/s) (p50.2). Stride
length and velocity did not significantly change with worse side ON, but
improved 0.09 m. (p50.03) and 0.08 m/s (p50.04) with best side ON.
Conclusions: Right STN-DBS might have specific beneficial
effects on gait parameters in PD patients. These asymmetric STN-
DBS effects could have implications in clinical practice but require
confirmation in larger studies.
584
Intraoperative MRI for deep brain stimulation lead placement in
Parkinsons disease: One year motor and quality of life outcomes
A. Mahajan, J. Schwalb, P. LeWitt, M. Schonberger, A. Ellenbogen,
D. Taylor, J. Wall, C. Sidiropoulos (Detroit, MI, USA)
Objective: To present motor findings and functionality results for
Parkinsons disease (PD) patients who underwent deep brain stimula-
tion (DBS) electrode placement with intraoperative MRI (iMRI)
using the ClearPointVR system (MRI Interventions, Inc.).
Background: iMRI for DBS lead placement is a novel approach
using neuroimaging rather than awake electrophysiologic mapping.
Many patients are not candidates for awake mapping due to anxiety
or discomfort from an unmedicated state while in the operating
room. Patients may also prefer not to undergo awake surgery. Multi-
ple passes through brain tissue to determine ideal lead placement
pose increased risk for hemorrhage and adverse neuropsychiatric
effects. There has been limited reporting of DBS for PD using iMRI.
Methods: Data on 9 PD patients who underwent DBS under gen-
eral anesthesia using iMRI were collected. The UPDRS Part III was
conducted by a Movement Disorders expert pre- and postoperatively,
using a standardized protocol and the PDQ-39 questionnaire was
completed by the patient post-surgery. Retrospective descriptive
analysis using paired t-test was performed with STATA, Version SE
12 for Windows (College Station, TX).
Results: Mean UPDRS III scores off medication before DBS,
39.89 (95% CI: 68.18). Mean score on medication before DBS;
16.89 (95% CI: 67.97). Post-DBS, the on stimulation UPDRS III
scores changed to 21.22 (95% CI: 65) and 17 (95%CI: 63.06) for
off and on medication scores, respectively. Patients had a 46.8%
improvement in the UPDRS III scores off medication, after iMRI-
guided DBS vs 57.4% on medication. The Mean PDQ-39 Score was
214.3, with the dimensions of Mobility (24%) and Activities of Daily
Living (16%) contributing most to functionality issues post-DBS.
Social support was the least pressing issue (6%).
Conclusions: Motor findings improved significantly in our 9
patients undergoing iMRI guided DBS, similar to previously-
published results after awake electrophysiologic mapping. Though
promising, more careful study is needed to establish the role of iMRI
for DBS lead placement in PD and other Movement Disorders.
585
The research on deep brain stimulation to improve non-motor
symptoms of Parkinsons disease
Z. Mao, S. Ji, Q. Yang, H. Ye, Z. Xue (Wuhan, Peoples Republic of
China)
Movement Disorders, Vol. 30, Suppl. 1, 2015
Objective: To investigate the improving situation related to the
non-motor symptoms of Parkinsons disease after receiving deep
brain stimulation(DBS) treatment .
Background: DBS can improve the motor symptoms of
Parkinsons disease, but the role on non-motor symptoms is not yet
clear.
Methods: 10 patients with advanced idiopathic Parkinsons dis-
ease receving DBS treatment during 2013.1-2014.1 from Tongji Hos-
pital were studied, including 4 males and 6 females. And 10 cases
had not received DBS therapy of primary Parkinsons disease, age-
and sex- matched were recruited .
One week before and three months after DBS treatment, the
patients were subjected to associated scores, including the third part
of unified Parkinsons disease rating scale (UPDRS-III), non-motor
symptoms of Parkinsons disease Scale (NMSS), Hamilton Anxiety,
depression Scale (HAMA, HAMD), Mini-Mental state Examination
(MMSE), and the Pittsburgh sleep Quality Index scale (PQSI). Com-
parative analysis of difference on each scale score of patients before
and after DBS treatment was conducted by T test. 10 cases of PD
patients in the control group were scored only by NMSS. Each item
score was obtained by disease severity score (0 to 3 points) multiply-
ing the frequency (1 to 4 points). In order to study the incidence of
non-motor symptoms, each non-motor symptom was classified as
yes or no, calculating the frequency of each item in DBS group
and the control group .Non-motor symptoms scores were compared
by paired design signed-rank test (Wilcoxon signed rank test) for the
two groups patients.
Results: 1) We can see lower scores after DBS treatment with
UPDRS-III, HAMA, HAMD, PQSI score, the scores before and after
treatment were with significant difference.
2) The total scores difference of non-motor symptoms of each
patient between DBS and control groups were statistically significant
(p 5 0.032), but the difference in the number of non-motor symptoms
appeared no statistically significant (p 5 0.162); Of the non-motor
symptoms between DBS and the control group,the frequency with
statistically significant differences were sleep disorder,depression,and
sweating,The scores with statistically significant differences were
sleep disorders, constipation and sweating.
Conclusions: Deep brain stimulation can not only improve motor
function in Parkinsons patients, but also plays a role in improving
the non-motor symptoms.
586
Short-term follow-up of bilateral subthalamic nucleus DBS in
advanced PD: Gait and balance outcomes
 Marta, R. Ignacio
V. Marta, A.O. Iciar, C. Lidia, S.M. Arantza, D.A.
(Madrid, Spain)
Objective: To assess short-term effects of bilateral deep brain
stimulation (DBS) of the subthalamic nucleus (STN) in patients with
advanced Parkinsons disease (PD).
Background: STN-DBS represents a well-established treatment
of the motor symptoms of PD; however, few studies have reported
gait and balance outcomes. To date the impact of STN-DBS on gait
and balance is less clear and remains a matter of debate.
Methods: A total of 26 PD patients (male/female 15/11, mean
age/disease duration at surgery 6SD 60.58 6 8.58/11 6 3,16 y)
treated with bilateral STNDBS were included in the present study.
Patients were assessed baseline and 3-6 months after surgery.
Evaluation of gait was performed using STEP 32 (a computerized
movement analysis system that records podobasographic, electrogo-
niometric and electromyographic signals) in ON medication condi-
tion. Balance and Postural Instability were assessed using Tinetti-
test.
Results: The table(1) summarizes the results.
Conclusions: Our results suggest that STN DBS has a relatively
large impact on axial symptoms. These data provide further support
 POSTER SESSION S229

Gait analysis parameters baseline and post-DBS

Baseline 3-6month P value

(Heel strike, foot, push off and 0.67(0.3;0.4) 0.71(0.6;0.7) 0.041
swing-(HFPS) cycles)
Number of steps 119.5(93;228) 99.5(86;120) 0.001
Foot contact (left) 49.2(38.7;54.7) 41.8(36.6;46.9) 0.02
Foot contact (right) 47.45(38.3;55.5) 41.35(38.5;44.5) 0.006
Tinetti-test 17(14-24) 25(24-27) 0.004
Data are reported as median (25th;75th percentiles).

for the potential role and future study of STN DBS effect on gait
and balance.
587
Postoperative apathy can neutralize benefits in quality of life
after subthalamic stimulation for Parkinsons disease
R. Martinez-Fernandez, P. Pelissier, J.L. Quesada, H. Klinger, E.
Lhomm ee, E. Schmitt, V. Fraix, S. Chabardes, P. Mertens, A. Cas-
trioto, A. Kistner, E. Broussolle, P. Pollak, S. Thobois, P. Krack
(Grenoble, France)
Objective: To elucidate whether the development of apathy after
bilateral subthalamic nucleus deep brain stimulation (STN-DBS) in
Parkinsons disease (PD) impacts negatively on patients health-
related quality of life (HRQoL) outcome independently of motor
improvement.
Background: STN-DBS for PD has shown to improve both
motor symptoms and HRQoL. However, despite motor improvement
patients do not always report amelioration in their well-being. There-
fore, other features, and particularly neuropsychiatric symptoms
known to have a high impact on HRQoL in the general PD popula-
tion, may be impacting surgical outcome.
Methods: From a cohort of 102 PD patients who underwent
STN-DBS 88 with complete data were selected for analysis. Patients
were divided into two groups, those who were apathetic at one year
and those who were not as measured with the Starkstein apathy
scale. HRQoL was assessed using the PDQ-39 scale and was com-
pared between the two groups. Motor outcome was assessed using

Fig. 1. (587). Fig. 2. (587).

Movement Disorders, Vol. 30, Suppl. 1, 2015

S230 POSTER SESSION
the UPDRS. Depression and anxiety were measured using the Beck
depression scale and the Beck anxiety inventory.
Results: One year after surgery, 27.1% of patients suffered from
apathy. While motor improvement was significant and equivalent in
both apathy (-40.4% of UPDRS motor score off medication) and
non-apathy groups (-48.6%), PDQ-39 score did not improve in the
apathy group (-5.5%;p=0.464) whereas it improved significantly (-
36,7%;p0.001) in the non-apathy group [figure1]. Change in apathy
scores correlated significantly with change in quality of life scores
(rho=0.278,p=0.009). In the non-apathy group five PDQ-39 dimen-
sions improved significantly from preoperative condition (mobility,
activities of daily living, stigma, cognition, and bodily discomfort).
In the apathy group, stigma was the only dimension which improved
significantly compared to baseline. Depression and anxiety scores
remained unchanged from baseline in the apathy group
(p50.409,p=0.075), while they improved significantly in non-
apathetic patients (p50.006,p0.001).[figure2]
Conclusions: Our results show that occurrence of post-operative
apathy in PD patients who have undergone STN-DBS can independ-
ently counteract the beneficial effect of motor improvement in terms
of HRQoL. In addition, apathy represents the tip of the iceberg of a
whole array of hypodopaminergic neurobehavioral symptoms includ-
ing depression and anxiety, which can also negatively impact
HRQoL.
588
Intraoperative objective assessment and quantification of rigidity,
akinesia, and tremor for optimized target-selection during DBS-
implantation in Parkinsons disease
J.H. Mehrkens, J.A. Coy, B. Kai, L. Tim (Munich, Germany)
Objective: To develop and evaluate a device for objective intra-
operative movement-measurement during DBS-implantation in Par-
kinsons disease (PD).
Background: Although the subthalamic nucleus (STN) as target
for DBS is well established, hitting the right target within the
target, still remains a challenge. The decision, where to finally
implant the electrode is usually not taken based on objective
movement-data, but on expert observations (including microrecord-
ings (MER)). Objective intra-operative quantification of PD-
symptoms during test-stimulation should increase the effectiveness of
DBS.
Methods: To prove our assumption, we started by developing a
novel measurement-device for the intraoperative evaluation of PD-
symptoms. Research was performed both in the lab (including
healthy subjects and PD-patients) and later in the OR during numer-
ous DBS-procedures. Intraoperatively, rigidity, akinesia and tremor
were evaluated by the standard manual and optical assessment as
well as with a combination of force and inertial sensors (fixed to the
patients wrist and index finger). The force needed to bend the elbow
as well as acceleration and angular viscosity of the wrist and the
index finger were recorded and processed by a customized software.
Results: We were able to develop and produce prototypes (reus-
able) of the measurement device we aimed for. The systems meet
the technical requirements of the European Union (EU) for medical
devices and are ready to be used in the OR. A prototype consists of
two force sensors and one inertial sensors fixed to wrist, one inertial
sensor fixed to the index-finger and a computational unit for the data
processing. During a first test-series, several data-sets were recorded
and analysed. Different algorithms were tested and optimized to
transform the raw data into easy to interpret quantified results to surgery were losses to follow-up after recommendation for surgery
enable objective intraoperative judgement of teststimulation-results.
Conclusions: It is possible to record and objectively quantify
movement-data in a reliable way during DBS-surgery. Integration of
this data into the MER-software will be the next step. Our results are
very promising and encourage further evaluation. Especially the clin-
ical outcome of DBS-implantations performed with the measurement
Movement Disorders, Vol. 30, Suppl. 1, 2015
device compared to the current standard procedure needs to be
studied in a larger cohort.
589
Neurologists or patients choice: Reasons Parkinsons disease
(PD) patients do not undergo deep brain stimulation (DBS)
surgery
N.F. Mercan, S.I. Gul, A. Savas, C.M. Akbostanci (Ankara, Turkey)
Objective: To determine the reasons why PD patients do not
undergo STN DBS surgery.
Background: DBS is an effective treatment for patients suffering
from PD with a good response to levodopa but with medication-
refractory motor complications or patients who are intolerant to anti-
Parkinsons drugs. Since DBS is an invasive, elective and relatively
expensive surgery, the decision to undergo DBS surgery is made
both by neurologists as well as the patients themselves. We analyzed
the reasons why PD patients did not undergo DBS surgery.
Methods: The medical data of all PD patients referred to our
Movement Disorders clinic for an evaluation to determine their suit-
ability for STN DBS treatment from 2008 through 2014 were retro-
spectively reviewed. The age, gender, education, disease duration
and the reasons for not undergoing surgery were determined. To
determine the reasons why Parkinsons disease patients do not
undergo STN DBS surgery.
Results: Of the 248 patients evaluated, 155 (62.5%) did not
undergo STN DBS surgery. 59 (38%) of the 155 patients were
women. Mean age of patients was 54 years (SD 10,2), mean disease
duration was 9 years (SD 5.9). 65 (41,9%) of them became lost to
follow-up after recommendation for surgery. 33 (21.3%) of them
excluded by neurologist due to having a good response after switch-
ing to optimum medical treatment and 14 (9%) due to neurological
contraindications like dementia. 27 (17. 4%) of them did not prefer
to have surgery. 15 (9.7%) of patients could not have treatment
because of financial issues.
The frequency of the reasons why Parkinsons disease patients
did not undergo deep brain stimulation surgery.
Number of the
Reason patients (n:155)
Lost to follow up 65 (41,9%)
Good response 33 (21,3%)
to medical treatment
Patient did not prefer to 27 (17,4%)
have surgery
Poor financial condition 15 (9,7%)
luded due to dementia 8 (5,2%)
Excluded due to having 3 (1,9%)
difficulty in walking as a
chief complaint
Excluded due to poor 2 (1,3%)
response to levodopa
Excluded due to non realistic 1 (0,6)
expectations
Conclusions: The most common reason patients did not undergo
and preferring not to have DBS. Spending more time with patients to
give detailed information for the procedure, the effects and risks of
DBS treatment has a critical role to understand the reasons for and
outcomes of patients lost to follow-up and patients not preferring
surgical option, and to guide more patients who can benefit from sur-
gery in this manner.
 POSTER SESSION
590
Bilateral subthalamic nucleus deep brain stimulation in elderly
patients with Parkinsons disease
K.T. Mitchell, S.A. Norris, S.D. Tabbal, J.L. Dowling, K.M. Rich,
J.S. Perlmutter, M. Ushe (St. Louis, MO, USA)
Objective: To evaluate the efficacy and safety of bilateral subtha-
lamic nucleus deep brain stimulation (STN DBS) for the motor
symptoms of idiopathic Parkinsons disease (PD) in patients 75 years
and older, and to compare the risks and benefits to a younger cohort.
Background: STN DBS is an effective treatment for moderate to
advanced PD. Clinical studies have shown improvement of motor func-
tion and quality of life but often exclude patients older than 75 years.
Methods: Ninety-one patients (46 < 75 years old, 45  75 years
old) with STN DBS were retrospectively analyzed. The primary out-
come measures were changes in unified Parkinsons disease rating scale
subscales III and IV (UPDRS III and IV) at 6 months and 1 year after
surgery compared to presurgical evaluation in an intention to treat
model with the last evaluation carried forward. Secondary outcome
measures were changes in UPDRS subscales I and II. DBS and surgery
related complications and survival were evaluated in both groups.
Results: Twenty-three patients were censored due to inadequate
follow up but were included in the adverse events analysis. In the
older cohort, STN DBS improved UPDRS III at 6 months
(mean6SD) (38.7%621.8%, p<0.001) and 1 year (36.7%628.2%,
p<0.001) as well as UDPRS IV at 6 months (-1.2 6 1.9 points, 19
improved, 4 worsened, p<0.001) and 1 year (-1.3 6 1.7 points, 19
improved, 3 worsened, p<0.001). The older cohort had worse UPDRS
I at 1 year (1.3 6 2.2, 19 worsened, 5 improved, p<0.005) and no
change in UPDRS II. Primary or secondary outcomes did not differ
between the younger and older cohorts. Two patients in the younger
cohort and four patients in the older cohort died prior to 1 year follow
up. Only one patient died as a direct result of DBS surgery. The
groups had a similar number of device infections (2/46 and 1/45) and
lead malfunctions (1/46 and 2/45). One patient suffered a fatal postop-
erative intraparenchymal hemorrhage, and one other patient was found
to have a small intraventricular hemorrhage, both in the older cohort.
Conclusions: Bilateral STN DBS provides similar motor benefit
and reduction in dyskinesia in younger and older patients. Although
all-cause mortality at 1 year was higher in the older cohort, only one
individual had a symptomatic hemorrhage. DBS remains effective
regardless of age.
591
Beta-band activity changes during sleep in the subthalamic
nucleus of patients with Parkinsons disease
L. Mueller, A. Auchter, M.M. Reich, F. Steigerwald, K. Reiners, I.U.
Isaias, J. Volkmann (Wurzburg, Germany)
Objective: We investigate changes in local field potential (LFP)
activity of the subthalamic nucleus (STN) in patients with Parkin-
sons disease (PD) during wakefulness and sleep.
Background: Continuous deep brain stimulation (DBS) in the
STN has shown a remarkable therapeutic effect on motor and non-
motor symptoms in patients with PD. Recent experimental and clini-
cal data suggest that adaptive DBS might be even more beneficial. In
a desired closed-loop setting the determination of the actual con-
sciousness level -from wakefulness to the different sleep stages-
could be performed through analyzing LFP of the STN. To our
knowledge little is known about changes of theses LFP spectra dur-
ing sleep.
Methods: We collected STN-LFP data of three PD patients (all
male, age 54-66 years, disease duration 10-19 years) during one
night of at least 6 hours sleep. LFPs were recorded by means of the
Activa PC1SV R (MedtronicV R Inc., Neuromodulation, Minneapolis,
USA), a new DBS device able to record via the stimulation elec-
trode. Data were acquired, in DBS-off state, every 12 minutes for 45
seconds simultaneously with continuous polysomnography. Power
S231
spectral density of LFP intervals were correlated with the actual
sleep stage according to the American Academy of Sleep Medicine-
classification.
Results: All three PD patients showed significant changes in the
power spectrum distribution during sleep stages. Most interestingly,
we observed a marked reduction of beta-band activity during slow
wave sleep with a greater sensitivity in the low-beta band (15-20
Hz) and an increase of theta- and delta-band activity. In one patient
we were also able to capture multiple rapid-eye-movement phases.
In this case, a recovery of beta-band-activity was observed.
Conclusions: In a closed-loop stimulation setting, the detection
of the oscillation behavior during sleep might be useful to adjust or
simply switch off the stimulation when not needed.
592
Personality and quality of life assessments before and after deep
brain stimulation surgery in patients with Parkinsons disease
M. Newlon, M. OConnor, L. Kapust, C. Pierce, A. Silver, D.K.
Simon, D. Tarsy, E. Papavassiliou, R. Alterman, L.C. Shih (Boston,
MA, USA)
Objective: To identify whether personality assessment can pre-
dict psychiatric complications and change in quality of life after
deep brain stimulation (DBS) surgery in patients with Parkinsons
disease (PD).
Background: Pre-operative neuropsychological assessment is
widely used before DBS surgery, but there is little agreement on
which assessments accurately predict the potential for post-operative
psychiatric complications. Personality assessment in epilepsy surgery
patients have been linked to post-operative outcome, but this type of
analysis has not been performed in PD patients undergoing DBS.
Methods: The Personality Assessment Inventory (PAI) is a self-
administered, validated scale of emotional health and psychiatric sta-
tus. The PDQ-39 is a self-administered, validated scale of function
and well-being for patients with PD. Questionnaires were adminis-
tered before and 4-10 months after DBS surgery to PD patients oper-
ated on between January 2013-June 2014 and to a control group of
PD patients participating in the National Parkinsons Foundation
registry between June-August 2014. Statistical analysis was per-
formed on Stata 11.1. Significance value was set at p50.05 for this
exploratory analysis.
Results: Thirty patients with confirmed PD were included in the
analysis, 21 who underwent DBS surgery and 9 controls not being
considered for DBS. Mean (SE) age and disease duration in the DBS
group was 63.2(2.6) and 10.5(1.1) years vs. 64.0(3.4) and 6.6(1.5)
years in the control group. On medication mean Hoehn and Yahr
stage was 2.5(0.1) and 2.5(0.2), respectively. Pre-operative PAI
Somatic Complaints-Health Concerns scores were significantly ele-
vated in the DBS group. Affective Instability PAI subscale was sig-
nificantly higher in the DBS group vs. controls. PDQ-Activities of
Daily Living significantly improved for the DBS group. Several pre-
operative PAI domains correlated with changes in PDQ subscales but
not total score.
Conclusions: Pre-operatively, patients undergoing DBS reported
higher levels of somatic complaints, health concerns, and affective
instability compared to the control group. Possible reasons include
longer disease duration, more severe motor impairment, or non-
motor symptom burden. Further studies with larger sample sizes are
needed to determine the relationship between personality factors and
quality of life outcomes following DBS surgery.
593
Susceptibility weighted magnetic resonance imaging for targeting
of the subthalamic nucleus in Parkinsons disease
R.C. Nickl, S. Johannes, F. Steigerwald, M.M. Reich, S. R
uckriegel,
T. Gunthner-Lengsfeld, R.I. Ernestus, V. Sturm, J. Volkmann, C.
Matthies (Wurzburg, Germany)
Movement Disorders, Vol. 30, Suppl. 1, 2015
S232 POSTER SESSION
Objective: To compare the subthalamic nucleus (STN) extensions
visualized by two magnetic resonance imaging (MRI) modalities,
classic T2-turbo-spin-echo (T2-tse) and iron sensitive susceptibility
weighted imaging (SWI), to the STN boundaries identified by intra-
operative microelectrode recordings (MER) in patients with Parkin-
sons disease (PD).
Background: DBS of the STN is a well-established treatment for
motor complications in PD. The dorsolateral aspect of the subthala-
mic nucleus is considered the optimal site of electrode implantation
and can be identified by the T2 hypo-intense ovoid outline of the
STN on axial and coronal MRI slices in close vicinity to the substan-
tia nigra (SN). SWI sequences are exquisitely sensitive to iron stor-
age in STN and SN and are currently discussed as an alternative
imaging modality.
Methods: 13 patients with PD underwent pre-operative MRI in
general anesthesia. The target and trajectory planning was carried
out in the Surgiplan Stereotactic Planning Program, including T2-tse
and SWI (TE of 20ms) and fusion to a stereotactic CT before realiz-
ing DBS of the STN. Two neurosurgeons specialized in stereotactic
neurosurgery measured postoperatively the length of the electrode
trajectory within its course traversing the STN, on SWI and on T2-
tsesequences, while being unaware of the results of MER. The STN-
typical MER signals were investigated independently and analyzed
by a neurologist for the length of their extension along the trajectory.
Results: 13 PD patients (age 49-62 years, 2 females) were inves-
tigated bilaterally resulting in an analysis of 26 STN. The trajectory
path through the STN was significantly longer in SWI ( 4.37mm;
SD 1.25mm) than on T2-tse ( 3.42mm; SD 0.95mm; t=3.941; p
=.001*). The extension of STN typical microelectrode signals was
larger than predicted by T2 signals (t=2.191, p5.038*) whereas the
extensions on SWI images and MER signals were matching closely
(t= .854, p5 .401).
Conclusions: Visualization of the STN via SWI images provides
an excellent contrast of the STN area with clear borders to the sub-
stantia nigra. Here, for the first time we demonstrate a good agree-
ment between SWI-target visualization and functional intra-operative
MER data, which is superior to T2 vizualization of the STN. Cur-
rently SWI images seem a useful supplement in STN targeting,
whose relevance for the functional surgical outcome requires further
investigation.
594
Ipsilateral somatotopy within the subthalamic nucleus
M.J. Nolt, T. Masnyk, M.T. McGraw, A.P. Monette, M. Rezak
(Winfield, IL, USA)
Objective: To demonstrate (1) a correlation between ipsilateral
somatotopy observed during MER and ipsilateral symptomatic bene-
fit obtained from unilateral STN DBS in PD and (2) that a subset of
patients with bilateral somatotopy and benefit argues against simulta-
neous bilateral STN DBS in PD.
Background: Deep brain stimulation (DBS) of the STN has
become the standard of care in treating some cases of medically
refractory PD. The value in performing MER has been well docu-
mented in defining the target in which to place the stimulating elec-
trodes. Classically the STN is identified by recording cellular
responses when passively moving the contralateral extremities of the
patient. Patients often receive bilateral implants.
Methods: MER was performed with an array of 4 electrodes
advanced from 10mm above the base of the STN, with an anterior
approach of 60 and a lateral approach of 15 . At approximately
each millimeter within the STN, the patients arms and legs were
passively moved in an effort to elicit cellular responses. Recordings
and macrostimulation were used to determine lead placement. The
patient returned to the clinic approximately 4 weeks after surgery for
DBS programming.
Results: We observed activation of cells from ipsilateral passive
movement of the shoulder in the lateral and posterior tracks, the
Movement Disorders, Vol. 30, Suppl. 1, 2015
elbow in the anterior track, and the hip in the anterior track. We
observed inhibition of cells from passive movement of the hip in the
anterior track and shoulder in the lateral and anterior tracks. The
anterior track was selected for lead implantation. Fusion of the post-
operative MRI and preoperative CT/MRI shows the tip of the lead to
be at 11.0mm lateral, 4.0mm posterior and 5.0mm inferior to the
midcommisural point. Upon programming DBS for optimal therapeu-
tic response on the contralateral side, the ipsilateral tremor and rigid-
ity also resolved.
Conclusions: 1) This case demonstrates a strong correlation
between ipsilateral somatotopy observed during MER and ipsilateral
symptomatic benefit obtained from unilateral STN DBS in PD.
2) MER in a subset of patients demonstrating bilateral soma-
totopy during unilateral implantation, and ultimately bilateral
symptomatic benefit, may preclude the need for bilateral DBS.
This argues against performing simultaneous STN DBS for PD.
3) Identification of bilateral STN somatotopy during MER can
only occur in an awake patient, providing additional evidence in sup-
port of performing DBS surgery in the awake state.
595
Intraoperative electrocorticography as a tool for the
understanding of Movement Disorders: Principals and
experience in 190 patients
F.E. Panov, E. Levin, C. de Hemptinne, N. Swann, S. Qasim, S.
Miocinovic, J. Ostrem, P.A. Starr (San Francisco, CA, USA)
Objective: To describe the technique, utility, and safety profile of
Electrocorticography (ECoG) in Deep Brain Stimulation (DBS)
Surgery.
Background: Contemporary theories of Movement Disorders
pathophysiology emphasize abnormal oscillatory activity in the basal
ganglia-thalamocortical loop, but have been studied in humans
mainly using depth recordings. Recording form the surface of the
cortex using ECoG provides a much higher amplitude signal than
depth recordings, is less susceptible to DBS artifact, and yields a sur-
rogate measure of population spiking via broadband gamma (50-
200 Hz) activity.We have therefore developed a technical approach
to Movement Disorders surgery that employs intraoperative ECoG as
a research tool.
Methods: 190 patients undergoing DBS for the treatment of
Movement Disorders were studied under an IRB approved protocol.
After a standard drilling of a DBS burhole, a strip electrode
(Adtech, 6 contacts or 28 contacts) was inserted to cover primary
motor or prefrontal cortical areas. Localization was confirmed by
reversal of the somatosensory evoked potential, or by intraoperative
CT/2D fluoroscopy. ECoG potentials were recorded at rest and dur-
ing a variety of tasks, and analyzed off line in the frequency
domain, focusing on activity between 3 and 200 Hz. Strips were
removed prior to closure. Postoperative MRI was inspected for
edema, signal change, or hematoma that could be related to the
placement of the ECoG strip.
Results: 182 (96%) of strips were successfully placed without
any intraoperative or postoperative complications. One ECoG place-
ment was aborted due to resistance during attempted passage of the
electrode. Postoperative complications in patients included 3 infec-
tions, 1 delayed chronic subdural hematoma requiring evacuation, 2
intraparenchymal bleeds, and 1 venous infarction distant form the
site of the recording. None of these appeared directly related to the
use of ECoG.
Conclusions: Intraoperative ECoG has been long used in neuro-
surgery for functional mapping and localization of seizure foci.
Applied during DBS surgery, it is becoming an important research
tool for understanding brain networks in Movement Disorders and
mechanisms of therapeutic stimulation. In experienced hands, the
technique appears to add minimal risk to surgery.
 POSTER SESSION S233

596
The maintenance of motor function with unilateral electrode
dysfunction in Parkinsons disease after bilateral subthalamic
nucleus deep brain stimulation
H. Park, B.S. Jeon, H.J. Kim, W.W. Lee, C.W. Shin (Seoul, Korea)
Objective: To report our findings in seven PD patients with uni-
lateral electrode dysfunction after bilateral STN DBS surgery.
Background: Bilateral subthalamic nucleus (STN) deep brain
stimulation (DBS) is widely used as an effective treatment in
advanced Parkinsons disease (PD) patients with motor complica-
tions. However, there was a report of patients whose one electrode
had to be removed but were in relatively good function with unilat-
eral STN stimulation for some period.
Methods: Of the 227 patients who had bilateral STN DBS surgery
at Movement Disorder Center of Seoul National University Hospital,
seven patients had unilateral electrode removed because of surgical site
Fig. 1. (597).
infections and extension wire breakage. They are being followed up
with our routine evaluation protocol with unilateral STN stimulation.
Results: The mean age at surgery of seven patients was 61 years Objective: 1) To confirm increase of audio-spinal reflex in
old (range 56-71). The mean preoperative disease duration was 11.1 patients with Parkinsons disease (PD), treated by deep brain stimula-
years (range 86-216 months), and follow up after unilateral electrode tion (DBS) of subthalamic nucleus (STN); and 2) evaluate the rela-
removal was 2.9 years (range 17-62 months). When evaluated in the tionship between the effects of DBS on both freezing of gait (FOG)
setting of medication-off/DBS-on, the mean postoperative UPDRS and audio-spinal reflex.
total motor score was reduced by 56% (p50.018), and the UPDRS Background: STN DBS is a surgical option in PD patients with
subscore in the side contralateral to removal was improved by 59% motor fluctuations. However, FOG is not always reduced, but some-
(p50.018), in the ipsilateral side by 66% (p50.017), axial subscore times increased after DBS. On the other hand, audio-spinal reflex
by 39% (p50.028) in the bilateral DBS state as compared to preop- (increase of Soleus H-reflex after acoustic stimulation) is known to
erative scores. After the onset of unilateral STN-DBS system, the be decreased in PD patients, and restored by dopaminergic drugs.
UPDRS total motor score (p50.028), subscores in the side contralat- STN DBS also increases this reflex. STN and basal ganglia have
eral to the electrode failed, ipsilateral (p50.027) and the axial sub- strong connections with brainstem nuclei, such as pedunculopontine
score are maintaining the improvement as compared with nucleus, which might be involved in gait control. Hence, a more
preoperative scores (41%, 32%, 54%, and 27% respectively). LEDD intense audio-spinal reflex after STN DBS might reflect an improve-
change was not different with other DBS control patients. ment in FOG.
Conclusions: This study shows that patients can maintain rela- Methods: We recorded audio-spinal reflex in 14 PD patients who
tively good function after one electrode removal from complications had undergone STN DBS for more than 3 months, keeping their
for some period. Immediate reoperation might not be needed in all usual medications. Each patient was recorded with DBS ON and
the patients with one electrode dysfunction. DBS OFF. Values were expressed in percentage of basal H-reflex.
Audio-spinal reflex usually peaks between 100ms and 150ms after
the acoustic stimulus. We searched the peak latency for each patient.
597 We then performed a paired-sample t-test between conditions ON
Restoration of audio-spinal reflex reflects gait improvement in and OFF. We also calculated the difference between peak values in
patients with subthalamic nucleus stimulation ON and OFF conditions for each subject (named DBS effect). We
also applied the UPDRS III with DBS ON and OFF. We also admin-
E. Parmentier, V. De Pasqua, G. Garraux, A. Maertens de
istered the FOG questionnaire (FOGQ, Giladi et al., 2000) to all
Noordhout (Seraing, Belgium)

Audio-spinal reflex, UPDRS and FOGQ values

Audio-spinal Audio-spinal Audio-spinal reflex UPDRS UPDRS

Subject Age reflex ON reflex OFF ON-OFF III ON III OFF FOGQ
1 63 128.48 104.93 23.55 26 38 2
2 63 149.45 118.66 30.79 27 50 7
3 51 144.48 198.86 -54.38 30 75 14
4 60 150.02 113.63 36.39 23 54 4
5 64 92.63 106.94 -14.31 17 29 10
6 73 115.62 105.37 10.25 31 57 12
7 56 173.99 140.64 33.35 11 38 4
8 64 151.98 133.16 18.82 12 24 7
9 57 191.38 108.89 82.49 10 27 5
10 63 159.17 91.48 67.69 33 64 9
11 49 135.56 133.16 2.4 26 60 5
12 53 160.77 112.38 48.39 42 64 6
13 51 105.96 130.52 -24.56 3 13 11
14 52 145.49 114.99 30.50 26 58 2
Values of audio-spinal reflex are given in percentage of the basal value of subjects H-reflex

Movement Disorders, Vol. 30, Suppl. 1, 2015

S234 POSTER SESSION
Fig. 2. (597).
patients. We calculated correlations between DBS effect, UPDRS
and FOGQ.
Results: A summary of results is presented below.
Audio-spinal reflex peak was significantly higher in DBS ON
condition than in DBS OFF condition (143.21% vs 122.40%;
p<0.05).[figure1] We did not find a correlation between changes in
UPDRS III score and DBS effect on audio-spinal reflex, maybe
because dopaminergic drugs were maintained. An inverse correlation
was found between FOGQ score and DBS effect on audio-spinal
reflex (r=-0.59; p<0.05).[figure2]
Conclusions: Our data confirms the effect of STN DBS on
audio-spinal reflex. We could also show a link between the increase
of audio-spinal reflex after DBS and a better score on the FOGQ.
Audio-spinal reflex might reflect function of structures implied in
gait control, and hence could be used to evaluate therapies aimed at
improving gait.
598
Hemorrhage risk associated with multiple simultaneous
microelectrode recording for deep brain stimulation
F.T. Phibbs, A. Wang, C. Tolleson, J.L. Stroh, J. Neimat, P. Konrad
(Nashville, TN, USA)
Objective: To determine the risk of intracerebral hemorrhage
associated with multiple simultaneous microelectrode recording
(MER) for DBS.
Background: Intracerebral hemorrhage can be a devastating com-
plication of DBS. There have been conflicting reports of hemorrhage
risk associated with MER, with the Parkinsons disease Study group
reported an increased risk with a higher number of single electrode
passes (1) while other studies have not found a correlation (2). Past
studies have evaluated hemorrhage risk in multiple single pass MER.
Since 2002, Vanderbilt has been performing multiple simultaneous
MER with up to 5 tracts unilaterally as standard of care (Ben-gun)
without an observed excessive hemorrhage rate.
Methods: A retrospective chart review was performed of
implanted DBSpatients from July 1995 thru June of 2011 at our
institution using primarily multiple simultaneous MER. A subset of
these patients had the number of simultaneous electrode passes
Movement Disorders, Vol. 30, Suppl. 1, 2015
recorded. A CT scan is obtained immediately post operatively and at
1 month post implantation.
Results: In total, 447 patients (823 leads) had surgery during
these dates. There were 23 intracerebral hemorrhages, 8 were symp-
tomatic (1.7%). Prior to 2002, the year the Ben-gun was used exclu-
sively there were 45 patients(69 leads) implanted. There were 5 ICH,
2 were symptomatic (2.9%). After 2002, there were 402 patients
with 19 ICH, 7 of which were symptomatic (0.9%). Of the subset
with the number of MER passes recorded, there were 151 patients
(1124 MER passes). This resulted in 5 ICH with only 1 being symp-
tomatic 0.08%). The mean number of MER passes for the hemor-
rhage group was 7.8 (all were bilateral cases (SD61.3). The non-
hemorrhage group had a mean number of MER passes of 7.5
(SD62.6).
Conclusions: Our data show that there is not an increased risk
for ICH associated with multiple simultaneous MER passes. Our
hemorrhage rates are well below the published rates of 3% by the
PSG and fall within the symptomatic reported range of 0.5-8.9%.
1. The Deep-Brain Stimulation for Parkinsons disease Study
Group. Deep-Brain Stimulation of the Subthalamic Nucleus or the
Pars Interna of the Globus Pallidus in Parkinsons disease. N Engl J
Med 345: 956-963, 2001.
2. Sansur CA, Frysinger RC, Pouratain N, Fu KM, Bittl M,
Oskouian RJ et al. Incidence of symptomatic hemorrhage after stero-
tatic electrode placement. J Neurosurg 2007; 107(50:998-1003.
599
Stuttering after deep brain stimulation in Parkinsons disease: A
case series
M. Picillo, G.B. Vincos, F. Sammartino, R.P. Munhoz, A. Fasano
(Toronto, Canada)
Objective: In this retrospective chart review we collected the
clinical features of a cohort of Parkinsons disease (PD) patients pre-
senting with stuttering before or after Deep Brain Stimulation (DBS)
of either the subthalamic nucleus (STN) or globus pallidus pars
interna (GPi).
Background: Stuttering is a speech disorder with disruption of
verbal fluency which is occasionally present in patients with PD. The
possible impact of DBS for PD on coincident stuttering is unclear,
 POSTER SESSION
although both worsening and improvement of stuttering following
STN DBS have been described.[1,2] Fewer data are available for GPi.
Methods: Four hundred and fifty-three charts of PD patients who
underwent DBS were reviewed. A group of PD patients with no stut-
tering after DBS (PD-NS) matched for gender, disease duration, dis-
ease severity (H&Y) and target was selected to compare the
demographic and clinical features by means of independent samples
t-test.
Results: Sixteen patients were found to have stuttering after DBS
(PD-S). Among the PD-S, 10 underwent bilateral STN DBS, 4 bilat-
eral GPi DBS and 2 right STN DBS. Four out of 16 patients already
presented stuttering before DBS: three of them reported a worsening
and one improvement of the stuttering after DBS. Other 3 patients
did not show stuttering during the adulthood, but have presented
transient stuttering during childhood with subsequent remission.The
other 9 patients had no history of stuttering, but 6 of them presented
a positive family history (2 with first degrees and 4 with second
degrees relatives affected). Among the PD-NS, none reported nei-
ther a personal or familial history of stuttering. PD-S presented
higher pre-operative motor scores under levodopa as compared to
PD-NS (p50.004). At 9-month post-operative follow-up, PD-S pre-
sented higher motor scores during treatment with both DBS and lev-
odopa, as compared to PD-NS (p50.032). No other differences in
either pre- or post-operative data were noticed.
Conclusions: This is the largest series of PD patients with stutter-
ing after DBS. Our data show that PD-S may often present with a
positive personal or familial history of stuttering. The majority of
patients presented with worsening or relapsing of pre-surgical stutter-
ing, while only one patient had an improvement after DBS. In our
study, PD-S presented higher motor scores in ON state.
References:
1) Burghaus L, et al. J Neural Transm 2006.
2) Thiriez C, et al. Parkinsonism Relat Disord 2013.
600
Deep brain stimulation (DBS) in Parkinsons disease (PD):
Single-center experience from 2000 to 2013
N.G. Pozzi, B. Minafra, R. Zangaglia, D. Servello, C. Pscchetti
(Pavia, Italy)
Objective: To review our experience to identify differences in
short- and long-term outcomes in order to find clinical predictors and
management strategies able to improve good clinical outcome and
reduce side effects development.
Background: Deep brain stimulation (DBS) in different basal
ganglia targets has been well established as a therapy for advanced
Parkinsons disease. The technique has been refined throughout the
years by improved imaging techniques, advanced neurophysiological
recording possibilities, and advances in hardware and software
technology.
Methods: 200 PD patients treated with DBS from 2000 to 2013
were retrospectively evaluated. The cohort was divided in three time-
slots: Ts1 (from 200 to 2005), Ts2 (from 2005 to 2010) and Ts3
(from 2010 to 2013). Patients were divided in two groups: Idiopathic
Parkinsons disease (161) and Early Parkinsons disease (39). Clini-
cal variables of the two groups were matched with the timeslot to
detect differences in clinical outcome and in side effect
development.
Results: The target of choice was STN for 174 patients, GPi for
17 patients, and STN1GPi for 9 patients. 74% of the patients are
still followed in our clinic, 26% were lost at follow up (LFU) after
at least 3 years. Age at surgery and the disease duration changed
during the timeslots: with an anticipation of DBS and more possibil-
ity in the elderly during years.
Conclusions: The preliminary analyses from our court show that
the study group is reliable and the evaluations within- and between-
groups and timeslots may help to define better clinical management
strategy.
S235
601
Impact of bilateral subthalamic nuclei deep brain stimulation on
gait in idiopathic Parkinsons disease patients
A.K. Puligopu, R.M. Kandadai, V.V.P. Kagita, J. Afshan, M.A.
Kanikannan, R. Borgohain (Hyderabad, India)
Objective: To assess change in gait in a cohort of patients with
idiopathic Parkinsons disease after bilateral subthalamic stimulation
from a tertiary care hospital in India.
Background: Gait disturbances and postural instability are main
reasons for morbidity in Parkinsons patients. The role of bilateral
subthalamic nuclei deep brain stimulation (STN-DBS) on gait is not
clear.
Methods: Consecutive patients with idiopathic Parkinsons dis-
ease (disease duration of minimum 5 years, good response to levo-
dopa, minimum UPDRS-III score of 30 points during off phase and
those who had motor complications that could not be controlled with
pharmacological therapy as per the CAPSIT protocol) who under-
went STN DBS were included in the study. Patients were evaluated
twice in the month before surgery and at least 12 months after sur-
gery with the use of the modified UPDRS part 1-4.
Results: Sixty patients (males-37, females-23) underwent surgery
with bilateral microelectrode implantation in the subthalamic
nucleus. Mean age was 56.4 610.1 years. Mean disease duration
was 10.6 6 4.4 years. Post surgery average levodopa equivalent dose
decreased from 855 6 367mg/per day to 494 6 260mg (p < 0.01) at
one yr. On period improved from 6.7 6 2.2 to 16.1 6 2.4 hrs/day at
one yr follow up (p value < 0.01). Overall UPDRS-III scores in on
and off state improved significantly from 55.4 6 14.1 and 16.5 6 8.7
to 32.2 6 12.5 (42%) and 11.9 6 6.2 (31%) respectively at one yr fol-
low up. Gait and postural stability subscores remained similar in on
state but improved significantly in off state at one year follow up
(2.5 1 0.9 and 2.3 1 1.0 to 1.5 1 0.9(p<0.0001) and 1.9 1 0.9
(p<0.0001) respectively). Freezing episodes reduced significantly in
both on and off states at one year follow up (0.7 1 0.9 and 2.2 1 1.2
to 0.3 1 0.5(p50.012) and 1.2 1 0.9(p<0.0001) respectively). The
impact of change in rate of STN stimulation was studied in a subset.
Frequency modulation with lower rates (80-100 hz) seem to reduce
festination while higher frequencies (160-200Hz) show a slight
improvement in freezing.
Conclusions: Deep brain stimulation of bilateral subthalamic
nuclei improve gait and postural instability markedly in off state
while freezing episodes were reduced both in off and on states. Fre-
quency modulation may further help in stabilizing gait.
602
Does the use of intraoperative microelectrode recording influence
the final location of lead implant in the globus pallidus interna
for deep brain stimulation?
S. Reddy, A.J. Fenoy, E. Furr-Stimming, W.G. Ondo, M.C. Schiess,
R. Mehanna (Houston, TX, USA)
Objective: To determine if the use of intra-operative microelec-
trode recording (MER) influences the final location of lead implant
in patients undergoing deep brain stimulation (DBS) of the Globus
Pallidus interna, and to assess the incidence of associated
complications.
Background: The usefulness of intraoperative MER in DBS is
debated by some DBS implanting centers, suggesting it increases sur-
gical complications and offers no additional benefit.
Methods: We conducted a retrospective chart review of all
patients who underwent DBS with MER targeting the GPi, at the
University of Texas Health Science Center in Houston from June 1st
2009 to October 1st 2013. Initial coordinates, as determined by pre-
operative MRI, and final coordinates of implant after intraoperative
MER were compared. To assess hemorrhagic and infectious compli-
cations, post operative CT scan of the head and outpatient follow-up
notes for a period of 1 year from the date of surgery were reviewed.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S236 POSTER SESSION

Results: A total of 42 lead implants on 21 patients were

reviewed. 13 patients were diagnosed with Parkinsons disease and 8
with dystonia. The mean age at implantation was 53 years (range 18-
84). The average duration from diagnosis to surgery was 11 years
(range 2-22). A statistically significant difference between the initial
and final coordinates was observed only in the superior-inferior plane
(p<0.05), with a mean difference of 0.85 mm inferiorly.
Two patients developed complications; infection of both leads
that required lead removal in one non-diabetic patient (4.8%) and the
other had a possible autoimmune reaction surrounding one lead
(2.4%), which was controlled with steroids. One non-hypertensive
patient (4.8%) had minimal asymptomatic sub-arachnoid bleed on
postoperative CT scan. No symptomatic intracranial hemorrhages
occurred with the 42 lead implants. None of the patients required
revision for lack of benefits or uncontrollable side effects from
stimulation. Fig. 1. (604).
Conclusions: In our DBS center, intra-operative MER signifi-
cantly modified final lead location when targeting GPi and was not
associated with increased surgical complications.
Objective: To transform the PDQ-39 scores from EARLYSTIM
603 to EQ-5D utility scores to support cost-utility analyses and to inform
resource allocation decision-making in the UK and France.
Unilateral STN DBS treats bilateral OFF dystonia in PD Background: A generic, preference-based quality of life (qol)
M. Rezak, A.P. Monette, M.T. McGraw, T. Masnyk, M.J. Nolt measure (utility measure) is the preferred health outcome in cost-
(Winfield, IL, USA) utility analyses informing payers making resource allocation deci-
sions. The EQ-5D is the most recommended utility measure in
Objective: To highlight a subset of PD patients that may obtain Europe. While the EQ-5D has shown to be a sensitive measure in
dramatic bilateral benefit from unilateral STN DBS. PD, studies reporting EQ-5D in patients on Deep Brain Stimulation
Background: Most PD patients with bilateral symptoms receive (DBS) therapy are limited to advanced PD populations. The EAR-
bilateral DBS implantation performed in either a staged or simultane- LYSTIM RCT demonstrated improvements in disease-specific qol
ous procedure. In this report we describe two cases in which unilat- with DBS & best medical treatment (BMT) compared to BMT in PD
eral STN DBS resulted in dramatic and sustained bilateral patients with early motor complications using the PDQ-39 [Schuep-
improvement in symptoms. Patient 1 was a 45 year old female with bach 2013].
a 5 year history of PD. Her major complaint was severe painful OFF Methods: A published mapping algorithm [Young 2013] was
dystonia involving her neck, right greater than left foot and leg, and applied on EARLYSTIM data to transform PDQ-39 scores to EQ-5D
an internal tremor bilaterally. Patient 2 was a 59 year old female utility. The mapping involved converting the eight PDQ-39 domain
with a 10 year history of PD. She had predominantly right sided scores into five EQ-5D domain scores. The 5 domain scores were
painful OFF dystonia and chorea. At the time of left STN DBS then converted to one EQ-5D score, using country-specific EQ-5D
implantation OFF dystonia was noted on left to a lesser degree. Both reference values for both France and the UK (reflecting how the gen-
patients exhibited excellent motor function when in the ON state. eral population values the EQ-5D health states). Individual patient
Methods: Anatomical coordinates of the STN were accomplished PDQ-39 data from all EARLYSTIM patients at baseline, and at
via merging the preoperative 3T MRI with a CT scan on the day of months 5, 12 and 24 were used for this analysis.
surgery. MER was then performed with an array of 4 electrodes Results: The EQ-5D values mapped from the EARLYSTIM
advanced from 10mm above the base of the STN. At approximately PDQ-39 results are presented in the figures below for the UK and
each millimeter within the STN, the patients arms and legs were France. For both countries, EQ-5D was improved for DBS & BMT
passively moved in an effort to elicit cellular responses. Recordings compared to BMT, mirroring the improvements in PDQ-39 for DBS
and macrostimulation were used to determine lead placement. Both observed in the EARLYSTIM study. The within-treatment difference
patients returned to the clinic approximately 4 weeks after surgery from baseline to 2 years was 0.01 and 0.04 for BMT, and 0.11 and
for initial DBS programming. 0.19 for DBS & BMT, for UK and France, respectively. Differences
Results: The two PD patients described herein manifested severe,
disabling, and painful OFF dystonia and dyskinesias as well as a nar-
row therapeutic window. Both patients were implanted unilaterally.
In both cases, initial programming resulted in bilateral resolution of
symptoms, persisting for 4 years in patient 1 and 1 year in patient 2.
Conclusions: 1) Bilateral benefit from STN DBS can occur in a
subset of PD patients.
2) The PD patients presented here share the characteristics of
severe, painful OFF dystonia and dyskinesias with excellent motor
function when ON.
3) The possibility of bilateral benefit from unilateral implantation
argues against performing simultaneous STN DBS in PD.

604
Quality of life of patients with Parkinsons disease: Development
of utility values by mapping PDQ-39 to EQ-5D using data from
the EARLYSTIM study
C. Rinciog, S. Walleser Autiero, I. Durand Zaleski, L. Timmermann,
J.L. Hueto, M. Schupbach (Herts, United Kingdom) Fig. 2. (604).

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
at 2 years between DBS & BMT and BMT were 0.10 for the UK,
and 0.14 for France.
(figure 1)
(figure 2)
Conclusions: This analysis is the first to generate utility values
from EQ-5D for PD patients with early motor complications under-
going DBS over 24 months, using data from the EARLYSTIM study.
Data for Germany and France were used to generate values for both
the UK and France, which is a limitation of the analysis. Nevertheless,
these values will be useful for DBS cost-utility analysis in this popula-
tion to support clinical guidelines and resource allocation decisions.
605
Comparison of therapeutic and adverse effects of pallidal and
subthalamic deep brain stimulation in Parkinsons disease
H.S. Ryu, J. Kim, Y.J. Kim, K. Kim, M.S. Kim, S. You, M.J. Kim, S.J.
Chung (Seoul, Korea)
Objective: To compare the therapeutic and adverse effects of the
globus pallidus interna (GPi) and subthalamic nucleus (STN) deep
brain stimulation (DBS) for the treatment of advanced patients with
Parkinsons disease (PD).
Background: DBS of both the GPi and STN has been shown to
be effective in the treatment of the cardinal motor signs of PD. How-
ever, it is still unclear whether there are definite advantages or disad-
vantages in selecting optimal target for DBS in PD patients.
Methods: We retrospectively analyzed the clinical data of PD
patients (N=16) who underwent bilateral GPi DBS and PD patients
(N=32) who underwent STN DBS. Study subjects were matched for age
at DBS operation and disease duration, and were selected by random
assignment of receiving either GPi vs STN DBS using a computer-
generated randomization sequence. The original Unified Parkinsons dis-
ease Rating Scale (UPDRS) scores at baseline and 12 months after DBS
operation were used to assess therapeutic effects of DBS.
Results: The age at DBS operation was 58.4 6 7.9 years for
patients undergoing GPi DBS (mean PD duration of 11.6 6 3.6
years) and 57.8 6 7.7 years for those undergoing STN DBS (mean
PD duration of 11.5 6 3.4 years). At 12 months, mean changes in the
UPDRS total, part III, and part IV scores did not differ significantly
between the two groups (P 5 0.43, P 5 0.17, and P 5 0.10, respec-
tively). However, dyskinesia sub-scores improved more after GPi
DBS than after STN DBS (P 5 0.01). Serious adverse events, includ-
ing intracranial hemorrhage, did not differ significantly between the
two groups (P 5 0.48).
Conclusions: PD patients undergoing GPi DBS showed more
improvement in levodopa-induced dyskinesia than those undergoing
STN DBS, although other UPDRS sub-scores and the occurrence of
adverse effects did not differ between the two groups.
606
Early subthalamic neurostimulation improves quality of life of
elderly patients with Parkinsons disease
H. Salimi Dafsari, P. Reker, P. Reddy, M. Silverdale, M. Pilleri, P.
Martinez-Martin, A. Rizos, K. Ashkan, M. Samuel, J. Evans, V.
Visser-Vandewalle, A. Antonini, K.R. Chaudhuri, L. Timmermann,
On Behalf of EUROPAR and the IPMDS Non Motor PD Study
Group (Cologne, Germany)
Objective: To study the effects of bilateral subthalamic nucleus
(STN) deep brain stimulation (DBS) in patients with advanced age
but short duration of Parkinsons disease (PD).
Background: STN-DBS is a well-established treatment option for
patients with PD improving motor symptoms and quality of life
(QoL). Since the EARLYSTIM trial, the expansion of the traditional
indication for DBS by intervention at earlier stages of PD has re-
emerged as a major topic of debate. In EARLYSTIM, patients aged
60 years were included (mean age 52.9 years). However, due to an
S237
increasing prevalence with advancing age, elderly patients form a
relevant part of the PD population.
Methods: We performed a post-hoc analysis of prospective
patient data recorded as part of clinical trials or clinical routine in
four centers (Cologne, London, Manchester, Venice). Subjects aged
61 years with a disease duration of 8 years at intervention were
included. Motor function, QoL (as measured by the PDQ8), and lev-
odopa equivalent daily doses (LEDD) were compared between base-
line and follow-up 3 to 6 months after surgery. Heterogeneous rating
instruments (UPDRS, MDS-UPDRS, SCOPA) were harmonized by
comparing percentages of the maximum scores. Employing the Wil-
coxon test and two-sided t-test when parametric criteria were ful-
filled, the Bonferroni method was used to correct for type I errors.
Cohens effect sizes (ES) were calculated for each outcome.
Results: Mean age and disease duration at surgery of the 22 sub-
jects identified were 65.77 (64.22) and 6.14 (61.28) years. Motor
impairment improved by 48% from baseline to follow-up (40.02%
vs. 20.99% of the maximum respective motor score, p<0.001,
ES=0.8), QoL improved by 38% (mean PDQ8-SI 29.55 vs. 18.18,
p50.009, ES=0.52) and LEDD was reduced by 51% (mean
957.67mg vs. 464.65mg, p<0.001, ES=0.81). Significance level was
reached for all outcomes.
Conclusions: The benefit from STN-DBS was well within the
range reported in the literature. Due to the small sample size, differ-
ent motor scores, and short follow-up period, our findings need to be
interpreted with caution. Nevertheless, they are relevant to the debate
about selection criteria for STN-DBS and encourage further studies
for the group of elderly patients with short disease duration, which is
currently underrepresented in the literature but important in daily
clinical decision making.
607
Gait and balance in Parkinsons disease (PD) following bilateral
subthalamic nucleus (STN) and globus pallidus interna (GPi)
stimulation: 36 month follow-up of CSP#468 cohort
A.I. Sarwar, K. Carlson, P. Luo, K.A. Follett, M. Stern, F.M.
Weaver, D.J. Reda, E.C. Lai, For the CSP 468 Study (Houston, TX,
USA)
Objective: To study the effect of bilateral deep brain stimulation
(DBS) of STN and GPi on gait and balance in patients with PD.
Background: The subject of long-term effects of DBS of STN
and GPi on gait and balance in PD remains in evolution. We ana-
lyzed the results pertaining to changes in gait and balance as meas-
ured by Unified Parkinsons disease Rating Scale (UPDRS)-items 13,
14, 15, 27, 28, 29 and 30 for subjects with 36-month follow-up data
who underwent bilateral STN or GPi DBS as a part of the CSP 468
study cohort.
Methods: The scores for UPDRS items 27, 28, 29, 30 were ana-
lyzed from unblinded assessments at 3, 6, 12, 18, 24 and 36 months
after surgery under 2 different settings: ON medication and ON stim-
ulation; OFF medication and ON stimulation. T-tests were examined
at each time point to detect differences in the mean change from
baseline to various time points. No adjustments were made for multi-
ple comparisons.
Results: 159 patients (STN=70, GPi=89) completed the 36
months follow up. Both groups showed an improvement in sum of
UPRDS items 27, 28, 29, 30 in the ON stimulation/OFF medication
state at all follow up time points. ON stimulation/ON medication,
improvement was seen only at 3, 6 and 12 months. No statistically
significant difference was found between the two surgical targets.
There was a significant improvement in the mean score of freezing
while walking (UPDRS item 14) at 6, 12 and 18 months (p5 0.04,
0.01, 0.01) in favor of STN with the same trend continuing at 24
and 36 months (p 5 0.05) There was no significant difference in sub-
jective reports of falls or walking between the groups. There were no
statistically significant interactions between the surgical target and
Movement Disorders, Vol. 30, Suppl. 1, 2015
S238 POSTER SESSION
certain characteristics including: age, years since diagnosis, years on
medications, baseline Hoehn & Yahr and UPDRS part 1 scores.
Conclusions: Bilateral deep brain stimulation of Subthalamic
nuclei and Globus Pallidus interna improves gait and balance in Par-
kinsons disease. The stimulation effect appears to be sustained to 36
months after surgery. There is no significant difference with respect
to these measures between the two surgical targets, except regarding
freezing of gait which is significantly less reported in the STN group.
No demographic or disease related feature could be identified as a
predictor for improvement in either group.
608
MRI guided focused ultrasound VIM thalamotomy for
Parkinsons disease-First case series
I. Schlesinger, A. Eran, A. Sinai, I. Erikh, M. Nassar, D. Goldsher,
M. Zaaroor (Haifa, Israel)
Objective: To report results of MRI guided focused ultrasound
(MRgFUS) VIM thalamotomy in a case series of patients suffering
from Parkinsons disease (PD).
Background: Thalamotomy has been proven effective for treating
medication resistant tremor in patients with PD. MRgFUS is a new
technology that enables non invasive intracranial focal ablation.
Methods: Five PD patients with severe refractory tremor, age
63.4 6 8.4 years (range, 51 to 74), mean disease duration of
6.0 6 3.1 years (range, 4 to 10) were treated. All patients were right
handed and PD tremor was more prominent on the right side in four.
Unilateral ventral intermediate nucleus thalamotomy was performed
by MRgFUS using ExAblate NeuroV R . Effect on tremor was eval-
uated using the UPDRS scoring and impact on quality of life was
assessed by the Parkinsons disease Questionnaire (PDQ-39).
Results: Tremor stopped in the contralateral upper extremity in
all patients immediately following ablation. UPDRS at baseline was
26 6 11.5 points and decreased to 13.8 6 8.3 points one week after
the sonications (p50.04). PDQ39 decreased from 40.2 6 16.2 to
21.4 6 21.4 (p50.007) at one week. The beneficial effect was sus-
tained at 3 months. Most side effects occurred during the sonications
only, including: frontal headache during last sonication (n51), dizzi-
ness (n52), vertigo (n52). Lip paresthesia during sonication (n51)
resolved after target was relocated 1 mm anterior to the original tar-
get coordinates. Side effects that lasted after the procedure included
unsteady feeling when walking without neurological deficit for 1
week (n51).
Fig. 1. (609).
Movement Disorders, Vol. 30, Suppl. 1, 2015
Conclusions: Thalamotomy using MRI-FUS was safe and effec-
tive in PD patients. Large randomized studies are needed in order to
assess safety and efficacy.
609
Changes in subthalamic nucleus local field potentials following
administration of levodopa in patients with Parkinsons disease
correlate with clinical improvement as measured by objective
sensor data
A.N. Sen, G. Meloni, I. Telkes, A. Abosch, N.F. Ince (Houston, TX,
USA)
Objective: To assess the relationship between power changes in
local field potential (LFP) subbands and performance on an objective
keyboard-task after levodopa administration in Parkinsons disease
(PD) patients.
Background: Levodopa and deep brain stimulation (DBS) of the
subthalamic nucleus (STN) are widely used in managing symptoms of
patients with PD. LFP, which represent the electrical activity of a popu-
lation of neurons, can be recorded from implanted DBS electrodes in
STN to study the electrophysiological correlates of PD. Previous studies
have shown a decline in beta band power and increase in high fre-
quency (HFO) power in the STN during the transition from medication
off to on states. These changes are known to correlate with the
UPDRS, a subjective PD grading scale. However, to our knowledge, no
studies have evaluated the relationship of STN LFP changes and
improvement in clinical performance using objective sensor data.
Methods: STN-LFP activity was recorded from the implanted
DBS electrode (model # 3389, Medtronic) of nine PD subjects post-
operatively over 36 hours with 1024 Hz and 16 bit A/D resolution
with XLTEK EMU40 system. Bradykinesia was assessed during an
alternating stroke keyboard task which lasted for 30s. Number of key
presses was recorded in all patients with 133Hz and aligned with
LFP data. Recordings were analyzed using MATLAB R2014a.
Results: Analysis of LFPs revealed strong baseline beta (12-30
Hz) activity in all patients prior to levodopa administration. Follow-
ing levodopa administration, beta activity was suppressed in seven
patients. The magnitude of beta power suppression positively corre-
lated with improvement in the bradykinesia score of the UPDRS
(R=0.72) and the number of key presses (R=0.75) (Figure 1). The
magnitude of HFO (300-330 Hz) power rise positively correlated
with keyboard task performance (R=0.83), but not with bradykinesia
UPDRS scores (R=0.03) (Figure 2).
(figure 1)
(figure 2)
 POSTER SESSION
Fig. 2. (609).
Conclusions: Changes in LFP in the STN following levodopa
administration correlate with improvements in objective sensor data
performance. Beta power decline and HFO band power enhancement
correlate with improvement in a keyboard task. These preliminary
findings suggest that objective sensors can be used to relate LFP
changes to quantitatively-measurable clinical changes in PD patients.
610
New frontiers in focused ultrasound treatment in Parkinsons
disease: A potential paradigm for staged lesioning of the
subthalamic nucleus
B.B. Shah, D.S. Huss, M.B. Harrison, G.F. Wooten, S. Sperling, W.J.
Elias (Charlottesville, VA, USA)
Objective: Investigate the safety and feasibility of unilateral,
staged lesioning of the subthalamic nucleus (STN) using MR-guided
focused ultrasound (FUS) in PD patients.
Background: The benefit of STN modulation is well established.
DBS has been favored over subthalamotomy due to safety considera-
tions as subthalamotomy can cause contralateral choreoballism.
FUS is a paradigm that allows for precise tissue heating free
from incision or craniotomy. Treatment location and intensity is
monitored with near real-time MR imaging thermometry. Previously,
we have shown safety and efficacy of unilateral FUS thalamotomy
for essential tremor.
Our observations have shown that lower heating (50 C) can
have transient effects on tremor and sensation, allowing for target
adjustment prior to ablation. Our hypothesis is that unilateral sub-
threshold sonications (50-55 ) to the STN is safe and produces a
reversible benefit in PD subjects.
Methods: 6 subjects are planned. Inclusion criteria are markedly
asymmetric PD, disease > 3 years, disabling PD motor features
defined as motor fluctuations or med-refractory tremor, and OFF
med UPDRS part III of greater than 40. Exclusion criteria include
severe dyskinesia, severe medical comorbidities, cognitive or mood
dysfunction, and claustrophobia.
Phase 1 involves unilateral STN sonications up to symptomatic
change in the contralateral body as assessed intraprocedurally. Sub-
jects will be monitored for at least one month for development of
involuntary movements. If benefit decays, phase 2 will be offered:
full sonication to the STN.
Assessments are OFF/ON med UPDRS at baseline, 1 week, and 1
month in each phase, Abnormal Involuntary Movement Scale, neuro-
psychological testing, patient/clinician global impression of change,
quality of life, MRI brain, and adverse events.
S239
Results: 1 of the anticipated 6 subjects has been treated to date.
Transient benefit was observed for 24-48hours following phase 1 in
tremor, rigidity, and bradykinesia. No adverse effects followed the
phase 2 lesion.
Conclusions: FUS allows for incremental delivery of minimally
invasive stereotactic lesions. Establishing a paradigm for testing ben-
efit and potential adverse effects prior to permanent treatment could
increase the safety of treating deep brain targets. If such a profile is
established, a new paradigm of serial treatment may increase options
for functional neurosurgyof PD.
611
Motion perception during subthalamic nucleus deep brain
stimulation: Current spread to vestibulothalamic tract
A.G. Shaikh, K. Mewes, K. Wilson, M.R. DeLong, A.G. Machado
(Cleveland, OH, USA)
Objective: Assessment of vertigo as a side effect of high-
frequency subthalamic nucleus stimulation.
Background: Electrical stimulation provides critical information
about proximity of the stimulation sight to the neighboring struc-
tures, determination of the stimulation parameters, and the position
of the deep brain stimulation electrode. For example, tongue and lip
movements during high-frequency subthalamic nucleus stimulation
suggests spread of the current to inferolateral corticobulbar tract,
tetanic contraction of the hand and face suggests spread to the
pyramidal tract, and parasthesia are due to the medial lamniscus
stimulation.
Methods: We studied subthalamic nucleus stimulation induced
motion perception in five patients with Parkinsons disease. The
patients reported direction of perceived motion in two ways. First
they matched the perceived motion with the real life experience. For
example, earth horizontal plane (yaw) rotations are comparable to
riding a merry-go-round; sagittal plane (pitch) rotations are analo-
gous to sitting in a giant-wheel, while coronal plane (roll) rotations
were analogous to motion of the cartwheel. Any complex motion
was described by real life analogy, such as swinging motion. The
subjects also mimicked the trajectory, plane, and the pattern of their
perception with hand gestures. We excluded patients who had light-
headedness, anxiety, and pre-existing vestibular disorder.
Results: Five patients had specific sense of motion after subthala-
mic nucleus stimulation using caudal and most medical electrode
contact. The percept was distinct compared to non-specific lighthead-
edness, oscillopsia, or anxiety. All patients described rotational
motion in the horizontal plane. One patient also had perception of
Movement Disorders, Vol. 30, Suppl. 1, 2015
S240 POSTER SESSION
Fig. 1. (611).
complex motion, as if riding a swing, which is a combination of
pitch and fore-aft motion. Table depicts the summary.[figure1]
Conclusions: We suggest that the spread of the current to the
vestibulothalamic tract located dorsal and medial to the subthalamic
nucleus can cause motion perception. Such side effect suggests an
important landmark during intraoperative mapping and stimulation
threshold during programming. Our results provide evidence for exis-
tence of vestibulothalamic track in humans, such pathway is well
recognized in macaques.
612
Deep brain stimulation for Parkinsons disease in Kazakhstan
C. Shashkin, S. Akshulakov, Z. Komarov (Astana, Kazakhstan)
Objective: Parkinsons disease (PD) is chronic progressive
degenerative disease of the central nervous system with prevalence
72 to 258,8 for 100 thousand people. We expect up to 20000 PD
patients in Kazakhstan.
Background: In National Center for neurosurgery in Astana,
Kazakhstan there is the stereotactic and functional neurosurgery unit.
The main goal of this team is to provede a wide range of neurosurgi-
cal service for Movement Disorders, epilepsy, chronic pain and spas-
ticity. The DBS progrem was started in 2013 with the first cases for
Parkinsons disease.
Methods: 67 PD patients were operated in the National center for
neurosurgery in period 2013-2014. We used international selection
criteria as age up to 70, idiopathic Parkinsons disease, positive
dopamine challenge, and diskinesias and motor fluctuations.
We used multipurpose stereotactic frame by Electa (Sweden) and
SurgiPlan software by Elekta (Sweden).
We stimulated subthalamic nucleus in 66 cases and globus pal-
lidus internus in 1 case. There were 30 male and 37 female. The
average age of the patients was 51 y.o. The average duration of dis-
ease was 10 years. Severe fluctuations and diskinesias were in 75%
of cases.
We implanted DBS therapy Activa PC system from Medtronic
(USA, Minneapolis), which were consisted from two leads, extension
cables and IPG. The most cases (80%) were implanted using
microelectroderecording.
Results: Improvement of motor functions was in 80% of cases.
Postural instability, gait problems and autonomic symptoms less
regressed. We decrease the dosage of dopaminergic drugs for 30%
and more thereafter the drug induced dyskinesia regressed in all
cases moreover in 6 cases we postponed medication completely. We
had complications in 5 cases: 1 bleeding, 1 stroke, 1 infection and 2
tromboembolism (1 of them died). The patient who bled was
Movement Disorders, Vol. 30, Suppl. 1, 2015
implanted again after intensive care and rehabilitation. The infected
patient was explanted but in 6 months implanted again with good
result.
Conclusions: Deep brain stimulation is effective treatment of PD
and can decrease main symptoms of the disease: rigidity, tremor and
bradykinesia and sometimes postural instability and gait problems.
The right patient selection is a key for good result of this procedure.
There are all possibilities to treat Parkinsons disease using DBS in
Kazakhstan on base of the National Center for neurosurgery. Thre
are the bright frontiers to use DBS therapy for Movement Disorders
in Kazakhstan.
613
Intraoperative MRI for deep brain stimulation lead placement in
Parkinsons disease: One year motor and neuropsychological
outcomes
C. Sidiropoulos, P. LeWitt, A. Mahajan, M. Schonberger, A.
Ellenbogen, D. Taylor, J. Wall, J.M. Schwalb (West Bloomfield, MI,
USA)
Objective: To present motor and neuropsychological outcomes
for Parkinsons disease (PD) patients who underwent deep brain
stimulation (DBS) electrode placement with intraoperative MRI
(iMRI) using the ClearPoint system (MRI Interventions, Inc.).
Background: iMRI for DBS lead placement is a novel approach
using real time intraoperative neuroimaging rather than awake elec-
trophysiologic mapping. Many patients are not candidates for awake
mapping due to anxiety, pain from orthopedic issues or discomfort
from an unmedicated state while in the operating room. Multiple
passes through brain tissue to determine ideal lead placement pose
increased risk for hemorrhage and adverse neuropsychiatric effects.
There has been a paucity of data on the efficacy and safety of DBS
for PD using iMRI.
Methods: Data on 12 procedures (7 bilateral STN, 4 bilateral
GPi and one contralateral STN to a preexisting electrode) in patients
who underwent DBS under general anesthesia using iMRI were col-
lected. The UPDRS Part III was conducted by a Movement Disor-
ders expert pre- and 13 months postoperatively (data available for 11
patients). The Repeatable Battery for Neuropsychological Status
(RBANS), total and index scores as well as the Delis-Kaplan Execu-
tive Function System (DKEFS) Verbal Fluency subtest scores were
calculated pre- and at 19 months post-surgery for all 12 patients.
Retrospective descriptive analysis using paired t-test was performed
with STATA, Version SE 12 for Windows (College Station, TX).
Results: The mean UPDRS Part III score off medication before
DBS was 38.75 6 11.78. Mean score on medication before DBS was
16.33 6 10.25. Post-DBS, the on stimulation UPDRS Part III score
changed to 21 6 6.88 and 16.18 6 5.36 for off and on medication,
respectively. Patients had a 45.8% improvement in the UPDRS Part
III score off medication, after iMRI-guided DBS whereas their
double-on condition did not differ from their pre-op on medication
score. There was no statistically significant difference in any of the
neuropsychological outcomes tested.
Conclusions: Motor findings improved considerably in our
patient cohort en-par to previously published results using awake
microelectrode recording. There were no adverse neuropsychological
outcomes in our patient population although larger numbers are
needed to validate iMRI as a safe and equally effective alternative to
awake DBS surgery.
614
Incidence of dyskinesia improvement following subthalamic DBS
with and without medication reduction
L. Solis-Cohen, D.K. Simon, D. Tarsy, E. Papavassiliou, R. Alter-
man, L.C. Shih (Boston, MA, USA)
 POSTER SESSION S241

Objective: To examine the time course and degree of improve-

ment of levodopa-induced dyskinesia in a cohort of Parkinsons dis-
ease patients (PD) who have undergone subthalamic nucleus (STN)
deep brain stimulation (DBS) and the relation to medication
adjustments.
Background: Levodopa-induced dyskinesia is a complication of
long-term treatment of PD with levodopa and is considered a chief
indication for STN DBS. While many studies have reported the anti-
Parkinsonian effect of STN DBS, few have documented the response
of dyskinesia to DBS in an objective manner or assessed the role of
medication adjustments to changes in dyskinesias. The goal of this
study was to use an objective dyskinesia rating score to quantify dys-
kinesia improvement after DBS at 2 months, 6 months and 1 year
following surgery.
Methods: We used a modified dyskinesia rating score, adapted
from Unified Dyskinesia Rating Scale items 16-22, to quantify dyski-
nesia burden for a cohort of 25 PD patients who underwent bilateral
STN DBS between Dec 2011 and Jul 2014 at Beth Israel Deaconess
Medical Center. Dyskinesia scores were obtained from clinical
examinations at the above time points before and after DBS. Levo-
dopa equivalent daily doses (LEDD) were calculated at each time
interval.
Results: The 25 PD patients in this study included 15 males and Fig. 1. (615).
10 females. Mean age was 66.8 (range 54-79). Mean disease duration
was 11.4 years at the time of DBS placement. Mean pre-operative month we also tested a blind lower frequency of 60HZ. We used
LEDD was 1385mg. Mean pre-operative modified UDysRS score FOG and the PDQ 39.
was 7.0. Overall, there was significant improvement in dyskinesia Results: We found a improvement in UPDRS III of 37,5% and
rating scores after DBS at 2 months (0.04, p<0.001), 6 months UPDRS axial of 59,4%. The FOG showed 47,9% and the PDQ 39
(0.40, p< 0.001) and 1 year (0.13, p<0.001). There was also a dura- 40,1% of improvement. The TUG revealed a decrease in the time by
ble decrease in LEDD at 2 months, 6 months and 1 year after DBS 57,7% at the sixth month . The Dual Task Walking Test showed a
to 1078 mg, 1038 mg and 1059 mg, respectively (all p<0.003). significant and stable improvement along time (57,09% at the third
Interestingly, there was a subset of patients (32% at 2 months, 25% month and 57,5% at the sixth). The 20-m also revealed a final
at 6 months, 26% at 1 year) whose individual LEDD increased or improvement of 64,8% in the number of steps and decrease the time
remained the same (mean change 100mg), while dyskinesia scores by 43,1% in average[figure1]. One patient of our sample was not
declined (p < 0.001; p<0.036; p<0.023, respectively). able to walk in preoperative condition and he could complete all the
Conclusions: In this retrospective study, levodopa-induced dyski- tests after the SCS. When we used the 60 hz SCS we found a severe
nesias showed significant and durable improvement following STN worsening in TUG, in the 20 m and also in the UPDRS III [figure2].
DBS. Although the main reason for improvement in dyskinesias was Conclusions: Although this is a pilot study with a limited number
likely a reduction in LEDD, we also found that dyskinesia improve- of patients, the data presented here suggests that high frequency
ment independent of LEDD reduction occurred in a subset of stimulation of the upper thoracic levels of spinal cord may improve
patients following bilateral STN DBS. considerably gait performance, freezing of gait, quality of life and
Motor UPDRS in advanced Parkinsons disease treated with STN
DBS. The present results contradict the results observed in SCS of
615 the cervical spine and should be explored deeply in the future.
Spinal cord stimulation improves gait performance in advanced
Parkinsons disease patients with chronic stn-dbs: Pilot study
C.P. Souza, C.O. Souza, W.L. Contreras, R.G. Cury, M.G.S.
Ghillard, M.J. Teixeira, E.R. Barbosa, E.T. Fonoff (Ribeirao Preto,
Brazil)
Objective: The aims are to present the results of SCS of upper
thoracic levels on gait,UPDRS III, freezing and quality of life in
advanced PD patients in long term follow-up, after bilateral STN
DBS.
Background: Whilst DBS improves quality of life of PD patients
by addressing the cardinal symptoms and reducing motor complica-
tions, benefits in postural instability and gait disturbance (PIGD)seem
to fade away in long-term follow-up.Data from animal PD model
suggest that spinal cord stimulation (SCS) can enhance locomotion
in mice.
Methods: Four PD patients (age of 64y; 18,5y of PD; 7,8y after
DBS in average) treated with bilateral STN-DBS, showed moderate
or severe PIGD. They received an implantable SCS system (16 chan-
nel paddle electrode) over the epidural space of upper levels of tho-
racic spinal cord. Evaluations were performed: Preoperative and at
the first, third and sixth months after SCS (always DBS on/Med off).
The SCS parameters consisted in high frequency (300Hz), 90mcs.
Gait evaluation consisted in Timed Up and GO test (TUG), 20- Fig. 2. (615).
meter-walk test (20m) and Dual task Walking trial. At the third

Movement Disorders, Vol. 30, Suppl. 1, 2015

S242 POSTER SESSION
616
Beta-band power: A suitable physiomarker for closed-loop deep
brain stimulation in Parkinsons disease?
F. Steigerwald, G. Arnulfo, I.U. Isaias, A. Canessa, M. Reich, R.
Reese, S. Johannes, C. Matthies, J. Volkmann (W
urzburg, Germany)
Objective: This study aimed to further explore the feasibility of
using beta band activity of the subthalamic nucleus (STN) as an
input signal for adaptive deep brain stimulation (aDBS).
Background: Abnormal synchronisation in the beta band (-osc)
within the basal ganglia-cortex loop is considered a pathophysiologi-
cal hallmark of Parkinsons disease (PD). -osc have been proposed
as an ideal control signal for aDBS, which adjusts to the fluctuating
clinical condition of PD patients.
Methods: Seven patients with akinetic-rigid PD and motor fluctuations,
which were selected for STN-DBS by standard clinical criteria, opted to be
implanted with a new DBS-system, which was extended by a recording
function via the stimulation electrode. 14 days and 3 months after implan-
tation we recorded STN local field potentials (LFP) in stimulation OFF
condition during rest, alternating pro-supination movements and walking
in medication OFF and ON state. Power Spectral Density of LFP was esti-
mated using Welchs averaged, modified periodogram. Activa PC1SV R
and additional hard- and software were provided under a request for appli-
cation agreement with Medtronic Inc. The company had no impact on
study design, patient selection, data analysis or reporting of the results.
Results: In contrast to previous reports of LFP recordings from external-
ised leads in the postoperative period, we found increased beta-band power
in only 8 of 14 STNs two weeks after implantation in the medication off
state, and in 7 of 14 STNs at the three months follow-up. Power spectral dis-
tributions remained remarkably stable across the three months study period.
L-Dopa reduced -osc in most, but not all STNs with significant -osc. Vol-
untary movements reduced the lower beta band and increased the middle -
frequencies in the grand average of these STNs, but effects varied greatly
from one STN to the next and between different kinds of movements.
Conclusions: Hence, increased -osc are not a general feature of
the Parkinsonian state, but may rather occur in a subset of STNs, and
the effect of dopaminergic drugs and movements are inconsistent. These
findings question the general usefulness of a simple beta-band power
analysis in the STN as the only control variable for aDBS in PD.
617
Deep brain stimulation and outcome: Hints out of the smoke
screen?
M.H. Strothjohann (Bad Camberg, Germany)
Objective: Nowadays there is a trend to treat younger patients
with motor fluctuations with deep brain stimulation (DBS). Younger
age is a risk factor for dopamine dysregulation syndrome (DDS),
known as a subtype of impulse control disorders (ICD). DBS is often
not successful in DDS patients. Most DBS centers screen their candi-
dates for ICD, but DDS is often hidden by patients.
Background: Although heavy smokers are rare among persons
developing Parkinsons disease (PD), they exist. These patients must
be rewarded by smoking, as they smoked over years. A smoking his-
tory is one known risk factor for ICD.
Methods: We report a 62 y old man, suffering from PD for 12
years, H1Y III- IV with fluctuations, wearing off, several hyperki-
netic phases during the day, who declared having been a strong
smoker with 18 pack years.
Results: Although experiencing good results of DBS, he did not
tolerated the L-dopa- withdrawal, although hyperkinetic phases were
markedly reduced. Several attempts changing the parameters of DBS
did not gave him satisfaction, he developed apathy and depression.
After administering l-Dopa in the dosage of the time before DBS
(500 mg of L-dopa equivalent), he was less depressed, but developed
hyperkinetic actions again. He took Madopar LT (immediate release
formulation) in unknown doses by himself during the entire treat-
ment leading to the diagnosis of DDS by us.
Movement Disorders, Vol. 30, Suppl. 1, 2015
Conclusions: Assessing the smoking behaviour could be a hint for
DBS candidates to assume the risk of DDS and in last consequence the
uselessness of DBS, because these patients will not tolerate l-Dopa-
withdrawal and will continue to stimulate their reward system by l-dopa.
It is known that reduction of those drugs can cause depression, apathy
and even suicides. However, PD patients bearing 1the risk of DDS may
admit their pack years more easily than other personality traits typical
fort he mentioned disordes. Therefore heavy smokers in PD-patients may
be at risk for developing DDS hampering DBS. Further studies that eluci-
date the role of smoking as a risk factor of successful DBS are warranted.
618
Effect of STN deep brain stimulation on autonomic functions in
patients with Parkinsons disease
P. Surathi, A. Lenka, K.R. Jhunjhunwala, A. Zafar, T.N.
Sathyaprabha, R. Yadav, M. Nethravathi, D. Srinivas, A.
Arivazhagan, P.K. Pal (Bangalore, India)
Objective: To evaluate the effect of STN Deep Brain Stimulation
(DBS) on autonomic functions in patients with Parkinsons disease
(PD) using (1) SCOPA- AUT (SCales for Outcomes in PArkinsons
disease- Autonomic function)Questionnaire; (2) laboratory cardiac
autonomic functions tests.
Background: The efficacy of DBS on motor symptoms in PD is
well known and its effect on non-motor symptoms is also being
increasingly recognized. However, there is sparse data on the modu-
lation of autonomic functions by STN DBS.
Methods: We evaluated 14 patients (men:women=2:1) with PD who
underwent STN DBS at the National Institute of Mental Health & Neu-
rosciences, Bangalore, India. They were assessed with SCOPA-AUT
questionnaire and cardiac autonomic function tests [including heart rate
variability parameters (HRV)]before and after approximately 12 months
after DBS. Both these observations were compared and analysed.
Results: The mean age of the patients was 51.1 6 8.9 years and mean
age of onset was 40.6 6 7.6 years. The mean UPDRS (part III) drug OFF
score prior to DBS was 63.4 and after DBS was 28.7(p50.001). Analysis
of the results of SCOPA-AUT questionnaire before and after DBS did not
reveal any significant difference in the total scores (reduction in mean total
score from 6.2 to 4.5; p50.14). Of the sub scores, urinary symptoms had
improved after DBS, though statistically not significant (p50.06).Cardiac
autonomic functions for HRV parameters were also not significantly dif-
ferent between baseline and post-DBS evaluations.
Heart Rate Variability (HRV) parameters before and after Deep
Brain Stimulation (DBS) in patients with Parkinsons disease
Parameter Pre DBS Post DBS P value
SDNN 34.46 6 14.01 40.15 6 18.71 0.37
RMSSD 28.89 6 29.35 38.85 6 27.23 0.32
TP 1051.63 6 853.33 1244.72 6 1124.73 0.61
LF 227.67 6 263.26 431.96 6 397.36 0.15
HF 304.56 6 342.03 409.75 6 303.18 0.39
LF in nu 38.76 6 22.37 42.67 6 16.28 0.60
HF in nu 41.87 6 19.95 46.41 6 23.22 0.58
LF/HF ratio 1.2 6 1.07 1.03 6 0.63 0.59
Time domain parameters: SDNN, in ms- Standard deviation of
normal-to-normal (NN) intervals, in millisecond; RMSSD, in ms-
square root of the mean of the sum of squares of differences between
adjacent NN intervals. Frequency domain parameters: TP, in ms2- total
power; LF, in ms2 HF, in ms2 high frequency power; LF in NU - LF
power expressed in normalized units; HF in nu- HF power expressed as
normalized units; LF/HF ratio- represents sympathovagal balance.
Conclusions: Our data suggest that STN DBS did not signifi-
cantly modulate the autonomic functions at least at 12 months after
 POSTER SESSION
DBS. However further long-term studies on larger cohort of patients
are needed to determine the effect of STN DBS on autonomic func-
tions in Parkinsons disease.
619
VANTAGE trial: Two year outcomes of a prospective, multi-
center trial evaluating deep brain stimulation with a new
multiple-source, constant-current rechargeable system (Vercise)
in Parkinsons disease
L. Timmerman, R. Jain, L. Chen, T. Brucke, F. Seijo, E. Suarez San
Martin, C. Haegelen, M. Verin, M. Maarouf, M.T. Barbe, S. Gill, A.
Whone, M. Porta, D. Servello, F. Alesch (Cologne, Germany)
Objective: The VANTAGE study assesses motor improvement in
moderate-to-severe Parkinsons disease (PD) following bilateral sub-
thalamic nucleus (STN) deep brain stimulation (DBS) using a new,
implantable, rechargeable, multiple-source, 8-contact, constant-
current DBS System (Vercise).
Background: DBS has been demonstrated to be effective for PD
symptom relief (Limousin, et al. 1995). We sought to characterize
the benefit of STN-DBS for PD patients using a recently CE-marked
multiple-source, constant-current system that permits a well-defined
distribution of applied current. We report the two year results of the
first clinical trial employing multiple independent current control
(MICC) DBS in the management of symptoms of Parkinsons disease.
Methods: VANTAGE is a monitored, prospective, multi-center,
non-randomized, open-label interventional trial sponsored by Boston
Scientific Corporation. Forty subjects with idiopathic Parkinsons dis-
ease (PD) were implanted bilaterally in the STN and followed up to
two years post-lead placement. Motor improvement was evaluated
using UPDRS III scores in stim ON/meds OFF as compared with
pre-operative scores. Other assessments such as CAPSIT motor tests,
Tremor Rating Scale, Dyskinesia Rating Scale, PDQ-39, SF-36,
Schwab and England, and resource utilization were administered.
Patient motor diaries were collected over 3 days. Adverse events
were also recorded.
Results: The accompanying report provides the safety and effec-
tiveness outcomes of VANTAGE subjects at two years post-
implantation as compared with baseline.
Conclusions: The VANTAGE trial is the first reported trial of a
multiple-source, constant-current rechargeable system for use in the
management of PD symptoms. The study outcomes will help provide
clinicians with more options and flexibility when managing symp-
toms of PD and thereby ultimately foster improvement in PD
outcomes.
620
Cost-effectiveness of deep brain stimulation for Parkinsons
disease with a multi-source, constant-current rechargeable
system: Results from the two-year follow-up of the VANTAGE
trial
L. Timmermann, F. Alesch, T. Br ucke, F. Seijo, E. Suarez San
Martin, C. Haegelen, M. Verin, M. Maarouf, M.T. Barbe, S. Gill, A.
Whone, M. Porta, D. Servello, R. Jain, L. Chen, N. Mekel-Bobrov
(Cologne, Germany)
Objective: The objective was to estimate the economic value of
bilateral subthalamic nucleus (STN) deep brain stimulation (DBS)
with a new, rechargeable, CE-marked system using a multiple inde-
pendent current controlled (MICC) implantable pulse generator (IPG)
and 8 electrodes per lead.
Background: While the clinical effectiveness of DBS has been
established in a number of multi-center clinical trials over the past
decade, evidence on cost-effectiveness remains relatively limited.
This is particularly true for rechargeable DBS systems. Conse-
quently, as part of the VANTAGE trial, a study of the first recharge-
able MICC DBS system, a comprehensive assessment of resource
S243
utilization and quality of life was included to estimate the treatments
economic value compared to conventional medical management
(CMM).
Methods: The cost-effectiveness of rechargeable MICC DBS
compared to CMM, was evaluated from a country-specific payer per-
spective. Patient-level resource utilization, motor symptoms, and
general and disease-specific quality of life assessments were used
from the 2 year follow-up of the VANTAGE trial to develop a Mar-
kov model representing clinical progression with treatment effect
versus expenditures. A lifetime of device time horizon was used, and
the incremental cost-effectiveness ratio was calculated in terms of
cost per quality-adjusted life-year. Deterministic sensitivity analyses
were performed to calculate the estimate uncertainty.
Results: The last patients two-year visit was underway at the
time of abstract submission. The accompanying report will provide
full detail of the cost-effectiveness outcomes of the VANTAGE trial
based on the two-year follow-up data and modeling out to lifetime
of device.
Conclusions: The VANTAGE trial is the first reported study of a
rechargeable multi-source, constant-current DBS system for use in
the management of PD symptoms. The comprehensive data collec-
tion in this study allows for in-depth economic characterization of
STN DBS with this device. This will both add to the limited eco-
nomic data currently published on DBS in general, as well as pro-
vide an estimate of the cost-effectiveness associated with this type of
system in particular.
621
Attenuation of STN beta oscillations persists immediately and 60
minutes after turning OFF chronic STN DBS
M.H. Trager, E. Quinn, Z. Blumenfeld, A. Velisar, M. Koop, L.
Shreve, C. Kilbane, T. Prieto, J. Henderson, H. Bronte-Stewart
(Stanford, CA, USA)
Objective: To determine whether resting state STN beta band
oscillations are attenuated after turning OFF chronic STN Deep
Brain Stimulation (DBS) and whether this persists at 60 min in Par-
kinsons disease (PD) subjects.
Background: STN local field potential (LFP) recordings demon-
strate oscillatory neuronal activity in the beta (13-30 Hz) band in the
resting state in PD, which are attenuated during high frequency STN
DBS. Beta oscillations are attenuated after turning OFF short periods
of DBS but it is not known whether and for how long attenuation
persists after turning OFF chronic (1-6 months) DBS.
Methods: Ten PD subjects (PDs) underwent bilateral implanta-
tion of STN DBS and a sensing neurostimulator (ActivaV R PC1S,
lead 3389, Medtronic, Inc. FDA IDE-, IRB-approved). PDs were
tested at rest, off medication/OFF DBS before initial activation of
DBS (baseline) and after 1, 3, 6, 9, and 12 months (m) of continuous
DBS. STN LFPs were recorded at baseline and immediately after
DBS was turned off (0 min) and every 15 min thereafter for 60 or
75 min. Metric- absolute LFP beta band power. A one-sample t test
or one-sample signed rank test was used to compare power at base-
line to the 0 and 60 min recording at the 1/3 m visit.
Results: Synchronous recording of kinematic data was used to
select periods of at least ten seconds of data without movement; 4
sides excluded due to persistent tremor. Mean age - 61 6 10.3 yrs,
disease duration - 5.8 6 2.8 yrs. Mean DBS voltage - 2.05 6 0.4 V
(1/3 m) and 2.55 6 0.3 V (6 m). Average impedance of active DBS
electrode - 2366.5 6 329.9 X (baseline), 1887.5 6 428.5 X (1/3 m),
and 1946.05 6 611.3 X (6 m). There was significant attenuation of
baseline beta band power immediately after DBS was turned off (0
min, N=14) after 1/3 m of DBS (P<0.05). At 60 min, there was a
trend towards attenuation of beta band power that reached signifi-
cance when one outlier was removed (P<0.001, N=10), Fig 1. After
6 m of DBS, attenuation of baseline beta band power was observed
in all sides except the outlier at 60 min after DBS was turned OFF,
but there were too few subjects for statistical comparison. [figure1]
Movement Disorders, Vol. 30, Suppl. 1, 2015
S244 POSTER SESSION
Fig. 1. (621).
Conclusions: STN beta oscillations were attenuated immediately
and at 60 min after chronic (1/3 m) STN DBS was turned OFF. This
effect was also observed after long-term (6m) DBS. The mechanism
of long-term effects of DBS on neural synchrony remains to be
determined.
622
Subthalamic deep brain stimulation can improve constipation
and other bowel dysfunction in Parkinsons disease
T. Uchiyama, T. Yamamoto, Y. Watanabe, K. Hashimoto, T.
Kadowaki, Y. Higuchi, T. Shingo, C. Shibata-Yamaguchi, K. Kaga,
T. Yamanishi, R. Sakakibara, S. Kuwabara, K. Hirata (Tochigi,
Japan)
Objective: To investigate the effects of STN-DBS on constipa-
tion and bowel dysfunction in patients with Parkinsons disease.
Background: It is established that deep brain stimulation of the
subthalamic nucleus (STN-DBS) improves motor dyfunction in
advanced PD. However, it remains unclear as to whether STN-DBS
would be effective in improving constipation and other bowel
dysfunction.
Methods: A total of 19 patients with PD who underwent bilateral
STN-DBS were enrolled. We performed questionnaire of bowel
symptom and colonic transit time (CTT) study before and 3 months,
1 year after the STN-DBS surgery. The CTT study was performed
using the repetitive ingestion method. We counted the number of
markers in each segment of the large bowel and then calculated the
right CTT, left CTT, rectosigmoid CTT, and total CTT.
Results: Subjective improvement in bowel frequency was shown
in 15 patients (88.2%) at 3 months post surgery and 10 (83.3%;
Movement Disorders, Vol. 30, Suppl. 1, 2015
n512) at 1 year post surgery. And stop or dose reduction of purga-
tives in 7 patients (42.2%) at 3 months and 10 (83.3%; n512) at 1
year post surgery. Improvement of the total CTT was shown in 15
patients (78.9%) at 3 months post surgery and 10 (83.4%; n512) at
1 year post surgery. The right CTT, rectosigmoid CTT and total
CTT were significantly decreased, but the left CTT was unchanged
at both 3 months and 1 year post surgery (Total CTT: 70.4 hours
[pre] to 57.8 [3M], 47.2 [1Y]).
Conclusions: STN-DBS can improve constipation and difficult
defecation, resulting in reduction of purgatives. One of the causes
may be improvement of colon and anorectal motility by STN-DBS.
623
A review of initial consultations for deep brain stimulation: The
NYU experience
R.K. Unia, A. Mogilner, M. Pourfar (New York, NY, USA)
Objective: To review the nature of deep brain stimulation (DBS)
consultations at a major academic center over the course of a year in
order to determine the distribution of patients referred for different
indications, the percentage deemed to be appropriate candidates as
well as reasons for ineligibility.
Background: DBS is used to treat conditions such as advanced
Parkinsons disease (PD), Essential Tremor (ET), dystonia, obsessive
compulsive disorder (OCD) and emerging indications such as Tour-
ette Syndrome (TS). The success of this technique depends largely
upon selection of appropriate candidates. Although DBS has been
approved for over a decade in the United States, many candidates
presenting for surgery are deemed ineligible, suggesting continued
uncertainty among patients and/or referring physicians regarding
appropriate criteria.
Methods: We retrospectively reviewed charts of all patients who
presented for DBS at the New York University Langone Center for
Neuromodulation and determined the appropriateness of DBS for
each indication. For those deemed inappropriate, we reviewed the
reasons for exclusion. Of those who were good candidates, we
reviewed how many underwent surgery.
Results: 158 patients presented for new DBS consultation, of
which 106 had PD, 12 ET, 5 had dystonia, 4 had OCD and 21 had
other indications (including 10 TS and 9 tremor not due to PD or
ET). Of the 106 PD patients, 35 (31%) were deemed appropriate for
immediate surgery and 29 were excluded from eligibility. The main
reasons for exclusion were gait/balance problems (48%) and
advanced age (45%), often concomitantly. Of the 12 ET patients,
none were deemed good immediate candidates and 5 were excluded
(80% too mild, 20% diagnostic uncertainty). Of the 5 dystonia
patients, 2 were ineligible (1 psychogenic, 1 too mild). 4 of the TS
patients were deemed eligible and 2 ineligible (1 too mild, 1 atypi-
cal). Twenty of 35 eligible PD patients, 2 of 4 eligible TS patients, 1
eligible OCD patient, and 1 MS tremor patient had the surgery.
Conclusions: At our center in 2014, PD was the most commonly
referred diagnosis for DBS followed by ET and TS. Only a quarter
of patients were deemed appropriate at time of presentation with the
most common reasons for exclusion being age and gait/balance prob-
lems. Of the patients thought to be good candidates, about half
underwent surgery and the remainder may in the future.
624
Peripheral nerve grafts reduce medication requirements and
reduce motor scores in Parkinsons disease patients with deep
brain stimulation therapy
C.G. van Horne, G. Quintero, J. Gurwell, G. Gerhardt, J. Slevin
(Lexington, KY, USA)
Objective: Our goal is to develop a regenerative treatment strat-
egy for Parkinsons disease (PD). No treatment reverses the degener-
ation or loss of cell function. This study is designed to test the safety
 POSTER SESSION
and feasibility of autologous peripheral nerve (PN) grafts into the
substantia nigra (SN) in participants with PD undergoing deep brain
stimulation (DBS). Clinical measures of disease progression are cap-
tured and analyzed.
Background: The safety of autologous PN grafts into the CNS is
supported by studies in both non-human primates and in patients
with PD. The safety of transplantation into the SN has been demon-
strated by studies of grafts of fetal dopaninergic tissue bilaterally
into the SN and putamen without perioperative or long term compli-
cations. For our study, PN tissue was selected because it has been
shown to produce growth factors that support for dopaminergic neu-
rons survival.
Methods: DBS targeting the subthalamic nucleus (STN) was per-
formed. After the DBS leads were implanted, sural nerve grafts
(5mm in length) were implanted unilaterally into the SN. Adverse
events were monitored. Our secondary aim was to measure changes
in motor function by UPDRS evaluation pre-op and at 1, 3, 6, 9, and
12 months post-op.
Results: We have implanted 8 participants. Post-op MRIs have
not shown evidence of abnormal tissue disruption. At 1 year, partici-
pants reported comparable adverse effects to standard DBS surgery.
UPDRS Part III scores off medication/off stimulation decreased after
nine months (36 6 8 baseline vs. 25 6 13, mean 6 SD; N=6). Scores
on medication and on stimulation improved by 8 points (16 6 11
baseline vs. 8 6 6, nine months), and daily levodopa equivalents
decreased from a mean of 844 6 691 mg at baseline to zero after
nine months.
Conclusions: We have completed implantation in 8 of 8 partici-
pants. Post-op MRIs have not indicated evidence of abnormal tissue
disruption. Participants reported comparable adverse effects to standard
DBS surgery. UPDRS Part III scores off medication/off stimulation
decreased after 9 months (36 6 8 baseline vs. 25 6 13, mean 6 SD;
N=6). On treatment scores improved by 8 points (16 6 11 baseline vs.
8 6 6, nine months). Daily levodopa equivalents decreased from a
mean of 844 6 691 mg at baseline to zero after 9 months.
625
Deep brain stimulation at the sub thalamic nucleus did not cause
cognitive impairment in elderly patients with idiopathic
Parkinsons disease six months after the operation
I. Velentzas, H. Seferis, P. Afentouli (Marousi Athens, Greece)
Objective: To examine if deep brain stimulation (DBS) at the
sub thalamic nucleus (STN) causes cognitive impairment in elderly
patients with idiopathic Parkinsons disease.
Background: It is controversial if DBS at the STN causes cogni-
tive impairment in elderly patients with idiopathic Parkinsonism or if
that is attributed to a dementia due to the progression of illness.
Methods: We tested before and six months post-operatively nine
patients who were between 67 and 74 years old with idiopathic Par-
kinsons disease and who received implantation for DBS between
2009 and 2013 in our hospital. Pre- and post-operative examination
included: AddenbrookesTest Examination,Trail Making Test A&B,
Rey Auditory Verbal Learning Test, Parkinsons Neuropsychometric
Dementia Assessment, Stroop Neuropsychological Screening Test,
Rey Auditory Figure, Frontal Assessment Battery. Since all patients
in pre surgical examination performed at least on an average, they
were considered good candidates for surgery.
Results: Post-operative examination revealed that under neurosti-
mulation one patient improved, seven patients remained stable and
one worsened in all tests. However, without significant difference,
verbal memory seemed on an average slightly reduced. All patients
showed significant motor improvement.
Conclusions: No evidence for significant cognitive impairment
could be observed in most of our elderly DBS patients six months
post-operatively. Despite the limited number of tested subjects, we
assume that the DBS method probably does not impact on cognitive
functions, if dementia is excluded in the pre-operative examination.
S245
626
Advanced target identification in STN-DBS with beta power of
combined local field potentials and spiking activity
R. Verhagen, D.G.M. Zwartjes, T. Heida, E.C. Wiegers, M.F.
Contarino, R.M.A. de Bie, P. van den Munckhof, P.R. Schuurman,
P.H. Veltink, L.J. Bour (Amsterdam, Netherlands)
Objective: To study the temporal relationship between neuro-
nal spiking and local field potentials (LFP) in different functional
areas of the STN and to investigate how well measurements in the
sensorimotor STN could be discriminated from measurements
elsewhere in the STN using combined coherence and spectral
power analysis.
Background: In deep brain stimulation of the subthalamic nucleus
(STN-DBS) for Parkinsons disease, often microelectrode recordings
(MER) are used for STN identification. However, for advanced target
identification of the sensorimotor STN, it may be relevant to use LFP
recordings. Then, it is important to assure that the measured oscilla-
tions are coming from the close proximity of the electrode.
Methods: We performed multiple simultaneous recordings of
LFP signals and neuronal spiking in the form of multiple-unit
spike train (MU-ST) signals. Thereby, we investigated the tempo-
ral relationship between local neuronal spiking and the more
global LFP. We analyzed the local oscillations in the LFP by cal-
culating power only over specific frequencies that show a signifi-
cant coherence between LFP and neuronal spiking. Using this
coherence method, we investigated how well measurements in
the sensorimotor STN could be discriminated from measurements
elsewhere in the STN.
Results: The sensorimotor power index (SMPI) of beta frequen-
cies, representing the ability to discriminate sensorimotor STN meas-
urements based on the beta power, was significantly larger using the
coherence method for LFP spectral analysis compared to other meth-
ods where either the complete LFP beta spectrum or only the promi-
nent peaks in the LFP beta spectrum were used to calculate beta
power.
[Figure1]
Conclusions: The results suggest that due to volume conduction
of beta frequency oscillations, proper localization of the sensorimotor
STN with only LFP recordings is difficult. However, combining
recordings of LFP and neuronal spiking and calculating beta power
over the coherent parts of the LFP spectrum can be beneficial in dis-
criminating the sensorimotor STN.
Fig. 1. (626).
Movement Disorders, Vol. 30, Suppl. 1, 2015
S246 POSTER SESSION
Fig. 1. (627).
627
STN model based on intraoperative microelectrode recordings
assists in postoperative management of DBS settings and clinical
research
R. Verhagen, P.R. Schuurman, P. van den Munckhof, M.F.
Contarino, R.M.A. de Bie, L.J. Bour (Amsterdam, Netherlands)
Objective: The use of intraoperative neurophysiological informa-
tion to create a detailed model of STN size and location which delin-
eates the exact boundaries of the nucleus in relation to the implanted
electrode.
Background: MRI images used for preoperative targeting in
STN-DBS surgery do not always show all STN boundaries clearly.
Therefore, intraoperative microelectrode recordings (MER) are often
used to fine-tune STN targeting.
[Figure1]
Methods: An optimization routine based on the classifications of
MER points both inside and outside the STN is used to fit an atlas-
Fig. 2. (627).
Movement Disorders, Vol. 30, Suppl. 1, 2015
based 3D model of the STN body onto the exact stereotactic location
of the measured MER 1 .
Independently fitted STN models for both hemispheres, based on
three or more MER trajectories (n544), are fused with preoperative
T2 MRI images to verify STN size and location.
Results: The overlay of STN models with the MRI image of the
STN were evaluated by an experienced neurosurgeon (64% good,
36% reasonable, 0% bad). Significant downscaling (mean 5 -
11.2%, p<0.001) and rotations may indicate an overestimation of
STN size, especially of the dorso-lateral and dorso-anterior part.
[Figure2]
Conclusions: An automated MER based model which delineates
STN boundaries can be used to compare electrode position relative
to the STN body between different patients, relate the effects of
DBS to the exact location of the stimulating electrode within the
STN and assist in postoperative management of DBS settings.
628
Deep brain stimulation of the subthalamic nucleus preferentially
alters the translational profile of striatopallidal neurons in an
animal model of Parkinsons disease
N.P. Visanji, I.K. Sarvestani, M.C. Creed, Z.S. Shoaei, J. Nobrega,
C. Hamani, L.N. Hazrati (Torotno, ON, Canada)
Objective: We employed two transgenic mouse lines, combining
translating ribosomal affinity purification (TRAP) with bacterial arti-
ficial chromosome expression (Bac), to selectively identify changes
in translational gene expression in either Drd1a-expressing striatonig-
ral or Drd2-expressing striatopallidal medium spiny neurons (MSNs)
following deep brain stimulation targeting the subthalamic nucleus
(STN-DBS).
Background: STN-DBS is an effective surgical treatment for the
motor symptoms of Parkinsons disease (PD), the precise neuronal
mechanisms of which both at molecular and network levels remain a
topic of debate.
Methods: 6-hydroxydopamine lesioned mice received either 5 days
stimulation via a DBS electrode implanted in the ipsilateral STN or 5
days sham treatment (no stimulation). Striatal polyribosomal RNA was
selectively purified from either Drd2 or Drd1a expressing MSNs using
the TRAP method and gene expression profiling performed.
Results: We identified 8 significantly altered genes in Drd2
MSNs (Vps33b, Ppp1r3c, Mapk4, Sorcs2, Neto1, Abca1, Penk1 and
Gapdh) and 2 overlapping genes in Drd1a MSNs (Penk1 and
Ppp1r3c) implicated in the molecular mechanisms of STN-DBS. A
detailed functional analysis, using a further 728 probes implicated in
 POSTER SESSION
STN-DBS suggested an increased ability to receive excitation (medi-
ated by increased dendritic spines, increased calcium influx and
enhanced excitatory post synaptic potentials) accompanied by proc-
esses that would hamper the initiation of action potentials, transport
of neurotransmitters from soma to axon terminals and vesicular
release in Drd2-expressing MSNs. Finally, changes in expression of
several genes involved in apoptosis as well as cholesterol and fatty
acid metabolism were also identified.
Conclusions: This increased understanding of the molecular
mechanisms induced by STN-DBS reveals novel targets for future
non-surgical therapies for PD.
629
Coordinated reset deep brain stimulation produces long-lasting,
dose-dependent improvement in motor symptoms in the
Parkinsonian non-human primate
J. Wang, S. Nebeck, A. Muralidharan, J.L. Vitek, K.B. Baker
(Minneapolis, MN, USA)
Objective: To characterize the acute and carry-over effects of
Coordinated Reset (CR) deep brain stimulation (DBS) of the sub-
thalamic nucleus (STN) region on Parkinsonian motor signs and
associated STN local field potential (LFP) activity.
Background: Novel DBS approaches are being explored in an
effort to improve therapeutic benefit for patients with Parkinsons
disease. Developed by Peter Tass, CR DBS in the STN region has
been shown to be effective at treating akinesia in the Parkinsonian
non-human primate (NHP), with carryover observed for weeks after
treatment cessation.
Methods: Two Parkinsonian rhesus macaques (P and F) were
conditioned to allow a modified UPDRS (mUPDRS) motor exam,
trained to perform a cued-reach task, and implanted with a scaled
STN DBS lead. A within-subject crossover design was used to com-
pare the effects of traditional (tDBS) to CR DBS, with CR delivered
for 2- (CR2) or 4-hours (CR4) per day over five days. Each block
was followed by an OFF period to characterize carry-over. Reach
data, mUPDRS scores and LFPs from the STN DBS lead (F only)
were collected daily.
Results: Acute mUPDRS scores were improved by both tDBS
and CR DBS. Significant carryover effects were observed only after
CR DBS, with OFF DBS mUPDRS improvements ranging from
25% - 50% for 10 or more days following a 5-day CR4 DBS treat-
ment block. mUPDRS scores following CR2 were mixed, with the
less affected animal (F) showing marked (>30%) improvement for
nine days post-treatment while limited effects were observed in the
moderately severe animal (P). Wrist velocity during cued reaching
was increased (up to 28%) after DBS, with carryover observed for 
4, 3 and 14 days for tDBS, CR2, and CR4, respectively. Gait
changes were marked by increased ankle velocity (up to 47%), with
carryover observed for more than a week following CR4. The time-
course of motor improvements in animal F occurred coincident
with an upward shift in beta peak frequency.
Conclusions: Our data are consistent with previous studies sug-
gesting both acute and long-term benefit can be achieved with CR
DBS. Uniquely, our data suggest that carry-over may be sensitive to
dose duration and associated with changes in STN neural activity.
Additional studies are needed to elucidate the mechanism(s) underly-
ing these effects and to further optimize treatment delivery.
630
Respiratory dyskinesia in a Parkinsons patient is successfully
treated with STN DBS
T. Xie, R. Guan, J. Staisch, D. Casaubon, V.L. Towle, P.C. Warnke
(Chicago, IL, USA)
Objective: We report a case of successful treatment of isolated
respiratory dyskinesia in a PD patient using bilateral STN DBS.
S247
Background: Dyskinesia in PD usually involves the neck, trunk,
limbs and face. Isolated or predominant respiratory involvement is
rarely reported. Diagnosis and treatment are often challenging. Treat-
ment of isolated respiratory dyskinesia using STN DBS has not been
reported before.
Methods: A 64 year-old man with an 8-year history of unilateral
onset PD and good response to carbidopa/levodopa came to us for
the evaluation of 10-month history of respiratory distress. He had
had multiple emergent department visits and hospitalizations for
extensive cardiopulmonary workups, but none was revealing. His his-
tory and response to the increased and decreased dosage of carbi-
dopa/levodopa in our clinics suggested his isolated respiratory
distress as peak-dose dyskinesia. His respiratory distress failed to
respond to amantadine. Given the fact that STN DBS could control
general dyskinesia and Parkinsonism and reduce the levodopa equiv-
alent dose, DBS was considered for him, with his good response to
levodopa. Bilateral STN DBS was subsequently placed as described
elsewhere, and he was followed up periodically for 6 months.
Results: His dyskinesia was completely controlled after the DBS
surgery, with left C1/2- 2.5volts/60ls/130Hz and right C1/10-
1.8volts/60ls/130Hz at 1-month post-surgical visit even at usual
medication onstate. His respiratory dyskinesia remained completely
controlled at his 6-month post-surgical visit with left C1/2- 2.7volts/
60ls/130Hz and right C1/10- 2.8volts/60ls/130Hz and 33% reduc-
tion of his pre-surgical levodopa equivalent dosage. His Parkinson-
ism was also well-controlled, with UPDRS-III scores of 22 at DBS
on and medication off state, and 14 at DBS on and medication
on state at both post-surgical visits, compared to pre-surgical score
of 20 at levodopa on and 45 at levodopa off state.
Conclusions: (1) We presented a case with isolated peak-dose
respiratory dyskinesia, rather than akathisia, non-motor respiratory
dysrhythmia or cardiopulmonary diseases, in a PD patient. (2) We
further demonstrated for the first time that bilateral STN DBS com-
pletely controlled the respiratory dyskinesia even at medication on
state, with well-controlled Parkinsonism as well. (3) This case might
help proper diagnosis and treatment of respiratory dyskinesia in PD
in the future.
631
The number of microelectrode passes during DBS surgery: Can
it really influence surgical outcomes?
X.X. Yu, H. Abboud, G. Genc, N. Thompson, S. Oravivattanakul, F.
Alsallom, D. Floden, A. Machado, M. Gostkowski, H.H. Fernandez
(Cleveland, OH, USA)
Objective: To investigate whether the number and side of micro-
electrode passes during DBS surgery influence surgical outcomes in
patients with Parkinsons disease (PD).
Background: Intraoperative microelectrode recording has been
widely used to refine DBS lead placement for Parkinsons disease.
The penetration effect from this procedure is not entirely understood.
It has been suggested that more microelectrode passes were associ-
ated with increasing hospital stay. Other immediate and long-term
outcome measures related to surgical passes have not been carefully
studied.
Methods: PD patients who underwent DBS surgery at our center
from 2006 to 2011 with complete charting were analyzed. Primary
outcomes included both immediate outcomes (i.e. presence of post-
operative confusion and prolonged hospitalization [> 2 days]) and
long-term outcomes (i.e. 6-month and 1-year postoperative quality of
life and functional scales [such as the EQ5D and UPDRS Part II]).
Results: We identified 130 patients [71% male, mean age:
63 6 9.1, PD duration: 10.7 6 5.1, total microelectrode passes: 544,
mean microelectrode passes: 4.1 6 2.1]. There was no association
between the number of right, left, and total microelectrode passes
with the occurrence of acute postoperative confusion or prolonged
postoperative hospitalization. In 56 patients who had complete pre-
and post-operative health status measures, there was a trend towards
Movement Disorders, Vol. 30, Suppl. 1, 2015
S248 POSTER SESSION
worse 6-month postoperative UPDRSII score and the number of left
microelectrode passes (P=0.0508). No other associations were found
with functional and QOL outcomes.
Conclusions: In our cohort, we found no association between the
number of microelectrode passes and the occurrence of acute postop-
erative confusion or prolonged postoperative hospital stay. However,
further studies are needed to determine if the number of microelec-
trode passes influences long-term functional outcomes.
632
Hesitation in deciding-deep brain stimulation of Parkinsons
disease
J.Y. Yun, M.R. Kim, Y.H. Lim, K.R. Kim, S.H. Paek, B.S. Jeon
(Seoul, Korea)
Objective: We tried to study reasons for hesitation in deciding-
deep brain stimulation of Parkinsons disease.
Background: In advanced Parkinsons disease (PD) with dis-
abling motor fluctuation and dyskinesias, deep brain stimulation
(DBS) is currently a well-recognized treatment. In clinical experi-
ence, however, many patients or caregivers were very reluctant to
allow the operation when operation was indicated and recommended.
Reasons for hesitation were not studied in the past.
Methods: We systemically asked a questionnaire in PD patients
who underwent subthalamic nucleus deep brain stimulation (STN-
DBS) from March 2005 to June 2014. A hesitant group for DBS was
defined as patients who underwent operation only after repeated urg-
ing and after a delay. Others were grouped to non-hesitant group.
Demographic information included age, PD onset age, disease dura-
tion, the Unified Parkinsons disease Rating Scale (UPDRS), Hoehn
and Yahr (H&Y) Stage and levodopa equivalent dose (LEDD) when
they underwent the evaluation to consider operation.
Results: We enrolled 186 PD patients who underwent STN-DBS
in SNUH. 74 patients (40.8%) belonged to the hesitant group. There
were no significant differences between the hesitant group and non-
hesitant group in their age and onset age, disease duration, LEDD
and the mean UPDRS motor score and total score in on-time and
off-time. Reasons for hesitation in the hesitant group were as fol-
lows: fear of side effects (N=60, 81.8%), economic burden (39,
52.7%), expecting new therapeutic options (29, 39.2%), limitations
to daily activities (14, 18.9%), comorbidities (5, 6.8%) and dysmor-
phic problems (5, 6.8%). The reasons that they finally underwent the
DBS were confidence in the doctors decision (N=66, 89.2%),
encouragement from their family (29, 39.2%), economic supporting
system (12, 16.2%), education for DBS (11, 14.9%) and aggravated
symptoms (6, 8.1%).
Conclusions: Fear of surgical complications was the most com-
mon reasons for hesitating DBS surgery. Even with special finan-
cial support by the National Healthcare System, economy was the
second most common reason for hesitation suggesting that there is
a need for further financial support in these advanced PD patients.
Building trust between patients and physicians will be an impor-
tant avenue to gently guide patients into this risk-bearing
treatment.
633
Role of the frequency of STN stimulation on bradykinesia in
Parkinsonian patients
A. Zacharia, I. Sastre, D. Georgiev, M. Hariz, L. Zrinzo, T. Foltynie,
M. Jahanshahi, J. Rothwell, P. Limousin (London, United Kingdom)
Objective: To evaluate the effect of low frequency subthalamic
nucleus (STN) deep brain stimulation (DBS) vs. high frequency on a
range of motor tasks in Parkinsonian patients.
Background: A superior effect of low frequency stimulation vs
high frequency on axial symptoms has been observed in some Par-
kinsonian patients on chronic STN DBS. The rationale for this could
Movement Disorders, Vol. 30, Suppl. 1, 2015
be a differential effect on the fibres running from the STN to the
Peduculopontine nucleus or a different effect on the STN itself. The
effect of the frequency of stimulation on upper limb bradykinesia is
not well established. Here we assess the effect of frequencies on dif-
ferent motor tasks of the upper limb.
Methods: We conducted a double blinded crossover study in 15
patients with advanced PD to assess high and low frequency stimula-
tion. The patients were stimulated with 80Hz or 130Hz randomly for
3 weeks and then switched to the other frequency for 3 more weeks.
Adjustments of voltage were made according to the best clinical
effect. Motor performance was assessed with the purdue pegboard,
finger tapping and repetitive proximal arm movements. In total the
patients were assessed 6 times.
Results: The mean age was 63.3 (SD 6.6) years, the mean dis-
ease duration was 15.5 (SD 5.2) years. The time since surgery was
4.45 (SD 3.9) . Preliminary analysis of the results show that 80 Hz
stimulation was superior to 130 Hz in improving the number of
repetitive proximal movements, while there was no differential
effect between 80Hz or 130Hz on the finger tapping and the number
of pegs tasks.
Conclusions: These data suggests a different effect of the fre-
quency of stimulation on proximal performance compared to distal
performance. The relation between this finding and the effect of fre-
quency on axial function remain to be established.
Surgical Therapy: Other Movement Disorders
634
Long-term clinical effects of cZI compared to VIM DBS on
essential tremor patients
B. Ahmed, D.M. Ramirez, L. Almeida, J.C. Giugni, E. Monari, K.D.
Foote, M.S. Okun (Gainesville, FL, USA)
Objective: To compare the long-term clinical effect from cZI
versus VIM DBS in ET patients.
Background: Ventralis intermedius nucleus (VIM) deep brain
stimulation (DBS) is now considered an effective therapy for Essen-
tial Tremor (ET) patients. Unfortunately, around 40% of the patients
will experience a decline of benefit over time.There has been recent
interest in stimulating caudal zona incerta (cZI) to control tremor,
and to avoid waning of benefit. Whether stimulating cZI will prevent
this long-term complication is debated.
Methods: A retrospective data/chart review from January 2002
July 2013 was conducted at the UF-CMDNR. Demographic informa-
tion, DBS settings and Tremor Rating Scale (TRS) scores were
obtained from patients charts and from our IRB approved database.
Patients were divided into three groups according to the stimu-
lated area derived from the active lead contact: thalamus VIM (group
1), thalamus VIM 1 cZI (group 2), and cZI (group 3). Stimulated
areas and lead locations were separated according to previously
reported stereotactic coordinates. Information from 181 leads was
reviewed.
Results: Data of 96 leads from 74 patients were included in the
analysis. Forty leads corresponded to group 1, 41 to group 2, and 15
to group 3. A significant decrease (improvement) in tremor
(p<0.001) and hand function (p<0.001) scores for contralateral
upper extremity was revealed in all groups at 6 months post-surgery.
This improvement in clinical scores was maintained over the studied
period when compared to baseline. Interestingly, a worsening of
tremor scores and hand function scores were observed in groups 2
and 3 when compared to group 1 at 3 years follow-up.[figure1]
When analyzing action and postural tremor scores separately over a
3-year period, no significant change in the postural tremor score was
observed, while the action tremor score significantly worsened back
to the baseline value (p<0.01).[figure2]
 POSTER SESSION S249

Demographics and clinical characteristics of population (n596 leads/74 patients)

Demographics VIM (n540 leads) VIM1cZI (n541 leads) cZI (n515 leads) p-value
Female, no. (%) 17 (47) 17 (47) 3 (20) 0.13
Age at surgery (yrs) 67.6 6 10.3 67.5 6 9.1 64.9 6 12.7 0.65
30 years or less since symptom 17 (42.5) 23 (56.1) 9 (60) 0.83
onset, no. (%)
Family history of tremors, no. (%) 16 (41) 14 (34.1) 9 (60) 0.23
On medications, no. (%) 17 (42.5) 23 (56.1) 10 (66.7) 0.23
Baseline TRS and lead details
Parts A and B 39.5 6 9.9 38.2 6 10.2 34.8 6 11.2 0.32
Part C 15.8 6 5.2 16.8 6 6.6 14 6 6.2 0.32
Total 55.4 6 12.9 54.2 6 16.3 48.8 6 15.6 0.35
Brain side of lead (Right/Left) 14/26 19/22 3/12 0.18
Bilateral leads, no. (%) 15 (37.5) 23 (56.1) 6 (40) 0.22
VIM=ventral intermediate nucleus; cZI=caudal zona incerta; TRS=Fahn-Tolosa-Marin Tremor Rating Scale

Fig. 1. (634).
Conclusions: Our results confirm all the three targets as viable
options for short term tremor control. However, worsening of tremor
scores may occur when stimulating cZI as compared to VIM when
followed over time. Tremor and hand function improvement were
maintained up to 3 years in all targets. Prospective clinical trials will
be required to confirm our results.
635
Improvement in disabling action tremor associated with
cerebellar multiple system atrophy by thalamic DBS: A case
report
P. Anprasertporn, N. Hidarilak, B.L. Guthrie, H.C. Walker
(Birmingham, AL, USA)
Objective: (1) To report a case of multiple system atrophy that tha-
lamic deep brain stimulation markedly alleviates cerebellar action tremor.
(2) To suggest that deep brain stimulation should be considered in
selected cases of multiple system atrophy especially with disabling tremor.
Background: Deep brain stimulation (DBS) is approved for the
medically refractory symptoms of Parkinsons disease and essential
tremor. DBS has generally not shown significant or sustained benefits
in patients with multiple systems atrophy, such that expert opinion
has recommended against surgery in these patients. Here we reported
a patient with multiple system atrophy, cerebellar type (MSA-C) in
whom unilateral thalamic DBS markedly improved tremor.
Methods: A 52-year-old right-handed Caucasian woman devel-
oped progressive limb and gait ataxia, frequent falls, scanning dys-
arthria, inspiratory stridor and urinary incontinence at age 47.
Metabolic testing for sporadic causes for ataxia and genetic testing
for autosomal dominant cerebellar ataxia were both negative. She
subsequently developed orthostatic hypotension and Parkinsonism
including rigidity, bradykinesia, rest tremor worse in the left than the
right sided body. Her brain MRI showed moderately severe cerebel-
lar and pontine atrophy, all consistent with MSA-C. Her tremor was

Fig. 2. (634).

Movement Disorders, Vol. 30, Suppl. 1, 2015

S250 POSTER SESSION
transiently suppressed with levodopa, but she eventually progressed
such that she could no longer feed herself because of severe action/
postural tremor.
Results: DBS targeted at the left ventral intermediate nucleus of
thalamus (Vim) was performed aiming to help relieve her feeding
disability. After the surgery, patient has a marked and satisfactory
improvement of her rest, postural and action tremor of the right hand
so that she can feed, dress and bath herself. Her ataxia, bradykinesia,
and dysarthria were unchanged by DBS. Her improvement in tremor
control has sustained upon the 6-month follow-up.
Conclusions: Although DBS is generally not recommended for atyp-
ical Parkinsons syndromes, this case report provides evidence that tha-
lamic DBS may confer important benefits in selected cases of MSA-C
with disabling action tremor. We did not observe improvement or wor-
sening in bradykinesia, rigidity, ataxia in the stimulated arm or leg.
636
Surgical treatment of post-traumatic midbrain resting-kinetic
tremor with stereotactic lesions with M.E.R. of the zona incerta
A.R.C. Azevedo, W.O. Contreras, P.R. Reis, R.G. Cury, F.E.F. Silva,
J. Navarro, E.T. Fonoff (S~
ao Paulo, Brazil)
Objective: To report the outcome of patients who underwent uni-
lateral ablative therapy lesioning of zona incerta (Zi) and Forels
field H1 and H2 to treat pharmacologic resistant post-traumatic mid-
brain resting-kinetic tremor using a single-cell parallel micro elec-
Fig. 1. (636).
Movement Disorders, Vol. 30, Suppl. 1, 2015
trode recording (M.E.R.) and stimulating of the posterior sub
thalamic area (PSA) to approach adequate the target.
Background: Post-traumatic midbrain tremor is frequently associated
to a period of coma and diffuse axonal injury after severe or moderate
brain trauma. Tremor mostly affects the upper extremities and presents
the peculiar simultaneous combination of rest, action and postural tremor
components resulting in severe functional impairment. Mundinger in 1965
described this treatment for many Movement Disorders in observation of
the axial exclusion of the subthalamic extrapyramidal afferent fibres to the
ventral oral nucleus in and around the region of the zona incerta.
Methods: Four males patients with a median of 35 years old suf-
fering of refractory post traumatic tremor underwent unilateral ablative
radio frequency (RF) stereotactic and target guided by M.E.R. double-
channel for lesion of the zona incerta. The Tremor Rating Scale
(TRS) was performed before and after surgery. [figure1]Software for
Fusion of atlases and MRI showing where to mark the lesion. [figur-
e2]M.E.R. print: The first column on the last but one line shows poor
activity pattern for Zi by medial electrode (first channel) near of the
target, and the second column on the same line shows single-cell
activity by lateral electrode (second channel) in STN.
Results: The patients had immediate tremor relief intraoperative
stimulation and continue symptoms free after the lesioning. A
improvement of 90% on TRS was noticed in all group. Eight months
of follow-up, all patients maintained improvement, enhancing their
quality of life, recovering independence and returning to their work.
Conclusions: The Zi RF lesioning provided sustained improve-
ment outcome in tremor control in all patients of this case series.
 POSTER SESSION
Fig. 2. (636).
The privileged anatomic position of the zona incerta, Forels field
H1 and H2 joining between the pallido-thalamocortical and the
cerebello-thalamocortical circuits makes it an ideal target for lesion-
ing. The use of M.E.R. was helpful in order to increase the precision
and it guided the electrode relying on neighbor structures of subtha-
lamic nucleus.
637
Effects of VIM-DBS on the speech motor system in ET patients:
An electromagnetic articulograph study
M.T. Barbe, D. M ucke, A. Hermes, J. Becker, T.A. Dembek, A.
Josten, I.G. Meister, V. Visser-Vandewalle, M. Grice, L. Timmer-
mann (Cologne, Germany)
Objective: To investigate the effect of bilateral VIM-DBS on
speech production in patients with essential tremor (ET). We use fast
syllable repetition tasks to employ acoustic and kinematic parameters
related to stimulation induced dysarthria (SID), both with and with-
out stimulation.
Background: Bilateral VIM-DBS is an effective treatment to
suppress medically resistant ET. However, SID is a common side
effect, reportedly affecting between 10% and 75% of the patients. In
recent studies, we used acoustic parameters to show deterioration in
speech of ET patients under stimulation. The previous acoustic data
suggests changes in the glottal and oral system while DBS is on. In
fast syllables tasks such as/papapa/,/tatata/and/kakaka/we found an
increase of voicing during the entire syllable cycle as well as friction
during the consonantal closure, indicating a reduced degree of glottal
abduction as well as imprecise oral articulation.
Methods: So far, we recorded 10 German ET patients (7 males
and 3 females) between 31 and 73 years (mean 61.4, SD 12.4 years).
Each patient was recorded with an electromagnetic articulograph (16
channels, AG501) and a time-synchronized acoustic signal with
DBS-on and DBS-off. To capture oral articulation sensors were
S251
placed at the tongue tip, tongue dorsum, jaw and lips. Speech materi-
als included fast-syllable repletion tasks (/papapa/,/tatata/,/kakaka/).
Measures in the acoustic waveform included syllable duration as
well as the amount of voicing and frication during the consonantal
closure. Measures in the kinematic domain included displacement,
duration and velocity profiles of the opening and closing gestures
during the production of the consonant-vowel sequences.
Results: Preliminary analysis suggests that DBS affects the oral
articulation, mainly in terms of reduced velocity and displacement.
There is a high amount of speaker-specific variability within and
across patients during the repetition of the syllable cycles.
Conclusions: Our results confirm our findings from acoustic data,
i.e. VIM-DBS has a detrimental effect on speech production. While
this has been so far captured only on the acoustic surface, with this
study, effects of stimulation on the underlying articulation can be
quantified in terms of velocity profiles and displacements leading to
articulatory imprecision.
638
Deep brain stimulation in rare movements disorders
I. Beaulieu-Boire, C.C. Aquino, A.E. Lang, R.P. Munhoz, Y.Y. Poon,
A. Valencia, M. Fallis, S. Kalia, M. Hodaie, E. Moro, A.M. Lozano,
A. Fasano (Sherbrooke, QC, Canada)
Objective: To evaluate the efficacy and tolerability of pallidal
deep brain stimulation (DBS) in rare causes of inherited, progressive
combined dystonia.
Background: Rare causes of inherited Movement Disorders some-
times present with a debilitating phenotype of dystonia often combined
with Parkinsonism, which is often refractory to medications. These
patients are often offered and treated with DBS despite lack of evidence.
Methods: We report the surgical outcome of pallidal stimulation
in a series of ten patients with identified genetic disease (ataxia-
telangiectasia, chorea-achantocytosis, congenital nemaline myopathy,
Movement Disorders, Vol. 30, Suppl. 1, 2015
S252 POSTER SESSION
dopa-responsive dystonia, neuronal ceroid lipofuscinosis, spinocere-
bellar ataxia type 2 and 3, Wilsons disease, Woodhouse-Sakati syn-
drome, and X trisomy).
Results: Pallidal DBS was varied but generally marginally effec-
tive in the series of patients here reported, with an improvement
ranging from 0 to 78% on dystonia rating scales, as observed 47.3
1/- 19.9 months after surgery.
Conclusions: The mixed phenotypes, some aspects of which may
not be responsive to current DBS targets, and the progressive nature
of the disorders are potential reasons for the poorer response in these
patients with rare Movement Disorders. Obviously, this is a hetero-
geneous group of disorders, and while in several cases DBS was not
effective, it did provide worthwhile improvement in specific patients
with well-defined disorders, namely chorea-achantocytosis, dopa-
responsive dystonia, and Wilsons disease, which is in keeping with
existing literature.
Our findings support the current knowledge that DBS is generally
less effective in treating rare inherited dystonias with a combined
phenotype than in isolated dystonia. Negative outcomes are impor-
tant to report, in order to improve patients selection and avoid
unnecessary procedures and excessive expectations.
639
Results from first year experience of dedicated pediatric DBS
dystonia program at Barrow Neurological Institute at Phoenix
Childrens Hospital
R.D. Bhardwaj, S. Flecky, N. Remec, J. Samanta (Phoenix, USA)
Objective: To review and quantify changes in a cohort of pediat-
ric patients with primary or secondary dystonia following bilateral
Deep Brain Stimulation (DBS) to the Globus Pallidus Internus (GPi).
Background: DBS as a treatment for dystonia in the pediatric
population has been demonstrated to be a safe and effective treat-
ment. We wanted to examine this in the context of creating a new
program in a population base that did not have previous access to
this treatment modality.
Methods: Ten children with dystonia who received treatment
with DBS were analyzed and measures of functional abilities, anthro-
pometrics (weight, height, BMI), and quality of life (QoL) were
scored. For patients who were or became ambulatory, specified gait
spatial-temporal measures (cadence, velocity) were also noted.
Results: Improvements in anthropometric data were noted for all
patients. QoL scores were also noted to increase, however, ambula-
tory patients showed more significant changes in QoL scores for par-
ticipation, whereas non-ambulatory patients showed greater
improvement in QoL scores for health and pain. After implantation,
two children were able to transition from non-ambulatory to ambula-
tory status, and ambulatory patients were able to walk faster with
fewer steps. All mobile patients showed decreased need for external
assistance for functional tasks and activities of daily living.
Conclusions: Deep brain stimulation provides good relief of
extraneous movements in children with primary and secondary dysto-
nia, but also can affords significant functional changes in mobile or
potentially ambulatory patients. For non-ambulatory patients, signifi-
cant changes in QoL measures appear to favor surgical DBS inter-
vention for dystonia.
640
Delayed scalp erosion after DBS surgery: Incidence, treatment,
outcomes, and prevention
A.R. Bona, A. Mantovani, S. Vaziri, R. Walz, M.S. Okun, K.D. Foote
(Gainesville, FL, USA)
Objective: To evaluate the incidence and impact of delayed scalp
erosion in a large single center series of DBS patients and report a
successful surgical technique for avoiding this complication.
Movement Disorders, Vol. 30, Suppl. 1, 2015
Background: DBS is a safe, effective surgical treatment for med-
ication refractory Movement Disorders, however, complications
related to the surgical procedure and the implanted hardware do
occur and must be minimized to optimize DBS outcomes. Delayed
erosion of the scalp overlying protruding DBS hardware is one such
adverse event that universally requires surgical treatment and may
result in discontinuation of DBS therapy. Reported rates of scalp ero-
sion vary among implanting groups, and multiple factors likely
underpin the differences. We have modified our surgical technique to
eliminate protrusion of DBS hardware, effectively preventing delayed
erosions.
Methods: We retrospectively analyzed cases of scalp erosion in a
consecutive series of 464 DBS lead implantations (taken from a
review in progress of more than 1000 DBS lead implantation proce-
dures) where two different surgical techniques were used. 174 recent
procedures included drilling a frontal countersink surrounding the
burr hole to eliminate protrusion of the cap, whereas the previous
290 procedures were performed without countersinking. 19 recent
procedures also included drilling a groove in the parietal bone to
eliminate protrusion of the DBS connector, while this technique for
recessing the connector was not employed in the previous 445 cases.
The study included all DBS patients implanted between January
2009 and June 2014.
Results: 5 patients (1% of procedures) developed delayed frontal
or parietal scalp erosions: 2 cases of erosion at the frontal cap site
and 3 at the parietal connector site. In 2 cases out of 5 (1 frontal, 1
parietal), a recurrent erosion developed after successful surgical
debridement and primary closure. No scalp erosions developed at
sites where the hardware had been recessed into the skull.
Conclusions: Delayed scalp erosion is a serious adverse event
that occurred in 1% of cases in this large DBS series. Drilling the
skull to countersink the frontal cap and recess the parietal connector
appear to be a successful strategies to eliminate protrusion of
implanted subgaleal DBS hardware and prevent delayed scalp ero-
sion. This technique also results in improved cosmesis, patient com-
fort and satisfaction.
641
The efficacy of VIM and VIM/ZI DBS in treatment of various
tremors
M. Bonello, J. Osman-Farah, P.R. Eldridge, B. Hammersley, L.
Lowry, P. Byrne, N.A. Fletcher, S.H. Alusi (Liverpool, United
Kingdom)
Objective: To compare efficacy of DBS in various tremors.
Background: Deep Brain Stimulation is an established treatment
for disabling tremor that is refractory to medical therapy.1,2 How-
ever, the outcome of DBS surgery is variable and largely dependent
on the aetiology of the tremor being treated. There are many studies
looking at the success of DBS for Essential Tremor (ET) and some
for Multiple Sclerosis associated Tremor (MST). However, there is
limited information on the outcomes of DBS surgery for Dystonic
Tremor (DT).
Methods: We carried out a retrospective analysis of a cohort of
patients treated for arm tremors of various types at our centre in the
period 2009-2014. These included ET, DT, MST and Holmes tremor
(HT). Patients were assessed at baseline and at six months post oper-
atively with the Fahn-Tolosa-Marin Tremor Rating Scale (FTM),
which was chosen to assess both the tremor severity and its impact
on activities of daily living (ADL).
Results: A total of 26 patients were studied, 14 had ET, 6 MST,
5 DT and 1 HT. All underwent VIM or VIM/ZI Stimulation. FTM
tremor scores improved significantly at 6 months, compared to base-
line (p<0.05). The best improvement, however, in arm tremor sever-
ity and daily function, was seen in ET patients with a median overall
improvement of 65.5%, then DT at 45%. Patients with MST had a
median overall improvement of 36%. The patient with HT improved
by 56%. There were no surgical complications.
 POSTER SESSION
Conclusions: VIM and VIM/ZI DBS is an effective treatment for
disabling tremor in general but the extent of its benefit depends on
the tremor type being treated and hence tremulous patients can be
informed accordingly.
References:
1. Cooper S, Bowes M. Surgical considerations for tremor and
dystonia. Cleveland Clinic journal of medicine 2012;79 Suppl 2:S40-
3.
2. Zakaria R, Vajramani G, Westmoreland L, et al. Tremor reduc-
tion and quality of life after deep brain stimulation for multiple
sclerosis-associated tremor. Acta neurochirurgica 2013;155:2359-64;
discussion 64.
642
Biochemical mechanisms of pallidal deep brain stimulation in X-
linked dystonia Parkinsonism
N. Br
uggemann, A. Moser, A. Domingo, C.K. Moll, D. Rasche, C.
Mohr, R. Rosales, P. Capetian, R.D. Jamora, L.V. Lee, A. M unchau,
C.C. Diesta, V. Tadic, C. Klein, V. Tronnier (Luebeck, Germany)
Objective: Invasive techniques such as in-vivo microdialysis pro-
vide the opportunity to directly assess neurotransmitter levels in sub-
cortical brain areas.
Background: X-linked dystonia-Parkinsonism (XDP) is an inher-
ited neurodegenerative disease which mainly affects male patients
due to the X-linked mode of inheritance. The disease is characterized
by adulthood onset of focal dystonia, which rapidly generalizes
within a few years. Given the unique phenotypic pattern XDP can
serve as an ideal model disease to study dystonia in patients sharing
the same underlying genetic effect (i.e., an otherwise highly homoge-
neous group).
Methods: Five male Filipino patients (mean age 42.4, range 34-
52 years) with severe XDP underwent bilateral implantation of deep
brain leads into the internal part of the globus pallidus (GPi). Intrao-
perative microdialysis and measurement of GABA and glutamate
were performed in the GPi in three patients and globus pallidus
externus (GPe) in two patients at baseline for 25/30 minutes and dur-
ing 25/30 minutes of high-frequency GPi stimulation (HFS).
Results: While the GABA concentration increased in the GPi
during HFS (231 6 102% in comparison to baseline values), a
decrease was observed in the GPe (22 6 10%) [figure1] . Extracellu-
Fig. 1. (642).
S253
lar glutamate levels largely remained unchanged by GPi HFS
(71 6 45%).
Conclusions: Pallidal microdialysis is a promising intraoperative
monitoring tool to better understand neural processes underlying
Movement Disorders and therapeutic mechanisms of HFS. The
increased inhibitory tone of GPi neurons and the subsequent thalamic
inhibition could be one of the key mechanisms of GPi DBS in dysto-
nia. Such a mechanism may explain how competing (dystonic)
movements can be suppressed in GPi/thalamic circuits in favor of
desired motor programs.
643
Deep brain stimulation artifact in cervical electromyography
M.V. Della Coletta, A.R. Marci~
ao (Manaus, Brazil)
Objective: Report the presence of artifacts related to DBS activ-
ity in electromyography in a patient with bilateral DBS.
Background: Patients with Movement Disorders are undergoing
deep brain stimulation (DBS) with increasing frequency. Is already
known that DBS can cause artifacts in electrocardiogram. Two previ-
ous reports refer artifacts in electromyography (EMG) in patients
with DBS. In several conditions is important to know this possibility
to avoid erroneous diagnosis.
Methods: We report the case of a 44 years old patient with
NBIA with previous right palidotomy and bilateral DBS (left GPI
and right STN). He presented with Parkinsonism that was aliviated
with DBS, but still present laringeal dystonia and bleparospasm.
Electromyography was performed to guide botulinum toxin injections
in laringeal muscles.
Results: During the EMG artifacts of high amplitude and fre-
quency compatible with DBS firing were detected. This artifacts
were very prominent and did not allow the visualization of muscle
activity. The change in EMG parameters do not cleaned the artifacts.
The DBS programming was: Left STN: OFF at the moment/Right
GPI: C1 1- 150 Hz, 90 us, 3,0 V.
The DBS generator was turned off with the disappearance of arti-
facts, and just after the botulinum toxin injection it was turned on,
with return of DBS activity signals.
[figure1]- EMG and DBS OFF.
[figure2] - EMG and DBS ON.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S254 POSTER SESSION
Fig. 1. (643).
Fig. 2. (643).
Conclusions: With the increasingly number of patients with
implantable devices like DBS, it is important recognize the possible
interferences in neurophysiological methods.
Even the Movement Disorders specialists must be present to
adjust or even turn off the system during procedures.
644
Target correlated mapping of therapeutic effects in deep brain
stimulation using voxel-based estimations of neuroanatomical
structures and volumes of tissue activated
T.A. Dembek, M.T. Barbe, M. Astr
om, V. Visser-Vandewalle, L. Tim-
mermann (Cologne, Germany)
Objective: To develop an effective and reliable method of map-
ping the effects of deep brain stimulation into a neuroanatomical
atlas and to perform statistical analysis in order to find the optimal
target for maximal therapeutic and minimal side effects.
Background: While deep brain stimulation is well accepted in
the treatment of several Movement Disorders, sufficient knowledge
about the exact target area responsible for good therapeutic outcome
as well as the neuroanatomical origin of certain side effects is still
lacking. Functional mapping of clinical effects might provide new
insights into the mechanisms of deep brain stimulation and the opti-
mal stimulation targets.
Movement Disorders, Vol. 30, Suppl. 1, 2015
Methods: Formal stimulation testing protocols from fifteen essen-
tial tremor patients who underwent deep brain stimulation of the
nucleus ventralis intermedius (Vim) containing over 500 stimulation
settings, were used as clinical data. A voxel-based version of a com-
monly used two dimensional neuroanatomical atlas (Mai et al., 2007)
was created. Volumes of tissue activated (VTA) were designed by
using electric field thresholds as previously described by A str
om
et al. (2014). For each patient VTAs were further combined with
their corresponding clinical data. Finally, voxel-based statistical anal-
ysis was performed using a randomized permutation algorithm as
described by Eisenstein et al. (2014). Voxels showing significant
tremor reduction were analyzed regarding their anatomical affiliation
through direct mapping into the voxel-based atlas.
Results: Preliminary results showed significant tremor reduction
around the target. Mean tremor reduction was higher for voxels near
or ventral of the ventral border of the Vim compared to voxels inside
the Vim proper.
Conclusions: These results are in line with other studies which
demonstrated stimulation of structures ventral to the thalamus (more
specifically the posterior subthalamic area or the zona incerta) to be
more effective in the suppression of tremor than thalamic stimulation
itself. The methods demonstrated here provide a computationally
simple, yet reliable solution for mapping therapeutic effects in deep
brain stimulation and could be of further use to target optimization
in different Movement Disorders.
645
Neuropsychological outcome of bilateral pallidal stimulation in
cervical dystonia: One-year follow-up results from a prospective
multicenter trial
L. Dinkelbach, J. Mueller, M. Delazer, S. Elben, A. Wolters, E.
Karner, W. Poewe, A. Schnitzler, J. Volkmann, M. Suedmeyer
(Duesseldorf, Germany)
Objective: To evaluate the safety of internal globus pallidus deep
brain stimulation (GPi-DBS) for the long-term treatment of primary
cervical dystonia regarding its impact on neuropsychological
parameters.
Background: GPi-DBS is an effective and well-tolerated treat-
ment for primary cervical dystonia, but its effects on cognitive func-
tions remain unclear. Previously published studies with patients
suffering from generalized dystonia or Parkinsons disease found that
GPi-DBS potentially affects various neuropsychological domains as
attention or verbal fluency.
Methods: This study was conducted as an ancillary part of an
international, prospective, multicenter trial of bilateral GPi-DBS on
primary cervical dystonia (Volkmann et al., Lancet Neurol
2014;13:875-884). Thirteen patients (age: 51.85 6 11.59 years)
underwent an extensive neuropsychological assessment prior and 12
months after surgery. The following cognitive domains were tested
while on active stimulation: Memory: Verbal and Nonverbal Learn-
ing, Digit Span forward, Spatial Span - Wechsler Memory Scale
(WMS-R); Executive functions: Digit Ordering Test (DOT), Phone-
mic and Category Verbal Fluency; Attention: Test of Everyday
Attention (TEA), Stroop Test; Visual perception: Visual Object and
Space Perception (VOSP), Benton Judgment of Line Orientation Test
(BJLOT); Mental arithmetic: Graded Difficulty Arithmetic Test;
Verbal intelligence: Multiple Choice Vocabulary Test.
Results: No global impact of GPi-DBS on neuropsychological
functioning has been observed. Only performance on one subtest of
verbal fluency including alternating categories deterioriated after one
year of neurostimulation (p 5 0.02). This finding did not correlate
with the effect of GPi-DBS on motor symptoms. All other compari-
sons failed to reach significance level (p > 0.05).
Conclusions: The present study supports the safety of GPi-DBS
for the treatment of primary cervical dystonia as no changes were
seen in the majority of assessed neuropsychological domains. The
defined deterioration of verbal fluency after neurostimulation should
 POSTER SESSION
be taken into consideration when selecting dystonia patients for GPi-
Stimulation.
646
Update on deep brain stimulation for refractory Tourette
syndrome: 10 patients with CM-Pf/Voi stimulation
R.S. Dowd, M.H. Pourfar, A.Y. Mogilner (New York, NY, USA)
Objective: 1)Understand the necessity of deep brain stimulation
as a therapy for Tourette syndrome. 2)Become familiar with a set of
patients treated using a thalamic target.
Background: Tourette syndrome (TS) is a complex neuropsychi-
atric disorder characterized by multiple motor and phonic tics. While
pharmacological and behavioral therapy can be effective, there is a
subset of patients who remain refractory with few other options.
Increasing clinical evidence from multiple centers suggests that Deep
brain stimulation (DBS) can be effective in refractory TS patients.
Currently, there are reports of 9 different targets being used with
DBS for TS, thus the roadblocks to its success include questions not
only of efficacy, but of optimal target selection.
Methods: 10 patients with refractory TS underwent DBS of the
centromedian thalamus by our team over a five-year period. Patients
were evaluated by a multidisciplinary team, with preoperative objec-
tive assessments including the Yale Global Tic Severity Scale
(YGTSS) and Yale-Brown Obsessive Compulsive Scale (YBOCS).
YGTSS scores were calculated at visits immediately post-operatively
and at their latest follow-up. Coordinates of the active DBS contacts
were calculated and projected onto the patients pre- and post-
operative imaging.
Results: Patients showed an average decrease of 49% (Z=-1.89
p50.062) in the total tic severity at their immediate post-operative
visit, which trended toward significance. At their last visit, their
scores achieved significance, decreasing from pre-operative scores by
50% (Z=-2.42 p50.014). The average position of the active contact
relative to the midcommissural plane was 7.1 mm lateral, 1.9 mm
posterior and 2.7mm superior on the left, and 6.2 mm lateral, 2.2mm
posterior, and 2.9 mm superior on the right. There were no long-
term complications. One patient suffered an extension lead fracture,
necessitating unilateral revision and temporary removal for infection,
followed by replacement. This same patient later developed an intra-
parenchymal cyst at the right lead tip, necessitating permanent
removal of right side lead.
Conclusions: Our data adds to the growing body of literature
suggesting that DBS of the CM-Pf/Voi thalamus is effective in the
treatment of refractory TS. The active contacts localize to the ante-
rior CM-Pf/posterior VOi/Vom region.
647
Impedance fluctuations in patients undergoing thalamic deep
brain stimulation for essential tremor and their effect on clinical
outcome
J. Eskenazi, E. Tan, A.N. Mamelak, M. Tagliati (Los Angeles, CA,
USA)
Objective: To investigate measured impedance variability and its
clinical effect in patients with essential tremor (ET) treated with tha-
lamic deep brain stimulation (DBS).
Background: The role of electrical impedance measured at the
interface between DBS electrodesand surrounding brain tissue is con-
troversial. Impedance variations may affect the amount of therapeutic
current delivered to brain tissue by constant-voltage devices currently
in use. Published data suggest that impedance values fluctuate over
time following DBS implantation, and differ depending on the ana-
tomical location of the electrode. Virtually no such information is
available for thalamic stimulation for ET. As a mono-symptomatic
disease, ET provides an ideal setting to test the clinical relevance of
DBS impedance variations.
S255
Methods: We collected therapeutic impedances from 24 ET
patients with thalamic DBS. Impendences were measured at the
beginning and at the end of each DBS programming session. In addi-
tion, patient reported subjective tremor changes (better, worse, sta-
ble) and adverse events that occurred in the time period between
programming sessions were noted. A significant impedance variation
was defined as a change greater than 5% of the impedence recorded
at the end of preceding programming session.
Results: Out of 134 intervals between adjustments, we recorded
71 (53%) significant impedance variations. In 55/134 intervals,
patients reported tremor improvement or stability. In 79/134 intervals
patients reported worsening symptoms (23 tremor-related, 32 DBS
side effects, 24 both). Significant impedance variations were recorded
after 29% of intervals with stable or improved tremor and after 70%
of intervals with worsening tremor or reported DBS adverse events.
50% of cases with tremor worsening alone had significantly
increased impedance. 63% of cases with DBS side effects had a sig-
nificant impedance reduction.
Conclusions: Impedance values change over time following tha-
lamic DBS for ET. Impedance variations appear to play a significant
role in the stability of clinical outcomes and the incidence of adverse
events.
648
Panic disorder following implantation of deep brain stimulation
(DBS) leads in the ventral intermediate nucleus of the thalamus
(VIM)
S.M. Fayad, U. Akbar, P. Zeilman, M.S. Okun, H.E. Ward
(Gainesville, FL, USA)
Objective: To describe new onset panic disorder following
implantation of DBS electrodes in the VIM.
Background: Panic disorder is characterized by unexpected panic
attacks which interfere significantly with quality of life and social
function. Commonly implicated brain regions involved in underlying
neural circuitry are the amygdala, cingulate cortex, and prefrontal
cortex. Some studies have suggested that the thalamus is involved.
Methods: The VIM is rarely implicated in negative neuropsychi-
atric sequelae. We report 2 cases of new onset panic disorder in
patients with PD and ET with severe medication refractory action
tremor following implantation of DBS electrodes in the VIM, prior
to stimulation.
Results: A 75 year old female underwent VIM DBS. She had
mild, intermittent anxiety and depression, well controlled pre-
operatively with medication. She had a lesional effect from electrode
implantation and tremor suppression from implantation alone. Fol-
lowing electrode implantation, she developed intense anxiety symp-
toms and panic attacks that occurred up to 3 times daily. Turning off
the IPG did not alleviate these symptoms. Medication changes were
made and anxiety was markedly reduced in approximately 3 weeks
and panic symptoms subsided in 5 weeks.
A 72 year old female with a history of depression and anxiety in
remission underwent VIM DBS. She had a marked lesional effect
and tremor suppression from implantation. Shortly after implantation
of DBS electrodes, she began experiencing panic attacks that
occurred 2-3 times per day which occurred prior to IPG activation.
Turning off stimulation did not alleviate panic. Medication adjust-
ments were made and in 1 month, her panic resolved.
Conclusions: Few negative neuropsychiatric side effects have
been reported from VIM DBS. However, our expert center has
encountered 2 patients who developed panic disorder immediately
following implantation of DBS electrodes in the VIM. This is likely
due to the role of the thalamus in the fear and panic neurocircuitry.
Clinicians should be aware of this possible side effect and be pre-
pared to aggressively manage symptoms as they can markedly inter-
fere with quality of life, despite excellent motor responses to DBS.
Both patients responded to adjustment in medication which led to
remission of their symptoms.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S256 POSTER SESSION
649
Deep brain stimulation (DBS) interleave contact configuration
with implementation of dual frequency stimulation fields
improves control in essential tremor (ET) and reduces adverse
effects
E.M. Feinstein, D.L. Caputo, D.P. Schneider, R.J. DiPaola, S.F.
Danish, E.L. Hargreaves (New Brunswick, NJ, USA)
Objective: To determine if a DBS interleaving contact configura-
tion for ET 1) provides better tremor control with fewer DBS
adverse effects than traditional monopolar or bipolar configurations
(Barbe et al., 2014; Neurology); 2) delivers overall less stimulation
to the surrounding brain tissue than traditional settings; and 3) gener-
ated a two tiered frequency field with a focal area of overlap running
at twice the programmed frequency.
Background: A retrospective chart analysis of 7 ET patients
implanted with Activa family of neurostimulators unilaterally or
bilaterally into ventral intermediate nucleus of the thalamus (VIM)
DBS were assessed for the efficacy of an interleaved contact configu-
ration set at approximately half the frequency parameter from their
previous contact configuration.
Methods: Tremors were assessed via standardized digital Archi-
medes spirals completed under 3 different DBS conditions: optimized
standard settings, post interleave implementation, and DBS off. A
blind observer analyzed line crossings. The total electrical energy
delivered (TEED; Koss et al., Moro et al., 2005; Ann of Neurol) was
calculated for DBS settings pre and post interleaving implementation.
Stimulation fields were visually modeled using Cicerone V1.3 (Mio-
cinovic et al., 2007; Acta Neurochir Suppl).
Results: There were significantly less line crossings in the spirals
performed while on interleaving (M=2.4, SD: 1.95) when compared
to previous optimized settings (M=6.2, SD: 6.2); t(5)=2.29, p50.042.
5 of 6 patients confirmed improved tremor control. Calculated TEED
scores were significantly less for the interleave configuration than for
the previous settings t(9)=2.74, p50.025. The stimulation field mod-
eling demonstrated that interleaving generated two overlapping
spheres of stimulation for all but one of the models. Finally, upon
implementation of interleaving 4 of 6 patients reported improved
speech, while 3 of 6 reported improved gait, clinician notes simi-
larly, confirmed this lessening of DBS adverse effects on speech and
gait.
Conclusions: We provide converging lines of evidence from the
clinic, basic science measurements, and neuroimaging modeling that
support the improved tremor control by a two-tiered frequency stim-
ulation field that also reduces DBS adverse effects.
650
Dorsal lead migration in a dystonia patient following deep brain
stimulation
W. Hu, A.R. Bona, D. Martinez-Ramirez, A. Wagle Shukla, K.D.
Foote, M.S. Okun (Gainesville, FL, USA)
Objective: We report a unique case of lead migration in a dysto-
nia patient following deep brain stimulation (DBS).
Background: DBS therapy has been expanding for the treatment
of Movement Disorders inclusive of dystonia. The occurrence of
lead migration, especially in younger populations has been an evolv-
ing concern, especially with growth of the head and trunk.
Methods: The patient was diagnosed with a non-DYT-1 positive
generalized dystonia. At age 16 he underwent frame-based MRI and
microelectrode-guided bilateral GPi DBS implantation. The post-
operative MRI confirmed proper placement of the DBS leads within
the GPi bilaterally. Following optimization of DBS programming,
his Unified Dystonia Rating Scale score was decreased from 43
points to 22 points. However, at age 23, there were high impedances
across all 4 electrodes of his right lead. Subsequently, an MRI was
also performed and demonstrated a change in lead position bilater-
ally. Finally, he underwent removal of the failed right GPi DBS
Movement Disorders, Vol. 30, Suppl. 1, 2015
lead, and new right GPi lead was implanted. Postoperative MRI con-
firmed proper placement of the right DBS lead within the GPi. We
assessed the leads for migration comparing them to the original
implanted images.
Results: Based on the lead measurements, we observed that both
leads migrated (2014 compare to 2006) prior to his most recent lead
replacement. His right lead migrated 2.9 mm dorsally while the left
lead migrated almost 2 mm dorsally. His height was 172.3cm in
2006, and 180.3cm in 2014 with an 8 cm height increase.
Conclusions: The factors for the lead migration are unknown.
The trunk and brain growth as well as the cervical dystonia symp-
toms may possibly be responsible, but the underlying factors remain
unknown.
651
Functional assessment and quality of life in essential tremor
following treatment with bilateral or unilateral deep brain
stimulation and unilateral focused ultrasound thalamotomy
D.S. Huss, R.F. Dallapiazza, B.B. Shah, M.B. Harrison, J.W. Elias
(Staunton, VA, USA)
Objective: The purpose of this study is to compare functional
outcomes and quality of life in ET patients treated with either bilat-
eral Vim DBS or unilateral procedures of MR guided Focused Ultra-
sound (FUS) ablation or DBS.
Background: Thalamic DBS has largely replaced thalamic radio-
frequency lesioning as the treatment of choice for disabling,
medication-refractory essential tremor. Recently, the development of
transcranial, MR guided high-intensity focused ultrasound (FUS) has
renewed interest in thalamic lesioning.
Methods: This is a retrospective study of medication-refractory
ET patients treated at the University of Virginia with bilateral Vim
DBS (N=57), unilateral Vim DBS (N=13), or unilateral MR guided
FUS Vim thalamotomy (N=15). Tremor was rated for all patients
before and after treatment using the Clinical Rating Scale for Tremor
and Quality of Life in Essential Tremor Questionnaire.
Results: Patients undergoing bilateral DBS treatment had higher
baseline CRST scores, and worse quality of life scores compared to
patients treated with unilateral FUS. Those with both unilateral treat-
ments had less axial tremor and equitable baseline tremor in their
treated hand compared to the patients with bilateral DBS. Patients
had significant improvements in tremor symptoms and quality of life
postoperatively with all treatment types. Bilateral DBS treatments
had greater improvements in tremor, tasks, and total CRST. There
was no difference in the degree of improvement in treated upper
extremity score, disability, or overall quality of life between bilateral
and unilateral procedures.
Conclusions: Bilateral thalamic DBS improves overall tremor
more than unilateral DBS or FUS treatment; however, unilateral
treatments are equally effective in treating contralateral hand tremor.
Despite the greater improvement in overall tremor with bilateral
DBS, there is no difference in disability or quality of life comparing
bilateral versus unilateral treatments.
652
Deep brain stimulation for dystonia: A programming algorithm
evaluated by long-term results of the German multicentre study
for generalized or segmental dystonia
A.D. Kirsch, A.A. Kuhn, J. Muller, J. Volkmann for the Deep-Brain
Stimulation for Dystonia Study Group (W urzburg, Germany)
Objective: To evaluate clinical efficacy of a programming algo-
rithm (PA) for device settings in pallidal neurostimulation for
patients with generalized or segmental dystonia followed up for 3
years (3y) in a controlled multicentre trial.
Background: There are no evidence-based standards for pro-
gramming deep brain stimulation in dystonia.
 POSTER SESSION S257

Objective: To present a series of two patients with a severe

tremor of peripheral origin which responded successfully to DBS of
the VIM.
Background: Charcot Marie-Tooth disease (CMT) is an inherited
disorder of the peripheral nervous system with many clinical and
hereditary variants. Many CMT2 patients are affected by very dis-
abling tremor syndrome which pathophysiology remains unclear.
Deep brain stimulation (DBS) of the ventral intermedium nucleus of
the thalamus (VIM) has been successfully applied to treat most types
of tremors of central origin.
Methods: We present two patients with CMT who during the
course of the disease developed a drug-resistant disabling neuro-
pathic tremor. Clinical course, complementary tests and neurophysio-
logic studies are presented. Due to the lack of response to
pharmacological treatment, they were considered good candidates to
treatment with DBS of the VIM.
Results: Both patients responded positively to stimulation, with a
significant reduction of their level of disability, and with an improve-
ment of their quality of life.
Conclusions: DBS of the VIM is an established treatment for
tremors of central origin. We presented two cases of tremors with a
peripheral cause which responded well to this treatment. Given that
hereditary neuropathies are considered to be clinically heterogeneous,
in our patients the polyneuropathy associated with tremor could be
considered a CMT variant with central nervous system involvement.
Fig. 1. (652). The good clinical response to Vim DBS supports this consideration.

Methods: A standardized monopolar review (130 Hz, 120ls, 60

second duration) for determination of the presumed best therapeutic 654
contact (figure1) [figure1] was applied in 40 patients who were
included in the original trial. Patients were programmed to a voltage Deep brain stimulation in the nucleus ventralis oralis anterior
0.5 V below the threshold of inducing stimulation induced adverse for post anoxic dystonia, case report and review of the
events at the contact chosen according to fig. 1 and kept on these literature?
settings for at least 3 months if tolerated. 38 patients agreed to be M. Mansour, Y.M. Mansour, J. Vaidyanathan (Abu Dhabi, United
followed up annually, of whom 31 attended the 3y follow-up. Effi- Arab Emirates)
cacy of the PA was evaluated based on these results. Changes in
motor performance as measured by proportional change in BFMDRS Objective: Confirm that ventral oralis anterior nucleus (Voa)
motor score, adverse events and need for adjustment of stimulation stimulation is a potential target in deep brain stimulation for the
settings were evaluated. Furthermore, the predictive value of these treatment of post-anoxic dystonia.
features on clinical outcome was detected. Background: Pallidal stimulation is considered the best choice
Results: Average decrease of motor score was 73 6 24% after 3y for primary dystonia patients. When there are structural lesions of
compared to baseline for electrodes showing acute improvement of the GPi, we usually refrain from implanting the electrodes in the
dystonia (n517 contacts; n512 subjects) during the monopolar injured area, although patients suffer from severe disabilities and
review session, whereas contacts without acute benefit (n563) exhib- pain. [figure1]
ited a change of 58 6 30%. Also acute worsening or induction of
dystonia/dyskinesia (n59 contacts, n59 subjects) correlated signifi-
cantly with improvement in motor score after 3y, which amounted to
an average decrease by 78 6 11% vs. 59 6 31% for the other con-
tacts (n571). The other acute stimulation effects showed no signifi-
cant influence on clinical outcome. Both acute worsening and
improvement of dystonia occurred mostly when the second lowest
contact of the quadrupolar electrode was stimulated. Settings were
compliant with the PA in 85% of the electrodes during the initial 6-9
months study period and 67% at 3 years.
Conclusions: A monopolar review session may be helpful in
detecting the best therapeutic stimulation contact in approx. 30% of
the patients exhibiting acute modulation of dystonic symptoms. Both
transient worsening of dystonia as well as acute improvement predict
good long-term outcome.

653
Long term effective thalamic deep brain stimulation (DBS) for
neuropathic tremor in patients with hereditary motor-sensory
polineuropathy
 Marta, R. Ignacio (Madrid,
C.M. Lidia, A.O. Iciar, V. Marta, D.A.
Spain) Fig. 1. (654).

Movement Disorders, Vol. 30, Suppl. 1, 2015

S258 POSTER SESSION
Fig. 2. (654).
Methods: A 38 year old male patient with severe generalized
post anoxic dystonia, and bilateral structural abnormalities of the
GPi was implanted with 2 DBS electrodes in the Voa. High Fre-
quency monopolar chronic Stimulation was conducted (185 Hz, 250
microseconds), the amplitude was increased gradually and the patient
was followed regularly for 12 months.
Results: The functional status and the daily life activities progres-
sively improved 2 weeks post-operatively. At 12 months, the BFM
dystonia scale improved by 48%, UPDRS improved by 54%, he was
able to walk with assistance, eat, vocalize, and had less joints and
muscular pain. [figure2]
Conclusions: Our case confirms the good results obtained in
DBS of the Voa in post-anoxic Dystonia. The Ventral oralis anterior
nucleus; pallidal receiving area in the thalamic nuclei could be an
alternative target when there are structural lesions of the GPi.
655
Therapeutic deep brain ablation via implanted DBS leads:
Technique and potential complications
A. Mantovani, A.R. Bona, M.S. Okun, K.D. Foote (Gainesville, FL,
USA)
Objective: Report a series of 8 brain ablation procedures per-
formed through chronically implanted DBS leads.
Movement Disorders, Vol. 30, Suppl. 1, 2015
Background: DBS has become the mainstay of surgical treatment
for Movement Disorders because it offers diminished risk of neuro-
logic deficits compared to ablative procedures.
In rare complicated cases, permanent removal of DBS hardware
may be indicated even when DBS therapy is providing substantial
clinical benefit. In such cases, we have performed therapeutic lesions
via the indwelling DBS lead prior to its explantation, resulting in
durable benefit to the patient despite loss of DBS therapy.
Methods: From 2004 to 2014, 8 patients had lesions via DBS
leads prior to permanent hardware removal. Mean age 76 6 8 years.
Indications for DBS removal: recurrent scalp erosion-3, infection-3,
enlarging cyst-1, elective-1. Two had PD (1 pallidotomy via GPI
DBS lead, 1 subthalamotomy via STN lead). Six tremor patients had
thalamotomy via VIM leads.
Ablation was performed by attaching a Radionics lesion generator
to the therapeutically active circuit on the DBS lead. Lacking a
thermistor for temperature monitoring at the lesion site, test stimula-
tion was delivered to the awake patient, followed by lesion genera-
tion with continuous neurologic monitoring. Impedance typically
rose with lesion generation and desiccated brain tissue was found
adherent to the therapeutic contacts on the explanted DBS lead.
Results: All 8 patients had durable relief of Movement Disorders
symptoms after ablation. Two (25%) had complications: An 84 yo
man developed a 13mm hematoma at his left thalamotomy site with
dysarthria and hemiparesis. He gradually recovered, and by 6-week
f/u had only mild right hand fine motor deficit and minimal dysarth-
ria. An 81 yo man developed post-thalamotomy dysarthria and dys-
phagia. Imaging showed perilesional edema extending to internal
capsule genu. His deficits had nearly completely resolved at 1-
month.
Conclusions: Brain ablation via indwelling DBS lead prior to its
removal offers a minimally invasive, therapeutic option in rare cases
when permanent explantation of beneficial DBS hardware is neces-
sary. Adhesion of brain tissue to DBS contacts at the lesion site may
increase hemorrhage risk associated with lead explantation. Ablations
may also result in neurologic deficits, especially in elderly patients
with low thresholds for stimulation induced side effects.
656
Two patients with dystonia treated with internal globus pallidus
deep brain stimulation (GPi-DBS) using a multiple independent
source current-controlled system, a case report
O. Morsi, J. Jimenez, B. Cuartero, J. Zamarro, R. Sanchez, M.
Felipe, B. Segura, J.J. Martin (Murcia, Spain)
Objective: To assess benefit of multiple source current steering
in two dystonic patients with GPi-DBS.
Background: GPi-DBS proved to be safe and effective in treat-
ing selected cases of disabling dystonia. The degree of control of the
electric current delivered to the neural tissue is important for optimi-
zation of the therapy. We used a novel DBS system capable of mul-
tiple source current steering to assess its possible extra benefit.
Methods: This case report is in accordance with Declaration of
Helsinki. Patient 1 is an 18 year-old male patient with severely dis-
abling primary generalized dystonia. He had severe dysarthria, dys-
phagia and was dependent for all activities of daily living. Patient 2
is a 43 year old male with a disabling primary generalized dystonia
mainly involving trunk, with a severely impaired gait, sitting and
supine positions. A bilateral GPi-DBS implant was performed,
employing an eight contacts lead for each hemisphere and a
rechargeable pulse generator.
Results: Patient 1 scored 76 on the Unified Dystonia Rating Scale
(UDRS), 91 on the Fahn Marsden scale (BFMS) part 1 and 25 on
part 2, pre-DBS. Sixteen weeks post-DBS, he improved by 32%,
31% and 8% respectively. A mild further improvement was observed
22 months post-op. Patient 2 scored 25 on UDRS, 34 on BMFS part
1 and 11 on part 2, pre-DBS. Sixteen weeks post-DBS, he improved
by 96%, 94% and 91% respectively. This remained stable 17 months
 POSTER SESSION
post-op. Best monopolar stimulation was used in both patients. Vari-
able combinations of multipolar fractionalized current stimulation of
two, three and four adjacent contacts were tried in 8 sessions with
one week intervals in patient 1, with no further clinical improvement.
This was tried in 4 sessions in patient 2 without obtaining superior
results than monopolar stimulation. No adverse events related to the
therapy occurred.
Conclusions: Current steering showed no extra benefit in any of
our two patients. Nonetheless, we suggest larger studies to be done
in dystonic patients to investigate possible benefits of current steering
on symptoms control. The system showed to be safe and clinically
effective in both patients. To our knowledge, patient 1 is the first
dystonia case described treated with this DBS system.
657
Combined anterior and posterior lumbar rhizotomy for
treatment of mixed dystonia and spasticity in children with
cerebral palsy
M.A. Nada, W.A. Abdel Ghany (Cairo, Egypt)
Objective: The aim of this study is to assess the combined rhizot-
omy procedure for treatment of mixed hypertonia in cerebral palsy
(CP) children.
Background: Dystonia is a sustained muscle contraction with
repetitive twisting movements. Children with CP may present with
severe secondary dystonia associated with spasticity of their
extremities.
Methods: 50 children with CP were subjected to combined ante-
rior and posterior lumbar rhizotomies. Post-operative clinical out-
come was recorded and evaluated at 2, 6, 12 months post-
operatively.
Results: This study demonstrates the potential of combined ante-
rior and posterior rhizotomies to improve hypertonia affecting the
upper or lower extremities in patients with mixed spastic dystonic
patients.
658
Reversal of acquired hepatocerebral degeneration with live
donor liver transplant
A.H. Qavi, S. Hammad, A.I. Rana, M. Salih, N.H. Shah, F.S. Dar, A.
Ahmad (Islamabad, Pakistan)
Objective: To determine the radiological and clinical reversibility
of Acquired (non-Wilsonian) Hepatocerebral Degeneration (AHD) in
Chronic Liver Disease (CLD) patients treated with live donor liver
transplantation (LDLT) or optimal medical treatment.
Background: AHD is a chronic neurological disorder, character-
ized by extrapyramidal and neuropsychiatric symptoms accompanied
with CLD and portosystemic shunts. The clinical signs include
Movement Disorders, for instance, ataxia, dystonia, dysarthria,
tremor, and cognitive deficits. Magnetic resonance imaging (MRI)
findings of AHD include hyperintensities of globus pallidus (GP) and
substantia nigra (SN) on T1-weighted sequences. No medical treat-
ment has been reported to reverse its progression. Recent studies
suggest that liver transplant in cirrhotic patients may be an effective
therapy for AHD.
Methods: In this study, we retrospectively reviewed data of
patients with CLD and/or cirrhosis. Data was retrieved, reviewed and
documented on our standard performa. Pre treatment (medically
treated or liver transplant) MRI scans were reviewed for presence of
AHD and compared to follow-up scans after transplant to identify
and document reversibility.
Results: From a total of 63 patients with CLD who underwent
MRI brain in the study period, we shortlisted 12 who underwent
brain MRI scans for Parkinsonism or Movement Disorders. 6 out of
these met the inclusion criteria. Of these 6 patients, 3 were treated
with LDLT and 3 with medical therapy. Clinical and radiological
S259
reversibility was seen in all patients following LDLT on follow-up
examination and MRI brain scans. All 3 patients treated conserva-
tively did not survive long enough for follow-up studies.
Conclusions: Our study suggests that liver transplant significantly
reverses clinical and neuroradiological features in patients with AHD
secondary to liver failure.
659
Does the use of intraoperative microelectrode recording influence
the final location of lead implant in the ventral intermediate
nucleus for deep brain stimulation?
S.T. Reddy, A.J. Fenoy, E. Furr-Stimming, W.G. Ondo, M.C. Schiess,
R. Mehanna (Houston, TX, USA)
Objective: To determine if the use of intra-operative microelec-
trode recording (MER) influences the final location of lead implant
in patients undergoing deep brain stimulation (DBS) of the Ventral
Intermediate Nucleus (VIM), and to assess the incidence of associ-
ated complications.
Background: The usefulness of intraoperative MER in DBS is
debated by some DBS implanting centers, suggesting it increases sur-
gical complications and offers no additional benefit.
Methods: We conducted retrospective chart review of all patients
who underwent DBS with MER targeting the VIM, at the University
of Texas Health Science Center in Houston from June 1st 2009 to
October 1st 2013. Initial coordinates, as determined by pre-operative
MRI, and final coordinates of implant after intraoperative MER were
compared. To assess hemorrhagic and infectious complications, post
operative CT scan of the head and outpatient follow-up notes for a
period of 1 year from the date of surgery were reviewed.
Results: A total of 45 lead implants on 24 patients were
reviewed. Twenty-one patients were diagnosed with essential tremor
and the remaining three had other tremors. The mean age at implan-
tation was 62.42 years (range 18-83). The average duration from
diagnosis to surgery was 21.5 years (range 1-52). A statistically sig-
nificant difference between the initial and final coordinates was
observed only in the superior-inferior plane (p<0.05), with a mean
difference of 0.52 mm inferiorly. A non-statistically significant dif-
ference (p>0.05) was also observed in the medial-lateral plane
(0.02 mm) and the anterior-posterior plane (0.06 mm). One patient
developed an infectious complication (4.2%) that required removal
of leads. On postoperative CT scan, two patients had minimal intra-
ventricular bleeding (8.3%) and one hypertensive patient had mini-
mal sub-arachnoid hemorrhage (4.2%). No symptomatic intracranial
hemorrhages occurred with the 45 lead implants.
Conclusions: In our DBS center, intra-operative MER signifi-
cantly modified final lead location when targeting VIM and was not
associated with increased surgical complications.
660
Does the use of intraoperative microelectrode recording influence
the final location of lead implant in the sub-thalamic nucleus for
deep brain stimulation?
S.T. Reddy, A.J. Fenoy, E. Furr-Stimming, W.G. Ondo, M.C. Schiess,
R. Mehanna (Houston, TX, USA)
Objective: To determine if the use of intra-operative microelec-
trode recording (MER) influences the final location of lead implant
in patients undergoing deep brain stimulation (DBS) of the Sub-
thalamic nucleus (STN), and to assess the incidence of associated
complications.
Background: The usefulness of intraoperative MER in DBS is
debated by some DBS implanting centers, suggesting it increases sur-
gical complications and offers no additional benefit.
Methods: We conducted a retrospective chart review of all
patients who underwent DBS with MER targeting the STN at the
University of Texas Health Science Center in Houston from June 1st
Movement Disorders, Vol. 30, Suppl. 1, 2015
S260 POSTER SESSION
2009 to October 1st 2013. Initial coordinates, as determined by pre-
operative MRI, and final coordinates of implant after intraoperative
MER were compared. To assess hemorrhagic and infectious compli-
cations, post operative CT scan of the head and outpatient follow-up
notes for a period of 1 year from the date of surgery were reviewed.
Results: A total of 62 lead implants on 32 Parkinsons disease
patients were reviewed. The mean age at implantation was 63.7 years
(range 49-79). The average duration from diagnosis to surgery was
9.7 years (range 4-20). A statistically significant difference between
the initial and final coordinates was observed only in the superior-
inferior plane (p<0.05), with a mean difference of 0.29 mm
inferiorly.
There were no infectious complications. One patient had a single
focal intraoperative seizure and one patients postoperative course
was complicated by a brief confusional state. On postoperative CT
scan, three non-hypertensive patients had minimal intra-ventricular
bleeding (9.4%), two patients had minimal sub-arachnoid hemor-
rhage (6.3%) and one had both intra-ventricular and sub-arachnoid
hemorrhage. No symptomatic intracranial hemorrhages occurred with
the 62 lead implants. None of the patients required revision for lack
of benefits or uncontrollable side effects from stimulation.
Conclusions: In our DBS center, intra-operative MER signifi-
cantly modified final lead location when targeting STN and was not
associated with increased surgical complications.
661
Intraoperative thresholds for capsular stimulation are predictive
of the chronic therapeutic window in pallidal deep brain
stimulation for dystonia
R. Reese, D. Falk, H.M. Mehdorn, G. Deuschl, J. Volkmann
(Wurzburg, Germany)
Objective: To compare intra- and postoperative capsular adverse
effects thresholds in pallidal deep brain stimulation (GPi-DBS) for
dystonia.
Background: The influence of the different intraoperative and
postoperative settings (anaesthesia, preinnervation, electrode configu-
ration) on the threshold for tetanic muscle contractions with GPi-
DBS (induced by stimulation of pyramidal tract fibres passing medial
and posterior to the GPi) is unknown. However, there is high clinical
relevance as this threshold is currently the only neurophysiological
marker for intraoperative refinement of the anatomically planned tar-
get point within the motor part of the GPi. The therapeutic window
of GPi-DBS critically depends on this adverse effect as tonic muscle
contractions do not habituate and interfere with the antidystonic
effect of GPi-DBS. On the other hand, muscle contractions induced
only at higher stimulation intensities (e.g. >4 mA) may indicate a
trajectory too lateral or anterior and potentially outside the motor
GPi.
Methods: 6 dystonic patients selected for GPi-DBS according to
commonly accepted clinical criteria, additionally took part in the
study which was approved by our local ethics committee. During our
routine implantation procedure, current amplitude thresholds for cap-
sular side effects were determined at the intraoperatively chosen tra-
jectory and target point for chronic stimulation (90ms pulse width,
130Hz frequency). Stimulation was performed through the uninsu-
lated tip of the microelectrode guide tube. General anaesthesia with
propofol and remifentanil was reduced in dosage to tolerance of the
endotracheal tube during all neurophysiological tests.
Results: Patients were studied in both hemispheres intraopera-
tively and 3 days after implantation. 4 patients could be followed in
the long term (at 6 to 17 months). Postoperative localisation of
chronic stimulation electrodes by MRI determined the stimulation
contact for comparing stimulation thresholds with intraoperative val-
ues. There was no significant change at three days postoperatively
(n512; Wilcoxon matched pairs test) nor in the long term (n58;
Friedman test, post-hoc Dun ns).
Movement Disorders, Vol. 30, Suppl. 1, 2015
Conclusions: The intraoperatively determined threshold for tonic
muscle contractions due to GPi-DBS in dystonic patients closely
matches the thresholds with the fully implanted DBS device.
662
Progressive ataxia under thalamic neurostimulation in essential
tremor, neurostimulation effect or disease progression?
M.M. Reich, J. Brumberg, F. Steigerwald, G. Marotta, T. Musacchio,
D.A. Kirsch, L. Muller, K. Herrmann, A. Buck, J. Volkmann, I.U.
Isaias (Wuerzburg, Germany)
Objective: We investigated brain metabolic changes under differ-
ent deep brain stimulation (DBS) parameters in patients with Essen-
tial Tremor (ET). We aimed to disentangle the effect of thalamic
stimulation from disease progression in the evolution of ataxia.
Background: In a minority of ET patients with bilateral thalamic
DBS, progressive cerebellar symptoms may appear over time and are
difficult to amend by acute changes in neurostimulation parameters.
This phenomenon has also been described as tolerance or rebound
ataxia.
Methods: Five subjects with ET (2 males; median age: 74years)
under stable bilateral thalamic DBS (no stimulation changes in the
last four weeks) with progressive and severe gait-ataxia (unable to
walk unassisted) by means of two sequential cerebral PET and fluo-
rodeoxyglucose (FDG). PET scans were conducted stim-on and 72h
after stim-off. Patients were instructed to fully relax in a lying posi-
tion without any voluntary movement between the FDG injection
and the scan. We performed a statistical parametric mapping voxel-
by-voxel group comparison (stim-on vs.-off) applying the propor-
tional global mean, threshold at p<0.1 and corrected for Family
wise-error (FWE).
Results: At 72h stim-off, gait ataxia dramatically improved in all
subjects (all were able to walk unassisted), whereas tremor reap-
peared with a pre-surgery severity. Compared to 72h stim-off, FDG
uptake in stim-on was significantly increased selectively in the cere-
bellar nodule (T=6.40, p<0.01) and reduced in bilateral precentral
gyri (left1right BA 4 p<0.001). Of interest, shortly after switching
DBS off (first 30min.), both tremor and gait-ataxia dramatically
worsened (rebound).
Conclusions: Our study suggests that progressive gait-ataxia in
ET patients, under chronic thalamic DBS, is a reversible cerebellar
symptom induced by neurostimulation. The increased FDG uptake in
the cerebellar nodule, combined with a reduced cortical metabolism
suggests cerebello-thalamo-cortical network effects including an anti-
dromic effect of thalamic DBS on outflow pathways of the vestibulo-
cerebellum. It is not consistent with an antidromic activation of
dentate-thalamic fibers -the presumed target of effective thalamic
DBS- which should result in metabolic changes of the cerebellar
hemispheres. The initial rebound and delayed improvement of ataxia
raises the possibility of neuroplastic or adaptive cerebellar
mechanisms.
663
Force platform analysis after deep brain stimulation of
peduncolopontine nucleus in progressive supranuclear palsy:
Report of one case
C.O. Souza, R. Brant, A.L. Pardini, D. Boari, L.A. Teixeira, M.J.
Teixeira, E.R. Barbosa, E.T. Fonoff (Sao Paulo, Brazil)
Objective: The aim of our study was to evaluate further the
potential role of bilateral pedunculopontine nucleus (PPN) deep brain
stimulation (DBS) as a treatment for balance disorders in PSP.
Background: Progressive supranuclear palsy (PSP) is a neurode-
generative disease due to mitochondrial dysfunction. The PSP syn-
drome presents generally with balance and gait disorders,
Parkinsonism, ophthalmoparesis and cognitive alteration. Few reports
exist on deep brain stimulation (DBS) in patients with atypical
 POSTER SESSION
Fig. 1. (663).
Parkinsonism, like in PSP. Targeting and neuromodulation peduncu-
lopontine nucleus (PPN) has emerged as a potential intervention for
patients with balance disorders.
Methods: A patient with PSP underwent bilateral PPN-DBS and
was followed clinically for over 03 months. Before and after the sur-
gery, her balance was assessed on a force platform in four conditions
resulting from the combination of vision availability and surface
kind (firm or foam). The patient performed 30 seconds of each bal-
ance evaluation without medication (OFF) and with medication (ON)
before the PPN surgery (pre-test), 30 after (PT30) and 60 days after
the surgery (PT60).
Results: Descriptive main results of force platform showed for
foam surface increased area, and mediolateral amplitude of center of
pressure (CoP ml) in PT60 in both visual conditions, only when the
patient was ON, and decreased of these variables in both visual condi-
tions when the patient was OFF. For firm surface, she showed
increased area of CoP and CoPml in ON conditions in PT60 [figure1].
Conclusions: Results showed that the performance of balance
control improved after the surgery only when the patient was OFF
medication. Increased dyskinesia due to antiParkinsonian medication
may be related to worsened postural control in ON medication condi-
tion after the PPN surgery. Larger cohorts with longer follow ups are
needed to evaluate more exhaustively the efficacy of bilateral PPN-
DBS in PSP.
664
Coaxial deep brain stimulation of ventral thalamic nuclei and
posterior subthalamic area for Movement Disorders
H. Toda, H. Saiki, R. Okumura, S. Matsumoto, K. Iwasaki (Osaka,
Japan)
Objective: Thalamic ventral intermediate nuclei (Vim) is the rep-
resentative target to surgically control tremors using deep brain stim-
ulation (DBS). Recent investigations also show posterior subthalamic
area (PSA) as a target to control tremors. The aim of this study is to
evaluate the clinical effects of coaxial stimulation of Vim and PSA.
S261
Methods: We have retrospectivelly analyzed 7 cases of various
tremors (7 males; age, 17-72 years; 4 cases of Vim-DBS, 3 cases of
Vim1PSA-DBS). The 2 patients with intentional tremors were
treated with Vim1PSA-DBS. Tremors were evaluated before and
after the DBS treatment. The preoperative investigation were mag-
netic resonance structural T1/T2 weighted imaging and diffusion
weighted imaging(DWI). Diffusion tensor imaging (DTI) analyses
were done with DWI. Postoperative computed tomography images
were fused with preoperative MRI images to evaluate the position of
the implanted electrodes. The follow-up periods were 2-8 years.
Results: In both groups, significant improvement of tremors were
confirmed. The DTI analyses evaluated the topographical relation-
ships between the electrodes and the fibers of the corticothalamic
projections or the dentatorubrothalamic fibers. The suppression of
intentional tremors were more significant by using the PSA stimula-
tion than by using the Vim stimulation. There were no severe com-
plications and the transient complications by stimulating the
spinothalamic tract and pyramidal tract were avoided by re-
programming of DBS parameters.
Conclusions: Both Vim stimulation and PSA stimulation are
effective to control tremors. PSA-DBS is effectively control inten-
tional tremors. Co-axial DBS of Vim and PSA is useful surgical
options to treat various tremors by minimizing the surgical invasion.
665
Subthalamic stimulation for tremor
A.T. Tran, G. Moguel-Cobos, R. Dhall, A. Lieberman (Phoenix, AZ,
USA)
Objective: A case where subthalamic nucleus (STN) Deep Brain
Stimulation (DBS) for the treatment of both essential tremor (ET)
and Parkinsons disease (PD) in a patient failed to control his tremor
despite accurate placement of the DBS lead.
Background: Jankovic has proposed that the presence of essen-
tial tremor perhaps predisposes a person to develop Parkinsons dis-
ease. He reports that about 20% of patients with ET has associated
Movement Disorders, Vol. 30, Suppl. 1, 2015
S262 POSTER SESSION
Parkinsonism. The term benign tremulous Parkinsonism is used to
describe patients with prominent resting and action tremor with mild
Parkinsonism, slowly progressive disease and limited response to lev-
odopa. These patients with mixed tremor present a treatment
dilemma in choosing a surgical target. The traditional target for
essential tremor treatment is the VIM thalamus; whereas for Parkin-
sons patient with tremor, the preferred target is the STN. However,
case reports by Lind state that STN targets are also effective in treat-
ing essential tremor. And Savica said that for benign tremulous Par-
kinsonism, tremor response to either VIM and STN targets.
From the current literature and from a case report by Vitek group,
one would conclude that STN DBS should be the target of choice for
the treatment of patient with combined PD and ET because it provides
both tremor control as well as control of rigidity and bradykinesia.
Methods: Case report.
Results: An 80 year old man with ET for 30 years and PD for 1
year, confirmed with positive DAT scan, with prominent right > left
hand mixed tremor. His tremor is 3=4 with right hand postural and
action tremor, and 2/4 with right hand rest tremor. Left hand without
rest and 1/4 postural tremor, 2/4 left hand action tremor. He had
minimal bradykinesia and rigidity. He had left STN DBS placed
with good placement verified with post-operative MRI 3D SPGR
aligned on stealth system. His tremor minimally improved after three
months of intensive programming by two different Movement Disor-
ders specialist, despite stimulation induced dyskinesia of the right
leg. His right hand tremor continues to impair his ADLs.
Conclusions: This case illustrates that for patient with long stand-
ing history of action-postural tremor of both hands who later develops
Parkinson, the target for treatment of tremor is not always clear cut.
Most case reports suggests STN DBS to be the preferred target. How-
ever, if hand tremor is the most disabling symptom to the patient, the
target perhaps should be the VIM thalamus instead of the STN.
666
STN DBS in dystonia modulates sensorimotor integration and
plasticity but not motor cortex excitability
A. Wagle Shukla, J. Ostrem, D. Vaillancourt, K. Foote, J. Shuster,
M. Okun (Gainesville, USA)
Objective: To determine the physiological effects of subthalamic
nucleus (STN) deep brain stimulation (DBS) in predominantly pri-
mary cervical dystonia (PCD).
Background: STN DBS is clinically effective for treatment of
medication refractory PCD however the underlying mechanism of
action is not known. We used transcranial magnetic stimulation
(TMS) techniques to examine the physiological effects of STN DBS.
Methods: PCD subjects were examined with STN DBS turned
ON and OFF (atleast 4 hours) and these were compared with DBS
nave PCD subjects and healthy controls. Short latency afferent inhi-
bition (SAI) was determined with TMS pulse delivered to the pri-
mary motor cortex preceded by median nerve stimulation at the wrist
at 20 and 30ms. Long latency afferent inhibition (LAI) was deter-
mined with a TMS pulse preceded by median nerve stimulation at
150 and 200ms. Additionally SAIdualstim and LAIdualstim were
recorded when the median nerve was simultaneously stimulated with
ulnar nerve (dual stimulation). Short interval intracortical inhibition
(SICI) and intracortical facilitation (ICF) was recorded for motor cor-
tex excitability. A paired associative stimulation protocol (PAS) was
used for assessment of sensorimotor plasticity in which 90 pairs
were delivered of the TMS pulse to the motor cortex and these were
preceded by median nerve pulse at the wrist.
Results: 18 subjects with PCD (9 men, 9 women) were enrolled
(study is actively enrolling). Mean (6SD) age was 58(612.9) years.
7 subjects had STN DBS, mean(6SD) duration after DBS was
5(63.2) years. In the interim analysis, SAI in PCD was significantly
increased (p50.03) but SAIdualstim was reduced (p50.04) at 20ms
only. With DBS turned ON, both SAI (p50.04) and SAIdualstim
(p50.05) normalized toward values of healthy controls. LAIdualstim
Movement Disorders, Vol. 30, Suppl. 1, 2015
was reduced at both 150ms (p50.04) and 200ms (p50.054) and was
corrected with DBS turned ON at 150ms (p50.03) and 200ms
(p50.001). STN DBS had no effects on SICI and ICF, however STN
DBS corrected the PAS (p50.04) that was abnormally increased in
PCD compared to healthy controls (p50.056).
Conclusions: STN DBS modulates sensorimotor integration (SAI,
SAIdualstim, LAIdualstim) and sensorimotor plasticity (PAS) but does
not influence the motor cortex excitability (SICI and ICF). These
findings suggest there are multiple differential mechanisms of action
for STN DBS in dystonia.
667
Combined deep brain stimulation in the internal globus pallidus
(GPi) and pallidothalamic tract (PTT) in a patient suffering from
a nigrostriatal lesion due to subarachnoid haemorrhage
N.A. Wegener, S. Haegele-Link, K. Georg, P. Anita, B. Thomas, B.
Ronald (St. Gallen, Switzerland)
Objective: Deep Brain Stimulation (DBS) with a combination of
different targets including the pallido-thalamic tract (PTT, fasciculus
thalamicus) can be a promising treatment option for midbrain tremor
with severe nigrostriatal lesions.
Background: DBS of the nucleus ventralis intermedius thalami
(Vim), the internal globus pallidus (GPi) and subthalamic nucleus
(STN) is a very effective treatment for Parkinsons symptoms, tremor
and dystonia. On the other hand data regarding its effectiveness to treat
midbrain tremor are sparse. Because some of these lesions involve
nigrostriatal fibres, stimulation of targets used in Parkinsons disease
(PD) could be a reasonable option. Apart from STN and GPi stimula-
tion it is known from lesional studies in PD that lesioning the PTT of
the subthalamic area is very effective to treat Parkinsonian symptoms.
We present the case of a 23-year old man who developed a unilateral
Parkinsonism after a subarachnoid hemorrhage with large midbrain
lesions at the age of 19. The disabling tremor showed a very low fre-
quency of 1-2 Hz as a combination of rest, posture and action tremor.
DatScan investigation showed a complete denervation of the left-sided
presynaptic dopaminergic neurons due to the nigrostriatal lesion. Levo-
dopa and other dopaminergic medication brought a significant improve-
ment but revealed intolerable side effects in terms of massive levodopa
induced dyskinesia and the patient was evaluated for DBS.
Methods: DBS was performed in the PTT, the STN and the GPi
contralateral to the side of the tremor dominant Parkinsons syn-
drome. After a suicide attempt STN was not used for the therapy.
Results: Stimulation of the PTT showed a significant improve-
ment of the tremor lasting to date 6 months after the operation. Stim-
ulation of the GPi enabled a dopaminergic therapy and reduced the
associated dyskinesia.
Conclusions: The stimulation of the PTT seems to be a promis-
ing target for tremor suppression using DBS. Additional stimulation
of the GPi reduced the hyperkinetic side effects of the dopaminergic
treatment in this patient suffering from symptomatic Parkinsonism.
Experience from further lesional studies could be helpful defining
new stereotactic targets in DBS.
Other
668
The Parkinsons disease and Movement Disorders program at
King Fahad Medical City
F.Y. AlSwaiti, J.A. Bajwa, R. Mayo (Greensboro, NC, USA)
Objective: To chronicle the initiation and development of the
Parkinsons disease and Movement Disorders program under the
umbrella of the National Neuroscience Institute at King Fahad Medi-
cal City in Saudi Arabia and illustrate the methodology and philoso-
phy behind achieving optimal care based on available resources and
evidence based practices.
 POSTER SESSION
Background: In depth research on neurodegenerative disorders
and Parkinsons disease specifically is limited in Arab countries; the
Kingdom of Saudi Arabia is no exception. While the Kingdom of
Saudi Arabia is an emerging entity in the medical arena as far as the
Arab World and the Middle East is concerned, Lack of research has
resulted in limited medical and rehabilitative care in the kingdom as
well as limited awareness about the disease. In 2004 King Fahad
Medical City was established to serve the population of Riyadh, the
capital of Saudi Arabia, and one of the most populated cities in the
region. King Fahad Medical City has launched the Parkinsons dis-
ease and Movement Disorders program to provide comprehensive
care for patients in the country and the Gulf region.
Methods: A complete chronicle of all the historical events that
lead to the initiation and development of the Parkinsons disease and
Movement Disorders program along with statistical data discussed in
the paper to illustrate the most recent achievement of the program in
a time span of more than two years.
Results: Currently, the program is the first in the country to pro-
vide comprehensive medical and rehabilitative services for patients
suffering from Parkinsons disease and other Movement Disorders,
setting high standards and establishing foundations for research and
regional awareness.
Conclusions: The benefits of starting a new program in a develop-
ing country is the opportunity to learn from previous experiences as
well as adopting a modern methodology in interdisciplinary approaches
in health management while using evidence based practices.
669
The effect of motor imagery on stepping characteristics and
motor control of gait in persons with Parkinsons disease
P.E. Atwood, W.J. Farrington, A.C. Brandt, A. Smiley-Oyen, K.A.
Lowry (Des Moines, IA, USA)
Objective: To determine the effect of a gait motor imagery prac-
tice (MIP) program on gait control in persons with Parkinsons dis-
ease (PD).
Background: MIP is the rehearsal of imagining an action without
physical execution. MIP facilitates motor skill learning in both
healthy adults and persons post stroke; there is limited clinical evi-
dence to support the use of MIP with persons with PD, and specifi-
cally to improve motor skill in walking.
Methods: 14 community dwelling persons with PD (2 men, mean
age 66.6 yrs 67.7, mean HY 2.4, range 1-3) participated in this pilot
study. The MIP gait program consisted of a self-paced computer pre-
sentation with embedded video and auditory cues. Participants prac-
ticed motor imagery of usual walking, of walking while negotiating
obstacles, and of walking a serpentine path. Usual and dual-task gait
(counting backwards by one) was assessed pre and post MIP using
an instrumented walkway and trunk accelerometer to determine
changes in: 1) stepping characteristics- speed (m/s), step length (cm),
cadence (steps/min); and 2) motor control of walking- stride time
variability(s), smoothness of walking in the forward direction. Wil-
coxon sign ranked tests were used to determine pre/post mean
changes in walking.
Results: For usual walking, gait improved. Both stepping charac-
teristics (mean gait speed change 5 0.11m/s, p5.016; mean step
length change=4.1cm, p5.022) and motor control of walking
increased (mean change in smoothness 5 0.39, p5.009), while stride
time variability decreased (mean change 5 0.02s, p5.008). For dual-
task walking, stepping characteristics improved (mean gait speed
change 5 .11m/s, p5.009; mean step length change= 5.9cm, p5.001)
but there were no changes in the motor control of walking.
Conclusions: Following MIP, persons with PD walked faster and
took longer steps in usual and dual-task walking, and demonstrated
improved motor control in usual walking. MIP had a specific effect on
increasing step length, despite no explicit instructions to imagine tak-
ing bigger steps. Based on the findings, improvements in motor con-
trol from imagery may be task-specific. Alternatively, more imagery
S263
practice may be required for transfer of motor control to dual-task
walking conditions. These data indicate that a gait MIP program may
be a safe, no-cost strategy that could be implemented in- home to
improve the motor skill of walking in individuals with PD.
670
Antibody spectrum in stiff person syndrome and related
disorders
B. Balint, I.M. Bl
ocker, M. Unger, W. St ocker, C. Probst, L.
Komorowski, H.M. Meinck (London, United Kingdom)
Objective: To determine the spectrum and prevalence of antibod-
ies associated with Stiff Person Syndrome and related disorders
(SPSD) in a large cohort.
Background: New antibodies targeting the glycine receptor
(GlyR), GABA A receptor (GABAAR), and dipeptidyl-peptidase-like
protein-6 (DPPX) have been recently described in SPSD. Such neu-
ronal surface antibodies are deemed pathogenic and to be associated
with a better response to immunotherapy compared to the hitherto
known antibodies against intracellular antigens like glutamic acid
decarboxylase (GAD), amphiphysin, and gephyrin.
Methods: We included 73 SPSD patients (SPS=44; SLS=6;
PERM=23) and 5 patients with acquired hyperekplexia, 3 of them
with brainstem encephalitis. Previous positive antibody results (labo-
ratories Prof Vincent, Oxford, and University Hospital Heidelberg)
were included in the evaluation. For antibody detection we used indi-
rect immunofluorescence applying frozen tissue sections (rat: hippo-
campus, cerebellum; monkey: cerebellum) and recombinant cell
substrates, each expressing a different neuronal antigen [GABABR,
GABAAR (A11B3), GlyR, GAD65, amphiphysin, gephyrin, DPPX,
SLC6A5/GlyT2].
Results: 54 SPSD sera contained GAD-ab (SPS=31; PERM=19;
SLS=4). 7 of the GAD-ab positive sera harboured also GlyR-ab
(n51, SPS), GlyT2-ab (n52, PERM), or amphiphysin-ab (low titre
n53, 1 SPS, 1 PERM; high titre n51, paraneoplastic SPS). 3 SPS
patients had high titres of amphiphysin-ab; in 2 cases a paraneoplas-
tic aetiology was established, for 1 patient data were incomplete.
GlyR-ab were present in 9 sera (SPS=7, PERM=2); in 3 of these,
other antibodies were also present (low titre DPPX-ab, n52 (SPS),
GAD-ab in 1 SPS patient). DPPX-ab at high titres were present in 2
sera of previously reported PERM patients. 1 patient with brainstem
encephalitis with hyperekplexia had GlyR-ab and gephyrin-ab. No
antibodies were detected in the remaining hyperekplexia patients and
in 6 SPSD patients. No patient had GABAAR-ab.
Conclusions: We found antibodies against the presynaptic
surface-expressed GlyT2 for the first time and report the second case
with gephyrin-ab. Altogether, GAD-ab were the most prevalent
(74%) followed by GlyR-ab (17%). Amphiphysin-ab were most fre-
quently associated with paraneoplastic disease. DPPX-ab and
GABAAR-ab seem not to be frequent in SPSD. Multiple antibodies
occurred overall in 13%. We did not observe any phenotype-serotype
correlation which might guide antibody testing.
671
NMDAR-antibodies in atypical corticobasal syndrome New
phenotype or (contributing) epiphenomenon?
B. Balint, R. Erro, M. Stamelou, F. Brugger, E. Antelmi, A. Batla, C.
Ganos, A. Vincent, K. Bhatia (London, United Kingdom)
Objective: To present 2 patients with NMDAR-antibodies and a
clinical syndrome atypical for anti-NMDAR encephalitis and for
known degenerative entities.
Background: N-methyl-D-aspartate receptor (NMDAR) antibod-
ies (ab) of IgG subtype are known to cause an autoimmune encepha-
litis with a characteristic clinical picture of acute psychiatric
disturbance, typical orofacial and limb dyskinesia, epilepsy, mnestic
deficits, and dysautonomia.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S264 POSTER SESSION
Methods: Case description; indirect cell surface immunocyto-
chemistry with live HEK293 cells transfected with cDNAs of NR1
and NR2B subunits, evaluated by a visual scoring system (visual cell
based assay score (vCBAs), range 0-4).
Results: Case1: A 45yr old man developed over 1yr an asymmetric
syndrome of dystonia, myoclonus, apraxia, along with cerebellar signs
and memory deficits. Routine investigations were normal. CSF con-
tained raised protein 0.84 g/l and unmatched oligoclonal bands.
NMDAR-IgG-ab were detected in the serum (vCBAs 1; later 0 in
serum/CSF) in absence of other antineuronal antibodies. After plasma
exchange he improved remarkably, but symptoms did not recover com-
pletely. He refused further treatment; after 1yr, he was unchanged.
Case2: A 55yr old man developed over 4yr an asymmetric syn-
drome with dystonic posturing and apraxia of the right hand,
stimulus-sensitive myoclonus, hyperreflexia (right>left), and ataxic
gait. He then deteriorated quite rapidly (cognition, speech, walking).
Routine investigations, onconeuronal and VGKC antibodies were
unremarkable/negative. A DaT-Scan was abnormal. The patient died
after 5yr from onset apparently from a sudden hearth attack. Stored
samples revealed serum NMDAR-IgG-ab (vCBAs: 1.5/2/1).
Conclusions: The clinical picture of both patients was neither in
keeping with the classical presentation of anti-NMDAR encephalitis
nor with typical etiologies causing corticobasal syndrome (cerebellar
signs; young age in case1; rapid deterioration in case2). Case1 showed
some response to immunotherapy and had an inflammatory CSF pro-
file. His antibody titre however was very low, and would be nowadays
considered negative. The questions raised by these cases are: Is there
a broadening clinical spectrum associated with NMDAR-ab? Could
NMDAR-ab be incidental or an epiphenomenon? Could NMDAR-ab
contribute to another underlying pathology? In summary, these cases
highlight a grey area which warrants further investigation.
672
Development and evaluation of a patient decision aid, should you
have botulinum toxin injections or surgery for hemifacial spasm
C.T. Barrett, D.A. Grimes, V. Parker (Ottawa, ON, Canada)
Objective: To develop and evaluate a patient decision aid to
improve the care choices for individuals with hemifacial spasm.
Background: Hemifacial spasm (HFS) is a chronic condition that
is unlikely to spontaneously improve, and can be functionally dis-
abling for those that it affects. Patients with HFS have only two
treatment options, botulinum toxin (BTX) injections or microvascular
decompression surgery (MVD). BTX injections have no long term or
significant side effects but require repeat injections. MVD is poten-
tially curative, but carries significant, albeit small, surgical risks. A
decision aid is a written tool that provides facts about options, shows
probabilities of benefit and harm, explores which benefit and harm
matters most to the patient, and guides them through the decision.
Methods: The initial decision aid was developed based on best
available evidence. The format of the patient decision aid is based on
the Ottawa Personal Decision Guide (OConnor et al 2000) and in con-
cordance with the International Patient Decision Aid Standards criteria.
6 HFS patients and 5 health care professionals (neurosurgeon who per-
forms the surgery, 2 neurologists who regularly give BTX, a general
neurologist who doesnt use BTX and a Movement Disorder nurse)
were then recruited, all of who completed questionnaires prior to
reviewing the patient decision aid, and again afterwards, to see if the
aid met their decision-making needs. The format of these surveys
(patients and health professional versions) were based on the Ottawa
Decision Support Framework, Decision Aid Acceptability (Barry et al
1995) and Preparation for Decision Making Scale (Graham et al 1995).
Results: A new decision aid has been developed to help guide
patients to better understand the benefits and potential side effects of
the two treatment options for HFS.
Conclusions: A decision aid may be helpful when there is more
than one reasonable option and patients may value the features of
the options differently. We are currently field testing this newly
Movement Disorders, Vol. 30, Suppl. 1, 2015
developed decision aid with 40 HFS patients. We will examine how
the new patient decision aid changes the patients baseline preferen-
ces and decisional needs, and whether their treatment choice is
affected by age, level of disability, and use of BTX.
673
Effect of progressive aerobic and large-amplitude training
(PWR!Moves) on advanced Parkinsons disease - A case study
J. Bazan-Wigle, K. Moynahan, B. Farley (Tucson, AZ, USA)
Objective: This case study was done to evaluate the achievability
and effects of high effort exercise training on functional mobility in
an individual with advanced PD.
Background: Vigorous exercise may improve functional mobility
in mild-moderate Parkinsons disease (PD). However, there are few
studies demonstrating its effect on individuals with advanced PD
progression (H&Y4/5). Per Hoehn & Yahr classification, persons in
stage 4 are still able to walk and stand unassisted, but they are mark-
edly incapacitated in their ability to perform activities of daily living
(ADL). Persons in stage 5 are confined to bed or wheelchair unless
aided (Hoehn & Yahr, 1967).
The subject of this case study is a 67 year old male, with a disease
duration of 22 years. He has been classified as H & Y stage 4/5.
Methods: The subject was seen for 13, 1-hour sessions, 3-5x per
week. Initial assessments performed were: 1X Sit <-> Stand, Timed Sit
<-> Supine, 10 Meter Walk Test, and 2 Minute Walk Test. The inter-
vention consisted of a combination of: progressive aerobic treadmill
training with a harness, and overground gait training with front wheeled
walker (60% of treatment), and PWR!Moves (functional, large ampli-
tude exercises) performed repetitively and in various positions, with
emphasis on maximum range of motion and effort to address posture,
weight shift, axial rotation, and transitioning (40% of treatment).
Results: All pre- to post-assessments were improved: 1X Sit <->
Stand: 64.1 seconds to 4.22 seconds (15.2X faster than baseline); Sit
<-> Supine: 152.47 seconds to 13.06 seconds (11.7X faster than
baseline); 10 Meter Walk Test: .15 m/s to .40 m/s (2.7X faster than
baseline); and 2 Minute Walk Test: 3.0 meters to 19.23 meters
(541% improvement). The subject also reports improved quality of
life, as he is able to increase duration of time out of wheelchair
(WC) vs. in WC at Assisted Living Facility.
Conclusions: Following intervention, the subject demonstrated
improved speed with all functional mobility, improved endurance and
increased ground walking distances, including turns. This case study
concludes that vigorous exercise for advanced PD progression may
show improved endurance, functional mobility, and impact quality of
life. The subject has continued with this program, additional assess-
ments have been performed and data collection is ongoing.
674
Ultrastructural distribution and features of dopaminergic and
cholinergic innervations of the primate subthalamic nucleus
H. Belaid, L. Parolari, D. Tande, M.P. Muriel, D. Chauvet, B. Lau,
C. Francois, C. Karachi (Paris, France)
Objective: To characterize the dopaminergic and cholinergic
innervation of the primate subthalamic nucleus (STN).
Background: Deep brain stimulation of the STN alleviates motor
as well as psychiatric symptoms highlighting its powerful role in
controlling behaviour in human. Cortical and pallidal inputs subdi-
vide the STN into three anatomofunctional territories: a dorsolateral
sensorimotor, a central associative and an anteromedial limbic. In
addition, the STN receives modulatory inputs from dopaminergic and
cholinergic neurons that could differentially modulate these territo-
ries. In this study we analyzed the distribution and features of these
inputs, which are poorly characterized in the primate STN.
Methods: We observed tyrosine hydroxylase (TH) and choline
acetyl transferase (ChAT) immunoreactivity by light and electron
 POSTER SESSION
microscopy in four postmortem STN (2 macaques, 2 humans). Each
STN was subdivided into medial, centrodorsal, centroventral and lat-
eral parts in order to describe the features of TH and ChAT positive
(1) elements. TH1 axons were quantified by counting the number
of TH1 fibers crossing regularly distributed 100 mm squares at two
anteroposterior levels.
Results: In both species, numerous TH1 axons entered the STN
anteromedially and coursed dorsally until its lateral part. These axons
consisted of numerous myelinated TH1 fibers that were more promi-
nent in humans than monkeys. In the anteromedial STN, we
observed many small unmyelinated varicose TH1 processes that
formed symmetric synapses, with rare asymmetric synapses. Few
TH1 cell bodies were encountered. TH immunoreactivity was weak
in the centroventral STN. TH1 axons exhibited a gradient in density
with 43 6 14 fibers in the anteromedial part, 32 6 8 in the centrodor-
sal part, 21 6 7 in the lateral part and 14 6 4 in the centroventral
part. Conversely, thin and varicose ChAT1 axons were abundant
and homogenously distributed throughout the monkey and human
STN, where they formed asymmetrical synapses.
Conclusions: We showed that dopaminergic innervation is denser
in the limbic territory of the STN. However, the associative and the
sensorimotor territories also receive dopaminergic innervation but
only dorsally. Conversely, cholinergic inputs terminate uniformly
throughout the entire nucleus. These findings suggest that dopaminer-
gic inputs may differentially modulate the anatomofunctional territo-
ries of the primate STN.
675
Using a wearable sensor to evaluate activity and motor response
fluctuations in patients with Parkinsons disease (PD):
Preliminary findings
H. Bernad-Elazari, A. Weiss, S. Oren, Y. Cohen, A. Mirelman, N.
Giladi, J. Hausdorff (Tel Aviv, Israel)
Objective: To evaluate if a body-worn sensor can help assess
activity and motor response fluctuations.
Background: Self-reporting and repeated testing by a clinician
are commonly used to assess motor response fluctuations; however,
these approaches are intrusive and may not be sensitive to therapeu-
tic changes.
Methods: This was an ancillary study of a phase II randomized,
placebo-controlled, double-blind trial with ND0612L, sponsored by
NeuroDerm Ltd. 22 patients with PD and motor response fluctuations
(age: 62.8 6 7.0 yrs, UPDRS motor score: 25.5 6 11.4) received their
optimized current oral treatment (dose reductions permitted), and
were randomized to adjunct therapy (treatment group, TG, n514) or
placebo (PG, n58). The TG received a proprietary liquid formulation
of levodopa/carbidopa (ND0612L) that enables subcutaneous admin-
istration to achieve steady levodopa plasma levels. Subjects wore a
3D accelerometer on their lower back for 6 days before (pre) and for
6 days while receiving the treatment (during). In each 6 day period,
the time spent walking and being inactive (i.e., lying or sitting) were
determined. Wilcoxon signed ranked non-parametric tests evaluated
the effects of the treatment (or placebo) on activity.
Results: Total time walked over the 6 days increased (p50.048)
from 652.9 6 266.6 min (pre) to 724.9 6 292.5 min (during) in the
TG, but did not change in the PG (p50.249). Total inactive time
tended to decrease in the TG (pre: 8,380 6 3,044 min, during:
7,760 6 2,728 min; p50.056), but not in the PG (p50.401). The
time spent walking between 4:005:00 AM, i.e., during sleep time,
decreased (i.e., improved) in the TG (pre: 73.5 6 88.7 sec; during:
50.4 6 77.8 sec; p50.011), but not in the PG (p50.161). The time
spent walking between 67 AM, i.e., at the start of the day,
increased (i.e., improved) in the TG (pre: 104 6 112 sec; during:
162 6 125 sec; p5 0.003), but not in the PG (p50.263).
Conclusions: These initial findings support the idea that a contin-
uously worn body-fixed sensor can provide objective assessment of
activity that is sensitive to a pharmacologic intervention. The
S265
changes in the sensor-derived metrics suggest that the treated patients
became more active during the day and more inactive at night, possi-
bly a reflection of a reduction in motor response fluctuations.
676
Optimizing CNS-delivery by lactyl stearate-coupled liposomes
M. Bhargava, S. Bhargava, N. Kapoor, G. Agarwal, V. Bhargava, S.
Jain (Kanpur, India)
Objective: Meningitis is the inflammation of tissues which covers
brain & spinal cord. Thus lactyl stearate coupled liposomes bearing
rifampicin (highly lipophilic) is used for effective management of
meningitis.
Background: Brain drug targeting brings a healthy skepticism to
the study of the BBB, which is the most frustrating obstacle for
pharmacologists wishing to find treatments for brain disorders. The
BBB restricts the brain uptake of many valuable hydrophilic drugs
and limits their efficacy in the treatment of brain diseases because of
the presence of tight junctions, high metabolic capacity, low pino-
cytic vesicular traffic and efficient efflux mechanisms.
Methods: Lactyl stearate synthesized from stearic acid & lactic
acid was used to prepare liposomes bearing rifampicin by Lipid cast
film method. Formulations were characterized for vesicle shape by
Transmission Electron Microscopy (TEM), average vesicle size, drug
entrapment efficiency, in-vitro drug release. The in-vivo studies the
drug distribution in various organs and blood of albino rats was
assessed after I.V. administration. The quantitative uptake of the for-
mulations by the brain in albino rats was assessed by fluorescent
microscopy.
Results: The average particle size ranged from 2.33 to 1.0 lm.
The % encapsulation efficiency was 41% & 34% in uncoupled &
coupled liposomes. Brain uptake was increased about 2-3 times in
case of uncoupled liposomes and plain drug. Accumulation was
increased about 6-8 times with coupled liposomes in comparison to
uncoupled and about 10-12 times higher compared to drug solution.
Conclusions: Higher uptake of lactyl stearate coupled liposomes
can be explained as, the mono carboxylic acid transporters present
on brain endothelial cells, cross the BBB by carrier mediated trans-
port mechanism. Fluorescence study indicates that the preparation is
crossing basal carotid system & accessing the nervous system. 6-CF
was distributed in blood vessels and accumulated in cerebellum and
cerebrum. This delivery system not only increased the brain uptake
of the drug but it also reduces the administered dose and toxic effect
of the drug. Hence it proves great potential in the delivery of the
drug into brain for the treatment of the diseases associated with the
brain where very limited drug are available for those diseases. Thus,
Lactyl stearate coupled liposomes effectively delivers the drug to the
brain and has great potential for brain targeting.
677
The figure-of-8 walk test: A clinical measure of motor skill in
walking for persons with Parkinsons disease
A.C. Brandt, P.E. Atwood, W.J. Farrington, J. Van Swearingen, K.A.
Lowry (Des Moines, IA, USA)
Objective: The purpose of this study was to examine the concur-
rent and construct validity of the Figure-of-8 Walk Test (F8WT) as a
measure of walking skill and motor planning in persons with Parkin-
sons disease (PD).
Background: F8WT is a test of curved-path walking that simu-
lates the complexity of walking in daily life. The F8WT is a reliable
and valid measure of walking skill and relates to executive cognitive
function in older adults with mobility limitations. Usefulness of the
F8WT as a measure of motor skill in walking in persons with PD
has not been reported.
Methods: Baseline data collected from a pilot study on the effect
of motor imagery in persons with PD (n514, 2 men, mean age 66.6
Movement Disorders, Vol. 30, Suppl. 1, 2015
S266 POSTER SESSION
yrs 17.7, mean HY 2.4, range 1-3) were used. For the F8WT, partici-
pants stood midway between 2 cones placed 5 ft apart and on a go
signal walked a figure-of-8 path around the cones. The F8WT total
time and the number of steps to complete the curved path were
recorded. Concurrent validity was determined by the relation of the
F8WT to measures of motor skill in walking, gait speed and stride time
variability, derived from the mean of 2 passes of usual walking over
the GAITRite instrumented walkway. Construct validity for motor
planning was determined by the relation of the F8WT time and steps to
the Montreal Cognitive Assessment (MoCA), a measure of cognitive
function necessary for planning and judgments. Spearmans rho corre-
lation coefficients were used to determine the associations between
F8WT, usual gait speed, stride variability, and cognitive function.
Results: The F8WT time and steps were both associated with the
motor skill of walking: usual gait speed (time rs= -.71, p5.01; steps
rs= -.65, p5 .01), and stride time variability (time rs=.63, p5.02;
steps rs= .67, p5.01). The F8WT time and steps were also associated
Fig. 1. (678).
Movement Disorders, Vol. 30, Suppl. 1, 2015
with cognitive functioning: total MoCA score (time rs= -.58, p5
.03;steps rs= -.66, p5.01).
Conclusions: For the sample of persons with mild to moderate
Parkinsons disease studied, the F8WT has concurrent validity for
motor skill and construct validity for cognitive functioning in walk-
ing. The cognitive functioning embedded in the F8WT to motor plan
and navigate the curved path may be a clinically useful assessment
of the ability of persons with PD to meet the challenge of mobility-
related physical functioning in daily life.
678
Auditory cues on postural control in Parkinsons disease: A pilot
study
W. Buated, T. Fujinami, S. Hidaka, N. Kashyap (Nomi, Japan)
 POSTER SESSION S267

Fig. 2. (678).

Objective: To evaluate the effects of auditory cues toward pos- present postural instabilities regarding the severity of the disease [2,
tural control in patients with Parkinsons disease (PD). 3]. Rhythmic Auditory Stimulation (RAS) has been justified to be a
Background: Auditory cues have been proved to be one of reha- standardized neurological motor therapy (NMTs) in PD, which cue-
bilitation strategies for PD [1]. Most of Parkinsons disease patients ing benefits may be associated with the activation of cerebellum-

TABLE 1. Characteristics of subjects in this study

Age H&Y DD
Subjects Gender (years) BMI 2.5 (years)
PD1 Female 75 20.3 3 16
PD2 Female 74 28.4 3 15
PD3 Female 69 19.2 3 13
PD4 Female 71 23.8 3 16
PD5 Male 74 19.2 3 15
PD 5 Parkinsons disease, BMI 5 Body Mass Index, DD 5 Duration of disease

Movement Disorders, Vol. 30, Suppl. 1, 2015

S268 POSTER SESSION

TABLE 2. Posturographic data in Parkinsons disease with no cue

Start Alternation Rest 1 Synchronization Rest 2
Path Length 99.59 6 15.63 188.27 6 71.72 147.94 6 65.6 263.98 6 141.94 145.98 6 55.09
Area 17.57 6 21.27 47.66 6 46.02 47.96 6 55.19 43.91 6 36.26 51.04 6 5
RMS 8.88 6 13.21 10.98 6 9.88 10.53 6 12.74 15.28 6 18.23 9.99 6 9.12
Max ML 2.07 6 4.41 3.3 6 5.31 2.45 6 4.78 2.43 6 4.29 2.14 6 4.03
Min ML -2.44 6 2.1 -4.64 6 2.58 -3.32 6 1.16 -2.3 6 2.33 -3.82 6 1.99
Max AP 6.62 6 1.05 6.97 6 1.05 7.25 6 1.06 7.89 6 1.18 7.69 6 1.93
Min AP 3.1 6 2.19 1.73 6 2.44 0.94 6 3.88 -0.4 6 3.23 0.69 6 2.97

thalamic-cortical circuitry [4]. A potential method to stimulate the

putamen that might help regulate PD brains circuits could be pro-
viding music as a rhythmical cue [4]. A distinct manifestation in PD
is also the arm swing reduction [5] which limits the capability of
maintaining balance. It is rare to explore the static standing balance
in Parkinsons disease.
Methods: 5 idiopathic PD patients (1 male and 4 female) aged
72.6 6 2.51 years, duration of the disease 15 6 1.22 years
(mean 6 SD), H&Y 2.5-3 participated in this study.
They were recruited from Yawata Medical Center, Ishikawa,
Japan in June and November, 2014. The subjects were instructed to
stand on the balance platform (Nintendo Wii Fit) and swing arm;
Alternation (Alt) and Synchronization (Syn) in 3 scenarios; with no
auditory cues (AC), with AC 5% increased and with AC 5%
decreased. The data were analyzed by Wilcoxon Signed Ranks Test
and the dimensional clustering method [6] on MATLAB.
Results: Tempo at 95% improved area, RMS and Min ML in
Alternation, and decreased the path length in rest 2. Tempo at 105%
decreased area and RMS in rest 2 statistically significant.
A case with H&Y stage 3 showed poorer postural control in both
Antero-Posterior (AP) and Medio-Lateral (ML) directions. Most
cases presented the higher Center of Pressure (CoP) displacement in Fig. 1. (679).
ML direction. AC with arm swing regulated the pattern of CoP tra-
jectories. [figure1] [figure2]
Conclusions: Auditory cues with arm swing - Alternation
improved postural control in the PD patients. This concept might be time on the faster trial used for data analysis while for the executive
considered clinically to be a rehabilitation program for Parkinsons function test, response time was used to calculate global switch cost
disease (PD) to improve standing balance. It is a need to enlarge the as an index of cognitive flexibility.
sample size and develop more rehabilitation programs for improving Results: A simple linear regression established that differences in
balance in PD. walking speed following 12 weeks of high - frequency exercise
could statistically significantly predict changes in global switch cost,
F(1, 21) 5 25.921, p < .0005 and walking speed differences
679 accounted for 53.1% of the explained variability in global switch
costs differences. In contrast, linear regression for the low-frequency
Walking speed and switching attention in individuals with exercise group indicated that differences in walking speed after 12
Parkinsons disease weeks of low - frequency exercise could not significantly predict
M.C. Caciula, M. Horvat, R. Croce (Statesboro, GA, USA) changes in global switch cost differences, F (1, 18) 5 3.404, p 5 0.
Objective: The purpose of the present study was to determine if 082 and walking speed differences accounted for 11.2% of the
Parkinsons disease (PD) walking speed after 12 weeks of exercise explained variability in global switch costs differences.
intervention could predict changes in executive function (EF) in indi- [Figure1]
viduals with PD without dementia. Conclusions: Our results indicated that alterations in physical
Background: The inability to ambulate, strength and balance dif- function of people with PD following a high-frequency exercise
ficulties are important components that affect quality of life, morbid- intervention can facilitate ambulation as well as changes in executive
ity and mortality, as well as cognitive decline and EF in patients function. We suggest that future research should continue to investi-
with PD. Previous work in healthy older adults has indicated an gate the mechanisms of movement that can be used in the treatment
association between walking speed and EF, with a decline in walking of physical decline associated with diminished cognitive function in
speed predicting a degeneration of RF. In contrast, this relationship people with PD.
between walking speed and executive function in individuals with
PD has not been documented.
Methods: A total of forty-three individuals diagnosed with PD
without dementia, from Atlanta metropolitan area completed an 8
feet walk task from a standing start, and an auditory switch task at 680
baseline, and at the conclusion of 12 weeks of exercise intervention.
For the walking task, participants were evaluated with the Short Movement Disorders after stroke
Physical Performance Batterys quartiles of performance, with the A. Chahidi, M. Chraa, N. Kissani (Beni Mellal, Morocco)

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
Fig. 1. (680).
Objective: The goal of this study is to describe the clinical, para-
clinical and evolutive features of patients having suffered a Move-
ment Disorder in the aftermath of an ischemic stroke.
Background: Movement Disorder following stroke represent an
uncommon situation. It has been suggested that the prevalence of
this complication varies from 1 to 5% in different studies. It repre-
sents an interesting condition because of the pathophysiological ques-
tions it raises.
Methods: Authors report a retrospective study from January 2004
to December 2013. This study collected 442 stroke cases. Data were
collected 442 patients folders who were hospitalized for ischemic
stroke in the Neurology Department, Mohammed VI university hos-
pital in Marrakesh, Morocco. Our department is a third level struc-
ture which covers much of southern Morocco. The diagnosis of
ischemic stroke was established in base of clinical and CT scan crite-
ria. Only patients who presented with a Movement Disorder in the
aftermath of stroke were included.
Results: Within our 442 stroke patients with ischemic stroke, 18
presented a Movement Disorder. There are 10 man and 8 women.
The mean age was 59 years. Patients presented this complication 3
Fig. 2. (680).
S269
days to 1 year after the acute episode. We had 8 patients who devel-
oped a Parkinsonism syndrome, 4 patients had a chorea, 3 others had
an isolated tremor and 3 presented a dystonia. Parkinsonism was the
later to develop in our patients whereas chorea developed some days
after the stroke. CT scan showed a subcortical ischemic stroke
impacting the basal ganglia in all cases. Finally, the evolution was
marked by a resolution (subsiding of all symptoms in all of the?) of
all cases of dystonia and chorea. On the other hand, patients who
had Parkinsonism were being followed in our department for up to 6
years without any major improvement.[figure1] & [figure2]
Conclusions: The present series report the clinical, paraclinical
and the outcomes of patients who presented a Movement Disorder
after an ischemic stroke. Even with the small number of patients in
this study, many finding and suggestions may be developed.
681
Mirror movement among patients with Parkinsons disease- An
under-appreciated clinical sign
P. Chatterjee, S. Choudhury, D. Naskar, S. Anand, B. Mondal, M.U.
Kulsum, H. Kumar (Kolkata, India)
Objective: Evaluate Mirror Movements (MM) in Parkinsons dis-
ease (PD) patients.
Estimate changes in MM in response to levodopa.
Compare MM in PD patients and healthy volunteers.
Background: Mirror movement (MM) is hitherto underappreci-
ated phenomenon see in Parkinsons disease (PD). We intended to
clinically evaluate MM in PD patients and also estimate change in
this phenomenon upon intake of levodopa (L-dopa).
Methods: In this analytical cross-sectional study, seventy patients
with PD were evaluated using a clinical scale for MM and Unified
Parkinsons disease Rating Scale (UPDRS) in OFF and ON phase.1
Five different tasks (finger tapping, hand movement, pronation -
supination, foot dangling and spiral movements) were instructed for
objective assessments of MM. Video recording of the evaluation
were performed in all patients. The changes in MM rating scores of
same patients from OFF to ON phase were compared using Wil-
coxon Sign Rank test. Thirty five matched healthy volunteers were
also evaluated for MM.
1. Mirror movements in Parkinsonism: evaluation of a new clinical
sign: A J Espay, J-Y Li, L Johnston, R Chen, A E Lang. J Neurol Neu-
rosurg Psychiatry 2005;76:13551359. doi: 10.1136/jnnp.2005.062950.
Results: The mean age of 70 PD patients was 64.53 (SD 8.80)
years and 75.7% of them were male. 95.7% of PD patients demon-
strated MM compared to 22.86% of healthy volunteers (p value
0.0001). Intensity of mirror movement increased significantly in ON
phase as compared to OFF phase (Median off MM score 24; Median
ON mirror score 26, p value 0.0001). Most of the patients (68.6%)
demonstrated mirroring in upper as well as lower limbs. Lower limb
mirroring (74.3%) was less frequent than upper limb mirroring (88.6%)
but when present, the mean mm score was more in lower limbs.
Conclusions: MM is common in Parkinsons disease. It can be
an important clinical guide for diagnosis of Parkinsons disease. The
mirroring is more prominent in ON phase. It can be present in both
upper and lower limbs but in case of lower limb mirroring, it is sig-
nificantly more pronounced. So, it is important to look for mirroring
in lower limbs because in four (5.7%) of PD patients, mirroring was
found only in lower limb.
682
Hypoglycemia induced acute bilateral basal ganglia lesions
presenting as generalized dyskinesia in a patient with diabetic
uremia
P.Y. Chen, S.H. Yan, S.C. Lai, C.S. Lu, T.H. Yeh (Taipei, Taiwan)
Movement Disorders, Vol. 30, Suppl. 1, 2015
S270 POSTER SESSION
Fig. 1. (682).
Objective: To describe the rare clinical manifestation and image
finding of acute bilateral basal ganglia lesions in patient with dia-
betic uremia after hypoglycemia.
Background: The syndrome of acute bilateral basal ganglia
lesions in diabetic uremic patient is uncommon and it mostly affects
Asian patients. Clinical manifestation includes acute onset of dyski-
nesia and/or Parkinsonism. These symptoms are often self-limiting
with gradual improvement under regular hemodialysis and sympto-
matic treatment. The typical neuroimaging finding is reversible sym-
metrical lesion in bilateral basal ganglia.
Methods: Clinical observation and neuroimaging study for a dia-
betic uremic patient with acute bilateral basal ganglia lesions.
Results: A 56-year-old female with 10 years history of type II
diabetic mellitus and end stage renal disease under regular hemodial-
ysis for 1 year. After one episode of hypoglycemia (sugar: 23mg/dl),
acute onset generalized involuntary movement with the presentation
of limbs ballism and dystonia, orolingual, facial and truncal dyskine-
sia developed. These symptoms were not responsive to biperiden
Fig. 2. (682).
Movement Disorders, Vol. 30, Suppl. 1, 2015
intramuscular injection initially. Brain computed tomography (CT)
and magnetic resonance imaging (MRI) showed bilateral basal gan-
glia lesions. [figure1] The Tc-99m-TRODAT showed a relatively
decreased uptake at left putamen. [figure2] Regular hemodialysis was
arranged and her blood sugar was corrected. We had tried clonaze-
pam, biperiden, amantadine and haloperidol and visual hallucination
developed for days so amantadine and biperiden were discontinued.
Her involuntary movement gradually improved on the 3rd week
under 10mg/day of haloperidol.
Conclusions: Acute bilateral basal ganglia lesions in diabetic ure-
mic patient is a rare and disabling condition. The possible pathoge-
nesis of this syndrome could be uremic toxins, metabolic acidosis
and diabetic microangiopathy. Hypoglycemia could be a trigger fac-
tor. Haloperidol is effective for intractable dyskinesia but closely
monitoring drug-induced extrapyramidal symptom is required in
those who have evidence of dopamine dysfunction.
683
Cytoarchitecture of the human nitrergic neurons in basal nuclei
B.L. Dos Santos, E.A. Del Bel, J.E. Pittella, V. Tumas (Ribeir~
ao
Preto, Brazil)
Objective: To investigate the distribution and morphology of
nitrergic neurons in the human basal nuclei.
Background: Nitric oxide (NO) is a gaseous molecule which
modulates several physiologic processes, including signal transmis-
sion in central nervous system. There are evidences supporting the
NO as a major neurotransmitter involved in motor and emotion/
behavior control. Presence of NO neurons was already described in
human basal nuclei, but it was noted a lack of concordance between
works.
Methods: We studied samples of striatum (caudate and putamen),
globus pallidus, subthalamic nucleus, substantia nigra and pedunculo-
pontine nucleus of 20 human brains from subjects without neuro-
logic/psychiatric diseases, stained by histochemistry for NADPH-
diaphorase and immunohistochemistry for neuronal NO synthase,
 POSTER SESSION
and analyzed the nitrergic neuronal density and its morphometric
parameters.
Results: Our data showed the posterior area of striatum has a
higher neuronal density than the anterior area of this nucleus, and
the limbic-associated areas of striatum have higher neuronal density
than others functional subdivisions. The subthalamic nucleus is a
region in which about 90% of its neurons express NO, and its mor-
phologic features suggest these neurons coexpress glutamate. The
pedunculopontine nucleus has a massive nitrergic neuronal density,
mostly at its rostral level. In globus pallidus, there is a marked pres-
ence of NO neurons in medial medullary lamina, and the nitrergic
neurons were not detected in substantia nigra.
Conclusions: A remarkable presence of nitrergic neurons in
human basal nuclei was seen, mainly in limbic striatum and subtha-
lamic nucleus. Considering the growing evidences about the role of
NO on clinical settings as levodopa-induced dyskinesia in Parkin-
sons disease and psychotic symptoms in schizophrenia, these results
reinforce the relevance of this atypical neurotransmitter on the basal
nuclei circuitry modulation.
684
Is change in physical performance in persons with Parkinsons
disease meaningful following LSVTV R BIG: A retrospective study
W.J. Farrington, T. Miller, G. McGaughy, K. Mercuris, K. Lowry
(Des Moines, IA, USA)
Objective: To determine meaningful individual change in physi-
cal performance measures following LSVTV R BIG intervention in
subjects with Parkinsons disease (PD).
Background: LSVTV R BIG is an exercise-based behavioral inter-
vention used in the PD population. It is an amplitude-based program
that uses cueing strategies to encourage bigness and maximum
effort during performance of multidirectional, movements. Though
improvements in physical function have been reported with LSVTV R
BIG, data on meaningful change in function has not been reported.
Methods: Clinical data from 32 subjects (16 men, mean
age 5 69.7 yrs 6 8.3, mean years since diagnosis 5 7.05 6 5.40) were
used. LSVTV R BIG certified clinicians provided the outpatient inter-
vention (one-hour individual sessions, 4x/week for 4 weeks) and col-
lected pre/post data on the following outcome measures: 6-Minute
Walk Test (6mw), 10-Meter walk (10mw), Timed Up-and-Go
(TUG), 9-Hole Peg Test (9HPT), 6-Button Test (6B); 30-second
Chair-Stand (30cs), 5-times Chair-Stand (5cs). A series of repeated
measures ANOVAs were used to determine the change in outcome
measures, and effect sizes (ES, meanpost meanpre/pooled standard
deviation) were computed; comparisons of the standardized change
were made across the physical performance measures.
Results: The repeated measures ANOVAs for the change in out-
come measures were all statistically significant (p 5 .001). The mean
difference (Meanpost Meanpre) and ES for each measure was as
follows: 6mw (109m, 0.88), 10mw (-1.2s, 0.67), TUG (-3.4s, 0.41),
9HPT (-8.3s, 0.52), 6B (-14.6s, 0.36), 5cs (-2.5s, 0.61), and 30cs (4,
1.00).
Conclusions: Participants improved on all outcome measures,
suggesting reduced bradykinesia post intervention. Based on the ES
for the sample, greater gains were made in walking and lower
extremity function than in upper extremity control and function
measures. Current LST intervention may have a differential impact
on tasks based on large muscle groups, lower or upper extremity, or
degree of fine motor control.
685
Clinical subtypes of Parkinsons disease and disease progression:
Data-driven comparison of new phenotypes with other cluster
solutions
S.M. Fereshtehnejad, S.R. Romenets, J. Anang, V. Latreille, J.F.
Gagnon, R.B. Postuma (Stockholm, Sweden)
S271
Objective: 1) To identify clinical subtypes of Parkinsons disease
(PD) 2) to compare the progression rate between PD phenotypes,
and 3) to compare the ability to predict prognosis in our subtypes
and those from previously-published clustering solutions.
Background: There is increasing evidence that PD is heterogene-
ous in its clinical presentation and prognosis. Defining subtypes of
PD is needed to better understand underlying mechanisms, predict
disease course, and eventually design more efficient personalized
management strategies. However, there is currently no clear way to
define and divide subtypes.
Methods: In this longitudinal cohort, 113 patients with idiopathic
PD were enrolled from two Movement Disorders Clinics in Mon-
treal, Canada during 2005-2013. A comprehensive spectrum of motor
and non-motor features were assessed at baseline evaluating motor
severity, motor complications, motor subtypes, quantitative motor
tests, autonomic and psychiatric manifestations, olfaction, color
vision, sleep analysis and neuro-cognitive testing. Two-step cluster
analysis was performed to identify PD phenotypes at baseline. After
a mean follow-up time of 4.5 years, 76 patients were reassessed. A
global composite outcome (GCO) was also created by merging
standardized scores for motor symptoms, motor signs, cognitive
function and other non-motor manifestations.
Results: The best cluster solution found was based on orthostatic
hypotension (OH), mild cognitive impairment (MCI), REM sleep
behaviour disorder (RBD), depression, anxiety, UPDRS part II and
UPDRS part III scores at baseline. Three subtypes were defined
(according to baseline phenotype/prognosis) as mainly motor/slow
progression, diffuse/malignant and intermediate. Despite similar
age and disease duration, many significant differences were found
between the clusters. PD patients with the diffuse/malignant phe-
notype had MCI, OH and RBD at baseline and on prospective
follow-up had more rapid progression in cognition (p<0.001), other
non-motor symptoms (p<0.001), motor signs (p50.002), motor
symptoms (p50.019) and the GCO (p<0.001).
Conclusions: It is recommended to screen PD patients for MCI,
OH and RBD even at baseline visits. These non-motor features iden-
tify a diffuse/malignant subgroup of PD patients in whom the most
rapid progression rate could be expected.
686
Continuous stimulation of the subthalamic nucleus improves
skilled forelimb grasping after photothrombotic infarction in
Wistar rats
F. Fluri, J. Volkmann, C. Kleinschnitz (W
urzburg, Germany)
Objective: To evaluate the effect of continuous stimulation of the
subthalamic nucleus (STN) on (1) fine motor control of skilled fore-
limb grasping using the single pellet reaching (SPR) test and (2) on
infarct size detected by MR imaging after photothrombotic infarction
in rats.
Background: Motor disability is the most common deficit after
ischemic stroke. Following initial damage, stroke patients can
recover from motor function to some extent which is probably due
to brain plasticity. Recent studies in both humans and animal models
strongly suggest that the activity in the motor cortical areas is altered
by stimulation of the STN by signals traveling in an antidromic
fashion.
Methods: Male Wistar rats (10-weeks old) pre-trained in a single
pellet reaching (SPR) task were subjected to a photothrombotic
infarct of the dominant hemisphere. A microelectrode was implanted
in the STN ipsilateral to the infarction. Animals were randomly
divided into a stimulated and non-stimulated group. Continuous
high-frequency stimulation of the STN was initiated on the day the
photothrombotic infarction was induced and conducted 24h a day for
1 week. A final assessment of reaching was performed on day 7 and
the success rate of grasping pellets was determined.
Results: Continuous high-frequency stimulation of the STN led
to an improvement of fine motor skills of the dominant forelimb
Movement Disorders, Vol. 30, Suppl. 1, 2015
S272 POSTER SESSION
within 7 days after induction of photothrombotic infarction compared
to non-stimulated animals (14.5% vs 7.3%). Furthermore, MR imag-
ing revealed smaller infarctions in rats which underwent STN stimu-
lation (76.1 6 3 mm3 vs 60.5 6 6 mm3; p 5 0.047).
Conclusions: Our data suggest that continuous stimulation of the
STN might contribute to an amelioration of prehension, i.e., the abil-
ity to use a paw to reach for and grasp an object. Whether STN stim-
ulation impacts ongoing neuroplasticity in the perilesional area or
influences brainstem/spinal structures which are involved in the con-
trol of fine motor skills of the forelimb remains to be elucidated.
687
Characterization of Movement Disorder phenomenology in
genetically proven frontotemporal lobar degeneration: A
systematic review and meta-analysis
C. Gasca-Salas, B.B. Shah, M. Masellis, E. Khoo, D. Fisman, A.E.
Lang, G. Kleiner-Fisman (Toronto, ON, Canada)
Objective: We conducted a systematic review and meta-analysis
of the literature characterizing the spectrum and prevalence of Move-
ment Disorder phenomenology in genetically proven FTLD; we eval-
uated the association between clinical phenotype and mutation status.
Background: Frontotemporal lobar degenerations (FTLD) are
clinically, genetically and pathologically heterogeneous disorders.
Autosomal dominant mutations in PGRN and MAPT, and hexanu-
cleotide repeat expansions in C9ORF72 are the most prevalent
causes of familial FTLD. Although behaviour, cognitive and move-
ment presentations are common, the relationship between mutation
status and Movement Disorder phenomenology is unclear.
Methods: Electronic databases (Embase and Pubmed) were
searched from 01/01/1986 to 09/2013 using search terms related to
FTLD and Movement Disorder phenomenology. Articles were
included only when cases had a proven diagnosis of genetic FTLD
(MAPT, PGRN, C9ORF72). Study-specific estimates of prevalence
for clinical features were transformed to logits, allowing summary
estimates of prevalence to be generated using random-effects models.
Between-study heterogeneity was assessed using the Cochrans Q
and I2 statistics.
Results: 79 studies meeting inclusion criteria were reviewed. The
mean age at onset for all subjects with genetic FTLD and a Move-
ment Disorder was 51. Men and women were represented equally
with average disease duration of 7 years across genotypes. The prev-
alence of dementia and/or behavioural presentations was 67% of
the cohort. Parkinsonism was the most common Movement Disorder
syndrome reported in 76% (95% CI 65.5, 83.8) followed by cortico-
basal and PSP-like syndromes in 17% (95% CI 12.1%-22.6%) and
14% (95% CI 9.3%-20.5%), respectively. While between-study heter-
ogeneity in prevalence was identified, mutation status did not explain
variability in motor and non-motor presentations or individual
phenomenologies.
Conclusions: This represents the first systematic review and
meta-analysis of the occurrence of Movement Disorder phenomenol-
ogy in genetic FTLD. While Movement Disorders were common
across all genetic FTLD cases, no difference in prevalence of Move-
ment Disorder presentations across the different FTLD genes was
observed. Prospective collection of clinical information in conjunc-
tion with genetic characterization will be crucial for accurate clinic-
genetic correlation.
688
Assessment of Parkinsonian motor symptoms using a
continuously worn smartwatch: Preliminary experience
E. Gazit, H. Bernad-Elazari, S.T. Moore, C. Cho, K. Kubota, L. Vin-
cent, S. Cohen, L. Reitblat, N. Fixler, A. Mirelman, N. Giladi, J.M.
Hausdorff (Tel Aviv, Israel)
Movement Disorders, Vol. 30, Suppl. 1, 2015
Objective: To test the feasibility of using a continuously worn
SmartWatch to assess Parkinsons disease (PD) symptoms.
Background: Previous work suggests that a body fixed sensor
placed on the shank or back can assess PD motor symptoms such as
freezing of gait (ST Moore et al., 2013) and falls (e.g., A Weiss
et al., 2014). The main objective of this study is to develop method-
ology for the long-term monitoring of PD symptoms using a Smart-
Watch that collects data continuously for several weeks. The data
can be streamed to the cloud for real-time processing to generate an
objective report of the patients status. Here, we evaluate the feasibil-
ity and validity of using a commercially available SmartWatch to
quantify PD motor symptoms.
Methods: Patients with PD (n59; age: 62.8 6 11.7 y; disease
duration: 11.3 6 4.3 y) and controls (CO: n57; age: 43.6 6 12.0)
wore the GENEActiv watch on the dominant hand while they per-
formed the Timed Up and Go (TUG) test and 60s of walking 1/-
dual tasking (DT). Patients were tested in clinically defined ON and
OFF states. Arm movement was quantified in the frequency and time
domain using the AP acceleration, e.g., cycle time, root mean square
(RMS), jerk (a measure of movement smoothness), frequency and
peak amplitude of the power spectral density. Non-parametric tests
explored differences between the groups and the effects of PD
medications.
Results: Several measures differed in CO and PD (OFF and ON)
and improved in ON, compared to OFF. For example, during the
TUG, RMS was higher (i.e., better, p50.04) in the ON (0.53 6 0.13)
vs. OFF state (0.41 6 0.13). During DT walking, the main frequency
was lower (p50.04) in CO (0.94 6 0.06 Hz) compared to PD ON
(1.54 6 0.53 Hz, p50.04). The jerk was lowest in CO
(0.005 6 0.003 m/s3), higher in PD ON (0.05 6 0.06 m/s3, p<0.05),
and highest in PD OFF (0.08 6 0.07 m/s3) and the peak amplitude of
the dominant frequency was highest (i.e., most consistent) in CO
(0.62 6 0.14 g2/Hz), lower (p<0.05) in PD ON (0.33 6 0.27 g2/Hz),
and lowest in PD OFF (0.28 6 0.19 g2/Hz) during DT walking.
Conclusions: Follow-up work in a larger cohort and long-term
monitoring is needed to further assess the validity of these prelimi-
nary results and to develop other measures of PD motor symptoms
using a SmartWatch. Nonetheless, these initial findings suggest that
a wrist worn device can assist with the evaluation of PD symptoms.
689
Clinical and dynamic balance measures can predict postural
instability in Parkinsons disease patients
L.T.B. Gobbi, P.H.S. Pelicioni, M.P. Pereira, J. Lahr, L.C. Morais,
N.M. Rinaldi (Rio Claro, Brazil)
Objective: To analyze the relationship between clinical and
dynamic balance parameters and postural control in quiet standing in
patients with Parkinsons disease (PD).
Background: Postural stability is the ability to maintain equilib-
rium under static and dynamic conditions, although the person is not
static during a quiet stance posture. Postural instability is a frequent
concern in PD patients who report an increased likelihood of falling
when changing position, turning, or walking. Since the center of
pressure (CoP) in quiet standing is used to assess postural instability
in PD patients we question the prediction of clinical and dynamic
balance parameters on center of pressure variables.
Methods: Forty nine subjects with idiopathic Parkinso ns disease
(female: 21; age: 69.65 1 6 years; height: 161.22 1 8.98 cm; weight:
71.04 1 12.49; disease duration: 60.22 1 44.91 months) were
assessed in ON medication state. Participants were in mild to moder-
ate disease stages (1 to 3 of Hoehn and Yahr and 38 1 12.34 points
in the UPDRS) and had the cognitive functions preserved (Mini-
mental State Examination=27.69 1 2.32 points). The CoP measures
[Sway Area (SA), Sway Trajectory (ST), Anteriorposterior Sway
(AS) and Mediolateral Sway (MS)] were collected with the subjects
stand barefoot on a force platform. The dynamic balance was
assessed by the timed up and go test (TUG), Berg Balance Scale
 POSTER SESSION S273

TABLE 1. Pearso
ns correlation between CoP measures and clinical and dynamic balance variables.
CoP variables UPDRS TUG BBS DGI FRT
Sway area (SA) r 0.413 0.349 -0.263 -0.353 -0.430
p 0.003 0.014 0.06 0.013 0.002
Sway trajectory (ST) r 0.341 0.152 -0.104 -0.186 -0.328
p 0.016 0.283 0.465 0.188 0.022
Anteriorposterior sway (AS) r 0.214 0.261 -0.248 -0.426 -0.299
p 0.128 0.062 0.077 0.002 0.037
Mediolateral sway (MS) r 0.381 0.375 -0.355 -0.417 -0.451
p 0.007 0.008 0.012 0.003 0.001

TABLE 2. Stepwise multiple regression analysis.

Dependent variable Predictor variable R2 p
Sway area Functional Reach Test 0.185 0.002
Sway trajectory UPDRS Total 0.116 0.016
Anteriorposterior sway Dynamic Gait Index 0.182 0.002
Mediolateral sway Functional Reach Test 0.203 0.001

(BBS), Dynamic Gait Index (DGI) and Functional Reach Test
(FRT). Only those clinical and dynamic balance variables that corre-
lated significantly (p<0.05) with the CoP measures were entered into
the hierarchical regression models (stepwise).
Results: The mean results were: TUG:8.55 1 4.05s;
BBS:52.39 1 4.97 points; DGI:20.86 1 2.98 points; FRT:24.1 1 5.82
2
cm; SA:0.19 1 0.18cm ; ST:413.59 1 140.12 cm; AS:9.62 1 4.97
cm; MS:4.01 1 3.21 cm. Correlation and multiple regression analysis
are presented in tables 1 and 2.
Conclusions: Even though the prediction reached the significant
level, these results can be used in clinical practice with caution since
the prediction values are small. Future studies can include demo-
graphic data in order to observe the prediction association.
690
Initial treatment choice is associated with medical resource use
in people aged 35 to 64 years with Parkinsons disease
E. Grubb, M. Treglia, M. Lage (Overland Park, KS, USA)
Objective: This research assesses key associations between initial
medication treatment choice in Parkinsons disease (PD) and health
care resource use.
Background: A retrospective, observational study of people aged
35 to 64 years and diagnosed with PD (ICD-9-CM 332.xx or 332.0)
in the Truven MarketScanV R Commercial Claims and Encounters
(CCAE) Database. For people who filled a PD prescription (Rx), the
date of first such Rx was the index date.
Methods: PD subjects who did not fill a PD Rx were matched 1-
1 (according to age, gender and region) to those filling a PD Rx.
The index date in the matched cohort was imputed to be the index
date of their match. All individuals had continuous insurance cover-
age from 1 year prior to index date through 1 year following. Multi-
variable logistic analyses examined differences between initial Rx
treatment cohorts (MAOB was the reference case) and office visits,
emergency room (ER) visits, hospitalizations, and fractures or falls.
Key results are presented as adjusted odds ratios (OR) and 95%
confidence intervals (CI). Chi-square statistics were used to test dif-
ferences between categorical variables while t-statistics were used
for continuous variables. The significance level was pre-specified as
5%.
Results: The PD patients were, on average, 56.8 years old and
the majority (60.15%) were male. Relative to those people initiating
PD Rx with MAOB, there were no statistically significant differences
between the active treatment cohorts on having any office visits dur-
ing the follow-up period. However, for those who did not receive a
PD Rx, there was a statistically significantly lower likelihood
(OR 5 0.052; CI 5 0.026 0.106) for any office visit. In contrast,
there were statistically significantly higher odds of an ER visit for
PD patients treated initially with carbidopa-levodopa (CL) (1.769;
1.204 2.600) or dopamine agonists (DA) (1.570; 1.059 2.329)
relative to treatment initiation with MAOB. Likewise, CL (2.258;
1.299 3.926) and DA (1.885; 1.069 3.321) use was associated
with a statistically significantly greater likelihood of hospitalization.
There were not any statistically significantly differences across initial
PD Rx treatment cohorts on the likelihood of fracture or fall.
Conclusions: These results suggest that initial PD Rx treatment
choice may have bearing on subsequent use of important medical
resource categories.
691
Smartphone-PD: Preliminary results of an mHealth application
to track and quantify characteristics of Parkinsons disease in
real-time
D.A. Harris, S.O. Abiola, K.M. Biglan, E.R. Dorsey, M.A. Little, S.
Saria, A. Zhan (Rochester, NY, USA)
Objective: Using a Parkinsons disease (PD)-specific application
(app) to: (1) assess the feasibility of remote, online recruitment and
completion of app installations, (2) objectively measure and quantify
five factors of PD (voice, balance, dexterity, gait, and reaction time),
(3) measure daily variability of these and other factors including
mobility and socialization, and (4) correlate Android app sensor data
and clinical assessments from the Unified Parkinsons disease Rating
Scale (UPDRS) in a subset of participants.
Background: Most clinical data on PD is low frequency and
recorded during periodic assessments. An Android app in a recent
pilot study has been shown to measure and quantify key characteris-
tics of PD, including daily variability, with a strong correlation to
the UPDRS.
Methods: We are conducting a 6 month study of approximately
2,000 unpaid individuals (1,500 with PD and 500 controls) globally
to use an Android application that prompts tests of voice, postural
sway, dexterity, gait, and reaction time twice each day for the study
duration. The app also uses embedded phone sensors to passively

Movement Disorders, Vol. 30, Suppl. 1, 2015

S274 POSTER SESSION
track characteristics of PD such as movement. Online surveys are
used to obtain information on demographics, familiarity with tech-
nology, PD status and history, and current medications. Participants
are identified and recruited using an email database of the Parkin-
sons Voice Initiative, online media, and patient registries such as
the Michael J. Fox Foundations Fox Trial Finder.
Results: To date, 457 individuals have enrolled in the
Smartphone-PD study: 232 PD (51%) and 224 control participants.
Individuals considered active (i.e., those who have submitted at
least one instance of testing and have not exited the study) currently
number 375 (82%): 190 PD and 184 controls. Participants are 18-79
years of age with predominant male representation. Over 46,000
hours of unstructured streaming sensor data and 8,000 structured
tests of voice, gait, posture, and dexterity have been collected over 6
months.
Conclusions: Smartphone-PD has produced a large repository of
PD-specific, raw smartphone sensor data. This ongoing, large-scale
global study continues to show that study recruitment can be con-
ducted entirely remotely, compliance with the study protocol can be
monitored in real time, and use of the application can allow for
exploration of daily fluctuations in patient symptoms.
692
Iron deposition and oxidative stress in the brain of the Zitter rat
T. Kadowaki, H. Lassmann, S. Ueda, C. Schuh, K. Hirata (Mibu,
Japan)
Objective: We have evaluated the distribution of iron accumula-
tion in the brain of the Zitter rats. To investigate relationship
between iron accumulation and inflammatory cells, we investigated
inflammatory cells, such as CD3-positive cells and ED1-positive
cells, in the brain of the Zitter rat. And we examined oxidative stress
in iron accumulation site in the brain.
Background: Neurodegenerative disease such as Parkinsons
disease have excess of iron accumulation in the brain. To eluci-
date the pathogenesis of iron accumulation is important for solv-
ing of the neurodegenerative disease. TH-positive cells reduce
with age in the brain of the Zitter rat. It has been suggested that
the inflammatory cells are related to the neurodegeneration. More-
over, it is expected that oxidative stress proceeds in iron overload
conditions.
Methods: From 7-month-old to 9-month-old of Zitter rats (n510)
and age-matched Lewis rats were used. ED1 staining, CD3 staining,
p22phox staining, and Turnbulls blue (TBB) staining, were per-
formed. We created an iron accumulation score from 0 to 3 in order
to measure the degree of iron accumulation was evaluated. The den-
sity of ED1-positive cells and CD3-positive cells were measured
using ImageJ densitometry. And we counted about the number of
p22phox positive cells.
Results: Iron accumulation was prominent in the cerebellum and
substantia nigra (SN) in all Zitter rats. Iron deposition score of Zit-
ter rats was significantly higher than Lewis rats in the SN and cere-
bellum. ED1 was statistically significant in the cerebellum in the
Zitter rat. There were no significant differences in the CD3 and
p22phox.
Conclusions: Iron deposition was not related in oxidative stress
in the brain of the aging Zitter rat.
693
Ethical and legal concerns for a highly vulnerable population of
701 cases of PD and dementia: A qualitative study in Indian
context
M. Kakoti, D. Misra (New Delhi, India)
Objective: The paper about the ethical and legal concerns in
research involving the 701 subject population with PD and/or
Movement Disorders, Vol. 30, Suppl. 1, 2015
dementia. The question of informed consent and the three principles
of autonomy, beneficence and justice are examined in this context.
Background: Alzheimers Disease (AD) is the most common
form of dementia and a disease that is rapidly on the rise. Parkin-
sons disease (PD) belongs to a group of conditions called motor sys-
tem disorders, which are the result of the loss of dopamine-
producing brain cells. Difficulty in production of speech however has
not been studies. As the disease progresses, the shaking, or tremor,
which affects the majority of PD patients may begin to interfere with
daily activities.
Methods: For this purpose, the methodology involves four differ-
ent questionnaires administered to four groups of interest:
i. Non-governmental organisations involved in geriatric care and
research.
ii. Patients of dementia and/or PD who have been involved, or
have chances of being.
iii. Relatives and caregivers of dementia and/or PD who have
been involved, or have.
iv. Medical professionals and other research groups involved in
clinical, behavioural, involved as subjects in geriatric research.
Results: Several problems were unearthed during the analysis of
the answers received.
i. 87% of the medical personnel who were asked replied that the
patient often considered them everything and would not refuse
anything that was asked of them to do.
ii. Another 9% of the medical personnel replied that after minor
questions, the patients were likely to agree to any procedure that
was recommended by the doctor.
iii. Almost 97% of the patients who took the survey were not
able to identify between research and treatment.
iv. Of the participants with rural background, a shocking 100%
did NOT know what informed consent was.
Conclusions: The paper concludes with the following set of rec-
ommendations for the general research community:
i. Cultural background of the society where the research is being
conducted must be taken into account.
ii. Questionnaires, tests etc. should be designed keeping in mind
the cultural sensitivity of the target population in general.
iii. Better awareness that no knowledge is futile, and even disor-
ders like PD or AD can be looked at from a humanities point of
view.
694
The Parkinsonian toxin 1-methyl-4-phenylpyridinium (MPP1),
and proteins a-synuclein and glia maturation factor (GMF)
activate mast cells and release proinflammatory mediators
D. Kempuraj, T. Ramasamy, S. Zaheer, D.A. Santillan, M.K.
Santillan, A. Zaheer (Iowa City, IA, USA)
Objective: To investigate whether brain protein glia maturation
factor (GMF) is expressed in mast cells, and if GMF and Parkinsons
disease (PD)-relevant stimuli 1-methyl-4-phenylpyridinium (MPP1)
and a-synuclein can activate mast cells to release PD-pathogenesis
relevant inflammatory mediators.
Background: PD is characterized by degeneration of dopaminer-
gic neurons. We have previously shown high GMF level in the
brains of neurodegenerative diseases such as Alzheimers disease
and Multiple Sclerosis. a-synuclein of Lewy body and MPP1, a
metabolite of neurotoxin 1-methyl-4-phenyl-1,2,3,6-
tetrahydropyridine (MPTP1) activates glial cells in PD. Mast cells
are implicated and suggested as a therapeutic target in neuroinflam-
mation. However, the role of mast cells in PD is not yet understood.
Methods: We have analyzed the effect of recombinant mouse
GMF, MPP1, a-synuclein, recombinant mouse IL-33 or recombinant
human IL-33 on mouse bone marrow-derived cultured mast cells
(BMMCs), human umbilical cord blood-derived cultured mast cells
(hCBMCs) or mouse embryonic brain-derived cultured astrocytes on
cytokines and chemokines release as determined by ELISA or the
 POSTER SESSION S275

expression of co-stimulatory molecules CD40 and CD40Ligand by
flow cytometry. We have analyzed the expression of GMF by
BMMCs and hCBMCs by immunocytochemistry (ICC).
Results: GMF significantly released chemokine (C-C motif)
ligand 2 (CCL2) from BMMCs when compared to un-treated con-
trol cells. BMMCs-derived from GMF knockout mice released less
CCL2 than BMMCs from wild type mice when incubated with
GMF in vitro. GMF, a-synuclein and MPP1 activated BMMCs to
release interleukin-1b (IL-1b), and IL-8 release from hCBMCs.
GMF released CCL5, and IL-33 induced the expression of GMF in
human mast cells. Novel GMF expression was detected in human
and mouse mast cells by ICC or immunoblotting. GMF-induced
more tumor necrosis factor-alpha (TNF-a) release from mouse
astrocyte-mouse mast cell co-culture than in isolation. Flow cytome-
try showed increased IL-33 expression by GMF and MPP1 in
mouse astrocytes. GMF-induced the expression of CD40 in mouse
astrocytes.
Conclusions: Proinflammatory mediator release by GMF, MPP1
or a-synuclein, and GMF expression by mast cells indicate a novel
drug target for neurodegenerative diseases including PD.
695
Finally its time for a perspective: Barriers and facilitators in
physical rehabilitation for Parkinsons disease from the Arabian
Peninsula
H. Khalil, J.A. Bajwa (Irbid, Jordan)
Objective: To identify barriers and facilitators for patients with
Parkinsons disease (PD) from the Arabian Peninsula to get engaged
in physical rehabilitation.
Background: There is evidence that physical rehabilitation has
positive effects on mobility, cognition and quality of life in people
with PD. Although regular engagement in physical rehabilitation pro-
grams seems to be important to sustain benefits, it is established that
perceived barriers to engaging people with PD in such therapies
becomes a challenge [1]. The available evidence however is largely
based on information obtained from developed countries, where cul-
tural, economic and health care structure differs in significant ways
from those in developing countries.
Methods: There is very limited reported literature about patients
with PD in the developing countries, their life experiences, chal-
lenges and the provision of the provided rehabilitation services espe-
cially from the Arabian Peninsula. As evidence is currently lacking,
consensus views of specialists working routinely with PD in Arab
countries is being reported in an attempt to categorize the barriers
for people with PD from Arab ethnicity in being engaged in physical
rehabilitation.
Results: We categorized these barriers into personal, social/cul-
tural and environmental including governmental policies, availability
and delivery of health care (Table 1). Some possible recommended
strategies to overcome these barriers have also been identified.
Conclusions: Theses barriers may be different from those
reported in other countries. Thus, a culturally sensitive and suitable
therapy program for PD in Arabic countries in which barriers are
identified and addressed could be feasible and beneficial for overall
quality of life. As this is an area which almost lacks research in the
region, studies are encouraged to be undertaken to expand our under-
standing regarding barriers for participation in physical rehabilitation,
best method and most-cost effective strategy in service delivery.
References:
[1] Ellis T, Boudreau JK, DeAngelis TR, et al. Barriers to exer-
cise in people with Parkinsons disease. Physical therapy 2013;
93(5): 628-36.
696
The effects of 12-week exercise therapy program on the gait
characteristics in people with Parkinsons disease
C.H. Kim, M.Y. Kim, B.O. Lim (Inchon, Korea)
Objective: The purpose of this study was to investigate the
effects of 12-week exercise intervention (12-ET) on balance and gait
characteristics (temporal-spatial parameters, joint angles, and muscle
activities) in Parkinsons disease (PD) patients .
Methods: Eleven people with PD (H and Y stage 3; 63.5 years)
participated in the study. They performed balance (timed up and go)
test and walked 3 times in the GAITRite system at a self-selected
speed. The participants undergone exercise programs (stretching,
Codi-X, ladder-X, gym ball and band) two times per week, 60 min
each time. The temporal-spatial variables were calculated by GAI-
TRite system. The electromyographic (EMG) signals from tibialis
anterior, medial gastrocnemius (MG), lateral gastrocnemius, soleus,
rectus femoris, vastus lateralis (VL), semitendinosus, biceps femoris
were recorded during reference voluntary contractions (RVC) using
EMG system (Noraxon, Inc.). Maximum hip, knee, and ankle joint
angles in the gait cycle were calculated using 3D wireless inertial
motion measurement system (Myomotion, Inc.). Statistical analysis
were done using paired t-test with Bonferroni adjustments.
Results: Theres were significant decreases in timed up and go
test (15.64 vs 11.92 s).
The ambulation time (6.94 vs 2.96 s), double support time (0.42
vs 0.27 s), stance of cycle (71.4 vs 63.0%cycle), and double support
cycle (43.8 vs 27.0%cycle), while significant increases in swing time
(0.27 vs 0.36 s), single support time (0.25 vs 0.35 s), swing of cycle
(28.6 vs 37.0%cycle), single support cycle (26.9 vs 36.1%cycle),
heel off on time (0.02 vs 0.12 s), gait velocity (0.61 vs 1.05 m/s),
normalized velocity (0.74 vs 1.29 m/s), stride velocity (0.62 vs
1.05 m/s), step length (0.37 vs 0.51 m), step extremity ratio (39.8 vs
62.6%), stride length (0.56 vs 1.02 m), and functional ambulation
profile (FAP) score (63.8 vs 87.3 point) after 12-ET.
MG (157.6 VS 124.8%RVC) significant decreases during the
mid-stance, while VL (79.4 vs 113.9%RVC) significant increases
during the initial swing after 12-ET.
Maximum hip joint angle (42.1 vs 38.0) significant decreases,
while maximum ankle joint angles (35.7 vs 46.0) significant
increases after 12- ET.
Conclusions: The temporal-spatial gait parameters, muscle activ-
ities, and joint angles changed after 12-ET. This study provides
important suggestion on combination of diverse exercise programs.

TABLE 1:. Potential barriers for people with PD in Arabic countries to get engaged in physical rehabilitation
Category Potential barriers
Personal Lack of knowledge, lack of informational resources, lack of interest and motivation, lower base of
physical activity and fitness level
Social/Cultural Gender discrepancies; social norms may impact on provision of services provided for women
Environmental Limited access to resources, lack of specialist therapists, lack of multi-disciplinary rehab centres, lack
of appropriate public transport system, governmental policies and lack of reimbursement

Movement Disorders, Vol. 30, Suppl. 1, 2015

S276 POSTER SESSION
697
Preliminary results for a national case study of virtual care visits
for Parkinsons disease
R.E. Korn, M.A. Achey, R. Rodriguez, K. Rizer, I. Richard, E.R.
Dorsey, H.T. Keenan (Rochester, NY, USA)
Objective: RACE-PD is a case series that aims to assess the fea-
sibility, utility, and impact of a national program providing one-time
video visits with Parkinsons disease (PD) specialists (investigators)
to individuals with PD in their homes.
Background: Travel distance and long waits for people with PD
have meant that many individuals in the United States are not able
to receive care from PD specialists.
Methods: Individuals with PD in five states are recruited and
enrolled remotely. Participants complete an electronic assessment
which includes the Parkinsons disease questionnaire 39 (PDQ-39)
and questions about time and travel and utilization of the internet
and technology. Participants receive telemedicine software and a
webcam if needed (Creative Labs Live HD Cam Chat). The study
team completes a test connection with the participant prior to a vir-
tual care visit with an investigator. Investigators report whether
they discussed 12 common recommendations for PD, complete a
satisfaction survey, and send a consultation note to patients (and
their usual physicians if desired). Participants complete a virtual
visit satisfaction survey after the visit, then at 6 months, they com-
plete another PDQ-39 and a survey about recommendations pro-
vided in the visit.
Results: As of January 2015, 52 individuals have enrolled, 44
(85%) have completed virtual care visits with 5 different investiga-
tors, and 8 (15%) have completed six month assessments. The major-
ity (91%) of visits have been completed as scheduled. All
participants report being satisfied or very satisfied with the care therapy in a therapeutic pool with the Watsu Method, which is char-
and comfort of virtual visits, and 79% would be interested in receiv-
ing future care via telemedicine. In addition, 33% prefer virtual visits
to in-person visits (42% are neutral). However, 9.3% of partici-
pants were unsatisfied with the technical quality of the connection.
Among the 8 participants who have completed six-month assess-
ments, PDQ-39 summary index scores improved by a mean of 4.7
points (range: 19 point improvement-9.2 point worsening).
Conclusions: Preliminary results of the RACE-PD study suggest
that a program providing one-time telemedicine visits from Parkin-
sons disease experts to individuals in their homes is feasible and
satisfactory to patients. Further participant-reported data will allow
the evaluation of the feasibility, utility, and short-term impact of this
method.
698
Validation of a smartphone application measuring bradykinesia
in Parkinsons disease
W. Lee, A. Evans, D.R. Williams (Melbourne, Australia)
Objective: To evaluate (1) the validity and repeatability of a cus-
tom designed smartphone application that quantitatively measures
bradykinesia and (2) the compliance and user-satisfaction of this
smartphone application.
Background: Measurement of motor function is critical to the
assessment of Parkinsons disease. Ambulatory quantitative measure-
ment of bradykinesia has the potential to provide a glimpse of the
patients clinical state beyond the consultation.
Methods: Over an eighteen-month period, we recruited 103
patients with Parkinsons disease from two Movement Disorders
clinics. Initial assessment included MDS-UPDRS motor assess-
ment (MDS-UPDRS-III), the two-target tapping test and the
smartphone application. Patients were then invited to complete the
smartphone application at home at designated times over three
days, followed by a questionnaire to assess their experience. A
group of patients underwent repeat assessment within two weeks
of the initial visit.
Movement Disorders, Vol. 30, Suppl. 1, 2015
Results: There was moderate to large correlation seen between
key smartphone application test parameters and MDS-UPDRS-III
total score (r=0.418-0.608, p<0.0001). A prediction model based on
these parameters generated by multiple linear regression accounted
for 52.3% of the variation in MDS-UPDRS-III total score
(R2=0.523, F(4,93)=25.48, p<0.0001). Forty-eight patients under-
went repeat assessment under identical clinical conditions. Test-retest
correlations for key smartphone application test parameters and the
predicted MDS-UPDRS-III total score were large (r=0.613-0.8) and
highly significant (p<0.0001). The follow-up questionnaire identified
that our patients were very familiar and comfortable with the smart-
phone application and mobile technology.
Conclusions: Our smartphone application showed good validity
and repeatability. It is a promising tool in both clinical and research
settings given its ease of use, cost-effectiveness and pervasiveness.
699
Improving of balance in patients affected by Parkinsons disease
by decreasing rigidity
A.P.C. Loureiro, V. Bauer, C.d.C. Loureiro (Curitiba, Brazil)
Objective: To verify the improvement of postural balance by
decreasing trunk rigidity with the approach of aquatic physical ther-
apy in patients with Parkinsons disease (PD).
Background: The deficiency of trunk mobility can lead to a loss
of balance and unexpected falls in individuals with PD.
Methods: Participated in these studies 33 individuals diagnosed
with PD. They were randomly divided into two groups. Control
group (15 individuals) who did conventional physiotherapy, and the
intervention group (18 individuals), which attended aquatic physio-
acterized by stretching, rotational and spiral rhythmic movements,
tractions and joint manipulations, both free and sequential, in which
the therapist offers total support, resembling a dance in the water.
Patients received 18 individual treatments of 30 minutes each, twice
a week. As data collection preceded, the following evaluation instru-
ments were used for both groups in the beginning and end of the
research: Trunk Mobility Scale ((TMS), Bergs Balance Scale (BBS)
and Time Up and Go Test (TUG) .
Results: Only 28 participants were able to conclude the study.
After statistical analysis it was verified that the Intervention Group
showed higher therapeutic efficacy when compared to the Control
Group, presenting statistically significant results in instruments: TMS
(p50, 02758) and BBS (p50, 00077) .
Conclusions: According to the results obtained in this research, it
is concluded that the aquatic physiotherapy application using the
Watsu method in people with PD had favored the work of muscle
relaxation, gaining movement amplitude and overall mobility facili-
tated contributing to postural stability.
700
Speech intelligibility perception of advanced Parkinsons disease
patients compared to early Parkinsons disease patients and first
degree relatives
Y. Manor, D. Shpunt, M. Chermon, L. Fregel, A. Ezra, A. Migirov,
J. Zitser, T. Gurevich (Tel Aviv, Israel)
Objective: To assess the self perception of speech intelligibility
of early stages of the PD (EPD) compared to advanced PD patients
(APD) and to first degree relatives (FDR).
Background: Speech disorders associated with Parkinsons dis-
ease (PD) are known as hypokinetic dysarthria and worsen as the
disease progresses. There is clinical impression that patients are often
unaware of their unintelligible speech. In order to assess the speech
intelligibility perception of PD patients in the different phases of the
disease, the speech intelligibility perception of patients in EPD was
compared to APD and to FDR.
 POSTER SESSION
Methods: The study included 31 participants mean age
55.56 6 18.19 (18 males) that were divided into 3 groups: 10 EPD
patients, 11 APD patients and 11 FDR. All participants underwent
the Montreal Cognitive Assessment (MoCA), Voice Handicap Index
(VHI) and Visual Analog Scale (VAS). They were recorded while
reading 5 words from the speech reception threshold list (SRT), 2
sentences from CUNNY topic related sentences and story retelling
that was read to them. Five nave judges were listened to the record-
ings and scored their ability to identify the words and sentences and
scored the level of intelligibility of the story (1intelligible 25
unintelligible).
Results: Mean age of EPD/APD/FDR 60.5 6 13.94/
62.27 6 15.32/43.5 6 20.1 respectively; Hoenh & Yahr 1.67 6 0.73/
2.07 6 0.47 respectively; disease duration 1.15 6 0.63/6.09 6 3.05
respectively; MoCA 26.20 6 2.35/27.45 6 2.54/28.50 6 1.35 respec-
tively. There was a significant difference between the 3 groups in the
VAS results 26.40 6 13.95/39.45 6 20.27/9.5 6 1.08 (p<0.01) respec-
tively, VHI function 7.70 6 8.73/11.82 6 13.29/0.2 6 0.63 (p<0.05)
respectively and judges evaluation of the story retelling 1.1 6 0.32/
1.91 6 1.3/1 6 0 (p<0.05 respectively). Nonsignificant differences in
the words and sentences recognition tasks between the 3 groups were
observed.
Conclusions: The perception of speech intelligibility both by
patients and naive judges of APD patients is reduced significantly
compared to EPD and FDR. Speech therapy should be directed to
increase awareness of the patients speech intelligibility.
701
Acoustic analysis of voice and speech of advanced Parkinsons
disease patients compared to early Parkinsons disease patients
and first degree relatives
Y. Manor, D. Shpunt, I. Ben Asher, A. Tsvion, N. Horev, A. Ezra, A.
Megirov, A. HILEL, T. Gurevich (Tel Aviv, Israel)
Objective: To assess the acoustic differences of the speech and
voice characteristics among early PD (EPD) patients compared to
advanced PD (APD) and first degree relatives (FDR).
Background: Hypophonia and dysphonia are dominant vocal dis-
turbances, characterizing the speech in Parkinsons disease (PD).
These vocal disturbances affect the speech intelligibility in different
phases of PD.
Methods: The study included 31 participants mean age
55.56 6 18.19 (18 males) that were divided into 3 groups: 10 EPD
patients, 11 APD patients and 11 FDR. All participants underwent
the Montreal Cognitive Assessment (MoCA), they were recorded
while performing maximum phonation time (MPT) prolong/a/, dia-
dokinetick task (7X PAPAPA), reading 5 words from the speech
reception threshold list, reading two sentences from CUNNY and
retelling a story that was read to them. Five nave judges listened
to the recordings and scored their ability to identify the words, sen-
tences and the level of intelligibility of the story (1intelligible 25
unintelligible). An acoustic analysis was performed using the Praat
software.
Results: Mean age of EPD/APD/FDR 60.5 6 13.94/
62.27 6 15.32/43.5 6 20.1 respectively; Hoenh & Yahr 1.67 6 0.73/
2.07 6 0.47 respectively; disease duration 1.15 6 0.63/6.09 6 3.05
respectively; MoCA 26.20 6 2.35/27.45 6 2.54/28.50 6 1.35 respec-
tively. A significant difference in vocal intensity was observed
between EPD, APD and FDR during: MPT 64.91dB611.89/
63.22dB68.74/74.7dB68.53 (p<0.05) respectively and during story
retelling 57.32dB62.11/49.73dB62.8/63.38dB62.4 (p<0.05) respec-
tively. A significant difference was observed in the ability to repeat/
PA/in terms of fluency and clarity, EPD 81%, APD 50% and FDR
100% of the patients (p<0.05). Nonsignificant differences in MPT
duration, pitch, shimmer and jitter during vowel prolongation were
observed between the 3 groups.
Conclusions: Vocal intensity is the major vocal characteristic
that is significantly reduced in APD when compared to EPD. A
S277
prospective follow up on FDR vocal characteristics may help
to determine if voice disturbances can be a diagnostic sign for
PD.
702
The self-perception of multiple system atrophy patients of
swallowing disorders and drooling and its relation to quality of
life and disease severity
Y. Manor, D. Shpunt, Y. Zlotnik, A. Megirov, L. Brounshtai, T.
Voler-Kohaner, T. Lupo, T. Gurevich (Tel Aviv, Israel)
Objective: To characterize the relation between the self-
perception of swallowing disorders and drooling in MSA patients
and their QOL and disease severity.
Background: Multiple System Atrophy (MSA) is a progressive
neurodegenerative disease. One of the severe outcomes of the disease
is dysphagia, accompanied by drooling which has a significant effect
on quality of life (QOL). Behavioral therapy is the common
approach for dysphagia treatment.
Methods: The study includes 12 MSA patients, 4 MSA-P, 8
MSA-C from the Movement Disorder Unit at Tel Aviv medical
center. All the patients responded to several questionnaires includ-
ing: drooling, swallowing disturbances questionnaire (SDQ), qual-
ity of life related to swallowing (SWAL-QOL) and United
Mulitple system Atrophy Rating Scale (UMSARS) parts 1,2 and
4. Montreal Cognitive Assessment (MoCA) was performed to all
patients.
Results: Mean age of the patients 65.33 6 8.77; disease duration
7.25 6 3.93; UMSARS 1 1 2 score 59.5 6 16.38; UMSARS 4 score
4.08 6 0.79; MoCA 22.5 6 4.5. The SDQ score demonstrated
patients report on swallowing disturbances with mean of
13.92 6 8.75 (11 significant swallowing disturbances). A significant
correlation was observed between disease severity (1st and 2nd part
of UMSARS) and report of drooling (r(12)=.62, p<.05.00 6 1.11). A
significant correlation was noted between the disease severity (sec-
ond part of UMSARS) (30.83 6 8.58) and the SDQ total score
(r(12)=.60,p<.05)(13.92 6 8.75). According to the SWAL-QOL
physical discomfort is the most affected part caused by the dysphagia
symptoms.
Conclusions: MSA patients with high disease severity will per-
ceive themselves with drooling and worst swallowing disturbances.
Feeling of discomfort while swallowing is the most common com-
plaint of MSA patients with swallowing disturbances. The SDQ is a
useful questionnaire that detects the swallowing disturbances in
MSA as expected along the natural history of the disease. These
findings may help developing swallowing interventional program for
MSA patients.
703
3D sensors, a new paradigm for assessing Parkinsons disease
A. Mario, B. Jorge, M. Daniel, V. Pedro (Havana, Cuba)
Objective: Create objective, automatic and relatively inexpensive
tools for the evaluation of Parkinsons disease using the new 3D sen-
sors like the Microsoft Kinect.
Background: Currently, motor control is evaluated by means of
scales or specific instruments. Each method has advantages and
disadvantages.
The scales are widespread because they are relatively inexpensive
and accessible. However, they have the problem of being subjective
and requiring a prolonged training time. Assessment tools, are more
precise and objective but they have the problem of being heterogene-
ous, generally expensive and focused on very specific objectives. In
our project we applied the first-generation Microsoft KINECT sensor,
as the motion capture system for the evaluation of motor control in
patients with Parkinsons disease.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S278 POSTER SESSION
Fig. 1. (703).
Methods: We use the Microsoft Kinect sensor for video games,
programming with the Software Development Kit (SDK) version 1.7.
We evaluate capabilities and functions that were defined as
Descriptive Parameters (DP).
Using the normal sample, linear age dependent regressions were cal-
culated for DP the mean (l) and standard deviation (l) were obtained.
In a second step we applied the valuation protocol to 10 normal
subjects (mean age 5 59.5 years, female 5 4) and 10 patients with Par-
kinsons disease (PD) (mean age 5 58 years, female 5 3; mean evolu-
tion time: 9.7 years; Hoehn and Yahr: 7 patients in state 2 and 3
patients in state 3). Patients with PD performed maneuvers at its best
ON, in the early hours of the morning to ensure the best performance.
Results: For the interpretation of the results we divided its analy-
sis in body segments and functions. The values of the PD for the
patients with PD had a worse performance than the normal subjects
In all DP. [figure1] Each color represents the trajectory of different
points of the body. To the left, a normal subject is shown. To the
right, a subject with Parkinsons disease.
Conclusions: The Kinect system is useful for the evaluation of
motor control and Movement Disorders. It distinguishes normal pat-
terns of posture and movements even in early states of Parkinsons
disease. This research demonstrates the utility of the Kinect sensor to
record and evaluate the postures and movement sequences in a set of
manoeuvres and opens new possibilities for assessment, diagnostis
and treatment of Movement Disorders.
704
Variability in Parkinsons disease quality improvement measure
documentation in a specialty center
J.P. Martello, M. Armstrong (Baltimore, MD, USA)
Movement Disorders, Vol. 30, Suppl. 1, 2015
Objective: To review documentation of Parkinsons disease
(PD) quality improvement measures (QIMs) at a specialty center
and to identify whether degree of compliance correlates with phy-
sician years of experience, patient age, Montreal Cognitive
Assessment (MoCA) score, number of visits, or caregiver
presence.
Background: QIMs are a growing trend to make physician reim-
bursement more objective and to assure comprehensive, standardized,
and structured patient care with the hope of improving outcomes.
The American Academy of Neurology (AAN) published ten PD
QIMs in 2010, but no study has yet assessed compliance with these
measures in routine practice.
Methods: We conducted a retrospective chart review of consecu-
tive PD patients seen by specialists in a Parkinsons disease outpa-
tient clinic to assess PD AAN QIM documentation over a years
time (index date in 2012). We also collected patient demographic
information, MoCA scores, number of visits within that year, and
caregiver presence at appointments.
Results: Fifty-two patient charts were reviewed. Only four
patients (7.7%) had all 10 QIMs documented. Reviewing medical
and non-medical treatment options was the only QIM with 100%
compliance. The 3 QIMs for reviewing sleep, cognitive, and psy-
chiatric related comorbid issues annually all achieved 90% com-
pliance. Documenting a re-review of idiopathic PD as the
patients diagnosis had the lowest documentation compliance at
29%. Fall history was reviewed at every patient visit only 31% of
the time. Greater years in practice had the largest correlation with
a lower number of documented QIMs, though this did not reach
statistical significance (correlation coefficient of -0.925, p50.075).
Patients age, MoCA score, number of visits, and caregiver pres-
ence did not significantly correlate with number of QIMs
documented.
 POSTER SESSION S279

Conclusions: Even at a specialty center, documentation of pub-
lished QIMs in clinic notes is variable. While the hope that docu-
menting QIMs improves outcomes remains unproven, QIMs are
based on issues of known importance in PD. Whether poor compli-
ance for some items reflects lack of assessment or lack of documen-
tation is unknown. Our study suggests room for improvement with
QIM documentation, particularly for high-impact concerns such as
falls for which published QIMs require documentation at every visit.
705
Decreased FOG following multi-system behavioral intervention-A
case report
C.E. McLean (Hermosa Beach, CA, USA)
Objective: This case study was done to evaluate the short and
long term effects of a multi-system Physical Therapy (PT) interven-
tion for an individual with PD and FOG.
Background: FOG is a complex disorder with contributions from
multiple systems including motor, cognitive and emotional. There is
limited evidence for treatment of FOG resistant to optimal medical
and surgical intervention. Historically, PT research and clinical prac-
tice utilize visual and auditory cues to compensate for impaired sys-
tems. Best practice is moving towards intervention that is designed
to improve an individuals functional ability by training impaired
systems. No PT framework currently exists to address multi-system
impairments in a systematic, progressive manner. The subject of this
case study is a 62 year old male, diagnosed with PD in 2002, under-
went bilateral STN-DBS in 2007.
Methods: DC was seen for 17 sessions, 45 minutes each, over
the course of 3.5 months. Evaluation and intervention systematically
assessed and addressed multi-system deficits and followed motor
skill acquisition principles including task specific practice, high repe-
tition, complexity, variable feedback, progressive challenge, variable
context, and relevant activities. Environment of session was based on
discussion of situations where FOG occurred, and efforts were made
to simulate real-life environment in the clinic.
Results: Following intervention DC demonstrated significant
reduction in frequency and severity of FOG. DC reported freezing 2-
3 times per day, 10 seconds or less each time. Improved confidence,
QOL, gait velocity, endurance, and stability.
Conclusions: Utilization of comprehensive, multi-system assess-
ment and intervention was successful in this case for reducing FOG
for an individual diagnosed with PD x 10 years. With on-going
access to an exercise class supervised by an experienced PT, DC
was able to maintain benefit greater than 1 year following individual
intervention.
706
One year dynamics of spatiotemporal gait parameters and ADL
performance in patients with Parkinsons disease
aasuke, P. Taba (Tartu, Estonia)
K. Medijainen, M. P
Objective: To investigate changes in gait parameters and disease
severity in an interval of one year in persons with PD.
Background: Slower and shorter stepped gait in well docu-
mented in patients with PD. Little is known of what is the rate of
disease progression in aspects of motor and ADL performance in
PD.
Methods: Thirteen patients (6 women and 7 men) with mild to
moderate PD diagnosed by the Queen Square Brain Bank (QSBB)
clinical criteria, with a mean (6SD) age of 65.2 6 6.7 years and
disease duration of 8.15 6 3.4 years participated. Patients were
tested twice - at baseline and approximately 1 year later. Spatio-
temporal characteristics of gait were assessed using 3-D optoelec-
tronic movement analysis system ELITE (BTS Bioengineering,
Italy). Six infrared cameras registered the displacement of 20
reflective markers positioned according to the Davies protocol.
Three trials of gait on 6-m walkway were performed. Participants
were treated with PD medication and had no access to physiother-
apy. Unified Parkinsons disease Rating Scale (UPDRS), the
Hoehn & Yahr scale (H&Y) were used for neurological assess-
ments. Schwab-England Activities of Daily Living Scale (S-E) and
ADL part of UPDRS was used to indicate changes in ADL
performance.
Results: A significant (p<0.05) decline in stride length (5.6%)
and walk ratio (9.8%), and shortening of swing time (7.3%) were
detected at one-year follow-up assessment. Walking velocity, step
with and cadence did not change significantly following 1-year
period.
From statistical data pertaining to clinical characteristics of PD
(UPDRS scores, H&Y and S-E) significant differences between base-
line and 1 year later were observed just in UPDRS ADL score
(p<0.01) and Schwab and Englands ADL score (p<0.05).
Conclusions: While disease severity according to neurological
assessment might remain constant during one year period for patients
with PD receiving only pharmacological treatment, several gait
parameters and ADL performance show significant decline. This is
indicative that in relatively short period, standard neurological
assessment measures of PD, might be misleading in assessment of

Results

Norms Initial Evaluation Discharge 1.5 year follow up

Assessment (age/fall cutoffs) (2/17/2012) (5/31/2012) (11/4/2013)
TUG/Dual Task TUG 13.5sec/14.5sec 12.9sec/27.38sec 8.4sec/12.4sec no freezing 8.2sec/12.8sec
freezing on turn no freezing
Gait Velocity 10 meter 1.36 m/s 1.93 m/s SS: 0.9 m/s Fast: SS: 1.2 m/s (16 steps) SS: 1.27 m/s
(Self-Selected//Fast) Not Tested Fast: 1.67 m/s (13 steps) (17 steps)
Fast: 1.76 m/s
(13 steps)
6 MWT 1877 feet 1028 feet=54% 1770 feet=94% 2096 feet=111%
Functional Gait 27/30 15/30 29/30 25/30
Assessment
ABC >67% 54% 77% 80%
PDQ-39 Lower=Better, 91/156 60/156 56/156
Higher=Worse
MOCA 26/30 25/30 (tested by OT) NT 23/30 (tested by OT)
Verbal Fluency 11 11 13 9
Trail Making (A/B) 33sec/72sec 67sec/123sec 42sec/100sec 52sec/102sec

Movement Disorders, Vol. 30, Suppl. 1, 2015

S280 POSTER SESSION
the impact of the disease. The effect of other possible PD treatment
methods (e.g physiotherapy) on different aspects of motor and ADL
performance needs further investigation.
707
Intraoperative microstimulation predicts outcome of post-
operative macrostimulation in STN DBS for PD
R. Mehanna, A.G. Machado, F. Alsaloum, S.E. Cooper (Houston,
TX, USA)
Objective: To assess if intra-operative micro stimulation can help
avoid positioning the deep brain stimulation electrode too close to
the internal capsule.
Background: In deep brain stimulation of the subthalamic nucleus
(STN DBS) for treatment of Parkinsons disease (PD), a commonly
encountered stimulation side effect is involuntary muscle contractions
from spread of electrical current to cortico-spinal and cortico-bulbar
fibers in the internal capsule (IC). During surgery, a variety of techni-
ques, including microelectrode recording (MER), are used to avoid posi-
tioning the DBS electrode too close to the IC. At some centers, MER
includes stimulating through the microelectrode (microstimulation).
Methods: From clinical records, we compiled micro- and DBS-
electrode locations, microstimulation effect thresholds and DBS side
effect thresholds.
Results: We found that capsular macrostimulation thresholds
were significantly lower in cases where capsular microstimulation
effects were observed (mean (SD) 2.4 (0.66) V, range 1.0-4.5), than
in those where they were not (mean (SD) 3.1 (0.88), range 1.5-
5.8)(p50.0000974 Students t) .In addition, we found that lower-
threshold for microstimulation-induced involuntary muscle contrac-
tions at shorter distances from a given DBS electrode contact pre-
dicts a lower threshold for involuntary muscle contractions as a side
effect of stimulation with that contact. Specifically, our results sug-
gest that capsular macrostimulation thresholds below 2 V are avoided
when the product of microstimulation threshold (in uA) and distance
(in mm) is greater than 500.
Conclusions: Intra-operative micro stimulation can help avoid
positioning the deep brain stimulation electrode too close to the
internal capsule.
708
Parkinsons disease: A regression based approach to motor
symptom progression
A. Mendes, A. Goncalves, N. Vila-Ch~ a, M. Calejo, I. Moreira, J.
Fernandes, J. Damasio, A.B. Lima, S. Cavaco (Porto, Portugal)
Objective: To explore the association between Parkinsons dis-
ease (PD) duration and motor disease severity.
Background: Individual prediction of motor symptom progres-
sion in PD is currently not feasible. A better understanding of how
PD motor symptoms progress would help patients make informed
decisions about their personal and professional lives and would sup-
port clinicians in treatment decisions and design of neuroprotective
clinical trials.
Methods: Three hundred consecutive PD patients were evaluated
using the Unified Parkinsons disease Rating Scale (UPDRS), sub-
scales III. UPDRS-III was applied after 12h without antiParkinsonian
medication (off) and one hour after the usual morning dose of
patient medication (on). Scatterplots and multiple linear regression
analyses were used to explore the association between UPDRS-III
scores and disease duration, while taking into account the following
covariates: sex, age (<74 vs. >75), age at PD onset (<54 vs. >55)
and levodopa equivalent dose (LED). Quadratic and cubic effects of
disease duration were accounted for in the regression model. The
assumptions of homoscedasticity and normal distribution of the resid-
uals were verified.
Movement Disorders, Vol. 30, Suppl. 1, 2015
Results: UPDRS-III off and on were significantly associated
with disease duration (linear, quadratic, and cubic scaling; p<.01).
The adjusted R2 was .319 for UPDRS-III off and .155 for
UPDRS-III on. When considering covariates sex, age at PD onset,
and LED, the association between disease duration and UPDRS-III
remained statistically significant (p<.05). In this analysis, UPDRS-III
scores were also significantly related with the covariates. The regres-
sion model with the covariates explained respectively 41% and 28%
of the variance of UPDRS-III off and on.
Conclusions: The observed cubic association between motor
symptoms and disease duration suggests that the rate of motor symp-
tom progression varies with disease duration. A model of motor
symptom progression can be developed based on the regression coef-
ficients. This regression-based approach would help clinicians get a
better estimation of patients individual motor symptom evolution.
709
Fluorodeoxyglucose positron emission tomography (FDG-PET) in
prion disease
K. Mente, J. ODonnell, P. Gambetti, S.E. Jones, B.S. Appleby
(Cleveland, OH, USA)
Objective: In this study, brain 18-fluorodeoxyglucose-positron
emission tomography (FDG-PET) scans will be examined retrospec-
tively in cases of definite or probable Creutzfeldt-Jakob disease
(CJD) and other prion diseases to determine if there are patterns of
FDG metabolism associated with prion disease.
Background: CJD and other prion diseases are rapidly progres-
sive spongiform encephalopathies that are invariably fatal after a
brief symptomatic period of usually several months. A constellation
of clinical features and abnormalities in MRI, EEG, and CSF analy-
ses can suggest possible or probable CJD, but a definitive diagnosis
can be only be made by means of autopsy with histology, immuno-
histochemistry, and Western blot of brain tissue. One neuroimaging
modality, FDG-PET, is not routinely used in the evaluation of
patients with probable or possible CJD.
Methods: The Cleveland Clinic electronic medical record system
was queried from 2003 to 2013. Cases fulfilling criteria for possible
or probable CJD from WHO or Zerr et al. were selected if FDG-
PET were performed (ICD-9 code 046.19). 13 cases were included
in this study. There were 8 autopsy confirmed sporadic CJD cases, 2
definite familial CJD cases with E200K mutation in the prion protein
gene, 1 case of fatal familial insomnia, and 2 cases of probable CJD
in which autopsies were not performed. Mean age at disease onset
was 60 years. FDG-PET images were reviewed independently by
two neuroradiologists. Then images were analyzed in MIM Neuro
software (MIM, Cleveland, OH, USA), which was compared against
a normal database of 43 cognitively-intact individuals with a mean
age of 63 years to determine presence of hypermetabolism and hypo-
metabolism. Hypermetabolism was defined as a z-score greater than
1.77 and hypometabolism was defined as z-score of less than -1.77
for p<0.05.
Results: Hypometabolism was found in the parietal lobe in all
thirteen cases of prion diseases. Hypermetabolism was found in the
medial temporal lobe structures in 12 out of 13 cases and in the
nucleus accumbens in 10 out of 13 cases.
Conclusions: This case series identified a pattern of parietal
hypometabolism and medial temporal and nucleus accumbens hyper-
metabolism in prion disease. Hypermetabolism has never been
reported in prion disease although parietal hypometabolism has been
previously reported.
710
Mimicking progressive supranuclear palsy and causing Tako-
Tsubo syndrome: A case report on IgLON5-encephalopathy
M.T. Montojo, V. Piren, F. Benkhadra, A. Codreanu, G. Wirtz, P.
Kerschen, N.J. Diederich (Mostoles, Spain)
 POSTER SESSION
Fig. 1. (710).
Objective: To describe a patient with AB to IgLON5, sudden
stridor and Tako-Tsubo syndrome (TTS).
Background: Sabater et al recently described eight patients with
a novel parasomnia characterized by severe sleep dysfunction and
atypical Movement Disorders associated with antibodies (AB) to
IGLON5. Acute stridor episodes, gaze abnormalities and sudden
death in five patients were reported.
Methods: Case report: 70-yr old woman, on visit to Luxembourg,
urgently admitted at the pulmonary department in June 2014 because
of daytime stridor; the bronchial fibroscopy showed a bilateral vocal
cord palsy and emergency tracheostomy was performed. Neurologi-
cal consultation was requested as the patient carried the diagnosis of
progressive supranuclear palsy.
Previous medical history: nonspecific gait problems since 2006,
horizontal gaze dysfunction and a first episode of acute suffocation
in 2012; inability to sneeze or cough in 2013. In February 2014 an
episode of acute laryngeal dyspnea was followed by TTS from which
the patient fully recovered.
[Figure1]
Image 1: Left ventricular angiography in diastole (left) and sys-
tole (right), showing akinesia of the mid ventricular segments with
normal contraction of the basal and apical regions.
Results: Neurological exam: mild dysarthria & dysphagia; supra-
nuclear gaze palsy mainly affecting horizontal eye movements; bilat-
eral Babinski sign; postural instability. MRI showed mesencephalic
atrophy with hummingbird sign; DAT- SCAN evidenced bilateral
asymmetric striatal uptake and MIBG-SPECT moderately reduced
myocardial uptake. Positive IgLON5 antibodies were found in the
serum and confirmed by three laboratories. Lumbar puncture, poly-
somnography and experimental treatment with immunoglobulins
were refused and the patient returned to her home country. By phone
the family confirmed stable condition three months later.
Conclusions: Conjunction of different syndromes in a patient
with AB to IgLON5. The daytime manifestation of the stridor is
remarkable. TTS could be due to primary or secondary catecholami-
nergic discharge or to primary involvement of the heart also express-
ing LON5. (Of note, in TTS sudden death can be due to secondary,
fatal arrhythmia.) Despite the long disease course, the movement
syndrome remained limited, suggesting self-limiting disease, at least
in some brainstem areas.
Reference:
Sabater L, Gaig C, Gelpi E et al. Lancet Neurol. 2014;13:575-
86.
S281
711
e-Motion: A reliability assessment for a prototype software to
complement the clinical evaluation of patients with Parkinsons
disease
B.E. Mu~noz, A. Navarro, Y.J. Ariza, J.D. Arango, J.L. Orozco (Cali,
Colombia)
Objective: Our interest is to determine the reliability between e-
Motion Capture System, incorporating KinectTM as main capture
device, and a multiple-camera 3D motion capture system gait labora-
tory during walking test.
Background: The gait pattern in patients with Parkinsons dis-
ease is characterized by reduced walking speed, increased stance
phase, decreased stride length and decrease in the amplitude of the
lower limbs. The gait variations cannot be objectively measured in
the clinical examination to track the course of disease and make
decisions in effective manner.
Methods: The e-Motion Capture System: is a software prototype
able to calculate cadence, stride length, and length step and spatio-
temporal (velocity and acceleration) variables. Three route-test for a
total of 18 paths, and the corresponding simultaneous captures with
e-Motion and the benchmark system. The AB paths are discarded
because the better performance of the KinectTM is when people
walk towards KinectTM, to finish with nine BA valid paths as show
on figure 1.
(figure 1)
Results: The index for the reliability to both systems and both
laterality (N=599) averaged together 0.96 (IC95% 0.94 - 0.97). To
left ankle, (N=103), the index was 0.96 (IC95% 0.88 - 0.98), and to
right ankle, (N=112) the index was 0.97 (IC95% 0.85 - 0.99).
According to guideline for the evaluation of intra-class correlation
coefficients, the inter-rater agreement between e-Motion and bench-
mark system shows an excellent agreement.
Conclusions: The e-Motion Capture System could develop and
quantify measurements of motor and spatial-temporal variables sensi-
tive to change in the timeline of the disease. In addition, this tool is
useful to complement the clinical assessment and measure efficacy
of pharmacology and non-pharmacology interventions of patients
with Parkinsons disease. This innovator system would fit into the
conditions to the neurology clinics in low and middle income coun-
tries. The KinectTM sensor compared to benchmark gait analysis has
advantages such as low cost, portability, no need to use landmark for
capture and less complex settings.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S282 POSTER SESSION

713
Withdrawn by Author

714
The mitochondrial serine protease HtrA2 degrades disease-
associated prion protein
M.M. Rahman, S. Akhter, S.T. Hong (Jessore, Bangladesh)
This abstract removed post-publication due to the use of non-
original work.

Fig. 1. (711).

712
A powered orthosis improves the magnitude and consistency of
gait initiation in Parkinsons disease with freezing of gait
M.N. Petrucci, C.D. MacKinnon, E.T. Hsiao-Wecksler (Urbana, IL,
USA)
Objective: Investigate the utility of a portable powered ankle-
foot orthosis (PPAFO) that provides modest dorsi and plantarflexor
torques to facilitate anticipatory postural adjustments (APAs) during
gait initiation.
Background: Recent evidence suggests that freezing of gait
(FOG) and start hesitation symptoms of Parkinsons disease (PD)
relate to diminished and prolonged APAs during gait initiation.
External sensory cues markedly improve APA generation; however,
APA magnitudes observed using these cues are still diminished
compared to healthy aged-matched controls. Externally applied
mechanical perturbations have been demonstrated to shorten and
amplify the magnitude of APAs, but no portable devices have been
tested.
Methods: Seven participants with PD (age 69.4 6 15.3 yrs,
Hoehn&Yahr 3-3.5, with FOG symptoms) initiated gait in two self-
initiated baseline conditions (normal walking shoes [Base-Shoe],
PPAFO in passive mode on right foot [Base-PPAFO]), and three
cued conditions within an instructed-delay paradigm (acoustic go-cue
with passive PPAFO [Acoustic], mechanical assist from PPAFO
[Assist], and acoustic go-cue simultaneous with mechanical assist
[Acoustic-Assist]). Vertical ground reaction forces (vGRF) and cen-
ter of pressure (COP) peak amplitude and timing data were analyzed 715
(5 trials per condition) and compared across conditions. Functional (psychogenic) neurological symptoms in patients with
Results: A main effect of condition (p50.029) and significant postural tachycardia syndrome (PoTS)
differences in vGRF (p50.038) and medial-lateral (ML) COP ampli- L. Ricciardi, A.P. Owens, G. Ferrazzano, V. Iodice, C.J. Mathias,
tude (p50.015) were found. Compared to Base-Shoe, vGRF ampli-
M.J. Edwards (London, United Kingdom)
tude was significantly increased in the Acoustic (67%) and Acoustic-
Assist (126%) conditions. The Acoustic-Assist condition significantly Objective: Aim of our study was to retrospectively investigate
increased ML-COP amplitude compared to Base-Shoe (83%), Base- functional symptoms, with a particular focus on neurological symp-
PPAFO (51%), and Acoustic (41%). We also found NS trends of toms, in consecutive patients referred to our London-based national
decreased coefficient of variance of vGRF (50% to 36%) and ML- referral centre for autonomic disorders over a three-year period.
COP (48% to 38%) amplitudes and a decrease (34%) of time to peak Background: Postural tachycardia syndrome (PoTS), a heterogo-
vGRF amplitude from onset between the Assist and Base-PPAFO nous disorder mainly occurring in females between 15 and 40 year, is
conditions. the most common form (170 per 100,000 in the general population)
Conclusions: These preliminary findings demonstrate that of orthostatic intolerance and is characterized by an increase in heart
mechanical assistance can increase force production and lateral COP rate >30 beats per minute (BPM) within 10 minutes of standing, or a
magnitude, shorten timing, and reduce variability of APAs in patients maximum HR >120 BPM without orthostatic hypotension while stand-
with FOG. Further investigations are needed to determine the opti- ing. Functional disability in patients with PoTS ranges from mild to
mal torque parameters required to robustly modulate APAs during severe depending on the severity of symptoms and the presence of
gait initiation for people with PD and FOG. comorbidities. PoTS is often included in the differential diagnosis of

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION S283

chronic unexplained symptoms, such as inappropriate sinus tachycardia, TABLE 1. Types of Reported Movement Disorders in Large
chronic fatigue, chronic dizziness, etc. Moreover, many patients with Series
PoTS present comorbid functional somatic disorders, such as functional
gastrointestinal or bladder disorders. Functional neurological symptoms Chorea1 Parkinsonism1
(FNS) are part of functional somatic disorders, to date no data are avail- Ataxia Chorea Dystonia Dystonia Dystonia (our case)
able regarding the co-occurrence of FNS in patients with PoTS.
Methods: We reviewed the medical records of all consecutive 87 7 3 1 1
patients referred for suspected dysautonomia between 2012 and 2014
who received a diagnosis of PoTS. We evaluated all cases for a diag-
nosis of FNS. We describe demographic and clinical characteristics ference with sympathetic innervation both primary or secondary to dopa-
of this population. minergic drug effects. Further studies will be required.
Results: We identified 559 patients with PoTS (F/M: 500/59,
mean age 36.0 6 11.4). Within this population, 33(6%) patients also
received a diagnosis of FNS (F/M: 2/33, mean age 35.8 6 10.1). 717
Non-epileptic attacks and muscle jerks/spasm/twitches were the most
Parkinsonism and dystonia: Predominant features in a case of
frequent clinical presentation of FNS, each occurring in 27% (9/33)
ADEM
of the PoTS/FNS cases. Functional tremor was present in 18% (6/
33), functional dystonia in 9% (3/33), functional weakness in 15% H. Sarva, R. Garcia-Santibanez, W.L. Severt, M. Fabian, D. Swope,
(5/33) and sensory symptoms in 1 patient. V.L. Shanker, J.C. Cabassa, J.C. Cabassa, S.B. Bressman, R.
Conclusions: Our results confirm that PoTS mainly occurs in Saunders-Pullman, N. Lubarr (Brooklyn, NY, USA)
young, female patients. FNS can co-occur with PoTS, with non- Objective: To describe a case of acute disseminated encephalo-
epileptic attacks and functional Movement Disorders the most frequent myelitis (ADEM) with hypophonia, bradykinesia, and dystonic gait.
clinical manifestations. These data highlight the potential significance Background: ADEM is a monophasic demyelinating condition,
of the interoception of autonomic arousal in the pathogenesis of FNS. which presents in children and less often in adults. Although, it is
known to follow an acute infection or vaccination, it is not always
the case. MRI findings demonstrate extensive, multifocal, subcortical
white matter abnormalities. The most common presentations are
716
ataxia, headache, and weakness.
Unilateral decreased palpebral fissure in patients with Rarely does it present with frank Movement Disorders as the sole
Parkinsons disease: A new sign to consider manifesting symptoms.
M. Sanchez Abraham, O.S. Gershanik, S.S. Garcia, G. Mizraji, A. Methods: Case report.
Chade, G. Gomez Arevalo (Buenos Aires, Argentina) Results: A seventeen year-old man presented with six months of
gait and speech changes. He dragged his right leg and had intermit-
Objective: To determine whether eyelid diameter asymmetry is tent bilateral toe curling while walking. His speech was inaudible
most prevalent in Parkinsons disease (PD) patients than in the general and mentation slow. Examination demonstrated inappropriate smiling
population. Determine whether the decrease of the palpebral fissure and severe hypophonia. Montreal Cognitive Assessment score was
(PF) coincides with the initial side of Parkinsonian symptomatology.
Background: In some cases clinical symptoms are subtle and
inconclusive so it is necessary to appeal to supportive criteria that
approach to the correct diagnosis. We propose the observation of the
size of the PF as an additional criterion for support rather than exclu-
sionary in PD patients.
Methods: We selected 112 consecutive patients with diagnosis of
PD and 112 controls. At the office visit, through clinical observation
it was established whether a PF asymmetry was present and if the
side of reduced diameter coincided with the side of initial and domi-
nant Parkinsonian symptomatology. Patients with an unexplained
asymmetry were included. A subanalysis was conducted in 10
patients recently diagnosed with PD de novo with no current or past
treatment with dopamine agonists (including L-dopa) and the pres-
ence of eyelid asymmetry was documented.
Results: Of the 112 patients with PD, 39(35%) had clinically evi-
dent eyelid asymmetry, and in 34(87%) of these patients, asymmetry
coincided with the prevailing side of the Parkinsonian symptoms. Of
the controls, 12%(112/14) had eyelid asymmetry(CI: 2.18- 9.09, P
<0.0001). In PD patients, 28 of 39(71%) were treated with L-dopa.
In the sub-analysis of 10 patients with initial PD, 7 had eyelid
asymmetry(70%) and the side of PF reduction coincided with the
affected side in all patients.
Conclusions: Although the data are purely observational, it can be
concluded that asymmetric reduced PF coincident with the side initially
affected by Parkinsonian symptoms in PD patients is a sign to consider.
This method is easy, fast and requires simple observation in patients in
which signs are subtle and inconclusive. The most likely explanation for
this observation in the few published reports is believed to be related to
interference with sympathetic activity due to L-dopa. However, this is
not an entirely valid hypothesis, as patients without prior exposure to L-
dopa present this sign in a high proportion. This phenomenon can be
hypothesized to be an incomplete form of Horner syndrome, due to inter- Fig. 1. (717).

Movement Disorders, Vol. 30, Suppl. 1, 2015

S284 POSTER SESSION
Fig. 2. (717).
22/30 with deficits in visuospatial function, attention, calculation, list
generation, and abstraction. Eye movements were full but optokinetic
nystagmus was mildly diminished in all directions. Tone was spastic
with diffuse hyperreflexia. Rapid alternating movements were waxy
and bradykinetic. Overflow toe curling was present. Strength, sen-
sory, and cerebellar examinations were normal. His gait was slow,
wide-based, with proximal right arm and leg dystonic posturing.
Brain MRI [figure1] showed non-enhancing patchy abnormal signal
in the ventral midbrain, bilateral posterior limbs of internal capsule,
lentiform nuclei, and corona radiata. Spine MRI and ophthalmologi-
cal evaluation were normal. Infectious, autoimmune, paraneoplastic
and metabolic laboratory tests were unremarkable. Cerebrospinal
fluid testing was positive for only oligoclonal bands. ADEM was
presumed. Immunomodulators were not given due to continued clini-
cal improvement and absent MRI enhancement. At six month follow
up, his symptoms improved and at nine months, MRI findings
improved [figure2]. One year after his initial evaluation, his speech
and gait were normal and he returned to school.
Conclusions: Our findings suggest that ADEM is an unusual
cause of reversible Parkinsonism and dystonia in an otherwise
healthy young patient. As with other large ADEM series, prognosis
was favorable.
718
Compliance with Parkinsons disease quality measures
R.B. Schneider, R. Holloway, K. Biglan, M. Burack (Rochester, NY,
USA)
Movement Disorders, Vol. 30, Suppl. 1, 2015
Objective: To evaluate documentation of compliance with the
American Academy of Neurology (AAN) Parkinsons disease quality
measures (Cheng, 2010).
Background: In an era where compliance with quality measures is
increasingly tied to financial reimbursement and maintenance of certifi-
cation, it is important to ensure that quality measures are clinically
meaningful and easily measurable. Little is known about the current
state of implementation of PD quality measures or the ease of extract-
ing compliance information from the electronic medical record (EMR).
Methods: We conducted a retrospective review of non-procedural
outpatient encounters with Movement Disorder specialists or general
neurologists and a visit diagnosis of ICD-9 code 332.0 at an aca-
demic medical center and National Parkinsons Foundation Center of
Excellence. An initial review of 104 index visits in January 2014
yielded 80 subject records eligible for inclusion. For these subjects,
all visits with Movement Disorder or general neurology providers
occurring within 6 months of the index visit (before or after) were
reviewed. For each of the ten quality measures, compliance was
coded categorically based on pre-defined operational criteria.
Results: For the eight quality measures requiring review on an
annual basis, compliance ranged from 19% to 96% (Table 1). Com-
pliance for the two quality measures requiring review at each visit
was 46% (falls) and 71% (medication-related motor complications).
Compliance was high for the four measures where completion of a
review of systems form was deemed sufficient; there was no docu-
mentation of further discussion or assessment of symptoms pertain-
ing to the measure in 13% to 36% of cases. The average number of
measures met per visit was 5.5.
 POSTER SESSION S285

TABLE 1. AAN PD Quality Measure Compliance Rates sensation. Each patient had visible orofacial movements, but pre-
sented the dental sensation as the most distressing component of
AAN PD Quality Measure Compliance Rate their symptom complex. Several medications were tried to treat this
condition, including levodopa, without success.
1: Annual Parkinsons disease diag- 19%
Conclusions: In this case series we report a clinical syndrome
nosis review (annual)
best described as non-tardive orofacial akathisia with dental sensory
2: Psychiatric disorders or distur- 90%
phenomenon, which is a primary sensory syndrome with secondary
bances assessment (annual)*
movements. Unlike tardive akathisia and dyskinesia, we believe this
3: Cognitive impairment (annual)* 96%
syndrome may be related to a hypo-dopaminergic state possibly
4: Querying about symptoms of 83%
related to Parkinsonism, chronic lithium exposure, and basal ganglia
autonimic dysfunction (annual)*
stroke. Given that the symptoms did not respond to levodopa, we
5: Querying about sleep disturban- 93%
believe this may be a post-synaptic phenomena. Further study is
ces (annual)*
needed to confirm these hypotheses.
6: Querying about falls (each visit) 46%
7: Parkinsons disease rehabilitative 30%
therapy options (annual)
720
8: Parkinsons disease-related safety 28%
issues counseling (annual) Psychogenic Movement Disorders: Are there neurocognitive
9: Querying about Parkinsons dis- 71% differences between patients with non-epileptic seizures vs those
ease medication-related motor with other hyperkinetic motor manifestations?
complications (each visit) B.M. Scott, A.M. Strutt, P.K. Lundberg-Love, A.L. Schmitt, E.R. Trifi-
10: Parkinsons disease medical and 95% lio, D. Bowers (Gainesville, FL, USA)
surgical treatment options
reviewed (annual) Objective: To determine cognitive and psychological differences
between two psychogenic variants.
*Review of systems form sufficient Background: It is well known that psychologic distress and fron-
tal lobe dysfunction are associated with impairments in attention,
Conclusions: Documentation of compliance with the AAN Par- working memory, and executive function. In this study, we compared
kinsons disease quality measures varies considerably across the two psychogenic variants those with non-epileptic seizures (PNES)
measures. Assessment of compliance is hampered by the absence of and those with other hyperkinetic psychogenic motor disorders
specific benchmarks for determining compliance, incomplete docu- (PMD-H). We hypothesized that patients with more dramatic motor
mentation, and problems inherent to the use of an EMR such as the manifestations (i.e., PNES versus PMD-H) would demonstrate
ability to copy forward and pre-populate notes. More work is needed greater neuropsychological impairments, more severe psychopathol-
to determine the effect of an EMR documentation tool on compli- ogy, and report either a greater chronicity or severity of traumatic
ance and to assess the effect of successful implementation of quality experiences.
measures on patient outcomes. Methods: Participants included 16 individuals with video-EEG
verified PNES and 16 with tremor variant of PMD-H (Fahn & Wil-
liams criteria). All participants were seen through a major medical
center. All participants underwent an abbreviated multi-domain neu-
719
ropsychological battery, including effort measures, and completed
Non-tardive orofacial akathisia with dental sensory phenomenon self-report psychological measures. Data were analyzed using regres-
L.M. Scorr, S.A. Factor (Atlanta, GA, USA) sion analyses.
Results: Education and PTSD Symptom Checklist total scores
Objective: We report four patients with an unusual syndrome were significant predictors of general cognitive status (i.e., MOCA)
that we describe as non-tardive orofacial akathisia with dental sen- for both psychogenic groups [F(2,23)=14.8, p<0.001]. PMD-H par-
sory phenomenon. ticipants outperformed PNES subjects across cognitive measures,
Background: We utilize the term akathisia, as used by Ford with statistically significant differences in attention, lexical fluency,
et al., to describe an abnormal state of focal motor restlessness corre- and set maintenance (WSCT). There were minimal differences on
lating to a bothersome sensation. In akathisia the most distressing psychological measures. Binary logistic regression analyses identified
component of the symptom complex is the purely subjective sensa- daily functional status (i.e., employment, relationships) and set main-
tion. The patients we report each described a specific dental sensa- tenance as significant predictors of group membership [omnibus
tion with secondary orofacial movements. The sensation was so v2(2)=20.8, p<0.001]. This model accounted for 47.863.7% of the
bothersome that it was their primary reason for presentation, but the variance in group membership, with 75.0% of both groups correctly
sensation was not painful. Although burning mouth syndrome and classified.
oral tardive pain syndromes have been previously described, we have Conclusions: We found that the PNES group performed worse
not seen this particular syndrome reported. than the PMD-H group on neurocognitive tasks of frontal lobe func-
Methods: Clinical case series. tion. Although PTSD symptoms were associated with general cogni-
Results: Case 1 is a 73 year-old man with a history of bipolar tive status overall, psychological distress did not account for
disorder on chronic lithium treatment, with no exposure to neurolep- cognitive differences between the two psychogenic groups. Treat-
tics. He presented with the sensation of beads and wire on his teeth, ment implications and the integration of these findings with cortico-
which he said led to constant restless movements of his tongue and limbic disconnection theories of psychogenic illness will be
mouth. Case 2 is an 81 year-old man with a history of hemorrhagic discussed.
thalamic stroke who presented with the sensation of a crust-like build
up on his teeth. The sensation caused him to have continuous move-
ments of the tongue, lip puckering, and tooth grinding. Case 3 is a 721
58 year-old woman with PSP who developed the sensation of a film
on the back of her teeth, which led to movements of her tongue and A pilot study of a plant-based diet intevention in Parkinsons
lip puckering. Case 4 is an 81 year-old woman with DLB who devel- disease
oped a sensation like an orange peel on the back of her teeth, which S.P. Shah, H.C. Watson, H.M. Kane, J.E. Duda (Philadelphia, PA,
caused her to frequently move her tongue in an attempt to clear the USA)

Movement Disorders, Vol. 30, Suppl. 1, 2015

S286 POSTER SESSION
Objective: Determine if the introduction of a plant-based diet is
feasible in Parkinsons disease and to determine its effect on consti-
pation, quality of life, and symptoms of Parkinsons disease (PD).
Background: Oxidative stress, mitochondrial dysfunction, inflam-
mation, apoptosis, and protein accumulation are mechanisms impli-
cated in the pathogenesis of PD. Currently, medications to slow
progression of PD are lacking. However, evidence suggests that
nutrition plays a role in PD, either via deleterious or beneficial
effects. Dairy consumption has been shown to increase the risk of
PD while coffee consumption lowers the risk. Flavonoids, found in
plant-based foods, may reduce the risk of PD by modulating oxida-
tive stress and inflammation. Phytochemicals, the natural chemicals
contained in plant foods, are being studied to determine their role in
the prevention of human disease. Increased intake of a plant-based
diet is associated with lower risk of inflammation. In PD, increased
intake of fruits and vegetables may alter progression of the disease.
Though epidemiological studies appear promising, the feasibility of
implementing such lifestyle changes in PD has not been determined.
Furthermore, additional data is needed on the effects of a plant-
based diet in the management of PD.
Methods: Recruitment is underway for 20 participants with PD
from the Philadelphia Veterans Affair Medical Center Parkinsons
disease Research, Education, and Clinical Center for a 3 month feasi-
bility study instituting a plant-based diet to be completed in May
2015. Participants will attend 7 biweekly educational seminars
focused on plant-based foods and ways to incorporate such a diet in
daily living. The Diet History Questionnaire II and 3-day food diary
will be used to assess dietary compliance. A constipation scoring
scale, UPDRS, and PDQ-39 will track changes in bowel patterns,
symptoms of PD, and quality of life, respectively.
Results: DHQ-II diet records will be analyzed by Diet*Calc soft-
ware program to give daily nutrient intake. Paired t tests from base-
line to week 6, baseline to end of study, and week 6 to end to study
for questionnaire responses will be calculated.
Conclusions: We hypothesize that compliance with a plant-based
diet can be accomplished with education and resources. Furthermore,
a change in constipation scores, UPDRS, and PDQ-39 would indicate
a plant-based diet is beneficial in PD.
722
The role of nutrition in Parkinsons disease
S.P. Shah, J.E. Duda (Philadelphia, PA, USA)
Objective: To review the association between nutrients and the
pathogenesis, risk, and progression of Parkinsons disease (PD).
Background: PD results from the loss of dopaminergic neurons
in the substantia nigra with the pathological hallmark of alpha-
synuclein deposits. Many mechanisms have been implicated in the
pathogenesis of PD such as oxidative stress, mitochondrial dysfunc-
tion, protein accumulation, dysfunctional protein degradation, and
inflammation. Neuronal dysfunction along with activation of micro-
glia may lead to a chronic inflammatory state resulting in the devel-
opment of various neurodegenerative diseases. Targeting
neuroinflammation provides a potential avenue of intervention in PD.
A plant-based diet contains many compounds that fight against oxi-
dative stress and inflammation. Emerging evidence suggests certain
foods and nutrients contribute to neuroprotection or neurodegenera-
tion by affecting the various mechanisms causing PD.
Methods: A literature search was performed using the database
of PubMed up to December 2014 using the following search terms:
Parkinsons disease, nutrition, pathogenesis, antioxidants, dairy, caf-
feine, flavonoids, phytochemicals, oxidative stress, nicotine. Full-
length articles were used to create a review of the current knowledge
of nutrition in PD.
Results: Caffeine exerts a neuroprotective effect in PD by antag-
onizing adenosine 2A receptors in the brain. Japanese and Chinese
teas have been shown to decrease the risk of PD through its antioxi-
dant and anti-inflammatory properties. Foods containing flavonoids
Movement Disorders, Vol. 30, Suppl. 1, 2015
may reduce the risk of PD by modulating oxidative stress, inflamma-
tion, and mitochondrial function by providing the necessary antioxi-
dants. Preliminary evidence suggests that cinnamons metabolite,
sodium benzoate, protects against inflammatory cytokines and sup-
presses nitric oxide production. On the other hand, dairy products,
particularly milk and cheese, increase the risk of PD. The role of
meats, carbohydrates, and saturated fats in PD is conflicting.
Conclusions: A plant-based diet high in fruits, vegetables, and
whole grains may provide a disease modifying intervention to slow
the progression of PD however further evidence-based research is
needed.
723
Psychodynamic and reality therapy for psychogenic Movement
Disorders: report on 9 cases
V.D. Sharma, R. Jones, G. Alexander, C. Testa, S. Factor (Atlanta,
GA, USA)
Objective: To evaluate outpatient treatment approaches utilized
in psychogenic Movement Disorder cases with good outcomes.
Background: Psychogenic Movement Disorders (PMD) are
among the most common psychogenic neurological disorders and
may mimic nearly any type of movement. Diagnosis is often difficult
as is the approach to informing the patient. As such, PMD are often
chronic and associated with considerable disability and resource utili-
zation. Treatment is challenging as there is little in the literature to
support effective approaches.
Methods: A retrospective chart review of 32 patients with a clini-
cal diagnosis of PMD at Movement Disorder specialty clinic and
treated as outpatients by a single psychologist.
Results: Nine patients (28%) had good outcome with near com-
plete resolution of symptoms, 8 (25%) had modest improvement, 7
(22%) had no response and 6 (19%) were lost to follow up. Two
patients are currently undergoing treatment. For this presentation we
focused on the good outcome cases. Of those, 7/9 females, age range
from 25-69 years, duration of symptoms at the time of diagnosis var-
ied from few months to 4 years. Six of the cases had good insight
into their diagnosis. Psychodynamic psychotherapy with a reality
therapy emphasis was utilized. History focusing on a time line of
events surrounding the onset of symptoms and their precipitants was
developed. Early history was explored with particular attention to
past trauma. In all the cases precipitants were identified, five patients
had a history of past trauma that was central in the onset and persist-
ence of symptoms. Such traumas included physical abuse from a par-
ent or spouse (2), sexual abuse from a parent (1), abrupt end to a
marriage (1), and premature death of a parent (1). In the other four
cases symptoms resulted from recent family or work stressors.
Conclusions: It would appear that the causes of PMD, not sur-
prisingly, are heterogeneous including varied roles of past and recent
events. This would indicate that the psychological approaches would
need to be individualized with psychodynamic psychotherapy and
reality therapy being two potentially useful options. Prospective stud-
ies are needed. However, the need for individualized therapy could
be a barrier to well controlled blinded trials.
724
Quantitative analysis of voice in Parkinsons disease
A.K. Silbergleit, P.A. Lewitt, E.L. Peterson, G.M. Gardner (West
Bloomfield, MI, USA)
Objective: To determine if there are significant differences in
acoustic measures of voice between subjects with milder and more
severe Parkinsons disease; and to evaluate the correlation between
acoustic parameters of voice and subtests of the UPDRS.
Background: The most prominent feature of voice disturbance in
PD is hypokinetic dysarthria, characterized by monopitch and mono-
loudness. Previous studies have reported that acoustic characteristics
 POSTER SESSION
Fig. 1. (725).
of voice impairment may offer a means for detecting disease specific
changes and may assist in monitoring disease progression. However,
these reports did not quantify Parkinsonian features, or control for
medication effects, therefore, the relationship between the pattern of
vocal change and disease severity is unclear.
Methods: Levadopa-responsive PD subjects were divided on the
basis of disease severity using the summed ADL section of the
UPDRS. A median split of scores defined the milder and more
severe PD groups. Goup 1=2 females and 9 males with scores
below 12; Group 2= 6 females and 9 males with scores greater than
or equal to 12. Controls were 10 females and 12 males. Subjects
voiced into a headband microphone with direct input into the com-
puter. The CSpeech waveform analysis program was used for acous-
tic analysis. All PD subjects had discontinued anti-Parkinsons
medication for at least 12 hours at the time of testing.
Each subject phonated/i/for 3 seconds at comfort, high and low
pitch for three trials per pitch. Subjects performed pitch glides to
determine frequency range.
Results: Pairwise comparisons indicated a significant difference
in semitone range between the controls and Group 2 (p 5 0.036). An
overall difference occurred for males for semitone range (p50.003)
and the lowest frequency obtained during the glide down task
(p50.001). For both of these variables the test for trends was signifi-
cant (p50.002, p50.001 respectively). There were significant differ-
ences in semitone range for males between controls and Group 1
(p 5 0.014) and controls and group 2 (p50.005). Significant differen-
ces occurred for males between controls and group 1 and controls
and Group 2 in the lowest frequency obtained during the glide down
task (p50.002, and p50.001, respectively).
As UPDRS speech and motor scores worsened for both groups,
semitone range diminished.
Conclusions: Semitone range may be a sensitive indicator of PD
severity, particularly for males with PD.
725
Beat complexity and variability may optimize the effects of
rythmic auditory cueing on walk in Parkinsons disease
B. Sophie, D.G. Dotov, C.D.C. Val
erie, K. Torre, B. Bardy, S. Dalla
Bella (Montpellier, France)
Objective: To study beat complexity and variability optimization
of the effects of rythmic auditory cueing on walk in Parkinsons dis-
ease (PD).
S287
Background: Rhythmical cueing improves the spatio-temporal
gait parameters of patients with Parkinsons disease (PD). A particu-
lar statistical parameter (the a-exponent that describes the self-
affinity of a noisy series and is used to quantify its auto-correlation,
or long-range correlation) has been proposed as an index of healthy
variability in physiological control and is known to decrease with
PD. Music can be more powerful than simple metronomes in entrain-
ing human rhythmical behavior.
Methods: Design: 3 (Music, Amplitude-Modulated Noise, and
Metronome) x 3 (White Noise, Pink Noise, and No Variability in the
inter-beat-intervals) within-subject x 2 (PD and Control). Stimuli:
prepared in advance from manipulated midi piano renditions of clas-
sical marches; Average tempo 5 110% the participant-preferred;
CV 5 2% (in white and pink) and 0% (in no variability conditions).
Data collection: 18 walking trials plus pre-test, (3 1 1)-minute-long,
on a small track inside the hospital rehabilitation hall, spread over
two days. IMUs were used to detect gait events and extract gait
parameters (MobilityLab, APDM). Synchronization: The phase of the
step cycle, linearly-interpolated from the foot-falls, was sampled at the
time of the beats implicit in the auditory stimulus. Circular statistics
were applied to this relative phase to obtain a measure of synchroniza-
tion (vector length R, which is inversely related to the circular var-
iance). Participants did not receive any instruction with respect to
synchronization. Long-range correlation: a (detrended fluctuation anal-
ysis). Participants:15 PD (early motor symptoms) and 15 control.
Results: Music and 1/f variability are associated with an increase
in a (consult the coefficients in the linear models table, Model B and
C). PD and controls respond similarly to the auditory cueing stimuli
(Model D). These effects are also mediated by synchronization with
the stimuli (Model F and G).
[Figure1]
Conclusions: PD patients with early motor symptoms do benefit
from the optimized cueing inasmuch as the given statistical coeffi-
cients can be interpreted as markers of a healthy control system.
726
Effects of singing on voice and swallow in Parkinsons disease
E.L. Stegemoller (Ames, ID, USA)
Objective: To examine the effects of singing on speech and swal-
low in people with Parkinsons disease (PD).
Background: People with PD experience progressive negative
changes in voice and swallowing. Studies indicate that singing treat-
ments are beneficial for improving voice but the effects on swallow
Movement Disorders, Vol. 30, Suppl. 1, 2015
S288 POSTER SESSION
have not been investigated. The objective of this study is to examine
the effects of singing training on voice and swallow. Given that sing-
ing involves many of the same processes as speech and musculature
as swallow, we hypothesize that singing training will improve voice
and swallowing measures for people with PD.
Methods: Thirty persons diagnosed with idiopathic PD completed
weekly one-hour singing sessions administered by a music therapist
for 8 weeks. One group met once per week and a second met twice
a week. Sessions targeted respiratory control, frequency range, and
intensity control using vocal exercise and group singing tasks. Out-
come measures of vocal duration, intensity, and range, as well as,
maximal respiratory pressure, and swallow function (measured with
electromyography (EMG)) were completed pre and post 8-week ses-
sions. Voice, swallow, and whole health quality of life (QOL) meas-
ures were also collected. Repeated measures analysis of variation
was completed to comparing differences between groups and pre/
post outcome measures.
Results: Results revealed significant improvements in vocal dura-
tion (p 5 0.001) and intensity (p < 0.001). There was a trend towards
improvement in vocal range (p 5 0.17). Both maximum inspiratory
and expiratory pressure was significantly improved (p < 0.03). For
swallow, there was a significant increase in EMG duration. For qual-
ity of life measures, only voice QOL significantly improved
(p 5 0.04). Whole health QOL improved (p 5 0.07) but not
significantly.
Conclusions: The voice and respiratory findings of this study
were similar to results from previous investigations of singing ther-
apy for patients with PD. For swallow, the increase in EMG duration
may suggest that participants gained increased control over the mus-
culature involved with swallowing, maintaining closure of the epi-
glottis for the entire swallow duration. Moreover QOL measures
improved suggesting that singing may have added benefits on overall
health. Taken together, the results of this study indicate that singing
training (as administered by music therapists) is a beneficial therapy
in the treatment of PD.
727
Repetitive finger movement, Purdue pegboard and buttoning in
persons with Parkinsons disease
E.L. Stegemoller, J. Uzochuckwu (Ames, IA, USA)
Objective: To determine if participants with Parkinsons disease
(PD) that demonstrate festination of repetitive finger movements per-
form worse on functional dexterity tasks compared to those that do
not festinate.
Background: Performance of repetitive finger movements is a
clinical tool used to assess severity, progression, and treatment effi-
cacy in PD. Previous studies have demonstrated that repetitive finger
movement performance dramatically deteriorates at rates near 2 Hz
in 60% of participants with PD tested. However, the relationship
between this task and other functional tasks of manual dexterity
remains unknown.
Methods: Fifty-two participants completed an unconstrained
index finger flexion/extension movement in synchrony with an acous-
tic tone presented at a starting rate of 1 Hz with a gradual increase
to 3 Hz. The tone rate increased in increments of 0.25 Hz with 15
tones at each rate until reaching a max rate of 3 Hz. Movement rate
and peak-to-peak amplitude were obtained. Participants also com-
pleted buttoning and Purdue pegboard and buttoning. The buttoning
task required participants to wear a vest with three medium sized
buttons. Participants were timed while starting from a neutral posi-
tion and buttoning going down the vest as fast as possible. The Pur-
due pegboard required assembly of four small pieces in order (pin -
washer - collar - washer) going down the board as fast as possible
for 1 minute. Each piece assembly was counted.
Results: Results revealed that the festination group performed
significantly worse on the buttoning task compared to the non-
festination group (p 5 0.02). While Purdue pegboard performance
Movement Disorders, Vol. 30, Suppl. 1, 2015
was worse in the festination group, it did not reach significance.
Both group demonstrated a significant relationship between buttoning
performance and Purdue pegboard performance (t < 0.008).
Conclusions: While there was a significant relationship between
buttoning and Purdue pegboard performance, only significant differ-
ences in buttoning performance were revealed between groups. The
added cognitive component (i.e. remember the order of assembly)
for the Purdue pegboard task may explain the differing effects. The
results of this study suggest that quantitative analysis of repetitive
finger movement may be an advantageous tool to assess functional
tasks involving finger dexterity in persons with PD.
728
A study on subjective and objective freezing phenomena in
Parkinsons disease
S. Tagashira, K. Wada, K. Tanaka, Y. Tajiri, K. Nakashima (Tottori,
Japan)
Objective: To investigate the freezing phenomenon in Parkin-
sons disease (PD) from diversified perspectives and discussed its
clinical correlates to gain a comprehensive overview.
Background: Freezing of gait (FOG) in PD is a symptom that
interferes with daily living by increasing the risk of falling. In addi-
tion to gait, freezing phenomena of upper limbs, speech, and think-
ing are occasionally observed. However, few reports suggest a
detailed investigation of the entire freezing phenomenon.
Methods: A self-administered questionnaire for assessment of the
freezing phenomenon was given to 130 PD patients (54 men; mean
age6SD, 72.8 6 8.7 years; Hohen and Yahr stage, 2.7 6 0.9; disease
duration, 8.1 6 6.0 years). A neurological examination evaluated the
Unified Parkinsons disease Rating Scale (UPDRS) motor score and
12 types of freezing phenomena (first step; straight gait; turning; nar-
row space; reaching destination; upper right, upper left, lower right,
and lower left extremities; blinking; speech; and simultaneous freez-
ing phenomena). We defined a New FOG questionnaire (NFOG-Q)
score of 1 point as subjective freezing positive and one or more
findings in the above 12 types of freezing phenomena as objective
freezing positive. We analyzed the correlation between the freezing
phenomenon and cognitive function, including the Mini-Mental State
Examination (MMSE).
Results: We identified 23 patients (17.7%) as subjective freezing
positive, 31 patients (23.8%) as objective freezing positive, and 56
patients (43.1%) as both subjective and objective freezing positive.
The positive rate of subjective FOG was 60.8%; on the other hand,
the positive rate of objective FOG was 9.5%. Subjective upper-limb
freezing was observed in 18.8% of PD patients, objective in 12.4%.
Subjective speech freezing was observed in 34.5%, objective in
14.7%. A positive correlation was observed between the NFOG-Q
and UPDRS motor score, and a negative correlation was observed
between the number of objective freezing phenomena and the
MMSE score. Although the NFOG-Q score was significantly associ-
ated with the presence of objective FOG, it was not associated with
freezing phenomena of upper limbs, speech, blinking, and simultane-
ous load.
Conclusions: The freezing phenomenon is a symptom that is fre-
quently seen in PD patients. Our results suggested a correlation
between subjective and objective freezing phenomena and a differ-
ence between awareness and findings for each site.
729
Stressful life events precede the onset of hemifacial spasm. A
retrospective study in Penang Hospital, Malaysia
K. Tan, G.B. Eow, H.B. Chow, C. Cheah, Y.K. Chia, R.
Kanesalingam, M.H. Rafia, R. Azman Ali, T.T. Lim (Georgetown,
Malaysia)
 POSTER SESSION
Objective: To study the demographics of hemifacial spasm
patients in Penang Hospital and to analyze the role of stress as a pos-
sible pathogenesis of hemifacial spasm.
Background: Stress compromises the immune system and is
associated with heart disease and cancer.
Methods: This is a retrospective analysis of patients with hemifa-
cial spasm and age-and-sex matched control (public individuals).
Patients who presented as new onset or follow-up cases for hemifa-
cial spasm were included. Interviewer administered questionnaires
based on the Perceived Stress Scale (PSS) was used to obtain demo-
graphic data and assess the patients stress level. Subjects were
required to answer the questionnaires based on recall of events prior
to the onset of hemifacial spasm. Higher PSS score suggests a higher
stress level.
Results: Forty hemifacial spasm subjects (17.5% Malays, 75%
Chinese, 7.5% Indians) and 37 controls were included. The age of
onset for hemifacial spasm ranged from 26 to 74 years. Mean age of
onset for females was at 52.9 years and 51 years for males. Fifty-
eight percent of the cohort were women and 50% of the cohort had
right hemifacial spasm. Seventeen subjects (42.5%) received a com-
bination of botulinum toxin injection and oral medication (Clonaze-
pam, Baclofen or Carbamazepine). Another 42.5% subjects received
exclusively botulinum toxin injection while 15% of the subjects were
only on oral medication. MRI brain was done for 42% (n517) of the
subjects whereas 58% (n523) did not have an MRI done. Of the 17
patients who had a MRI brain done, 59% (n510) were reported as
normal, 41% (n57) were abnormal. Two out of the 7 abnormal MRI
demonstrated vascular compression of the facial nerve by an ectatatic
vertebral artery. The other 5 were reported as having microangiop-
athy and lacunar infarcts. Hemifacial spasm subjects had higher PSS
mean scores (18.80) compared to the control group (11.51)
(p<0.0001).
Conclusions: Our study shows that hemifacial spasm subjects
experience significantly more stress prior to the onset of illness. This
is consistent with the study by Johnson et al who concluded that sub-
jects with closely spaced stressful life events may be at increased
risk of developing hemifacial spasm. The result of this study raises
the awareness regarding the impact of psychological stress on the
manifestation of physical illness. However, larger randomized studies
are needed to confirm this finding.
730
Neurotological disease in intracranial tumors
H.A.G. Teive, B.S. Zeigelboim, V.R. Fonseca, H.A. Carvalho, J.H.
Faryniuk (Curitiba, Brazil)
Objective: To verify the labyrinthine alterations in patients with
intracranial tumors.
Background: The balance disorders may have their origins in the
malfunction of the vestibular receptors or be caused by lesions of
various vestibular pathways in the central nervous system, especially
the structures located in the cerebellopontine angle region, where the
clinical manifestations are externalized, according to areas compro-
mised by many neurotological dysfunctions.
Methods: It was performed a retrospective cross-sectional study.
We evaluated 21 patients with 13 cases of Vestibular Schwannoma,
4 cases of Von Recklinghausens disease, 1 case of squamous cell
tumor, 1 case of cerebral hematoma, 1 case of craniopharyngioma
and 1 case of arachnoid cyst, aged from 19 to 78 years (14 females
and 7 males). All patients underwent the following procedures:
anamnesis, ENT examination and vestibular assessment
(electronystagmography).
Results: Patients showed prevalence of imbalance when walking
(83.7%), motion incoordination (48.8%), nystagmus (42.7%) and
headache (41.8%). There was prevalence of alteration in the central
vestibular system with a predominance of unilateral vestibular deficit
disorder (62.0%).
S289
Conclusions: Central signs were very variables in each case and
the bidirectional and multiple semi-spontaneous nystagmus type was
the most often central sign.
731
Effectiveness of allied health therapy in the symptomatic
management of progressive supranuclear palsy: A systematic
review
E. Tilley, S. White, M. Peters, S.A. Koblar, S. Doeltgen, J.
McLoughlin (Adelaide, Australia)
Objective: To examine the effectiveness of physical, occupational
and speech therapy interventions in the symptomatic management of
progressive supranuclear palsy (PSP).
Background: Physical, occupational and speech therapy clini-
cians have a critical role in managing the various progressive symp-
toms of PSP. These include falls, speech and swallowing difficulties
from the early stages, and a rapid progression of disease. Aspiration
pneumonia, pulmonary embolism and other consequences of reduced
mobility are the leading course of death in PSP.
Methods: Systematic review methodology was utilized and thus a
priori protocol was published to mitigate possible bias. Quantitative
research published in English from the development of the diagnostic
criteria for PSP in July 1996 until April 2014 was sought. Studies
that satisfied the following criteria were included: 1) patients diag-
nosed with possible or probable PSP as per the established diagnostic
criteria, 2) effects of physical, occupational or speech therapy inter-
ventions, 3) outcomes relevant to physical, occupational or speech
therapy.
Results: Of the eight studies included, following critical appraisal
with standardized instruments, none examined occupational or speech
therapy interventions in current practice. Physical therapy interven-
tions included eye movement exercises with balance training, balance
training with audiobiofeedback, robot assisted gait therapy, supported
treadmill training and a dynamic antigravity postural system/vibra-
tion sound system. The programs ranged from 45-90 minutes/3-5
times a week for a length of 4-8 weeks for patients in the community
who could stand assisted or walk short distances. Positive outcomes
included improvement in gait parameters, balance and gaze control.
Two experimental intervention studies, transcranial magnetic stimula-
tion for language/gait, identified the need for larger studies with
sham-stimulation control.
Conclusions: There is preliminary evidence for a range of physi-
cal therapy interventions targeting gait parameters, balance and gaze
control that may be effective in patients with PSP. Further research
is required, including a focus on occupational and speech therapy, to
streamline access to and quality of care for patients with PSP and
their carers.
732
Spinal and bulbar muscular atrophy with dementia of frontal-
lobe type
K. Togo, A. Umemura, T. Oeda, J. Suzuki, H. Sugiyama, H. Sawada
(Kyoto, Japan)
Objective: To evaluate frontal lobe function in spinal and bulbar
muscular atrophy (SBMA) patients.
Background: SBMA is a motor neuron disease caused by the
extension of CAG repeats in the X chromosome androgen receptor
gene. Unlike amyotrophic lateral sclerosis, frontal lobe dysfunction
in SBMA has been thought uncommon so far. However, in recent
years, there several studies demonstrate that impaired frontal lobe
function was identified in some of a large number of SBMA patients.
Here, we present three patients with SBMA, one of whom exhibited
frontal-lobe type dementia.
Methods: The clinical data, including history, physical and neuro-
logical examinations, neuropsychological tests, brain MRI, IMP-
Movement Disorders, Vol. 30, Suppl. 1, 2015
S290 POSTER SESSION

SPECT and numbers of expanded CAG repeats in the androgen recep- TABLE 1. Profile of patients with Parkinsons disease
tor gene were investigated in three Japanese patients with SBMA. who participated in a rehabilitation program in the period
Results: Case 1 was a 69year-old man with 45 CAG repeats. He
developed nasal voice and weakness of the bilateral upper limbs 5
from March 2009 to May 2014. Rio de Janeiro, Brazil, 2014
years ago or earlier. On admission, he showed irritability and positive Variables n %
sucking and forced grasping reflexes. Mini-mental state examination
(MMSE) and frontal assessment battery (FAB) scores were 22/30 and Gender (Male/Female)1 218/134 62/38
6/18, respectively. Brain MRI revealed atrophy in the frontal lobes Average age (years)* 66 6 11 -
and the pontine tegmentum. 123I-IMP SPECT showed decreased cere- Average duration of disease (years)* 765 -
bral blood flow in the large areas of the frontal lobes. Case 2 was an Hoehn & Yahr Scale Modified* 2,6 6 0,8 -
80-year-old man with 41 CAG repeats. He had suffered from hand Type of DP (M/RA/T)1 189/96/20 54/27/6
postural tremor for 40-50 years. Case 3 was a 60-year-old man with Average of ND per patient* 6,8 6 46 -
54 repeats, and disease onset was 50s of age. He showed no symp-
toms and signs of frontal lobe impairment. MMSE scores were normal PD- Parkinsons disease; M- Mixed; AR- Akinetic-rigid; TD-
in Case 2 and Case 3. FAB scores were reduced (14/18) in Case 2 but Tremor-dominant; ND - Nursing Diagnosis. 1categorical variables n
preserved (17/18) in Case 3. In Case 2, brain MRI revealed mild fron- (%); *average; 6 standard deviation
tal lobe atrophy, and in both case 2 and case 3, the 123I-IMP SPECT
showed decreased blood flow in the frontal pole cortices. Background: The use of standardized language for a classification
Conclusions: We reported three SBMA cases and one of them system is essential in the modern world, especially in the transmission
showed frontal-lobe type dementia. In the other two cases without of information in the scientific, technological and professional commu-
clinical symptoms except for motor symptoms, MRI revealed mild nications. Therefore, the development of researches that one theme of
frontal lobe atrophy and SPECT showed low cerebral flow in the the nursing care to the patient with Parkinsons disease, based on
frontal regions, suggesting subclinical frontal lobe dysfunction. standardized terminologies, converges with the need for greater con-
solidation and global current generalization of nursing rehabilitation in
the context of multidisciplinary attention.
733 Methods: A descriptive, retrospective study, of documentary
research, using records as a source of primary data collection to per-
Nursing diagnoses related to motor and nonmotor symptoms in form the cross mapping. Probabilistic sample, random simple, con-
Parkinsons disease sisting of 352 records of patients with Parkinsons disease who
M.H.S. Tosin, B.G.R.B. Oliveira (Rio de Janeiro, Brazil) participated in a rehabilitation program in the period from March
2009 to May 2014. Research conducted in three stages where nursing
Objective: To perform the cross mapping of the Nursing Diagno- diagnoses were mapped with non-standard language, crossed with
ses of non-standard language, with the standardized language Inter- R
the ICNPV and validated by experts.
national Classification for Nursing Practice (ICNPV R ), version 4.0,
Results: The profile of 352 patients was characterized by 62%
2013, described in medical records of patients with Parkinsons dis- male, aged 61 to 80 years old (60%) and 72.5% with time of disease
ease in rehabilitation.

Fig. 1. (733).

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
Fig. 2. (733).
evolution between 1 to 10 years; 29% in stage 2 of the H&Y Scale
and 54% with the Mixed form of Parkinsons disease.
From the records analyzed 2398 non-standard diagnoses have
emerged that, after the crossing with the taxonomy, resulted in 75
R
standardized diagnoses according to ICNPV (6.8 6 46). It is observed
the prevalence of diagnoses related to motor symptoms of the disease
(52%), being Hypoactivity the most mapped (32%).[figure1]Al-
ready nursing diagnoses related to nonmotor symptoms showed
slightly lower average, but with greater dispersion between the diag-
noses (3.3 6 52). Of these, Impaired Urinary System Process was
the most mapped (74 percent). [figure2]
Conclusions: The cross mapping allowed the comparison of
Nursing Diagnoses with non-standardized with standardized language
R
ICNPV, recognized worldwide. It allowed better meeting the profile
of patients cared for by nursing staff, even in the face of sympto-
matic variability introduced by this universe.
734
A metabolomic study in post-mortem DBS human tissue
V. Vedam-Mai, S. Sternberg, M. Williams, T.J. Garrett, M.S. Okun
(Gainesville, FL, USA)
Objective: Metabolomics is becoming increasingly applied to the
study of several metabolic diseases as well as neurodegenerative dis-
eases. Currently there are little to no investigations for its use in the
study of biomarkers of Parkinsons disease (PD). We propose to uti-
lize this technique for detecting metabolic changes resulting from
Deep Brain Stimulation (DBS) for PD.
S291
Background: Metabolomics is the investigation of small mole-
cule metabolites in biofluids and tissues and is emerging as a power-
ful tool for characterizing and identifying biomarkers and for
fingerprinting the metabolic status of physiological processes in tis-
sue, blood and other samples.
Methods: Snap frozen tissue from patients who had previously
undergone Deep Brain Stimulation for Parkinsons disease will be
used. Tissue will be sampled from the region immediately surrounding
the DBS electrode from both hemispheres of the DBS brain, as well
as control brain and prepared. Metabolomic analysis will be performed
on a Thermo Q-Exactive high resolution mass spectrometer with Dio-
nex Ultimate 3000 UHPLC in both positive and negative ion mode.
Peak alignment and mass spectral data reduction will be performed
with MZmine and Metaboanalyst will be used for statistical analysis.
Results: A total of 2500 features were detected in positive mode.
Principal components analysis (PCA) was used to identify potential
metabolites that separate DBS regions from non-DBS regions. A PCA
score plot along with the sample areas from the DBS side of the brain
tissue shows separation of samples near the DBS lead on PC2. Several
features were identified from the loadings that are highly correlated to
the DBS region. A metabolite of cysteine (2-amino-2-enoate) was
highly elevated in the DBS regions (nearly 2x increase). This metabo-
lite is involved in several KEGG pathways as a metabolite of cysta-
thione, homocysteine, and/or methionine. Faulty sulphation has been
reported in patients with Parkinsons disease and supplementation
with cysteine, methionine, and molybdenum is reported.
Conclusions: We have shown the sampling of small regions of
the brain to evaluate metabolomic response to DBS. Additional work
is needed to validate detected metabolite expression correlated to
electrical stimulation. Metabolites related to sulphation were
Movement Disorders, Vol. 30, Suppl. 1, 2015
S292 POSTER SESSION
detected, which has been reported to be faulty in patients with DBS
suggesting a correlation to sulphate metabolites and possible product
of electrical stimulation.
735
Histopathological observations from 50 human deep brain
stimulation cases
V. Vedam-Mai, A.T. Yachnis, K.J. Otto, A. Gunduz, A. Wagle Shukla,
C. Hess, M.S. Okun (Gainesville, FL, USA)
Objective: Our objective was to provide a comprehensive update
of the UF DBS Brain Tissue Network (DBS-BTN) which was estab-
lished in 2010 and we include clinical and histopathologic findings
concerning the DBS tissue interface.
Background: Despite deep brain stimulation (DBS) use in clinical
practice rising, there have been very few postmortem studies demonstrat-
ing the safety and the effects of chronically implanted electrodes and the
potential effects of high frequency electrical stimulation on human brain
tissue. Further, very little is understood regarding the cellular mecha-
nisms that are responsible for symptom improvement. There have been
several hypotheses, including vascular remodeling and progenitor cell
proliferation, but the question still remains largely unanswered.
Methods: Standard operating procedures for processing postmor-
tem DBS brains were employed. Tissue blocks were prepared, and
sections cut and stained for routine pathological diagnosis. Individual
patient data files were generated, and were maintained.
Results: Since our previous publication in 2011, we have added 31
new brains (19 DBS previously reported) brains. We provide summary
of neuropathological findings from the cohort, and the tissue responses to
the DBS electrode. Neuropathological findings from our study demon-
strate minimal histopathological changes and the long-term safety of cur-
rent neuromodulation devices. Our analysis demonstrates that the most
common tissue response is a minimal GFAP immunoreactive gliosis,
with the exception of two cases which present with thick, collagenous
sheathed fibrosis. A few cases with focal hemosiderin deposition were
observed, and some cases of scanty lymphatic inflammation at the edge
of the DBS lesion were noted. Results from research using the tissue as
well as projects that are currently underway will be presented.
Conclusions: Our data demonstrate the DBS-BTN as a useful
resource for the scientific community. Based on our preliminary results,
we demonstrate that DBS is well tolerated, and leads to minimal sur-
rounding tissue damage. We plan to continue expanding the Network
to facilitate collaborative research efforts directed at better understand-
ing the biology and mechanisms of action of DBS. We also plan to
explore other opportunities such as high resolution MR microscopy,
genomic and metabolomic studies, as well as changes in precursor cells
in up and downstream locations from the electrical current.
736
Withdrawn by Author
737
Demodex sp prevalence in Parkinsons disease patients
O. Yilmaz Kusbeci, O. Miman, M. Gedizlioglu (Izmir, Turkey)
Objective: To investigate the frequency of De:modex sp. among
Parkinsons disease (PD) patients.
Background: Changes in the skin are common symptoms of Par-
kinsons disease. Many people with Parkinsons develop oily or flak-
ing skin, especially on the face and scalp. Demodex live in the face,
hair-roots, hair follicle and oil glands in the skin. Symptoms of
demodicosis (demodex) are often similar to other skin diseases.
Demodex folliculorum is commonly found in the skin and is the
most common ectoparasite in humans.
Methods: In this study we evaluated age matched study and con-
trol groups of which were composed of 43 patients with PD and 40
Movement Disorders, Vol. 30, Suppl. 1, 2015
healthy subjects respectively. Standardized skin surface biopsy
(SSSB) and Cellophane-tape preparations taken from their face, espe-
cially at the base of the nose, underside of the jaw and the side of
the forehead, were examined microscopically.
Results: The mean age of patient and control groups were
63,81 6 6,60 and 62,75 6 6,1 (p50,45), respectively. Demodex sp.
was found to be positive 39% in patient and 30% in control groups
and there was not a statistically significant difference in Demodex
sp. infestation rate between patient and control groups (p50,36).
Conclusion: Our study showed that skin changes as seborrhea
does not cause a significant increase in the frequency of Demodex
spp. infestation in Parkinsons disease patients.
Conclusions: Our study showed that skin changes as seborrhea
does not cause a significant increase in the frequency of Demodex
spp. infestation in Parkinsons disease patients.
738
Infantile systemic hyalinosis presenting as neurological
hypertonic Movement Disorder
Z. Yusuf, V. McClelland, G. Anderson, M. Irving, R. Hinds, J.
McGrath, T. Hedderly (London, United Kingdom)
Objective: These case reports aim to highlight an important dif-
ferential diagnosis in the assessment of infants with hypertonia.
Background: Hypertonia in young children has a range of
causes, some of them rare. With possible severe consequence for
development and life span, establishing a diagnosis is important
although not always possible.
Methods: We describe the course of 2 unrelated patients referred
to the paediatric neurology department for evaluation of Movement
Disorder both with accompanying failure to thrive.
Results: Two female patients aged 2 months (case 1) and 11
months (case 2) presented with developmental delay, high tone with
apparent stiffness of limbs, unusual shaped joints and contractures with
paucity of movement. Poor head control and distress on handling was
noted. Reflexes were normal in case 1, but in case 2 brisk in the upper
limbs and reduced in the lower limbs. Both patients were born to con-
sanguineous parents. Gastrointestinal disorders were present, the first
patient suffering from a protein losing enteropathy and the second from
constipation. Both cases had prominent anal skin lesions. Extensive
workup revealed diffuse osteopenia, (case 1) and hyaline depositions
(case 1 and 2) in the anal skin tag biopsies. This prompted genetic test-
ing for Infantile Systemic Hyalinosis (ISH). Both cases were found to
have mutations in the ANTXR2 gene, confirming the diagnosis of ISH.
For case 1 a homozygous single nucleotide substitution, c.1090C>T,
was found in exon 15 of the ANTXR2 gene, which is a novel mutation.
Conclusions: ISH (OMIM 236490) is rare recessive autosomal
disorder with progressive hyaline deposition in a number of tissues
and previously has been reported as the more severe form of Juve-
nile Systemic Hyalinosis. Both are classified under the umbrella term
Hyaline Fibromatosis Syndromes. Symptoms may begin shortly
after birth and involve pain on handling, enlarged joints with con-
tractions leading to restricted mobility and mimicking hypertonic
neurological conditions. This syndrome needs to be recognised as a
differential diagnosis for infants and children.
739
Speed influences handwriting in persons with Parkinsons disease
A.F. Zaman, E. Stegemoller (Ames, IA, USA)
Objective: The purpose of this study was to examine the effect
of speed on handwriting in persons with PD.
Background: Previous research has shown that many people with
Parkinsons disease (PD) suffer from micrographia,small and/or cramped
writing. Writing at faster speeds can exacerbate this impairment.
Methods: Twenty-two persons diagnosed with mild to moderated
PD completed a series of writing tasks. Participants used their
 POSTER SESSION
dominant hand to write both P and d in print style 1) at a com-
fortable speed and as fast as possible, and 2) at two different sizes
(1, and 2 cm) for a duration of 20 seconds. The writing tasks were
presented in a random order. Participants were seated in a comforta-
ble position and were allowed to change the angle of the paper to
match their preferred writing position and wrote using a pen with an
electromagnetic sensor attached to the tip. The total height and width
of each letter was calculated and averaged across conditions and par-
ticipants. A two-tailed paired t-test (a 5 0.05) was used to compare
the means.
Results: The results showed that the height of both P
(p 5 0.038) and d (p 5 0.019) were significantly reduced when
writing as fast as possible at the 2 cm height. For the 1 cm height,
only the height of P was significantly reduced. Neither the P nor
d was significantly different for the 1cm height. There were no sig-
nificant differences for the width on any of the tasks.
Conclusions: This study supports previous research showing that
writing speed influences letter size, specifically height, in PD. Future
research studies are needed to examine whether strategies that focus
on height may prove beneficial in deterring micrographia.
740
Anti-GAD65 negative stiff-person syndrome with a favorable
response to pregabalin: A case post-thymoma excision
accompanying central sleep apnea
G. Zhang, L. Liu, N. Xiong, J. Huang, T. Wang (Wuhan, Peoples
Republic of China)
Objective: To present a case report of anti-GAD65 negative stiff-
person syndrome with a favorable response to pregabalin accompa-
nying central sleep apnea.
Background: Stiff-person syndrome (SPS) is a rare immune-
mediated disorder characterized by muscle stiffness and painful
spasms. Circulating antibodies against the 65-kDa isoform of glu-
tamic acid decarboxylase (GAD-65) block gamma amino butyric
acid (GABA) synthesis, resulting in dysfunction of GABAergic
inhibitory pathways and consequently clinical manifestation.
Methods: We present a 48-year-old woman developing clinically
severe anti-GAD65 negative SPS following thymoma excision.
Results: The patient experienced paroxysmal painful spasms pre-
dominant in abdomen and both proximal leg muscles. Electromyog-
raphy of lower limbs and paraspinal muscles revealed continuous
motor unit activity at rest that could be terminated by diazepam. Due
to severe drug dependence and side effects of benzodiazepine, prega-
balin was prescribed with simultaneous benzodiazepine decrement.
Dramatic improvements in rigidity, painfulness were observed after-
ward. To our knowledge, the patient is the first case that not only
develops SPS syndrome after thymectomy but also responds favor-
ably to pregabalin. Two years later after SPS attack, daytime somno-
lence and central sleep apnea developed, firstly reported and
diagnosed by overnight polysomnogram and multiple sleep latency
test, and was controlled after intravenous immunoglobulin therapy.
Conclusions: Here we firstly report a case of anti-GAD65 negative
SPS after thymoma excision that has a favorable response to pregabalin
accompanying central sleep apnea, which may be related to SPS progres-
sion, implicating brainstem and respiratory center gradually, but the
exact pathogenesis remains unknown, and needs further investigation.
Drug-induced Movement Disorders
741
Distractible multifocal myoclonus following a single dose of
neuroleptic
R.J. Adam, F.C.F. Chang, A. Duggins, N. Mahant, V.S.C. Fung
(Sydney, Australia)
S293
Objective: To demonstrate the clinical and neurophysiological
findings in a patient inadvertently given a single dose of oral
clozapine.
Background: Clozapine-induced myoclonus is reported after
chronic administration. Distractibility is often used as evidence that
Movement Disorders are psychogenic. We present a case of distracti-
ble, delayed onset myoclonus, 4 days following a single dose of clo-
zapine, with both clinical and neurophysiological findings.
Methods: Surface EMG (sEMG) was recorded from flexor and
extensor carpi radialis (FCR & ECR) bilaterally and right zygomati-
cus major, tibialis anterior, gastrocnemius and quadriceps. Acceler-
ometers were fixed to the right hand and right knee. A C-reflex
study was performed with surface EMG recording from abductor
pollicis brevis, FCR, ECR, biceps and triceps and sensory evoked
potentials were recorded from Erbs point, C7, C2, C3 and C4;
both in response to stimulation of median nerve at wrist.
Results: A 78-year-old man with a history of osteoarthritis,
gastro-oesophageal reflux, type 2 diabetes mellitus, ischaemic heart
disease and atrial fibrillation was admitted to the Emergency depart-
ment complaining of abdominal pain. He was inadvertently adminis-
tered clozapine 350mg that initially caused delirium and stupor. He
recovered uneventfully within 24 hours. However, 4 days after oral
ingestion, he developed brief involuntary jerks and shaking. Exami-
nation showed multifocal myoclonus of all four limbs and his face
(see videotape). sEMG recordings of spontaneous jerks 5 days after
ingestion showed brief bursts throughout the record of <50ms dura-
tion in all recorded muscles. Within a limb these bursts were syn-
chronous in joint antagonists, but usually independent in different
limbs. At times bursting was near-synchronous in both upper limbs,
typical of cortical myoclonus. SEP and C reflexes were normal. Dur-
ing externally paced left hand tapping at 2.5Hz, sEMG bursts were
much diminished in all muscles but infrequent jerking of the R hand
(and simultaneous sEMG bursting) persisted and did not entrain with
the pacing stimulus.
Conclusions: We provide documented clinical and neurophysio-
logical evidence of delayed, drug-induced cortical myoclonus follow-
ing a single dose of oral clozapine. Furthermore, we show that the
myoclonus was distractible. Distractibility should not be used as a
sign of psychogenicity in this clinical setting.
742
Aripiprazole-induced Movement Disorders A case-series
S. Chouinard, P. Huot (Montreal, Canada)
Objective: To further describe the spectrum of Movement Disor-
ders caused by aripiprazole.
Background: Aripiprazole is an atypical anti-psychotic that was
approved for use in Canada for treatment of schizophrenia and bipo-
lar disorder in 2009. Aripiprazole exhibits strong potency and is a
partial agonist at serotonin 1A (5-HT1A), 5-HT2C, dopamine D2
and D3 receptors, in addition to being a potent antagonist at 5-HT2A
receptors. Because its pharmacological profile differs to the mecha-
nism of action of typical anti-psychotics, it was initially believed
that aripiprazole would have a better tolerability profile and would
elicit less Movement Disorders such as Parkinsonism and tardive
dyskinesia. However, there have been reports of aripiprazole-induced
Movement Disorders such as akathisia, tardive dyskinesia, and acute
dystonia. We here present a case-series of patients who developed
tardive dyskinesia and Parkinsonism following treatment with
aripiprazole.
Methods: Patients referred to the Andre Barbeau Movement Dis-
order Clinic exhibiting tardive dyskinesia and Parkinsonism while
under aripiprazole treatment are included in this report. This is both
a retrospective and observational study.
Results: Patients from either sex presented with aripiprazole-
induced Movement Disorders. Tardive dyskinesia, including stereo-
typical bucco-lingual movements, stereotypical limb movements, and
stereotypical truncal movements, was encountered. In most cases,
Movement Disorders, Vol. 30, Suppl. 1, 2015
S294 POSTER SESSION
Patient profile
Pt 1 2
Age F F
Sex(years) 60
Dose/day 25mg
Onset of symptoms 8 days
Clinical features Tongue protrusion
dyskinesia, rt leg tremers
Duration 1.5mths
Outcome Complete
ecovery
majority of symptoms were mild, but in two cases, they persisted
despite treatment with tetrabenazine. Parkinsonism was also encoun-
tered in two patients and improved following aripiprazole discontinu-
ation. Details regarding patients characteristics and Movement
Disorder phenomenology will be presented at the conference.
Conclusions: Aripiprazole induces Movement Disorders similar
to those elicited by other anti-psychotics. Whereas the prevalence of
aripiprazole-induced Movement Disorders remains unknown, clini-
cians need to be aware of this potential adverse effect when prescrib-
ing the drug.
743
Lithium induced lingual dystonia: A case report
R.K. Dhamija, R. Aggarwal (New Delhi, India)
Objective: To report a lithium induced oro buccolingual
Dystonia.
Background: Secondary dystonias can be brought on by an incit-
ing event, such as a stroke, trauma, or drugs. Medications associated
with tardive dystonia include neuroleptic, antiemetics and antidepres-
sants.We report here the experience of a patient with dystonia that
was limited to the oromandibular area and was probably induced by
the prolonged use of lithium.
Methods: A 60 years old male presented to us with difficulty in
speaking since last 2 years. He developed involuntary movements of
his tongue and mouth which were exaggerated while speaking. He
had history of bipolar disorder for which he was started lithium 25
years back and was taking it regularly. He was also taking eltroxin
for hypothyroidism. Subsequently he developed pancreatitis and was
treated. His parents were non-Jewish, and there was no family his-
tory of dystonia. His general physical examination was essentially
normal. Neurological examination revealed dysarthric speech along
with orobuccolingual dystonia . Rest of his examination was normal.
There were no Kayser-Fleischer rings on slit-lamp examination. His
Serum ceruloplasmin and 24 hrs Urinary Copper levels were nor-
mal.His MRI revealed multiple lacunar infarcts in subcortical white
matter in the bilateral frontoparietal region.
Results: VIDEO.
Conclusions: There are only few case reports of lithium induced
Orobuccolingual Dystonia and our case is probably one of them. The
Clinicians should be aware if this potential disabling complication of
chronic lithium therapy.
744
Levosulpiride induced Movement Disorder A case series
A.G. Diwan (Nashik, India)
Objective: To report Levosulpiride induced Movement Disorder
symptoms.
Movement Disorders, Vol. 30, Suppl. 1, 2015
3
F
68 71
25mg 25mg
20 days 3 days
Symmetric Parkinsonism, 4-5 Hz perioral tremers,
gen Bradykinesia, lingual dystonia
rigidity, stooped posture,
mask face
1mth 18 days
Complete ecovery Complete ecovery
Background: Levosulpiride is commonly used as a gastrokinetic
agent, sometimes in fixed drug combination with proton pump
inhibitor (Pantoprazole, SOmeprazole) for dyspepsia and gastropa-
resis. Its peripheral anti dopaminergic action is robust, but even
with poor BBB penetration, extrapyramidal adverse effects are
known.
Methods: In last 1year (May13-April14), patients with acute
onset Movement Disorders induced by Levosulpiride were recorded.
Here, I present a case series of 3 patients, who took Levosulpiride in
a fixed drug combination with antacids for dyspepsia and developed
various Movement Disorders within short period.
Results: (Patient Profile)
Conclusions: Levosulpiride is a benzamide derivative used in the
treatment of dyspepsia. Because it exerts its pharmacologic activity
mainly by blocking dopaminergic D2 receptors, levosulpiride is
known to cause extrapyramidal symptoms (EPS), like perioral slow
tremers, dyskinesia and generalized Parkinsonism.
Careful drug history and examination is important to discover
this reversible and preventable uncommon condition. Detailed drug
history can prevent unnecessary investigations and simply stopping
offending drug can cure this condition.
Conclusion-Levosulpiride should be cautiously used particularly
in elderly subjects.
745
Tremor and ataxia due to chronic toluene exposure: Case report
F. Genc, C. Altunc, Y.B. G
omceli, A. Erdal, A. Tiltak, A. Yaman
(Antalya, Turkey)
Objective: To show the consequences of substance abuse in
terms of neurological results.
Background: Generally volatile solvents (paint thinner, glue etc.)
abuse is seen in lower education and socioeconomic groups children
and youngs . Toluene and hexane are the two important volatile sol-
vents (1).
Methods: Case Presentation: We present a case of 32 years old
man admitted to neurology outpatient clinic with complaints of
ataxia, amnesia and tremor in both arms to be more pronounced on
the right side. His complaints had two years, but the last six months
they have increased. In medical history there was no other property
than paint thinner abuse. In his neurological examination, tremor,
rigidity in both hands and elbows, ataxic gait to the right side was
seen. Deep tendon reflexes were hyperactive in all extremities. His
obvious anxiety was remarkable and he got 27/30 points from
MMSE test, short-term memory and figure copying skills were
affected. In his MR imaging (MRI) third and lateral ventricles were
dilated, T2 weightened (T2W) MRI shows hypointense, T1weight-
ened MRI shows hyperintense signal changes in bilateral basal gan-
glia, thalamus and mesencephalon. Also diffuse gliosis was detected
 POSTER SESSION
Fig. 1. (745).
Fig. 2. (745).
in bilateral periventricular white matter by T2W MRI and FLAIR .
In treatment he has benefited from propranolol 80 mg per day, for
his anxiety and substance abuse psychiatric consultation was
demanded and they suggested SSRI treatment.
[Figure1]
[Figure2]
Results: Discussion: The primary target of toluene is the periph-
eral and central nervous system (1). Its shown that chronic exposure
to volatil substances lead to demiyelination and gliosis especially at
basal ganglia, cerebral and cerebellar white matter (4,5). And so
atrophy were encountered at vermis, brainstem and capsula interna
(1,4). In our case there was long term exposure (>4 years) and MRI
findings like as the literature too (4). As reported previous publica-
tions we also have found cerebellar dysfunction, cognitive and per-
sonality changes, spasticity and Parkinsonism (4-6). Although,
reported in literature clonazepam is the first choice terapy in cases
where the tremor is the predominant, we did not prefer by the con-
cern of abuse (7).
Conclusions: When suspected particularly in young population
substance abuse should be questioned because these substances have
the potential to make a permanent loss of functions.
S295
746
Can the clinical phenotype in suspected drug induced
Parkinsonism reliably predict the presence of abnormal
functional imaging suggesting dopaminergic deficiency?
E. Jabbari, S. Molloy (London, United Kingdom)
Objective: To ascertain whether the extrapyramidal phenotype in
patients with suspected drug induced Parkinsonism (DIP) can predict
those with underlying Parkinsons disease (PD) as confirmed by
abnormal DAT scan imaging.
Background: The clinical phenotype of DIP is classically
described as symmetrical Parkinsonism without rest tremor (1). In
practice, diagnosing idiopathic PD in patients on medications that
cause extrapyramidal features remains difficult. The similar clinical
features of DIP and PD indicate that patients with DIP may have
been in a pre-clinical stage of PD which was then unmasked by the
offending drugs (2). DAT scans detect presynaptic dopaminergic
deficiency and can be used to differentiate between DIP and PD.
Methods: Data was retrospectively collected from a Movement
Disorder service over 6 years. The data included patient demo-
graphics, class of drug potentially causing DIP, medication use dura-
tion, extrapyramidal symptom duration, whether there was presence
of rest tremor, bradykinesia, rigidity and postural instability, whether
signs were symmetrical or asymmetrical and whether subsequent
DAT scan appearances were normal or abnormal. A logistic regres-
sion analysis was applied to interrogate the association between the
presence and pattern of clinical signs and the DAT scan appearances.
Results: Data on 30 patients was obtained (17 female:13 male).
Average age at presentation was 62.6 years. 83% of patients were
taking more than one drug suspected of causing DIP. The common-
est class of medication was typical anti-psychotics (45%), although
atypical anti-psychotics, Lithium and Sodium Valproate also fea-
tured. Average durations of medication use and symptoms before
presentation were 11.7 years and 2.9 years respectively. The pres-
ence of postural instability was associated with asymmetrically
abnormal DAT scan appearances (Coeff 3.12; OR 24; CI 3.36 -
171.55; p50.0015). There was no significant association between the
presence of rest tremor (p50.23), bradykinesia (p50.99), rigidity
(p50.07) or symmetrical/asymmetrical signs (p50.23) and the pres-
ence of normal or abnormal DAT scan appearances.
Conclusions: Postural instability is the only classical Parkinso-
nian feature whose presence in patients with suspected DIP can pre-
dict those with underlying PD. Larger, prospective studies could
explore this possible correlation further.
747
Worst side effect of drugs-Parkinsonism
S. Khachaturyan, A. Badalyan, G. Avagyan, H. Amirjanyan, C.
Harutunyan, A. Voskanyan, H. Manvelyan (Vararshapat, Armenia)
Objective: Parkinsons disease (PD) ia a neurodegenerative dis-
ease. The mail cause of PD is a low level of dopamine in substantia
nigra. There is a concept such as Parkinsonism or Parkinsons plus.
During this condition the level of dopamine is too low, but has other
etiology and reasons. For esample drug induced Parkinsonism.
Background: Two young males were diagnosed with drug
induced Parkinsonism.
First pationt: 28 years old male has been using drugs since age
16. Last 3 years he has been using synthetic drugs (Ephedron,Amph-
hetamine). He started to discribed symptoms of Parkinsonism have
when he was 26 years of age. The pationt has tremor (more from the
right hand), bradikinesia, postural instability, rigidity.
Second pationt: 35 years old male used marijuana from time to
time and synthetic drugs SPICE twice. The petiont has tremor
(postural and rest), chin tremor, slowness while walking and talking,
retropulsion and anteropulsion. The pationts father suffered from
Essential tremmor, diagnosed at age 45. Treatment with L-dopa and
dopa agonist was ineffective.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S296 POSTER SESSION
Methods: MRI scan, physical and laboratory tests were
performed.
Results: MRI scan, blood and urine analysis were without
changes.
Conclusions: Drug use resulted physical and mental dependen-
cee, hallucinations, abstinence and severe neurological syndrome
such as Parkinsonism. During the time using drugs there is an
increase of dopamine 5-10 times in brain, which explains the feeling
of satisfaction and euphoria. Exploring these 2 cases concluded that
addiction may be reason of Parkinsonism. Petiont who use synthetic
drugs more inclinable to Parkinsonism then pationt who uses non -
synthetic drugs, becouse synthetic drugs consist of heavy metals
which quickly accumulate in basal ganglia leading to Parkinsonism.
748
Propriospinal myoclonus provoked by tramadol use
H.S. Kim, Y. Kim, H. Lee (Seongnam, Korea)
Objective: To present a unique case of propriospinal myoclonus
(PSM) provoked by tramadol ingestion in a patient with chronic sub-
dural hemorrhage (SDH) at the thoracic level.
Background: PSM is a rare Movement Disorder whereby myo-
clonus originates from the spinal cord, usually at the thoracic level.
It spreads rostrally and caudally at a relatively slow rate of 3 to
15 m/s by means of propriospinal pathways. The underlying mecha-
nism may be hyperexcitability of spinal interneurons, resulting in
rhythmic spinal discharge. Most often idiopathic, PSM may present
following spinal trauma and structural spinal cord lesions such as
ischemia, tumors, multiple sclerosis, and syringomyelia. There have
been case reports of PSM following administration of certain drugs.
Methods: We investigated a 65-year-old woman presented with
involuntary abdominal jerks of gradually increasing frequency ten
days after taking tramadol-acetaminophen combination tablet. Neuro-
logical examination, electrophysiologic studies including surface
electromyography (EMG) and imaging studies of brain and spinal
cord were performed to identify the origin of the PSM.
Results: Neurological examination showed repetitive flexor jerks,
which were limited to the trunk and most pronounced on lateral
decubitus position. Laboratory investigations were unremarkable. On
surface EMG, the first activity was identified at the T6 level and sub-
sequently spread to T8 and T10. The latencies of jerks increased
with their distance from T6, and the average propagation velocity
was 4.4m/s. MRI of the thoracolumbar spine revealed a small
amount of chronic SDH at the anterior portion of the spinal canal, at
the level of T1 through T5 and mild disc bulging at T6-7 to T9-10.
The frequency of myoclonus decreased dramatically after tramadol
discontinuation and the patient reported only a couple of episodes
per day by the third hospital day and no attacks by the fifth hospital
day.
Conclusions: This case illustrates PSM provoked by tramadol use
in a patient with chronic spinal SDH. Tramadol might have provoked
myoclonus in this patient by inhibiting GABAergic receptors in the
spinal interneurons already excitable from the neighboring SDH to
start with.
749
Acute and reversible Parkinsonism with phorate
A. Kumar (Patna, India)
Objective: To describe acute and reversible Parkinsonism follow-
ing organophosphate pesticide (phorate) exposure,
Background: Phorate is a widely used organophosphorus pesti-
cide, whose environmental degradates are more toxic and stable than
the parent chemical. Phorate get absorbed by intact skin, by inhala-
tion of spray mist and by GIT. It causes irritation of eye, skin, respi-
ratory system and GIT. It produces cholinergic toxicity. Symptoms
are lacrimation, redness of eye, miosis, sneezing, nasal discharge,
Movement Disorders, Vol. 30, Suppl. 1, 2015
salivation, tightness of chest, laryngeal spasm, nausea, vomiting,
diarrhoea, excess urination, muscle fasciculations, sweating, cyanosis,
anorexia, ataxia, convulsion, tremor, weakness, confusion and coma.
It produces cholinergic toxicity, like lacrimation, salivation, muscle
fasciculation, exophthalmos, excessive urination and defecation. Dur-
ing handling and use of phorate, workers must must wear spash
proof googles, face shield and fume mask.
Methods: A 45 years old farmer has admitted with acute Parkin-
sonism, ataxia, tremor, lacrimation, nasal discharge, salivation with
altered sensorium. On examination, he has rigidity of all limbs with
normal reflexes, neck was rigid, redness of eye, lacrimation and nasal
discharges. No history of fever preceding the illness, but patient
become febrile after the illness. No family history of similar or
major illness. No history of use of antipsychotic, antiemetic and
toxin exposure was found. CSF examination was normal. All routine
blood tests were normal. Magnetic resonance imaging (MRI) was
done on 4th day with T1, T2 weighted and proton density (PD)
images, showed symmetrical hyper intensities in Putamen and Cau-
date nucleus on PD and T2W . History of toxin exposure was again
probed after MRI findings. History of spray of pesticide in field
without wearing safety measures was found and patient has devel-
oped irritation of eye and nose during spray of pesticide and Parkin-
sonism symtoms has appear after several hours. The packet of
pesticide shows name of Thimet 10 G containing Phorate 10%.
Patient treated with atropine and other supportives measures and
improve over 15 days.
Conclusions: Suspect toxin exposure as cause of acute Parkinson-
ism when patient has additional features like redness of eye and dis-
charge from nasal mucosa. Parkinsonism due to phorate is acute and
reversible. Our observations has also strengthen epidemiologic stud-
ies implicating organophosphorus pesticides in the etiology of PD.
750
Phenomenology and dopamine transporter density in a patient
with amphetamine induced hyperkinetic facial Movement
Disorders
J.P. Michelis, J.R. Bedarf, F. Gaertner, S. Paus (Bonn, Germany)
Objective: To describe a complex hyperkinetic facial Movement
Disorder induced by extensive amphetamine abuse in a 22-year-old
male, including dystonic, myoclonic, and tic elements. The patients
phenomenology is put into context with more common facial Move-
ment Disorders. In addition, results of work up including 123I-FP-
CIT SPECT (DaTSCANTM) are discussed.
Background: Amphetamine and metamphetamine might induce
hyperkinetic Movement Disorders such as tremor, dystonia, choreoa-
thetosis, and tics, eventually persisting after withdrawal (1). Amphet-
amines lead to an increase of noradrenaline and dopamine-levels in
the synaptic cleft, and 123I-FP-CIT SPECT revealed a decrease of
dopamine-transporter activity in amphetamine treated animals. How-
ever, there is scarce information about dopamine transporter density
in human amphetamine users.
Methods: Extensive clinical workup of the case was conducted in
our outpatient Movement Disorders unit. Abnormal movements were
videotaped and analysed using slow motion technique. Videos of typ-
ical facial Movement Disorders in our database were reviewed and
compared with the actual footage. SPECT was performed 4 hrs after
injection of 123I-FP-CIT. Data were analysed in a semiquantitative
procedure. An off-label treatment with tiapride 300 mg/day was
initiated.
Results: The Movement Disorder was classified as a predominant
tic-disorder, but also had dystonic and myoclonic elements. Dopa-
mine transporter density in 123I-FP-CIT SPECT was increased as
reported for tic-disorders (2). Treatment with tiapride led to an
improvement of symptoms.
Conclusions: Substance abuse has to be taken into account in
hyperkinetic Movement Disorders of the face, and can manifest as a
tic-disorder. 123I-FP-CIT SPECT might support diagnosis of
 POSTER SESSION
phenomenologically ambiguous facial Movement Disorders, and
helps to evaluate the effects of amphetamine on the motor system.
1) Brust JC. Substance abuse and Movement Disorders. 2010
Mov Disord. Oct 15
2) Cheon KA et al. Dopamine transporter density of the basal
ganglia assessed with [123I]IPT SPECT in drug-naive children with
Tourettes disorder. 2004 Psychiatry Res. Jan 15
751
Pilot study of cardio-vascular risks, insulin resistance and
neurocognition in neuroleptic-induced Parkinsonism in
schizophrenia: Post-hoc analysis of RCT study
H. Raheb, S. Chiu, Z. Cernovsky, K. Terpstra, J. Vaughese, H. Jirui,
Y. Bureau, C. John, M. Husni, R. Campbell (London, ON, Canada)
Objective: Objective of our study in schizophrenia patients was
to examine: 1)whether 2nd-generation-antipsychotics (SGA) treat-
ment results in Neuroleptic-induced Parkinsonism(NIP);2)whether
cardio-metabolic risks and cognitive deficits are correlated with NIP;
3) whether insulin resistance (IR) underlies NIP.
Background: Spontaneous extrapyramidal motor signs(sEPS):bra-
dykinesia, muscle rigidity and dyskinesia were first described in 4%
-11% drug-nave schizophrenia patients. NIP, and Tardive Dyskinesia
(TD)account for major adverse events of 1st-generation-
antipsychotics (FGA). EPS correlates of SGA remain largely
unexplored.
Methods: We conducted a post-hoc analysis of NIP in patients
diagnosed with schizophrenia screened for entry to RCT trial of
Ginsana-115. We used Simpson Angus scale (SAS) for EPS and the
Abnormal involuntary Scale (AIMS) for dyskinesia. Insulin resist-
ance (IR) was indexed with Homeostasis assessment model: HOMA,
Framingham risk score (FRS) was calculated for cardio-vascular
risks. The standardized Neurocognitive Screening (NCS) [Gur-U.
Penn]was administered to schizophrenia subjects.
Results: We recruited a sample of 44 SGA-treated schizophrenic
subjects: mean age: 38 yrs, male/female:29/15) with mean baseline
SAS scores 4.2 (SD=3.9): 52.3% (23/44) SAS score > 3.0 and 34.1%
(15/44)SAS score > 6. We calculated Pearson correlation coefficients
of SAS and AIMS scores to neurocognitive measures, IR and FRS
scores. Baseline SAS scores correlated significantly with log-IR
(r=44,p=0.007) and FRS scores (r=0.60, p<0.001) independent of
(r=0.20) Body mass index (BMI). NIP severity was correlated
directly with insulin resistance and cardiovascular risk. Higher SAS
scores correlated significantly with impaired neuropsychological per-
formance on composite neurocognitive index (r>0.30, p<.05) and
cognitive domains of visual perception, executive reasoning, spatial
processing, abstraction and flexibility, and psycho-motor performance
(r >0.30, p<.05). AIMS scores correlated significantly with FRS
scores (r=0.36, p =0.039) and memory (r=0.32, p50.037).
Conclusions: We demonstrate for the first time that in schizo-
phrenia, NIP is related to neurocognitive deficits and cardio-vascular
stress. NIP may share with idiopathic Parkinsons disease in linking
dysregulated insulin signaling and insulin resistance to mitochondrial
dysfunction.
752
Clinical characteristics of tetrabenazine-induced Parkinsonism
D.P. Shah, J. Jimenez-Shahed (Houston, TX, USA)
Objective: Describe the clinical characteristics of patients with
tetrabenazine-induced Parkinsonism.
Background: Tetrabenazine (TBZ) is dopamine depleting drug
used for treatment of Huntingtons disease (HD) chorea and off-label
for other hyperkinetic disorders. Amongst other side effects, Parkin-
sonism may occur, but little is described about the clinical manifesta-
tions and management.
S297
Methods: Patients treated with TBZ over 1 month with follow up
within the past year were included. By retrospective chart review,
we collected diagnosis, total duration of TBZ treatment, presence of
DIP and date of diagnosis, latency to onset of DIP, TBZ dose at
time of diagnosis, features of DIP and treatment.
Results: Of 144 charts reviewed, 58 met inclusion. Exclusions
were for noncompliance (n53), lost to follow up over 1 year
(n568), deceased (n58), unknown TBZ start date (n57). Indications
for treatment were dystonia (n54), HD (n512), hemiballismus
(n52), tardive dyskinesia (TD, n523), Tourette syndrome (TS,
n514), myoclonus (n51), and non-HD chorea (n52). Overall,
29.3% (n517) were diagnosed with DIP of which 52.9% had TD
(n59), 11.8% had TS (n52), 23.5% had HD (n54), and 11.8% had
dystonia (n52) (p50.249). Mean dose of TBZ at DIP diagnosis was
61.41/-27.1mg [TD=58.31/-28.6 mg, TS=65.61/-48.6 mg,
HD=71.91/-15.7 mg (p50.73)] vs. 67.51/-37.8 mg for non-DIP
patients at last follow-up. Latency to onset of DIP was 501/-52.1
months [TD=50.21/-67.3 months, TS=39.51/-30.4 months,
HD=50.51/-40.8 months (p50.97)]. DIP symptoms were bradykine-
sia (82%), rigidity (53%) and shuffling gait (53%). Initial manage-
ment strategies included carbidopa-levodopa (n57), amantadine (n5
4), and pramipexole (n51), 3 with concurrent TBZ dosage reduction.
Conclusions: In this cohort, DIP related to TBZ was most com-
mon in patients with TD though not statistically significant. Dosage
of TBZ and duration of therapy did not predict DIP. Bradykinesia,
rigidity and gait changes are the common symptoms. Prospective
studies are warranted.
753
5-Meo-DALT-induced cyclic myoclonus
T. Thammongkolchai, P. Termsarasab, A. Malkhachroum, Y. Gujrati,
S.J. Frucht, B. Katirji (Cleveland, OH, USA)
Objective: To report the first case of myoclonus as neurologic
presentation of 5-MeO-DALT abuse.
Background: 5-Meo-DALT (N,N-diallyl-5-methoxytryptamine) is
a relatively new hallucinogen, initially sold online in 2004. It is a
psychedelic compound from the tryptamine family which affects
monoamine neurotransmitters including dopamine and serotonin. It is
a psychostimulant with strong visual hallucinogenic and entheogenic
effects. It can be smoked, taken orally or sniffed; It is not detected
in routine toxicology screen. Typical symptoms include extreme agi-
tation, tachycardia, and combativeness. Little is known about neuro-
logic symptoms. Delirium was reported in one case, but myoclonus
or other Movement Disorders have never been reported.
Methods: A case report.
Results: A 29-year old-man was admitted for markedly reduced
oral intake for four days. He became unresponsive on the next day
in hospital, and developed intermittent myoclonus. He had history of
heroin and marijuana abuse, and was on buprenorphine. Myoclonic
jerks involved all extremities, trunk, and neck with possible spread
to lower jaw. The movements coalesced and recurred in cyclic pat-
tern, approximately every 10 minutes (see Video). Somesthetic stim-
uli aggravated the jerks. Electrophysiologic testing was not available,
but clinical examination suggested a brainstem or high spinal origin.
After a dose of intravenous lorazepam, he partially regained con-
sciousness, and myoclonus stopped, but the effects were transient.
Urine toxicology screen was positive for opioid and cannabinoid.
Electroencephalography did not reveal ictal or interictal epileptiform
discharges. MRI brain was unremarkable. Myoclonus and encephal-
opathy gradually improved over a week. Once he returned back to
his baseline, he reported 5-Meo-DALT use prior to this admission,
and prior visual hallucinations and delusions.
Conclusions: This substance abuse should be considered in
patients with cyclic myoclonus and negative toxicology screen. Fur-
ther studies are helpful in expanding the knowledge on neurologic
features of 5-Meo-DALT abuse, and development of the screening to
cover this substance.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S298 POSTER SESSION

754
The effects of early versus late L-DOPA initiation in Parkinsons
disease
G. Yahalom, O.S. Cohen, N. Warmann-Alaluf, C. Shabat, H. Strauss,
S. Elincx-Benizri, S. Israeli-Koren, E. Stein, S. Hassin-Baer (Ramat-
Gan, Israel)
Objective: To study the impact of timing of levodopa (L-dopa)
initiation on motor complications and disease progression in Parkin-
sons disease (PD).
Background: Long-term L-dopa therapy in PD is associated with
motor fluctuations and dyskinesias. The time to appearance of these
motor complications varies among individuals and relates to both
patient factors and characteristics of treatment regimen. The role of
timing of L-dopa initiation on these complications and on rate of dis-
ease progression is disputable.
Methods: Data was obtained from the PD database of the Move-
ment Disorders Institute and included patients at follow up between
the years 2008-2013 who were treated with L-dopa. Patients were
divided to 2 groups below and above the median time from PD onset
to L-dopa initiation. The primary outcomes explored were the time
from L-dopa initiation to appearance of motor fluctuations and/or
dyskinesias. The secondary outcome measure was time from L-dopa
initiation to reaching Hoehn and Yahr stage III (HY3).
Results: Data from 200 PD patients (131 males, age at onset 65.0
611.1 years) was analyzed. The mean duration of L-dopa treatment
was 4.84 6 1.65 years. Patients who started L-dopa early (n5 107)
were older than the late initiation group [68.9 6 10.6 vs. 60.2 6 9.9
years (n5 90), respectively, p<0.001]. Members of this group devel-
oped both motor fluctuations and dyskinesia later (25.4 6 16.7 vs.
18.7 6 16.96 months, respectively, p50.07; 40.3 6 21.3 vs.
26.6 6 21.2 months, respectively, p50.02) and had a more rapid dis-
ease progression (time to HY3 of 2.2 6 1.2 vs. 4.8 6 1.7 years,
respectively, p<0.001).
Conclusions: In this initial analysis, starting L-dopa later and not
earlier in the course of PD, was associated with earlier appearance of
motor complications and more rapid disease progression; the effect
of age on these outcomes cannot be ruled out.
Neuropharmacology
755
Parkinsons disease polypharmacy: A crucial issue in the
management of elderly patients
S. Ataei, M. Noroozian, A. Kargar (Hamedan, Iran)
Objective: To express the most important interactions between
Parkinsons disease medications with other common drugs which has
being used in the treatment of prevalent diseases in the elderly
patients.
Background: Parkinsons disease is a common disabling neuro-
degenerative illness that is prevalent in 1 percent of people over 65
years old. Parkinsons disease incidence increases with age, as it
reaches to 2.5 percent in 80 years old. Elderly patients have more
susceptibility to provoke drug interactions due to consumption of
multiple medications. Given that renal function capacity is dramati-
cally declined in elderly clients, such issue make them more vulnera-
ble to adverse drug reactions. Interestingly, those patients who
suffered from Parkinsons disease are more sensitive to drug interac-
tions compared to other elderly population, which can be ascribed to
their autonomic dysfunction, physical disabilities, and cognitive
impairment.

Drug Interactions Between Parkinsons disease Medications and Antihypertensive Agents

Parkinsons
disease
Medications Enalapril Losartan Hydrochlorothiazide Verapamil Diltiazem Amlodipine Furosemide

Levodopa Increase Orthostatic Increase Orthostatic Increase Orthostatic Increase Orthostatic Increase Increase Increase
Hypotensive Effect Hypotensive Hypotensive Hypotensive Effect Orthostatic Orthostatic Orthostatic
of Levodopa Severity Effect of Levodopa Effect of of Levodopa Severity Hypotensive Hypotensive Hypotensive
Of Interaction is Severity Levodopa Severity Of Interaction is effect of Effect of Effect of
Moderate Of Interaction is Of Interaction is Moderate Risk Levodopa Levodopa Levodopa
Risk Rating Of Moderate Moderate Rating Of Severity Severity Of Severity Of
Interaction: C Risk Rating Of Risk Rating Of Interaction: C Of Interaction Interaction is Interaction is
Interaction: C Interaction: C is Moderate Moderate Risk Moderate
Risk Rating Rating Of Risk Rating
Of Interaction: C Interaction: C Of Interaction: C
Selegiline Selegiline Increase Selegiline Increase Selegiline Increase Selegiline Increase Selegiline Selegiline Selegiline
Orthostatic Orthostatic Orthostatic Orthostatic Increase Increase Increase
Hypotensive Hypotensive Hypotensive Hypotensive Orthostatic Orthostatic Orthostatic
Effect of Effect of Effect of Effect of Hypotensive Hypotensive Hypotensive
Antihypertensive Antihypertensive Antihypertensive Antihypertensive Effect of Effect of Effect of
Agents, Risk Agents, Risk Agents, Risk Agents, Risk Antihypertensive Antihypertensive Antihypertensive
Rating is C Rating is C Rating is C Rating is C Agents, Risk Agents, Risk Agents, Risk
Rating is C Rating is C Rating is C
Ropinirole NO Interaction NO Interaction NO Interaction NO Interaction NO Interaction NO Interaction NO Interaction
Pramipexole NO Interaction NO Interaction NO Interaction NO Interaction NO Interaction NO Interaction NO Interaction
Amantadine NO Interaction NO Interaction NO Interaction NO Interaction NO Interaction NO Interaction NO Interaction

Risk Rating: A: No Known Interaction; B: No Action Needed; C: Monitor Therapy; D: Consider Therapy Modification; X: Avoid Combination;
Interaction Severity: 1. Severe: The effects are potentially life threatening or capable of causing permanent damage. 2. Moderate: The effects
may cause deterioration in a patients clinical status. Additional treatment, hospitalization or an extended hospital stay may be necessary. 3.
Mild: The effects are usually mild; consequence may be bothersome or unnoticeable but should not significantly affect the therapeutic outcome.
Additional treatment is usually not required.

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION S299

Drug interactions between Parkinsons disease medications and Antithrombotic Agents

Parkinsons disease medications Warfarin Dabigatran

Amantadine No No
Levodopa No No
Ropinirole Ropinirole may increase the anticoagulant effect of Warfarin No
Risk Rating is C Monitor for: increased INR/effects of
warfarin if ropinirole is initiated/dose increased, and
decreased INR/effects if ropinirole is discontinued/dose decreased.
Severity is Moderate
Pramipexole No No
Selegiline No No
Risk Rating: A: No Known Interaction; B: No Action Needed; C: Monitor Therapy; D: Consider Therapy Modification; X: Avoid Combinatio-
n;Interaction Severity: 1. Severe: The effects are potentially life threatening or capable of causing permanent damage. 2. Moderate: The effects
may cause deterioration in a patients clinical status. Additional treatment, hospitalization or an extended hospital stay may be necessary. 3.
Mild: The effects are usually mild; consequence may be bothersome or unnoticeable but should not significantly affect the therapeutic outcome.
Additional treatment is usually not required.

Methods: The PubMed and Elsevier databases were searched for
surveys published over past 5 years (December 2009-December
2014) using pertinent keywords, including Parkinsons disease, Phar-
macotherapy, Medication, Interaction, Polypharmacy, Elderly. Other
applicable resources, such as Harrisons Principles of Internal Medi-
cine, Pharmacotherapy: A Pathophysiologic Approach by Joseph
T.Dipiro, Koda-Kimble and Youngs Applied Therapeutics, UpTo-
Date subscription based resource database, and American Geriatric
Society Updated Beers Criteria for Potentially Inappropriate Medica-
tion Use in Older Adults.
We have designed some tables in order to elucidate and reveal
the most crucial drug interactions in Parkinsons disease based on
the data obtained from the above mentioned resources.
Results: Since we could not include all of the tables herein, we
have placed [table1] and [table2] as instance.
Conclusions: Specialists and practitioners who manage elderly
patients suffering from Parkinsons disease should draw attention to
potential drug interactions. Furthermore They should adjust medica-
tions in terms of dosing based upon patients circumstance. Our pre-
sented tables might be of interest for practitioners owing to time
saving feature and being comprehensive.
756
Dopaminergic modulation of neural progenitor cells in the
hippocampal dentate gyrus in a mouse model of Parkinsons
disease
W.H. Chiu, G.U. H oglinger, W.H. Oertel, V. Ries (Marburg,
Germany)
Objective: The study focuses on the histological analysis of adult
neurogenesis in the subgranular zone and the granule cell layer of
the dentate gyrus in 6-OHDA lesioned mice. We investigated
whether proliferation, survival, and neuronal maturation of neural
progenitor cells were affected by dopamine depletion and subsequent
treatment with L-DOPA and/or selegiline.
Background: L-DOPA and selegiline are standard medications
for Parkinsons disease (PD) patients. A deficiency in the prolifera-
tion of neurogenic areas has been shown as a consequence of cere-
bral dopamine depletion and suggested as a possible
pathophysiological mechanism underlying some of the non-motor
symptoms of PD. We showed a distinct regulation of neural progeni-
tor cells in the olfactory bulb treated with L-DOPA and/or selegiline
after an intranigral 6-OHDA lesion. However, it remains unclear,
whether dopamine depletion and pharmacological restoration mod-
ulate neural progenitor cells in the dentate gyrus in this model.
Methods: Adult mice received an intranigral injection of 6-
OHDA. Three days prior to treatment BrdU was applied intraperito-
neally twice per day to label neural progenitor cells. After 3 weeks,
L-DOPA and/or selegiline were given to mice via drinking water for
a period of 4 weeks.
Results: 1. The number of PCNA1 cells represents proliferation
in the subgranular zone. It was decreased after 6-OHDA, but L-
DOPA reversed it back to control. 2. The total number of DCX1
cells was decreased in the group with a 6-OHDA lesion but without
treatment. It was increased significantly in all treated groups. More-
over, the regulation pattern of DCX was later reflected in the number
of newly generated neurons. 3. The proportion of mature DCX1
cells within the total number of DCX1 cells was increased in the
lesioned group alone; in contrast, the proportion of immature DCX1
cells was decreased. These proportional changes were partially
reversed toward control values in all treated groups, but only the
group treated with selegiline alone reached a significant difference
compared to the lesioned animals without treatment.
Conclusions: Dopamine seems to be a necessary neurotransmitter
for proliferation and neuronal maturation in the dentate gyrus. L-
DOPA restores the proliferation, while selegiline redistributes the
proportional shift of DCX subgroups after 6-OHDA.
757
Brain delivery of microencapsulated GDNF promotes functional
and structural recovery in a primate model of Parkinsons
disease
E. Garbayo, H. Lana, G. DAddario, M.d.M. Carmona-Abellan, I.
Marcilla, J.L. Lanciego, M.R. Luquin, M.J. Blanco-Prieto (Pam-
plona, Spain)
Objective: To assess if the local release of glial cell line-derived
neurotrophic factor (GDNF) via microparticle-based drug delivery
systems is a useful strategy for improving motor performance and
promoting dopaminergic fiber/neuron recovery in a primate model of
Parkinsons disease (PD).
Background: Glial cell line-derived neurotrophic factor (GDNF)
is one of the most promising molecules due to its potency to slow
down and improve motor manifestations of PD. Since the delivery of
this neurotrophic factor to the brain remains an important issue,
GDNF microencapsulation in bioresorbable microparticles (MP)
could represent a therapeutic approach.
Methods: 9 adult male primates were used. 1-methyl-4-phenyl-
1,2,3,6-tetrahydropyridine was weekly administered intravenously
until they reached a stable severe Parkinsonism. Animals were ran-
domly assigned to receive unilateral injections of GDNF-MP or non-
loaded MP (control). Each animal received 25 lg of GDNF within
the putamen. Motor skills were weekly evaluated. Animals were sac-
rificed 9 months after MP injection for histological analysis

Movement Disorders, Vol. 30, Suppl. 1, 2015

S300 POSTER SESSION
(immunohistological and double immunofluorescence techniques).
Cell counting was estimated by stereology.
Results: Microencapsulated GDNF improved fine motor tasks in
the contralateral limbs to GDNF injections and gross motor abilities.
Histological analysis showed bilateral increased number of nigral
dopaminergic neurons in the GDNF-injected animals (56327 6 6066
and 48409 6 3877 cells) but no in the controls (18905 6 1059 and
20638 6 4767 cells). Total number of neurons was two-fold
increased in the SN of the GDNF-injected animals. The number of
striatal dopaminergic neurons was increased in the GDNF-group
(116 6 21 and 104 6 22 vs control 42 6 11 and 35 6 1 cells/mm2)
with a marked increased percentage of TH1/calretinine1 expressing
neurons. No GDNF protein or antibodies against GDNF were
detected 9 months after treatment in the cerebrospinal fluid or serum.
Conclusions: MP is an efficient vehicle for sustained GDNF
delivery to the brain and produces long-term motor improvement of
Parkinsonism. Recovery was associated with bilateral increase in the
number of nigral and striatal dopaminergic neurons indicating that
GDNF might induce the differentiation of quiescent nigral progenitor
cells into dopaminergic cells. The increased number of dopaminergic
cell populations might account for the motor recovery.
758
The critical role of Beclin 1 up regulation in dopamine D2 like
receptor agonists-induced autophagy activation
L.F. Hu, J.D. Wang, C.F. Liu (Suzhou, Peoples Republic of China)
Objective: To investigate whether dopamine D2-like receptor
activation modulates autophagy activity in dopaminergic cells.
Background: Autophagy dysfunction is increasingly implicated
in the development of Parkinsons disease (PD). Beclin 1 is an
autophagy-related protein critical for autophagosome formation; how-
ever, the alterations of its expression and regulation in PD remains
poorly understood.
Methods: The expression of autophagy related markers were
determined by western blot. The formation of GFP-LC3 dots were
visualized under Zeiss confocal microscope. The siRNA duplexes
and plasmids were transfected using lipofectamine 2000. Intracellular
calcium level were assayed using a molecular probe Fura-2 AM
coupled with a calcium imaging system.
Results: we found that dopamine D2 like receptor agonists pra-
mipexole and quipirole elevated the levels of autophagy-related
markers LC3-II and Beclin 1, as well as the formation of LC3 dots
in PC12 and MES23.5 cells. BECN1 knockdown with specific
siRNA abolished the effects of these agonists on autophagy. More-
over, we identified a c-Fos binding site (5-TGCCTCA-3) in the rat
and human BECN1 promoter. The ChIP and luciferase analysis with
mutations in BECN1 promoter revealed that the c-Fos binding was
critical for pramipexole-induced increases in BECN1 transcription.
Furthermore, pramipexole treatment elevated the intracellular Ca21
level by inducing its release from intracellular stores, which is asso-
ciated with the phosphorylation increases of CaMKIV and CREB.
Intracellular Ca21 chelating reagent BAPTA/AM markedly dimin-
ished the increases of c-Fos, Beclin 1 and LC3-II expression levels.
In addition, with both pharmacologic and genetic tools, we demon-
strated that the effects of pramipexole were dependent on dopamine
D2/D3 receptor activation. More importantly, pramipexole attenuated
the rotenone-induced accumulation of a-synuclein in PC12 cells
overexpressing wild type a-synuclein.
Conclusions: Our data reveal a new c-Fos binding sequence in
rat and human BECN1 gene promoter and illustrate the molecular
mechanisms that underlie the dopamine D2/D3 receptor agonists
induced autophagy activation and the subsequent a-synuclein
degradation.
759
Movement Disorders, Vol. 30, Suppl. 1, 2015
Withdrawn by Author
760
Changes in a-7 nicotinic acetylcholine receptor specific binding
in the brain of dyskinetic Parkinsonian monkeys
V.A. Jourdain, L. Gr
egoire, T. Di Paolo (Manhasset, NY, USA)
Objective: To investigate the changes of a-7 nicotinic acetylcho-
line receptor (a7nAchR) in Parkinsonian monkeys displaying or not
L-DOPA-induced dyskinesia (LID).
Background: LID are disabling side of effects of pharmacological
therapy for Parkinsons disease (PD). A dysregulation in the choliner-
gic system is observed in PD. a7nAchR has not yet been fully investi-
gated and may be a potential target in the treatment of PD and LID.
Methods: In this study, a total of 21 monkeys were used. Four of
them served as controls, four monkeys were treated only with MPTP,
four monkeys received MPTP and L-DOPA for one month, developed
LID and were killed at 4 hours after their last dose of L-DOPA, four mon-
keys received MPTP and L-DOPA, developed LID and were killed at 24
hours after their last dose of L-DOPA, and five monkeys received MPTP,
L-DOPA and the compound Ro 61-8048, an inhibitor of kynurenine
hydroxylase, developed less LID and killed at 24 hours post-L-DOPA.
The compound Ro 61-8048 possesses antiglutamatergic activities and
also antagonizes a7nAchR. Specific binding to a7nAchR was measured
by autoradiography using the [121I] a-bungarotoxin radioligand.
Results: Specific binding to a7nAchR increased in the putamen
of MPTP monkeys treated with L-DOPA compared to controls.
MPTP-induced increased a7nAchR specific binding in the external
globus pallidus in all MPTP monkeys. Addition of Ro 61-8048 to L-
DOPA increased a7nAchR specific binding in the internal globus
pallidus. MPTP-induced decreases in a7nAchR specific binding in
motor thalamic nuclei (ventroanterior/ventrolateral and centromedian/
parafascicular complex) were corrected with Ro 61-8048. No effect
of the MPTP lesion and the drug treatments was observed in the cau-
date nucleus and the pedunculopontine nucleus.
Conclusions: These results suggest that levels of a7nAchR are
modified in the basal ganglia following L-DOPA and Ro 61-8048 in
MPTP monkeys. Cholinergic pedunculothalamic and pedunculopalli-
dal pathways should therefore receive more attention in PD and LID.
761
The adenosine A2A receptor antagonist, istradefylline enhances
and prolongs the anti-Parkinsonian activity by combined
treatment with low doses of L-DOPA and dopamine agonists in
MPTP-treated common marmosets
T. Kanda, S. Uchida, K. Soshiroda, E. Okita, M. Kawai-Uchida, A.
Mori, P. Jenner (Shizuoka, Japan)
Objective: To investigate whether istradefylline enhances anti-
Parkinsonian effects by combined treatment with L-DOPA and a dopa-
mine agonist (pergolide or ropinirole) in the 1-methyl-4-phenyl-1,2,3,6-
tetrahydropyridine hydrochloride (MPTP)-treated common marmosets.
Background: The adenosine A2A receptor antagonist, istradefyl-
line decreases OFF time in patients with Parkinsons disease who are
already treated with optimal dopaminergic medication. However, the
effects of istradefylline in combination with a dopamine agonist have
not been studied.
Methods: Experiments were performed using eight MPTP-treated
common marmosets. On the first day of each experiment, basal loco-
motor activity was measured and basal motor disability was scored
in the marmosets after oral administration of vehicle. On the second
day, motor disability and ON time were scored, and locomotor activ-
ity was measured in the animals after oral administration of L-
DOPA. On the third day, motor disability and ON time were scored,
and locomotor activity was measured in the animals after oral admin-
istration of L-DOPA in combination with istradefylline and/or a
dopamine agonist (pergolide or ropinirole).
 POSTER SESSION
Results: The suboptimal dose of L-DOPA (2.5 mg/kg) induced
weak anti-Parkinsonian effects in MPTP-treated marmosets. Co-
administration of istradefylline (10 mg/kg) or a dopamine agonist
with the suboptimal dose of L-DOPA increased and prolonged the
anti-Parkinsonian effects and increased ON time of L-DOPA alone.
Istradefylline combined with L-DOPA plus a dopamine agonist
enhanced the increased and prolonged anti-Parkinsonian effects and
the increased ON time.
Conclusions: Co-administration of istradefylline with L-DOPA and
a dopamine agonist significantly enhanced and prolonged the anti-
Parkinsonian effects of L-DOPA plus a dopamine agonist. These results
suggest that istradefylline in combination with dopaminergic drugs is
useful for the treatment of Parkinsons disease. In particular, in patients
with wearing-off and on-off response fluctuations, istradefylline may
increase the efficacy and duration of dopaminergic medication.
762
Withdrawn by Author
763
Withdrawn by Author
764
The protective effect of curcumin on tyrosine hydroxylase
immunoreactivity in both substantia nigra and the ventral
tegmental area, after acute aluminum intoxication
W. Laabbar, A. Elgot, H. Gamrani (Marrakesh, Morocco)
Objective: The present study evaluates the possible protective
effect of curcumin on Al intoxicated rats (animals receiving Al acute
treatment).
Background: Aluminum (Al) is a potent neurotoxic metal wich
has been associated to several neurodegenerative diseases, it has no
known function in human; however, this metal is accumulated in
substantia nigra, and considered by some authors as a risk factor for
developing Parkinsons diseases.Moreover, some few studies demon-
strated that Al can include changes in many neurotransmitter levels
including the dopaminergic system. Among several medicinal plants
having a beneficial effect on health; curcumin is extracted from Cur-
cuma longa rhizomes, and well known as a multi-functional drug
with antioxidative activities.
Methods: Using the immunohistochemistry procedure, with tyro-
sine hydroxylase antibody (TH: the key enzyme of dopamine synthe-
sis)Experiments were carried out on male wistar rats intoxicated
acutely with an intraperitoneal injection of Al (25mg/Kg B.W.),) and
(100mg/Kg B.W.), these two groups received concomitantly Curcu-
min by oral gavage (30mg/kg B.W.).
Results: Our results showed, a significant and gradual increase of
TH immureactivity in both the substantia nigra (SN) and the ventral
tegmental area (VTA) in acute Al intoxicated rats. This increased
TH immunoreactivity has been remedied with daily curcumin
administration.
Conclusions: Data with others, suggested that Al causes altera-
tions on dopamine neurotransmission, this inconvenience might be
treated by curcumin exhibiting a potential protective effect.
765
Incidence and prescribing trends of antipsychotic and antiemetic
dopamine receptor blocking agents (DRBAs) in patients with
Parkinsons disease
M.A. Lising, M. Lee, L.H. Poon, G. Manipon, N.B. Galifianakis (San
Francisco, CA, USA)
Objective: To report the incidence of antipsychotic and antie-
metic DRBAs prescribed to patients with Parkinsons disease (PD).
S301
Background: Patients with PD are often prescribed medications
that can worsen their motor and non-motor symptoms. These agents
include, but are not limited to, typical and atypical antipsychotics,
dopamine blocking antiemetics, and phenothiazine antiemetics.
Patients with PD commonly develop Parkinsons disease psycho-
sis (PDP) with a prevalence of 20-40% that are associated with nega-
tive outcomes such as behavior disturbance, caregiver burden, and
mortality.1 Previous studies showed that up to 50% of PDP were
prescribed an antipsychotic to treat psychosis.1
Nausea and gastroparesis in PD patients are often managed with
DRBAs such as metoclopramide or phenothiazine. Guidelines recom-
mend avoiding such antiemetics, but to our knowledge the incidence
of DRBAs prescribed as antiemetics in PD patients has not been
described in a large cohort.
Methods: This retrospective cohort study was conducted between
January 1, 2010 and December 31, 2013 at the San Francisco Veter-
ans Affairs Medical Center and included patients with Parkinsons
disease receiving dopamine agonist (pramipexole and ropinirole)
and/or levodopa. Patients were followed up to identify the incidence
and prescribing patterns of antipsychotic and/or antiemetic DRBAs.
Results: A total of 795 patients were initially screened over the 4
year interval. Of the 202 PD patients who met inclusion criteria,
29.2% (59 out of 202) were prescribed DRBAs. All the patients
included were evaluated for changes in motor and non-motor symp-
toms along with prescribing trends. Long-term results and details of
outcomes in our cohort will be presented.
Conclusions: Empirical data regarding the incidence and pre-
scription patterns of antipsychotic medications in patients with PD
are limited. To our knowledge, there is no published descriptive data
regarding the use of antiemetic DRBAs in patients with PD. Our
incidence of DRBA exposure in patients with PD is 29.2% which
similar to prior studies1. Details of outcomes including non-motor
and motor outcomes of patients with PD exposed to DRBAs will be
presented which to our knowledge has not been described in prior
studies.
1.Weintraub D et al. Patterns and trends in antipsychotic prescrib-
ing for Parkinsons disease psychosis. Arch Neurol. 2011;68(7):899-
904.
766
Withdrawn by Author
767
Neuroprotective and neurotrophic effects of apigenin and luteolin
in MPTP induced Parkinsonism in mice
S.P. Patil, S. Sathaye (Mumbai, India)
Objective: In the present study, we aim to investigate the neuro-
protective and neurotrophic effects of naturally occurring polyphe-
nols like apigenin and luteolin and also to explore the underlying
mechanisms with respect to Parkinsons disease (PD).
Background: Flavonoids are the largest group of polyphenols
present in many plants which are known to promote a number of
physiological benefits, especially in scavenging free radicals, neuro-
genesis, learning and memory etc.
Methods: MPTP (25 mg/kg) along with Probenecid (250 mg/kg)
was administrated for five consecutive days to induce Parkinsonism
in mice. Apigenin (5, 10 and 20 mg/kg), luteolin (10 and 20 mg/kg)
and Bromocriptine (10 mg/kg) were administrated orally for 26 days
including 5 days of pretreatment. Behavioural analysis and biochemi-
cal estimation of oxidative stress biomarkers were conducted. Tyro-
sine hydroxylase (TH), glial fibrillary acidic protein (GFAP) and
brain derived neurotrophic factor (BDNF) were evaluated in substan-
tia nigra (SN) region of the brain by immunostaining. TNF-a was
estimated using ELISA technique.
Results: Our results demonstrate that apigenin and luteolin treat-
ment improved the locomotor and muscular activities in MPTP
Movement Disorders, Vol. 30, Suppl. 1, 2015
S302 POSTER SESSION
treated mice. TH-positive cells decreased up to 7% in MPTP treated
mice compared to normal mice (P < 0.001) and were found to be
protected from degeneration in apigenin (69%) and luteolin (63%)
treated mice (P < 0.001). Levels of GFAP were found to be
decreased in the SN of the brain due to apigenin and luteolin treat-
ment as compared to MPTP mice. BDNF levels were elevated signif-
icantly in apigenin and luteolin treatment groups when compared to
MPTP treatment mice.
Conclusions: In conclusion, apigenin and luteolin protected the
dopaminergic neurons probably by reducing oxidative damage, neu-
roinflammation and microglial activation along with enhanced neuro-
trophic potential. The above results propose both these flavonoids as
promising molecules in the therapeutics of PD.
768
Modulation of NADPH oxidase: A plausible candidate to prevent
or slow down the neurodegneration process in lipopolysaccharide
induced Parkinsons disease
N. Sharma, B. Nehru (Chandigarh, India)
Objective: The aim of this study was to investigate the neuropro-
tective effects of apocyanin, a NADPH oxidase inhibitor in a LPS
induced PD model.
Background: Neuroinflammation plays an important role in
broad spectrum of neurodegenerative diseases of aging. However, it
is thought to play a more important role in case of PD as the SN has
the highest density of microglia as compared to other regions of
brain. Therefore, role of inflammation becomes so vital to the neuro-
degenerative process that injection of immunogen such as LPS in the
SN region directly leads to microglial activation and initiation of PD
like neurodegeneration. Upon activaton microglia induces oxidative
stress induction which is governed primarily by microglial NADPH
oxidase complex. Therefore, targeting NADPH oxidase represents an
attractive therapeutic target to inhibit an inflammation driven disease.
Methods: LPS at a dose of (5ug/5ul) was injected intranigral
using stereotaxic apparatus once and Apocyanin was administered
daily at a dose of 10mg/kg b.wt (i.p) during the experiment.
Results: LPS injected into the SN reproduced the characteristic
hallmark features of PD in rats as it elicited an inflammatory
response characterised by glial cell activation as indicated by IHC
analysis and increased expression of Iba-1,GFAP, proinflammatory
cytokines i.e (TNF-a and IL-1b) and increased Total ROS formation,
Subsequently, this leads to loss of dopaminergic neurons as indicated
by IHC of Tyrosine Hydroxylase (TH) which was further confirmed
by the reduction in mRNA expression of TH and substantial loss in
neurotransmitter dopamine and its metabolites. Furthermore, LPS
upregulated the expression of NFkB, inducible iNOS, NOX 2 i.e
gp91phox in rats and also resulted in elevated PHOX activity.
Whereas, administration of apocyanin significantly mitigated LPS
induced inflammatory response and microglial PHOX associated oxi-
dative stress as indicated from reduction in PHOX activity, ROS pro-
duction, nitrite and MDA formation. Hence, apocyanin prevented
dopaminergic cell loss.
Conclusions: Apocyanin exhibit profound neuroprotective effect
in LPS induced PD model by attenuating PHOX mediated oxidative
damage as well as neuroinflammatory response. Thus based on the
findings the neuroprotective role of apocyanin in treatment of PD
should be evaluated further.
769
Effects and side-effects on Chinese patients with Wilson[apos]s
disease by unithiol (DMPS) intravenous infusion
X. Wang, H. Liu (Shanghai, Peoples Republic of China)
Objective: The authors performed a retrospective analysis about
effects and side-effects for a series of 46 Chinese patients with Wil-
Movement Disorders, Vol. 30, Suppl. 1, 2015
son[apos]s disease, treated by Unithiol (DMPS) intravenous infusion,
at Shanghai First Peoples Hospital Affiliated to Shanghai Jiaotong
University.
Background: In Europe and America, therapy drugs approved
for treating the patients with Wilson[apos]s disease (WD) mainly
include penicillamine and trientine. But in China, trientine is not
available for its price is so especially high to the patients. The WD
patients with penicillamine allergy or intolerance are recommended
to have orally dimercaptosuccinic acid (DMSA) in mainland China
safer and cheaper. The main WD specialists in China give Unithiol
(DMPS) intravenous infusion fo ra few of weeks . The authors
observed that data about effects of DMPS infusion on blood routine
(WBC,N,Hb,Plt) and liver function(ALT,AST,GGT,Alb) is insuffi-
cient. We aimed at finding the effects with data from a single center
at Shanghai First Peoples Hospital.
Methods: All of these 46 patients had blood routine
(WBC,N,Hb,Plt) before and after DMPS, and along with liver func-
tion(ALT,AST,GGT,Alb) before and after the DMPS infusion . We
did analysis with SPSS 20.0.
Results: 1.The blood routine(WBC,N,Hb,Plt) had no significant
change before and after DMPS treatment(P>0.05); 2.The liver func-
tion(ALT,AST,GGT,Alb) had no significant change before and after
DMPS treatment(P>0.05); 3. The Urine copper contents increased
by 5.5 times.
Conclusions: The DMPS infusion therapy has on effect on WD
patients blood routine (WBC,N,Hb,Plt) and liver function(AL-
T,AST,GGT,Alb). DMPS is a kind of safe and benificial treatment
for WD patients.
770
Autophagy is involved in age-related sensitivity to Parkinsonian
pathogenesis
Y.P. Yang, H.F. Zheng, C.J. Mao, F. Wang, L.F. Hu, C.F. Liu
(Suzhou, Peoples Republic of China)
Objective: To explore the underlying mechanisms of autophagy
in high sensitivity to MPTP-caused neurotoxicity in aged C57BL
mice.
Background: Autophagy is demonstrated to contribute to the
pathogenesis of Parkinsons disease (PD). PD is age-related neurode-
generative disease and autophagy level decline during the ageing.
Methods: 3 and 16 months old male C57BL mice were intraperi-
toneally injected with MPTP four times a day at 2-h intervals. Pole
climbing tests was performed after MPTP exposure. TH-positive neu-
rons and fibers in SNpc and striatum were detected with immuno-
staining. TEM was used to examine autophagosome. Western
blotting was used to examine the protein levels of TH, a-synuclein,
LC3-II, P62 and HDAC6 as well.
Results: Compared with 3-month-old PD mice, 16-month-old PD
mice showed significant shorter pole-climbing time after MPTP treat-
ment. Age-associated changes in 16-month-old PD mice included the
reduction in the densities of TH positive cells/fibers in SNc and stria-
tum, lower TH protein expression, and a-synuclein accumulation as
well. Under TEM, we observed increased lipofuscin and swollen
mitochondria in 16-month-old Parkinsonian mice. In 16-month-old
mice treated with saline, the protein levels of LC3-II and P62
declined while P62 protein increased with age. Compared with 3-
months-old PD mice, 16-months-old PD mice showed lower protein
expressions of LC3-II and HDAC6.
Conclusions: Ageing aggravated the DA neurons injury caused
by MPTP. 16-month-old mice showed a high sensitivity to MPTP
neurotoxicity. In 3-month-old mice, autophagy stress mediated by
HDAC6 weakened the cytotoxicity of MPTP to a certain degree.
While in 16-month-old mice, autophagy decompensation may be
responsible for the higher sensitivity to MPTP neurotoxicity in aged
mice.
 POSTER SESSION
POSTER SESSION 5
Wednesday, June 17, 2015
12:0013:30
Grand Hall
Parkinsonism
(secondary and parkinsonism-plus)
771
Incidence and characteristics of serious injuries due to falls
resulting from Movement Disorders- Japanese prospective fall
study in elderly patients under home nursing care (J-FALLS) -
I. Aiba, Y. Saito, M. Kaneko, M. Kawai, M. Yoshioka, H. Matsuo, H.
Fujimura, M. Tobita, T. Inui, K. Chida, A. Tamakoshi (Nagoya,
Japan)
Objective: To determine the incidence and characteristics of seri-
ous fall-related injuries such as fractures resulting from Movement
Disorders.
Background: Falls and injuries are common problems associated
with Movement Disorders. Some studies have reported the incidence
and characteristics of falls, but those of serious injuries due to falls
have not been revealed.
Methods: We conducted a prospective cohort study with a one-
year follow-up. A total of 1,013 outpatients under home nursing care
were recruited from 43 hospitals in Japan (407 with Parkinsons dis-
ease (PD); 308 with cerebrovasucular diseases (CVD); 118 with Alz-
heimers disease (AD), 95 with spinocerebellar degeneration (SCD);
55 with multiple system atrophy (MSA); and 30 with progressive
supranuclear palsy (PSP)). We investigated the annual incidence of
fractures, injuries leading to hospitalization, and death due to falls
using a fall diary and analyzed the details of injuries.
Results: Incidence of serious injuries (patients with serious inju-
ries/total patients3100%): PD, 7.4%; CVD, 4.9%; AD, 3.4%; SCD,
9.5%; MSA, 5.5%; PSP, 26.7%. Incidence of fractures (patients with
fractures/total patients3100%): PD, 6.9%; CVD, 4.5%; AD, 3.4%;
SCD, 9.5%; MSA, 5.5%; PSP, 16.7%. Region of injuries (number of
regions/total number of injuries3100%): PD: head/face, 11%; upper
extremities, 26%; upper trunk, 20%; lower trunk, 34%; lower
extremities, 3%. CVD: head/face 12%; upper extremities, 29%;
upper trunk, 6%; lower trunk, 41%; lower extremities, 6%. AD:
upper extremities, 20%; upper trunk, 60%; lower trunk, 20%. SCD:
head/face, 15%; upper extremities, 8%; upper trunk, 31%; lower
trunk, 23%; lower extremities, 8%. MSA: lower trunk, 67%; lower
extremities, 33%. PSP: head/face, 25%; upper extremities, 13%;
upper trunk, 63%.
Conclusions: The incidence of serious injuries was high in
patients with PSP. Common regions of injuries were various in PD,
the lower trunk in CVD, trunk in AD and SCD, lower body in MSA,
and upper body in PSP patients.
772
Prevalence of depression in atypical Parkinsonian disorders
versus Parkinsons disease
L. Almeida, M.S. Okun, D. Bowers, H. Ward, S. Fayad, C. Jacobson,
N. McFarland (Gainesville, FL, USA)
Objective: To compare the prevalence of depression in patients
with atypical Parkinsonism (aPD) and idiopathic Parkinsons disease
(PD) during their initial evaluation in a Movement Disorders center.
Background: Depression is a major psychiatric comorbidity
affecting nearly 50% of patients with Parkinsons disease. Despite
numerous studies in PD, few studies have addressed depressive
symptoms in atypical Parkinsonian disorders. Emotional well-being
is widely recognized as having an important impact on quality of life
S303
and is especially important in this patient population since many
symptoms often fail to respond to standard dopaminergic therapy. A
better understanding of the prevalence of depression in atypical Par-
kinsonism is crucial for optimizing treatment and quality of life.
Methods: An IRB approved retrospective chart review of the UF-
INFORM database was performed. We included patients with atypi-
cal Parkinsonian disorders, including PSP, MSA, CBD, and DLB
and a gender-matched control group of PD patients. We obtained
demographic data and reviewed the Beck Depression Inventory
(BDI) which was performed at the initial visit. We compared preva-
lences across different groups and assumed a p50.05 for statistical
significance.
Results: A total of 337 aPD and 820 PD were included in the
analysis. We defined a BDI > 13 as clinical depression. The mean
BDI values were 11.9 6 7.4 for PD and 13.7 6 8.1 for aPD (14 6 7.1
for PSP, 14.8 6 9.6 for DLB, 12.6 6 7.2 for MSA, 11.4 6 6.6 for
CBD). The prevalence of depression was 44% for PSP, 43.8% DLB,
33.3% CBD, 37.7% MSA. The overall prevalence of depression was
significantly greater in aPD in comparison to PD (43.4% and 31.3%,
respectively, p50.001). The presence of depression in the moderate-
severe range (BDI>19) was 23.1% and 13.7 for aPD and PD, respec-
tively (p50.001). In PD patients, there was a positive correlation
between UPDRS scores and depression (r=0.169, p<0.001, but this
was not observed in the aPD group (r=-0.05, p50.7).
Conclusions: Our findings suggest that, on their initial evaluation,
near half of the patients with aPD suffered from depression. When
present the majority have moderate-severe symptoms. There was no
correlation between motor scores and depression in the aPD group,
suggesting that mood disturbances may affect aPD patients regardless
of degree of motor disability. These findings stress the need to better
characterize depression in atypical Parkinsonian disorders.
773
Prevalence of anxiety in atypical Parkinsonian patients
L. Almeida, M.S. Okun, D. Bowers, H. Ward, S. Fayad, C. Jacobson,
N. McFarland (Gainesville, FL, USA)
Objective: To evaluate the prevalence of anxiety in patients with
atypical Parkinsonism.
Background: Despite an extensive literature on mood disorders
in Parkinsons disease (PD), only a few studies have examined the
prevalence of mood disorders in atypical Parkinsonian disorders.
Quality of life is especially important in this patient population
which often transitions rapidly into severe motor disability. Many of
the symptoms are refractory to standard dopaminergic therapy.
Methods: An IRB approved retrospective chart review of the UF-
INFORM database was performed. We included patients with PSP,
MSA, CBD, and DLB in the analysis, and also a gender-matched PD
control group. The variables included demographic data and rating
scales including UPDRS, PSP Rating Scale, UMSARS, and the Spiel-
berger State-Trait Anxiety Inventory (STAI). For the anxiety scores we
used previously suggested cutoff values from PD validation studies.
Results: A total of 337 atypical Parkinsonian and 820 PD patients
were. Data on anxiety was available in 110 atypical patients, defined
as STAI>54 as suggested by previous validation study. Anxious
symptoms were present in 20.9% of atypical patients, (19% of PSP,
15.6% of MSA, 31.6% of CBD, and 23.3% of DLB patients). The
mean State STAI of 59 6 5 points among all the atypical patients
(39.9 6 9.5 for MSA, 44.2 6 12 for PSP, 45.1 6 11 for CBD, and
44.1 6 7.3 for DLB).
In considering their initial visit to clinic, the mean STAI scores
were 41.8 610.1 and 42.6 6 10 for PD and atypical Parkinsonism,
respectively (p50.5). Anxiety was prevalent in 11% and 15.5% of
the PD and atypical patients, respectively (p50.24). The STAI corre-
lated positively with UPDRS scores in PD patients (r=0.170,
p50.03), but not in atypical Parkinsonism (r=0.013, p50.93).
Conclusions: Our findings suggest that, during the initial evalua-
tion, the prevalence of anxiety seems similar between PD and
Movement Disorders, Vol. 30, Suppl. 1, 2015
S304 POSTER SESSION
atypical Parkinsonian patients. Throughout subsequent clinic visits, the
number of patients developing anxiety increased from 15 to 20%.
Interestingly, there was no correlation between motor scores and
symptoms of anxiety, suggesting that this mood disturbance affects
atypical patients regardless of degree of motor disability, which seems
different from patients with PD. These findings stress the need to bet-
ter characterize and to treat anxiety in atypical Parkinsonian disorders.
774
Usefulness of transcranial ultrasound in atypical Parkinsonism:
A cross sectional study
A. Alonso-Canovas, J.L. Lopez-Sendon, A. deFelipe-Mimbrera, M.C.
Matute-Lozano, S.S. de laMaza-Cantero, R. Alvarez-Velasco, J. Bui-
san, G. Garcia-Ribas, I. Aviles-Olmos, J. Masjuan, J.C. Martinez
Castrillo (Madrid, Spain)
Objective: To assess diagnostic reliability of transcranial ultra-
sound (TUS) in Atypical Parkinsonian Syndromes (APS).
Background: APS diagnosis is challenging and ancillary tests may
be misleading. TUS has proven reliability in Parkinsons disease (PD)
diagnosis and a building evidence indicates a potential role in APS.
Methods: Analysis of clinical and sonographic features of
patients with APS (progressive supranuclear palsy-PSP, multiple sys-
tem atrophy-MSA, corticobasal degeneration-CBD). Clinical diagno-
sis was established by Movement Disorders specialists following
consensus criteria (NINDS for PSP, Gilman for MSA and Armstrong
for CBD), after a minimum follow up of 4 years for the sake of
accuracy. TUS was performed by an experienced sonographer fol-
lowing a standarized protocol. Sonographic findings were compared
with a cohort of 105 PD patients and 138 controls (C). Consensus
TUS criteria for APS (substantia nigra-SN and lenticular nucleus-LN
echogenicity, III ventricle-IIIV amplitude) were applied. Statistical
methods: descriptive statistics, Fishers test.
Results: Twenty two patients with diagnosis of APS (63.6%
male, 73 6 10 years) underwent TUS. Clinical diagnosis was PSP in
9 cases, MSA in 8 and CBD in 1 case, and overlapping syndromes
in the remaining (PSP/CBD in 2; PSP/MSA in 2). Two patients
(9,1%, diagnosis MSA and PSP/MSA) had billaterally absent trans-
temporal bone window. In the remaining 20, TUS showed atypical
findings in 18 cases (90%) and typical PD findings in 2 (10%). Clini-
cal and ultrasound diagnoses were concordant in 15 cases (5 MSA, 9
PSP, 1 CBD), while in 1 case were discordant (clinical diagnosis
CBD, TUS PSP), and 2 patients had Parkinsonism without TUS
abnormalities. Ultrasound criteria for APS were completely met (3/3)
in 7 studies, while 6 met 2/3 criteria and 3 met 1/3. SN hyperechoge-
nicity was found in 40% of APS (83,3% in PD, p<0.0001; 10% of
C, p:0.0022), LN hyperechogenicity in 63% (20,5% in PD, p:0.0005;
6,8% in C, p:0.0001), and enlargement of the IIIV in 40% (24,7% in
PD, NS; 11,5% in C, p:0.0001).
Conclusions: TUS showed significantly distinct features in our
APS patients when compared with PD patients and control subjects,
particularly when SN and LN echogenicity were considered. These
findings strengthen the reliability and feasibility of this non invasive
tecnique in APS diagnosis, when applied by skilled sonographers fol-
lowing consensus criteria.
775
Progression of clinical symptoms and survival in progressive
supranuclear palsy
J.E. Arena, S.D. Weigand, J.L. Whitwell, S.D. Eggers, G.U.
Hoglinger, I. Litvan, K.A. Josephs (Rochester, MN, USA)
Objective: To determine the prevalence of symptoms at different
stages of disease in progressive supranuclear palsy (PSP) to estimate
their time of appearance, and to characterize early PSP. Addition-
ally we aim to determine the association between clinical symptoms,
and survival.
Movement Disorders, Vol. 30, Suppl. 1, 2015
Background: The clinical characteristics and natural history of
PSP have been previously described and a few prospective studies,
also aiming to link the presence of clinical features with prognosis,
have been published. Nonetheless, the timeframe of appearance of
these milestones have not been accurately addressed and how these
relate to survival remains unknown.
Methods: We prospectively recruited and followed 35 patients with
a clinical PSP diagnosis for a period of up to 2 years, with visits to our
clinic every 6 months. Clinical symptoms were assessed in each visit and
clustered into different categories. Descriptive statistics were performed,
and ANOVA, X2 test, Wilcoxon test, and Spearman r were used as
appropriate for analyses. Kaplan-Meier analysis was used to assess the
time of appearance of symptoms and association with survival.
Results: Median time from onset to first visit was 2.4 years [IQR
1.9-2.9]. All 35 patients (100%) had presented with motor symptoms at
the time of their first visit; therefore the appearance of motor symptoms
as new was not registered in subsequent visits. Of those that exhibited
cognitive/behavioral symptoms at any time during follow up, 93.9%
had such signs at the time of their first visit. This was also noted for
90.3% of bulbar symptoms; 90.3% of systemic symptoms; 87.5% of
sleep disturbances, and 85.3% of other symptoms. Older age at onset
was associated with systemic symptoms (p50.007). Higher PSP rating
scale (PSPRS) scores were associated with a higher prevalence of sys-
temic symptoms (p<0.0001), more executive dysfunction on the Fron-
tal Assessment Battery (r=-0.53; P<0.0001) and more behavioral
dyscontrol on the Frontal Behavioral Inventory (r= 0.51; p<0.0001).
Conclusions: The understanding of the clinical characteristics of
PSP can be important in patient care, especially when it comes to
offering prognostic information. Some symptoms develop over time
and may depend on age at presentation. However, most symptoms
are already present at the time of presentation.
776
Diagnosing dementia in multiple system atrophy with MDS
criteria for Parkinsons disease dementia
N. Auzou, K. Dujardin, R. Biundo, A. Foubert-Samier, C. Barth, F.
Tison, L. Defebvre, A. Antonini, W.G. Meissner (Bordeaux, France)
Objective: To assess the usefulness of the Parkinsons disease
dementia (PDD) diagnostic procedures for diagnosing dementia in
patients with multiple system atrophy (MSA).
Background: Dementia is an exclusion criterion in current con-
sensus diagnostic criteria, while growing evidence suggests the occur-
rence of cognitive dysfunction and even dementia in MSA patients.
Methods: In this retrospective study, the International Parkinson
and Movement Disorder Society diagnostic criteria for PDD were
applied in 111 MSA patients.
Results: According to these criteria, 11.7% of MSA patients were
demented on LEVEL-II examination (extensive neuropsychological
assessment). LEVEL-I examination (short screening checklist) showed
strong specificity (96.9%) and negative predictive value (94.1%),
while sensitivity (53.8%) and positive predictive (70%) value were
moderate compared to LEVEL-II evaluation. Sensitivity increased to
84.6% when using a Mini Mental State Examination threshold < 27
for LEVEL-1. Executive dysfunction was the main prevalent finding
(73%), while memory (33.3%) and visuospatial (34.2%) impairment
were also observed in a significant number of patients.
Conclusions: Our findings suggest that the screening checklist
may be useful for the diagnosis of MSA dementia.
777
Perry syndrome Characteristics of the first Portuguese family
R. Barreto, M. Lopes, J.M. Roriz, M. Magalh~ aes (Santa Maria
Feira, Portugal)
Objective: To characterize the first known Portuguese family
with Perry syndrome.
 POSTER SESSION
Fig. 1. (777).
Background: Perry syndrome is a rare autosomal dominant disor-
der, caused by mutations in the DCTN1 gene. Early-onset Parkinson-
ism, hypoventilation, weight loss and psychiatric disturbances are the
clinical hallmarks, but the availability of genetic diagnosis is expand-
ing the diseases spectrum.
Methods: Genealogical, clinical, genetic and imaging studies
were conducted in a Portuguese kindred.
Results: The proband is a 55-year-old woman with onset, at the
age of 49, of frontal lobe cognitive dysfunction characterized by
gradual, progressive decline in behavior with severe apathy, later
associated with symmetrical Parkinsonism with slight response to
dopaminergic treatment as well as staring-eyes, eyelid apraxia,
decomposition and slowness of saccades, oculogyric crisis and cervi-
cal dystonia. Neuropsychological evaluations showed progressive
decline of verbal initiative, attention and executive functions. Cere-
bral MRI was unremarkable, FDG-PET imaging showed fronto-
temporal and striatal hypometabolism, DATAscan SPECT revealed
bilateral striatal dopaminergic degeneration. Two out of four of the
probands siblings developed pronounced, rapidly progressing, apathy
and subsequent Parkinsonian signs starting at age 47 and 53, respec-
tively. In both, cognitive evaluation showed severe frontal dysfunc-
tion. Proband and siblings showed no signs of weight loss or
hypoventilation, but all had staring-eyes, frequent falls and terminal
refractory insomnia. Genetic analysis confirmed heterozygotic
pPhe52Leu mutation of exon 2 in DCTN1 gene in the proband. In
genealogical review, the probands paternal grandmother, father and
seven paternal uncles had similar phenotypes, starting at the fifth
decade of life and died within 10 years of symptom onset, with
severe weight loss and respiratory failure reported at least in one
case. Genetic counseling was offered to all at-risk relatives.[figure1]
Conclusions: Apathy as an early manifestation of frontal lobe
dysfunction and terminal insomnia are consistent signs of Perry syn-
drome in the patients of these Portuguese kindred. The presence of a
progressive supranuclear palsy-like syndrome, autosomal dominant
pattern of inheritance and absence of mesencephalic atrophy in cere-
bral MRI pointed to Perry syndrome. Prevention of death by hypo-
ventilation and genetic counseling will be paramount to patients and
relatives.
778
The effects of comorbid traumatic brain injury on motor and
non-motor symptoms of Parkinsons disease
B.R. Barton, C. Stachnik (Chicago, IL, USA)
Objective: Determine whether documentation of motor and non-
motor symptom profiles in a United States Veterans Affairs (VA)
S305
hospital is more frequently present in Parkinsons disease (PD)
patients with prior traumatic brain injury (TBI) as compared to with-
out TBI, and whether evaluation by a Movement Disorders specialist
improves this documentation.
Background: Although there is an epidemiological association
between PD and TBI, no studies have investigated potential different
phenotypes in PD patients with previous TBI. In theory, TBI may
cause a more severe phenotype with more non-motor symptoms or
less classical motor features.
Methods: Retrospective case-control study of charts of veterans
with PD ICD-9 codes at one VA hospital between 2011-2013. Only
9/431 (2.1%) of subjects had chart documentation of TBI and met
Queen Square Brain Bank criteria for probable PD. Chart reviews on
43 veterans surveyed presence or absence of motor and non-motor
PD symptoms. Chi-square and t-test were used to compare cases and
controls.
Results: Average age was 75. The incidence and categories of
documented non-motor symptoms was no different between TBI and
non-TBI groups. There was a borderline significant difference
(p50.06) between motor symptoms, with the TBI group having more
documented motor symptoms. The number of documented non-motor
symptoms was higher in patients seen by a Movement Disorder spe-
cialist, as compared to other physicians (p50.0009), including symp-
toms considered important for clinical quality measures (e.g. sleep,
hallucinations).
Conclusions: TBI was infrequently noted in our Veteran cohort.
Documentation supports possibly more motor symptoms in veterans
with TBI and PD, but non-motor symptoms occur at a similar rate to
those without TBI. Differences in phenotype may ultimately serve as
a basis for understanding the link between TBI PD pathophysiology.
Examination by a Movement Disorder specialist makes evaluation of
critical non-motor symptoms much more likely.
779
Abnormal insulin/IGF-1 signaling together with insulin resistance
in the putamen of MSA patients
F. Bassil, P.O. Fernagut, M.H. Canron, A. Vital, E. Bezard, W.G.
Meissner (Bordeaux, France)
Objective: To assess insulin/insulin like growth factor-1 (IGF-1)
signaling in multiple system atrophy (MSA).
Background: Recent studies indicate that IGF-1 serum levels are
increased in MSA patients and that IGF-1 brain tissue levels are
reduced in a transgenic MSA mouse model. Alterations of the insu-
lin/IGF-1 signaling pathway have been observed in other neurodege-
nerative disorders such as Alzheimers disease and Parkinsons
disease and targeting it in preclinical studies has shown beneficial
effects on behavioral outcomes and surrogate markers of
neurodegeneration.
Methods: Immunohistochemistry was performed on post-mortem
brain tissue of MSA patients (n57) and healthy controls (n57) to
assess in the putamen the expression of insulin receptors, IGF-1
receptors (IGF-1R), glucagon like peptide-1 receptors (GLP-1R),
activators of the insulin/IGF-1 signaling pathway along with the
downstream effector FOXO-1. Double immunofluorescence was used
to assess markers of insulin resistance (IRS-1pS312 and IRS-
1pS616). Neurons showing insulin resistance were isolated and their
intensity of staining was measured using ImageJ.
Results: The number of IGF-1R and FOXO-1 positive cells was
higher in the putamen of MSA patients compared to controls, while
the number of IGF-1R, GLP-1R and insulin receptor positive cells
was not different. As a result of severe neuronal loss, numbers of
IRS-1pS312 and IRS-1pS616 positive neurons were decreased in
MSA patients. Neurons positive for IRS-1pS312 showed a significant
increase in staining intensity compared to healthy controls. A trend
for increased staining intensity was also found for IRS-1pS616 posi-
tive neurons in MSA patients compared to healthy controls.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S306 POSTER SESSION

Furthermore, a significant increase in non-neuronal cells positive for
IRS-1pS312 and IRS-1pS616 was observed in MSA patients.
Conclusions: Our preliminary results suggest abnormal insulin/
IGF-1 signaling together with insulin resistance in the putamen of
MSA patients. These abnormalities may contribute to the underlying
neurodegenerative process.
780
Region-specific alterations of matrix metalloproteinase activity in
multiple system atrophy
F. Bassil, A. Monvoisin, M.H. Canron, A. Vital, W.G. Meissner, F.
Tison, P.O. Fernagut (Bordeaux, France)
Objective: To assess the potential role of matrix metalloprotei-
nases (MMPs) in multiple system atrophy (MSA) pathophysiology
by investigating MMP-2 and MMP-9 in MSA postmortem brain
tissue.
Background: The pathological hallmark of MSA is the accumu-
lation of a-synuclein aggregates in the cytoplasm of oligodendro-
cytes along with neuronal loss and neuroinflammation, as well as
blood brain barrier (BBB) dysfunction and myelin deterioration.
MMPs are zinc-dependent endopeptidases involved in the remodel-
ling of the extracellular matrix, demyelination and BBB permeability
and several lines of evidence indicate a role for these enzymes in
various pathological processes including stroke, multiple sclerosis,
Parkinsons and Alzheimers disease.
Methods: Gelatin zymography was used to measure the enzy-
matic activity of MMP-2 and MMP-9. Densitomotric analysis and
cell counts of MMP-2 immunohistochemistry were performed to
assess the extent and pattern of MMP-2 expression. The presence of
MMP-2 in different cell types was assessed using double
immufluorescence.
Results: Gelatin zymography revealed increased MMP-2 activity
in the putamen of MSA patients relative to controls but not in the
frontal cortex. No significant difference was found for MMP-9.
Immunohistochemistry revealed a markedly increased number of
glial cells positive for MMP-2 in the putamen of MSA patients, and
to a lesser extent in the frontal cortex. Double immunofluorescence
revealed that MMP-2 colocalized primarily with a-synuclein in GCIs
in MSA patients but also colocalized to a higher extent with astro-
cytes and microglia compared to healthy controls.
Conclusions: Our results indicate that the expression and global
activity of MMP-2 are increased preferentially in a brain region that
is severely affected such as the putamen, while being less altered in
the frontal cortex. Elevated MMP-2 activity in MSA may thus con-
tribute to the disease process by promoting blood brain barrier dys-
function and/or myelin degradation.
781
Young onset MSA can mimic young onset PD- clues to help the
diagnosis
A. Batla, M. Reich, G. Calandra Buonaura, P. Cortelli, J. Volkmann,
R.P. Erro, K.P. Bhatia (London, United Kingdom)
Objective: To report six consecutive cases with young onset
MSA and find clinical clues that may help in early recognition of
MSA.
Background: The term young onset is applied to MSA with
symptoms onset before 40 years of age(1), There are no pathologi-
cally proven cases with onset earlier than 30 years of age (2-4). Con-
sidering significant overlap between the onset symptoms of
Parkinsons disease (PD) and MSA, we aimed to study these cases.
Methods: We reviewed clinical records of consecutive patients
with young onset MSA (YOMSA) presenting to Movement Disorders
clinics of the authors-KPB at NHNN, Queen square, London, JV at
University Hospital of W urzburg, Germany and PC at Institute of
Neurological Sciences of Bologna, Italy. The case definition
included- onset of MSA before age 40, patients fulfilling the second
consensus criteria of probable MSA with additional imaging features
of possible MSA(5) and a negative family history (5). Based on
patient notes, clinical information was recorded on a predesigned
proforma. Written consent was taken from each patient for the video
recording and for accessing their medical records, and imaging.
Results: We included six patients mean age 35.67 years (range
33-40 years). The mean disease duration was 8.33 years (SD=4.88).
All the patients had akinetic rigid syndrome as their main clinical
feature, and all had autonomic features. All patients had pyramidal
features 5 (83.33%) had cerebellar features. 5 patients (83.33%) had
an asymmetric presentation and a jerky postural tremor was seen in

Clinical and imaging features of six patients with young onset MSA

Case 1 Case 2 Case 3 Case 4 Case 5 Case 6

Gender F M M M F M
Age of onset 35 33 33 37 36 40
Disease duration 74 11 17 5 4 6
Main clinical fea- Akinetic rigid Akinetic rigid Akinetic rigid Akinetic rigid Akinetic rigid Akinetic rigid
ture syndrome syndrome syndrome syndrome syndrome syndrome
at diagnosis of
MSA
First symptom Asymmetric Asymmetric Asymmetric Bladder Horners syn- Asymmetric
tremor tremor tremor drome and voice tremor
difficulty
Tremor Postural tremor at Jerky action Asymmetric Bilateral postural Left sided jerky Left sided jerky
onset tremor tremor hand tremor postural postural
of leg at rest
Levodopa- Peak-of-dose after No No Yes No No
induced- 4 years
dyskinesia
Postural Yes after 3 years Yes after 5 years Yes Yes Yes Yes
impairment
Voice Spasmodic Dysarthria Dysarthria Dysarthria Dysarthria Dysarthria
dysphonia

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION S307

TABLE . Continued

Clinical and imaging features of six patients with young onset MSA

Case 1 Case 2 Case 3 Case 4 Case 5 Case 6

Dystonia Limb-dystonia No No No Laryngeal Limb-dystonia
Anterocollis No No No Yes Yes No
Inspiratory Sigh No No No Yes Yes No
Tendon Reflexes Pathologically Pathologically Pathologically Pathologically Pathologically Pathologically
brisk brisk brisk brisk brisk brisk
Babinskis sign Positive on right Positive Mute Positive negative negative
side
Cerebellar signs No Yes Yes Yes Yes Yes
Autonomic Neurogenic blad- Neurogenic blad- Neurogenic Neurogenic blad- Neurogenic blad- Neurogenic blad-
der and der and bladder der and der and ortho- der and ortho-
orthostatic orthostatic orthostatic static hypotension static hypotension
hypotension hypotension hypotension
Cognition Normal Normal Normal Normal Normal Normal
MRI High-signal lat- normal High-signal lat- High-signal lat- Ponto cerebellar High-signal lat-
eral rim to eral eral rim in the atrophy eral rim to the
the putamen rim to the putamen and putamen
putamen Ponto cerebellar
atrophy
Other imaging I-123-FP-CIT- None Dat SPECT Dat SPECT Dat SPECT Dat SPECT
Asymmetric abnormal abnormal abnormal abnormal
reduced primarily
putamen
Genetics LRRK2 and PARK2 SCA Parkin HD SCA SCA 1,2,3,7,12,17 SCA 1,2,3,7,12,17 SCA 1,2,3,7,12,17
(negative) PARK2 1-2-3-6-17, 1,2,3,7,12,17
dynactin
mutation fragile
X
Abbreviations MSA- multisystem atrophy, SCA, Spinocerebellar degeneration, NA not available

most. Breathing abnormalities including stridor were noted in 4
(66.67%) and dysarthria was present in all the patients.
All patients fulfilled the criteria for probable MSA-Parkinsonism
(MSA-P) 4 patients had been diagnosed as PD at onset and had a
partial levodopa response with dyskinesia in 2 patients. All patients
by definition had imaging abnormalities on imaging suggestive of
MSA. All the patients are still alive.
Conclusions: We report six patients of onset of MSA younger
than 40 years. Although a confirmation will be possible only on
autopsy, YOMSA can present very much like YOPD with asymmetric
resting tremor in the younger age group and often responds to Levo-
dopa initially. Apart from autonomic features and neuroimaging, care-
ful examination for presence of subtle cerebellar and corticospinal
signs, may help in in early diagnosis of YOMSA in this subgroup.
782
Epidemiological aspects in a Tunisian cohort of Parkinson-plus
syndromes
M. Ben Djebara, A. Nasri, I. Kacem, L. Sellami, Y. Hizem, A.
Gargouri, R. Gouider (Tunis, Tunisia)
Objective: To determine the epidemiological aspects of
Parkinson-plus syndromes (PPS) in a Tunisian population and to
point the differences between subgroups of PPS.
Background: PPS constitute an evolving group of degenerative
atypical Parkinsonian syndromes. There has been no prior systematic
review of epidemiological aspects of all types of PPS in North Afri-
can population.
Methods: In a 12 year retrospective study (2002-2014), we
included all the patients diagnosed with degenerative Parkinsonism
and classified as non Parkinsons disease. Frequencies, age, sex, con-
sanguinity rate, family and personal history were analyzed.
Results: We included 220 patients with PPS, which represented
16% of all patients with Parkinsonism followed in in the same
period. Mean age was 73,46 11,3years [40-97]. Consanguinity rate
was 32,7%. Family history of neurodegenerative pathologies was
found in 60,4%. Main etiologies were DLB in 39,1%, CBD in
13,6%, MSA in 10,9% and PSP in 7,3%. Alzheimers Disease with
Parkinsonism represented 3,6% and FTLD-Parkinsonism 3,2% of
cases. Degenerative Parkinsonism was of undetermined origin in
22.3%. Sex-ratio was 1.27 (mainly males in DLB, CBD, AD-Park;
mainly females in MSA and FTLD-Park, no sex differences in PSP).
Mean age at onset was 66,8 years. The highest age of onset was
found in the DLB group (72 years) and the lowest in MSA (56
years). Mean evolution period was 6,6 years.
Conclusions: Our data suggest that PPS rate in Tunisians is the
same as in western countries. It constitute 15-25% of all degenerative
Parkinsonism depending on included subgroups and studied population.
DLB, the second most common cause of degenerative dementia, is the
most common PPS in our series. It has been recently included in epide-
miological studies of Parkinsonism. Male predominance is established
in Parkinsonian syndromes. The female predominance in MSA found
in our series differs from the literature. The high consanguinity rate in
our series, suggest genetic specifities in Tunisian patients with PPS.

Movement Disorders, Vol. 30, Suppl. 1, 2015

S308 POSTER SESSION
783
Cortical excitability and sensorimotor integration correlates with
cognitive profile in vascular Parkinsonism

S. Bentez-Rivero, F.J. Palomar, J.F. Martn-Rodrguez, P. Alvarez
de Toledo, M.J. Lama, I. Huertas-Fern andez, M.T. C aceres-
Redondo, P. Porcacchia, P. Mir (Seville, Spain)
Objective: Our aim was to study sensorimotor integration and
intracortical circuits using transcranial magnetic stimulation in vascu-
lar Parkinsonism and to correlate the potential abnormalities in this
technique with the cognitive profile of these patients.
Background: Vascular Parkinsonism is a Parkinsonian syndrome
that develops as a result of ischaemic cerebrovascular disease.
Although several studies on clinical features and neuroimaging can
be found in the literature, little is known about the pathophysiologi-
cal mechanisms involved in this disease.
Methods: We studied 11 vascular Parkinsonism patients, 11 Par-
kinsons disease patients and 13 controls. We applied transcranial
magnetic stimulation to investigate sensorimotor plasticity and intra-
cortical circuits and we performed extensive neuropsychological
examinations.
Results: Vascular Parkinsonism patients showed lack of long
term potentiation-like plasticity after paired associative stimulation
protocol and reduced short latency afferent inhibition. Furthermore,
these patients showed decreased short interval intracortical inhibition
and intracortical facilitation, as well as shortening of the cortical
silent period. Correlations were found in these patients between short
interval intracortical inhibition and the Mattis dementia rating scale,
as well as between sensorimotor plasticity and short latency afferent
inhibition with verbal memory tests. These correlations were not
found in Parkinsons disease patients.
Conclusions: Our neurophysiological findings suggest cortical
glutamatergic, cholinergic and GABAergic deficiencies in vascular
Parkinsonism, which may be a consequence of the disruption of
subcortical-cortical connections caused by vascular lesions. The cor-
relations found suggest that these neurotransmitter systems are
involved in the processes of cognitive decline in these patients. The
absence of these correlations in Parkinsons disease patients suggests
that the pathophysiological mechanisms involved in these two condi-
tions may be different.
784
Diagnostic accuracy of magnetic resonance Parkinsonism index
in progressive supranuclear palsy in Indian patients
K. Bharambe, C. Sankhla, S. Gupta, N. Savant (Mumbai, India)
Objective: To assess the diagnostic accuracy of Magnetic reso-
nance Parkinsonism index (MRPI) in differentiating Progressive
supranuclear palsy (PSP) from Parkinsons disease (PD) and controls
and its correlation with duration of disease.
Background: MRI measurements of brainstem structures have
been proposed as useful markers in differentiating PSP from PD. We
measured midbrain and pons areas, superior and middle cerebellar
peduncle widths, midbrain-to-pons area (M/P) ratio and MRPI in
patients with PSP, PD and age matched controls to evaluate the
accuracy of MRPI and compared it with M/P ratio.
Methods: 26 consecutive patients with PSP were enrolled in this
study, satisfying the diagnostic criteria by NINDS-SPSP, along with
13 patients with PD and 30 age matched controls. Radiologists were
blinded to the clinical diagnoses. MRPI was calculated by multiply-
ing pons area/midbrain area ratio by middle cerebellar peduncle
(MCP) width/superior cerebellar peduncle (SCP) width ratio. M/P
ratio was measured as the ratio of midbrain area to pons area.
Results: Mean MRPI in patients with PSP (23.48 6 9.61) was
significantly higher than that in patients with PD (9.07 6 2.23) and
controls (9.45 6 1.87). In this study, MRPI was 100% sensitive, spe-
cific and accurate in differentiating patients with PSP from patients
with PD and was 96.3% sensitive, 100% specific and 98.21% accu-
Movement Disorders, Vol. 30, Suppl. 1, 2015
rate in differentiating patients with PSP from controls. No correlation
was found between duration of disease and MRPI in patients with
PSP in the present study. MRPI was marginally superior to M/P ratio
in diagnosing patients with PSP from patients with PD on an individ-
ual basis. No overlapping values were observed in PSP and PD
patients.
Conclusions: MRPI can differentiate patients with PSP from
those with PD on individual basis.
785
Palliative care in Parkinsons disease: Patients perspectives
I. Boersma, J. Jones, J. Carter, D. Bekelman, J. Miyasaki, J. Kutner,
B. Kluger (Mount Pleasant, SC, USA)
Objective: To identify and define the palliative care needs of Par-
kinsons disease (PD) patients through direct patient interviews.
Background: A growing body of literature suggests that PD
patients have many unmet needs under current models of care that
may be better addressed through palliative care models. As palliative
care needs may vary across illnesses, a first step in developing
disease-specific palliative services is to identify and define the pallia-
tive care needs of PD patients.
Methods: 30 PD patients and 4 focus groups underwent semi-
structured, in-depth interviews regarding unmet palliative care needs
and preferences for addressing those needs. We used standard quali-
tative data analysis techniques to interpret and summarize responses.
Results: Patients articulated significant challenges in living with
a diverse and complex set of motor and non-motor symptoms;
described profound feelings of loss and grief related to PD; and
expressed concerns regarding relationships, cosmetic appearance and
finances. Patients expressed worry about the future, particularly how
their illness might progress and how it might affect their family.
Overall, PD had a major impact on identity. Participants noted sev-
eral gaps in their care, including: communication at time of diagno-
sis, PD education and advance care planning. Participants expressed
interest and openness to interdisciplinary approaches for addressing
these needs.
Conclusions: PD has a profound impact in multiple domains of a
persons life starting at the time of diagnosis. Participants desired
individualized, team-based care and were receptive to early outpa-
tient palliative care services as an adjunct to usual care. Future
research efforts are needed to determine the prevalence and impact
of these issues and to test the effectiveness of palliative services or
other novel approaches to improve the care of PD patients.
786
Relationship between uric acid levels and progressive
supranuclear palsy (PSP)
D.M. Brody, I. Litvan, S.N. Rai, A.C. Cambon, D.E. Riley, D.A. Hall,
B.M. Kluger, C.R. Cunningham (La Jolla, CA, USA)
Objective: To determine whether Progressive Supranuclear Palsy
(PSP) is associated with low serum concentrations of uric acid.
Background: Uric acid is a major antioxidant and an association
between high uric acid blood levels and reduced risk of Parkinsons
disease and its rate of progression has been reported. Despite find-
ings that a pro-oxidant state is associated with the pathophysiology
of progressive supranuclear palsy (PSP), the relationship between
uric acid blood levels in this disorder has not been elucidated. We
investigated whether a low serum concentration of uric acid is asso-
ciated with PSP.
Methods: We measured uric acid serum concentrations in a sub-
sample from the ENGENE PSP study that included 56 cases and 56
paired age-matched healthy controls (spouses) from 4 centers: Case
Western, Rush University, University of Utah, and University of
Louisville. Cases were characterized using Mattis Dementia Rating
Scale, total PSP-Rating Scale, and Unified Parkinsons disease
 POSTER SESSION
Rating Scale. Unconditional logistic regression, Pearsons chi-
squared test and Analysis of Variance (ANOVA) were used as
appropriate.
Results: There were no between-group statistical differences in
uric acid levels, controlling for gender. Uric acid levels were not
associated with disease severity. This study has moderate power to
detect between-group differences, thus, a small inverse association
between PSP and uric acid cannot be excluded.
Conclusions: The results of this study suggest that uric acid lev-
els may not have a moderate protective role in PSP, even if oxidative
injury is important in the pathophysiology of this disorder.
787
Acute onset of shuffling gait from hypertensive hemorrhage
J.Y.C. Chen, I. Keshet, J. Weinberger (San Francisco, CA, USA)
Objective: To describe a case of acute onset of Parkinsonian gait
secondary to intracerebral hemorrhage.
Background: Movement Disorders secondary to cerebral vascular
accidents either ischemic or hemorrhagic are a well described phe-
nomenon. However, these tend to be delayed sequelae, presenting
some time after the inciting event. When they do present acutely,
they are usually accompanied by other cortical signs corresponding
to the site of the lesion. Furthermore rarely do they present with gait
changes that are not otherwise secondary to weakness. And while
vascular Parkinsonism is classically characterized by gait disorder, it
presents with gradual symptoms from chronic vascular damage of
the brain with or without clearly known ischemic events. We present
a case of acute onset of shuffling gait secondary to hypertensive
hemorrhage.
Methods: A single case report.
Results: An 88 year old previously completely physically func-
tional and independent woman developed acute onset of a shuffling
gait. Her symptoms consisted of a narrow-based but slow, small-
stepped, and hesitant gait with en bloc turning. She described her
problem as needing to remind herself to take a step particularly
when getting into a bus. Exam showed no mental status changes,
weakness, sensory disturbance or ataxia but very slight rigidity and
bradykinesia on her left side. Blood pressure was significantly ele-
vated at 206/84 mmHg. Computed tomography (CT) and magnetic
resonance imaging (MRI) of her brain showed an acute right basal
Fig. 1. (787).
S309
Fig. 2. (787).
ganglia hemorrhage, particularly in the region of the right putamen.
[figure1] [figure2] Her symptoms resolved over the course of 2-3
weeks with physical therapy and did not require a trial of levodopa.
Conclusions: To our knowledge, though it is well known that
repeated ischemic events can lead to vascular Parkinsonism, there has
been no case reported of an acute onset of a Parkinsonian gait from
intracerebral hemorrhage as the sole presenting symptoms. This case
highlights that Movement Disorders, though an unusual presentation
of strokes, especially acute hemorrhages, still warrant imaging in the
setting of an acute or subacute presentation. In addition it also shows
that a unilateral lesion can cause symptoms that appear bilateral.
788
Gait disturbance and Parkinsonism in a patient with hereditary
diffuse leukoencephalopathy with axonal spheroids and CSF1R
mutation
Y.F. Chen, M.Y. Lan, J.S. Liu, Y.Y. Chang (Kaohsiung, Taiwan)
Objective: To demonstrate a patient with hereditary diffuse leu-
koencephalopathy with axonal spheroids presented with gait disturb-
ance and Parkinsonism features.
Background: Hereditary diffuse leukoencephalopathy with axo-
nal spheroids (HDLS) is a rare cause in leukodystrophies. It is inher-
ited in an autosomal-dominant pattern and is caused by a mutation in
the macrophage colony-stimulating factor 1 (CSF-1) receptor gene,
CSF1R. It is clinically characterized by adult-onset, progressive
course and a constellation of symptoms including personality change,
cognitive dysfunction and motor impairments such as gait disturb-
ance, atypical Parkinsonism, tremor, bradykinesia and rigidity.
Methods: We conducted a complete exam of Parkinsonism with
leukoencephalopathy, including laboratory studies, brain MRI, CSF
study, neuropsychological tests. We also conducted stereotactic
biopsy of brain and genetic study for HDLS.
Results: A 34-year-old woman with a 2-year history of unsteady
gait, bilateral hands tremor, rigidity and nonfluent speech, and uri-
nary incontinence presented with exaggerated emotional responses
characterized by bursts of tears or laughter with trivial affective stim-
uli. Neurological examination revealed postural and action tremors in
the upper limbs, mild truncal and limbs rigidity, postural instability,
gait disturbance with shuffling and mild freezing in turning, primitive
reflexes, and impaired verbal fluency. Conscious state, cranial nerves,
muscle power of the limbs, sensory system, and cerebellar system
were normal. Brain MRI revealed frontal lobe-predominant, conflu-
ent hyperintense lesions in the periventricular white matter and the
corpus callosum on T2-weighted and FLAIR images. Stereotactic
biopsy of the right frontal lobe and histopathologic examination
Movement Disorders, Vol. 30, Suppl. 1, 2015
S310 POSTER SESSION
revealed white matter vacuolization with demyelinating foci, gliosis,
and axonal spheroids that were immunoreactive to neurofilament and
synaptophysin. CSF1R mutation, a mutation c.2381 T > C in exon
18, which led to a missense mutation (p.I794T), was identified.
Conclusions: HDLS may clinically present with neurological def-
icits linked to gait disturbance, Parkinsonism and frontal lobe dys-
function. Atypical Parkinsonism with gait disturbance and
characteristic white matter lesions may serve as diagnostic clues for
HDLS and support further molecular genetic testing.
789
Longitudinal follow-up and neurophysiological findings in two
Chinese siblings with compound heterozygote mutations in
ATP13A2 (PARK9) causing juvenile onset Parkinsonism (Kufor-
Rakeb syndrome)
H.L. Chiang, D.S.Y. Tsui, S.D. Kim, V.S.C. Fung (Sydney, Australia)
Objective: To describe the longitudinal history and neurophysiologi-
cal findings in two Chinese Siblings with Kufor-Rakeb syndrome (KRS).
Background: KRS is a rare form of autosomal recessive Parkinson-
ism due to ATP13A2 mutations. The syndrome, first described by
Najim et al, is characterized by juvenile onset, levodopa-responsive
Parkinsonism with additional symptoms of supranuclear gaze palsy,
dementia, hyperreflexia and facial-faucial-finger mini-myoclonus
(FFF). To date, only 10 families with 25 patients were reported. Here,
we describe the neurophysiological findings and longitudinal history of
the 2 Chinese siblings with KRS and compound heterozygous muta-
tions, c.3176T>G (p.L1059R) and c.3253delC (p.L1085WfsX1088) in
ATP13A2 with a follow up period of >10 years.
Methods: Case report.
Fig. 1. (790).
Movement Disorders, Vol. 30, Suppl. 1, 2015
Results: The proband is a 33-year-old male, who developed
obsessive-compulsive disorder and anxiety at the age of 17 followed
by tremulous movements in face and upper limbs, recurrent falls 2
years later. On examination at 22, there was impaired saccadic and
pursuit upgaze, asymmetric Parkinsonism, impaired postural reflex,
facial and wrist dystonia, mini-myoclonus and action tremor in face
and upper limbs and hyperreflexia. The Parkinsonian symptoms were
dopa-responsive and motor fluctuation developed 5 years later. His
gait gradually deteriorated needing the use of a walker at age 31. Sur-
face electromyography (sEMG) showed myoclonus and tremor in the
face and upper limbs. The younger sibling of the proband is a 29-
year-old female who developed anxiety and depression at the age of
17 followed by increasing stiffness and tendency to extend her neck
and recurrent falls 2 years later. On examination 21, there was cogni-
tive impairment, mini-myoclonus in the upper limbs and face, asym-
metric Parkinsonism, loss of saccadic and pursuit upgaze and and
neck dystonia. The response to levodopa was excellent. Motor fluctua-
tions developed one year after medication. Psychotic symptoms devel-
oped at the age of 25. sEMG recordings showed myoclonic activity.
Conclusions: We illustrate the longitudinal history of KRS over a
10 year period and demonstrate neurophysiological findings in KRS
patients, which suggested the presence of facial action tremor in
addition to the previously described FFF.
Najim al-Din AS et al. Acta neurologica Scandinavica 1994
790
Progressive supranuclear palsy showing pure akinesia with gait
freezing Clinicopathological report of an autopsy case
E.J. Choi, D.G. Lee, S.K. Khang, C.S. Lee (Seoul, Korea)
 POSTER SESSION
Fig. 2. (790).
Objective: The purpose of this study is to understand the patho-
logic features of progressive supranuclear palsy(PSP) showing pure
akinesia with gait freezing(PSP-PAGF).
Background: The clinical diagnostic criteria for PSP-PAGF is
having progressive gait ignition failure and subsequent freezing of
gait, speech, or writing, without eye movement abnormality,rigidity,
tremor or dementia during the first 5 years of the disease (David R
Williams et al., 2009). Thus, the task of differentiating idiopathic
Parkinsons disease (IPD) from PSP could be confusing because of
freezing of gait. (David J Brooks et al.,2002).
Methods: We tested on MR imaging, PET CT scan and autopsy
as methods for differentiating PSP-PAGF from idiopathic Parkin-
sons disease.
Results: In his brain MR images, the sagittal and coronal sections
showed the humming bird sign and prominent atrophy of midbrain
was evident [figure1]From the autopsy, substantia nigra was pale
with almost complete loss of pigment, and neuronal loss was also
observed in red nucleus of midbrain, globus pallidus and dentate
nucleus of cerebellum (Zeshan Ahmed et al.,2008) (A.Mochizuki
et al.,2003). [figure2] Tau-positive neurofibrillary tangles were
observed in red nucleus and periaqueductal gray matter of midbrain
(Kersi Bharucha et al.,2013). [figure2]
Conclusions: We can see that this was a PSP patient with a 10-
year history of pure akinesia with gait freezing (PAGF), judging
from clinical findings and pathological results.
791
Parkinsonism due to neurosyphilis
M. Chraa, N. Kissani (Marrakech, Morocco)
Objective: The goal of this presentation is the describe 4 cases
who presented with an early onset Parkinsonism due to
neurosyphilis.
Background: Syphilis has become very rare in the western coun-
tries. In Morocco by contrast syphilis and neurosyphilis is still very
common. The most common form of neurosyphilis in our series is
chronic encephalopathy with dementia, but we had also experienced
some rare phenotypes like amyotrophic lateral sclerosis syndrome
and Parkinsonism.
Methods: We reviewed our series of neurosyphilis (from 2002 to
2014) followed in neurology department, Mohammed VI university
hospital of Marrakesh, and looked specifically into cases with Parkin-
sonism; we analyzed the clinical, radiological, biological and evolutif
profile of these cases.
S311
Results: We found 4 patients who presented with an early onset
Parkinsonism; they were all males, with an age between 22 and 46
years old. The clinical presentation of Parkinsonism was dominated
by rigidity without any case of tremor, one patient had also a focal
dystonia in his right upper arm, and two had mild dementia and hal-
lucinations, other atypical signs were also present in all cases. The
MRI performed in all cases was normal. The biological assessment
included liver function, complete blood cell counts, Blood sedimen-
tation rate and other inflammation tests, serology of hepatitis, HIV
and syphilis. All of these assessments were negatives except for
syphilis, we tested it also in CSL and found it positive. The patients
underwent a long treatment for their neurosyphilis based on penicil-
lin G (30M IU/day for 0 days every 3 month for one year). The evo-
lution was marked by an improvement in 1 case and stabilization in
the other cases after a follow up of 3 to 12 years.
Conclusions: We suspected the clinical presentation to be due to
neurosyphilis because of the early onset and the atypical presenta-
tions, but we were more confident in our diagnosis when we found
no other case in the patients respective families, when no other cause
was found and when the long follow up showed improvement or sta-
bilization in all cases. In light of these cases, we would like to
emphasize the importance of performing a syphilitic assessment in
rare presentation like Parkinsonism especially if the clinical presenta-
tion is atypical; this is truer if the patients are from countries with
high prevalence of syphilis like Morocco.
792
Corticobasal syndrome due to Creutzfeldt-Jakob disease: Report
of a case
C. Cosentino, Y. Nu~
nez, M. Velez, E. Sarapura, R. Suarez, L. Torres
(Lima, Peru)
Objective: To report a case of sporadic Creutzfeldt-Jakob disease
(CJD) with a corticobasal syndrome as initial and main feature.
Background: The term corticobasal syndrome was created to
include some diseases, others than Corticobasal degeneration, that
harbor clinical features like asymmetric Parkinsonism, apraxia, dys-
tonia, myoclonus and alien limb. The term CJD refers to a distinctive
cerebral disease in which a rapid progressive and profound dementia
is associated with diffuse myoclonic jerks and a variety of other neu-
rologic abnosrmalities mainly visual or cerebellar. A marked cortico-
basal syndrome has been rarely reported as the initial and main
clinical feature of CJD.
Methods: We present a case report of a 70 y-o woman who had
a duration of disease of four months before admission. She presented
Movement Disorders, Vol. 30, Suppl. 1, 2015
S312 POSTER SESSION

mild behavioral changes, sadness and a clumsy and jerky left arm.
Moderate hypokynesia and rigidity was found in left hemibody as
well as apraxia, heminegligence and alien limb phenomenon.Asterog-
nosia and agraphestesia were also found on admission. Less than six
weeks later she developed a mute state with diffuse myoclonic jerks.
Results: MRI showed T2 signal changes in the rigth lenticular
nuclei and frontal cortex. The EEG initially showed pseudoperiodic
sharp-wave complexes in the rigth hemisphere and some weeks later
in both hemispheres. Increased level of protein 14-3-3 in CSF.
Conclusions: This is one of the few reports of a prion disease
(CJD) initially manifested as an atypical Parkinsonism which
resembled to Corticobasal Degeneration. Close surveillance of clini-
cal features and awareness of neuroimaging signs will help making a
correct diagnosis.
mal pressure hydrocephalus, 2 post intraventricular bleed and 5 post
tubercularmeningitis], 7 patients had post-encephalitic Parkinsonism
[2 Human Immuno Virus associated], 18 patients had drug induced
Parkinsonism [9 neuroleptic associated, 4 antiemetic associated, 2
cinnarizine associated, 3 sodium valproate associated]. Acute disse-
minated encephalomyelitis was the cause in 5 patients, Osmotic
demyelination syndrome in 7 patients, Hyponatremia in 11 patients,
hypothyroidism in 2 patients, hypercalcemia in 3 patients, 4 patients
had Hashimotos encephalopathy, 7 patients had post hypoxic injury
Parkinsonism.
Conclusions: Our data suggests that vascular Parkinsonism is the
commonest cause of secondary Parkinsonism. Various metabolic and
drug induced factors are also an important and preventable cause of
secondary Parkinsonism.

793
To study falls in Parkinsons disease (PD)
A. Deep, A. Lieberman, R. Dhall, A. Tran, M.J. Liu (Phoenix, AZ,
USA)
Objective: To study falls in Parkinsons disease (PD).
Background: Falls, especially recurrent falls, are a major cause
of disability and morbidity in Parkinsons disease (PD). The costs
associated with falls in older people are estimated, by the Rand Cor-
poration, to reach $30 billion by 2020. These figures are higher in
PD, because more people with PD fall . If falls can be reduced in
PD, they could be reduced in other disorders.
Methods: 404 patients with PD were followed for a year in an
outpatient setting at The Muhammad Ali Parkinsons clinic.
Results: Twenty of the 404 patients underwent On- Off testing.
Of the 404 patients, 207 (51.2%) fell. 142 fell once, 65 fell more
than once. Single fallers resembled non- fallers in duration and
severity of PD. Recurrent fallers differed significantly, from single
and non- fallers in duration and severity of the PD and in impaired
locomotion: short steps. They also differed significantly from single
and non- fallers in prevalence of freezing of gait (FOG), postural
instability (the pull test) and static balance (inability to stand on
one leg < 3 seconds).
Conclusions: Locomotion, short steps, were significantly
decreased in recurrent versus single fallers and was less decreased in
single versus non- fallers. On off testing in 20 patients demon-
strated that locomotion (short steps) was improved by levodopa, bal-
ance was not. Overall in fallers, balance was more impaired than
locomotion. This suggests that impaired balance not locomotion is
the main causes of falls in PD.
795
Sudden onset Parkinsonism following hyponatraemia correction
G. Fabiani, H.A.G. Teive (Curitiba, Brazil)
Objective: To report a case of acute and severe Parkinsonism in
a patient during hyponatraemia correction associated with extrapon-
tine myelinolysis.
Background: Parkinsonism is a rare complication of central pon-
tine and extrapontine myelinolysis. Hyponatraemia is defined as a
serum sodium concentration bellow 135 mmol/L.
Results: We report a 70-year-old man admitted with complaints
of asthenia, hiccups, behavioral changes and somnolence. The patient
had hypertension and was under treatment with hydrochlorothiazide
25 mg daily. Laboratory exams showed Sodium levels of 102 mmol/
L. The medical team corrected the sodium slowly and after 48 hours
the sodium levels were 133 mmol/L, and the patient was discharged
absolutely normal.
After 2 days he came back to the hospital complaining of slow-
ness of movements, slurred speech, rest tremors, gait ataxia, facial
myokymias, drooling, rigidity and bradipsychism. He fulfilled the
diagnosis criteria for Parkinsonism. Brain MRI showed aspects of
osmotic demyelination syndrome/extrapontine myelinolysis.[figure1]

794
Spectrum of disorders presenting as secondary Parkinsonism in
a rural based medical teaching college in Western India
D.S. Desai, S.D. Desai (Anand, India)
Objective: To evaluate the different etiologies amongst patients
presenting with secondary Parkinsonism in a rural medical charitable
teaching hospital in Western India.
Background: Amongst patients presenting with Parkinsonism,
secondary Parkinsonism are an important group of disorders as many
amongst them are reversible/treatable if indentified early.
Methods: We retrospectively reviewed our hospital records
between Jan 2012 to October 2014 to look for patients who had a
secondary cause for Parkinsonism. Frequency of different causes of
secondary Parkinsonism was recorded. Parkinsomism was defined as
presence of 2 of rigidity, bradykinesia or tremor. All patients with
degenerative Parkinsonism were excluded. All patients were eval-
uated by a single neurologist.
Results: We found 104 patients who had secondary Parkinson-
ism. The mean age was 56 [23-79]. Vascular Parkinsonism was seen
in 31 of 104 patients, hydrocephalus was present in 9 patients [2 nor- Fig. 1. (795).

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION S313

Fig. 2. (795).

We decided to treat him with levodopa/benserazide 100/25 4 niam symptoms worsened progressively. Her Vitamin levels were
times daily. The patient responded very well to the medication. almost normal, except by slightly low levels of D Vitamin. Brain
Brain SPECT with TRODAT 99mTc showed normal distribution MRI was normal and Brain SPECT with TRODAT 99mTc [figure1]
of dopaminergic transporters [figure2] although it was done done
three months after we had initiated the treatment with levodopa. The
patient stopped with the medication for three days to do it.
Conclusions: We report a rare and severe case of Parkinsonism
and encephalopathy following rapid sodium correction. The patient
improved with Levodopa but he demands high doses of Levodopa/
benserazide: 200/50 4 times daily. The MRI was typical and the
Brain SPECT with TRODAT 99mTc was normal, one hypothesis is
the insufficient wash out period of only three days.

796
Young onset Parkinsonism after bariatric surgery
G. Fabiani, H.A.G. Teive (Curitiba, Brazil)
Objective: To report a case of young onset Parkinsonism after
bariatric surgery.
Background: Bariatric surgeries are increasing worldwide. Sev-
eral acute and long-term neurological complications have been iden-
tified. Ba F and Siddigi ZA published a paper that describes 3
patients one who developed Wernicke encephalopathy and two
developed clinical features of Parkinsonism.
Results: We report a 42-year-old woman who developed Parkin-
sonism after undergoing bariatric surgery. The patient had a rapid
weight loss (40 Kg in 4 months), hyperemesis during 2 months fol-
lowing the surgery. She was treated with domperidone. On the fourth
month after the procedure she started with bradykinesia, rest tremor
on left hand and left foot. Her olfaction was normal. The Parkinso- Fig. 1. (796).

Movement Disorders, Vol. 30, Suppl. 1, 2015

S314 POSTER SESSION
showed reduction in specific right striatal uptake(mainly posterior
putamen projection).
We decided to treat her with levodopa/benserazide 100/25 thrice
daily. The patient responded very well to our intervention.
Conclusions: We report a case of young onset Parkinsonism after
the patient underwent a bariatric surgery. There is only one paper
describing Parkinsonism after bariatric surgery. Our patient showed a
positive response to Levodopa and the Brain SPECT with TRODAT
99mTc showed reduction in specific right striatal uptake.
797
Progressive supranuclear palsy and statin use
A. Fuentes, D. Standaert, C. Marras, D. Riley, D. Hall, B. Kluger, J.
Juncos, S. Reich, D. Shprecher, Y. Bordelon, J. Jankovic, E. Carl, I.
Litvan (La Jolla, CA, USA)
Objective: To determine whether statin use is associated with a
decreased risk, later onset and benign phenotype of Progressive
Supranuclear Palsy (PSP).
Background: Recent studies have demonstrated that statins may
have neuroprotective effects, given their newly discovered anti-
inflammatory and immunomodulating characteristics. While the rela-
tionship between statin use and the risk of Parkinsons disease is
being researched, currently, no studies exist on the role of statins in
PSP.
Methods: Demographic and statin use information was collected
from 300 PSP cases and 300 age-and gender matched controls from
October 2006 to February 2013 via phone interview. Movement Dis-
order specialists used three validated instruments to collect neurolog-
ical data from the PSP cases: the PSP Rating Scale (PSP- RS), the
Unified Parkinsons disease Rating Scale (UPDRS) and the Mattis
Dementia Rating Scale (M-DRS). Subjects with missing data for the
statin questions were dropped from the analysis requiring that data.
A matched case-control analysis was conducted with a total of 297
case-control matched pairs. Odds ratios and 95% confidence intervals
were computed using conditional logistic regression models adjusting
for income, college degree obtainment, and ever having lived within
one mile from an agricultural area. For the PSP cases, linear regres-
sion models were fit to assess (1) the relationship between statins
and the age of onset of PSP and (2) the relationship between statins
and the severity of the disease, controlling for disease duration.
Results: Statin use for more than 6 months prior to the reference
date (10 years prior to the onset of symptoms in the cases) was noted
in 51 subjects (8.6%), of which 19 (6.4%) were cases and 32
(10.8%) were controls. There was no significant between-group dif-
ference for statin use. A significant association was observed
between statin use and a later age of onset of PSP (p50.024). How-
ever, when adjusting for the demographic variables, statin use was
no longer significant. Statin use did not show an association with the
disease rating scale scores.
Conclusions: We found that use of statins was not associated
with PSP risk or a more benign phenotype, although an association
was observed between the cholesterol- lowering medication and a
later onset of the disease. The possibility that long-term use of par-
ticularly blood-brain-barrier penetrating statins may reduce PSP risk
deserves further consideration.
798
Usefulness of cardiac 123I-MIBG uptake, olfactory function and
substantia nigra hyperechogenicity in distinguishing between
Parkinsons disease and Parkinsonian syndrome
H. Fujita, K. Suzuki, A. Numao, Y. Watanabe, M. Miyamoto, T.
Miyamoto, H. Takekawa, T. Kadowaki, K. Hashimoto, K. Hirata
(Mibu, Japan)
Objective: The purpose of this study was to evaluate the useful-
ness of combined use of cardiac 123I-metaiodobenzylguanidine
Movement Disorders, Vol. 30, Suppl. 1, 2015
(MIBG) uptake, olfactory function test, and substantia nigra (SN) hypere-
chogenicity on transcranial sonography (TCS) in differentiating Parkin-
sons disease (PD) from Parkinsonian syndrome (PS) such as multiple
system atrophy (MSA) and progressive supranuclear palsy (PSP).
Background: It is sometimes difficult to clinically differentiate
PD and PS.
Methods: Cardiac MIBG scintigraphy, a card-type odor identifica-
tion test (Open Essence, Wako, Japan), and TCS were carried out in 85
patients with PD (age, 68.4 6 9.0 years), 21 patients with MSA (age,
67.8 6 7.8 years), and 16 patients with PSP (age, 71.9 6 7.6 years).
Results: The delayed heart-to-mediastinum (H/M) ratio of cardiac
123
I-MIBG uptake (1.95 6 0.87 vs. 2.90 6 0.51) and scores of open
essence (4.0 6 2.3 vs. 6.1 6 2.7) were significantly lower in patients
with PD compared with patients with PS (MSA and PSP). SN hyper-
echogenic area on TCS was larger in patients with PD compared
with patients with PS (0.21 6 0.14 vs. 0.08 6 0.07 cm2). The area
under the ROC curve for cardiac MIBG scintigraphy, olfactory func-
tion test, and SN hyperechogenic area in differentiation of PD from
PS were 0.8 (95%CI, 0.72-0.89), 0.8 (95%CI, 0.70-0.90), and 0.76
(95%CI, 0.67-0.86), respectively. The sensitivity and specificity of at
least one positive result of olfactory function test (open essence score
4), cardiac MIBG scintigraphy (delayed H/M ratio <2.00) and SN
hyperechogenicity (SN hyperechogenic area 0.18cm2) in diagnosis
of PD were 93% and 68%, respectively.
Conclusions: A combined use of cardiac MIBG scintigraphy, SN
hyperechogenicity, and olfactory function test may be useful in dis-
tinguishing PD and PS.
799
Relationship between serum uric acid concentration and disease
progression in multiple system atrophy
J. Fukae, S. Yanamoto, S. Fujioka, T. Hatano, A. Mori, T. Nomi, K.
Fukuhara, N. Hattori, Y. Tsuboi (Fukuoka, Japan)
Objective: In this study, we evaluated whether the uric acid
(UA) concentration might influence disease progression in patients
with multiple system atrophy (MSA).
Background: Serum UA concentration may affect the progres-
sion of neurodegenerative disorders, such as Parkinsons disease,
Huntingtons disease, and amyotrophic lateral sclerosis.
Methods: A total of 46 Japanese MSA patients (21 male patients,
25 female patients) were enrolled in this study. All MSA patients
met the probable MSA clinical diagnostic criteria. The severity of
MSA was assessed by the unified MSA rating scale (UMSARS) part
IV (Global Disability Scale: GDS). The progression rate of MSA
was defined as GDS changes per year. Spearman rank correlation
was used to estimate relationship between disease progression in
MSA and UA concentration.
Results: The average of UA concentration of all MSA patients
was 4.7 6 1.2mg/dl. The average of UA concentration were higher in
male MSA patients (5.2 6 1.1mg/dl) compared to female MSA
patients (4.2 6 1.2mg/dl). Correlation analysis revealed serum UA
concentration had a negative correlation with GDS changes per year
in male MSA patients (g 5 - 0.45, p 5 0.04), while there is no corre-
lation in female MSA patients (g 5 - 0.16, p 5 0.45).
Conclusions: Although pathogenic cause of MSA is still
unknown, it has been suggested that oxidative stress may be associ-
ated with MSA pathology according to several evidences. This study
also demonstrated that serum UA concentration inversely correlated
with disease progression in male MSA patients, possibly because UA
is natural antioxidant.
800
A case of vascular Parkinsonism simultaneous with progressive
supranuclear palsy (PSP)
I. Gabrielyan, H. Amirjanyan, K. Harutyunyan, G. Avagyan, H.
Hambardzumyan, H. Manvelyan (Yerevan, Armenia)
 POSTER SESSION
Objective: Parkinsonism is a neurological syndrome, character-
ized by bradykinesia, rigidity, rest tremor and postural instability,
which most often is due to Parkinsons disease (PD) and rarely
Parkinson-Plus syndromes or various secondary causes.
Background: A 58 year old male with a history of Hypertension,
Ischemic Heart Disease and vascular Parkinsonism presented in the
out-patient department with slowness of movements, gait disturbance
and frequent falls within last few months. Patient is receiving L-
DOPA for 3 years, which was slightly effective.
Methods: Complete neurological examination, laboratory analy-
ses, neuroimaging studies and cognitive tests were performed. Neuro-
logical examination revealed dysarthria, vertical gaze restriction,
bradykinesia, axial rigidity and postural instability. Laboratory tests
were within normal ranges. Brain MRI was performed a year ago,
which showed multiple widespread vascular lesions.
Results: Despite of increasing L-DOPA dosage and adding
DOPA-agonist, neurological deterioration occurred with worsened
vertical gaze palsy and multiple falls. Brain MRI was repeated,
which showed multiple vascular abnormalities and brainstem changes
in form of hummingbird sign. Based on these findings additional
diagnosis of PSP was established.
Conclusions: Even though the case was typical for vascular Par-
kinsonism other causes should be taken into consideration.
801
Lose-dose lithium therapy improved off time without worsened
dyskinesias in a patient with Parkinsons disease
T. Guttuso (Buffalo, NY, USA)
Objective: To determine if low-dose lithium therapy (target
serum level 0.4-0.5 mmol/L) was associated with a reduction in off
time without worsened dyskinesias in Parkinsons disease patients
with motor fluctuations.
Background: Lithium has shown neuroprotective actions in many
preclinical Parkinsons disease (PD) models including an ability to
prevent alpha-synuclein aggreation, in vivo. Previous clinical trials
have shown lithium therapy to be associated with a mean 70%
reduction in off time among 5 of 6 patients with Parkinsonism
experiencing a mean 14 hours of off time/day. However, all 5
patients eventually (after 3-28 weeks) developed severe dyskinesias
and 2 also developed hallucinations. The serum lithium levels for
these 5 patients ranged from 0.78-0.85mmol/L.
Methods: After a patient with PD for 9 years and bipolar disor-
der for 4 years reported a subjective 65% reduction in off time
within 2 months after starting low-dose lithium therapy, 5 more
patients with PD and bothersome off time were started on low-
dose lithium therapy (target serum level of 0.4-0.5mmol/L) in an
open-label fashion and followed for subjective changes in off time
and dyskinesias.
Results: The original PD patient with bipolar disorder has been
on lithium for 32 weeks without any worsened dyskinesias and with
a sustained subjective 65% decrease in off time despite a slight
reduction in his daily levodopa dose over this time period. The
serum lithium level was 0.37mmol/L for the first 16 weeks and, after
the dose was increased, 0.48mmol/L for the last 18 weeks. The other
5 PD patients have received lithium for 7-9 weeks and none have
developed any worsened dyskinesias at serum lithium levels of 0.32-
0.50mmol/L. One patient with Hoehn & Yahr stage 4 PD and
dementia developed nocturnal urinary incontinence that resolved
after discontinuing lithium. Three of the other 4 patients have
reported noticeable improvements in their off time and 1 has
decreased her daily levodopa dose.
Conclusions: Low-dose lithium therapy may not be associated
with worsened dyskinesias as has been reported with regular dose
lithium therapy, however, longer follow-up among more PD patients
is needed. Low-dose lithium therapy may also improve off time;
however, this preliminary finding would need to be evaluated in a
S315
randomized controlled trial considering the high placebo effects that
occur in this patient population.
802
Observing of the incidence and characteristics of Parkinsons
disease in the neurology clinic of University of Uyo Teaching
Hospital, Uyo, Nigeria
P.H. John, T.L. Agunbide, L.O. Agumbide, G.A. Omisore, F.O. Dike
(Uyo, Nigeria)
Objective: To describe the incidence and characteristics of Par-
kinsons disease[PD] among Neurology outpatients in the University
of Uyo Teaching Hospital, Uyo, Nigeria.
Background: PD is a progressive degenerative Movement Disor-
der.It is a disease that affects individuals above the age of 65. Due
to previously inadequate data and publications on incidence of PD in
Nigeria, the disease had until recently been thought to be hard to
come by in Nigerian communities. However, Owolabi
et al(2012)reported 83.3% in northern Nigeria.
Methods: This is a retrospective study in which case, a register
of all neurology outpatients was used to retrieve all new PD cases
between October 2013 and October 2014.
Results: Out of 95(12.7%) new referral in the neurology clinic
twelve had features of Parkinsonism during the period, this
accounted for the most common Movement Disorder cases. Eight
(67%) were males whereas four (33%) were females with a mean
age of 68. Eleven of the patients (91.7%) had idiopathic PD while
the other present with young onset atypical Parkinsonism. While
only four (33%) present within the first six months of onset of first
symptom, a majority 67% presented after six months. Majority
(58.3%) of the cases were either civil servants or retired while
41.7% were artisans or farmers. Most (58.3%) of the patients pre-
sented the Hoehn and Yahr Stage II of the disease while quarter
(25%) had cognition impairments on initial presentation. Most
(91.7%) of the patients were on Levodopa-Carbidopa medications
with anticholinergic while deep brain stimulation (DBS) has never
been tried within the hospital facility of study. Poor clinic compli-
ance and default were challenges as a significant 58.3% were found
either to have missed a clinic appointment (of three) or defaulted.
Conclusions: PD is more common in our neurological practice
than earlier thought, with an established male preponderance. Late
presentation and early defaults are common. There should be general
education at community level on early presentation while general
practitioners should also be educated to refer cases of PD to the Neu-
rologist promptly.
803
Meningioma presenting as tremor dominant Parkinsonism
T. Khan, S.A. McMahan (Weston, FL, USA)
Objective: We describe a case of secondary tremor dominant
Parkinsonism due to meningioma.
Background: Brain tumors are a rare cause of Parkinsonism, but
there have been cases noted in the literature with regard to meningio-
mas presenting as Parkinsonism.
Methods: Case report.
Results: A 73 year old woman came for evaluation of right hand
tremors. Started 3-4 months prior. Tremor did not interfere with
overall functionality. No particular trigger and not relieved by
alcohol.
Neurological examination showed decreased arm swing on right,
right arm resting tremor and rigidity noted at metacarpal joints bilat-
erally. Reflexes, sensory and gait exam normal. Cognitive impair-
ment noted per family.
DAT scan came back suggestive of Parkinsons disease. MRI
brain ordered later to evaluate cognitive impairment showed large
left frontal mass consistent with meningioma. After resection, patient
Movement Disorders, Vol. 30, Suppl. 1, 2015
S316 POSTER SESSION
had minimal residual tremor but arm swing and rigidity improved
completely. Some features of cognitive impairment persisted.
Conclusions: Meningiomas are common benign central nervous
tumors, but an uncommon cause of Parkinsonism. In this case, dis-
tortions from meningioma made DAT scan appear abnormal. This
case demonstrates importance of fully evaluating for secondary
causes of Parkinsonism before starting any potential therapies.
804
123I-MIBG myocardial scintigraphy and neurocirculatory
abnormalities in dementia with Lewy bodies
J.S. Kim, H.E. Park, Y.S. Oh, I.S. Park, K.S. Lee (Seoul, Korea)
Objective: The hypothesis tested in this study was that the spon-
taneous feature of Parkinsonism might contribute neurocirculatory
abnormalities and cardiac sympathetic denervation attending Demen-
tia with Lewy bodies (DLB).
Background: DLB is the second most common cause of degener-
ative dementia after Alzheimer disease (AD). To improve the diag-
nosis of DLB, the latest diagnostic criteria incorporate findings from
neuroimaging studies including cardiac sympathetic denervation. The
spontaneous feature of Parkinsonism is one of the core features of
probable DLB, however it is not essential for diagnosis of this
disease.
Methods: Twenty-two consecutive patients with probable DLB
were enrolled in this study; 25 age-matched controls, 22 AD and 24
Parkinsons disease dementia (PDD) patients were also evaluated.
The DLB patients were classified as DLB with Parkinsonism and
without Parkinsonism by assessing Parkinsonian motor manifesta-
tions. MIBG uptake was assessed using the ratio of the heart to the
upper mediastinum (H/M) according to planar scintigraphic data and
orthostatic vital signs and ambulatory 24-hour blood pressure moni-
toring were recorded.
Results: The mean H/M ratio was significantly lower and the pro-
portion of orthostatic hypotension (OH) and supine hypertension
(SH) were higher in patients with DLB and PDD than in those with
AD and age-matched controls. In patients with DLB, spontaneous
Parkinsonism was not related the degree of cardiac sympathetic
denervation or did not influence the neurocirculatory abnormalities
such as OH, SH, non-dipping or nocturnal hypertension.
Conclusions: Our results provide that myocardial postganglionic
sympathetic denervation found in PD is also present in patients with
DLB regardless of presence of spontaneous Parkinsonism. MIBG
scintigraphy and autonomic function tests may be useful to help dis-
tinguish between DLB and AD patients in clinical practice.
805
A neuroimaging rating scale with adjustable diagnostic validity
to enhance the inter-rater reliability of hummingbird sign
Y.J. Kim, Y.E. Kim, S.Y. Kang, H. Ma (Anyang, Korea)
Objective: To enhance inter-rater reliability (IRR), we developed
a new radiologic rating scale for HBS (HBS-RS).
Background: Although Hummingbird sign (HBS) is a distinctive
feature of progressive supranuclear palsy (PSP) vs. idiopathic Parkin-
sons disease (IPD) and other Parkinsonian disorders, there are no
consensus criteria for its identification.
Methods: Two raters blinded to the clinical diagnoses reviewed
T1 midsagittal magnetic resonance images of 133 patients with
IPD (n593) or PSP (n540). The existence of HBS was assessed
in two steps, separated by two weeks, based first on their own
experience and then according to the HBS-RS. The HBS-RS com-
prises 4 items (contour of third ventricle floor, shape of beak,
shape of Hummingbird head, and midbrain atrophy), with weighted
scores from 0 to 2.
Results: IRRs of individual items in HBS-RS and of composite
scores showed moderate to good agreement (Cohens kappa [j],
Movement Disorders, Vol. 30, Suppl. 1, 2015
0.479 - 0.766) and were observed to be highest in item #1. IRRs
for HBS-RS total scores were better than for HBS (j, 0.666 VS.
0.596). Sensitivities and specificities varied depending upon cut-off
for each item or for composite scores. Sensitivities for each item
were high (85.0 - 92.5) at a low cut-off (0 VS. 1 or 2). Specific-
ities reached higher than 80% by using composite scores of HBS-
RS. Receiver operating characteristic curves for HBS-RS total
score showed fair diagnostic accuracy for PSP (AUC, 0.76 and
0.73).
Conclusions: HBS-RS is a simple and measurable visual assess-
ment tool to identify HBS with higher inter-rater agreement and
adjustable diagnostic validity for PSP.
806
Things better than levodopa in post-encephalitic Parkinsonism
R. Kim, C.W. Shin, H.J. Kim, B.S. Jeon (Seoul, Korea)
Objective: To present a patient with post-encephalitic Parkinson-
ism caused by tick-borne encephalitis showing better response to
dopamine agonists than to levodopa.
Background: Post-encephalitic Parkinsonism is a rare disorder
reported in patients with encephalitis by a variety of viruses includ-
ing Japanese B virus, Influenza Type A, St Louis virus and HIV, and
in patients with tick-borne encephalitis. According to previous cases,
levodopa is usually very effective in post-encephalitic Parkinsonism.
Methods: Case report.
Results: In May 2006, a 26-year old man was admitted to a hos-
pital in Russia with daytime hypersomnolence, recurrent fever and
headache after a tick bite. He was diagnosed with tick-borne enceph-
alitis. By May 2007, he began to drag his feet and often fell down
losing his balance. He developed resting tremor and generalized
rigidity. Levodopa was given with good response. However, he
became unresponsive to levodopa since 2010. He was maintained on
levodopa 100 mg three times a day without dose increment due to
levodopa-induced dyskinesia. In April 2014, he was referred to us
for a second opinion. Neurologic examination at admission showed
severe postural instability and bradykinesia. He had subtle tremor
and rigidity. MRI of the brain showed diffuse brain atrophy (figure
A) without a definite lesion in the midbrain (figure B). 18FP-CIT
positron emission tomography (PET) study demonstrated a severely
reduced uptake in the bilateral putamen and caudate (figure C).[fig-
ure1] Discontinuation of levodopa for 10 days did not make any
change in the condition. Pramipexole was gradually increased to
3mg/d with gratifying improvement in bradykinesia, rigidity and
alertness and waking hours. At last follow-up in July 2014, he
showed marked improvement of postural instability (postural stability
score of UPDRS 0 from 3). However, impulse control disorder such
as compulsive playing with the computer was reported.
Conclusions: Clinicians should be aware that dopamine agonists
might be more effective than levodopa in late stage of post-
encephalitic Parkinsonism. However, dopamine agonist should be
cautioned against the risk of developing impulsive control
disorders.
Fig. 1. (806).
 POSTER SESSION
Fig. 1. (807).
807
Unusual manifestation of dural arteriovenous fistula presenting
with Parkinsonism and impaired smooth pursuit eye movement
K.H. Kim, Y.S. Park, W.T. Yoon, B.C. Suh, H.S. Moon, P.W. Chung,
Y.B. Kim (Seoul, Korea)
Objective: Our aim is to report a case of unusual manifestation
of dural arteriovenous fistula (DAVF) which shows reversible Parkin-
sonism and impaired smooth pursuit eye movement.
Background: Dural arteriovenous fistula (DAVF) is an abnormal
direct connection between dural arteries and dural venous sinus or
cortical veins and potentially treatable neurologic conditions. Parkin-
sonism has been reported presenting as manifestation of DAVF. But
Parkinsonism with impaired smooth pursuit eye movement was not
reported in DAVF. We report a patient with DAVF who presented
with Parkinsonism and impaired smooth pursuit movement of eye.
Methods: Single case report.
Results: A 52-year-old complained of gait disturbance and hypo-
phonia for 2 months duration.At admission, the patient had apparent
asymmetric bradykinesia and rigidity, masked face, hypophonia,
short-stepped gait and impaired smooth pursuit eye movement.
Diffusion-weighted, FLAIR and T2-weighted magnetic resonance
(MR) imaging revealed diffuse high intensity lesions in deep white
matter of right temporoccipital area and both basal ganglia. [figure1]
3D TOF MRA revealed the apparently inflated right middle menin-
geal cortical vein connected with the right transverse-sigmoid sinus.
Tracking test showed symmetric cogwheel pattern and the gain was
left 1.26, right 1.56, vertical 1.59 at 0.30Hz, 0.50Hz. Conventional
carotid angiography was performed and digital subtraction angiogra-
phy (DSA) revealed the obstruction of right transverse sigmoid sinus
and feeding artery was right occipital artery. The patient was treated
with anticoagulation and embolization of the occipital feeder vessels
by Onyx. One month later, Parkinsonism and smooth pursuit eye
movement were fully recovered.
Conclusions: The pathogenesis of DAVF with Parkinsonism is
not unclear, but it was postulated that venous congestion in basal
ganglia and frontal lobe hypoperfusion may be associated with devel-
oping Parkinsonism in DAVF. Our patient showed the suspicious
MRI findings of the venous congestion in basal ganglia. Also,
smooth pursuit eye movement is associated with various area of
brain included cerebral cortex, cerebellum, brain stem. In general,
the clinical and imaging features of DAVF are non-specific and diag-
nosis is often delayed or missed. This case could propose that pro-
gressive Parkinsonism with impaired smooth pursuit eye movement
might be associated with DAVF.
808
Diagnostic accuracy of multiple system atrophy: An autopsy
study of 134 patients
S. Koga, N. Aoki, R.J. Uitti, J.A. van Gerpen, W.P. Cheshire, K.A.
Josephs, Z.K. Wszolek, W. Langston, D.W. Dickson (Jacksonville,
FL, USA)
Objective: To determine ways to improve diagnostic accuracy of
multiple system atrophy (MSA), we assessed the diagnostic process
in autopsy-examined patients diagnosed with MSA during life, com-
pared clinical and pathological features between those who proved to
S317
have MSA pathologically and those who did not (non-MSA patients),
and reviewed causes of misdiagnosis in non-MSA patients.
Background: MSA is a sporadic, progressive neurodegenerative
disorder characterized by a variable combination of autonomic fail-
ure, Parkinsonism, cerebellar ataxia, and pyramidal symptoms. Even
with the well-established diagnostic criteria for multiple system atro-
phy (MSA), clinical features overlapping other neurodegenerative
disorders pose a major challenge for an accurate clinical diagnosis.
Methods: A retrospective examination was performed of 134
consecutive patients that had a clinical diagnosis of MSA at the time
of death. All cases underwent a standardized neuropathological
assessment for Alzheimer-type and Lewy-related pathologies. One
hundred twenty-five clinical records were available for review. Clini-
cal and pathological features were compared between patients with
autopsy-confirmed MSA and those with other pathological diagnoses,
including pathologically-confirmed dementia with Lewy bodies
(DLB), Parkinsons disease (PD), and progressive supranuclear palsy
(PSP).
Results: Of the 134 clinically diagnosed MSA patients, 83 (62%)
had the correct diagnosis at autopsy. DLB (14%) was the most com-
mon misdiagnosis, followed by PSP (11%) and PD (6%). Despite
meeting pathologic criteria for intermediate-to-high likelihood DLB,
several DLB patients did not have dementia and none had significant
Alzheimer-type pathology. Autonomic failure was the leading cause
of misdiagnosis in DLB and PD, and cerebellar ataxia was the lead-
ing cause of misdiagnosis in PSP.
Conclusions: The diagnostic accuracy for MSA was poor in this
autopsy study. Pathologically confirmed DLB, PD, and PSP were the
most common diseases to masquerade as MSA. This has significant
implications not only for patient care, but for research studies in
MSA that do not have pathological confirmation.
809
Effects of isradipine in a transgenic mouse model of multiple
system atrophy
F. Krismer, M. Schonfeld, H. Oberacher, J. Striessnig, W. Poewe, N.
Stefanova, G.K. Wenning (Innsbruck, Austria)
Objective: To examine the neuroprotective efficacy of Isradipine
in a transgenic multiple system atrophy (MSA) mouse model.
Background: MSA is a relentlessly progressive neurodegenera-
tive disorder of unknown etiopathogenesis. The clinical presentation
is variable with autonomic, Parkinsonian and cerebellar symptoms in
any combination. There is currently no interventional therapy avail-
able that has a positive impact on the rapidly progressive nature of
this devastating disease. Similar to Parkinsons disease (PD), a-
synuclein (aSYN) is meant to be a key protein in the pathogenesis
of MSA. The subcellular hallmark feature of MSA are aSYN-
immunoreactive glial cytoplasmic inclusions. In preclinical research,
MSA inclusion pathology may be replicated by transgenic (tg) ovex-
pression of aSYN under oligodendroglial promoters. In preclinical
toxin models of PD, Isradipine, a L-type calcium channel blocker,
was neuroprotective.
Methods: A total of 20 (PLP)- a-synuclein transgenic mice at 2
months of age were enrolled in our study. Isradipine was delivered
by subcutaneous implantation of continuous release pellets with
biodegradable-carrier bound Isradipine (target doseage: 3lg/g b.w./
day, increasing Isradipine/pellet concentrations were used to account
for age- and housing-related weight gain). Control animals were
implanted a subcutaneous inert placebo pellet. The implantation pro-
cedure was performed in week 1 of the experiment and repeated
every second month.
Results: As expected, Isradipine could not be detected in any of
the control animals, whereas treated mice had an average Isradipine
plasma level of 6.6 6 1.9 ng/ml. There was no significant difference
in any of the performed motor behavior tests which included pole
test, beam walking, grip strength. Stereology-based cell counts of
TH-immunoreactive neurons within the Substantia nigra pars
Movement Disorders, Vol. 30, Suppl. 1, 2015
S318 POSTER SESSION

compacta failed to show significant neuroprotection in Isradipine- (ATR) and left cingulumhippocampus (CgH). The associations
treated mice. Measurements of relative optical densitiy of TH- between clinical symptoms of INPH and DTI measures were most
immunreactive nerve terminals within the striatum were not different commonly found in the CgH. Higher MD in the CgH correlated with
between the two treatment arms. poorer cognitive performance. Higher MD in the right CgH also cor-
Conclusions: Long-term Isradipine treatment did not alleviate related with gait or motor dysfunction. Lower FA in the right CgH
motor impairment in a transgenic MSA mouse model. Based on was correlated with urinary disturbance and cognitive impairment.
immunohistochemistry, there was no clear evidence of neuroprotec- Lower FA values in the corticospinal tract (CST) and right ATR sig-
tion at the nigral level. These results suggest that continuous Isradi- nificantly correlated with poorer cognitive performance, and corre-
pine treatment at the dose given did not mediate a functionally lated with gait dysfunction. Higher MD in left CST correlated with
relevant neuroprotection in a transgenic MSA mouse model. cognitive impairment.
Conclusions: Our findings may suggest a possibility for consider-
ing microstructural changes in white matter in ventriculomegaly
810 patients as potential imaging markers for the prediction of CSFTT
Possible neuroprotective mechanism of atorvastatin and responders. We suppose that DTI parameters may help to assess cog-
simvastatin in experimental model of Parkinson-like symptoms nitive dysfunction, gait, and motor deterioration in INPH, along with
urinary disturbance.
A. Kumar, N. Sharma, J. Mishra (Chandigarh, India)
Objective: The present study was carried out to evaluate the neu-
roprotective effect of HMG-CoA reductase inhibitors (atorvastatin 812
and simvastatin) against 6-hydroxydopamine (6-OHDA) model of
PD. Cognitive impairments associated with morphological changes in
Background: Neuroinflammation and oxidative stress plays key cortical and subcortical structures in multiple system atrophy of
role in pathophysiology of Parkinsons disease (PD). Studies demon- the cerebellar type
strated that neuroinflammation and associated infiltration of inflam- M.J. Lee, J.H. Shin, J.K. Seoung, J.H. Lee, U. Yoon, J.H. Oh, D.S.
matory cells into central nervous system is inhibited by 3-hydroxy-3- Jung, E.J. Kim (Busan, Korea)
methylglutaryl co-enzyme A (HMG-CoA) reductase inhibitors. Objective: We investigated the association between morphomet-
Methods: In the present study, the animals were divided into ric changes in cortical and subcortical structures and cognitive
nine groups, comprising 15 animals in each group. Group I: Nave impairments in MSA-C to explore the neural correlates responsible
(without treatment); Group II: Sham (surgery performed, vehicle for cognitive deficits in MSA-C.
administered); Group III: Intrastriatal 6-OHDA (20 mg) (single, uni-
lateral injection); Group IV: Atorvastatin (20 mg/kg) per se; Group
V: Simvastatin (30 mg/kg) per se; Group VI & VII: 6-OHDA (20
mg) 1 atorvastatin (10 & 20 mg/kg) respectively; Group VIII & IX:
6-OHDA (20 mg) 1 simvastatin (15 & 30 mg/kg) respectively.
Results: Intrastriatal administration of 6-OHDA (4 ml of 5 mg/ml)
significantly caused impairment in body weight, locomotor activity
and rota-rod performance, oxidative defence (increased lipid peroxi-
dation, nitrite concentration and depleted glutathione levels) and
mitochondrial enzyme complex activities (decreased complex-I activ-
ity and redox activity) as compared to nave animals. Atorvastatin
(20 mg/kg) and simvastatin (30 mg/kg) drugs treatment for 14 days
significantly improved these behavioural, biochemical and mitochon-
drial enzyme complex activities as compared to control (6-OHDA)
group.
Conclusions: In conclusion, the findings of the present study
demonstrate the neuroprotective potential of atorvastatin and simva-
statin in experimental model of 6-OHDA induced Parkinsons like
symptoms.

811
Diffusion tensor imaging of idiopathic normal-pressure
hydrocephalus and the cerebrospinal fluid tap test
H.W. Lee, P.W. Ko, D. Choi, K. Kang, U. Yoon (Daegu, Korea)
Objective: We evaluated relationships between diffusion tensor
imaging (DTI) parameters and clinical profiles in idiopathic normal-
pressure hydrocephalus (INPH) patients, along with differences in
these DTI measures between CSF tap test (CSFTT) responders and
non-responders.
Background: Damaged neural tracts contribute to the symptoma-
tology of INPH. DTI is sensitive to microstructural changes in white
matter not always detectable with ordinary MRI.
Methods: Fifty-four INPH patients (26 CSFTT responders and 28
CSFTT non-responders) constituted the final group for analysis. Frac-
tional anisotropy (FA) and mean diffusivity (MD) were assessed
using atlas-based tract mapping methods for 12 different fiber tracts.
Results: CSFTT non-responders, when compared to responders,
showed lower FA values in the left anterior thalamic radiation Fig. 1. (812).

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
Fig. 2. (812).
Background: Patients with the cerebellar variant of multiple sys-
tem atrophy (MSA-C) often show cognitive deficits in various cogni-
tive domains. However, the pathogenic mechanism of neural
correlates causing the cognitive impairments in MSA-C are still
unknown.
Methods: Using surface-based morphometry, we examined
regions of interest (ROIs) cortical thickness and the volumes and
shapes of subcortical structures in 18 patients who fulfilled the crite-
ria of probable MSA-C and compared them to fifty healthy controls.
The association between regional changes and cognitive functions in
MSA-C were investigated by applying linear regression analyses
after controlling for confounding factors.
Results: Compared with controls, the patients with MSA-C
showed significant cortical thinning in the fronto-temporo-parietal
regions and volume reduction in subcortical structures with shape
changes (figure 1A). When shapes of subcortical structures were
compared without correction for multiple testing, MSA-C patients
showed multifocal regional atrophies in the bilateral caudate
nucleus, putamen, thalamus, pallidum, hippocampus and amygdala
(figure 1B).[figure1] Cerebellar volume had no significant effect
on cortical and subcortical volumes. The severity of atrophic
changes in the bilateral thalamus, the left cerebellum, and the
left pericalcarine gyrus were significantly correlated with atten-
tional, executive, and visuospatial dysfunctions (figure 2).
[figure2]
Conclusions: Cognitive impairment in MSA-C might result
from functional disruption of corticostriatal and pontocerebellar
circuit mediated by primary cortical, cerebellar, or thalamic
pathology.
S319
813
Retinal nerve fiber layer and retinal thickness changes in
multiple system atrophy
J.Y. Lee, J. Ahn, T.W. Kim (Seoul, Korea)
Objective: To evaluate in this study, we compared both peripapil-
lary retinal nerve fiber layer (RNFL) and perifoveal retinal thickness
in multiple system atrophy (MSA) patients with analyzing retinal
thickness according to the severity of this disease, and also to compare
retinal changes in subgroup of MSA-C and MSA-P patients.
Background: MSA is a rapidly progressive neurodegenerative
Parkinsonian disorder. Patients often go totally dependent within sev-
eral years whereas current treatment of MSA is only symptomatic,
thus development of biomarkers for early detection of the disease
and for monitoring progression are necessary. There is a report that
retina is pathologically involved in neurodegenerative diseases such
as PD and DLB. Optical coherence tomography (OCT) studies have
shown retinal thining in these disorders. Thus, retinal layer evalua-
tion using the OCT may be a potential in-vivo biomarker for MSA.
Methods: A total of 36 MSA patients and 71 control subjects
underwent general ophthalmologic examination and OCT scans.
MSA patients were subtyped into MSA-P (27 patients, 52 eyes) and
MSA-C (9 patients, 17 eyes) groups. Peripapillary RNFL thickness
and perifoveal retinal thickness were compared.
Results: MSA patients showed significantly decreased superior,
inferior, superotemporal and inferotemporal RNFL thickness and
perifoveal retinal thinning in the superior and inferior outer sectors
compared to controls. The superior, inferior, nasal, superotemporal,
inferotemporal, and global average RNFL thicknesses were markedly
Movement Disorders, Vol. 30, Suppl. 1, 2015
S320 POSTER SESSION
decreased when MSA-P patients were compared to the control group
whereas there was no significant difference between MSA-c and con-
trols. As for perifoveal retinal thickness, the superior and inferior
outer sectors were decreased in MSA patients and for MSA-P
patients, the temporal outer sector also showed significantly
decreased retinal thickness compared to control. The unified MSA
rating scale (UMSARS) scores and the Global disability scores
(GDS) showed a consistent and significant negative correlation with
perifoveal retinal thickness .
Conclusions: Peripapillary RNFL and perifoveal retinal thinning
was observed in MSA patients, especially the MSA-P subtype. Para-
macular retinal thinning showed negative correlation with UMSARS
and GDS. The topographic pattern of RNFL and retinal thinning
may correlate with the degree and pattern of neurodegeneration
occurring in MSA.
814
The contribution of cerebellar cortex to cognitive impairment in
multiple system atrophy using a probabilistic MR atlas-based
topographic analysis
J.J. Lee, D.K. Lee, J.H. Ham, J.M. Lee, Y.H. Sohn, P.H. Lee (Seoul,
Korea)
Objective: To investigate contribution of cerebellar cortex to
cognitive impairment in patients with multiple system atrophy
(MSA).
Background: The cortical-subcortical deafferentiation has been
well recognized as a main pathomechanism of cognitive dysfunctions
in MSA. In addition, the cerebellum has been suggested to have an
additional role in cognitive process in healthy controls and neurode-
generative disorders via several cortico-cerebellar pathways.
Methods: A total of 61 consecutive MSA patients (30 men and
31 women) who completed the brain magnetic resonance image and
comprehensive neuropsychological tests at initial evaluation were
enrolled. Using a probabilistic MR atlas of the human cerebellum,
the correlation analyses were conducted between cognitive perform-
ance and topographic volume of the cerebellum. Age at diagnosis,
sex, disease duration and intracranial volume were determined as
basic adjustment factors, and furthermore, an additional adjustment
for the basal ganglia volume was carried out to identify independent
role of cerebellar cortex in cognitive performance.
Results: When adjusting basic demographic factors, cerebellar
cortices that exhibited a significant correlation with cognitive per-
formance were as followed; cerebellar lobule IX (for verbal episodic
memory; lobules V, VIIb, VIIIa for visual episodic memory; lobule
X for contrasting program; lobules I-IV, V, VI, Crus II, VIIb, VIIIa,
VIIIb, IX and X for Go-no-go test. After further adjusting the basal
ganglia volume, these associations of cerebellar volume and cogni-
tive performance remained significant; lobule IX for episodic mem-
ory, lobule X for contrasting program; lobules I-IV, VI, Crus II, IX
and X for Go-no-go test; lobule VIIIa for stroop color test.
Conclusions: Our data demonstrate that cerebellar cortex may
play an important role in cognitive dysfunction in patients with
MSA, of which the frontal executive and episodic memory function
are closely associated with cerebellar cortex.
815
American multiple system atrophy natural history study
P.A. Low, S.G. Reich, J. Jankovic, C.W. Shults, M.B. Stern, P.
Novak, C.M. Tanner, S. Gilman, F.J. Marshall, F. Wooten, B.
Racette, T. Chelimsky, W. Singer, S. May, D.M. Sletten, P. Sandroni,
J. Mandrekar (Rochester, MN, USA)
Objective: We undertook a prospective study of North American
MSA with the following objectives: 1. To determine natural history
of MSA; 2. To compare MSA-P with MSA-C; 3. To determine pre-
dictors of outcome.
Movement Disorders, Vol. 30, Suppl. 1, 2015
Background: Multiple system atrophy (MSA) is a rare and fatal
neurodegenerative disorder exhibiting a combination of Parkinsonism
and/or cerebellar ataxia and autonomic failure. We report the first
North American prospective natural history study of MSA, and the
effect of phenotype and autonomic failure on progression and
prognosis.
Methods: 175 subjects with probable MSA, both MSA-P and
MSA-C, were recruited and prospectively followed for 5 years with
6 monthly evaluations in 12 centers. Subjects were evaluated with a
standard minimal dataset, UMSARS I (a functional score of symp-
toms and ability to undertake activities of daily living), UMSARS II
(neurological motor evaluation), the Composite Autonomic Symp-
toms Scale (COMPASS)-select (a measure of autonomic symptoms
and autonomic functional status), and COMPASS-select-change (a
derivative of COMPASS-select where participants scored how much
their autonomic symptoms had changed).
Results: Mean age of symptom onset was 63.4 (SD 8.6) years.
Median survival from symptom onset by Kaplan-Meier analysis was
9.8 years (95% CI, 8.8-10.7) and MSA-P was not significantly differ-
ent to MSA-C. Subjects with an early autonomic mode of onset had
a worse prognosis, surviving 7.9 years (95% CI, 6.5-9.4) while sub-
jects with late autonomic onset survived a median of 10.3 years
(95% CI, 9.3-11.4). At baseline MSA-P and MSA-C were not differ-
ent in symptoms and function (UMSARS I), by examination
(UMSARS II), or in neurologic status. Median time to death from
enrollment was 1.9 years.
Conclusions: Probable MSA represents late-stage disease with
short survival. Natural history of MSA-P and MSA-C are similar.
Early autonomic failure is associated with worse prognosis. These
findings provide novel insights on natural history and have implica-
tions on the design of treatment trials. Subjects with probable MSA
are at the plateau phase of rate of progression, while those with ear-
lier disease are at the steeper phase and the number needed to power
a treatment trial would be considerably smaller.
816
PROMESA: Progression rate of MSA under EGCG
supplementation as anti-aggregation-approach
S. Maass, J. Levin, M. Schuberth, A. Giese, U. Mansmann, F.
Krismer, G. Wenning, K. B
otzel, G. H
oglinger (Munich, Germany)
Objective: To evaluate (1) safety and tolerability of EGCG and
(2) effects of EGCG on motor impairment and functional disability
after twelve months of epigallocatechin gallate (EGCG) therapy in
patients with Multiple System Atrophy (MSA) using the Unified
MSA Rating Scale (UMSARS) as primary readout parameter.
Background: Multiple system atrophy (MSA) is a synucleinop-
athy leading to death within 6-9 yrs. on average. There is a high
need for a disease modifying therapy, since no potent symptomatic
treatment is currently available. Intracellular formation of toxic
oligomers of a-synuclein appears to be the underlying pathological
mechanism of the disease. Thus, MSA is an important model disease
to investigate disease-modifying effects in a-synuclein-dependent
neurodegeneration.
Several lines of evidence including epidemiological, in vitro, and
in vivo data suggest that EGCG might be able to delay disease pro-
gression of MSA by modifying several aspects in the pathogenesis of
MSA including alpha-synuclein aggregation and iron accumulation.-
Therefore, we designed this study to investigate the influence of
EGCG on disease progression in patients with MSA.
Methods: Three independent studies (EMSA, NNIPPS and
MEMSA) reported a similar rate of disease progression over a 12
month period. Power calculation was performed on a subset of the
EMSA data regarding the Motor Examination (ME) of the
UMSARS. Patients with MSA with a Hoehn & Yahr score  3 were
included.
Results: To assess the efficacy of EGCG vs. placebo regarding
the reduction of disease progression measured by the UMSARS-ME
 POSTER SESSION
during the study period of 52 weeks (80% power, 5% P-level, 50%
effect size, i.e. an expected mean yearly UMSARS-ME increase of
3.9 under verum treatment compared to 7.8 6 6.8 (mean 6 SD) under
placebo-treatment) a number of 36 patients per group will be needed.
Considering a drop-out rate of 20% a total of 86 patients will be
recruited in the 12 centres of the study. Recruitment started in March
2014. So far 46 patients have been recruited in 11 centres. Two seri-
ous adverse events have been recorded. None was related to the
study treatment.
Conclusions: These data provide a solid rationale for testing in
an investigator initiated trial (IIT) if supplementation of EGCG can
interfere with the core disease mechanism in MSA and delay the
progression of the MSA-related disability. If recruitment continues as
planned data are expected for 2017.
817
The visual estimation of midbrain to pons ratio combined with
cerebrospinal fluid biomarkers improves the diagnostic accuracy
of PSP
N. Magdalinou, H. Ling, A. Noyce, L. Massey, R. Paterson, J.
Schott, I. Davagnanam, C. Micallef, N. Fox, T. Warner, H.
Zetterberg, A. Lees (London, United Kingdom)
Objective: To evaluate whether a combination of visual estima-
tion of MP ratio with CSF biomarkers can improve the diagnostic
accuracy of PSP.
Background: Quantitative mid-sagittal midbrain to pons ratio
(MP) using magnetic resonance imaging (MRI) has shown promise
in differentiating PSP from other Parkinsonian syndromes.
Methods: MRI and CSF examinations were performed in patients
with progressive supranuclear palsy (PSP) (n530; 17 PSP-
Richardson syndrome (RS) and 13 non-RS PSP variants), Parkin-
sons disease (PD, n518), multiple system atrophy (MSA, n523),
and corticobasal syndrome (CBS, n510). Pathological diagnosis
became available in 10 patients (PSP, n56; MSA, n53; corticobasal
degeneration, n51) during the study. An MP ratio <0.50 was con-
sidered abnormal. A panel of CSF markers was tested to evaluate
their diagnostic accuracy in Parkinsonian disorders. Logistic regres-
sion was used to assess relationships between radiological and CSF
markers, and PSP diagnosis.
Results: 88% of the PSP participants were classified correctly on
the basis of the MP ratio. MP ratio determined by visual inspection
was found to be superior to objective midbrain measurement in accu-
rately identifying PSP-RS as well as non-RS PSP variants. Neurofila-
ment light chain (NFL) and soluble metabolites of amyloid precursor
protein (sAPPa) were found to be the most discriminatory CSF bio-
markers. Combining visual estimation of MP ratio and CSF, the
diagnostic accuracy improved to 94% in discriminating PSP from
MSA, PD and CBS. Of the ten patients out of 81 who were misclas-
sified using MRI visual estimation alone, eight were identified cor-
rectly when CSF markers were used in addition.
Conclusions: Visual inspection of MP ratio is more useful than
midbrain diameter measurement as a biomarker to diagnose both
classic PSP-RS and other PSP variants. It can be used with readily
available CSF markers to differentiate PSP from other Parkinsonian
syndromes.
818
Movements disorders due to toxoplasma abscess in patients with
AIDS
A.M. Magnerou, V. Sini, P. Ongolo-zogo, Y. Fogang, L. Kaptue
(Dakar, Senegal)
Objective: Evaluate the movements disorders in HIV patient.
Background: Movement Disorders may be the result of direct
central nervous system infection by human immunodeficiency virus
S321
(HIV) or the result of opportunistic infections like toxoplasma
encephalitis.
Methods: It was a cross-sectional descriptive study during 3
years, in adult young patient with AIDS followed at Yaounde central
hospital.
Results: In 105 HIV positive patients followed for toxoplasma
encephalitis; 3 patients (2,8%) had involuntary movements: one hem-
ichorea/hemiballismus and two hemidystonia. The mean age was
35.3 6 9.2 years. All were men and HIV 1 was the viral type
encountered. The mean CD4 cell count of the patients was
58.5 6 46.2/ll.
The brain lesions were all heterogeneous with contrast enhance-
ment associated with peripheral edema. The abscesses were multiple
in all patients, supratentorial, in the frontal lobes and basal ganglia.
Movement Disorders are completely resolved after two weeks
since starting treatment and disappearance of other associated neuro-
logic symptom. Brain CT scan control showed marked resolution of
cerebral lesion. The most encountered treatment options were
sulfadiazine-pyrimethamine in one patient and by Trimethoprim-
sulfamethoxazole associated with steroid in two patients. They did
not receive dopamine blocker.
Conclusions: Reports of extrapyramidal Movement Disorders in
AIDS patients due to toxoplasma abscesses are rare. Toxoplasma
encephalitis should be considered in HIV-positive patients presenting
with hemichorea/hemiballism, dystonia associated or not with focal
neurologic deficits of progressive onset, seizures or headache. The
CT-scan showed ring-enhanced lesion in the basal ganglia.
Sulfadiazine-pyrimenthamine or sulfamethoxazole-trimethoprim asso-
ciated with highly active antiretroviral therapy leads to significant
improvement of involuntary movement.
819
Elimination of neurotoxic gangliosides protects against MPTP-
induced neurodegeneration and executive dysfunction in mouse
model of Parkinsons disease
P. Maiti, M.P. McDonald, T. Rex (Memphis, TN, USA)
Objective: To determine whether Ganglioside 3 synthase (GD3S)
knockdown can eliminate neurotoxic gangliosides and can protect
dopaminergic neuronal loss and prevent executive dysfunction fol-
lowing a subchronic regimen of MPTP in animal model of Parkin-
sons disease.
Background: More than half of Parkinsons patients exhibit
fronto-striatally-mediated executive dysfunction, including deficits in
sustained attention, planning, judgment, and impulse control. We
have previously shown that modification of brain gangliosides by tar-
geted mutation of Ganglioside 3 synthase (GD3S) is neuroprotective
against Alzheimers disease and same can be applicable to Parkin-
sons diseases too.
Methods: Male C57BL/6N wild-type mice were trained on a 3-
hole serial reaction-time (SRT) task, which included measures of
sustained attention and impulse control, and a battery of sensorimo-
tor tasks. Sustained attention was measured by response accuracy
and reaction time. Impulsive behavior was measured by premature
responding in the response holes or the food well during the pre-cue
period. After reaching stable performance mice were given intrastria-
tal injections of a recombinant adeno-associated viral (rAAV) vector
expressing a short-hairpin RNA (shRNA) construct targeting GD3S,
or a scrambled-construct control. After 3 weeks, mice received
MPTP (25 mg/kg body weight) injections or saline vehicle and were
re-trained on the SRT task. After 5 weeks all behavioral parameter
were recorded and then the animals were sacrificed and evaluated
neurochemical and histological changes.
Results: Elimination of neurotoxic gangliosides by knocking
down of GD3S expression partially protects against dopaminergic
neuronal loss, improves executive and motor dysfunctions in MPTP-
lesioned mice.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S322 POSTER SESSION
Conclusions: Strategic modification of brain gangliosides by
inhibiting GD3S protects against dopaminergic neuronal loss and
improves behavioral impairments in MPTP-lesioned mice.
820
Meningioma presenting as Parkinsonism
S.A. McMahan, N. Galvez (Weston, FL, USA)
Objective: We describe a case of secondary Parkinsonism due to
meningioma.
Background: Brain tumors are a rare cause of Parkinsonism, but
there have been cases noted in the literature with regard to meningio-
mas presenting as Parkinsonism.
Methods: A case report.
Results: An 84 year old right handed woman with history of dia-
betes came with chief complaint of leg heaviness. Symptoms started
4 months prior. Painless heaviness sensation in both legs with gait
imbalance. Also noted right thumb twitching worse when nervous
and at rest for the past month. Admitted to difficulty with turning in
bed and handwriting changes which she attributed to carpal tunnel
syndrome.
Neurological exam showed rest tremor of right thumb; bradykine-
sia, rigidity and cog wheeling of right UE/LE greater than left.
Reflexes were hyperactive in bilateral upper extremities and intact in
lower extremities. Had mildly abnormal sensory exam of both legs
with proprioception intact. Gait steady but slow with slightly stooped
posture. Diminished arm swing on right. Negative pull test.
Electrodiagnostic studies were unremarkable. Contrast MRI brain
showed a large extra-axial mass at the left frontoparietal vertex with
mildly heterogeneous solid enhancement. Patient underwent surgery
and pathology confirmed meningothelial type meningioma, grade 1.
On phone follow up, patient reported improved symptoms.
Conclusions: Meningiomas are common benign central nervous
tumors, but an uncommon cause of Parkinsonism. There were never
signs of increased intracranial pressure. This case demonstrates
importance of fully evaluating for secondary causes of Parkinsonism
before starting any potential therapies.
821
Unusual phenotype of pathologically confirmed progressive
supranuclear palsy
K. Mensikova, L. Tuckova, J. Ehrmann, P. Kanovsky (Olomouc,
Czech Republic)
Objective: To report two cases of patients with unusual manifes-
tation of pathologically confirmed PSP.
Background: The clinical variability of different PSP phenotypes
is caused by the different distribution and density of tau-pathology
within the brain. Based on the results of recent clinical-pathological
studies it seems that clinical heterogeneity of PSP is much more
wider than it has so far seemed.
Methods: Detailed clinical and laboratory examinations and post
mortem neuropathological examinations were done in both patients.
Results: The first case was 60-year old woman, in whom rapidly
progressive micrografia and stuttering speech with hypophonia
occured at the age of 53 years. Bilateral horizontal nystagmus,
pyramidal syndrome, postural instability, asymmetric Parkinsonian
syndrome and severe dysarthria with bradykinesia, quadruhyperre-
flexia, gaze palsy, bulbar syndrome and postural instability with fre-
quent falls were present after 6 years. There were not any signs of
cognitive deterioration or executive dysfunction. The patient died
due to the cardiac arrest; at autopsy, the brain pathology matched to
the diagnosis of 4R tauopathy meeting the Williams diagnostic crite-
ria of PSP.
The second case was 67-year old woman, in whom the progres-
sive cerebellar syndrome with increased urinary frequency and ortho-
static hypotension appeared at the age of 60 years; these were
Movement Disorders, Vol. 30, Suppl. 1, 2015
followed by the bradykinesia, hypokinesia, rigidity and pyramidal
syndrome. Speech impairment progressed into complete anarthria
and dystonia of the limbs and anterocollis manifested. There were no
signs of cognitive or executive deficits. The patient died due to bron-
chopneumonia; at autopsy, the brain pathology has been found dual,
corresponding to the combination of 4R tauopathy (meeting the Wil-
liams diagnostic criteria of PSP) and neocortical amyloidopathy.
Conclusions: The unusual combination of clinical symptoms in
both cases was so diverse that it was dificult to determine the correct
clinical diagnosis of PSP. The symptoms which are classified as
exclusion criteria for PSP were present in both patiens, so they were
both clinically diagnosed as suffering from multiple system atrophy
(MSA-P). The unexpected yet definite brain pathology meeting Wil-
liams diagnostic criteria of PSP raises the question about the next
possible clinical phenotype of PSP, PSP-MSA.
Supported by the grant IGA UP LF-2014-023
822
Fahrs syndrome presenting with atypical Parkinsonian signs:
Case report
N.F. Mercan, S. Ozdemir, H. Uyanik, N. Oztekin, F. Ak (Ankara,
Turkey)
Objective: Herein we report the findings of a patient presenting
with atypical symptoms of Parkinsonism and after the evaluation
diagnosed as Fahrs disease, for drawing attention of the importance
of differential diagnosis.
Background: Fahrs disease is a neurodegenerative disorder char-
acterized by symmetrical and bilateral calcification of the basal gan-
glia. Familial cases of Fahrs disease have been documented,
predominantly with autosomal-dominant inheritence. Also patients
without any evident disease is called as idiopatic form. Parkinsonism
or other Movement Disorders seem to be the most common presenta-
tion, followed by cognitive impairment and ataxia.
Methods: 53-year-old male admitted with complaints of focal
dystonia of the whole right arm, progressive slowness of movements,
unsteady gait, frequent falls and swallowing and eating difficulties.
He had no relevant medical and family history. He was diagnosed as
Parkinsons disease 4 four years ago and used various antiParkin-
sons drugs without any benefit. There were no abnormalities in the
general physical examination. Neurologic examination revealed
hypomimia, hypophonia, right upper and lower bradykinesia and
rigidity, slowness of walking, positive falling test and mild rest
tremor of right hand.
Results: Blood count, liver and kidney tests, cholesterol and vita-
min B12 levels are normal. His brain computed tomography (CT)
showed bilateral almost symmetric hyperdensity involving striatum,
Fig. 1. (822).
 POSTER SESSION
Fig. 2. (822).
pallidum, thalamus thougt to be compatible wiith Fahr syndrome.
Gradient-echo T2 wieghted sequence brain magnetic resonance imag-
ing (MRI) showed hypointensity throughout the entire area of calcifi-
cation matching the calcified region as seen on CTwhich is
compatible with deposits of paramagnetic metals. Later on we
checked his ceruloplasmine level for Wilsons disease and his iron
and ferritine levels for iron overload syndromes, calcium, phospho-
rus, parathormone levels for parathormone disases were all normal.
[figure1], [figure2].
Conclusions: This patient who initially diagnosed as Parkinsons
disease was finally concluded as idiopathic Fahrs diasese due to lab-
oratory and imaging findings. This case emphasizes the importance
of considering Fahrs disease in the differential diagnosis of Move-
ment Disorders particularly presenting with atypical features. Also
Fahrs disease should be differentiated from other conditions that can
cause intracranial calcification.
823
Underlying dopaminergic deficit in suspected drug-induced
Parkinsonism is associated with olfactory impairment
J.F. Morley, G. Cheng, J. Bubroff, J.R. Wilkinson, J.E. Duda
(Philadelphia, PA, USA)
Objective: To characterize underlying striatal dopaminergic
denervation in presumed drug-induced Parkinsonism (DIP) and
investigate its relationship to olfactory impairment (OI), a common
prodromal finding in Parkinsons disease (PD).
Background: DIP associated with dopamine receptor-blocking
antipsychotic drugs is common and can be indistinguishable from
idiopathic PD. When symptoms persist after drug withdrawal, DIP
may represent unmasking of prodromal PD. We have previously
reported that OI was more common in patients with persistent symp-
toms after drug withdrawal.
Methods: We reviewed DAT-SPECT scans that label striatal pre-
synaptic dopaminergic neurons from 18 consecutive patients (17
male) evaluated for DIP. Scans were read as normal or abnormal by
a radiologist without knowledge of clinical status. Semi-quantitative
analysis of uptake in the caudate, anterior putamen and posterior
putamen was performed by a separate observer blinded to clinical
and olfactory data. Olfactory scores (University of Pennsylvania
Smell Identification Test or Brief Smell Identification Test) below
the 10th percentile for age and gender were considered abnormal.
S323
Results: DAT SPECT was abnormal in 4/18 (22%) of DIP sub-
jects. Olfactory testing was available for 12 subjects and was con-
cordant with DAT SPECT result in 10/12 (83%). One discordant
subject (abnormal olfaction/normal imaging) had a history of schizo-
phrenia and encephalitis, both of which are independently associated
with OI. In semi-quantitative DAT SPECT, uptake was significantly
lower in DIP/OI (N=3) compared to those with normal olfaction
(N=4) in the anterior putamen (1.4 6 0.88 vs. 3.1 6 0.66, p50.01),
posterior putamen (1.1 6 0.95 vs 2.5 6 0.55, p50.03) and lower pos-
terior putamen (1.0 6 0.87 vs.2.3 6 0.52, p50.03). Uptake in DIP/OI
was similar to a PD group (N=4) whereas DIP subjects with normal
olfaction were similar to tremor patients (N=6) in all striatal regions.
Better olfactory score was associated with higher uptake for the aver-
age anterior putamen (r=0.68, p50.06), average posterior putamen
(r=0.74, p50.04) and lowest posterior putamen (r=0.78, p50.03)
adjusting for age.
Conclusions: Olfactory testing may be a simple screen to help
identify DIP subjects with underlying dopaminergic denervation,
consistent with prodromal PD. Identification prodromal cohorts offers
opportunities for study and intervention at the earliest stages of
disease.
824
Clinical feature of progressive supranuclear palsy with cerebellar
ataxia
M. Nagai, T. Tsujii, H. Iwaki, R. Andoh, H. Yabe, N. Nishikawa, M.
Nomoto (Toon, Japan)
Objective: We demonstrate the clinical feature of progressive
supranuclear palsy with cerebellar ataxia (PSP-C).
Background: PSP is a neurodegenerative disorder, clinically
characterized by supranuclear gaze palsy, Parkinsonism, dystonia,
and cognitive impairment. It shows some clinical phenotypes, such
as classic Richardsons syndrome and PSP-Parkinsonism. Japanese
PSP patients with cerebellar ataxia as the initial and principal symp-
tom (PSP-C) have been reported.
Methods: We reviewed the clinical records of four patients who
were clinically diagnosed as PSP-C.
Results: We diagnosed three male and one female patient as
PSP-C. The mean age of the four patients was 65.75 years old. Ini-
tial symptom of three patients was gait disturbance and that of one
patient was dysarthria. All the patients had truncal ataxia (ataxic
speech, ataxic gait) and limb ataxia which showed markedly bilateral
difference. Only one patient had supranuclear vertical gaze palsy at
the first visit. The other patients developed vertical gaze palsy during
the course of the disease. No patients showed muscle rigidity of
limbs and tremor. Applause sign was observed in all the patients.
MRI findings showed midbrain atrophic changes on mid-sagittal
view (hummingbird sign) and mild cerebellar atrophy without
obvious laterality.
Conclusions: We experienced four patients with PSP-C. Although
none of the patients was evaluated pathologically, the clinical feature
was consistent with that which reported previously.
825
Low serum uric acid levels in progressive supranuclear palsy
J.M. Oropesa, S. Jesus, I. Huertas, M. Caceres, F. Carrillo, M.
Carballo, P. Gomez-Garre, P. Mir (Seville, Spain)
Objective: To compare cross-sectional serum uric acid (UA) lev-
els between patients with progressive supranuclear palsy (PSP) and
patients with Parkinsons disease (PD) and healthy controls (HC).
We also analyzed longitudinal UA levels in PSP group to evaluate
whether UA levels decrease as disease progresses.
Background: UA is a natural antioxidant and its action may reg-
ulate the cerebral damage induced by oxidative stress. It has been
shown that low levels of UA could be a risk factor for the
Movement Disorders, Vol. 30, Suppl. 1, 2015
S324 POSTER SESSION
development of neurodegenerative diseases such as Parkinsons dis-
ease (PD). It is unknown whether it could also play a role in other
types of Parkinsonism.
Methods: We included 47 PSP patients, 225 PD patients and 185
HC. Univariate analyses to compare UA concentration between these
three groups were performed using ANOVA and post-hoc Tukeys test.
Logistic regression was further used to adjust for age and sex. The lon-
gitudinal analysis was conducted with 30 PSP patients who had two or
more UA measurements using individual growth curves (IGC).
Results: PSP patients showed reduced levels of serum UA as
compared to HC (PSP: 4.34 mg/dl; HC: 5.35 mg/dl). This reduction
was similar to that found in patients with PD (4.66 mg/dl). The dif-
ferences with HC remained significant after adjusting for sex and
age (p<0.001). The IGC analysis revealed that the factor time was
not associated with UA levels of PSP patients.
Conclusions: Serum UA levels are reduced in PSP as well as in
PD compared to HC, and these levels do not decrease in PSP with
disease progression. Our data suggest that high levels of UA could
be a natural protective factor against PSP.
826
Highly specific radiographic marker predates clinical diagnosis
in progressive supranuclear palsy
E.K. Owens, K.N. Krecke, J.E. Ahlskog, R.D. Fealey, A. Hassan,
K.A. Josephs, B.T. Klassen, J.Y. Matsumoto, J.H. Bower (Rochester,
MN, USA)
Objective: To assess whether the midbrain to pons ratio (MTPR)
is useful in differentiating subjects with Parkinsonism, and to deter-
mine the timing of its presence in relation to a clinical diagnosis of
progressive supranuclear palsy (PSP).
Background: The diagnosis of PSP is often challenging early in
the course of the disease, when clinical signs of the condition may
be less apparent and patients do not clearly meet diagnostic criteria.
Numerous radiographic markers of the condition have been investi-
gated. However, many of these signs often are not present until the
diagnosis is already observable clinically, or are difficult to practi-
cally apply on a routine basis. Massey and colleagues (Neurology.
2013 May 14;80(20):1856-61) described the use of the MTPR in
PSP. We sought to further assess the MTPR in a cohort of 75 sub-
jects with Parkinsonism, and to determine if it is positive before the
patient fulfills clinical criteria for PSP.
Methods: We performed a retrospective review of 25 patients
each fulfilling clinical diagnostic criteria for MSA, PD, and PSP. A
radiologist, blinded to the clinical diagnosis, determined the MTPR
in neuroimaging preceding and post-dating the diagnosis date. The
timing of the presence of a MTPR of less than or equal to 0.52 was
assessed in the PSP group in relation to the date of clinical
diagnosis.
Results: The midbrain to pons ratio was significantly reduced in
the PSP cohort, and a MTPR of less than or equal to 0.52 was 68%
sensitive and 100% specific for PSP (p<0.0001). This radiologic
sign predated a clinical diagnosis of PSP by 1 month or more in 14
of 17 (82%) of patients in whom it was found, by a mean of 15
months (range 1 to 47 months).
Conclusions: The MTPR is an easily applied and highly specific
tool in the diagnosis of the Richardsons phenotype of PSP. As it is
commonly positive before the clinical diagnosis, including it in revised
diagnostic criteria could lead to an earlier diagnosis for these patients.
827
Clinical and pathological characteristics of progressive
supranuclear palsy (PSP) clinically misdiagnosed as
synucleinopathy: A preliminary analysis
A. Pantelyat, L. Rosenthal, K. Mills, G. Pontone, C. Bakker, J.
Troncoso, Z.M. Mari (Baltimore, MD, USA)
Movement Disorders, Vol. 30, Suppl. 1, 2015
Objective: To evaluate the clinical and pathological characteris-
tics of autopsy-determined PSP cases clinically misdiagnosed with
synucleinopathy during patients lifetime in a longitudinal prospec-
tive patient cohort at the Morris K. Udall Parkinsons disease
Research Center at the Johns Hopkins University School of
Medicine.
Background: PSP is a 4-repeat tauopathy that according to cur-
rent diagnostic criteria (Litvan et al. Neurology.1996; 47(1):1-9)
involves early onset of falls and vertical oculomotor dysfunction.
However, there is accumulating evidence that PSP has multiple phe-
notypes, and that the classic PSP-Richardson syndrome is a less
common PSP presentation than previously considered (Respondek
et al. Mov Disord. 2014; 29(14):1758-66).
Methods: We identified 12 cases (10 male) in our brain donation
cohort who had been clinically diagnosed with synucleinopathy (10
Parkinsons disease (PD), 2 Dementia with Lewy bodies), but on
autopsy were found to have definite PSP according to pathologic cri-
teria. Descriptive statistics and partial correlation analyses were per-
formed. Additional analyses are under way at our center.
Results: The mean (sd) at symptom onset was 70.4 (10.5) years;
age at diagnosis was 72.0 (11.0) years; age at death was 80.5 (9.0)
years; and the mean disease duration was 11.1 (6.5) years. None of
the patients met current PSP diagnostic criteria while alive, and all
had at least a partial response to dopaminergic therapy. Two of 12
patients had concomitant PD pathology, while 6 others had evidence
of AD pathology (4 probable, 2 definite), and one other patient had
vascular pathology in the basal ganglia. Eleven of the 12 patients
had neurofibrillary tangles in the basal ganglia, while basal ganglia
Lewy bodies were present in only two cases.
Conclusions: Our clinicopathological data support the notion that
PSP has a broad clinical spectrum; moreover, mixed pathology is
more common than previously thought. These factors contribute to
inaccuracy of clinical diagnosis and underscore the need for revision
and expansion of the current diagnostic criteria for PSP to include its
variants.
828
Corticobasal syndrome in a female in a FXTAS family
M. Paucar, S. Beniaminov, P. Svenningsson (Stockholm, Sweden)
Objective: To report a family with Fragile X Premutation
Tremor/Ataxia Syndrome (FXTAS) in which one patient exhibits a
corticobasal syndrome.
Background: FXTAS is caused by premutations in the fragile X
mental retardation 1 (FMR 1) gene and diagnosed based on clinical
and radiological features (Jacquemont et al., 2003). It is most com-
mon among elderly men, but is also present among females.
Methods: Clinical description, neuroimaging, cerebrospinal fluid
analyses.
Results: The subject is a 48 years old Swedish woman whose
son is affected by fragile X syndrome (FXS). Her older sister has
two sons with FXS. The sisters andtheir father suffer from tremor
andmild cognitive impairment. Upon genotyping, they were found to
have premutations in the FMR 1 gene with 82, 90 and 79 CGG
repeats, respectively. Over a course of three years, the subject has
developed progressive unsteadiness,loss of postural control,frequent
falls and she is now bound to a wheelchair. From the beginning, she
suffers from speech abnormalities with palilalia, expressive dysphasia
leading toa state of mutism. Her working memory is impaired and
she displays preservative behavior andorobuccal apraxia. A neuro-
psychological assessment showed marked executive dysfunction with
impairments in working memory, verbal episodic memory, planning,
concentration and attention. Over the past two years, the subject has
developed diplopia, hypometric saccades and vertical supranuclear
gaze palsy. She has also developed tremor and mild rigidity. She has
become urine incontinent and has lost weight. She has been diag-
nosed with OSAS. Neuroimaging suggests increased atrophy in the
mesencephalon, but lacks the MCP sign. Her father demonstrates
 POSTER SESSION
similar MRI changes. A DaTSCAN shows major loss of DAT in
nucleus caudatus and putamen bilaterally and a FDG-PET shows
reduced blood flow in both frontal lobes. All three affected family
members have normal levels of Tau, P-Tau, beta-amyloid and oxy-
sterols in the cerebrospinal fluid.
Conclusions: All subjects in the reported family with FMR1pre-
mutations display clinical feature of FXTAS. However, none of them
display the MCP sign, but rather atrophy in the mesencephalon. The
subject with the rapid clinical progression fulfils the clinical criteria
of corticobasal syndrome, which is further supported by a positive
DaTSCAN.
829
Subacute anterocollis in dementia with Lewy bodies
J. Paulson, Y. Zabar, J. Leegwater-Kim (Burlington, MA, USA)
Objective: To characterize a case of subacute anterocollis in a
patient with Dementia with Lewy Body (DLB).
Background: Disproportionate anterocollis has been described in
a variety of Parkinsonian disorders; it is a clinical hallmark of multi-
ple system atrophy (MSA) and a rare complication of Parkinsons
disease [1], [2]. While Parkinsonism is a recognized feature of DLB,
dystonia has been rarely described [2]. Moreover, anterocollis, to our
knowledge, has not been reported in DLB.
Methods: The patient was followed regularly at 3 month intervals
and evaluated one week after the onset of the anterocollis. The clini-
cal features of the patients disease are highlighted in Table 1. Table
2 shows the complete workup including blood work, radiological
imaging, and EMG findings after the discovery of the anterocollis.
Results: Case Report: 60 year-old right-handed woman with a
history of depression initially presented with a 3-year history of
declining mental status, hallucinations and delusional behavior. Ini-
tial exam was notable for cognitive deficits as well as mild Parkin-
sonism. There was no history of exposure to dopamine receptor
blocking agents. Brain FDG PET scan showed hypometabolism in
the bilateral temporal and parietal lobes as well as the occipital cor-
tex and she was diagnosed with probable DLB. She was started on
rivastigmine and low dose carbidopa-levodopa. After one year she
developed severe anterocollis over a 1-week period. Workup
revealed normal TSH, CK, AchR antibodies. MRI of the cervical
spine showed C5-C6 kyphosis, but no other pathology. EMG was
negative for myopathy or neuromuscular junction defect but did
show a few polyphasic MUAPs in cervical paraspinal and sternoclei-
domastoid muscles. The patients doses of rivastigmine and
carbidopa-levodopa were lowered without resolution of anterocollis,
and botulinum toxin injections resulted in minimal improvement.
Conclusions: We aim to describe a case of anterocollis in a
patient with DLB. While anterocollis has been described in other
Parkinsonian disorders, to our knowledge, this is the first docu-
Clinical Characteristics of DLB Patient
Age at onset of cognitive difficulty
Age at onset of Parkinsonism
Medications
Parkinsonian features
FDG PET Scan
Anterocollis Workup
Lab results
C-spine results
EMG
S325
mented case in DLB. The clinical course and phenomenology of
anterocollis in our subject are similar to published data on anterocol-
lis in PD and MSA, suggesting a common pathophysiological
mechanism.
[1] Van de Warrenburg; et al. Mov Disord. 2007 2325-2331
[2] Louis, E; et al. Neurology. 1997 376-380
830
Movement Disorders in basal ganglia infarction
I. Petrov (Skopje, Macedonia)
Objective: Aim is to present patients who developed Movement
Disorders after ischaemic stroke of basal ganglia especially infarction
of nucleus subtalamicus due to the lenticulostriate arterie occlusion,
branch of the a.cerebri media.
Background: Basal ganglia are part of many neuron circuits.
They are target of stroke in many places due to arteries occlu-
sion.The effects of stroke can depence of the area of basal ganglia
hit by stroke.
It can affect body movement,vision,body sensation,judgment,per-
sonality,speech.Most important body movements are tremors,rigidi-
ty,ataxia,left side neglect.Choreatic movements,hemiballism and
dystonia can also occur.Investigations of this problem are in direc-
tion of neuroimaging examination and follow up of the patients.
Methods: Three patients with basal ganglia infarction were exam-
ined at the Movement Disorders department by the university neurol-
ogy clinic in Skopje,R.of Macedonia.Patient were followed in the
period of three years after stroke.2 were man and one woman at the
age between 48-55 years. One man was with infarction in globus
palidus,one in putamen and the woman was with nucleus subtalami-
cus infarction.Detailed neurological examination was made. MRI and
neuropsychological tests were also made.
Results: MRI in woman revealed lacunar infarction in subtalamic
nucleus.She had hemiballistic movements contralateral to the infarc-
tion.Hemiballistic movements had sudden onset after infarction and
were reduced in the follow up period.The patient with putaminal
infarction developed contralateral chemichorea which was still pres-
ent after three years.MRI revealed lacunar infarct in contralateral
putamen.The third patients had dystonia and Parkinsonism and MRI
revealed bilateral infarction of globus palidus.Dystonia diminished
after 6 months.
Conclusions: Hemiballism usually occur in the contralateral sub-
talamic nuclei lesion.It can be presented as chemichorea hemiballism
in ipsilateral ischaemic lesion in subtalamic nucleus.Putaminal infarct
can be presented with contralateral choreatic movements which can
be also seen in globus palidus infarction and sometimes in last one
with lower limb chorea.Bilateral and unilateral lesions of globus pali-
dus can be presented with dystonia.Parkinsonism occur in bilateral
globus palidus lesions with rigidity and bradykinesia.
56 (hallucinations, executive and visuospatial dysfunction)
58
Levodopa (200); rivastigmine 9.5mg/24h
micrographia, mild balance difficulty, mild symmetric upper
extremity bradykinesia, narrow-based gait, reduced arm swing bilaterally
hypometabolism in bilateral temporal, parietal lobes, occipital cortex
TSH 1.28, AchR ab 0.00, CK 51
mild c5-c6 kyphosis, and mild degenerative changes
R SCM/SS/SC: few polyphasic MUAPs, normal duration and amplitude,
normal recruitment. No signs of myopathy or NMJ disorder
Movement Disorders, Vol. 30, Suppl. 1, 2015
S326 POSTER SESSION
As a conclusion infarction of the basal ganglia is very rare in the
pathogenesis of the extrapyramidal syndrome and is refractory to
antiParkinsonian therapy.
831
Nigrostriatal degeneration and response to L-dopa in
amyotrophic lateral sclerosis: A single patient report
P. Pita Lobo, S. Reim~ ao, M. de Carvalho, J.J. Ferreira (Torres
Vedras, Portugal)
Objective: Case Report.
Background: The differential diagnosis of Amyotrophic Lateral
Sclerosis (ALS) variant with predominant upper motor neuron
involvement (UMN-ALS) includes Atypical Parkinsonism Syn-
dromes. Some studies have also shown that ALS patients can show
DAT-scan abnormalities, hence a subclinical nigrostriatal involve-
ment has been hypothesized.
Methods: Case Report.
Results: A 56-year-old woman presented with progressive gait
impairment that started two years before with left leg stiffness,
which progressed to loss of independent gait one year later, associ-
ated with slight dysarthria, dysphagia, daytime drowsiness, increased
diurnal urinary frequency, overnight choking and extensor spasms in
lower limbs.
Two maternal uncles had Parkinso ns disease. On neurological
examination it was disclosed facial hypomimia, dysarthria, very brisk
tendon reflex in the four limbs but more marked in the legs, bilateral
lower limb spasticity (more severe on the left side), mild left upper
limb spasticity, ankle clonus on both sides, upper and lower limb
rigidity and bradykinesia (predominantly in left side), abnormal spas-
tic gait with hyperextension posture of the legs and abnormal posture
of the left foot, and no postural response on pull test.
DAT-scan showed a moderate and asymmetrical reduction
uptake, predominantly in left striatum, I-MIBG presented a reduced
uptake; MR brain imaging showed a T2 and FLAIR hypointensity in
the motor cortex and hyperintensity in the motor pathways bilaterally
that have an additional fractional anisotropy reduction in the DTI
study more prominent on the right side; EMG detected mild motor
units loss, with unstable motor unit potentials and fasciculations in
the lower limbs, suggestive of ALS.
She was treated with L-dopa, its reduction lead to increased gait
and balance impairment, which improved after L-dopa doses re-
introduction.
Conclusions: We report an ALS patient with DAT-scan abnor-
malities, responsive to L-dopa. In this case, nigrostriatal neurodegen-
eration gave relevant information to understand clinical phenotype.
We speculate that this finding may predict a specific population of
ALS patients that could benefit with dopaminergic treatment.
832
Role of Manganese in hepatolenticular degeneration: Another
pespective of epatic encephalopaty, case report
D. Rebolledo, A. Espay, S. Contreras, Z. Rebolledo, J. Esquivel
(Toluca, Mexico)
Objective: Not Wilsonian Hepatolenticular degeneration is a
chronic encephalopathy having an engine extrapyramidal clinical
spectrum due to dysfunction of the basal ganglia in the context of
severe liver disease.
There is strong evidence that manganese deposits are associated
with extrapyramidal phenotype that develops a subgroup of patients
with hepatic encephalopathy.
Therefore the neurological semiology has a valuable role in the
search engine spectrum involving nigrostriatal system dysfunction in
patients with liver cirrhosis with risk factors such as iron deficiency
anemia and portosystemic shunt.
Movement Disorders, Vol. 30, Suppl. 1, 2015
Background: Male of 61 years old bearer with Child Pugh C
liver failure and esophageal varices. 3 months before prior dengue
hemorrhagic fever; six weeks after debuted with Guillain Barre
syndrome.
Refers to present for two months resting tremor in his right hand
which is aggravated by periods of stress and disappear during sleep,
which then progresses to the contralateral hand and axial; also pre-
sented decreased facial gestures and difficulty performing rapid alter-
nating movements straight and curving in the last 4 weeks;
integrating a picture of Parkinsonism.
Methods: In studies of serum, ammonia requested extension 60
mg (15-45 mg/dl) was found, serum Mn: 2450 mg (0.824 to 1.648 mg/
dl), serum copper 3 mg (1-4 mg/dl) and urinary copper 24 hrs: 25 mg
(20-50 mg/dl) ceruloplasmin 24 mg (25-65 mg/dl), all other exams
were normal.
Results: With the analysis of the findings in the semiological,
biochemical and neurophysiological results we made the diagnosis of
non-Wilsonian hepatolenticular degeneration. It is emphasized that
the patient had sequelae of paralysis of Landry previously presented,
but no correlation between clinical and peripheral extrapyramidal
affectation was found, so we believe that these entities do nt have a
common pathophysiologic link; current founds in the last hematic
biometry add to the prior existence of shunt shown in esophageal
varices two key points that could accelerate manganese deposits in
the basal ganglia, and progressive Parkinsonism presented by the
patient.
Conclusions: There is evidence that the manganese deposits in
the basal ganglia interfere with modulation of GABAergic and dopa-
minergic systems synergistically with ammonium glutamate leads to
a state of neurodegeneration, with different pathophysiological idio-
pathic Parkinsons disease.
833
Benign progressive supranuclear palsy: A clinico-pathological
analysis of cases with prolonged survival
G. Respondek, C. Kurz, M. Stamelou, L.W. Ferguson, A. Rajput,
W.Z. Chiu, J.C. Van Swieten, C. Troakes, S. al Sarraj, E. Gelpi, C.
Gaig, E. Tolosa, S. Wagenpfeil, A. Giese, T. Arzberger, G.
Hoeglinger (Munich, Germany)
Objective: To report the clinical and pathological characteristics
of patients with Progressive Supranuclear Palsy (PSP) with a disease
duration of 10 years, compared to patients with shorter survival.
Background: PSP has been recognized as a rapidly progressive
neurodegenerative disease with a mean survival of 5 to 8.6 years (De
Bruin et al., 1994; Birdi et al., 2004). However, several studies
reported cases of autopsy-confirmed PSP that survived longer than
10 years (Birdi et al., 2004; Litvan et al., 1996; Respondek et al.,
2014).
Methods: Clinical charts of autopsy-confirmed PSP cases from
five brain banks were systematically reviewed and multiple brain
areas were centrally analysed.
Results: Of 137 PSP patients with sufficient clinical data, 37 had
a disease duration of 10 years (mean: 14.0 [10 27]). Compared
to cases with a survival of <10 years, these patients were younger at
disease onset (63.6 years [41 78] vs. 66.2 years [52 91]), pre-
sented less frequently with supranuclear gaze palsy and showed a
higher prevalence of tremor, asymmetric onset, and initial L-dopa
response. Only 38% of patients with long disease duration qualified
for the diagnosis of PSP-P. Although the frequency of falls, cognitive
impairment frontal dysfunction, and dysphagia did not differ at final
record, the time to onset of these clinical milestones was signifi-
cantly prolonged in patients that survived 10 years, indicating a
slower progression of disease. The primary cause of death in both
patient groups was aspiration pneumonia. Histopathologically,
patients with a disease duration of 10 years had more Lewy body
and -amyloid co-pathology, a greater extent of neuronal loss in the
caudate nucleus and substantia nigra, less tau pathology in the
 POSTER SESSION
occipital cortex, and more tau pathology in the striatum, thalamus
and medulla oblongata.
Conclusions: A surprisingly high percentage of cases survived
longer than 10 years after disease onset. The natural history of this
benign PSP variant is characterized by younger age at disease onset,
and the late development ofclinical milestones. Due to the assimilation
of the clinical picture at final record, histopathological differences
present during the early disease course might be abolished at post-
mortem examination. Yet, neuropathological analysis revealed regional
differences in neuronal loss, tau pathology and co-pathology.
834
Exploring the link between serum uric acid levels, clinical
factors, transcranial sonography and cardiac MIBG uptake in
Parkinsons disease and related disorders
H. Sakuta, K. Suzuki, A. Numao, M. Miyamoto, T. Miyamoto, Y.
Watanabe, H. Fujita, K. Hirata (Mibu, Japan)
Objective: To evaluate the associations between serum uric acid
(UA) levels, clinical factors, substantia nigra (SN) hyperechogenicity
and cardiac 123I-metaiodobenzylguanidine (MIBG) uptake among
patients with Parkinsons disease (PD), multiple system atrophy
(MSA) and progressive supranuclear palsy (PSP).
Background: Recent studies have suggested a link between lower
levels of serum UA and the development of PD. In patients with PD
and MSA, serum UA levels have been reported to be lower than in
control subjects. However, few studies have compared serum UA
levels among patients with PD-related disorders, including PD, MSA
and PSP.
Methods: Serum UA levels were determined in 73 patients with
PD, 31 patients with MSA, 18 patients with PSP and 71 controls.
Transcranial sonography and cardiac MIBG scintigraphy were per-
formed in patients with PD, MSA and PSP.
Results: Serum UA levels were significantly lower in patients
with PD, MSA and PSP compared with controls in men but not
women. Serum UA levels were negatively correlated with disease
duration and disease severity in MSA patients and disease severity in
PSP patients, but no correlations were observed in PD patients. No
correlation was observed between serum UA levels and hyperecho-
genic area in the SN by transcranial sonography or between serum
UA levels and cardiac MIBG uptake.
Conclusions: We found decreased serum UA levels in male
patients with PD-related disorders (PD, MSA and PSP) compared
Fig. 1. (835).
S327
with male controls, and significant correlations between serum UA
levels and disease severity in MSA and PSP patients. No significant
association was observed between serum UA levels and cardiac
MIBG uptake in PD-related disorders. The relationship between
serum UA levels and SN hyperechogenicity requires further
examination.
835
DeglutiSom- Software assist in the clinical evaluation of
swallowing in patients with Parkinsons disease
R.S. Santos, M.S. Aoki, A.R. Aoki, C.V. Moraes, H.G. Teive
(Curitiba, Brazil)
Objective: To analyze the sounds of swallowing in subjects with
Parkinsons disease, using as Doppler Sonar and software
DeglutiSom.[figure1]
Background: DeglutiSom software developed to assist in the
capture and analysis of swallowing sounds, with a wide variety of
functions and parameters, allowing the audiologist follow up and
comparisons between files of the same client and between models
swallowing sounds. The software is able to scan the sounds and pro-
cess noise produced by swallowing in visual representations of wave-
form, allowing accurate measurements and therefore a more accurate
description thereof.
Methods: 90 volunteers with a diagnosis of Parkinsons disease,
40 F and 50 m, aged between 37 and 81 years. The control group of
50 adult volunteers with no diagnosis of neurological disease,
18 females and 32 males. Cross-sectional study, prospective trial
evaluated the sounds of oropharyngeal swallowing in the associated
Doppler sonar and DeglutiSom to the results of videofluoroscopy.
Variables measured sounds of the sound wave, the initial frequency
(IF); peak frequency (FP); initial intensity (II); peak intensity (IP)
and time (T).
Results: The initial frequency (IF) and the initial intensity (II)
represents the beginning of swallowing, were lower intensity in Par-
kinsons patients than in adults, there was a lower strength and a
reduced speed in swallowing pharyngeal phase. The same was
observed in the final frequency (F2P) and final intensity (FI), which
represents the opening cricopharyngeal. Only 18 (20%) of patients
with Parkinsons showed the frequency of the first peak (F1P), which
represents the removal of the larynx. The time (T) was lower in
patients with Parkinsons disease.[figure2]
Movement Disorders, Vol. 30, Suppl. 1, 2015
S328 POSTER SESSION
Fig. 2. (835).
Conclusions: Based on the results presented in standard curves
are modified sound signal swallowing of a patient with Parkinsons
disease, compared with the curve of healthy adult.
836
Coenzyme Q10 levels are reduced in the cerebellum of multiple
system atrophy patients
L.V. Schottlaender, C. Bettencourt, A. Kiely, A. Chalasani, V.
Neergheen, J.L. Holton, I.P. Hargreaves, H. Houlden (London,
United Kingdom)
Fig. 1. (836).
Movement Disorders, Vol. 30, Suppl. 1, 2015
Objective: The objective of this study was to evaluate whether
the levels of coenzyme Q10 (CoQ10) in brain tissue of multiple sys-
tem atrophy (MSA) patients differ from those in elderly controls and
in patients with other neurodegenerative diseases.
Background: Multiple system atrophy (MSA) is an incurable
neurodegenerative condition. COQ2 is a gene that encodes for an
enzyme that participates in the synthetic pathway of Coenzyme Q10
(CoQ10), the predominant coenzyme Q in humans. Through linkage-
analysis and whole-genome-sequencing, variants in COQ2 have been
linked to clinically diagnosed Japanese MSA patients in a multicen-
ter study. The authors of that study, by analyzing a small sample,
 POSTER SESSION
suggested decreased levels of CoQ10 in brain tissue of MSA cases.
We were unable to replicate the genetic finding. However, in view
of the brain tissue result, we decided to investigate further the role
of the CoQ10 pathway. We determined the level of CoQ10 in brain
tissue from pathologically confirmed MSA cases and compared these
levels to those of normal controls as well as to other neurodegenera-
tive disorders.
Methods: Flash frozen brain tissue of a series of 20 pathologi-
cally confirmed MSA patients [9 olivopontocerebellar atrophy
(OPCA) type, 6 striatonigral degeneration (SND) type, and 6 mixed
type] was used for this study. Elderly controls (n537) as well as idi-
opathic Parkinsons disease (n57), dementia with Lewy bodies
(n520), corticobasal degeneration (n515) and cerebellar ataxia
(n518) patients were used as comparison groups. CoQ10 was meas-
ured in cerebellar and frontal cortex tissue by high performance liq-
uid chromatography.
Results: We detected a statistically significant decrease in the
level of CoQ10 in the cerebellum of MSA cases (P=0.001), specifi-
cally in OPCA (P=0.001) and mixed cases (P=0.005), when com-
pared to controls as well as to other neurodegenerative diseases
[dementia with Lewy bodies (P<0.001), idiopathic Parkinsons dis-
ease (P<0.001), corticobasal degeneration (P<0.001), and cerebellar
ataxia (P=0.001)]. [figure1]
Conclusions: Our results suggest that a perturbation in the
CoQ10 biosynthetic pathway is likely involved in the pathogenesis
of MSA but the mechanism behind this finding remains to be
elucidated.
837
Clinicopathological features and diagnostic criteria for
progressive supranuclear palsy with predominant cerebellar
ataxia
T. Shimohata, M. Kanazawa, H. Takahashi, M. Nishizawa (Niigata,
Japan)
Objective: To establish the diagnostic criteria for progressive
supranuclear palsy with predominant cerebellar ataxia (PSP-C).
Background: We previously reported patients with pathologically
confirmed progressive supranuclear palsy (PSP) who developed cere-
bellar ataxia as the initial and principal symptom. Compared to
patients having PSP without cerebellar ataxia, all patients with cere-
bellar ataxia exhibited more neuronal loss with gliosis and higher
densities of coiled bodies in the cerebellar dentate nucleus. Tau-
positive inclusion bodies were also observed in Purkinje cells of
patients with cerebellar ataxia. Similar PSP patients were reported by
different Japanese groups, a group from Mayo Clinic in the USA,
and a Canadian group. Therefore, we proposed a new variant of PSP
called PSP-C. PSP-C is likely to be clinically misdiagnosed as multi-
ple system atrophy with predominant cerebellar features (MSA-C) or
other spinocerebellar degenerations, especially early in the disease
course.
Methods: We reviewed the medical records of 4 and 11 patients
with pathologically proven PSP-C and MSA-C, respectively. We
recorded the presence or absence of clinical features that developed
within 2 years after disease onset. We also described the MRI fea-
tures. Based on these findings, we proposed the diagnostic criteria
for PSP-C.
Results: Adult onset, early falls, and supranuclear vertical gaze
palsy without dysautonomia may predict the diagnosis of PSP-C.
Brain MRIs have shown that dilatation of the pontocerebellar cistern
accompanying a well-proportioned small-sized pons and cerebellum
might be the characteristic imaging feature of PSP-C, and that hot
cross bun sign was not observed. We proposed preliminary diagnos-
tic criteria for PSP-C; required items include (A) slowly progressive
course (B) onset > 40 years (C) supranuclear palsy (D) truncal and
limb ataxia within 2 years after symptom onset (E) postural instabil-
ity with fall within 2 years after symptom onset. Exclusion items
include marked dysautonomia and hot cross bun sign on brain MRI.
S329
Probable PSP-C requires A1B1C1D1E, and possible PSP-C
requires A1B1D1E.
Conclusions: We consider PSP-C to be an adult-onset slowly
progressive disease characterized by truncal and limb ataxia, supra-
nuclear palsy, and postural instability with falls and without the pre-
sentation of dysautonomia and the hot cross bun sign.
838
Heterozygous GBA mutation in a patient with MSA-C: A
clinicopathologic report
M. Sklerov, A. Vinuela, E. Cortes, R. Kornreich, J.P. Vonsattel, R.
Alcalay (New York, NY, USA)
Objective: We report the case of a 62 year-old woman with a
progressive cerebellar syndrome, autonomic dysfunction, and Parkin-
sonism, with Multiple System Atrophy C (MSA-C) pathology on
postmortem examination and heterozygous glucocerebrosidase gene
mutation.
Background: Neurodegenerative conditions that are characterized
by aberrant accumulation of alpha synuclein include Parkinsons dis-
ease (PD), Dementia with Lewy Bodies (DLB), and Multiple Sys-
tems Atrophy (MSA). Recent clinical and neuropathological data
strongly associate glucocerebrosidase (GBA) mutations with
increased risk of developing Parkinsons disease and Lewy Body
Disease. Only 4 studies, to our knowledge, have looked at the link
between GBA mutations and multiple systems atrophy (MSA)1,2,3,4.
Overall, these studies found only 1 GBA mutation among 213 cases.
GBA mutations are relatively common in the Ashkenazi Jewish pop-
ulation with carrier frequency of 1/12-16.
Methods: The patient developed symptoms at age 54 with epi-
sodes of lightheadedness and gait instability. Gait problems contin-
ued progressing and, in the following 2-3 years she developed
dysarthria and dysmetria. At age 59 she further developed asymmet-
ric rigidity and bradykinesia. Parkinsonism was partially responsive
to levodopa, but treatment was limited by orthostatic hypotension.
Cognition was preserved. She had no family history of neurological
conditions. She passed away at age 62 and brain autopsy including
DNA analysis for 8 most common GBA mutations in the Ashkenazi
Jewish population was performed.
Results: Post-mortem examination revealed glial intracytoplasmic
inclusions that were widespread but predominantly located in the
oliv-ponto-cerebellar complex. Genetic analysis revealed a heterozy-
gous GBA p.R535H (R496H) mutation.
Conclusions: To our knowledge, there is only one other reported
case of GBA mutation in MSA. It is unclear if the occurrence of the
GBA mutation and the MSA-C in our patient is coincidence;
sequencing Ashkenazi Jewish MSA clinical cohorts and/or large
MSA brain banks may help establish a link between GBA mutations
and MSA.
839
Focal 123I-FP-CIT SPECT abnormality in a patient with
midbrain vascular Parkinsonism
P. Solla, A. Cannas, G. Orofino, R. Arca, M. Meloni, D. Fonti, F.
Marrosu (Cagliari, Italy)
Objective: To report the case of a patient affected by hemiPar-
kinsonism related to a left midbrain infarct with focal putaminal
degeneration at 123I-FP-CIT SPECT and responsive to levodopa.
Background: Parkinsonism with acute/subacute onset is uncom-
mon and other conditions, different from a neurodegenerative pro-
cess, should be excluded. Cerebrovascular diseases are considered
possible causes of Parkinsonism, representing up to 22% of second-
ary Movement Disorders. In this regard, infarcts in basal ganglia
have been related to Parkinsonism, often with rapid onset, and dopa-
mine transporter SPECT is highly recommended to confirm or
exclude nigrostriatal dopaminergic degeneration.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S330 POSTER SESSION
Methods: A 69-year old male patient come to our observation
suffering from motor slowness and rigidity at right limbs suddenly
started. His medical history revealed diabetes and a previous psychi-
atric history of depression. Neurological examination showed severe
bradykinesia and rigidity in his right hemibody, with inconstant mild
rest tremor.
Results: Brain MRI revealed a lacunar infarct in the substantia
nigra (Fig. 1) and associated features of cerebral small vessel disease
with multiple subcortical lacunar infarcts.
123I-FP-CIT SPECT showed an absent ligand binding in the left
putamen and a less marked reduction in the omolateral caudate (Fig.
2).
Levodopa (400 mg/daily) was prescribed with moderate response.
UPDRS motor score performed before levodopa introduction was
equal to 27, while after 3 months was 18. After 1 year, UPDRS
motor score was not increased.
Conclusions: In our patient, we identified a peculiar SPECT
abnormality secondary to nigral dopamine terminals degeneration
related to the midbrain lesion. In this regard, the selective vascular
damage in the midbrain might have played a similar action observed
in neurolesional animal models used in experimental settings.
The asymmetric uptake at dopamine transporter SPECT was dif-
ferent to findings commonly observed in typical PD pattern. While
in PD patients the asymmetric affectation of SPECT is characterized
by a striatal reduced uptake more pronounced in putamen with a ros-
trocaudal gradient, in this case there was a focal deficit of tracer
accumulation on left striatum, likely associated to the midbrain
lesion.
840
Multiple system atrophy: About one case
P.E. Sounga Bandzouzi, M.A. Magnerou, K. Toure, M. Ndiaye
(Dakar, Senegal)
Objective: describe one case of Multiple system atrophy.
Background: Multiple system atrophy is a neurodegenerative dis-
order in adults of unknown etiology. It is clinically characterized by
the combination of Parkinsonism, cerebellar syndrome, dysautonomia
and pyramidal syndrome. We report a case of multiple system atro-
phy in the Department of Clinical Neurology of the Fann Teaching
Hospital.
Results: A 35 years old man was hospitalized for disturbances of
stance and gait, and speech disorder due to difficulty in articulation
of words evolving progressively for 2 years. He is the first born in a
consanguineous family of four children whose other members are
apparently healthy.
The general examination revealed a good general state, a temper-
ature at 36.8 centigrade, a blood pressure of 80/60 mmHg with a
heart rate of 62 bpm. Physical examination revealed, dysarthria with
an explosive voice, dysmetria with a significant adiadochokinesia
while sitting, unsteady gait with expanding the supporting polygon
and a negative Rombergs sign. We also noticed a bradykinesia and
a light rest and intention tremor of the limbs. There were no other
abnormal sign. The Brain MRI found a large ponto-cerebellar atro-
phy. The patient received symptomatic treatment made of dihydroer-
gotamine and L-dopa. The clinical evolution was marked by the
persistence of signs.
Conclusions: Multiple system atrophy (MSA) is a rare neurode-
generative disorder, under-diagnosed in Africa with a poor prognosis.
Drug therapy remain disappointing.
841
Some aspects of life quality improvement in the patients with
Parkinsons disease who underwent treatment using embryo-fetal
preparations
N.S. Sych, M.A. Klunnyk, E.V. Ivankova, I.G. Matiyashchuk (Kyiv,
Ukraine)
Movement Disorders, Vol. 30, Suppl. 1, 2015
Objective: Investigation of life quality in patients with Parkin-
sons disease (PD) under the effect of treatment using preparations
of embryo-fetal material.
Methods: The study involved 20 patients diagnosed with Parkin-
sons disease between the ages of 48 to 74 years (mean age
62,14 6 2,12 yrs.), including 14 males and 6 female patients. The
diagnosis of Parkinsons disease was established according to the cri-
teria after Hughes AJ et al., 1992. Neurological status was assessed
using the Unified Parkinsons disease Rating Scale. PD patients con-
dition severity was consistent with the stages I-III by Hoehn and
Yahr. Hospital Anxiety and Depression Scale was used to study the
level of anxiety among the patients, for assessment of quality of life
(QOL) - SF-36 test. Assessment of motor and non-motor manifesta-
tions in the patients with PD was evaluated using a NMSPD scale.
All patients were administered a suspension of stem cells of fetal
liver and fetal brain 8-9 weeks of gestation. Control neurology exam-
ination, evaluation of the level of anxiety and QOL parameters were
carried out before treatment using embryo-fetal preparations and 3
and 6 months after patients treatment.
Results: As a result of treatment PD patients experienced a
decrease in symptoms of anxiety - 10,25 61,21 scores 3 months
after treatment vs. baseline - 11,43 61,21 scores, p> 0.05. 6 months
later, there was a significant decrease in anxiety levels compared to
the baseline - 8,43 60,61 and 11,43 6 1,21 scores respectively, p
<0.05.
3 months after fetal stem cells (FSCs) treatment role emotional
performance and physical functioning parameters significantly
(p<0.05) improved on SF-36 scale compared to the baseline. This
tendency also continued 6 months after FSCs treatment.
Significant decrease in non-motor manifestations of disease was
also observed 3 months after treatment (96,3 1 2,12) and 6 months
(92,131 3,21) after the above mentioned therapy in accordance with
the NMSPD scale, if compared to the baseline parameters before
treatment 104,85 1 3,32 (p<0,05).
Conclusions: Thus, as a result of PD patients treatment with use
of embryo-fetal preparations, a decrease in the level of anxiety from
severely pronounced up to sub-clinically expressed anxiety was iden-
tified, as well as improving life quality and decrease in non-motor
symptoms of the disease 6 months after treatment were observed.
842
Picks disease presenting with corticobasal syndrome: A review
of Parkinsonian features in 23 patients
P. Tacik, M. Sanchez Contreras, A. Wojtas, R.B. Perkerson, M.C.
Baker, P. Brown, A.J. Strongosky, K.M. Hinkle, S. Fujioka, M.
DeTure, N. Kouri, M.E. Murray, N.R. Graff-Radford, R. Rademakers,
O.A. Ross, Z.K. Wszolek, D.W. Dickson (Jacksonville, FL, USA)
Objective: To evaluate frequency of Parkinsonian features in
Picks disease.
Background: Picks disease (PiD) is a three-repeat tauopathy
microscopically defined by the presence of argyrophilic (except for
Gallyas silver staining) neuronal inclusions, called Pick bodies. PiD
is a very rare cause of frontotemporal dementia. Behavioral changes
predominate over language impairment.
Methods: We collected clinical, genealogical and genetic data of
23 autopsy proved Picks disease patients. None had mutations in the
microtubule-associated protein tau gene (MAPT).
Results: There were 12 women and 11 men with a mean age of
onset of 59.5 years (43-76 years), mean age of death of 69.7 years
(55-90 years), and mean disease duration of 10.2 years (4-23 years).
Six patients (26%) had a family history of dementia among siblings,
parents, or grandparents. Seven patients presented initially with lan-
guage decline, 9 with behavioral symptoms, one with memory loss
and 6 with corticobasal syndrome (rigidity, impaired dexterity,
apraxia, imbalance, bradykinesia, myoclonus, tremor, numbness).
Anti-dementia agents, antioxidants, and dopaminergic drugs (levo-
dopa-carbidopa n53, amantadine n51) were unsuccessful.
 POSTER SESSION
Genotyping of MAPT haplotypes revealed H1H1 (n512), H2H2
(n54) and H1H2 forms (n57).
Conclusions: In this Picks disease series Parkinsonian features
in the form of corticobasal syndrome affected 26%. Behavioral
changes occured more frequently than language disturbances. There
was no gender difference. Since several individuals in our series had
a positive family history but no MAPT mutation, other genetic fac-
tors may play a role in disease pathogenesis and should be pursued.
843
Did Charcot have vascular Parkinsonism?
H.A.G. Teive, F.M.B. Germiniani, R.P. Munhoz (Curitiba, PR,
Brazil)
Objective: To describe symptoms suggestive of vascular Parkin-
sonism (VP) in the last years of professor Charcots life.
Background: Jean-Martin Charcot (1825-1893) can be recog-
nized as the founder of Neurology as well as the first teacher of
nervous system diseases in a formal way. Charcot suffered from a
chronic low back pain and attacks of angina pectoris. He died on the
16th August, 1893, due to acute pulmonary edema secondary to
myocardial infarct.
Methods: Historical review of papers and books about Jean-
Martin Charcot and his unhealthy life.
Results: Charcot had short stature, with obesity, and poor
physical hygiene, sedentary, with strong appetite, chronic heavy
smoker, combined with intensive intellectual activity. He suffered
of chronic low back pain, and intermittent episodes of precordial
pain, suggestive of coronary insufficiency, associated to anxiety.
During a new years eve 1890 (Charcot was 65 years old) he had
acute precordial pain, and professor Potain, a famous Parisian cli-
nician, confirm the diagnosis of angina pectoris, and suggested
the fatal outcome in two years. In the last years of Charcots life
there were several descriptions of gait and posture disorder (shuf-
fling of gait, with petit pas and a flexed posture of the trunk),
mimicked Parkinso ns disease. Interestingly enough, there was no
reference to the presence of upper limbs symptoms, suggesting
the diagnosis of lower-half Parkinsonism, due to cerebrovascu-
lar disease (VP).
Conclusions: Professor Charcot probably had VP in the last years
of your life, associated to others vascular problems (angina pectoris,
probable cerebrovascular disease, and finally myocardial infarct).
844
The effectiveness of zolpidem in progressive supranuclear palsy
D.S.Y. Tsui, F.C.F. Chang, N. Mahant, S.D. Kim, J.M. Griffith, M.
Drury, V.S.C. Fung (Westmead, Australia)
Objective: To determine the effectiveness of zolpidem in patients
with PSP.
Background: Progressive supranuclear palsy (PSP) is an atypi-
cal Parkinsonian syndrome characterised by supranuclear gaze
palsy, akinesia, rigidity and postural instability. It is theorised that
some of the symptoms may be caused by a reduction in neuro-
transmission by the inhibitory gamma-aminobutyric acid (GABA)
receptor neurons. Zolpidem is a GABA agonist which targets
GABA receptors in the internal pallidum. There have been three
publications that suggest zolpidem produces motor improvements
in PSP patients.
Methods: We reviewed the results of an acute zolpidem chal-
lenge in 10 patients with possible or probable PSP seen at the Move-
ment Disorders Unit, Westmead Hospital from 2008 to 2014.
Patients were initially given a dose of 5mg with repeat 5mg dose
increments given every 1 hour to a maximum of 10mg, with the
dose limit determined by drowsiness. Motor function was assessed
using the Unified Parkinsons disease Rating Scale (UPDRS) and the
degree of drowsiness before and after zolpidem was also recorded.
S331
Statistical analysis was performed with SPSS 20.0 software, using
Wilcoxon signed-rank test. P value < 0.05 was set as statistically
significant.
Results: In 7 patients, the UPDRS was available. The baseline
UPDRS was 53.381/-16.04 (28-69) and after 5mg zolpidem was
48.71 1/-14.45 (27-63). The mean reduction in UPDRS was 4.00
1/- 7.83 (-3-21) after 5mg zolpidem but did not reach statistical sig-
nificance. 5 subjects performed the peg board task. Peg board time at
baseline was 31.69 1/- 12.84 (15.00-49.90) seconds and 39.80 1/-
12.11 (21.40-55.40) after 5mg of zolpidem. A >20% improvement
in UPDRS was observed in only 1 out of 10 patients but in the
majority, improvements were modest and did not translate into func-
tional benefit. Drowsiness was prominent after a total of 10mg was
administered.
Conclusions: The results suggest that zolpidem does not provide
functional improvement in majority of the patients despite modest
improvement in motor rating scales for PSP patients. Drowsiness
was a dose-limiting side effect in all patients.
845
Reversibility of the putaminal dopamine (DA) denervation
process during Parkinsonian syndrome: A clinical case report
with DA tranporter imageries
F. Viallet, D. Gayraud, J.B. Puech, P. Desvignes, S. Siles, B.
Bonnefoi (Aix en Provence, France)
Objective: To report a single unusual clinical case report of a
Parkinsonian syndrome (PS), initially presumed to be degenerative
because of a clear putaminal dopamine denervation (PDD) on a
dopamine transporter (DAT) imagery, with an unexpected clinical
improvement leading to a second DAT imagery, 34 months later,
showing a clear reduction of the PDD.
Background: Degenerative PS are characterized by a PDD pro-
cess: it is usually considered as progressive and not reversible. DAT
imagery now provides an in-vivo semi-quantitative assessment of the
PDD.
Methods: case N 141690: This 67 year-old female patient has
started in 2009 a progressive gait disorder further completed by falls
with dysgraphia, dysphagia and REM sleep behavioral disorder. In
May 2011, clinical examination showed an axial akinetic-rigid syn-
drome with a slight truncal ataxia and orthostatic hypotension. MRI
was not contributive and the MMS score was 30/30. A diagnosis of
MSA was suspected and L-Dopa was progressively started, not
beyond 150mg/d because of nausea. In January 2012, a clear PDD
was observed on DAT imagery (putamen/occipital ratios: 0.47 left
side, 0.40 right side).
Results: During follow-up, L-Dopa was poorly tolerated
because of nausea and hypotension, then limiting the titration
within 300mg/d. Surprisingly, the clinical status clearly improved
and the L-Dopa was gradually reduced until 150mg/d in December
2013 and further stopped in June 2014. This unexpected evolution
led to perform a second DAT imagery (with same detection system
and procedure and operator) in October 2014, then showing a clear
reduction of PDD (putamen/occipital ratios: 1.49 left side, 1.40 right
side).
Conclusions: During the course of degenerative PS, a good corre-
lation between the clinical motor impairment and the PDD on DAT
imagery has been reported in longitudinal studies (Tolosa E et al
Mov Disord 2007;16: 2346-51; Nandhagopal R et al Brain 2009;
132:2970-9), then globally confirming the non reversible progression
of the PDD, even if some attenuation was patent in few individual
cases.
When a clinical recovery is persistent after the L-Dopa washout
in presumed degenerative PS, the DAT imagery can provide a clear
information about the possible partial reversibility of the PDD.
Acknowledgements: GE Healthcare for providing the semi-
quantitative assessment software and centralised reading of the
data.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S332 POSTER SESSION

Parkinsons disease: Cognition Background: Dementia is a devastating yet difficult-to-predict

complication of Parkinsons disease (PD). Identifying people with
846 PD who are at high short-term risk of developing dementia can be
important in planning care and at the same time help understand het-
Validation of predictors of dementia in Parkinsons disease erogeneity of disease mechanisms, and even create cohorts of
J.B.M. Anang, S.R. Romenets, T. Nomura, R.B. Postuma (Montreal, patients who are potential participants in clinical trials aimed at
QC, Canada) dementia prevention.
Objective: Validate predictors of dementia in two independent Methods: We validated 8 selected predictive variables of demen-
cohorts and develop dementia prediction tool that can identify high- tia (previously published) in 2 external prospective cohorts (Montreal
risk patients in the clinic. and Japan). Using regression analysis, receiver operating characteris-
tic curves, sensitivity analysis in the primary cohort, 8 variables
were chosen to generate a dementia scoring algorithm. Model 1 is a
TABLE 1. Dementia Prediction Models Developed in Pri- comprehensive and includes age greater >70, male sex, bilateral dis-
mary Cohort ease onset, RBD, freezing and/or falls, orthostatic blood pressure
drop, MCI and hallucinations. Model 2 does not include MCI and
Predictors Model 1 Model 2 hallucinations.
Results: The dementia conversion rate was 34% in the develop-
Male sex 1 1 ment cohort (n580) and 19% in the validation cohort (n5134) over
Age greater than 70 years 1 1 a mean follow-up duration of 4.4 years and 3.6 years respectively.
Falls or Freezing 1 1 Of the selected 8 predictive variables from the development cohort,
Bilateral disease onset 1 1 5 of these were significantly associated with dementia in the valida-
Orthostatic BP drop >10 mmHg 1 1 tion cohort (bilateral disease onset, hallucinations, freezing and/or
REM sleep behaviour disorder 1 1 falls were not significant, but all odds ratio >1.0.
MCI 1 - Both models reliably predicted the dementia status; prediction
Hallucinations 1 - accuracy was 82.5% for model 1 and 78.8% for model 2 in the
Max Score 8 6 development cohort. The accuracy in the validation cohort was
Mild cognitive impairment (MCI), blood pressure (BP) 80.6% and 76.1% for model 1 and model 2 respectively using a

TABLE 2. Predictive variables in the development and validation cohorts

Development cohort Combined validation cohort
Variable
% with variable odds ratio (95%CI), p-value % with variable odds ratio (95%CI), p-value
age >70 36.3 5.8 (2.1 16.0), 0.001 56.0 3.93 (1.38 11.22), 0.011
Male sex 63.7 3.64 (1.2 11.1), 0.023 50.0 3.15 (1.22 8.15), 0.018
Bilateral disease onset 21.3 3.87 (1.3 11.8), 0.017 36.8 1.95 (0.80 4.75), 0.144
*Freezing 6falls 38.8 13.9 (3.0 64.5), 0.001 35.8 1.66 (0.6 4.3), 0.294
*RBD 58.8 49.7 (5.1 480.3), 0.001 38.1 6.24 (2.09 18.67), 0.001
*SBD drop 58.8 7.5 (1.9 30.5), 0.005 45.5 4.15 (1.08 15.97), 0.038
*Hallucinations 17.5 13.0 (2.3 72.9), 0.003 22.4 1.86 (0.6 6.0), 0.299
*MCI 51.2 22.5 (4.0 126.3), <0.001 26.9 2.8 (1.0 7.7), 0.044
*Adjusted for age, sex, duration of disease at baseline and duration of follow-up. Mild cognitive impairment (MCI), systolic blood pressure
(SBP), REM sleep behaviour disorder (RBD), confidence interval (CI)

Fig. 1. (846).

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION S333

binary cut-off. The triple combination of baseline RBD, MCI and

orthostatic systolic blood pressure drop conveyed the highest risk.
Scores were also stratified into low, intermediate and high categories
to represent risk for dementia with 2.5% and 88.9% of demented
patients classified in the low and high risk categories respectively
(development cohort). 6.3% in low vs 57.1% in high risk categories
were demented in the validation cohort based on model 1.[figure1]
Conclusions: A 6-8 item clinical prediction tool was able to
clearly delineate medium-term risk of dementia in PD. Further con-
firmation of predictors and validation of tool is needed in larger
cohort.

847
Urinary dysfunction in progressive supranuclear palsy in
comparison to Parkinsons disease and multiple system atrophy
T. Yamamoto, M. Asahina, T. Uchiyama, S. Hirano, Y. Yamanaka,
M. Fuse, Y. Koga, M. Yanagisawa, R. Sakakibara, S. Kuwabara
(Chiba, Japan)
Objective: We aimed to clarify the characteristics of the urinary
dysfunction in progressive supranuclear palsy (PSP) by using urinary
symptoms questionnaire and urodynamic study in comparison to Par-
kinsons disease (PD) and multiple system atrophy (MSA).
Background: Although autonomic dysfunctions are considered to
be mild in PSP as compared to PD and MSA, it is not uncommon
that patients with PSP show urinary symptoms.
Methods: We recruited 26 patients satisfied with probable or pos-
sible criteria of national institute for neurological diseases and
stroke-society for PSP (NINDS-SPSP) who underwent urinary symp-
toms questionnaire and urodynamic study. We compared the urinary
symptoms and urodynamic findings of PSP patients with those of PD
patients (n5218, mean duration 3.2 years) and MSA patients
(n5193, mean duration 3.2 years).
Results: The mean age and the mean disease duration of PSP
was 70.1 6 6.6 years old and 2.6 6 1.6 years, respectively. The
scores of minimental state examination (MMSE) and frontal assess- Fig. 1. (847).
ment battery (FAB) were 22.5 6 5.6 and 10.4 6 3.8, respectively.
Twenty two patients with PSP showed decreased blood flow in fron-
tal lobe in single photon emission computed tomography (SPECT).
Urinary storage symptoms were seen in 45% of PSP patients, Objective: To determine whether educational level exerts a dif-
whereas urinary voiding symptoms were seen in 60% of PSP ferential impact on pre- and post-DBS neurocognitive test perform-
patients. The prevalence and severity of urinary symptoms in PSP ance among Hispanics (H) and Non-Hispanics (NH).
patients were equivalent to those of PD and MSA patients except for Background: Educational attainment is likely related to DBS
intermittency and straining. Urodynamic study revealed that 73% of cognitive outcome and an important factor in candidate selection.
PSP patients showed detrusor overactivity, which was slightly larger Determining DBS candidacy in PD is challenging, especially among
than that of patients with PD (69%) and MSA (67%) without statisti- individuals whose native language is not English and ethnic minor-
cally significance.[Figure 1-A] Post-void residual of PSP patients ities. Given the well-documented disparity in DBS utilization among
was 122 6 111ml, which was significantly larger than that of PD ethnic minorties vs. Caucasians in the USA, understanding the
(34 6 45ml) and was equivalent to that of MSA (113 6 111ml). [Fig- unique role of education in cognitive test performance is particularly
ure 1-B] The bladder contractility of PSP as evaluated by Schafers important for determining DBS candidacy as well as documenting
nomogram was equivalent to that of PD and was significantly better post-DBS outcome.
than that of MSA. The mean duration of motor unit potentials of Methods: Thirty-six individuals with idiopathic Parkinsons dis-
PSP was 9.0 6 2.5ms, which was equivalent to that of MSA ease, 20 H and 16 NH, underwent pre- and post-DBS neuropsycho-
(9.3 6 2.2ms) and was significantly longer than that of PD logical evaluation. Education (M=12.47), months since DBS
(7.7 6 1.8ms). (M=24.12), and disease duration (M=13.52 years) were comparable
Conclusions: Many patients with PSP showed various urinary between groups. Independent and paired sample t-tests were used to
dysfunctions, which is important in differentiating PSP from PD and compare pre- and post-surgical test scores. Multiple regression was
MSA. conducted to examine the relationship between years of education
and post-surgical scores, after controlling for age and baseline (pre-
surgical) performance.
848 Results: Pre-surgically, the H group showed significantly lower
scores on digit span and confrontation naming compared to the NH
Demographic factors in pre- and post-surgical DBS group (p<.05). Following DBS, the H group exhibited a more perva-
neuropsychological evaluation sive pattern of cognitive decline than NH, with significantly lower
S.A. Anderson, C. Bermudez, C. Ghilain, N. Sun-Suslow, M. Forte, I. scores on MMSE, Similarities, BNT, COWAT, Immediate and
Babakhanyan, B. Gallo, C. Luca, J. Jagid, C. Singer, B.E. Levin Delayed Recall CVLT-II, and Hooper VOT (p<.05). The relationship
(Miami, FL, USA) between education and post-surgical performance was unique, where

Movement Disorders, Vol. 30, Suppl. 1, 2015

S334 POSTER SESSION
years of education was a significant predictor of outcome, but for
different measures in H and NH groups.
Conclusions: These findings show that ethnicity is an important
factor in understanding the role of education as a predictor of DBS
outcome. These findings argue against using a uniform approach to
evaluating DBS candidacy across different ethnic groups. Further
research is needed to disentangle the impact of ethnicity and lan-
guage on DBS outcome.
849
Is it possible to improve cognitive functions through complex gait
training in patients with Parkinsons disease?
C. Bedeschi, K. Guedes, F. Iotti, D. Bauer, A. Manfredi, L.
Rodrigues, M.E. Piemonte (S~ao Paulo, Brazil)
Objective: The aims of this study were (1) to assess the effects
of cognitive training associated with walking on the cognitive func-
tion of Parkinsons disease (PD) patients and (2) to assess the effects
of cognitive training associated with walking on gait performance
during a dual-task.
Background: Decreasing gait efficiency is associated with declin-
ing cognition with age. This association is more evident in PD
patients, which suggests that approaches integrating cognition and
gait training could be beneficial for their treatment. This integrative
training could improve cognitive functions associated with gains
derived from the motor components of training. These cognitive
gains could positively impact gait performance during a dual-task,
which is frequently required during daily life activities. To investi-
gate this hypothesis, we developed a cognitive training paradigm
based on functional tasks that are performed during walking.
Methods: A total of 20 PD patients (early and moderate stages)
performed 10 sessions (2 per week) of cognitive training associated
with walking. The training consisted of five tasks requiring various
cognitive functions that were performed concomitantly with walking
during daily living situations. The cognitive functions practiced were
divided attention, working memory, planning, response monitoring
and response inhibition. The effects of training on general cognitive
ability and gait performance during a dual-task were assessed with
the Montreal Cognitive Assessment (MoCA) score and the number
of steps performed during the dual-task. These assessments were
conducted before training, immediately after training and 60 days
after training.
Results: Patients significantly increased their MoCA scores and
the number of steps performed during the dual-cognitive test after
training, and these improvements were maintained after 60 days of
no training.
Conclusions: The intervention in this study trained patients with
challenging cognitive tasks, which reproduced daily living situations.
With this intervention, PD patients during the early and moderate
disease stages could improve their global cognitive functions and
their ability to divide their attention while walking. This findings
suggests that is possible to recruit cognitive reserves in PD patients
and that this cognitive improvement could reinforce the efficiency of
compensatory mechanisms related to gait performance.
850
Progression of mobility impairment and motor related quality of
life in individuals with Parkinsons disease: Results from NPF-
QII
J. Ben, A. Stone, M.S. Okun, J. Nocera, P. Schmidt, S.S. Wu, Q. Pei,
C.J. Hass, NPF QII Investigators (Gainesville, FL, USA)
Objective: The aims of the study were to investigate the extent
and progression of mobility and cognitive impairment and quality of
life over 36 months in the National Parkinsons Foundation QII
registry cohort.
Movement Disorders, Vol. 30, Suppl. 1, 2015
Background: Little is known about the natural history of mobil-
ity impairment in persons with Parkinsons disease (PD). The major-
ity of the extant literature and our understanding are grounded in
cross sectional studies of patients with moderate to advanced PD.
Comparisons across Hoehn and Yahr staging and quartiles of
UPDRS motor severity represent a complex interplay between dopa-
minergic and non-dopaminergic pathology, incidence of increased
non-motor symptoms, deconditioning, compensatory strategies, and
clinical management, all of which can confound interpretation. Lon-
gitudinal assessment is therefore critical.
Methods: We included 1,665 subjects from the NPF QII database
who were evaluated once a year for three consecutive years across
all NPF centers of excellence using standardized protocols.
Results: The analyses indicated patients with higher Hoehn and
Yahr (HY) stage had more impaired mobility, indicated by a higher
standardized TUG (p<0.0001) and PDQ-39 mobility (PDQm) values
(p<0.0001). Similarly, patients with more severe cognitive impair-
ment levels had higher TUG (p<0.0001) and PDQm values
(p<0.0001). In addition, we performed multiple regression analyses
to assess the effect of HY stage, cognitive impairment, time of visits
and their interactions on TUG and PDQm, controlling for baseline
demographics and characteristics.The models indicated that both HY
stage and cognitive impairment were significantly associated with the
outcomes (all p<0.0001). In addition, the correlation between poor
cognition and impaired mobility was found to be higher at follow up
visits 2 and 3 than at baseline (p50.026 for TUG and p50.002 for
PDQ-mobility). A similar regression model was constructed for the
PDQ-39 summary index (excluding the PDQm) and we obtained
same conclusion.
Conclusions: Higher Hoehn and Yahr stage, cognition impair-
ment, cognition impairment by time interaction were significant fac-
tors associated with TUG, PDQ-mobility and PDQ index summary
scores.
851
PD-MCI: Application of the level I criteria and prediction of
PDD
J.A. Boel, J. Hoogland, R.M.A. de Bie, J.G. Goldman, B. Schmand,
A.I. Tr
oster, D.J. Burn, I. Litvan, G.J. Geurtsen, The MDS PD-MCI
Validation Study Group (Amsterdam, Netherlands)
Objective: To evaluate the prognostic value of Level I MDS PD-
MCI criteria using Parkinsons disease dementia (PDD) as the pri-
mary outcome.
Background: Mild cognitive impairment (MCI) is considered a
transitional stage between normal cognitive functioning and demen-
tia. Mild cognitive impairment in Parkinsons disease (PD-MCI) is
of potential importance in the early identification and management
of patients at risk for the development of dementia. A clear defini-
tion of PD-MCI is essential for future research on etiology, disease
course, and disease modifying or causative treatment of cognitive
decline in PD.
The International Parkinson and Movement Disorder Society
(MDS) proposed diagnostic criteria for PD-MCI, comprising two
operationalizations: Level I (abbreviated neuropsychological assess-
ment) and Level II (comprehensive neuropsychological assessment).
Methods: Level I PD-MCI criteria will be retrospectively applied
to several databases provided by the MDS Study Group Validation
of Mild Cognitive Impairment in Parkinsons disease. These data-
bases include PD patients with longitudinal neuropsychological
assessment and available PDD status. Level I PD-MCI criteria will
be applied in several forms: namely by, 1) scales for global cognitive
abilities, 2) varying numbers of tests per domain, and 3) different
cut-offs for cognitive impairment. Analyses include survival analysis
while correcting for relevant demographic variables (e.g. age and
years of education) and clinical variables (e.g. symptom duration and
UPDRS-III scores).
 POSTER SESSION S335

Results: Longitudinal data on approximately 1400 patients fulfill- 853

ing level I PD-MCI criteria will be analyzed. Follow-up duration
ranges from 1 to 8 years. The results will include the prognostic
value of Level I PD-MCI for PDD.
852
High-frequency exercise improves executive function in
individuals with Parkinsons disease
M.C. Caciula, M. Horvat, R. Croce (Statesboro, GA, USA)
Objective: To identify the effects of chronic exercise training on
aspects of executive function, specifically working memory (WM)
and cognitive flexibility in PD.
Background: Parkinsons disease (PD) is characterized by pro-
gressive loss of motor function, followed by behavioral, physiologi-
cal, and cognitive modifications in a great proportion of patients.
Cognitive function impairments are observed relatively early after
the onset of PD and if not treated accordingly, can progress to
dementia. Although exercise is considered a valuable tool in delaying
the progression of disease related outcomes, the optimal frequency of
exercise interventions has not been identified.
Methods: Forty-three participants (M age 5 68.5 (SD 5 11.3), 26
males), with idiopathic PD completed an N-back task and a category
switching task at baseline and after 12 weeks of multimodal exercise
training. Global switch costs (ms) and response accuracy (% correct
responses) were calculated for the switch task, and response time
(RT) (ms), and accuracy (% correct responses) for the N-back task.
The participants were divided into two training frequency groups: a)
a high - frequency: 4 - 5 times each week (N 5 23, M age 5 68.6
(SD 5 5.8), 16 males), and b) a low - frequency: 3 times or less each
week (N 5 20, M age= 67.6 (SD 5 4.5), 10 males)
Results: Both frequency groups improved in executive function,
showing improved N-back accuracy (F (1, 41) =17.37, p<.001,
h_p^2=0.29) and global switch-cost accuracy (F (1, 41) =5.08,
p<.05, h_p^2=0.11). The high - frequency group displayed signifi-
cantly greater reductions in global switch costs (F (1, 41) 5 5.53,
p<.05., h_p^2=0.09), and response time (F(1,41)=14.96, p<.001,
h_p^2=0.26), than the low-frequency group.
Conclusions: The results of the study suggest that a high fre-
quency, multimodal exercise program involving functional move-
ment, strength, and flexibility can facilitate executive functioning in
PD, and could be an important component in the overall treatment of
individuals with PD.
Subcortical functioning and its relationship to risk detection in
patients with Parkinsons disease on different cognitive
impairment
S. Cano Galindo, D.A. Manjarrez Gardu~ no, H. Dur an Meza, M.
L
opez, E. Soto Abraham, F. Velasco Campos, D. Trejo Martnez, D.
Santana d (Mexico City, Mexico)
Objective: To compare subcortical scores of PD-CRS and its
relation to the percentage of cards risk in a group of patients with
Parkinsons disease.
Background: The IOWA Gambling Test (IGT) principally acti-
vates functions related to the orbitofrontal cortex, which is relevant in
the generation of outcome expectancies and the processing of rewards.
The analysis of IGT performances in patients with Parkinso ns disease
is important because represents a good clinical model to study reward
processing when its neural bases are affected by a neuropathology or
are overdosed by dopaminergic therapies (Poletti, Cavedini & Bonuc-
celli; 2011). In Parkinso
ns disease patients exists an incorrect evalua-
tion of context-relevant outcomes that could be the reason of a poor
performance in decision-making tasks, and could explain cognitive
and behavioral problems related to impulse control disorder (Mapelli,
DiRosa, Cavaletti, Shiff, Tamburin; 2014).
Methods: The study included 44 patients between 40 and 80
years old with H&Y 1-2 with a scheme of standard drug treatment
(basis on Levodopa). The patient group was divided into four sub-
groups (quartiles) according to the total score obtained of the sub-
cortical index from the Parkinsons disease-Cognitive Rating Scale
(PD-CRS). We compared the four groups of subcortical score (high/
low) in each subgroup and the relationship with the percentage of
risk cards obtained in a task type Iowa Test for Mexican population.
All patients were evaluated on state ON. It was used a Students t-
test to compare the subcortical scores in each subgroup and a corre-
lation coefficient for the relationship with the percentage of risk
cards.
Results: It is found that a higher score on the subcortical PD-
CRS index has an increased risk percentage, while for a lower sub-
cortical score there is a decrease in the percentage of risk (group
1=32%, group 2=33%, group 3=39%, group 4=40%).
Conclusions: There is a disociation between the high and low
subcortical scores in the PD-CRS and the risk percentage, this is
important because most of the investigations take the orbitofrontal
cortex as one of the most relevant references in the performing of
the gambling task, however using a dynamic model its crucial to
include the involvement of subcortical structures in the performing
of these tasks.

854
TABLE 1. Demographic and clinical features of 43 patients Association of serum uric acid level with cognitive function
with Parkinsons disease (PD). among patients with multiple system atrophy
B. Cao, Q. Wei, R. Ou, J. Yang, B. Zhao, H. Shang (Chengdu,
Variable HF Exercise LF Exercise p Peoples Republic of China)
Number of patients 23 20 Objective: To clarify the correlations between serum uric acid
Male/Female 16/7 10/10 and cognitive function as well as frontal lobe function in Chinese
mean (SD) mean (SD) MSA patients.
Age (years) 68.6 (5.8) 67.65 (4.5) 0.55 Background: Oxidative stress involves in the pathogenesis of
Age of PD onset (years) 57.5 (12.9) 58 (13.5) 0.62 multiple system atrophy (MSA) and cognitive impairment. Uric acid
PD duration (years) 10.6 (5.2) 9.8 (4.9) 0.83 has an anti-oxidative effect.
Hoehn and Yahr 2.3 (0.5) 2.5 (0.4) 0.27 Methods: The Chinese version of the Addenbrookes Cognitive
Education (years) 18.3 (2.9) 17.9 (2.7) 0.81 Examination-revised (ACE-R) and the frontal assessment battery
Exercise habits (times/week) 5.1 (1.1) 2.2 (0.6) <0.0001* (FAB) were applied to evaluate cognitive function in 89 probable
MoCA score 25.5 (2.7) 25.4 (2.5) 0.88 MSA patients and 64 healthy controls.
UPDRS motor score 26.4 (4.3) 26.5 (5.0) 0.95 Results: Thirty-three patients (37.1%) had global cognitive defi-
cits according to ACE-R. Based on FAB, 27 patients (30.3%) had
HF, high frequency; LD, low frequency; SD, standard deviation; frontal lobe dysfunction. After adjusting for educational years,
MoCA, Montreal Cognitive Assessment; *significant difference (p2 patients with cognitive deficits had lower uric acid level than patients
0.05); UPDRS, Unified Parkinsons disease Rating Scale. without cognitive deficits. Patients with frontal lobe dysfunction had

Movement Disorders, Vol. 30, Suppl. 1, 2015

S336 POSTER SESSION
lower uric acid level after adjusting for UMSARS scores. In a for-
ward multiple linear regression, uric acid level and educational years
were the variables predicting the ACE-R score (F=36.540, R2=0.459,
P=0.0001), uric acid accounting for 14% of the total variables. Uric
acid was the only variable contributing to the FAB score (F=18.551,
R2=0.176, P=0.0001).
Conclusions: Our study suggested that low level of serum uric
acid was associated with cognitive deficits in MSA. Low uric acid
level predicting cognition decline in MSA needs more studies.
855
Increasing arm motion when walking enhances lower limb
coordination in individuals with Parkinsons disease
C. Dalton, J. Nantel (Ottawa, ON, Canada)
Objective: The objectives of the present study were to determine
the impact of arm movement on gait performance and gait symmetry
in individuals with Parkinsons disease (PD).
Background: Slow gait speed, asymmetry and reduced gait coor-
dination are commonly seen in individuals with PD and are associ-
ated with higher risk of falling. Gait in healthy individuals consists
of highly consistent cyclical movement of legs and arms as well as a
tight interlimb coordination, both within and between lower and
upper limbs. However the interdependence of the cyclical motion of
the legs and arms and how it contributes to gait performance in PD
needs to be further explained.
Methods: Gait performance was assessed in 25 individuals with
PD (disease duration 6.5 6 4.5 years). Participants walked in three
conditions: normal walking, walking with both arms immobile
(strapped on the chest), and while consciously moving the arms. Gait
performance and limb coordination was quantified using 6 wireless,
body-worn inertial sensors (APDM) placed on the upper, lower limbs
and torso. Gait performance between the three walking conditions
was assessed using one way repeated measure ANOVAs followed
with the appropriate All Pairwise Multiple Comparison Procedures
when permitted.
Results: As shown in Table 1, the arm conditions had an effect
on both stride length (p<0.001) and gait speed (p<0.05). Phase coor-
dination index was also different between the arm conditions
(p<0.05), while gait arrhythmicity showed a tendency (p50.06). No
differences were seen in stride asymmetry. The arm symmetry index
significantly improved between normal gait and consciously moving
the arms (p<0.05).
Conclusions: Arm swing had distinctive effects on different gait
components as speed, stride length and phase coordination improved
with deliberate arm motion, while stride asymmetry did not.
Although participants did increase arm movement, it is possible that
the increases motion was not sufficient to have a significant impact
on lower limb symmetry. While consciously moving the arms seems
to have a positive effect on aspects of gait related to risk of fall, as
this strategy possibly increases attentional demand, future studies
should determine if this strategy is sustainable over a longer period
of time and during activities of daily living.
TABLE 1:. Spatial-temporal gait parameters with normal and no arm movement and when consciously moving the arms.
N=25 Normal arm motion
Stride Length (m) 1.48 6 0.12*,**
Gait Speed (m/s) 1.40 6 0.14
Arrhythmicity (CV) 2.18 6 0.48
Stride Length Asymmetry (%) 1.74 6 0.64
Arm Symmetry Index (%) 32.72 6 12.75
Phase Coordination Index (%) 5.36 6 3.73**
Significantly different from no arm motion, p < 0.05 Significantly different from increased arm motion, p < 0.05 * Significantly different
from no arm motion, p < 0.01 ** Significantly different from increased arm motion, p < 0.01
Movement Disorders, Vol. 30, Suppl. 1, 2015
856
Language-mediated eye movements in Parkinsons disease
M. Delgado-Alvarado, J.A. Du~
nabeitia, H. Jimenez-Urbieta, B.
Gago, C. Caballero, M. Carreiras, M.C. Rodriguez-Oroz (San
Sebasti
an, Spain)
Objective: To investigate the eye-movement patterns of patients
with Parkinsons disease (PD) with normal cognition (PDNC) and
with mild cognitive impairment (PDMCI).
Background: There is discrepancy regarding the amplitudes of
saccades, the fixation time and the error rates in visual search for PD
patients without dementia when compared with control subjects. In
contrast, most studies suggest that oculo-motor performance is
impaired in PD patients with dementia. However, little is known
about potential differences between PDNC and PDMCI patients and
controls when confronted with higher order visual tasks requiring
executive control and enhanced visuo-attentional skills.
Methods: 20 PDNC, 11 PDMCI patients and 20 healthy controls
completed an eye-tracking study in which they had to identify the
picture that matched a given auditory input among a set of visual
distractors that could be semantically related or unrelated to the tar-
get (e.g., hearing cat and being presented with the distractor pic-
ture of a dog; i.e., a test based on the visual-world paradigm).
Participants also completed a behavioral flanker task designed to
characterize each groups inhibitory skills based on their executive
functions.
Results: PDMCI patients showed significantly higher error rates
than controls in the general accuracy in the task (p50.02), while
PDNC and controls did not differ (p>0.55). PDNC and PDMCI
patients showed no differences between them and with controls in
number and duration of fixations and saccade amplitudes (p>0.10).
When required to inhibit semantic distractors, both groups of PD
patients showed significantly higher fixation probabilities on the
competing elements than on unrelated distractors as compared to
controls (ps<0.02). Accordingly, all PD patients showed significantly
larger incongruity effects than controls in the accuracy data from the
flanker task (p<0.05).
Conclusions: The basic ocular movements are similar in PD
patients and controls in an ecologic language-mediated visual task.
PDMCI patients do not differ from PDNC patients in their ocular
behavioral performance. However, patients with PD
(PDMCI 1 PDCN) show a different pattern of visual performance
when the visual analysis of a display requires higher order cognitive
mechanisms based on inhibitory skills.
857
Cognitive impairment and fall rate in Parkinsons disease (PD)
in Nigeria
T.H. Farombi, J.O. Yaria, M.O. Owolabi, A. Ogunniyi (Ibadan,
Nigeria)
Objective: To investigate the associations between cognitive
impairment and fall rate in PD patients.
No arm motion Increased arm motion P-Value (ANOVAs)
1.45 6 0.11** 1.50 6 0.12 <0.001
1.39 6 0.13 1.42 6 0.12 <0.05
3.21 6 1.58 2.52 6 0.97 0.06
1.90 6 0.74 1.66 6 0.54 NS
27.90 6 13.34 <0.05
5.11 6 2.60 4.32 6 2.16 0.01
 POSTER SESSION S337

TABLE 1:. Showing demographics and other variables associated with falls
NON FALLERS(40) FALLERS(27) P Value

SEX (N,%)
MALE 28(70.0) 19(70.4) 0.97
FEMALE 12(30.0) 8(29.6)
AGE(MEAN,SD) 65.6 (10.6) 67.7(7.1) 0.48
DISEASE DURATION(MEDIAN,IQR) 23 (9-36) 84(36-132) 0.00
POLYPHARMACY(N,%) 16 (41.0) 12 (44.4) 0.78
PARKINSON MEDICATION(N,%) 37 (94.9) 26 (96.3) 0.79
UPDRS-MOTOR(MEAN,SD) 15.1(6.7) 21.9 (8.9) 0.00
UPDRS-ADL(MEAN,SD) 8.4 (5.1) 14.7 (5.5) 0.00
UPDRS-MENTATION(MEAN,SD) 1.3 (1.2) 3.3 (2.6) 0.00
TOTAL TINNETTI SCORE(MEAN,SD) 23.3 (5.8) 18.6 (8.3) 0.01
HOEYN &YAHR(MEAN,SD) 1.9 (0.8) 2.5 (0.9) 0.00
TIME UP &GO TEST (MEDIAN,IQR) 15 (13.0-22.7) 18.5(15.0 - 28.0) 0.12
ORTHOSTATIC HYPOTENSION(N,%) 4 (10.5) 5 (20.0) 0.29
HYPERTENSION(N,%) 20 (52.6) 10 (40.0) 0.33
GDS (MEAN,SD) 6.5 (1.5) 7.3(1.9) 0.07
TOTAL CSID SCORE (MEAN,SD) 46.4 (4.8) 43.5 (5.1) 0.02
COGNITIVE IMPAIRED (N,%) 21(53.8) 20 (80.0) 0.03
Unified Parkinsons disease rating scale (UPDRS), Activities of daily living (ADL),Community screening interview for Dementia (CSID), Stand-
ard deviation (SD)

Background: Falls in Parkinsons disease (PD) patients were ear-
lier thought to result from failure of motor mechanism in the central
nervous system. Recent studies had shown possible association
between cognitive dysfunction, gait abnormality and fall in PD
patients. However it is not clear if cognitive dysfunction an inde-
pendent risk factor or if its effect on falls is associated with gait
abnormality. We studied this possible association with the intent to
prevent falls by improving cognitive dysfunction.
Methods: This was a descriptive study conducted among PD
patients at the University College Hospital Ibadan. Diagnosed PD
patients were assessed for risk factors and frequency of falls using
Tinneti gait and balance test, Hoehn and Yahr severity scale, Unified
Parkinsons disease Rating Scale, Timed Up and Go tests and modi-
fied Community Screening Instrument for Dementia (CSID). Com-
parison between fallers and non-fallers was performed using
statistical univariate analyses followed by multivariate logistics
regression.
Results: 40.3% of PD patients experienced falls since the onset
of the disease, with 74.1% having 2 or more fall episodes in the last
one year. Disease duration was significantly longer in the fallers,
with significant difference in Tinetti Balance, Hoehn and Yahr,
UPDRS, Geriatric Depression Scale and CSID score when compared
to non-fallers. Daily life disabilities measured by the UPDRS was
the only independent predictor of fall after a multivariate logistic
regression was modeled.
Conclusions: PD patients with cognitive impairment fall more
compared with cognitively intact PD patients. Cognitively impair-
ment, gait abnormality, disease duration and severity were signifi-
cantly associated with falls among PD patients. However cognitive
impairment was not independently associated with falls.
858
Visual hallucinations in Parkinso
ns disease with mild cognitive
impairment do not imply a more severe cognitive deficit but a
more severe cerebral hypometabolism
C. Gasca-Salas, P. Clavero, D. Garca-Garca, R. Gonz alez-
Redondo, J. Obeso, M.C. Rodrguez-Oroz (Toronto, ON, Canada)
Objective: We aimed to investigate if PD-MCI patients with VH
have a more severe degree of cognitive impairment and hypometabo-
lism than PD-MCI patients without VH.
Background: Mild cognitive impairment (MCI) and visual hallu-
cinations (VH) are considered risk factors for dementia in Parkin-
sons disease (PD). FDG-PET studies have shown that both MCI and
VH in PD patients are associated with cerebral hypometabolism

Fig. 1. (858).

Movement Disorders, Vol. 30, Suppl. 1, 2015

S338 POSTER SESSION
mainly in posterior regions, which is more widespread in PD patients
with dementia. However, they are common co-morbidities in PD and
the specific value of each of them in the risk of dementia is not
known.
Methods: Twelve PD-MCI patients without VH (n-VH) and 9
with VH (p-VH) according to the UPDRS-I scale, and 19 healthy
controls were studied using an extensive battery of neuropsychologi-
cal tests and a cerebral 18FDG-PET. Analysis of neuropsychological
differences was performed with SPSS software. Regional glucose
metabolism was analyzed using statistical parametric mapping
(SPM8) corrected for age.
Results: No differences in clinical features and in cognitive tests
but in the Boston (better score in p-VH) were observed between p-
VH and n-VH patients. p-VH patients had lower FDG uptake bilater-
ally in the occipital, parietal and temporal lobes, and to a lesser
extent in the middle cingulum and right frontal lobe than n-VH
patients. In comparison with controls, p-VH patients showed exten-
sive widespread hypometabolism whereas n-VH patients did not
show differences [figure1]
Conclusions: Even in the absence of cognitive differences, PD-
MCI patients with VH have a more severe pattern of hypometabo-
lism than PD-MCI patients without VH. This pattern resembles to
what has been reported in PD patients with dementia. These findings
support and expand the value VH as biomarker of progression to
dementia in PD-MCI patients.
859
Using virtual reality to investigate the deficits in voluntary gait
initiation and cessation in patients with Parkinsons disease and
freezing of gait
M.J. Georgiades, M. Gilat, J.M. Shine, S.J.G. Lewis (Sydney,
Australia)
Objective: To explore start hesitation and stop failure in a cohort
of patients with Parkinsons disease (PD) with and without freezing
of gait (FoG) by assessing their behavioral responses to cues of vari-
able cognitive load within a virtual reality (VR) gait task.
Background: Gait disturbances and FoG are common in
advanced PD, with deficits in voluntary gait initiation (start hesita-
tion) and cessation. These features have significant morbidity and are
poorly understood. Difficulties in reliably eliciting these phenomena
in the clinical setting have led to the use of VR environments to
investigate the neurobiological mechanisms underlying gait disorder.
Methods: A validated VR gait task was used to explore start hes-
itations and stop failures in a cohort of patients with PD (10 freezers
and 10 non-freezers, both on and off medication), along with 10 age-
matched, healthy controls. The VR gait task consisted of a series of
start and stop cues presented to patients while they navigated a real-
istic 3D environment using foot pedals. Performance measures of
patients behavioral responses to these cues, such as the modal foot-
step latency, the response delay to a walk cue, and the number of
steps taken after a stop cue of variable cognitive load were col-
lected and analysed for between-group differences, and within groups
for an effect of medication, and of cognitive load.
Results: When compared to healthy controls and non-freezing
patients, individuals with FoG displayed impaired performance on
the VR gait task, including significantly more episodes of ineffective
voluntary initiation and cessation of walking. Unlike the other
groups, freezers exhibited more severe deficits in the off-medication
state, and during periods of high cognitive load.
Conclusions: The VR gait task was successfully used to detect
the key starting and stopping deficits that are more prominent in PD
patients who experience FoG. These results contribute to understand-
ing of gait disturbance in PD and are consistent with deficits in set-
shifting across motor and cognitive domains, along with executive
dysfunction and deficits in error monitoring. Virtual reality offers a
viable way of safely eliciting and studying freezing of gait in a clini-
cal setting that also permits integration with neuroimaging studies
Movement Disorders, Vol. 30, Suppl. 1, 2015
and direct-cell recordings to gain insight into this poorly understood
phenomenon.
860
Dissociable roles of beta and theta rhythms in the subthalamic
nucleus in response inhibition
A. Ghahremani, B. Neagu, K. Udupa, U. Saha, A.M. Lozano, S.
Najafi, M. Hodaie, S.K. Kalia, R. Chen (Toronto, Canada)
Objective: To investigate the roles of rhythmic neural activity in
the beta (15-25Hz) and theta (4-8Hz) bands in the subthalamic
nucleus (STN) during a stop signal task in Parkinsons disease (PD).
Background: Cortical-basal ganglia circuits are important in
motor control, especially in inhibition of motor responses. These cir-
cuits have been shown to have distinct functional characteristics in
the beta and theta frequency bands. Beta-band synchrony is sup-
pressed by preparation and execution of motor responses and is
enhanced during response inhibition. In addition, the theta-band is
modulated during decision-making and is stronger in the face of con-
flicts when the speed of responses needs to be slowed down. How-
ever, little is known about the functional differences and specific
roles of these two frequency bands during motor control. Hence, we
aimed to investigate the roles of beta and theta bands during a stop
signal task, a laboratory task to investigate response inhibition.
Methods: We recorded local field potentials from bilaterally
implanted deep brain stimulation electrodes in the STN of eight PD
patients during the stop-signal task. The stop-signal task involved
responding to a Go cue and inhibiting the response if a Stop cue
occurred after the Go cue. We investigated STN rhythms in the theta
and beta bands time locked to the Go and Stop cues.
Results: In response to the Go and Stop cues, we observed signif-
icant time-locked theta-band power that was linked to the speed of
responding to the Go cues, but not to the outcome of stopping.
Accordingly, trials with faster Go-reaction times exhibited greater
theta-band power than slower Go-reaction times. In contrast, the
time-locked theta-band power did not depend on the outcome of
stopping that was either successful or unsuccessful. A significant dis-
sociable finding was observed in the beta-band. The beta-band power
was greater on successful trials compared with unsuccessful stop tri-
als. Moreover, these beta-band oscillatory activities occurred later
than the significant time-locked theta band activities and before the
mean reaction time in response to the Go cues.
Conclusions: Our results support the hypothesis that the syn-
chrony of beta rhythms reflects response inhibition. In contrast, the
theta rhythms play a more general role during the stop-signal task by
being involved in neural computations associated with both Go and
Stop processes.
861
Are emotional factors associated with cognitive outcome
following DBS?
C. Ghilain, S.A. Anderson, N. Sun-Suslow, C. Bermudez, M. Forte, I.
Babakhanyan, B. Gallo, C. Luca, J. Jagid, C. Singer, B.E. Levin
(Miami, FL, USA)
Objective: This pilot study examined whether emotional factors
predating DBS surgery influence post-surgical outcomes.
Background: Deep Brain Stimulation (DBS) has been shown to
offer significant symptom relief in select patients with Parkinsons
disease (PD). However, there is no consensus to date how to best
screen for DBS eligibility. Depression and anxiety symptoms in PD
are pervasive, yet it is unknown whether depressed or anxious affect
prior to surgery will impact post-surgical cognitive performance.
Methods: Thirty-severn PD patients (Mage=63.48,sd=7.85),
underwent pre- and post-DBS neuropsychological evaluations.
Patients were grouped based on severity of emotional symptoms, 13
depressed (BDI-II>13) and 25 anxious (BAI>9). Groups did not
 POSTER SESSION S339

differ by gender, race, ethnicity, age, language of evaluation, span
between pre/post evaluation or disease duration. Years of education
were significantly different in the depression (t(34)=3.23,p=.007) and
anxiety (t(34)=2.117,p=.042) groups, respectively. ANCOVAs were
used to determine differences in post-surgical outcomes by group,
controlling for pre-surgical performance and years of education.
Results: Depressed and non-depressed groups did not differ sig-
nificantly post-DBS on MMSE, digit span, confrontation naming,
phonemic and semantic fluency, mental object assembly or judgment
of line orientation, after controlling for both pre-surgical scores and
years of education. Clinically anxious and non-anxious groups
showed the same performance pattern.
Conclusions: In this small sample, PD patients who meet criteria
for clinical depression or anxiety did not exhibit more impaired neu-
ropsychological performance post-DBS than their non-depressed/non-
anxious counterparts. Given that depression and anxiety are so com-
mon in PD, these data highlight the need to further elucidate what
role emotional factors should play when assessing DBS candidacy.
Flexibility (CogFlex) and Episodic Memory (EM), to different cogni-
tive test scores and selected MoCA subscores (table 1). Cognitive
function scores, representing posterior probabilities of a subjects
highest level of functioning, were derived for each subject through
POSET models and Bayesian analysis. Based on 10th percentile cut-
off of cognitive function scores of HC, and reported cognitive
decline (from MDS-UPDRS Part I), the impairment in each cognitive
function was classified and termed as POSET based cognitive func-
tion impairment (pCFI). We used t-tests and chi-square statistics for
testing significant (p < 0.05) differences between HC and PD.
Results: Cognitive test scores were significantly worse in PD
compared to HCs for all measures except two (table 1). Although
cognitive function scores were not significantly different in PD from
HC, all four pCFI types occurred more significantly in PD (table 2).
EM was the most frequently impaired cognitive function. The num-
ber of subjects with pCFI in one, two, three and all four domains
was also significantly higher in PD compared to controls.

Distribution of PD-MCI and CFI.

862
Category HC (n, %) PD (n, %)
POSET based cognitive function impairment (pCFI): A novel
approach for delineating heterogeneity of cognitive impairment PD-MCI Level Ia 0 (0) 29 (6.9)*
in Parkinsons disease PD-MCI Level Ib 1 (0.5) 36 (8.6)*
D.K. Gupta, J.G. Goldman, J. Jaeger, C. Tatsuoka (Cleveland, OH, pCFI-ATTN 1 (0.5) 20 (4.8) *
USA) pCFI-VSJ 1 (0.5) 17 (4.1) *
Objective: To apply partially ordered set (POSET) modeling for pCFI-CogFlex 2 (1.0) 16 (3.8) *
classifying impairment in cognitive functions in Parkinsons disease pCFI-EM 2 (1.0) 24 (5.7)*
(PD).
Background: Mild cognitive impairment in PD (PD-MCI) is
common and heterogeneous in nature. Current paradigms of classify- p < 0.05 indicated by *
ing cognitive impairment lack specificity with regards to particular
cognitive functions as many neuropsychological measures tap into
several different or overlapping cognitive domains. POSET models Conclusions: We report for the first time a novel approach for
serve as a basis for novel methods to classify the performance of distinguishing different cognitive phenotypes of PD-MCI. This may
subjects with respect to specific cognitive functions. have important clinical and research implications (e.g., biomarkers
Methods: De novo PD subjects (n5418) and healthy controls discovery for PD-MCI).
(HC), n5195) from the Parkinsons Progression Marker Initiative
(PPMI) study were studied. PD subjects were classified as PD-MCI 863
level Ia (Montreal Cognitive Assessment, MoCA) and PD-MCI level
Ib (< 5 domains tested) as per the International Parkinson and Deficits in communication between attentional networks in
Movement Disorders Society (MDS) Task Force PD-MCI criteria. patients with visual hallucinations in Parkinsons disease
Based on expert opinion, we mapped four specific cognitive func- J.M. Hall, J.M. Shine, C. OCallaghan, A.J. Muller, C.C. Walton, J.
tions: Attention (ATTN), Visuospatial Judgment (VSJ), Cognitive Phillips, A.A. Moustafa, S.J.G. Lewis (Camperdown, Australia)

Distribution of Cognitive Test Measures and Cognitive Function Scores

Cognitive test score

Cognitive test measure ATTN VSJ
Benton Judgment of Line Orientation Score X X
Letter Number Sequencing Score Raw Score X -
Semantic Fluency Animal Score X -
Semantic Fluency Vegetable Score X -
Semantic Fluency Fruit Score X -
Symbol Digit Modalities Score X X
HVLT Immediate Recall X -
HVLT Delayed Recall X -
HVLT Discrimination Recognition X -
MoCA Visuospatial Executive X X
MoCA Memory X -
MoCA Word Fluency X -
Cognitive function score .922 (.139)/ .525 (.333)/
[HC/PD, mean(SD)] .901 (.182) .513 (.348)
HVLT- Hopkins verbal learning test; p < 0.05 indicated by *
CogFlex EM
- -
- -
X -
X -
X -
- -
- -
- X
X X
- -
- X
X -
.529 (.439)/ .548 (.311)/
.525 (.408) .503 (.333)
[HC/PD, mean(SD)]
13.11 (1.98)/12.75 (2.13)*
10.87 (2.58)/10.58 (2.67)
22.13 (5.35)/20.92 (5.36)*
15.14 (4.12)/14.19 (4.52)*
14.64 (4.21)/13.47 (4.08)*
46.77 (10.56)/41.24 (9.70)*
26.04 (4.51)/24.45 (5.00)
9.29 (2.32)/8.36 (2.51)*
10.07 (2.80)/9.63 (2.63)
4.66 (.59)/4.49 (.80)*
3.88 (.98)/3.37 (1.42)*
14.21 (4.34)/13.06 (4.65)*

Movement Disorders, Vol. 30, Suppl. 1, 2015

S340 POSTER SESSION
Objective: The aim of this study was to investigate the function-
ing of the dorsal and ventral attentional networks in Parkinsons dis-
ease (PD) patients with visual hallucinations (VH).
Background: VH affect over half of patients in the advanced
stages of PD. Recently, mechanistic insights into VH in PD have
suggested a role for impaired interactions within and between large-
scale attentional networks. In this study, we tested PD patients with
and without VH and healthy controls on a cognitive task that
allowed for the characterisation of specific deficits in the dorsal and
ventral attentional networks.
Methods: A total of 21 patients with VH and 26 patients without
VH and 12 healthy older adults, matched for age, gender, and dopa-
mine dose equivalent, were included in this study. Motor, cognitive
and affective functioning were assessed using standard neuropsycho-
logical tests. Patients then completed the Attentional Network Test
(ANT) to explore coordinated activity within the attentional
networks.
Results: PD patients with VH performed worse on the ANT
measurements for alerting (ventral attentional network) networks in
comparison to the PD patients without VH and the healthy controls,
but only the latter showed a significant difference. No differences
were found between the groups in terms of the measurements for ori-
enting (dorsal attentional network) and executive function networks.
However, on trials in which both the dorsal and ventral attention net-
works would be required to work in combination, patients with VH
were significantly slower and had a lower response percentage than
non-VH group.
Conclusions: The results of this study highlight the crucial role
for large-scale attentional network dysfunction in the genesis of VH
in PD, which represents an important target for future pharmacologi-
cal and behavioral treatment strategies.
864
Ecological validity of executive functions: Predicting disability in
Parkinsons disease
B. Hanna-Pladdy, K. Mordecai, T. Hill, M. Mickens, F. Ivey, L.
Shulman (Baltimore, MD, USA)
Objective: To evaluate cognitive vs. motor contributions to per-
formance of instrumental activities of daily living (IADLs) in Parkin-
sons disease (PD).
Background: Cognitive deficits show a weak relationship to
timed IADLs (TIADLs), with processing speed as the best predictor
of disability. However, the relative cognitive and motor contributions
to IADLs remain unclear.
Methods: We administered cognitive, UPDRS motor and IADL
performance measures to 50 PD patients [mean age 5 67 (SD=10.1)
Y; mean disease duration 7.1(5.3) Y; H&Y 2 to 3]. Cognitive assess-
ments included MMSE, a measure of premorbid intelligence
(NAART), and executive tests of abstract formation/problem solving
(DKEFS Sorting), selective attention/inhibition (Stroop), and genera-
tional capacity (Semantic Fluency). TIADLs assessed performance in
(i) making change, (ii) finding/reading ingredients on a can, (iii) find-
ing food items on a shelf, (iv) reading instructions on a medicine
container, and (v) finding a telephone number. A hierarchical step-
wise regression model evaluated cognitive and motor predictors of
TIADL performance, after controlling for age, education and
NAART.
Results: Making change was predicted by the Stroop (R-
squared=.27). Reading a can was predicted by the MMSE (20%) and
Stroop (27% total variance). Fluency predicted 22% of the variance
in finding items on a shelf, and DKEFS Sorting predicted 20% of
the variance in reading a medicine bottle. After controlling for age,
education and NAART (26%), the MMSE increased the explained
variance for telephone number to 43%. Age, education and NAART
did not significantly predict making change, reading a can, items on
a shelf, or medicine bottle. The UPDRS motor did not significantly
predict any of the TIADL tasks.
Movement Disorders, Vol. 30, Suppl. 1, 2015
Conclusions: In patients with PD, IADL performance is related
to cognitive performance independent of age, education or premorbid
intelligence. Executive measures demonstrated promising ecological
validity and predicted 4 of 5 IADL tasks. This is in contrast to a
global cognitive measure (MMSE), which only predicted two IADL
tasks, and the UPDRS motor score which did not predict IADL per-
formance in any of the models. While executive functioning was pre-
dictive of disability, no single executive test demonstrated
superiority or consistency in predicting the full range of IADL per-
formance in PD.
865
Substantia nigra hyperechogenicity and cognitive functions:
Results from the TREND study
S. Heinzel, R. Yilmaz, I. Liepelt-Scarfone, B. Roeben, R. Niebler,
G.W. Eschweiler, A.J. Fallgatter, F.G. Metzger, W. Maetzler, D.
Berg (Tuebingen, Germany)
Objective: To investigate associations between substantia nigra
hyperechogenicity (SN1) in transcranial B-mode sonography (TCS)
and slight cognitive deficits in healthy older individuals.
Background: Cognitive changes are detectable even in premotor
or early motor stages of Parkinsons disease (PD). SN1 represents a
strong PD marker and is associated with other prodromal features,
such as slight motor abnormalities, hyposmia and REM sleep behav-
ior disorder. However, the relationship between SN1 and cognitive
performance in prodromal PD is not well established.
Methods: Healthy elderly adults were investigated with TCS and
the CERAD-plus cognitive test battery as part of the longitudinal
Tuebinger Evaluation of Risk Factors for Early Detection of Neuro-
degenerative Disorders (TREND) study. Exclusion criteria were
acute depression, MMSE score below 28 and insufficient TCS qual-
ity. Cross-sectional data of 598 participants were analyzed for differ-
ences in z-scores of cognitive performance (corrected for age and
education) between individuals with SN1 ( 22 mm2) and without
hyperechogenicity (SN-).
Results: Individuals with SN1 (24.1%) were older (p < 0.001)
and more frequently male (p < 0.05) compared to SN-. The SN1
group performed significantly worse than the SN- group in the modi-
fied Boston Naming Test (BNT) (p < 0.001) and semantic fluency
(SF) (p < 0.05) of the CERAD-plus battery (Fig. 1a/b). A trend
towards decreased performance was found for the word list delayed
recall subtest (p 5 0.07). [figure1]
Conclusions: Individuals with SN1 who have an increased risk
for PD perform worse in the SF and BNT compared to those with
Fig. 1. (865).
 POSTER SESSION
SN-. As cognitive deficits may even be present in premotor PD
stages, future longitudinal studies should investigate whether the
combination of SN1 and slight cognitive deficits may contribute to
the identification of individuals in whom a neurodegenerative process
has already started.
866
Impact of STN-DBS on cognitive functions in Parkinso ns disease
patients: Long-term follow-up study
E. Herrera, F. Seijo, E. Su
arez-San Martn, F. Cuetos, R. Renee
(Oviedo, Spain)
Objective: The objective of this study was to examine the cogni-
tive changes as a consequence of STN-DBS and the influence of age
at the moment of neurosurgery in the posterior cognitive decline. We
also aimed to classify the subtypes of mild cognitive impairment
(MCI) presented in our sample.
Background: Deep Brain Stimulation of the subthalamic nucleus
(STN-DBS) is an effective treatment for patients with advanced
Parkinsons disease (PD) when motor complications are unsuitably
controlled with medication. Despite evidence of mild short term cog-
nitive impairments, long term cognitive effects of STN-DBS have
not been as thoroughly assessed.
Methods: a group of 49 PD patients was followed-up with a neu-
ropsychological battery five to eleven years after neurosurgery. The
cognitive assessment included: executive functions, memory, visuo-
spatial abilities and language.
Results: Paired t-test analyses reported statistical differences for
all tests between the baseline and the follow-up. Then, regression
analyses showed that the difference between the baseline and the
follow-up in the phonological fluency was explained by the total
years of disease, in semantic verbal fluency by the years before
follow-up, and in the visuospatial skills by the age of the patients at
the moment of surgery. Moreover, 77,55% of patients were consid-
ered cognitively intact at the baseline while at the follow-up the per-
centage of patients with preserved cognitive abilities only reached
32.65%. Only 4 out of 25 patients who underwent surgery over the
age of 60 years were cognitively intact.
Conclusions: While semantic verbal fluency and visuospatial
skills could be impaired directly as a consequence of STN-DBS, the
age of the patients at the moment of DBS may be considered a risk
factor for posterior cognitive decline.
867
Predictive validity of level II PD-MCI criteria for PDD
J. Hoogland, J.A. Boel, R.M.A. de Bie, J.G. Goldman, B. Schmand,
A.I. Tr
oster, D.J. Burn, I. Litvan, G.J. Geurtsen, The MDS PD-MCI
Validation Study Group (Amsterdam, Netherlands)
Objective: To assess the predictive validity of Level II MDS PD-
MCI criteria using Parkinsons disease dementia (PDD) as the pri-
mary outcome.
Background: Mild cognitive impairment in Parkinsons disease
(PD-MCI) represents a stage of cognitive decline between normal
cognition and PDD. Diagnostic criteria for PD-MCI were proposed
by the International Parkinson and Movement Disorder Society
(MDS). They comprise two operationalizations: level I (abbreviated
assessment) and level II (comprehensive neuropsychological assess-
ment). Both can be used as a descriptive entity and are of potential
value as a risk factor in studies on the etiology, disease course, and
treatment or prevention of cognitive decline in Parkinsons disease.
The current study focused on level II PD-MCI.
Methods: Level II criteria were retrospectively applied to four large
databases of PD patients with comprehensive and longitudinal neuro-
psychological assessments. Conversion to dementia was the main out-
come. We used a Cox model to evaluate whether level II PD-MCI at
S341
baseline adds to the risk of PDD as estimated by age, gender, level of
education, disease duration, UPDRS-III, and MMSE score.
Results: Follow-up data on 470 PD patients were available. The
mean age was 68.7 years (SD 8.8), median duration since PD symp-
tom onset was 4.0 years (IQR 2.0-8.0), median UPDRS-III total
score was 20 (13-27) and median MMSE score was 28 (27-29).
Fourteen percent developed PDD during 1573 person-years of
follow-up. Adjusting for the other variables, preliminary analyses
indicated an increased risk for PDD with increasing age, a lower
MMSE and level II PD-MCI (using a cut-off of -1.5 SD for neuro-
psychological performance).
Conclusions: Level II PD-MCI increases the risk of PDD beyond
the risk estimated by demographic and PD-specific measures.
868
The effect of dopaminergic medication on perceptual decision-
making in Parkinsons disease as a function of task difficulty
and speed-accuracy instructions
Y.T. Huang, D. Georgiev, M. Speekenbrink, T. Foltynie, P. Limousin,
M. Jahanshahi (London, United Kingdom)
Objective: The aim of our study was to examine the effect of
dopaminergic medication in Parkinsons disease (PD) on (i) speed
and accuracy of responding under speed instructions that may induce
fast but errorful behaviour (ii) perceptual decision-making when the
effort involved to make a decision was manipulated.
Background: Dopaminergic medication is associated with
impulse control disorders in about 14% of patients with Parkinsons
disease. Dopamine has been proposed to influence energetic cost/
benefit analysis and vigor of movements and cognitive effort.
Methods: 14 PD patients and 14 healthy controls were tested on
two versions of the moving-dots task, one manipulated coherence of
moving dots/task difficulty, the other required decision-making under
speed versus accuracy instructions. The tasks were repeated twice off
and then on dopaminergic medication for patients. Reaction times
and errors were measured and the drift diffusion model was fitted to
the behavioural data.
Results: In the speed-accuracy task, no main effect or interaction
effects for dopaminergic medication was observed. Patients had higher
response thresholds and lower drift rates than controls across medica-
tion states and speed/accuracy instructions. In the difficulty task, a sig-
nificant main effect of medication was found on the error rate and
drift rate parameter obtained from applying the diffusion model, which
suggested that PD patients ON medication extracted information more
poorly from sensory stimuli, leading to more errors.
Conclusions: Dopaminergic medication was associated with
poorer extraction of information from sensory stimuli, which led to
more errorful responses in PD.
Acting under speed pressure was not associated with impulsive
behaviour on medication. Dopamine-induced impulsivity may be
more common in patients with specific characteristics such as
younger, single, male, with a sensation- seeking personality and a
family/personal history of addiction.
869
Deep brain stimulation of the subthalamic nucleus is associated
with lower response thresholds when patients with Parkinsons
disease act under speed pressure
M. Jahanshahi, I. Pote, M. Torkamani, Z.M. Kefalopoulou, L.
Zrinzo, P. Limousin, T. Foltynie, M. Speekenbrink (London, United
Kingdom)
Objective: We tested the hypothesis that acting under time pres-
sure of speed instructions would be associated with lower response
thresholds and fast, errorful responses for patients with Parkinsons
disease with deep brain stimulation (DBS) of the STN on compared
to DBS off.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S342 POSTER SESSION
Background: It has been proposed that the subthalamic nucleus
(STN) modulates response thresholds and speed-accuracy trade-offs
(SAT). More specifically, in situations of conflict, the STN is ordi-
narily considered to raise response thresholds, preventing premature
responses and allowing time for the accumulation of information to
occur before a response is selected.
Methods: The moving dots motion discrimination and percep-
tual decision-making task was used to assess SATs under both speed
and accuracy instructions by measuring reaction times and errors.
We assessed twelve patients with bilateral STN-DBS and twelve
age-matched healthy controls. Participants completed the task twice;
patients with stimulation on or off, with order counterbalanced.
Results: All participants were able to modulate reaction times
according to speed and accuracy instructions. Stimulation of the STN
was associated with significantly and differentially faster RTs, but
more errors under speed instructions relative to STN-DBS off. Appli-
cation of the drift diffusion model showed that under speed instruc-
tions, STN stimulation resulted in lower response thresholds relative
to when the stimulators were off.
Conclusions: Such STN stimulation-induced impulsivity,
reflected by fast and errorful responses when acting under time pres-
sure, may contribute to the development of post-operative psychiatric
problems including de novo impulse control disorders in some
patients. These results support involvement of the STN in SATs.
870
Relationship between neuropsychological function and speech in
individuals with Parkinsons disease
C.B. Johnson, J.E. Huber, G.C. Sprehn, S.E. Zauber (Indianapolis,
IN, USA)
Objective: To investigate the relationship between cognition,
motor function, and speech in individuals with PD.
Background: Cognitive and speech changes are demonstrated in
individuals with PD; however, few studies have examined the contri-
butions of motor and cognitive function to specific speech measures.
We previously reported that patients with the postural instability and
gait subtype (PIGD) have more speech dysfunction with slower rate,
more pauses, and more speech revisions. As these patients are known
to have more cognitive deficits, we hypothesized that their speech
deficits may be due to cognitive dysfunction.
Methods: Eleven patients with PD were evaluated neurologically
and underwent motor, cognitive, and speech testing before deep brain
stimulation (DBS) surgery. Cognitive testing included processing
speed (Trails), phonemic verbal fluency, working memory, and mem-
ory (verbal and visual). Speech measures (i.e., speech rate, pause
duration, pause patterns related to syntax, and reformulations) were
obtained from recordings of patients reading a short passage and
speaking on a topic of their choice (monologue).
Results: Processing speed correlated with the average duration of
pauses during monologue (r 5 0.63, p 5 .039), but not with pause
patterns related to syntax, reformulations, or rate. Verbal fluency
inversely correlated with reformulations (r 5 -0.77, p 5 .006), but did
not correlate with speech rate, pause duration, or pause patterns.
Six patients were classified as PIGD subtype, 4 as intermediate,
and 1 as tremor dominant. Patients in the PIGD subtype demon-
strated poorer verbal memory initial learning (43.54 1/- 7.01 vs.
59.27 1/- 6.90) and poorer verbal memory delayed recall (26.25 1/-
18.08 vs. 58.75 1/- 24.82) than the non-PIGD patients, t(9) 5 3.73,
p 5 .005 and t(9) 5 2.52 p 5 .033, respectively. There were no signif-
icant differences between groups on other cognitive variables.
Conclusions: Cognitive processing speed correlated with pause
duration as was verbal fluency with reformulations. The PIGD sub-
type was associated with lower verbal memory initial learning and
recall. Although in this pilot study no single cognitive domain was
selectively related to speech impairments or gait dysfunction, results
suggest that speech and cognitive impairments in people with PD are
Movement Disorders, Vol. 30, Suppl. 1, 2015
related and that poorer cognition may be linked to gait dysfunction.
Further study, in a larger cohort, is warranted.
871
Leptin and insulin; biomarkers for cognitive impairment in
Parkinsons disease? ICICLE-PD 36 month interim analysis
F.A. Johnston, R.A. Lawson, T.K. Khoo, A.J. Yarnall, G.W. Duncan,
S. Coleman, D. Brooks, R.A. Barker, D.J. Burn (Newcastle upon
Tyne, United Kingdom)
Objective: To evaluate baseline insulin and leptin levels as bio-
markers for decline in cognition in incident Parkinsons disease (PD)
36 months after diagnosis.
Background: Underweight and obesity have been linked with
increased risk of dementia. Leptin and insulin both increase with adi-
posity, providing negative feedback to restore energy homeostasis.
Feedback is lost in obesity. Leptin and insulin have been proposed to
improve cognition. No studies have examined the relationship
between leptin or insulin and cognition in PD to date.
Methods: The Incidence of Cognitive Impairment in Cohorts
with Longitudinal Evaluation-PD (ICICLE-PD) recruited 159 patients
with incident PD between 2008 and 2011. This interim analysis
includes the first 37 followed up at 36 months. Two were excluded
due to comorbid diabetes, 3 died and 4 withdrew. Data for 28 partic-
ipants were analysed. Fasting insulin and leptin had been measured
at baseline. Cognition was measured using the mini-mental state
examination (MMSE).
Results: Backwards linear regression showed that increasing
UPDRS predicted decline in cognition (p50.02). Age, education,
gender and geriatric depression scale score had no significant associ-
ation and were removed from the model. Leptin was added and sig-
nificantly predicted decline in MMSE (p50.013), accounting for
15% of the variance. This effect was blunted on inclusion of BMI
(p50.082). Insulin had a non-significant negative association with
change in MMSE when entered into regression analysis with BMI
and change in UPDRS (0.201), although this became significant if an
outlier was excluded (p50.018).
Conclusions: Leptin at baseline was associated with decline in
cognition at 36 months, although significance was lost when BMI
was included in the analysis. This pattern is unexpected and may
represent an abnormal neural response to leptin in PD.
Baseline insulin may be negatively associated with cognition over
36 months although this relationship did not reach statistical signifi-
cance. If genuine, the observed relationship is contrary to that
expected and may represent sub-clinical insulin resistance or a differ-
ence in response to insulin in PD.
Given the small effect sizes and the sample size our data should
be interpreted with caution. Analysis of 36 month data for the whole
ICICLE-PD cohort will be performed to determine whether the
observed effects are real and clinically relevant.
872
Can we improve attention in Parkinsons disease? A pilot study
S.A.H. Jones, J. Green, G.A. Eskes (Halifax, NS, Canada)
Objective: We examined if working memory (WM) training
could benefit attention and WM in those with Parkinsons disease
(PD) compared to a control group.
Background: More than half of PD patients exhibit cognitive
impairment, including WM deficits (Kehagia et al. 2010). WM is the
ability to actively hold and manipulate information in ones mind
and is needed for many tasks (e.g. reading and conversation). WM
training is a non-invasive tool for aiding cognitive function. To date,
no specific cognitive treatment is routinely offered to PD patients to
improve WM.
Methods: Twelve participants with a clinical diagnosis of idio-
pathic PD (Hoehn & Yahr Stage 1 or 2), with stable medications,
 POSTER SESSION
participated (Mean age 5 66.9 6 8.5 yrs). PD participants were ran-
domly assigned to one of 2 groups, a WM or a control task (CT)
training group; each task was used 5 times per week (30 minutes/
day) for 5 weeks. WM task: an adaptive dual n-back task in which
participants had to monitor a series of visual and auditory stimuli
and press keys when the current stimulus matched a previous stimu-
lus n items ago; n was increased adaptively according to the per- (FDG-PET) studies in PD reported extensive cortical hypometabo-
formance of the individual. CT task: participants moved and rotated
blocks to form horizontal lines. All participants completed a compu-
terized battery of attention tasks (simple reaction time, choice reac-
tion time, go-no-go, flanker, item and location WM, visual search) at
two time points: baseline and post training. Fifty-four age-matched
healthy older adults served as a comparison group at baseline (Mean
age 5 70.8 6 7.4yrs). We examined baseline differences in the mean,
standard deviation and coefficient of variation of reaction time, as
well as accuracy for each independent variable within each of the
attention tasks. Hedges g (Hedges, 1981) was used to quantify the
change between pre and post training scores across the WM and CT
groups.
Results: At baseline, PD participants showed attention and WM
deficits similar to previous reports (problems with initiation, inhibi-
tion, response interference, monitoring and WM). After training, the
WM training group showed particular improvement on tasks requir-
ing initiation, response interference and verbal WM compared to the
control group.
Conclusions: These preliminary results suggest that WM training
can benefit specific attentional processes that are problematic in per-
sons with PD. Further investigation of these effects is warranted and
ongoing.
873
Cognitive impairment in Parkinsons disease with SWEDDs
S.J. Kang, J.Y. Ahn, H. Choi, H.T. Kim (Seoul, Korea)
Objective: To assess cognitive dysfunction in patients of Parkin-
sons disease with SWEDDs, in comparison with Parkinsons disease
and age-matched controls.
Background: Patient diagnosed with Parkinsons disease (PD) on
clinical grounds who subsequently turn out to have normal dopamine
transporter imaging have been referred to as SWEDDs (scans with-
out evidence of dopaminergic deficits). Cognitive dysfunction is fre-
quent manifestation in Parkinsons disease. In this study we
determined the similarities and differences in the cognitive dysfunc-
tion between PD and SWEDDs.
Methods: This study enrolled 42 patients with SWEDDs, 107
patients with early PD and 32 healthy controls. Neuropsychological
tests covering different cognitive domains were performed on all
subjects for evaluation of cognitive function.
Results: PD with/without SWEDDs patients reported lower cog-
nitive performances than healthy controls in several cognitive
domains (attention, executive function, verbal/visual memory, and
language). But there are only one test of attention (digit span_for-
ward) shows difference between PD and PD with SWEDDs group.
Other cognitive domains were nealy correspond with two groups.
Conclusions: Cognitive dysfunction in PD with SWEDDs were
not previously reported. This study shows that Parkinsons disease
have multi-domain cognitive dysfunction, additionally presynaptic
dopaminergic deficits were not contributed cognitive dysfunction in
early Parkinsons disease. In summary, cognitive impairment in
patients with SWEDDs was relatively common, present in most of
the cognitive domains and similar to PD.
874
Cerebral hypometabolism based on a cutoff point on the mini-
mental status examination for cognitive impairment in de novo
PD
S.J. Kim (Busan, Korea)
S343
Objective: The aim of the present study was to evaluate cortical
hypometabolism based on a diagnostic cutoff-point of MMSE in de
novo PD.
Background: The Mini-Mental State Examination (MMSE) is the
most popular tool for identifying cognitively impaired individual
with PD. F-18-fluorodeoxyglucose positron emission tomography
lism including frontal and parietal hypometabolism.
Methods: We recruited 24 de novo PD patients and 15 healthy
controls (HC) to analyze FDG-PET. We divided the patients into
two groups by the diagnostic cutoff point of MMSE for diagnosing
dementia, with scores of 25 vs. <25. PET images were converted
to DICOM files and then processed using SPM 8 running on Matlab
11. For SPM 8 analysis, a two-sample t-test was used to analyze
rCMRglc between normal subjects and de novo PD patients. The sig-
nificant threshold was set to p < 0.01. Coordinates of local maxima
were converted from MNI to Talairach space.
Results: Patients with a MMSE  25 showed hypometabolism in
the fronto-temporo-parietal area. Hypometabolism in patients with a
MMSE <25 extended to wider areas than those of patients with
MMSE  25. Differences in cortical hypometabolism between
patients with a MMSE  25 and <25 was found in the right inferior
parietal lobule.
Conclusions: Patients with a MMSE  25 and <25 showed hypo-
metabolism in the right inferior parietal lobule suggesting that the
posterior cortical deficit is the main region of de novo PD with cog-
nitive impairment.
875
Withdrawn by Author
876
Sensitivity of the Greek version of the Montreal cognitive
assessment (MoCA) in the dementia of Parkinsons disease
K. Konstantopoulos, E. Petsa, T. Stefanaki, T. Doskas (Nicosia,
Cyprus)
Objective: To show the sensitivity of the Montreal cognitive
assessment (MoCA) in the dementia of Parkinsons disease.
Background: Dementia in Parkinsons disease is a common
problem which affects the quality of life of the patients. However,
there is a paucity of data relating to the sensitivity of the Greek ver-
sion of the MoCA in the Parkinsonian dementia.
Methods: The MoCA test was given to 18 demented Parkinso-
nian patients as compared to 18 pair-matched in age and gender con-
trols and 17 nondemented Parkinsonian to 17 pair-matched controls.
All patients and controls were seen in the Neurology department of
the Navy hospital of Athens between December 2013 and December
2014.
Results: The mean MoCA score for the demented Parkinsonian
patients was 14.76 (SD=6.93) and 24.29 (SD=2.02) for its pair-
matched control group. The mean score for the nondemented parkis-
nonian group was 25.44 (SD=1.82) and 27.19 (SD=1.28) for its pair-
matched control. Between subjects ANOVA was used to show differ-
ences between the 4 groups. The main effect of disease (existence of
Parkinsons disease or not) was significant (F(1,62)=35.764,
p5.000). The main effect of dementia (existence of dementia or not)
was significant (F(1,62)=51,735, p5.000). The combined effect of
disease and dementia was significant (F(1,62)=17.012, p5.000).
Post-hoc Mann-Whitney tests showed significant differences between
both, the demented (U=225,500, N1=17, N2=17, p5.004) and non
demented Parkinsonian groups (U=290,500, N1=18, N2=18, p5.000)
as compared to their pair-matched control groups.
Conclusions: The Greek version of the MoCA test is sensitive to
show differences in the dementia of Parkinsons disease. More
research is needed to show its sensitivity in groups employing larger
number of participants.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S344 POSTER SESSION
877
Does prolonged use of anticholinergic medication contribute to
cognitive impairment in early Parkinsons disease?
R.A. Lawson, A.J. Yarnall, G.W. Duncan, D.P. Breen, T.K. Khoo, D.
Brooks, R.A. Barker, D. Collerton, J.P. Taylor, D.J. Burn (Newcastle
upon Tyne, United Kingdom)
Objective: To determine the effect of anticholinergic burden on
cognition over 18 months in newly diagnosed Parkinsons disease
(PD).
Background: Anticholinergic medication prescribed for common
medical problems, such as bladder dysfunction and pain, may con-
tribute to cognitive decline. Other medications, often prescribed in
PD, whilst individually possessing low anticholinergic potency may
additively contribute to overall anticholinergic burden.
Methods: Patients with newly diagnosed PD (n5219) and age-
sex matched healthy controls (n599) completed a schedule of neuro-
psychological tests and detailed medical history as part of the
ICICLE-PD study. These measures were repeated after 18 months.
Anticholinergic burden for each participant was calculated according
to the Anticholinergic Drug Scale (ADS).
Results: 89% PD subjects (n5195) and 84% of controls (n584)
returned at 18 month follow up with a mean interval between visits
of 1.6 6 0.1 years. Significantly more PD participants were pre-
scribed anticholinergic medication than controls (43% vs 25%,
p<0.01) although mean ADS score was not significantly different
(0.8 6 1.3 vs 0.9 6 1.5, p>0.05). There were no significant differen-
ces in neuropsychological tests at baseline or 18 months between
those who were on medications with anticholinergic activity (ADS
score1) and those that were not (ADS score=0). Within groups,
participants with no anticholinergic burden significantly improved on
MoCA scores (mean =25.1 6 3.4 vs 26.3 6 3.3 respectively, p<0.01)
and verbal fluency scores (mean =11.9 6 4.8 vs 13.0 6 4.9 respec-
tively, p<0.01) from baseline to follow up but no significant changes
were seen in the ADS score1 group. Regression models showed
ADS score was not a significant predictor of cognitive performance
over 18 months and accounted less than 1.5% of the variance for
each neuropsychological test.
Conclusions: We found that anticholinergic burden over 18
months did not contribute to cognitive impairment in newly diag-
nosed PD. Low ADS scores in this cohort could reflect the cautious
use of anticholinergic medication by clinicians due to potential
effects on cognition. Previous studies have shown anticholinergic use
over prolonged periods of time may have an impact on cognitive
decline. Though this cohort did not show a significant change in cog-
nition over 18 months, we cannot exclude the long term impact of
anticholinergic burden.
878
Cognitive change in Parkinsons disease and progression of
frontal-striatal deficits
S.A.T. Levy, J.J. Tanner, M.S. Okun, D. Bowers, C.C. Price
(Gainesville, FL, USA)
Objective: This study (companion submission to Price et al.)
sought to: 1) examine cognitive changes in a sample of idiopathic
non-demented PD participants from baseline to 12 months, and 2)
confirm the progression of frontal-striatal cognitive deficits expected
in PD.
Background: Processing speed, working memory, and inhibitory
abilities are frontal-striatal deficits common in PD. The progression
of these deficits over time remains poorly understood, however.
Methods: Forty participants with idiopathic PD were recruited
and case matched with 40 non-PD healthy control participants. Par-
ticipants completed a baseline and one year neuropsychological pro-
tocol from which nine cognitive composites were derived (attention,
processing speed, working memory, inhibition, abstract reasoning,
language, visuoperceptual/spatial reasoning, memory, and motor
Movement Disorders, Vol. 30, Suppl. 1, 2015
function). Independent t-tests assessed group differences in each cog-
nitive domain. Cognitive change was determined by reliable change
methods based on non-PD peers practice effects. Pearson correlations
assessed the relationship of processing speed to other cognitive
domains at baseline and 12 months.
Results: At baseline, group comparisons revealed that processing
speed was significantly reduced in PD (p < .001; see Price et al). At
12-months, decline occurred dominantly in attention (24.3%
declined) and working memory (18.9% declined) domains relative to
all other domains (all other domains < 10.8%). Contrary to the base-
line performance where processing speed and working memory were
relatively independent, at 12 months post baseline processing speed
and working memory deficits were positively associated (r=.43,
p<.01).
Conclusions: PD frontal-striatal deficits increased over time and
progressed from striking processing speed to additional impairments
in working memory and sustained/selective attention. The collective
findings support hypotheses of subcortical to cortical disease
progression.
879
Plasma epidermal growth factor as a cognitive biomarker in
Parkinsons disease and Alzheimers disease
N.S. Lim, C.R. Swanson, D. Weintraub, J.Q. Trojanowski, A.S. Chen-
Plotkin (Philadelphia, PA, USA)
Objective: To determine whether plasma epidermal growth factor
(EGF) is a predictor of cognitive inhibition in Parkinsons disease
(PD) and Alzheimers disease (AD) patients.
Background: We have previously shown in a small cohort
(n 5 70) that low levels of plasma EGF are correlated with poor cog-
nition at baseline, and predictive of cognitive decline to dementia at
follow-up. Thus, plasma EGF may be a biomarker for progression of
cognitive decline in PD.
Methods: A cohort of 236 PD patients from Penn were evaluated
by MoCA annually, and baseline plasma levels of EGF were deter-
mined by ELISA. The effect of plasma EGF on cognitive decline
over time was analyzed. A second cohort of 566 individuals from
the Alzheimers Disease Neuroimaging Initiative (ADNI) were eval-
uated by MMSE and plasma EGF were measured by multiplex
immunoassay. A third cohort of 165 at-risk, asymptomatic individu-
als from the Parkinsons Associated Risk Study (PARS) were admin-
istered a neuropsychiatric battery to assess the association between
plasma EGF level and performance in five cognitive domains.
Finally the EGF receptor (EGFR) was measured in the subventricular
zone (SVZ) of 20 post-mortem brains of patients with PD, AD, and
PD with dementia by IHC.
Results: In a mixed effects analysis of the Penn cohort, lower
levels of plasma EGF were associated with cognitive decline over
time ( 5 0.00059, p 5 0.047), adjusting for age and sex. In a cox
proportional hazard analysis of the ADNI cohort, patients with mild
cognitive impairment (MCI) with the lowest EGF were significantly
more likely to convert to dementia and at a higher rate ( 5 -0.565,
p < 0.001). In the PARS cohort, visuospatial domain performance
was significantly associated with EGF level ( 5 0.0044, p 5 0.01).
Lastly, analysis of post-mortem brain tissue of several disease groups
revealed that EGFR positive cells in the (SVZ) are significantly
higher in NC than in the disease groups (p < 0.05).
Conclusions: Individuals with low EGF appear to be more likely
to show symptoms of cognitive impairment and convert to dementia
earlier than their peers. This was found to be true in PD and AD
patients, as well as asymptomatic individuals at high risk for PD.
Immunohistochemical analysis reveals that there is a correlation in
the brain between low EGFR and neurodegeneration as well. Thus,
our data suggests that EGF may be a biomarker for cognitive decline
in PD and AD.
 POSTER SESSION
880
Daily living functionality and cognitive functions in Parkinsons
disease: Functional diversity across cortical and subcortical
systems
D.A. Manjarrez, H. Dur an, S. Cano, M. Lopez, E. Soto, F. Velasco,
D. Trejo, D. Trejo (Mexico City, Mexico)
Objective: The aim of this study was evaluate the daily living
activities in Parkinsons disease patients and to determine the cortical
and subcortical cognitive functions associated to daily living
functionality.
Background: Parkinsons disease (PD) is a neurodegenerative
disorder presenting with subcortical pathology and characterized by
motor and cognitive deficits. Cognitive difficulties associated with
Parkinsons disease (PD) often impair the performance of activities
of daily living. It has been suggested cognitive impairment in Parkin-
sons disease affect the daily lives of patients.
Methods: The study included 44 patients between 40 and 80
years old with a H&Y 1-2 with a scheme of standard drug treatment
(basis on Levodopa). The patient group was divided into four sub-
groups (quartiles) according to the total score obtained adding the
cortical and subcortical division from the Parkinsons disease-
Cognitive Rating Scale (PD-CRS). We compared the cortical and
subcortical score in each subgroup and the associated to daily living
functionality using Parkinsons disease-Cognitive Rating Scale (PD-
CRS). It was used a Students t-test to compare cortical and subcorti-
cal scores in each subgroup.
Results: Three subgroups (1st, 2nd and 3rd quartile) exhibited a
subcortical score higher than the fourth group (4th quartile). The
patients with lower functionality score had a lower subcortical cogni-
tive rating (21.6 613.5). While these same patients had the best
results in the cortical cognitive domain (63.7 6 14.8).
Conclusions: These results suggest that the decrease in subcorti-
cal cognitive rating in patients with low daily living functionality
reflects cognitive difficulties which may be attributed to disruption of
the sucortical circuitry. While better performance in cortical tasks
implies a likely mechanism of cognitive compensation in the daily
living activities. These scores suggest a neurocognitive disoaci on
between cortical and subcortical dynamic system and its influence on
the activities of daily living.
881
Gait predicts decline in attention over three years in an incident
cohort of Parkinsons disease
R. Morris, J. Bunce, B. Galna, S. Lord, D. Burn, L. Rochester
(Newcastle upon Tyne, United Kingdom)
Objective: To examine whether gait impairment measured within
4 months of being diagnosed with Parkinsons disease (PD) can pre-
dict decline in attention over the subsequent 3 years.
Fig. 1. (881).
S345
Background: Impaired cognitive function is associated with gait
impairment in incident PD in cross sectional studies1. Our prelimi-
nary work suggests walking speed can predict decline in attention in
incident PD2. We sought to replicate our preliminary work in a sub-
set of the same cohort once disease advanced a further 18 months. If
gait can predict attentional decline, it may provide further evidence
for gait as a non-invasive surrogate marker to identify those at risk
of cognitive impairment and PD dementia.
Methods: 51 idiopathic PD and 49 age-matched controls completed
assessments for gait and attention at baseline and 3 years later. Partici-
pants walked continuously for two minutes at their normal pace during
which step velocity and step length were collected using a 7m GaitRiteTM
instrumented walkway. Attention was assessed using the cognitive drug
research (CDR) computerized battery. Scatterplots and linear multiple
regression analysis were used to assess the predictive value of baseline
gait in relation to change in attention over 36 months controlling for age.
Results: In PD but not control participants a decline in fluctuat-
ing attention over 3 years was associated with slower velocity
(p.013) and a shorter step length (p<.01) at diagnosis. Both step
velocity and step length were entered into a regression model con-
trolling for age. Step velocity was found to be an independent pre-
dictor of change in fluctuating attention (F(2,50) 5 5.513, p<0.05,
adjusted r2=.153, b=-.311) and step length was a stronger independ-
ent predictor (F (2,50)=6.323, p<0.01, adjusted r2=.209, b=-.354).
Conversely, fluctuating attention at baseline was unable to predict
change in fluctuating attention or change in step length over 3 years.
Conclusions: Baseline step velocity and step length but not base-
line fluctuating attention were significantly associated with change in
fluctuating attention over 36 months in an incident PD cohort. This
confirms earlier findings and suggests that gait may be a useful sur-
rogate marker of change in cognitive function in PD that is not due
to the normal ageing process.
1Lord, S et al. Front. Aging Neurosci,6: 249.
2Lord, S. et al. Mov Disord 2013;28 Sup 1: 361
[Figure1]
882
Executive dysfunction in a sample of patients with Parkinso
ns
disease in Cali Colombia
B.E. Mu~noz, Y.J. Ariza, J.L. Orozco (Cali, Colombia)
Objective: The aim of this study was to describe dysexecutive
syndrome in a sample of patients non-demented with Parkinso ns dis-
ease (ndPD) in Cali Colombia.
Background: The cognitive impairment of patients non-demented
with PD is characterized for poor performance in neuropsicological
tests of executive function. The profile of these patients can to
exhibit behavioral, cognitive and motor dysfunctions. Report of MCI
in ndPD suggest that impairments in other domains like attention,
memory recovery and visuospatial abilities are secondary to
Movement Disorders, Vol. 30, Suppl. 1, 2015
S346 POSTER SESSION
executive dysfunction. However, because the early detection and
adequate characterization is important for management of these
patients, is necessary to consider how neuropsychiatric symptoms
like a depression can affect to performance in executive tests.
Methods: The dysexecutive syndrome was evaluated in 40
patients non-demented with PD. The distribution of years of school
for men and women was 35% for more than 11 years, 22.5% for 11
years, 15% for 8 years, 20% for 5 years and, 7.5% less than 3 years.
MOCA Test was used like screening however, the mean for each
group was menMOCA 5 18 (SD 4.1) and womenMOCA 5 21 (SD
4.8). Frontal behavioral inventory (FBI) was used to describe behav-
ioral dysexecutive symptoms and Frontal Assessment Battery (FAB)
was used to describe motor dysexecutive symptoms.
Results: Significative differences between the results obteined in
FBI for behavioral symptoms in each groups. The mean for women
was 15 (SD 11.68) while for men the mean was 24 (SD 13.67). The
questions related with mood disorders (apathy, aspontaneity, irritabil-
ity) obtained highest punctuation in the group of women and ques-
tions related with behavioural impairment (inflexibility and
impulsivity) were highest in men group. The FAB not showed signi-
ficative differences for groups.
Conclusions: The cognitive impairment in patients ndPD is char-
acterized for a dysexecutive profile. Neuropsychiatric symptoms,
maybe related with gender, could affect to performance in these kind
of tests and to generate bias in the final description of each patient.
883
Individualised medicine using an abbreviated cognitive screen for
dementia prediction in Parkinsons disease
D.J. Myall, K.L. Wood, L. Livingston, T.L. Pitcher, T.R. Melzer,
M.R. MacAskill, T.J. Anderson, J.C. Dalrymple-Alford (Christchurch,
New Zealand)
Objective: To provide individual prediction of dementia risk in
Parkinsons disease (PD) based on a brief cognitive screen.
Background: Most people with PD eventually develop dementia,
which is the most burdensome aspect of this progressive condition.
Early identifiers of future risk of dementia would improve clinical
management and planning, encourage enhanced quality of life prior
to dementia, and facilitate the selection of patients for intervention
studies to delay progression. From a clinical perspective, a short
screen of cognitive tests would be ideal.
Methods: We followed 119 people with PD, initially all without
dementia, over 4 years. At baseline and follow-up assessments each
individual had a large battery of tests evaluating cognition and clini-
cal status. During this period 26 patients developed dementia. We
determined the most predictive cognitive tests and established indi-
vidualised probabilities of developing dementia within 4 years using
a Bayesian probabilistic Gaussian process model. Cross-validation
was used to derive independent predictions for each individual.
Results: Age, and MoCA, Stroop Interference, Map Search, and
Trails B scores were most predictive of conversion to dementia. The
model using these 5 variables achieved an AUC 5 0.92 (95% CI
0.85-0.98) for discriminating between converters to dementia and
non-converters in the 4-yr time period. This compares to an AUC of
0.93 (95% CI 0.86 0.99) for a model using the large battery, which
fulfils the International Parkinson and Movement Disorder Society
Task Force (MDSTF) criteria for mild cognitive impairment and
dementia in PD.
Conclusions: A limited number of tests has been identified that
gives similar predictive performance compared to using a large bat-
tery of tests that fulfil MDSTF criteria. The ability for a limited
number of tests to accurately predict which individuals will develop
dementia has great potential utility for studies to identify biomarkers
for dementia and clinical intervention trials looking to enrol an
enriched dementia-risk sample. An optimised probability cutoff for
making clinical decisions or research studies could be determined by
Movement Disorders, Vol. 30, Suppl. 1, 2015
taking into account the cost-benefits of false-positives and false-
negatives.
884
Contribution of auditory P300 test in the diagnosis of mild
cognitive impairment in Parkinsons disease
S. Ozkaynak, F. Yilmaz, E. Barcin (Antalya, Turkey)
Objective: We aimed to investigate whether additional electro-
physiological tests to help clinical diagnosis of mild cognitive
impairment in Parkinsons disease and we evaluated P300 changes in
patients with non demended Parkinsons disease and analyze correla-
tion between cognitive features and P300 changes.
Background: In Parkinsons disease (PD) there is a spectrum of
cognitive dysfunction, ranging from mild cognitive impairment
(MCI) to PD dementia (PDD). The International Parkinson and
Movement Disorder Society (MDS) proposed diagnostic criteria for
mild cognitive impairment in Parkinsons disease (PD-MCI) in 2012.
Event-related potentials provide measuring cognitive functions.
Abnormalities in P300 event-related potentials have been observed in
PDD patients. However, in non demended ones, the P300 showed
controversial results. There has not been any study about P300
changes in PD-MCI patients diagnosed according to MDS PD-MCI
criteria.
Methods: 20 patients with Parkinsons disease who are diagnosed
mild cognitive impairment (PD-MCI group) according to MDS 2012
PD-MCI level II criteria, 21 patients with Parkinsons disease with-
out cognitive impairment (PD-Normal group) and 20 neurologically
normal age, sex and education matched controls (Control group)
were examined by standard auditory odd ball paradigm. N100, P200,
N200, P300 latencies and peak-to-peak N100-P200, P200-N200,
N200-P300 amplitudes were measured and analized.
Results: P300 latencies recorded from Fz, Cz and Pz and N200
latency recorded from Fz were significantly longer in PD-MCI group
than in PD-Normal and Control group (respectively, p<0.001,
p50.041). P300 amplit ud recorded from Fz was significantly lower
in PD-MCI group than the other groups (p50.038). While P300 was
obtained all patients in PD-Normal and control group, it was loss
35% of PD-MCI patients.
Conclusions: The results show that P300 provide us a diagnostic
tool for detecting mild cognitive impairment in Parkinsons disease.
We suggest that P300 prolongation and loss of P300 latency could
be included PD - MCI diagnostic criteria as a supportive criteria.
885
Cognitive effects of atomoxetine in the chronic low-dose (CLD)
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated
macaque model of Parkinsons disease
E. Pioli, J. Schneider, Y. Jianzhong, Q. Li, A. Crossman, E. Bezard,
W. Martin (Manchester, United Kingdom)
Objective: The purpose of the study was to examine the effect of
Atomoxetine in the gold standard primate model of cognitive defects
in Parkinsons disease, the so-called chronic low-dose (CLD) 1-
methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) macaque model.
Background: Atomoxetine (ATX), a selective norepinephrine
reuptake inhibitor, is approved for the treatment of attention deficit
hyperactivity disorder (ADHD) and has shown beneficial effects on
working memory in healthy monkeys. Parkinsons disease (PD), in
which there is widespread degeneration of the catecholamine system,
is characterized by both motor symptoms and impairment of cogni-
tive performance and executive functions.
Methods: The cognitive effects of ATX were assessed in 5 CLD
cynomolgus macaques, displaying cognitive deficits and mild Parkin-
sonian motor deficits, produced by chronic exposure to low doses of
MPTP. Three doses of ATX (0.3, 1.0 or 3.0 mg/kg) as monotherapy
were tested in the Variable Delayed Response (VDR) and the
 POSTER SESSION
Continuous Performance Task (CPT) on a touch-screen computerized
system.
Results: No significant overall effect of ATX was reported on the
VDR or CPT tasks. However, when using a best dose analysis, ATX
significantly increased the percent of correct responses at a medium
delay in the VDR task and decreased the number of commission
errors on both the easy and difficult versions of CPT task.
Conclusions: Although no clear cognitive improvement was
found after ATX administration in the CLD macaque model of PD,
the best dose analyses reflected a small positive effect on working
memory and on the control of impulsive responding. These modest
effects of ATX are consistent with the available clinical literature
seem to suggest of lower likelihood of response to ATX for patients
with PD-MCI.
886
Withdrawn by Author
887
Improving dementia diagnosis in Parkinsons disease
M.S.G. Rocha, M.O. Oliveira, A.T. Neves, C.D.M. Costa, R.G.
Kauark, S.M.D. Brucki (Sao Paulo, Brazil)
Objective: The aim of this study was to compare sensitivity and
specificity of two other screening scales (ACE-R and MoCA) replac-
ing MMSE in Level I criteria algorithm for dementia in PD.
Background: MDS level I uses Mini-Mental Status Examination
(MMSE) in its algorithm as the screening tool for dementia. Two
studies observed low sensitivity (<50%) and high specificity (>90%)
when it was compared with an extensive neuropsychological assess-
ment. Studies that analysed the performance of the Level I of MDS
with screening scale for dementia (DRS-2) and DSM-4 criteria
observed higher sensitivity (70%) and specificity above 95%.
Methods: A neuropsychologist blinded to ACE-R and MoCA
results administrated full neuropsychological battery recommended
by Movement Disorders Society (MDS) for PD dementia (PDD)
diagnosis. The neurologist administered MoCA and ACE-R scales.
ACE-R and MoCA were also administered to healthy controls
matched to age and educational level. PD patients had motor and
nonmotor evaluations. ACE-R and MoCA scores were used to
replace MMSE score in Level I criteria for PDD. ACE-R, MoCA
and MMSE cut-off scores for dementia, defined for Brazilian popula-
tion, were used. Statistic analysis included ROC curve of each scale,
and sensitivity and specificity for each scale compared with gold
standard (MDS level II criteria).
Fig. 1. (887).
S347
Results: 86 PD patients (mean age: 64.1 years mean disease dura-
tion: 8.5 years mean schooling time: 5.8 years) were studied. Mean total
UPDRS score was 73.3 points and mean HY stage was 2.6. Twenty-nine
patients (33.7%) fulfilled MDS level II criteria for PDD. Twenty-six
patients fulfilled MDS level I criteria for PDD when ACE-R was used as
the screening tool, whereas 25 patients were demented when MoCA and
MMSE were the screening tool chosen. Area under ROC, taking the
MDS Level II diagnostic procedures as reference, was 0.89 [95% CI:
0.830.96] for ACE-R, 0.89 (95% CI: 0.820.96) for MoCA. When
ACE-R was the screening tool, MDS level I disclosed sensitivity of
82.8% and specificity of 96.5%; MoCA showed a sensitivity of 82,1%
and specificity of 96.5%; and when Brazilian cut-off scores for MMSE
were used, we had sensitivity of 48.3% and specificity of 100%.
MDS Level I criteria for PDD: sensitivity and specificity of dif-
ferent screening scales
Sensitivity Specificity
Screening scale (%) (%) PPV NPV
MMSE cut point < 25 79.3 96.5 92 90.1
ACE-r 82.8 96.5 92.3 91.7
MoCA 82.1 96.5 92 91.6
MMSE Brazilian 48.3 100 100 79.2
cut point
PPV - positive predictive value; NPV- negative predictive value
There was no significant difference between areas under ROC
(p50.9528) [figure1].
Conclusions: ACE-r and MoCA have better sensitivity than
MMSE in separating demented PD patients from the non-demented
ones, with a slight advantage on sensitivity for ACE-R.
888
Pattern of working memory deficit in REM sleep behaviour
disorder is the same as in Parkinsons disease
M. Rolinski, N. Zokaei, C.E. Mackay, M. Husain, M.T.M. Hu
(Oxford, United Kingdom)
Objective: To determine the extent and pattern of visual working
memory deficits associated with REM sleep behaviour disorder
(RBD), and evaluate whether the impairment signature is similar to
that found in Parkinsons disease (PD).
Background: Patients with idiopathic RBD are known to be at
an increased risk of developing a clinically defined neurodegenera-
tive disorder, with the majority developing PD. We examined
whether the pattern of visual working memory deficit is equivalent
in PD and RBD groups relative to controls, therefore supporting the
hypothesis that idiopathic RBD represents prodromal PD.
Methods: Visual working memory was assessed in 21 patients
with polysomnography-proven idiopathic RBD, 15 drug-nave PD
cases and 21 healthy controls. A serial order task designed to test
both precision of recall and the pattern of impairment was used
(Zokaei et al, Brain 2013). Errors were defined as either misbinding,
caused by the systematic increase in interference from features of
other items maintained in memory, or random, for example associ-
ated with fluctuations in attention. Three tasks using the same stimuli
were used to control for perceptual, motor and temporal decay.
Results: There was a significant deficit of memory precision in
the PD and RBD groups, when compared to the healthy controls. In
both groups, the deficit was associated with an increase in random
responses but not a significant difference in the number of misbind-
ing errors as previously found in carriers of a mutation in the gluco-
cerebrosidase (GBA) gene, most of whom do not develop PD.
Conclusions: The pattern of visual working memory impairment
in idiopathic RBD is equivalent to that observed in early PD. These
Movement Disorders, Vol. 30, Suppl. 1, 2015
S348 POSTER SESSION

results support the hypothesis that idiopathic RBD is representative
of the prodromal stages of sporadic PD.
889
Cognition in Parkinsons disease and essential tremor: A
population-based comparative study
 S
A. anchez-Ferro, J. Benito-Leon, I. Contador, J. Hernandez-
Gallego, V. Puertas-Martn, F. Bermejo-Pareja (Cambridge, MA,
USA)
Objective: Parkinsons disease and essential tremor share many
common features, i.e. risk factors and form of presentation. Our goal
was to define the cognitive performance of subjects affected by both
conditions when compared with healthy individuals.
Background: In a study including 18 patients from each condi-
tion an impaired performance in verbal fluency, naming, recent
memory, working memory, and mental set-shifting was found (Lom-
bardi 2001). The cognitive behavior of both entities was never com-
pared at large in population-based samples, where the risk of
ascertainment bias is reduced.
Methods: This investigation was part of the NEDICES study, a
population-based survey of the elderly in central Spain. We com-
pared the follow-up neuropsychological battery of 2,438 dementia-
free participants. Besides, raw scores, regression models were fitted
to adjust for any confounding effect of age, gender, literacy and
intake of drugs with central nervous system effect.
Results: Parkinsons disease (N=46) and essential tremor
(N=180) patients had a poorer global cognition than controls
(N=2212) with a 2.3 points and 1.6 difference, respectively, in a 37-
item version of the Mini-Mental State Examination (p < 0.01). Par-
kinsons disease patients remembered 0.7 less items in the Six Object
Test (p < 0.05). Both essential tremor and Parkinsons disease sub-
jects showed a slower cognitive speed processing traduced (Trail
Making Test part A), respectively, in 1.1 more mean errors
(p < 0.01) and 22.3% more subjects finishing the test in > 5-minutes
(p < 0.01).
Conclusions: This large population-based study confirmed that
both Parkinsons disease and essential tremor patients had a lower
neuropsychological performance than controls. Both diseases differed
in the affected areas, whereas Parkinsons disease performed less in
memory tests, both shared a common effect in global cognition and
cognitive speed processing. Future studies should expand our results
and help define the responsible mechanisms.
890
Usefulness of MoCA in cognitive function evaluation of
Parkinsons disease patients
M. Saruwatari, K. Hasegawa, A. Kumon, Y. Kobayashi (Sagamihara,
Japan)
Objective: In order to verify the validity of MoCA as a cognitive
function test of PD patients, we were statistically examined the rela-
tionship of each cognitive function testingMoCA, MMSE, FAB,
and RBMT.
Background: The cognitive function of Parkinsons disease with
dementia, tends to decrease attention, memory, executive function,
and visuospatial function.
In recent years, it is said to have a high effectiveness of the
MoCA cognitive function evaluation of PD. Because, MoCA is pos-
sible to screen also mild cognitive impairmet, and it is said that there
is a high exhaustive validity inspection area in key cognitive function
testing.
Methods: Subject is 65 PD patients was able to perform a num-
ber of cognitive tests between within six months. Of the total sub-
jects, 64 subjects underwent three testsMMSE, FAB, MoCA. And
35 subjects underwent four tests MMSE, FAB, MoCA, RBMT
We have a test of the correlation coefficient of the test results by
using the SPSS.
Results: The average age of the subject was 71.3 6 8.9 years,
gender was 31 males and 34 females . The average of each test,
MMSE is 25.9 6 3.3, MoCA 21.5 6 5.2, FAB 12.8 6 3.2, RBMT
18.1 6 4.9.
Positive correlation was found between the all of the testing and
other testing, higher positive correlation was observed between the
MoCA and other inspection.
Correlation coefficient of MoCA and the other test were, r 5 0.75
in MMSE, r 5 0.77 in FAB, r 5 0.72 in RBMT, the highest correla-
tion is MoCA and FAB.
Conclusions: MoCA has a high correlation with other major cog-
nitive function test, and MoCA is a useful test to screening the cog-
nitive decline of PD patients captured from a wide range of
perspectives, such as attention, memory, executive function and
visuospatial function. In the future, we will continue to longitudinal
measurement, and want to consider over time changes in cognitive
function of PD patients.
891
Effort to reduce postural sway decreases both cognitive
performance and postural stability in individuals with
Parkinsons disease
R. Sciadas, C. Dalton, J. Nantel (Ottawa, ON, Canada)
Objective: The objectives of the present study were to determine
the effect of consciously reducing postural sway on postural stability
as well as to assess the attentional demand of such a postural strat-
egy on the regulation of stability in individuals with Parkinsons dis-
ease (PD).
Background: Postural instability and increased risk of falling are
major causes of disability in individuals with PD. Reducing postural
sway in an attempt to increase postural balance is a common strategy
used by individuals with PD. However, there are few studies assess-
ing the effect of still standing on postural stability, as opposed to
standing quietly, and attentional demand.
Methods: Postural stability was assessed in 25 individuals with
PD (disease duration 6.5 6 4.5 years) while standing quietly and as
still as possible for 60 s, with or without concomitant cognitive task

TABLE 1. CoP displacement and velocity in the ML and AP directions during quiet and still stance with and without cognitive
task.
Single task Single task Dual task Dual task

N=25 Quiet standing Still standing Quiet standing Still standing

CoP ML 0.40 60.17 0.42 6 0.21 0.45 6 0.23 0.54 6 0.28
CoP AP 0.70 60.34 0.78 6 0.28 0.77 6 0.29 0.75 6 0.25
VCoP ML 0.46 60.22 0.53 6 0.26 0.65 6 0.45 0.73 6 0.45
VCoP AP 0.82 60.29 0.91 6 0.29 0.94 6 0.33 1.00 6 0.43
Significantly different from quiet standing dual task p < 0.05 Significantly different from single task, ML p < 0.01, AP p  0.05.

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
(category task). Postural sway was measured using the center of
pressure root mean square displacement (CoP) and mean velocity
(VCoP). The effect of both the postural and attentional conditions on
postural stability was assessed using two way repeated measures
ANOVAs followed by the Holm-Sidak post hoc test when necessary.
At baseline, the category task was performed while sitting, thus a
one way repeated measures ANOVA was used to compare the per-
formance between the three position conditions.
Results: CoP in the ML direction increased during still versus
quiet standing (p<0.05), Table 1. The cognitive task significantly
increased VCoP in the ML (p<0.01) and AP (p50.05) directions.
Standing still showed a tendency to increase VCoP in the ML direc-
tion (p50.06). The total number of responses in the category task
was different between baseline (44.4) and both quiet (23.5) and still
(19.6) standing (p<0.001). The cognitive performance was also dif-
ferent between standing positions (p<0.01).
Conclusions: Participants postural stability decreased when using
a still postural strategy. The performances on the cognitive task
worsened while standing and even more when standing still. As both
cognitive and postural performances decrease in an attempt to con-
sciously reduce postural sway, this strategy should be avoided in
individuals with PD. This could be especially important when trying
to increase postural balance in the lateral direction as the regulation
of postural stability in this direction was more affected by this
strategy.
892
Cognition and depression in Mexican early-onset Parkinso ns
disease patients
A.N. Seubert Ravelo, G. Y an~ez T
ellez, R.E. Escartn P
erez, H.
Salgado Ceballos, G.A. Neri Nani (Mexico City, Mexico)
Objective: To (1) describe the characteristics of Mexican EOPD
patients in: attention/working memory, executive function, language,
memory, visuoperceptual/visuospatial function, and depressive symp-
toms; (2) determine if any patients presented PD associated dementia
(PDD), and (3) explore if performance across cognitive domains dif-
fered depending on Hoehn and Yahr (H&Y) stages or severity of
depression.
Background: Despite the detrimental effect they could have in
this younger population, few studies have analyzed in detail cogni-
tion and depression in EOPD.
Methods: 74 patients with EOPD (disease onset age 50) in
H&Y stages 1-4 were administered a comprehensive battery of
standardized neuropsychological tests, the WAIS III vocabulary subt-
est as a premorbid intelligence estimate and the Beck Depression
Inventory. Cognitive scores were compared to age/education appro-
priate norms. Cognitive performance and depression between patients
in H&Y stages 2 and 3 was compared, as well as cognitive perform-
ance between non, mildly and moderate/severely depressed patients.
Results: Mean age was 52.6 (67.3), age at disease onset 40.3
(66.9), disease duration 12.1 (66.1), and education 12.2 (64.1)
years. A high percentage of patients presented executive, visuospa-
tial/visual discrimination and memory deficits when considering exe-
cutions <1 SD or percentile 30; percentage of patients with
cognitive dysfunction decreased when changing the criteria to <2
SD or percentile 10. Half of the sample presented depressive symp-
toms, 31.8% mild, 12.1% moderate, and 6.1% severe. No patient met
MDS criteria for PDD. Patients in H&Y stages 2 and 3 did not differ
in their cognitive or depression scores. Performance depending on
depression status only differed in estimated intelligence level
F(2,59)=6.69 (p5.002); moderate/severe depression patients had
lower intelligence scores (8.45 6 1.29) than mildly
(10.14 6 1.95,p=.028) and non-depressed (10.67 6 1.67, p5.002).
Conclusions: Although no patients met PDD criteria, cognitive
dysfunction is common in Mexican EOPD patients. Depression was
also common and had no relation to motor symptoms, nor did it
affect cognitive performance. Intelligence level did seem to have an
S349
effect in depression in our sample. Cognitive dysfunction and depres-
sion should not be dismissed in EOPD patients.
893
Deterioration of semantic memory in Parkinsons disease and the
implications to embodied cognition
H.S. Silva, M.S.G. Rocha, R.R. Baradel, M.A.P. Parente, F.F.
Godinho, A. Cravo, J.R. Sato, M.T. Carthery-Goulart (Sao Paulo,
Brazil)
Objective: To compare the performance of PD patients without
dementia and healthy controls in semantic memory tests for nouns
and verbs; and the association between performance on these tests to
the age, education, gender and overall cognitive performance.
Background: The Embodied Cognition theory (EC) proposes that
the semantic processing of action verbs (for comprehension and
expression of language) recruit the primary motor cortex following a
somatotopic organization. The semantic deficits in patients with Par-
kinsons s disease (PD) are common, affecting about 70% of
patients on oral expression tasks (Saldert et al., 2014) . There is con-
troversy, however, whether such deficits are also manifested in
understanding and are more pronounced than in verbs into nouns,
which would have favorable implications for EC.
Methods: 19 patients with PD without dementia and 64 healthy
controls with similar age, education level, economic status and per-
formance on the Mini Mental State Examination (MMSE) were eval-
uated by semantic memory tests and association that do not involve
verbal response and assess the understanding of actions - the Kissing
and Dancing Test (KDT) and nouns - Camels and Cactus Test
(CCT). The scores in KDT and CCT were Transformed in Z score
value using the mean of control group minus the mean of each
patient and is divided for standard deviation of control group (CG)
(formula: M -PD - M- GC/SD of CG). Data were analyzed by non-
parametric tests, with a significance level of 5% (p> 0.05).
Results: There was worse performance of patients compared to
controls both the semantic association tasks. Comparative perform-
ance analysis between KDT and CCT, after processing into Z scores
indicated that patients performed significantly worse in verbs into
nouns (Z score of -1.2 and -0.8 in verbs into nouns). In addition to
age, education and overall cognitive performance, only the Z score
in KDT was correlated with H & Y scores (0.648, p.0.009) and clini-
cal phenotype (0.729 - p.0.003).
Conclusions: The semantic deficits in PD patients were more
pronounced in verbs than nouns, supporting the theory of CI . Per-
formance in association tasks involving figures of action verbs is
associated with clinical measures of PD.
894
Word finding difficulty and its functional significance in
Parkinsons disease: A novel measure using pauses in speech
K.M. Smith, S. Ash, M. Grossman (Philadelphia, PA, USA)
Objective: To develop and assess the utility of a novel measure
of word finding difficulty in Parkinsons disease (PD) by a) evaluat-
ing pauses in speech in PD vs. controls, and b) assessing correlations
with caregiver questionnaires.
Background: Word finding difficulty is a common cognitive
complaint in PD, but little is known about its prevalence and impact
on daily function. Studies have been limited by a lack of quantitative
measures. Neuropsychological tests of verbal fluency and confronta-
tion naming have been used, but are not representative of daily com-
munication. We report a quantitative analysis of pauses in a semi-
structured speech sample, and assess impact on everyday communi-
cation with a caregiver questionnaire.
Methods: We performed a retrospective analysis of non-
demented PD patients (n526, mean disease duration 13.0 years (SD
5.5), UPDRS-III 26.5 (SD 11.4), MMSE 27.6 (SD 3.2)) and elderly
Movement Disorders, Vol. 30, Suppl. 1, 2015
S350 POSTER SESSION
controls (n523). Speech samples were recorded digitally during
description of the Cookie theft picture. Speech was analyzed with
Praat software for linguistic measures using a validated scoring pro-
cedure. Pauses of at least 1 second duration within an utterance were
considered clinically relevant and the number per minute was calcu-
lated. We administered tests of category naming fluency and con-
frontation naming, and a caregiver questionnaire about daily
communication (PCIDAT).
Results: The PD group had significantly more pauses within
utterances than controls (control-PD difference= -1.03, SE 0.50
(p5.046)). The PD group performed significantly worse than controls
on letter (p5.034) and semantic (p5.036) category naming fluency,
and confrontation naming (p5.019). Pauses within utterances corre-
lated with semantic category naming (r=-0.36, p5.033) and confron-
tation naming (r=-0.43, p5.013). PCIDAT score correlated with
pauses within utterances (r=-0.68, p5.028), but not with category
naming fluency or naming. There was no significant correlation
between the pause measure and motor severity, disease duration,
global cognition, or education.
Conclusions: Pauses within utterances in a speech sample distin-
guish PD from elderly controls. This measure reflects functional
communication as assessed by an independent caregiver question-
naire, and may be a powerful quantitative measure of word finding
difficulty in everyday communication.
895
Visual exploration during gait in Parkinsons disease and
association with cognitive characteristics
S.G. Stuart, H. King, B. Galna, A. Godfrey, S. Lord, L. Rochester
(Newcastle upon Tyne, United Kingdom)
Objective: To understand visual exploration during gait in Par-
kinsons disease (PD) and potential contributing factors such as cog-
nition. To address this we studied 1) real-time visual exploration
during gait in PD in response to environmental and attentional load;
and 2) the association of visual exploration during gait with cogni-
tive characteristics.
Background: Visual exploration is important during real-world
gait for accurate navigation and attenuation to environmental risk
factors. Visual information gathered through exploration is processed
and mediated by cognitive mechanisms, however visual and cogni-
tive deficits are common in PD and may contribute to gait dysfunc-
tion and falls.
Methods: 20 PD participants and 20 age-matched controls
walked under different environmental load (straight walking, walking
through a door and turning), during single and dual-task (attentional
load). Real-time visual exploration (saccade frequency) during gait
was measured using a Dikablis mobile eye-tracker. Participants
underwent visual, cognitive (global cognition, attention, visuo-spatial
ability, executive function) and clinical assessments. The effect of
environment and dual-task was assessed using a mixed model
ANOVA. The association between cognition and saccadic frequency
within each group was assessed using Spearmans rho correlations.
Results: PD participants took longer to complete all tasks
(p 5 .015) and made less frequent saccades (p 5 .009). For both
groups, saccade frequency significantly increased with environmental
complexity (p < .001) and reduced during dual-task (p < .001).
Poorer cognition and attention were associated with increased sac-
cade frequency during several of the walking tasks for PD but not
for control participants. These included turning during single-task
(rho 5 -0.53, p 5 .021) and straight-line single-task walking
(rho 5 0.67, p 5 .003).
Conclusions: PD explore their environment less than controls
despite walking slower but alter their visual exploration in the same
as controls in response to environmental and attentional demands.
Visual exploration during gait is associated with cognitive character-
istics in PD which may underpin exploration impairment, and may
contribute to gait deficit and falls risk. Further work is required to
Movement Disorders, Vol. 30, Suppl. 1, 2015
understand the underlying cognitive mechanisms involved in visual
exploration during gait in PD.
896
The relationships between mild cognitive impairment and
phenotype in Parkinsons disease
J.Y.Y. Szeto, C. OCallaghan, J.M. Shine, C.C. Walton, S.L.
Naismith, G.M. Halliday, S.J.G. Lewis (Camperdown, Australia)
Objective: To explore the expression of mild cognitive impair-
ment (MCI) in relation to the heterogeneity of idiopathic Parkinsons
disease (PD).
Background: The concept of differing clinical phenotypes within
PD is well represented in the literature. However, there is no consen-
sus as to whether any particular disease phenotype is associated with
an increased risk of MCI using the newly proposed International Par-
kinson and Movement Disorder Societys diagnostic criteria for this
feature.
Methods: A cluster analysis incorporating a range of specific
demographic, clinical and cognitive variables was performed on 209
patients in the early stages of PD (between Hoehn and Yahr stages I
and III). Post hoc analyses exploring variables not included in the
clustering solution were performed to interrogate the veracity of the
subgroups generated.
Results: This study identified four distinct PD cohorts: (1) a
younger disease-onset subgroup, (2) a tremor dominant subgroup, (3)
a non-tremor dominant subgroup, and (4) a subgroup with rapid dis-
ease progression. The present study identified a differential expres-
sion of PD-MCI across these PD subgroups, with the highest
frequency observed in the non-tremor dominant cluster. The non-
tremor dominant subgroup was also associated with higher prevalen-
ces of freezing of gait, hallucinations, daytime somnolence and rapid
eye movement sleep behaviour disorder compared to other
subgroups.
Conclusions: This study confirms the existence of heterogeneity
within the early clinical stages of PD and for the first time highlights
the differential expression of PD-MCI using the newly defined diag-
nostic criteria for this feature. An improved understanding of PD-
MCI and its clinical relationships may lead an improved understand-
ing of the pathophysiology underlying heterogeneity in PD. Further-
more, an appreciation of distinct clinical subgroups may allow better
targeting of treatments for those patients who have an increased risk
of developing dementia.
897
Withdrawn by Author
898
Linguistic ability in patients with Parkinsons disease: Can it
predict future memory deficits?
N. Valle Guzman, C. Williams Gray, R. Barker (Cambridge, United
Kingdom)
Objective: To assess whether linguistic ability in newly diag-
nosed PD patients is associated with a higher chance of developing
memory problems at follow up.
Background: There is evidence that low linguistic ability in early
life could predict memory impairments in later life . We wondered
whether this would also be the case in patients with PD.
Methods: Linguistic ability was assessed for 19 patients by ana-
lysing idea density and syntactic complexity in sentences that
patients were asked to write down as part of a standard neuropsycho-
logical assessment. We collected data for the first visit, relatively
close to date of diagnosis, and for a follow up visit on average 3
years after visit 1. Linguistic scores were correlated with memory
assessment scores for the last visit to the clinic.
 POSTER SESSION
Results: Though there were no significant differences there was
trend towards a larger decrease in memory scores for patients with
lower linguistic ability at visit 1 compared to those with higher lin-
guistic ability. a higher correlation was found for syntactic complex-
ity compared to idea density.
Conclusions: Though we found no significant link between lin-
guistic ability in newly diagnosed patients and future memory
impairment, we did see a trend towards a larger decrease in memory
scores for patients with lower linguistic ability compared to those
with higher linguistic ability. Repeating the analysis with a larger
sample will confirm whether linguistic ability can predict future
memory impairment in patients with PD.
899
Improving cognitive functioning and quality of life through
Dance for PD: A pilot intervention trial
M.I. Ventura, J.M. Ross, K.E. Lanni, K.A. Sigvardt, E.A. Disbrow
(San Francisco, CA, USA)
Objective: To evaluate effects of dance on cognitive and emo-
tional functioning and quality of life in people with Parkinsons dis-
ease (PD).
Background: PD is a chronic and progressive neurodegenerative
disease which can result in motor, cognitive and emotional dysfunc-
tion. However, current treatments primarily target motor symptoms
while ignoring other symptoms that contribute to decreased quality
of life.
Methods: We recruited people with PD from two sources: partic-
ipants who self-enrolled in Dance for PDV R classes and additional
volunteers from PD support groups. Those enrolled in dance classes
who met inclusion criteria and were willing to volunteer as research
participants were enrolled in our study and designated as our Inter-
vention group (N=8). Those not enrolled in dance classes were desig-
nated our Control group (N=7). The Intervention group completed
neuropsychological testing at baseline, participated in 10 dance inter-
vention sessions (1.25 hours once per week), then completed the
same neuropsychological assessment at follow-up. The Control group
completed the identical battery of neuropsychological tests at base-
line and follow-up, but did not receive the dance intervention. After
study completion, Control participants were invited to enroll in
Dance for PDV R classes. Repeated measures analysis of variance was
used to test for differences in performance on the Test of Everyday
Attention: Visual Elevator subtest, Alternate Uses, Digit Span, Falls
Efficacy Scale-International, Geriatric Depression Scale and Parkin-
sons disease Questionnaire-39.
Results: There were no significant differences between groups in
age (p50.7), years of education (p50.5), PD symptom severity
(p50.7), global cognitive functioning (p50.8) or IQ (p50.3) at base-
line. The Intervention group showed significantly improved cognitive
set-switching completion times (p50.04), experienced a greater
decline in fear of falling (p50.02), and reported significantly
improved quality of life (p50.02) and satisfaction in activities of
daily living (p50.01) relative to the Control group. There were no
significant changes in levels of creativity, memory or depressive
symptoms.
Conclusions: Our findings indicate that dance interventions may
be an effective form of complementary and adjunctive treatment for
people with PD, and appears to improve cognitive and emotional
functioning and quality of life.
900
Is exercise more important for cognition and mood in
Parkinsons disease patients than normal elderly?
D.M. Wald, J.D. Jones, T.L. Cummings, A. Mikos, R. Rodriguez,
M.S. Okun, C. Hass, D. Bowers (Gainesville, FL, USA)
S351
Objective: This study examined cognition/mood and reported
aerobic exercise in individuals with Parkinsons disease (PD) versus
age and education matched controls. We hypothesized that exercise
would be significantly associated with better cognition and mood in
both PD and control groups, with no differential effects.
Background: Exercise has been shown to have positive effects
on both cognition and mood in healthy adults.
Methods: Participants included nondemented individuals with idi-
opathic PD (N=54) and matched controls (N=31) who were part of
an NIH-supported RCT for treatment of masked faces. Data from a
self-report exercise measure was converted into metabolic equiva-
lents (METS) following the guidelines of Strath et al. (2013). Cogni-
tive tasks included a dementia screen (DRS-2), memory measures
(CVLT-2, Logical memory), confrontation naming (BNT), semantic
fluency, and measures of mood (apathy, anxiety, depression). Multi-
ple hierarchical regression analyses examined the influence of exer-
cise (mets) on cognition and mood.
Results: The PD and Controls did not differ in demographic vari-
ables, DRS-2 scores, or reported exercise (METS). A significant
group (PD, control) by exercise interaction was found for CVLT-II
delayed recall. Specifically, increased participation in exercise related
to better delayed memory scores for Controls but not for individuals
with PD. Exercise did not relate to other measures of cognition or
mood. Importantly, PD patients accurately performed other tasks of
self-appraisal, suggesting that they were able to adequately self-
monitor their behavior, including exercise.
Conclusions: Contrary to our hypothesis, aerobic exercise inten-
sity may be less related to memory performance for PD patients,
compared to Controls. Underlying reasons/mechanisms will be dis-
cussed. Further research with objective measures of exercise intensity
is needed to determine if high intensity aerobic exercise is a suitable
intervention for cognition and mood in PD patients.
Supported by RO1-NS50633 (DB).
This research was accepted for poster presentation at the 43rd
Annual Meeting of the International Neuropsychological Society,
February 2015.
901
Cognitlvely protective effects on PD model rats by electrical
acupuncture treatment
X. Wang, L. Han (Shanghai, Peoples Republic of China)
Objective: Electrical acupuncture has been proved to be an effi-
cient and safe treatment against Parkinsons disease (PD), but there
is remarkably little consensus on its role on the cognitive function
improvement. This study was designed to illustrate the cognitive-
improving effect of electrical acupuncture treatment on the rats mod-
eled by Parkinsons disease.
Background: Cognitive effects on the patients with PD by DBS
treatment, shows contridictive results. Also the positive evidence
about PD by Taiji has been reported. So the authors would hope to
search for the possible benefit PD-model rats by acupuncture
treatment.
Methods: Using Y-maze, Tissue Homogenization and Immuno-
histochemical test (IHC), we examined the Choline Acetyl Transfer-
ase (ChAT) level on the 6-OHDA-induced Parkinsons models
treated with acupuncture and drugs and explored the difference on
the cognitive function between different groups.
Results: We demonstrated that higher brain ChAT level
(P<0.01)and less hippocampus and striatum cell necrosis in the acu-
puncture group (P<0.01) which also showed significant memory
improvement (P<0.01), compared to control group. And there is lit-
tle difference in study ability between acupuncture treatment and
drug treatment (P>0.1).
Conclusions: We found electrical acupuncture treatment
improved cognitive function on Parkinsons models due to its poten-
tial protective role on acetylcholine neurons and up-regulating effect
on brain ChAT level.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S352 POSTER SESSION
902
Long-term outcomes for Parkinsons disease patients with
normal cognition
D. Weintraub, K. Pigott, J. Rick, S.X. Xie, H. Hurtig, A. Chen-
Plotkin, J. Duda, J. Morley, L. Chahine, N. Dahodwala, R. Akhtar,
A. Siderowf, J. Trojanowski (Philadelphia, PA, USA)
Objective: We report here the rates and predictors of progression
from normal cognition to either mild cognitive impairment (MCI) or
dementia using standardized neuropsychological methods.
Background: Cognitive impairment is common in late-stage Par-
kinsons disease (PD), but the natural history of normal cognition in
earlier PD patients with normal cognition is not well known.
Methods: One-hundred and forty-one patients diagnosed with PD
and baseline normal cognition were assessed for cognitive decline,
performance, and function at the Parkinsons disease and Movement
Disorders Center of the University of Pennsylvania. A panel of
Movement Disorders experts classified patients annually or biannu-
ally over a 2-6 year period as having normal cognition, MCI, or
dementia, with 55/68 (80.9%) of eligible patients seen at year 6.
Kaplan-Meier curves and Cox proportional hazard models were used
to examine cognitive decline and its predictors.
Results: The cumulative incidence of cognitive impairment was
8.5% at year, increasing to 47.4% by year 6. All incident MCI cases
had converted to dementia by year 5. In bivariate analyses, baseline
predictors of incident cognitive impairment were male sex (p50.02),
increasing PD severity (p<0.001), and all cognitive test scores. In a
multivariate analysis, predictors of future decline were male sex
(p50.02), higher UPDRS motor score (p5<0.001) and worse global
cognitive score (p<0.001).
Conclusions: Approximately one-half of PD patients with normal
cognition at baseline develop cognitive impairment within six years,
and all new MCI cases convert to dementia within five years. Our
results show that the transition from normal cognition to cognitive
impairment, including dementia, occurs frequently and quickly. Cer-
tain clinical and cognitive variables many be useful in predicting
conversion to cognitive impairment in PD.
903
Frequency of subthalamic nucleus (STN) stimulation in
Parkinsons disease (PD) modifies response accuracy in a
decision making task
K. Witt, T. Sauer, G. Deuschl (Kiel, Germany)
Objective: This study assessed the impact of a high and a low
frequency stimulation of the STN on decision making process in the
context of response execution (go) and response inhibition (no-go)
task.
Background: High frequency stimulation (120 Hz) of the STN
improves motor symptoms in PD. High frequency stimulation inhib-
its STN neurons and weakens the indirect so called no-go pathway
of the cortical-basal ganglia loop. However, STN-DBS also cause
some decline in certain aspects of executive functioning. In contrast,
low frequency STN stimulation (20 Hz) has an excitatory effect on
neurons and might worsen motor function.
Methods: 17 PD patients (mean age of 64 years) with chronic
STN-DBS (mean time from surgery 3.2 years) were examined in
three stimulation conditions: (i) no STN-DBS, (ii) 120Hz high-
frequency stimulation and (iii) 20 Hz low-frequency stimulation. We
examined the motor state and cognitive functions. The cognitive tests
assessed simple reaction times (RT), a flanker task and a Go/No-Go
task that assess the inhibition of a motor response.
Results: Only the 120 Hz stimulation setting improved the motor
state significantly compared to the off stimulation setting, whereas
the motor state of the 20Hz stimulation setting remained unchanged.
All stimulation settings showed comparable RT performances. Accu-
racy data in the simple reaction task significantly ascended in the 20
Hz stimulation setting compared to both the 120 Hz high frequency
Movement Disorders, Vol. 30, Suppl. 1, 2015
and the no stimulation setting. While accuracy data during 120 Hz
stimulation showed no change in the Go/No-Go task, significant
increase occurred in the 20 Hz low frequency stimulation setting.
Conclusions: Although 20 Hz stimulation of the STN did not
alter the motor state of the patients 20 Hz stimulation enhances the
selection of a motor response. This finding might be caused by the
excitatory effect of the 20 Hz stimulation within the STN. Given the
fact that 20 Hz stimulation did not alter motor performance, the 20
Hz effect might be much higher in the associative cognitive loop
than in the motor loop. 20 Hz stimulation might as well enhance
the hyperdirect loop between the cortex and the STN. Such gain in
the hyperdirect way may induce increased efficiency of the decision
making process in the cognitive associative cortex, which in turn
results in improved in response accuracy.
904
Characterizing neuropsychological impairment in Parkinsons
disease
D.T. Woods, A.C. Kneebone (Sydney, Australia)
Objective: To report the frequency of mild cognitive impairment
(MCI) in an Australian cohort of Parkinsons disease patients using
the recently published Level II International Parkinson and Move-
ment Disorder Society (MDS)-Task Force diagnostic criteria and to
compare this to recently published reports.
Background: The concept of MCI in Parkinsons disease (PD-
MCI) has received more focussed attention with the release of the
2012 MDS Task Force consensus criteria. The criteria represent the
beginning toward a standardized definition of PD-MCI. However,
several issues have emerged that require clarification regarding
which standard deviation (SD) cutoff score to employ to define neu-
ropsychological impairment and whether performance on a neuropsy-
chological test should be compared to a standardized normative
mean or a score of premorbid intellectual functioning (IQ).
Methods: One-hundred and thirty-two PD patients underwent
comprehensive neuropsychological assessment that met requirements
for a Level II category of testing as indicated by the MDS Task
Force criteria. The frequency of PD-MCI was examined using a
range of standard deviation cutoff scores (1SD, 1.5SDs, 2SDs). Dif-
ferences in frequencies were examined when comparing neuropsy-
chological test scores to normative data, as opposed to decline from
premorbid IQ, as indication of cognitive impairment.
Results: When cognitive impairment was defined as 1SD,
1.5SDs, and 2SDs below premorbid IQ, 48.4%, 22.2%, and 15.9% of
the sample met criteria for PD-MCI, respectively. This proportion
rose to 53.7%, 31.8%, and 21.2% when using the same cutoffs when
based on comparisons with normative data. Multiple-domain impair-
ment (80%) was more frequent compared to single domain, and a
deficit in executive function was the most prevalent cognitive
domain impaired with language showing least impairment.
Conclusions: Significant differences in frequencies of PD-MCI
were observed across the different cutoffs. It is more likely that PD
patients will show impairment in multiple cognitive domains which
is consistent with all previously reported data, and supports the prop-
osition that cognitive impairment in PD is heterogenous. Further val-
idation studies are required to identify sensitive neuropsychological
tests in multiple domains to detect the earliest clinical manifestations
of PD-MCI.
905
The analysis of cognitive impairment associated with Parkinsons
disease (PD-CI)
Q. Yang, Z. Mao, S. Ji, H. Ye, Z. Xue (Wuhan, Peoples Republic of
China)
Objective: To investigate the traits, the related factors and the
impact on quality of life of PD-CI patients.
 POSTER SESSION
Background: Recent researches indicated that the incidence rate
of cognitive impairment associated with Parkinsons disease (PD-CI)
were non-low, and PD-CI seriously affected the quality of life of
patients.
Methods: One hundred idiopathic PD patients were recruited.
The Hoehn-Yahr staging scale, the UPDRS-III Scale, the Clinical
Dementia Rating Scale (CDR), the Mini-Mental State Examination
(MMSE), the Montreal Cognitive Assessment table (MoCA), activ-
ities of daily living questionnaire (ADL) and Parkinsons disease 39
quality of Life Questionnaire (PDQL-39) were used for assessment.
Moreover, we also analyzed the interaction between PD-CI and the
course of disease, severity of illness and education.
Results: (1) According to the results, 47 cases had cognitive
impairment (PD-CI group), accounting for 47%, and 53 cases con-
sisted of non-cognitive impairment group (PD-NCI group).
(2)The MoCA scores and the MMSE scores of PD-CI group were
(19.93 6 3.50) and (22.93 6 2.90), which of PD-NCI group were
(26.74 6 1.48) and (28.74 6 1.36). It showed a statistical difference.
(3)The scores which concluded visuospatial, executive ability,
naming, attention and calculation ability, language, abstract thinking,
delayed memory, orientation of PD-CI group were lower than the
PD-NCI group. In addition, the scores of attention, calculation abil-
ity, memory latency, visuospatial and executive ability were signifi-
cantly lower in the PD-CI group. There were statistical differences;
(4) Multiple linear regression found that PD-CI were negatively
correlated with age, age of onset, UPDRS-III score, HY score, while
positively correlated with education and ADL, of which education
and HY scores had the most significant impact on cognitive ability .
However, it had no relevance of the course of disease.
(5) Activities of daily living and quality of life: The scores of
UPDRS-III, ADL and PDQL-39 of PD-NCI group were higher than
which of the PD-CI group, with a statistical difference.
Conclusions: The major affected factors of PD-CI were the atten-
tion of the calculation ability, delayed memory, visuospatial and
executive ability. Besides, PD-CI which seriously affected the quality
of life of patients was related to the severity of the disease and the
education.
Pathophysiology (other Movement Disorders)
906
Neurodegeneration or neuroinflammation in Parkinsons and
Huntingtons diseases. What goes first?
D.A. Labunskiy, T.A. Fedotova, V.V. Poleshchuk (Santa Rosa, CA,
USA)
Objective: Parkinsons disease (PD, also known as idiopathic or
primary Parkinsonism, hypokinetic rigid syndrome, or paralysis agi-
tans) is a degenerative disorder of the central nervous system. The
motor symptoms of Parkinsons disease result from the death of
dopamine-generating cells in the substantia nigra, a region of the
midbrain; the cause of this cell death is unknown. Huntingtons dis-
ease (HD) is characterized by a progressive course of disease until
death 15-20 years after the first symptoms occur and is caused by a
mutation with expanded CAG repeats in the huntingtin protein. The
aim of our study was cytokine level analysis and alpha SYN oligo-
dendroglial protein in mice models of PD and HD.
Background: Both diseases (PD and HD) characterized by neuro-
degenerative and neuroinflammatory processes in their patogenesis.
Activation of microglia with expression of proinflammatory cyto-
kines, impaired migration of macrophages, and deposition of comple-
ment factors in the striatum indicate an activation of the innate
immune system. The aim of our study was cytokine level analysis
and alpha SYN oligodendroglial proteins in PD and HD patients and
mice experimental models of these diseases.
Methods: We had 36 PD and 23 HG patients, both genders, age
from 37 to 68 years old. Control group comprised from 57 neurolog-
S353
ically healthy donors. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-
probenecid mouse model of progressive PD and HD mouse model,
BACHD, which many HD features, including neuronal cell loss, htt
aggregates, motor incoordination and memory impairment, were
used. To investigate the expression of IL-19, we examined its
expression in C57BL/6 mice astroglial cells in response to lipopoly-
saccharide, using reverse-transcription polymerase chain reaction
(RT-PCR) method.
Results: It was revealed that astrocytes can express IL-19 mRNA
following LPS stimulation. Degenerative processes in the CNS
showed the different pattern in PD and HD models. It was revealed
that astrocytes can express IL-19 mRNA following LPS stimulation.
Degenerative processes in the CNS showed the different pattern in
PD and HD models. Result of cytokines dynamics correlated in
patients and animal models of corresponding conditions.
Conclusions: Pathogenetic mechanisms of PD and HD compli-
cated. It is diffucult to distinguish what appeared first: neurodegener-
ation or neuroinflammation. Probably both these processes act
together.
907
Analysis of heart rate variability in functional Movement
Disorder patients
V.T. Liu, C.W. Maurer, K. LaFaver, R. Toledo, M. Hallett (Bethesda,
MD, USA)
Objective: To assess heart rate variability, a biomarker of central
autonomic function, in patients with functional Movement Disorders
(FMD) compared to healthy controls.
Background: Autonomic activity is of interest in FMD patients
given the hypothesis that the abnormal movements seen in FMD are
in part the result of converted psychological stress and increased vul-
nerability to emotional reactivity. Studies have shown that the auto-
nomic nervous system participates in regulation of emotion. Heart
rate variability (HRV) provides a quantitative assessment of central
autonomic activity. Reduced HRV can be reflective of autonomic
dysregulation, with decreased parasympathetic input relative to sym-
pathetic input. While reduced HRV has been demonstrated in a vari-
ety of mood and anxiety disorders, autonomic regulation has not
been well studied in the conversion disorder population.
Methods: Clinically definite FMD patients and age- and
gender-matched healthy controls were hospitalized overnight for con-
tinuous electrocardiogram (ECG) recording. ECG data was analyzed
using Impresario software, artifacts were removed, and data was
imported into Matlab for calculation of multiple HRV time and fre-
quency domain measures. HRV parameters analyzed included stand-
ard deviation of the N-N interval (SDNN), and power spectral
density analysis in very low frequency (VLF), low frequency (LF)
and high frequency (HF) ranges. Patients on heart rate altering medi-
cations or with history of cardiovascular disease were excluded.
Results: 33 FMD patients and 35 healthy controls were assessed
in this ongoing project. FMD patients demonstrated reduced HRV, as
determined by significantly diminished daytime SDNN (p50.04) and
daytime VLF (p50.04). FMD patients also showed increased index
of sympathetic to parasympathetic activity compared to healthy con-
trols, as indicated by significantly increased nighttime LF/HF ratio
(p50.03).
Conclusions: Alterations in regulation of the autonomic nervous
system may play a significant role in the pathophysiology of FMD
and merit further exploration.
908
Frontal gait disorders: DTI corpus callosal integrity correlates
with stride width and cognitive function
M. Livingston Dale, B.W. Fling, M. Mancini, D.S. Peterson, C.
Curtze, K. Smulders, M. Fleming, F.B. Horak, J.G. Nutt (Portland,
OR, USA)
Movement Disorders, Vol. 30, Suppl. 1, 2015
S354 POSTER SESSION
Objective: 1) To compare the integrity of the anterior corpus cal-
losum in frontal gait disorder (FGD) and idiopathic PD (iPD) sub-
jects; (2) To evaluate the relationship between corpus callosal
integrity and freezing of gait, stride width and cognitive dysfunction.
Background: Frontal gait disorders are recognized clinically by
predominantly lower body Parkinsonism and balance deficits
(Thompson and Nutt 2007), often with increased stride width and
sometimes freezing of gait (FOG). Corpus callosal microstructural
deficits on diffusion tensor imaging (DTI) have been noted in this
population (Wang 2012). We evaluated the relationship between the
integrity of the genu of the corpus callosum and FOG, stride width
and cognitive dysfunction in both FGD and iPD subjects.
Methods: Nine iPD subjects (mean age 66) and four FGD sub-
jects (mean age 74), all with clinical FoG, underwent DTI to assess
white matter microstructural integrity through the genu of the corpus
callosum. Participants also performed cognitive and mobility testing
including the SCOPA-COG, FoG severity during turning with Opal
sensors, dual task cost, and stride width. We correlated fractional
anisotrophy of the genu of the corpus callosum to behavioral metrics
where group performance was different.
Results: Idiopathic PD subjects performed better on the SCOPA-
COG {PD: 25.4 (3.8); FGD: 17.25 (2.2)}, and had greater FoG
severity, reduced dual task cost, and narrower stride width {PD:
11.9 cm (3.2); FGD: 21.6 cm (3.7)} compared to participants with
FGD. Idiopathic PD subjects also had significantly better fractional
anisotropy through the genu of the corpus callosum {PD: 0.43
(0.04); FGD: 0.36 (0.03)}. Callosal integrity was positively related to
total SCOPA-COG score (r 5 0.82) but negatively associated with
stride width (r 5 0.90) when pooling groups together. No relation-
ships were observed between callosal integrity and FoG severity or
dual task cost during walking.
Conclusions: Frontal gait disorder subjects show decreased integ-
rity of white matter through the genu of the corpus callosum, which
is associated with diminished cognitive function and increased stride
width, but not with freezing of gait severity. Although both iPD and
FGD subjects experience of gait dysfunction, distinct pathophysiol-
ogy between these Parkinsonism syndromes reveals differential
behavioral deficits and underlying neural mechanisms.
909
Detection of alpha-synuclein seeding activity using a novel assay
T.R. Yamasaki, B.B. Holmes, J.L. Furman, D. Dhavale, P.T.
Kotzbauer, M.I. Diamond (St. Louis, MO, USA)
Objective: To develop a sensitive and quantitative system to
detect seeding activity of alpha-synuclein from recombinant sources
and human tissues.
Background: There is growing evidence from both in vitro and
in vivo studies that in many neurodegenerative diseases, including
synucleinopathies, cell-to-cell transmission of a pathological protein
occurs and may be a vehicle for spreading of pathology throughout
the brain. Traditional methods such as ELISA or Western blot detect
synuclein sensitively, but are not able to distinguish the form or
seed that engenders further pathological aggregation. An assay that
detects and quantifies synuclein seeding activity could be useful to
monitor disease progression or to test synuclein anti-aggregation
therapies.
Methods: We have developed a system which combines the sen-
sitivity of a fluorescent system with the quantitative power of flow
cytometry. Our assay uses Fluorescent Resonance Energy Transfer
(FRET), to detect small amounts of aggregated synuclein. We gener-
ated monoclonal cell lines that stably express synuclein fused to
cyan or yellow fluorescent protein (syn-CFP/YFP). Upon aggrega-
tion, quenching of CFP by YFP produces spectroscopic changes
which are readily detected and quantified by flow cytometry.
Results: This system is able to sensitively detect recombinant
synuclein fibrils. It also robustly detects synuclein seeding activity in
Movement Disorders, Vol. 30, Suppl. 1, 2015
both soluble and insoluble fractions extracted from brains of patients
with multiple systems atrophy (MSA).
Conclusions: We have developed a cell-based assay that detects
and quantifies synuclein seeding activity, not only from recombinant
fibrils, but also from human brain tissue of patients with MSA. With
further optimization, this assay could potentially be useful as a bio-
marker for synucleinopathy diagnosis, progression or response to
treatment.
Ataxia
910
Anti-glial nuclear antibody (AGNA) associated encephalitis
without underlying malignancy presenting with opsoclonus and
ataxia
L. Avedian, S. Rashid, E. George, O. Oguh, E. Gaitour, N. Shneyder
(Detroit, MI, USA)
Objective: We present anti-glial nuclear antibody (AGNA) posi-
tive encephalitis manifesting as progressive neurological deteriora-
tion, epilepsy, opsoclonus and ataxia.
Background: Paraneoplastic limbic encephalitis is a heterogene-
ous group of neurological disorders associated with occult or detecta-
ble systemic malignancy. AGNA antibody has been shown to be
associated with small cell lung cancer (SCLC). [1] In our literature
search, this is the only case report with voltage gated potassium
channel antibodies (VGKC-abs) negative but AGNA positive enceph-
alitis without detectable malignancy. The other 2 cases reported with
AGNA encephalitis were found to be VGKC-abs positive with
SCLC. [2]
Methods: 36 years old African American female with history of
gradual cognitive decline for last 5 years, language regression with
acquired hearing loss for last 4 years and seizure disorder for last 3
years presented to us with lethargy, weight loss, abnormal eye move-
ments and right facial weakness for the previous 2 weeks. Patients
examination was noticeable for opsoclonus and ataxia. Patient was
treated with 5 days of IV steroids with moderate improvement in
gait, communication and opsoclonus.
Results: MRI showed diffuse cerebral atrophy with T2 hyperin-
tensities involving left temporal lobe, posterior thalamus, medulla
and bilateral inferior olivary nuclei and bilateral hippocampi without
evidence of diffusion restriction or enhancement. Initial longterm
EEG showed electrographic seizures in the left fronto-temporal area.
Extensive autoimmune and infectious work up was negative, except
mildly elevated anti TPO with normal thyroid functions. CSF studies
were significant for oligoclonal bands of 10. Serum paraneoplastic
panel came back positive for AGNA antibodies only (titer 1:1024).
Work up for malignancy remained negative.
Conclusions: Opsoclonus myoclonus ataxia syndrome is known
to be associated with SCLC and anti Hu antibodies in adults. [3]
This is a novel case of AGNA positive and VGKC-abs negative lim-
bic encephalitis with opsoclonus myoclonus ataxia without evidence
of systemic malignancy.
911
Spinocerebellar ataxia type 6 in Eastern India: A new
observation
K.B. Bhattacharyya, D. Pulai, D. Guin, G. Ganguly, A. Biswas, A.
Pandit, A. Joardar, S. Roy, A. Roy, A. Senapati (Kolkata, India)
Objective: To study the prevalence of spinocerebellar ataxia type
6 (SCA6) in the Eastern Indian population.
Background: SCA6 is rarely documented from India and so far
only 2 cases from western and 1 case from eastern India have been
described. Recently, in a study on 83 consecutive cases of SCA, 6
 POSTER SESSION
cases have been seen in Kolkata, West Bengal, a district in eastern
India.
Methods: 83 consecutive cases of suspected SCA were recruited
for clinical and genetic analysis. The inclusion criteria was progres-
sive degenerative cerebellar ataxia with or without family history
and negative history for any known metabolic defect. Patients with
toxic, nutritional, infective, neoplastic, vascular, vitamin E defi-
ciency, hypothyroidism and alcohol related degeneration were
excluded from the study. Serum lactate and vitamin E level were
studied in selected cases to exclude progressive ataxia of known met-
abolic etiology. Electrophysiological evaluation including nerve con-
duction studies and imaging studies were done in all cases.
Molecular genetic study was aimed at the detection of trinneu-
cleotide repeat expansions in known SCA genes. DNA was isolated
from blood by phenol-chloroform method and polymerase chain
reaction was carried out using primers of SCA1,2,3,6 and 12. Agaro-
segel (12.4%) electrophoresis was carried out followed by visualiza-
tion of bands using ethidium bromide. The number of CAG repeats
was ascertained by comparing with a 100 bp DNA ladder.
Results: Out of the 83 clinically suspected cases of SCA, 45
turned out to be genetically positive with the use of the available pri-
mers. Of these, 6 cases were positive for SCA6. The clinical features
conformed to what is described in the literature and MRI showed
marked cerebellar atrophy.
Conclusions: SCA6 is frequently observed in Japan and Taiwan
and is relatively less common among Caucasians. In India, 3 cases
have been reported so far. In our study on 83 consecutive cases of
progressive degenerative cerebellar ataxia, 6 cases of SCA 6 were
observed, which was not seen in India before. The clinical features
conformed to what have been described in the world literature. One
of the reasons for finding more cases of SCA6 is the occurrence of
new mutation or more likely, use of the appropriate primer which
was not available earlier. In conclusion, SCA6 is not uncommon in
India, particularly in the Eastern part.
912
Ataxia: Classification and epidemiology
R.S. Boddepalli, K. Kurako, N. Galvez-Jimenez (Weston, FL, USA)
Objective: To describe the distribution of several ataxic syn-
dromes in different ethnic groups presenting at a busy Movement
Disorders center.
Background: Ataxia is a clinical condition characterized by poor
coordination/imbalance and consequent gait disturbances. The etiol-
ogy may be congenital, non-congenital and acquired usually mani-
festing with a intricate and diverse clinical picture.
Methods: A retrospective chart review from 2003 to 2013. Ptes
were grouped by ethnicity. Prevalence, clinical features and genetics
of various ataxias between these ethnicities were studied.
Results: 156 patients were studied. 104 were Caucasian, 23 His-
panics, 7 Afro-Americans, 3 Asians and 19 wo reported ethnicity. Of
the 104 Caucasians, 64 had sOPCA. Of the remaining 40 ptes, five
TABLE 1. Clinical and demographic characteristics of patients with MJD according to the presence of psychotic symptoms
No psychotic
symptoms (N 5 107)
Age (years); mean 6 SD 45.63 6 12.34
Gender (female to male ratio; % female) 57:50; 46.72%
Age of disease onset (years) mean 6 SD 35.77 610.18
Disease duration (years); mean 6 SD 10.68 6 6.13
SARA; mean 6 SD 14.89 6 9.03
CAG; mean 6 SD 72.08 6 4.82
MJD: Machado-Joseph disease; SD: standard deviation; SARA: Scale for the Assessment and Rating of Ataxia
S355
had SCA 1, 2, 3, 8, and 10 respectively. Another pte had a Bx con-
firmed eosinophilic vasculitis, one with brainstem infarction, one
with acoustic neuroma, and another with thiamine deficiency due to
gastric bypass surgery. Of the hispanics ptes, 13 had MSA, 3 NPH, 1
Kearns Sayre, SCA 3 and 14, one each; 1 cerebellitis, 1 Friedreichs,
and 1 Miller Fisher. In the black group 2 NPH, one gunshot injury, 2
NPH, one DRPLA and one with syringomyelia. 19 wo reported eth-
nicity: 1 alcoholic cerebellar degeneration, 1 paraneoplastic, 10
MSA, 4 NPH, 1 trauma, and 2 unclassified. 12/24 patients had a neg-
ative commercially available testing.
Conclusions: MSA was most common, Caucasians (61.4%), His-
panics (56.5%). NPH was present in most groups (7%/156) and
genetically proven SCA in 4%.
913
Psychosis in Machado-Joseph disease: Clinical correlates,
pathophysiological discussion and functional brain imaging.
Expanding the cerebellar cognitive affective syndrome
P. Braga-Neto, J.L. Pedroso, M.R. Laureano, A. Gadelha, C.d.S.
Noto, G.E.J. de Garrido, O.G.P. Barsottini (S~
ao Paulo, Brazil)
Objective: To investigate the psychiatric manifestations of a
large cohort of Brazilian patients with MJD in an attempt to charac-
terize the presence of psychotic symptoms.
Background: Machado-Joseph disease (MJD) is the most com-
mon spinocerebellar ataxia worldwide with a broad range of clinical
manifestations, but psychotic symptoms are not well characterized.
Methods: We evaluated 112 patients with clinical and molecular
diagnosis of MJD from February 2008 to November 2013. Patients
with psychotic symptoms were referred to psychiatric evaluation and
brain perfusion SPECT (single-photon emission computed tomogra-
phy) analysis. A specific scale - Positive and Negative Syndrome
Scale (PANSS) - was used to characterize psychotic symptoms in
MJD patients. We also performed an autopsy from one of the
patients with MJD and psychotic symptoms.
Results: Five patients presented psychotic symptoms. Patients
with psychotic symptoms were older and had a late onset of the dis-
ease (p< 0.05) (Table 1). SPECT results showed that MJD patients
had significant regional cerebral blood flow (rCBF) decrease in the
cerebellum hemispheres bilaterally and vermis compared with
healthy subjects (Figure 1). No significant rCBF differences were
found in patients without psychotic symptoms compared to patients
with psychotic symptoms. The pathological description of a patient
with MJD and psychotic symptoms revealed severe loss of neuron
bodies in the dentate nucleus and substantia nigra.
Conclusions: MJD patients with a late onset of the disease and
older ones are at risk to develop psychotic symptoms during the dis-
ease progression. These clinical findings may be markers for an
underlying cortical-cerebellar disconnection or degeneration of spe-
cific cortical and subcortical regions that may characterize the cere-
bellar cognitive affective syndrome.
With psychotic
symptoms (N 5 5) p value
68.40 6 13.57 [bold]0.02[bold]
2:3; 40% 0.449
53 6 14.50 [bold] 0.013[bold]
15.40 6 4.87 0.053
25 6 12.72 0.158
71.50 6 5.06 0.662
Movement Disorders, Vol. 30, Suppl. 1, 2015
S356 POSTER SESSION
914
The use of adjustments to facilitate writing in patients diagnosed
with spinocerebellar ataxia
F.M. Branco Germiniani, T.V. Canelossi Rosa, R. Nickel, P.R.S.
Liberalesso, H.A.G. Teive (Curitiba, Brazil)
Objective: The aim of this study was to investigate whether the
use of specific adaptations improves the standard of writing of these
patients and whether these adaptations would be used by them.
Background: Spinocerebellar ataxia is a heterogeneous group of
neurodegenerative diseases, characterized by the presence of progres-
sive cerebellar ataxia, resulting in impairment in the planning and
execution of voluntary movements, either of the whole body or
limbs, due to a cerebellar lesion. Although the cerebellum plays an
important role in the control of motor function and motor learning,
the benefits of training remain controversial for patients with cerebel-
lar degeneration due to disease progression. This change in coordina-
tion leads to difficulties in the control of fine movement and
manipulation of objects, compromising the patients occupational
performance.
Methods: This study compared the use of devices aimed to
improve the writing of 63 patients with spinocerebellar ataxia
through a qualitative assessment of writing, by the Spiral Test, which
evaluated the time of writing and the SARA Rating Scale, whose
goal is to measure the severity of spinocerebellar ataxia.
Results: Of the 63 patients evaluated, 40 agreed that the use of
such adaptations improved their quality of writing and would use
them on a daily basis. The average time for completion of the Spiral
Test without adaptation was 36.9s and with the use of adaptive
means was 32.51s. For all tests we considered a significance level of
5% (p  0.05).
Conclusions: This study shows that the use of adaptations may
improve the writing performance of patients with spinocerebellar
ataxia.
915
Reliability and discriminant validity of ataxia rating scales in
early onset ataxia
R. Brandsma, T.F. Lawerman, M.J. Kuiper, J.T. van Geffen, I.J.
Lunsing, H. Burger, T.J. de Koning, J.J. de Vries, M.A.J. de Koning-
Tijssen, D.A. Sival (Groningen, Netherlands)
Objective: To determine observer-agreement and discriminant
validity of ataxia rating scales.
Background: In children and young adults, Early Onset Ataxia
(EOA) is frequently concurrent with other Movement Disorders,
resulting in moderate inter-observer agreement among Movement
Disorder professionals. To investigate whether subjective phenotypic
assessment is replaceable by quantitative measures, we aimed to
determine inter-observer agreement and discriminant validity of
ataxia rating scales.
Methods: In 40 EOA patients (15 (5-34) years; mean (range)),
three independent pediatric neurologists assessed quantitative ataxia
rating scales (ICARS, SARA and BARS), and phenotyped the pri-
mary Movement Disorder characteristic (i.e. ataxic, dystonic, myo-
clonic, choreatic, tics) in each patient. We determined inter- and
intra-observer agreement and specified outcomes for primary (i.e.
unanimous ataxia identification as the primary feature by all asses-
sors and/or genetic ataxic diagnosis (n526)) and secondary (i.e.
incomplete identification of ataxia as the primary Movement Disor-
der (n512)) subgroups.
Results: Inter- and intra-observer agreement of ataxia rating
scales revealed high intra-class correlation coefficients (ICC: .92 -
.99; for ICARS, SARA and BARS), with no significant differences
between primary and secondary subgroups. Total ataxia rating
scale scores revealed higher outcomes in the primary than the
secondary subgroup (p<.001). A multivariable regression analysis
revealed that the severity of the primary Movement Disorder charac-
Movement Disorders, Vol. 30, Suppl. 1, 2015
teristic (b .57- 1.0; p .011 - <.001) predicted these higher quantita-
tive outcomes. The primary movement characteristic itself did not
predict higher outcomes.
Conclusions: In EOA, quantitative ataxia rating scales reveal
high inter- and intra-observer reliability, reflecting reliable applicabil-
ity. However, multivariable regression analysis revealed low discrim-
inant validity between ataxia and other Movement Disorder
characteristics. Despite high reliability of quantitative ataxia scores,
these data implicate that preceding phenotypic characterization
remains irreplaceable.
916
Congenital pyramidal signs and cerebellar ataxia with abnormal
pyramidal decussation - A new syndrome
A. Castro Caldas, S. Reim~ao, L. Correia Guedes, M. Miguel Rosa, J.
J Ferreira, M. Coelho (Lisbon, Portugal)
Objective: To report a unique syndrome characterized by congen-
ital pyramidal signs, cerebellar ataxia and aberrant pyramidal
decussation.
Background: Non-progressive congenital ataxias are a heteroge-
neous group of rare disorders characterized by delay of motor devel-
opment and hypotonia followed by cerebellar signs. They may be
associated with pyramidal signs, mental retardation and eye Move-
ment Disorders.
Methods: Case report.
Results: Case 1. 35 year-old white female presented for investi-
gation of her chronic neurologic status. She had severe motor delay
with hypotonia and crawling until 7 years of age, when she gained
bipedal gait. Her parents are first-degree cousins. Neurological exam-
ination showed normal MMS, bilateral hyperreflexia and left clonus,
and pancerebellar signs with titubation, horizontal nistagmus, hyper-
metric saccades, and slight axial and appendicular ataxia. Blood tests
with CBC, albumin, ceruloplasmin, cooper, AFP and vitamin E were
normal. Serum lactic acid was twice the normal. MRI showed cere-
bellar hypoplasia with elongated midbrain and superior cerebellar
peduncles, without pons size reduction and slightly increased diame-
ter of the cervical spinal cord at C3-C5 level. Tractography showed
decussation of pyramidal tract between pons and medulla. Genetic
tests for Friedreich ataxia and autosomal recessive spastic ataxia of
Charlevoix-Saguenay were negative. Case 2. 43 year-old male, first-
degree cousin of case 1, presented motor delay and gait acquisition
at the age of 10 and mental retardation. Neurological examination
showed marked mental retardation, oculomotor apraxia (OMA), hori-
zontal and vertical nistagmus, hypometric saccades, facial dystonia,
ataxic dysartria, generalized hyperreflexia, slight appendicular and
moderate axial ataxia. MRI and tractography showed identical find-
ings as case 1, however with more severe cerebellum hypoplasia.
Case 3. 36 year-old male, younger brother of case 2, presented with
an identical but more severe neurological syndrome than his brother,
with severe mental retardation, severe axial ataxia, scoliosis and
short stature. MRI and tractography showed identical findings as his
brother, with additional marked dysgenesis of the corpus callosum
and multiple areas of polymicrogyria.
Conclusions: We report 3 family members who display a new
and unique clinical and imagiological congenital ataxic syndrome
occurring as an autosomal recessive inheritance.
917
Impaired brain GABA in spinocerebellar ataxia type 7: A
magnetic resonance spectroscopy study
H.J.S. Cho, P. Panyakaew, B.P. Brooks, S.G. Horovitz, M. Hallett
(Bethesda, MD, USA)
Objective: To explore GABA levels in the cerebellum in patients
with spinocerebellar ataxia type 7 (SCA 7) compared to controls
 POSTER SESSION S357

Fig. 1. (917).

using multi-metabolite proton magnetic resonance spectroscopy (1H was significantly decreased in cerebellum but not in mid frontal lobe
MRS). in SCA7 group (table2). There was no significant volumetric differ-
Background: SCA 7 is an autosomal dominant neurodegenerative ence in grey and white matter between two groups.
disorder characterized by progressive neurological manifestations and
retinal degeneration. Cerebellar tissue from SCA7 patients has evi-
dence of extensive loss of cerebellar Purkinje cells where GABA Spectroscopy and segmentation result
serves as a major neurotransmitter. Biochemical changes associated Cerebellum
with neuronal dysfunction can be quantified by 1H MRS and may
serve as biomarkers of the disease. We speculated that GABA con- GABA/ GABA/ NAA/ NAA/ %GM %WM
centrations in cerebellum will be low in SCA7 patients which may Cr GM* Cr WM Cr GM* Cr WM
be an indicator of loss of GABAergic Purkinje cells.
Methods: Four SCA patients (4 females, mean age 31.33 6 4.16) SCA7 0.18 0.16 1.99 1.86 0.44 0.40
and 4 matched controls (4 females, mean age 26.25 6 5.31) partici- HV 0.37 0.20 3.86 2.04 0.63 0.34
pated in this on-going study. MRS and MRI data were collected in a Mid frontal lobe
3T scanner. A voxel of 18.00 cc was centered on the right cerebellar GABA/ GABA/ NAA/ NAA/ %GM %WM
hemisphere and mid frontal area for each participant. Point-resolved Cr GM Cr WM Cr GM Cr WM
spectroscopy (PRESS) pulse sequence and the J-edited method were
used to measure metabolites of interest (figure 1). Creatine (Cr) was SCA7 0.19 0.18 1.86 1.99 0.44 0.46
used to normalize the GABA signal. N-acetyl aspartate (NAA) was HV 0.36 0.40 2.04 3.86 0.44 0.39
also measured to assess overall neuronal loss or dysfunction. The cere-
bellum and mid frontal voxel of each participant was segmented into *p<0.05, Mann-Whitney U test, GM=grey matter, WM=white
grey and white matter to account for possible volumetric differences matter, NAA=N-acetyl aspartate
between the groups. GABA/Cr and NAA/Cr ratios were extrapolated
according to fraction of grey matter and white matter.[figure1]
Conclusions: This is the first pilot study using 1H MRS to dem-
Results: Demographic and clinical data for patients are in Table 1.
onstrate that GABA level in cerebellum is significantly decreased in
SCA7 patients. Longitudinal study with larger sample is required to
Demographic data of the patients
Age Sex Disease duration SARA score

Patient 1 28 F 15 18.5
Patient 2 30 F 9 7.5
Patient 3 36 F 6 11.5

SARA=Scale for the assessment and rating of ataxia

The GABA/Cr ratio in cerebellar grey matter was reduced in the

SCA 7 patients compared to controls (figure 2). The GABA/Cr ratio
in the mid frontal area showed a trend for lower level in patient
group but it did not reach statistical significance. The NAA/Cr ratio Fig. 2. (917).

Movement Disorders, Vol. 30, Suppl. 1, 2015

S358 POSTER SESSION
address whether GABA MRS can be considered as a potential bio-
marker of the disease.
918
Spinocerebellar ataxia type 10 in Peruvian population: Clinical
features of 17 families
I.F. Cornejo-Herrera, D.M. Veliz-Otani, M.R. Cornejo-Olivas, M.A.
Inca-Martinez, K.A. Espinoza-Huertas, V. Marca, O. Oterga, R. Cas-
tilhos, G. Bampi, M. Flores, M.L. Saraiva-Pereira, L.B. Jardim, P.
Mazzetti (Lima, Peru)
Objective: To describe the clinical features of 17 Peruvian fami-
lies with Spinocerebellar ataxia type 10 (SCA10).
Background: Spinocerebellar ataxia type 10 (SCA10) is an
autosomal-dominant neurodegenerative disease caused by an abnormal
ATTCT expansion within the ATXN10 gene. SCA10 has been only
reported in populations of Latin-American admixture and Amerindian
ancestry, mainly in Mexico and Brazil, where it is the second most
common SCA after SCA2 and MJD/SCA3 respectively. There is lim-
ited information regarding SCA10 in other Latin-American regions.
Methods: We identify all subjects who had positive diagnosis for
SCA10 from the Neurogenetics Research Center database at Instituto
Nacional de Ciencias Neurologicas, Lima, Peru. Standardized neuro-
logical examination, cognitive assessment based on MoCA, SARA
and NESSCA ataxia scales, neuroimaging was performed for each
participant when possible.
Results: We identified 22 SCA10 affected individuals from 17
families with a mean age at onset of 39.9 68.77[range: 21, 55], 59%
were male, and 13 had family history. Main clinical features
included: Ataxia 100%, eye Movement Disorders 33.3%, nistagmus
52.3%, neuropathy 9.5% and pyramidalism 9.5%, and cognitive
impairment based on MoCA 19%. Four cases (4 families) reported
seizures. The mean of SARA and NESSCA scales scores were
11 6 4.11 and 8.436 2.37, respectively. Nine of 11 individuals
showed cerebellar atrophy on MRI/TC neuroimaging. Twelve out of
17 families declared most ancient ancestor in the highlands of Peru.
Conclusions: The SCA10 families are characterized by predomi-
nant ataxia phenotype, with low frequency of seizures and neuropa-
thy. Most families come from Quechua-speaking areas from the
Peruvian highlands, in accordance with the Amerindian origin
hypothesis for this mutation.
919
Mutation screening of AFG3L2 in Indian cerebellar ataxia
patients: an early onset cerebellar ataxia with digenic mutations
in AAAproteases ideintified through whole exome sequencing
M. Faruq, R. Kumari, V. Suroliya, A.K. Srivastava (New Delhi,
India)
Objective: To define the frequency of SCA28/AFG3L2 mutations
in Indian cases of cerebellar ataxias.
Background: Spinocerebellar ataxia type 28 (SCA 28) is a novel
and rare form of autosomal dominant cerebellar ataxia characterized
by slow progression and ophthalmoparesis.Genetically, caused by
mutation in the mitochondrial protease AFG3L2 and the reported
mutations are restricted to exon 4-5, exon 10, exon 15 and exon 16
of the gene.
Methods: We have sequenced mutation hot spot region of
AFG3L2(Exon-4-5, 10, 15 and 16) in 350 genetically uncharacter-
ized cases of progressive cerebellar ataxias. We have also performed
Whole exome sequencing and mitochondrial genome sequencing in
one cases with a novel mutation in AFG3L2.
Results: Sequencing of hot spot mutation region showed novel
putative pathogenic and polymorphic nucleotide variations in hetero-
zygousity in AFG3L2. A known mutation p.R702Q in a patient was
observed. Among novel variations, we found p.F503C in a family
with multiple affected individuals where all affected harbors varia-
Movement Disorders, Vol. 30, Suppl. 1, 2015
tion but one unaffected individual was also the carrier. An another
novel base change leading to R679C aminoacid substitution in two
unrelated patients was found. Interestingly we observed differential
age at onset these 2 patients, where one patient679a had disease
onset at 14 years and 679b had onset at 60 years of age. A re-
evaluation of clinical phenotype showed that 679a had some addi-
tional features comprised optic atrophy, spastic paraplegia over cere-
bellar signs which patient 679b have not manifested. Mitochondrial
genome sequencing of these two patients showed no additional varia-
tions in 679a. We then performed whole exome sequencing in 679a
which allowed us to identify an additional known protein truncating
mutation (p.L78*) in SPG7 (spastic paraplegia 7 associated) in a
homozygous state.
Conclusions: We conclude that patient 679a is a carrier of
digenic mutations in functional closely relate mitochondrial AAA
proteases genes (AFG3L2 and SPG7). The phenotypic manifestation
in 679a represents either the effect of dysfunction of SPG7 alone or
in combination with AFG3L2. The frequency of SCA28 in India
seems to be significant and warrants further studies. Whole exome
sequencing represents a powerful tool for genetic discoveries in com-
plex but overlapping hereditary neurodegenerative disorders.
920
Neurotechnology biomarkers in Friedreichs ataxia
S. Nageshwaran, C. Gavriel, A. Sylaidi, P. Lourenco, S.
Athanasopoulos, R. Lorenz, A. Thomik, R. Festenstein, A. Faisal
(London, United Kingdom)
Objective: To develop a novel objective biomarker for measuring
clinical progression in Friedreichs Ataxia using motion capture
technology.
Background: Friedreichs ataxia (FRDA) is a progressive neuro-
degenerative disorder that affects 1 in 50 000 people. FRDA research
has now transitioned from the bench to the bedside with several
drugs in clinical trials worldwide. Clinical outcome measures in
FRDA trials include recognised validated scales such as the Scale
for the assessment and rating of ataxia (SARA), the Friedreichs
Ataxia Rating Scale (FARS) as well as patient reported activities of
daily living (ADL) scales. Due to rater-dependent variation and
recall bias, as well as relatively low rate of change with each rating
scale (e.g. SARA: -1 point/year), there is a need for objective assess-
ment tools in clinical trials.
Methods: Kinematic data will be collected from 9 FRDA patients
and age-sex matched controls using novel motion capture technology
to objectively assess disease progression over 1 year and ADLs in a
number of natural environment scenarios (e.g. having breakfast,
preparing for work and preparing for bed). SARA assessment will
also be undertaken at each time point to investigate if subtle changes
in disease progression could be elucidated without meeting the
threshold for change in SARA.
Results: The final outcome of this study aims to identify objec-
tive measures of ataxia that can be incorporated into a clinical trial
of therapeutic interventions for Friedreichs Ataxia. Preliminary
results using principle component analysis have highlighted a possi-
ble FRDA movement fingerprint.
Conclusions: Due to the slowly progressive nature of FRDA,
changes in a patients movement may not be be adequately resolved by
SARA measurements alone. With the advent of possible disease modi-
fying therapies in FRDA, objective outcome measurements for clinical
trials will help for more robust measure of intervention effect, shorter
trial duration and permit studies to be powered with fewer subjects.
921
The splenium of the corpus callosum sign in fragile X associated
tremor ataxia syndrome (FXTAS)
D. Hall, M. Hermanson, M. Jhaveri, G. Stebbins, E. Dunn, D.
Merkitch, E. Berry-Kravis (Chicago, IL, USA)
 POSTER SESSION S359

Objective: To investigate the prevalence of white matter lesions

in the corpus callosum splenium (CCS sign) in individuals with
FXTAS.
Background: FXTAS is an adult-onset Movement Disorder that
manifests as tremor, ataxia, and Parkinsonism in premutation carriers
of 55-200 CGG repeats in the 5 promoter region of FMR1.
Recently, FXTAS was associated with hyperintensities in the corpus
collosum splenium (CCS) in a small case series at a frequency simi-
lar to the middle cerebellar peduncle (MCP) sign.
Methods: Demographics, FXTAS parameters (e.g. CGG repeats,
symptoms), and MRI scans were collected from FXTAS subjects and
age-matched controls, who had other Movement Disorders and nega-
tive FMR1 testing. A neuroradiologist who was blinded to carrier
status assessed the scans for cerebral atrophy and hyperintensities in
the MCP, brainstem, and CCS.
Results: Twenty-two FXTAS (61% men, mean CGG repeat size
of 89) and 23 control (65% men, mean repeat size of 29) MRI scans
were included. Both groups were predominantly white, non-Hispanic,
and had a mean age at imaging of 67.5 (FXTAS, sd=6) and 64.7
(control, sd=12.4) years. Of the FXTAS subjects, 9 had definite, 10
had probable, and 3 had possible FXTAS. The majority of the con-
trols had Parkinsons disease (35%) or ataxia (25%). The following
imaging findings were more frequent in the FXTAS subjects: CCS
sign (p<0.01), MCP sign (p<0.01), cerebral atrophy (p50.03), brain-
stem white matter disease (p50.02). None of the clinical neuroradi-
ology reports noted the CCS sign.
Conclusions: FXTAS subjects had a higher prevalence of cere-
bral atrophy and hyperintensities in the CCS, MCP, and brainstem
compared to age-matched controls. While cerebral atrophy and
hyperintensities in the MCP and brainstem are current diagnostic cri-
teria for FXTAS, the CCS sign is not widely recognized as a radio-
logic manifestation. However, this study demonstrates that the CCS
sign may be an under-reported useful clinical marker to aid in the
diagnosis of FXTAS.

922
Neuropathology of Parkinsonism in spinocerebellar ataxia type
6: A case report
D. Kaul, K.W. Morley, M. Pakalniskis, W.F. Hickey, S.L. Lee
(Lebanon, NH, USA)
Objective: Spinocerebellar ataxia type 6 (SCA6) is a rare autoso-
mal dominant neurodegenerative Movement Disorder, part of the
group of CAG repeat diseases. Parkinsonism has been reported in
SCA6 as well as several other SCAs, but pathological information
regarding this association has been rarely described in the literature.
Background: The patient was a 69-year-old woman, who pre-
sented with gait ataxia and diagnosed with SCA6 expansion of 22
repeats. She then developed a unilateral resting hand tremor that was
partially levodopa-responsive. She subsequently deteriorated rapidly,
becoming immobile with rapid cognitive decline and died three years
later.
Methods: Laboratory ataxia evaluation and restricted autopsy
performed at the request of the patients family to evaluate for con-
comitant neurodegenerative disorders.
Results: Histological examination of the brain confirmed substan-
tial Purkinje cell loss, typically found in cases of SCA6. Polyglut-
amine related inclusions were not seen, but rather, typical Lewy
body pathology and loss of pigmented neurons was found in substan-
tia nigra and other brain stem regions.
Conclusions: These results suggest that Parkinsonism associated
with SCA6 is pathologically similar to idiopathic Parkinsons
disease.
923
Atypical spinal cord atrophy in Friedreich ataxia
P. Khemani, Z. Yetkin (Dallas, TX, USA)
Fig. 1. (923).
Objective: To present a case of Friedreich Ataxia with the
uncommon radiographic finding of severe thoracic spinal cord
atrophy.
Background: Friedreich ataxia (FA), caused by an unstable GAA
repeat expansion in the frataxin gene (FXN) located on chromosome
9, has been identified as the most commonly inherited autosomal
recessive ataxia. FA can present with varying clinical phenotypes
and neuroradiographic findings. While marked cervical spinal atro-
phy seen on MRI has been recognized in FA, thoracic cord atrophy
is an uncommon finding.
Methods: A 26 year old man was referred to our clinic for evalu-
ation of gait and balance difficulties that had started in his early 20s.
He sought a consultation due to recent worsening of in his balance
resulting in a fall. He had also noticed mildly slurred speech over
the years. Despite his symptoms, he was was fully independent with
all activities and was employed as a chemical engineer. He had no
visual, sensory, or bladder and bowel complaints. He didnt complain
of weakness in arms or legs. Overall, there had been a mild progres-
sion in his symptoms since their onset. There was no consanguinity
between parents or family history of similar symptoms. Alcohol
intake was at least 15-20 beers per week. Neurological examination
was remarkable for normal cognition, subtle dysarthria, brisk reflexes
with clonus at the ankles, and impaired tandem gait and stance. No
other abnormal findings were noted at initial consultation. Investiga-
tion was ordered for acquired causes of myelopathy and ataxia.
Results: Serum and cerebrospinal fluid studies did not reveal an
acquired etiology for myelopathy or ataxia. Electrodiagnostic tests
were normal. Brain MRI showed mild cerebellar vermian atrophy for
his age; spine MRI showed marked atrophy of the thoracic spinal
cord (figure 1) compared to cervical spinal cord (figure 2). Genetic

Movement Disorders, Vol. 30, Suppl. 1, 2015

S360 POSTER SESSION
Fig. 2. (923).
tests ordered for ataxia revealed 399 and 333 GAA repeats (pos-
itive > =67) in the FXN gene confirming FA.
[figure1] [figure2]
Conclusions: While the most commonly reported spinal abnor-
mality in FA is cervical cord atrophy, thoracic cord atrophy is not
well documented in the literature and it should be a diagnostic clue
for an atypical FA phenotype. Whether FA subjects with thoracic
cord atrophy have a clinical course that is discrete from those with
cervical cord atrophy merits further study.
924
Clinical evaluation in children with ataxia in a children
rehabilitation centre
A.P. Kleinert-Altamirano, F.G. Perdomo-Rebollo (Tuxtla Guti
errez,
Mexico)
Objective: To assess the clinical condition of children with ataxia
using the items of the Brief Ataxia Rating Scale (BARS) as well as
determine the etiology of the ataxic syndromes in a Children Reha-
bilitation Centre.
Background: Ataxias are a very heterogeneous group of diseases
with different etiologies, including genetic and non-genetic forms.
There are many reasons for the lack of treatment for cerebellar
ataxia, one of them being its relatively low population frequency,
and the relatively new development of standardized, well-validated
scales to understand better its natural history and evaluate properly
drug efficacy in clinical trials. Therefore, most ataxic disorders (spo-
radic or inherited) still have no current effective pharmacological
treatment, and patients endure the inevitable degenerative course of
their disease. However the clinical improvement through therapies,
rehabilitation and follow-up in clinical trial can be measured by
scales. SARA and ICARS have been the best studied and validated
so far, and their reliability sustain their use. BARS based on a modi-
Movement Disorders, Vol. 30, Suppl. 1, 2015
fied form of the ICARS is valid, reliable and sufficiently fast por
clinical purposes.
Methods: Transversal, descriptive study, with performance of
BARS items in children with age 4-18 years old, with ataxic syn-
drome, without cognitive impairment, in active status, from february
2007 to september 2014, at the Telethon Children Rehabilitation
Centre, in Tuxtla Gutierrez, Chiapas, Mexico.
Results: We recruited 25 patients, 9 patients eliminated (1 died,
2 came in down status at the center, 6 with cognitive impairment).
Only 14 were considered for the BARS, 57% (8) female and 43%
(6) male, main age 12.2, main age of begining of symptoms 2.2. Eti-
ology: 21.4% ataxia-telangiectasia,(AT) 21.4% 4H syndrome (central
hipomielinization, hipodontia, hypogonadotropic hypogonadism),
14.3% ataxic-cerebreal palsy, (A-CP) 42.9% others causes. Main
BARS score 17.9/30, 4H syndrome with the worst score 27.6/30, AT
15.6/30, A-CP 12/30, and others 16.1/30.
Conclusions: In children there is no an specific scale to use, the
most common like ICARS, SARA and BARS are reliable in them,
but should include age-dependent interpretation in children up to 12
years of age. The BARS tems were an easy way to assess ataxic
clinic in children, worse condition was found in neurodegenerative
ataxias and better in ataxic cerebral palsy.
925
European SARA age validation trial in children -Preliminary
results-
T.F. Lawerman, R. Brandsma, N. Barisic, P. Baxter, E. Bertini, V.
Brankovic, J.G.M. Burgerhof, G.E. Calabro, C.E. Catsman-
Berrevoets, D. Craiu, I.F.M. de Coo, B. Dan, J. Gburek-Augustat,
F.F. Kamoun, C. Kennedy, R.J. Lunsing, F. Mancini, M. Mirabelli-
Badenier, M. Steinlin, M. Synofzik, C.C. Triki, E.M. Valente, G.
Vasco, D.A. Sival (Groningen, Netherlands)
Objective: To obtain international age-related normative values
for pediatric SARA scores.
Background: Early Onset Ataxia (EOA) is caused by a group of
relatively rare and heterogeneous disorders, often with an autosomal
recessive inheritance mode.
To elucidate the phenotypic disease course, ataxia interest groups
have assembled one longitudinal Early Onset Ataxia (EOA) database,
from childhood to adulthood. In both children and adults, EOA pro-
gression is quantified by the Scale for Assessment and Rating of
Ataxia (SARA). However, since pediatric coordination develops over
time, age-related normative values should be determined, first1.
Methods: Sixteen independent pediatric neurologists (from seven
countries) are presently scoring SARA in 156 healthy children (from
eight European countries). Present abstract concerns the preliminary
results obtained in the first 52 healthy children (4-16 years; 4 chil-
dren per year of age; m/f=1).
Results: Preliminary results reveal a strong SARA age-
dependency (R2=.71). SARA inter-observer agreement (ICC .62) is
interpretable as substantially present2, with the highest variance
amongst scores in the youngest age groups (4-6 years). From 11
years of age onwards, SARA scores tend to approximate adult out-
comes (i.e. optimum values).
Conclusions: Preliminary EPNS CACG pilot data reveal SARA
age-dependency, at least until 11 years of age. For reliable longitu-
dinal interpretation of SARA scores from childhood to adulthood,
we advise to await the international age-related normative values,
first.
1
Brandsma R, Spits AH, Kuiper MJ, Lunsing RJ, Burger H,
Kremer HP, et al. Ataxia rating scales are age-dependent in healthy
children. Dev Med Child Neurol 2014 Jan 7
2
Landis JR, Koch GG. The measurement of observer agreement
for categorical data. Biometrics 1977 Mar;33(1):159-174.
 POSTER SESSION
926
Sleep architecture observed in the patients with SCA 10
E. London, A.C. Crippa, H.A.G. Teive, A. Moro, M. Moscovich, T.
Ashizawa (Curitiba, Brazil)
Objective: To evaluate sleep architeture and identify sleep distur-
bances in patients with spinocerebellar ataxia type 10(SCA10).
Background: Disruption of sleep structure during rapid eye
movement (REM) sleep and high respiratory disturbance indexes
(RDIs) have been reported in another neurodegenerative diseases and
in some types of spinocerebellar ataxia (SCA), including SCA3. To
our knowledge there are no studies on SCA 10 and sleep disturban-
ces in the literature.
Methods: Twenty -three patients with SCA10 and thirty healthy
controls were recruited and evalueted based on their clinical histori-
es,genetic examination, theScale for the Assessment and Rating of
Ataxia (SARA), the Epworth Sleepiness Scale(ESS), the Berlim
Questionnaire and polysomnography according to the criteria pro-
posed by American Academy of Sleep Medicine.
Results: Patients with SCA10 presented longer REM sleep onset
latency and had had more REM sleep without atonia. They did not
show reductions in the percentage of sleep REM, which were not
correlated with the severity of ataxia as evaluated by SARA. The
RDI average and the prevalence of respiratory disturbances were sig-
nificantly higher in the patients with SCA 10 when compared to the
control group.
Conclusions: The findings of the present study provide evidence
that SCA10 patients show REM sleep onset latencies delay, increase
REM sleep without atonia and higher RDIs. Moreover, SCA10
patients appear to have REM sleep structure disruption. Therefore,
future longitudinal studies with larger populations are necessary and
opportune.
927
Wide spectrum of clinical presentation of ataxia with
occulomotor apraxia type II
S.O. Mittal, D.G. Machado (Cleveland, OH, USA)
Objective: To present the wide range of symptoms of Ataxia
with Oculomotor Apraxia 2 (AOA2) and provide three case studies
at both ends of the age spectrum as examples.
Background: AOA2 is rare autosomal recessive inherited disease,
with a prevalence of 1 in 900,000, that affects mainly the cerebel-
lum. It is caused by mutations in the SETX gene encoding for a
large DNA/RNA helicase protein involved in the defense against
DNA damage and in processing RNAs. Clinical features include
polyneuropathy (98%), cerebellar atrophy (96%), occasional oculo-
motor apraxia (51%), pyramidal signs (21%), head tremor (14%),
dystonia (14%), strabismus (12%) and chorea (10%).
Methods: The patients are a young brother and sister (patients 1
and 2, age 20 and 18 years respectively) and a 57 year old man
(patient 3). Patient 1 had onset of symptoms at age 17, mostly trou-
ble walking in a straight line and occasional falls, no diplopia or sen-
sory complaints. Patient 2 had minimal symptoms of occasional
trouble with dexterity and balance. Patient 3 had onset at age 54
years, presenting with numbness in lower extremities and imbalance
requiring a cane. On neurological exam, patient 1 had saccadic
smooth pursuit, ocular dysmetria and overshoot, horizontal direction-
changing nystagmus and upgaze nystagmus, mild scanning dysarthia,
dysmetria on finger-to-nose and heel-to-shin, bilateral dysdiadochoki-
nesia, ataxic gait, and loss of lower extremity vibration sense. Patient
2 had milder signs relative to her brother. Patient 3 had horizontal
nystagmus to either direction with upgaze nystagmus, mild to moder-
ate cerebellar findings, wide base gait and decreased sensation to all
modalities below his calves.
Results: MRI brain for all three patients showed marked cerebel-
lar atrophy. Nerve conduction studies were abnormal and consistent
with sensory neuropathy. Alpha-fetoprotein was elevated in patient 1
S361
and 2. All 3 patients showed mutations in the SETX gene in a heter-
ozygous pattern suggestive of AOA2.
Conclusions: We have discussed a spectrum of patients here pre-
senting with sign and symptoms that can be seen inAOA2 demon-
strating a heterozygous pattern. There is a possibility that these
patients have a second mutation not detected because of its presence
in a non-coding region on the SETX gene for which advanced
genetic analyses are warranted. AOA2 should be considered in
patients presenting with ataxia and neuropathy.
928
Characteristic Movement Disorders in patients with
spinocerebellar atrophy type 2
N. Miyaue, R. Ando, T. Iwaki, H. Yabe, N. Nishikawa, M. Nagai, M.
Kaneda, H. Takashima, M. Nomoto (Tohon Ehime, Japan)
Objective: We studied early neurological signs in cases with
spinocerebellar atrophy (SCA) type 2.
Background: SCA type 2 is a classification of ataxia. However,
we have found that Movement Disorders are common as the first
neurological symptom. We have reported several cases with SCA
type 2, some of whom developed Parkinsonism, myoclonus, or motor
neuron disease-like muscle atrophy or weakness in addition to cere-
bellar ataxia [Nishikawa et al. 2011]. Some of them initially devel-
oped symptoms of Movement Disorders and were treated for
Parkinsons disease or other Movement Disorders.
Methods: Three families with SCA type 2 in the Ehime area in
Japan were studied. Their clinical signs and course of the Movement
Disorders were investigated.
Results: Three cases from family M were studied. One case
developed Parkinsonism showing tremor and bradykinesia at 39
years of age and then developed ataxia at 62 years of age. The sec-
ond case developed bradykinesia at 47 years of age and showed
ataxia 11 years later. The third case did not develop Parkinsonism,
but rather motor neuron disease-like signs. Two cases from family N
were studied with one case developing myoclonus at 18 years of age
and several years later he developed ataxia. Two cases of family O
were studied with one case developing Parkinsonism. She was
referred because of dysarthria and developed Parkinsonism 3 years
later. Their symptoms of Parkinsonism improved and were well con-
trolled on treatment with levodopa long term. No relationships were
observed between the number of CAG trinucleotide repeats and clini-
cal symptoms or disease course in the patients.
Conclusions: Four of six patients with SCA type 2 developed
Movement Disorders. The first clinical symptom was Parkinsonism
in two cases and myoclonus in one case. One case developed ataxia
at first and then showed Parkinsonism 3 years later. We found Move-
ment Disorders are common as the first neurological symptom in
cases with SCA type 2. Family history and genetic analysis are
important for early diagnosis of SCA type 2.
929
Analysis of gait parameter in spino-cerebellar ataxia patients
using electronic walkway: With and without cognitive load
B. Mondal, S. Choudhury, P. Chatterjee, M.U. Kulsum, S.S. Anand,
H. Kumar (Kolkata, India)
Objective: 1. To compare the gait parameters of spino-cerebellar
ataxia (SCA) patients with healthy controls.
2. To understand the effect of cognitive load on gait in SCA
patients and healthy controls.
3. To study the correlation between ataxia scales.
Background: The gait parameters of SCA patients might be
affected by dual tasking. We have evaluated the walking parameters
of SCA patients and healthy volunteers with or without cognitive
tasks.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S362 POSTER SESSION
Methods: In this study, the gait parameters of 23 SCA patients
were assessed through electronic walkway and compared with
healthy volunteers.Differences between gait parameters with or with-
out cognitive load (100-7 test, reverse counting) of SCA patients and
healthy volunteers was assessed. The severity of ataxia in these
patients was evaluated by International Co-Operative Ataxia Rating
Scale (ICARS) and SARA scale. Their balance, cognition and func-
tional gait assessment were evaluated using falls efficacy scale
(FES), MMSE and FGA scale respectively.
Results: Mean age of 23 SCA patients was 47.17 (SD 12.06) and
60.9% were male. The mean ICARS and SARA score were 38.35
(SD 16.95) and 19.39 (SD 7.45). With cognitive load, the gait veloc-
ity and cadence reduced significantly in ataxic patients {velocity=
72.77 (28.95) Vs 46.38 (18.89) cm/sec, p value 0.0001. cadence=
97.92 (20.52) Vs 80.78 (20.27), p value=0.0001} whilst few gait
parameters (base width, Toe in/Toe out) were unaffected. Baseline
velocity and ambulation time were lower in SCA patients compared
to healthy volunteers. However, cadence of SCA patients and healthy
volunteers were comparable. Change in step count with dual tasking
was significantly higher among SCA patients as compared to healthy
control. The SARA static, kinetic, speech components showed strong
correlation with similar of ICARS components score except ICARS
oculomotor score. We also found a strong correlation between FGA
and ICARS static, SARA static and FES score.
Conclusions: We present objective gait parameters of SCA
patients using validated instrument which significantly changed dur-
ing dual task. The gait of SCA patients are attention demanding and
hence dual tasking while walking can lead to slowness, interruption
or even fall among SCA patients. A strong correlation between FGA
and FES implied that SCA patients having high FGA score, have a
tendency to lose balance and fall.
930
Idiopathic very late-onset cerebellar ataxia: A Brazilian case
series
A. Moro, M.M. Moscovich, W.O. Arruda, R.P. Munhoz, H.A.G. Teive
(Curitiba, Brazil)
Objective: To present a Brazilian case series of eight patients
with idiopathic very-late onset cerebellar ataxia (IVLOCA).
Background: Idiopathic sporadic cerebellar ataxia comprehends a
group of neurodegenerative, non-hereditary disorders, including mul-
tiple system atrophy cerebellar type (MSA-C), and idiopathic late
onset cerebellar ataxia (ILOCA). ILOCA represents an obscure group
of sporadic cases of late onset cerebellar ataxia, without adequate
clinical, pathological, and genetic definition, described by Harding in
1981.
Methods: Clinical and paraclinical findings of 26 adult patients
with a diagnosis of ILOCA were analyzed in a Brazilian ataxia out-
patient clinic and followed regularly over 20 years. Among them, 8
elderly patients were diagnosed as probable IVLOCA. These patients
were evaluated with neurological, ophthalmologic and Mini-Mental
Status examinations, brain MRI, and EMG. Genetic testing for
Friedreichs ataxia, Spinocerebellar ataxias (SCAs) types 3, 6, 17,
Huntingtons disease, and Fragile X-associated tremor ataxia syn-
drome (FXTAS). Diagnosis of probable REM sleep behavior disorder
(RBD) was based on clinically validated criteria.
Results: In this case series of IVLOCA, 62.5% of patients were
males, mean age was 81.9 years-old, and mean age of onset of 75.5
years. Gait cerebellar ataxia was observed in all patients, as well as,
cerebellar atrophy on brain MRI. There was no incoordination in the
upper limbs, and mild dysarthria was found in 50% of patients. Mild
choreiform movements were detected in three patients. There were
no pyramidal signs and no dysautonomia. There was no family his-
tory of ataxia. Genetic tests for Friedreichs ataxia, SCAs 3, 6, and
17, and Huntingto ns disease and FXTAS, were negative. In two
patients, mild sensory peripheral neuropathy was diagnosed on EMG.
None had RBD. Visual loss, with macular degeneration, and amnes-
Movement Disorders, Vol. 30, Suppl. 1, 2015
tic mild cognitive impairment (MCI) were detected in four (50%)
cases each.
Conclusions: The authors present a Brazilian case series of eight
patients with idiopathic very-late onset cerebellar ataxia, featuring pre-
dominantly gait ataxia, associated with cerebellar atrophy. Mild cogni-
tive impairment and visual loss, due to macular degeneration, were
observed in 50% of cases. Chorea was concomitantly found in 3 patients.
931
Comparison of non-motors symptoms in patients with
spinocerebellar ataxia type 10 and type 3
A. Moro, R.P. Munhoz, M. Moscovich, M. Farah, W.O. Arruda, S.
Raskin, T. Ashizawa, H.G. Teive (Curitiba, Brazil)
Objective: To compare the frequency of NMS among patients
with genetically confirmed SCA10, and an age and sex-matched
SCA3/Machado-Joseph disease control group.
Background: Non-motor symptoms (NMS) have been described
in several neurodegenerative diseases, impacting on quality of life.
There is no systematic evaluation of these clinical features in spino-
cerebellar ataxia type 10 (SCA10).
Methods: Twenty-eight Brazilian patients with SCA10, and a
control group with 28 SCA3 patients underwent assessment with a
standardized protocol that evaluated chronic pain, autonomic symp-
toms, fatigue, sleep disturbances, depressive and anxiety symptoms,
and cognitive assessment using the Mini-Mental Status Examination,
Frontal Assessment Battery, verbal fluency and Clock Drawing Test.
Results: Mean age was 46.8 6 11.6 years in SCA10 patients ver-
sus 49.7 6 9.7 years in control group. Symptoms started earlier in
SCA10 group (31.7 vs 36.4 years; p50.02). Chronic pain and fatigue
were more frequent in SCA3 patients, although the difference was
not statistically significant. In SCA3 group, 22% of patients related 3
or more autonomic symptoms (vs 8% in SCA10 patients; p<0.01).
REM behavior disorder and restless legs syndrome were significantly
more prevalent in the control group (12% vs 0, p<0.01; 10% vs 1%,
p50.005, respectively). Mean daytime sleepiness scores were higher
in SCA10 patients [8 (4-11.5) vs 6.5 (3-10); p50.49]. The control
group presented higher scores in Beck Depression Inventory (14.5 vs
12.5; p50.60) and in Hamilton Anxiety Scale (15 vs 8.5; p50.04).
Except verbal fluency, that showed below average in the control
group (11.5 vs 13.3; p50.02), all other tests of cognition showed
similar results between the two groups (p>0.05).
Conclusions: Except for daytime sleepiness, all other NMS were
more prevalent among SCA3 cases, confirming SCA10 as a more
pure form of SCA.
932
HMG-CoA reductase inhibitors induced cerebellar ataxia. A
Brazilian case series
M.M. Moscovich, A. Moro, W.O. Arruda, R.P. Munhoz, H.A.G. Teive
(Curitiba, Brazil)
Objective: To report a case series of progressive cerebellar ataxia
induced by HMG-CoA reductase inhibitors (statins).
Background: Drug-induced cerebellar ataxias (DICA) represent
an expressive group of secondary cerebellar ataxias.
Methods: Observational study with a Brazilian case series of
patients with cerebellar ataxia due to statins use.
Results: We present 4 patients with cerebellar ataxia, predomi-
nantly gait ataxia, due to statins use. Mean age was 67.5 years old,
predominantly male, with several comorbidities, such as dyslipide-
mia, diabetes mellitus, hypertension, and myocardial revasculariza-
tion. After statin withdrawal, and treatment with coenzyme Q10,
progressive improvement of gait ataxia was observed.
Conclusions: We present a case series of four patients with cere-
bellar ataxia due to statins use. Its represents a new rare side-effect
of statins, probably related to coenzyme Q10 deficiency.
 POSTER SESSION
933
Cerebellar features in spastic paraplegia: A cohort analysis
W. Nachbauer, A. Neureiter, A. Eigentler, W. Poewe, S. Boesch
(Innsbruck, Austria)
Objective: To (1) retrospectively study occurrence of cerebellar
symptoms and imaging abnormalities in a cohort of patients with
lower limb spasticity and (2) to prospectively define cerebellar
involvement and progression based on validated ataxia rating scales.
Background: Spastic paraplegias and cerebellar ataxias are rare
neurodegenerative disorders. Both are hereditary disorders with dif-
ferent modes of inheritance and distinct mutations. There is consider-
able overlap between these disorders. Numerous hereditary spastic
paraplegia (HSP) mutations are associated with a cerebellar syn-
drome. In turn, ataxias are often accompanied by lower limb spastic-
ity. Recently, the term spastic ataxia has become a common
expression for a clinical syndrome which contains spastic and ataxic
features and is not clearly attributable to one of the two groups.
Methods: Patients with the emerging clinical symptom of lower
limb spasticity were identified from the clinical database of the
Department of Neurology at the Medical University Innsbruck. Symp-
tomatic causes were excluded from analysis. Medical records were
systematically analysed for demographic data, clinical symptoms,
genetic and radiological findings. Standardized ataxia rating scales and
functional measures were implemented during routine examination.
Results: 56 patients with a mean age of 48 years (range 20 78)
were identified from the database. 39% had a positive family history
for spastic paraplegia; genetic diagnosis was established in 27%.
Atrophy of the cerebellum was detected in 16.1% of patients with
increasing percentage in patients with complicated course of spastic
paraplegia (37.5 vs. 12.5%). 15.8% additionally exhibited atrophy of
the spinal cord. 18 patients with a mean age of 43 years (range 20
65) were prospectively followed up. 61.1% had a score of >5 on the
scale for assessment and rating of ataxia. In 72.2% mild upper
limb ataxia was present. Dysarthria was detected in 27.7% of
patients and stated as the initial clinical symptom in 2 patients.
Impairment on the composite cerebellar functional severity score
(CCFS) was more prominent in complicated spastic paraplegia.
Conclusions: These data give further clinical and radiological
evidence for cerebellar involvement in spastic paraplegias with
increasing incidence in complex disease courses. More specific phe-
notype characterization of spastic ataxias will help to narrow the
differential diagnoses of this overlapping syndrome.
934
Nicotinamide given once daily is more effective than twice daily
at increasing frataxin expression in Friedreichs ataxia
S. Nageshwaran, S. Athanasopoulos, C. Georgiadou, C. Yandim, T.
Natisvili, P.P. Law, P.K. Chan, V. Libri, N. Loyse, P. Giunti, R.
Festenstein (London, United Kingdom)
Objective: To assess the effect of twice daily dosing of nicotina-
mide on (1) maximum tolerated dose (MTD), (2) side effects and (3)
frataxin expression in patients with Friedreichs ataxia.
Background: Nicotinamide is a histone deacetylase (HDAC)
inhibitor which we have recently shown to increase Frataxin (FXN)
expression in patients with Friedreichs ataxia (FRDA) by overcom-
ing heterochromatin silencing, when administered at a high-dose (3-
6g) single oral tablet over 8 weeks providing a potential modifying
therapy for this incurable and frequently devastating condition. In
this study the MTD was determined by the development of nausea or
liver function test derangement.
Methods: We conducted an 8 week open-label dose escalation
study in a cohort of 9 additional subjects with FRDA (aged 18 years
or older). Subjects were gradually escalated from 3g (1.5g twice
daily) of nicotinamide and assessed weekly until an MTD was estab-
lished. Blood was taken at each time point and frataxin levels were
measured from peripheral blood mononuclear cells (PBMC) using
S363
the Mitosciences Frataxin Protein Quantity Dipstick Assay Kit (Mito-
Sciences Inc.).
Results: Nicotinamide was generally well tolerated, however sur-
prisingly, compared to single dosing; there was an increase in the
number of reported adverse events (e.g. nausea) with twice-daily
dosing. Subjects showed improvement in FXN expression; although
this effect was not sustained throughout the study. The greatest
increase was observed at week 5, where the increase in frataxin pro-
tein was 1.44 fold compared to baseline (P=0.16) and FXN mRNA
increased by 1.70 (P=0.03) fold. As expected, in a slowly progressive
neurodegenerative disease, there was no improvement in SARA scale
after 8 weeks.
Conclusions: These findings support the use of nicotinamide
given as a single dose in a randomized placebo controlled trial to
determine clinical efficacy over a longer period.
935
49 year old male with rapidly progressive cerebellar ataxia
secondary to non-paraneoplastic voltage-gated calcium channel
antibodies (VGCC): Case report
S. Patel, I. Itin (Cleveland, OH, USA)
Objective: To present a case of rapidly progressive non-
paraneoplastic cerebellar ataxia due to VGCC antibodies responsive
to IVIG treatment.
Background: Patient is a 49 year old man with a past medical
history of hypertension, hyperlipidemia and diabetes mellitus present-
ing with rapidly progressive ataxia. He was wheelchair-bound five
months after onset of symptoms. His speech was dysarthric and he
had dysphagia. The patient also developed orthostatic hypotension.
The patient did not have bowel or bladder problems. He had no fam-
ily history of similar symptoms. However, he had history of
smoking.
Methods: On presentation he had preserved cognition and cere-
bellar scanning speech. No Parkinsonian signs were appreciated. He
had severe appendicular and gait ataxia. He was unable to write or
drink from a cup. He was unable to walk more than a few steps
even with assistance.
Results: Diagnostic work-up revealed positive titer of VGCC
antibodies (both P/Q and N) in serum. CSF studies showed evidence
of intrathecal inflammation. CSF paraneoplastic antibody panel was
unremarkable although it did not include VGCC. Lambert-Eaton syn-
drome was excluded both by absence of specific findings on physical
examination and appropriate studies (negative serology and EMG).
Brain imaging showed cerebellar atrophy but not signs pathogno-
monic for multiple systems atrophy (MSA). Dysautonomia work-up
(QSART, TST and tilt-table test) showed post-ganglionic changes
responsible for orthostatic hypotension. Thorough neoplastic work-up
excluded underlying malignancy. Extensive testing for alternative
cause of cerebeller ataxia was also unremarkable.
He had two IVIG treatments bringing about functional improve-
ment in ataxia and gait. Furthermore, VGCC antibody titers demon-
strated decline after two rounds of treatment.
Conclusions: This is the second published report of non-
paraneopalstic rapidly progressive cerebellar ataxia responsive to
IVIG. One should include this entity into diferential diagnosis of rap-
idly progressive cerebellar ataxia.
936
A family affected by SCA27 caused by interstitial chromosome
13q33.1 deletion
M. Paucar, J. Lundin, P. Svenningsson, E. Iwarsson, Movement
Disorder Group (Stockholm, Sweden)
Objective: Our objective is to characterize the phenotype and
genotype of a four-generation Swedish kindred affected by a rare
spinocerebellar (SCA) type. The phenotype consists of varying
Movement Disorders, Vol. 30, Suppl. 1, 2015
S364 POSTER SESSION
degrees of ataxia, abnormal eye movements, cognitive impairment
and neuropsychiatric symptoms.
Background: Spinocerebellar ataxia type 27 (SCA27) is a very
rare SCA form caused by mutations in the FGF14 gene. Only three
families and a sporadic case affected by SCA27 have been reported
so far. The first SCA27 family described was a Dutch kindred with
14 affected individuals, their disease was caused by a missense muta-
tion. A recent report (J.A. Coeberg, 2013) described a partial dele-
tion of FGF14 and ITGBL-1 in a SCA27 family.
Methods: A comprehensive phenotype work-up that included
neurological exam, review of medical charts, imaging studies and
psychometric evaluation was carried out on this family. Genetic stud-
ies included aCGH and test for poly-Q SCAs.
Results: Seven subjects were identified as symptomatic in this
kindred, the index case (a 14 y.o. girl) was previously diagnosed
with ADHD and postural tremor. Upon closer evaluation she has
found to be affected by ataxia and posturing. MRI of her brain was
normal. An array CGH (aCGH) was performed first. Her mother (35
y.o) is also affected by a similar phenotype and mild ENeG abnor-
malities. Review of charts in her case was notorious for the presence
of cervical dystonia during the neonatal period. Varying degrees of
intellectual disability were found in some of the affected. An intersti-
tial chromosome 600 kb deletion in 13q33.1 was identified in all
the affected subjects. The deleted area contains the entire genes
FGF14 and ITGBL-1; the function of the latter gene is unknown.
Poly-Q SCAs were ruled out in the index case.
Conclusions: In conclusion, this is the first Swedish SCA27 fam-
ily. Our findings supports the role of haploinsufficiency in this disor-
der. The variable disease expressivity and slow progression in our
kindred reminds of the original SCA27 Dutch kindred (J van Swieten
et al 2003). We also found new phenotype features in this kindred
like dystonia, psychotic symptoms, earlier cerebellar atrophy, spinal
cord atrophy and impaired metabolism not only in the cerebellum
but also in cortical areas and in the basal ganglia. Finally, aCGH
seems to be a useful diagnostic tool in unclear SCA cases.
937
A new SCA19/SCA22 family with the T377M variant in the
KCND3 gene
M. Paucar, M. Nordenskj
old, P. Svenningsson (Stockholm, Sweden)
Objective: Clinical characterization and genotype of a small
Swedish family affected by cerebellar ataxia.
Background: SCA19, also allelic with SCA22, is a rare SCA
channelopathy caused by mutations of the KCND3 gene. Only nine
SCA19 families of different ethnic backgrounds have been described
so far. The SCA19 phenotype is variable and consists usually of
mild and slowly progressive ataxia. Myoclonus and cognitive impair-
ment have been described in some cases.
Methods: Comprenhensive clinical work-up and genotype by
means of NGS.
Results: The variant T377M in the KCND3 gene was identified,
this variant segregates with the disease and has been described as a
putative mutation in a Japanese family (Y Lee, 2012). The index
case (III:1) is a 43 year old female whose exact age of onset is hard
to determine. Since early childhood the subject described clumsiness
and inability to perform tandem gait. At the age of 23 years she
experienced a clear progression. A MRI of her brain displays mild
vermis atrophy and mild white matter abnormalities. Case II:2
mother of the proband is 63 year old and affected by a mild cerebel-
lar ataxia and type 2 diabetes but never considered herself as neuro-
logically affected. She described the presence of head and postural
tremor, as well as inability to perform tandem gait since childhood.
The subject describes a non-progressive disease and is still ambula-
tory. Her MRI of the brain displays mild vermis atrophy and wide-
spread white matter abnormalities. Case II:1 is an uncle of the index
case who is affected by a severe ataxia and is confined to a wheel
chair. His current age is 75 years; age at onset for ataxia was
Movement Disorders, Vol. 30, Suppl. 1, 2015
reported to be 21 years. This subject is also affected by diabetes
complications and by a sensory polyneuropathy. Marked white mat-
ter abnormalities, interpreted as microangiopathy, and moderate ver-
mis atrophy were found on a MRI of the brain. Psychometric
evaluation and functional imaging are ongoing.
Conclusions: This is the first time a non-progressive phenotype
has been described in SCA19 (case II:2). Also new is the suspected
onset during childhood, ethnic background of this family and the
presence of polyneuropathy. The latter has to be interpreted with
great caution since diabetes is a condition usually associated with
damage to periphery nerves. A functional study to ascertain the true
pathogenicity of the T377M variant is planned.
938
Adult-onset cerebellar ataxia as a presentation of Langerhans
cell histiocytosis
J.M. Pyun, H.Y. Park, K.C. Moon, B.S. Jeon (Seoul, Korea)
Objective: To present a patient with cerebellar ataxia as an initial
presentation of Langerhans cell histiocytosis.
Background: Langerhans cell histiocytosis is a rare disease of
childhood involving skin, lung, bone, posterior pituitary mostly.
Adult onset and cerebellar ataxia as an initial symptom of Langer-
hans cell histiocytosis was not reported.
Methods: Case report.
Results: In April 2014, a 45-year-old female was admitted to our
clinic with progressive gait disturbance with imbalance and dysarth-
ria over two years. She was diagnosed as idiopathic degenerative cer-
ebellar ataxia at another hospital in August 2013. However, brain
MRI during that evaluation showed more than cerebellar atrophy:
there were tiny multifocal T2 high lesions involving the brainstem,
periventricular area and 4th ventricle, and pituitary stalk thickening.
Her past medical history was significant for diabetes insipidus since
age 35. Follow up brain MRI in 2014 showed mass like lesion
attached to the right frontal skull. 1.5 cm size round lytic skull defect
was seen on skull X-ray. Langerhans cell histiocytosis was confirmed
by skull biopsy.
Conclusions: Focusing on the past medical history of diabetes
insipidus and skull lesion led to the correct diagnosis of this unusual
presentation of adult-onset cerebellar ataxia in Langerhans cell his-
tiocytosis. Careful review of past medical history and search into
more than the nervous system are important in the differential diag-
nosis of ataxia.
939
Quantitative gait and balance testing for NPH
J.F. Quinn, S. Jewell, M. Fleming, S. OConnor, M. Mancini
(Portland, OR, USA)
Objective: To determine if an instrumented gait and balance
assessment is sensitive to effects of large volume lumbar puncture
(tap test) and surgery in patients with Normal Pressure Hydroceph-
alus (NPH).
Background: Predicting response to cerebrospinal fluid (CSF)
diversion surgery in suspected NPH is challenging, due to the lack
of objective assessments of response to large volume spinal tap.
Quantitative gait and balance testing is attractive as a means to
assess this response, and user-friendly instrumentation for this pur-
pose has recently become available in the form of wearable sensors.
Methods: We evaluated a series of 8 patients with probable
NPH. Each subject was evaluated with wearable Opals inertial sen-
sors before and after large volume spinal tap. The sensors were used
to collect Instrumented Stand and Walk (ISAW) data before and
after CSF removal. One patient was also evaluated after ventriculo-
peritoneal shunt, and one patient was also evaluated after endoscopic
third ventriculostomy.
 POSTER SESSION
Balance and gait parameters known to be correlated with falls
and Parkinsonism were compared between the 8 probable NPH
patients and a normative population. The same parameters were com-
pared before and after tap test in the probable NPH subjects.
Finally, the same parameters were compared pre and post surgery in
the two subjects followed through surgery.
Results: 1) Compared to a normative population, the probable
NPH patients had increased sway jerkiness (0.53m2/s5 6 0.2 vs
0.08 m2/s5 6 0.05, p50.04), dispersion (0.14 m/s2 6 0.06 vs 0.08 m/
s2 6 0.05, p50.006), and velocity (0.24 m/s60.07 vs 0.11m/s60.06,
p50.002), reduced stride length (59 6 11 vs 86 6 6, %stature,
p50.0002) and gait speed (46 6 10 vs 83 6 9%stature/s, p<0.0001),
as well as reduced turn peak velocity (96 6 20 vs 184 6 33, degrees/
s, p<0.0001).
2) Compared to before CSF removal, sway jerkiness, dispersion,
and velocity were reduced after CSF removal while stride length and
gait speed showed an increase towards normative values. However,
those differences did not reach statistical significance.
3) Compared to pre-surgery, sway and gait measures markedly
improved (more than 50% change) in the single patient after third
ventriculostomy, while there was no significant change in the single
patient after ventriculoperitoneal shunt.
Conclusions: The assessment of tap test and surgical outcomes
in NPH may be objectified with gait and balance data derived from a
brief assessment using wearable sensors.
940
Withdrawn by Author
941
Exome sequencing as a diagnostic tool for hereditary ataxias:
Our experience in a neurogenetic center from Buenos Aires,
Argentina
S.A. Rodrguez-Quiroga, C. Marta, D. Gonzalez-Moron, E.M. Gatto,
S. Gonorazky, P. Vega, N. Medina, C. Vazquez Dusefante, T. Ara-
kaki, N.S. Garretto, M.A. Kauffman (Caba, Argentina)
Objective: To explore the utility of exome sequencing in a group
of patients with hereditary ataxias.
Background: Hereditary ataxias are clinically and genetically
heterogeneous conditions, where the path to a molecular diagnosis
has been traditionally complex in an important number of patients.
Methods: We studied 7 patients with progressive ataxia of unde-
fined cause that were evaluated into the Chronic and Progressive
Ataxia Program of our Hospital. After excluding common genetic
and non-genetic causes of ataxias (SCA 1,2,3,6,7 and Friedreich
ataxia), we used whole exome sequencing and a comprehensive bio-
informatic analysis for molecular diagnosis proposes.
Results: A likely pathogenic variant was found in 3 of 7 analyzed
pedigrees, which equals to a diagnostic yield of 43%. A homozygous
nonsense mutation in APTX gene (c.879G>A; p.Trp293X) causing
Ataxia with Oculomotor Apraxia type 1 was identified in two sib-
lings showing early onset ataxia and mild chorea. A 23 years-old
man presenting progressive ataxia and myoclonus was compound
heterozygote for 2 likely pathogenic variants (c.612 1 1G>C and
c.823C>G; .Leu275Val) in STUB1 gene. A 23 year-old woman with
learning disability, hypogonadotropic hipogonadism, ataxia and
hypomyelination in MRI since the age of 4 was compound heterozy-
gote for mutations in PolR3A gene (c.3781G>A and c.3014G>A;
p.Glu1261Lys, p.Arg1005His).
Conclusions: Through the use of whole exome sequencing and
local resources we can arrive to a confirmatory molecular diagnosis
in 3 of 7 undefined ataxia patients. Our findings support exome
sequencing as an efficient diagnostic tool for heterogeneous neurode-
generative disorders such as the hereditary ataxias.
S365
942
Sensor-based gait assessment in ataxia: disturbance of armswing
and trunk motility does not run in parallel with impaired
stepping
T. Schmitz-Hubsch, A.U. Brandt, C. Pfueller, A. Seidel, T. Klock-
gether, F. Paul, A. K
uhn, M. Minnerop, S. Doss (Berlin, Germany)
Objective: To comprehensively describe movement patterns dur-
ing walking in cerebellar ataxia.
Background: From previous kinematic descriptions of gait
ataxia, an increased variability of stepping is the most consistent
finding, although not specific to ataxic gait. We use a sensor-based
system to explore if distinctive kinematic features can also be
described in other body parts that may add to a more specific charac-
terisation of gait ataxia.
Methods: Nine SCA14 patients, clinically characterized by
almost pure cerebellar ataxia and 9 healthy subjects (CTR) matched
for sex, age and height were assessed with 6 wireless inertial sensor
units (Mobility LabTM) attached to shanks, lumbar and sternal trunk
region and close to both wrists. Multiple walks of 8 m distance were
recorded at different subjective speeds. Cadence and range of motion
(RoM) are reported as means of all gait cycles, along with coeffi-
cients of variance. Multivariate linear models were applied with
group, subjective speed, their interaction and gender as main effects
and height, weight and age as covariates.
Results: Shank RoM was reduced in ataxic subjects while its var-
iability was higher than in CTR. No main group effect was seen for
cadence and arm RoM, which increased with subjective speed in
both groups, again with higher variability in SCA14. The sagittal
and horizontal, but not frontal, trunk excursions were larger in
SCA14 than in CTR, without effects of subjective speed. Variability
of trunk motion in all directions was increased in SCA14 (all effects
p<0.001).
Conclusions: The addition of arm and trunk motion in gait analy-
sis reveals interesting discrepancies between different body parts in
our ataxia cohort. In contrast to decreased motion range of the legs,
trunk excursions in the sagittal and horizontal plane were even larger
in ataxic subjects, while an increased variability of movement range
was seen for all sensor locations. Thus, changes in leg motion in
ataxic gait may not only be explained by disturbed control of step-
ping, but also regarded as secondary to a specific disturbance of
trunk control with increased sagittal excursions. Interestingly, lateral
trunk excursion and arm swing did not differ from CTR in our
cohort. The inclusion of trunk kinetics may yield a more complex
and specific description of cerebellar gait disturbance.
943
Strabismus and eye movement deficits in Machado-Joseph
disease
A.G. Shaikh, G. Wilmot, A. Ahmed, F.F. Ghasia (Cleveland, OH,
USA)
Objective: We describe eye movement deficits and strabismus in
patients with Machado-Joseph disease (MJD).
Background: MJD is a common form of spinocerebellar ataxia.
Dystonia and ataxia are commonly seen neurological deficits of
MJD. Nystagmus and ophthalmoplegia are also described. We report
deficits of ocular alignment and saccadic oscillations in patients with
MJD.
Methods: Twelve patients with MJD were studied. Clinical
assessments and quantitative ocular alignment measures were per-
formed. Eye movements were assessed with corneal curvature tracker
and video-oculography.
Results: Eight patients had ophthalmoplegia with mild abduction
deficit and three patients later developed an upward deficit. Ten
patients had strabismus. Three patients had esotropia, one patient had
skew deviation, one had a hypotropia accompanying the asymmetric
upward deficit, four patients had mild to moderate intermittent
Movement Disorders, Vol. 30, Suppl. 1, 2015
S366 POSTER SESSION
exotropia, and one had moderate exophoria. Three patients had V-
pattern strabismus. The near point of convergence was normal in the
exotropic patients. Eight patients had gaze-evoked nystagmus, eight
had saccadic dysmetria, whereas all twelve patients had saccadic pur-
suit. Two patients had slowing of the saccades and five had
microopsoclonus.
Conclusions: Strabismus and ophthalmoplegia were most com-
mon in MJD, but saccadic oscillations were also notable in many
patients. The type of strabismus could not be explained by the co-
existing ophthalmoplegia or vergence abnormalities in our patients
with exotropia that comprised 50% of the cohort. It is possible that
involvement of the brainstem, the deep cerebellar nuclei and the
superior cerebellar peduncle are driving the exotropia in these
patients. Brainstem and deep cerebellar nuclei lesion also explains
microopsoclonus, while brainstem deficits can describe slow saccades
seen in our patients with MJD.
944
A unique combination of spinocerebellar ataxia type 2 and 3
mutations in a patient
S. Shakya, V. Suroliya, M. Faruq, A.K. Srivastava, I. Singh, A. Garg,
M. Mukerji, G. Shukla, V. Goyal, M. Behari (New Delhi, India)
Objective: We are reporting first time the co-occurrence of
SCA2 and SCA3 mutations in a patient.
Background: Spinocerebellar ataxias are clinically and geneti-
cally heterogeneous group of neurodegenerative disorders. More than
one type of SCA mutations in a single patient has rarely been
reported including one case report from our group (co-existence of
SCA2 and SCA12 in two families).
Methods: DNA was isolated by salting out method from the
peripheral blood collected from patient with prior consent. We
screened proband and their family members for SCA1, 2, 3, 6, 8, 12
and DRPLA mutations using fluorescent labelled primers, analyzed
by GeneScan and confirmed the trinucleotide repeats in SCA2 and
SCA3 using Sanger Sequencing. All subjects were clinically eval-
uated in Ataxia Clinic at AIIMS, New Delhi.
Results: We identified a proband who was genetically positive
for SCA-3 mutation consisting 43/24 CAG repeats. One of the sib-
ling was identified positive for both SCA2 (40/23) and SCA3 (61/
24). Other family members from maternal side were affected with
SCA-2. We could not collect blood samples from paternal side. Sub-
jects who were positive for either of one SCA type had typical fea-
tures of that particular SCA. Patient with coexistence of both SCA2
and 3 had prominent symptoms suggestive of SCA2 phenotype. Sur-
prisingly Muscle stiffness, rigidity and sensory neuropathy were
absent in this patient which are typical symptoms of SCA3.
Conclusions: This is the first ever report of co-occurrence of
SCA2 and SCA3 in a single patient. Proband presented with typical
symptoms of SCA3 and interestingly his sibling was showing symp-
toms of SCA2. In India SCA2 is the most prevalent ataxia and
SCA3 is the fourth common type. This case raises the dilemma faced
by clinicians and geneticist while reporting the diagnosis as well as
prognosis of the case.
945
India shares the common mitochondrial lineage with Caucasians
with increased load of mitochondrial variations in Friedreichs
ataxia (FRDA) patients
I. Singh, S. Shakya, M. Faruq, A.K. Srivastava, M.V. Padma, M.
Behari, M. Mukerji (New Delhi, India)
Objective: To study the overall load of variations as phenotypic
modifier in targeted mitochondrial (MT) regions and MT lineage for
Indian FRDA patients through haplogroup identification.
Background: Friedreichs ataxia (FRDA) is an autosomal reces-
sive disorder caused by GAA repeat expansions (<66) in FXN gene.
Movement Disorders, Vol. 30, Suppl. 1, 2015
The protein product frataxin role is implicated in MT as biogenesis
of iron-sulphur cluster (ISC).
Methods: We studied clinically and genetically 30 FRDA
patients and 60 controls. Sequencing was performed for obtaining
the MT-genome sequence for patient and controls. MT-variations
were identified by aligning the obtained sequence with revised Cam-
bridge reference sequence using MITOMASTER. HAPLOGREP pro-
gram was applied for haplogroup estimations in both groups.
Pathogenicity of the variations were predicted with in-silico tools,
POLYPHEN and SIFT. Mt-SNP scores were assigned to the
variations.
Results: Mean (1SD) age at disease onset was 14.06 (4.38) years
and mean disease duration was 6.8 (14.2) years was estimated for
the patients, with mean GAA repeats from 688 and 877. The overall
average load of MT-variations per individual was statistically higher
(p-<0.03) in patients with trend towards coding region (ND and
ATP) than Non-coding region (p-0.04). Higher frequency of Non-
synonymous (NS) changes in complex I and ATP6 was observed.
Significant over representation of variation at p.L237M in MT-ND2
gene was observed (p-0.04). We also observed over representation of
Caucasian H haplogroup among FRDA patients. An inverse correla-
tion between GAA (expanded lower size allele) alleles and age of
the onset of FRDA was observed (r-0.64,p-<0.005). No influence of
Mt-SNP scores on the age at onset of the disease in FRDA on multi-
ple regression analysis.
Conclusions: The statistical significant increase in per individual
load of Mt-variation with a trend towards coding region variations in
FRDA patients may influence the mitochondrial function in patients.
H haplogroup which is the most common Caucasian haplogroup, was
also observed in our majority of FRDA patients suggesting a com-
mon mitochondrial lineage for both Indian and Caucasian FRDA.
Higher frequency of NS variation in Complex-I and ATP genes
could possibly influence the FRDA pathogenesis.
946
Autosomal recessive cerebellar ataxias in India: Genetic
heterogeneity and mutation spectrum revealed by whole exome
sequencing
A.K. Srivastava, M. Faruq, S. Shakya, R. Kumari, P. Dakle, D.
Dash, M. Mukerji, A. Garg, G. Shukla, V. Goyal, M. Behari (New
Delhi, India)
Objective: To identify mutation spectrum of Autosomal Reces-
sive Cerebellar Ataxias (ARCAs) in India.
Background: The Autosomal Recessive Cerebellar Ataxias are
group of little known and often less explored diseases. Genetic stud-
ies are lacking for recessive ataxia in India, except for FRDA. More
than 50% cases of hereditary ataxias remain molecularly
undiagnosed.
Methods: Whole Exome Sequencing (WES) was carried out in
18 ARCA patients (17 unrelated families) from northern part of
India. All ARCA cases were initially screened negative for SCA1, 2,
3, 6, 8, 12, 17, FRDA and DRPLA.
Results: After bioinformatics analysis, we identified likely candi-
date genes in 11 ARCA patients (61%). Ataxia with Oculomotor
Apraxia-2 (SETX gene) was found in six patients (33%). AOA2 was
identified as most common ARCA type in our study. Other identified
ARCAs were Ataxia with Vitamin-E Deficiency (TTPA gene), Auto-
somal Recessive Spastic Ataxia of Charlevoix-Saguenay (SACS
gene), Wilsons Disease (ATP7B) and SCAR10 (ANO10 gene). One
variation was found in GRID2 gene which is also implicated in
ataxia.
Conclusions: This study reveals that AOA2 may be the most
common ARCA type after FRDA and Ataxia Telangiectasia in north-
ern Indian population. This study also reveals the power of whole-
exome sequencing as a rapidly evolving clinical tool for diagnosis of
Mendelian disorders. We will further screen all uncharacterized
 POSTER SESSION
ARCA patients for AOA2 as well as for other variations found in
this study by Sanger sequencing method.
947
Case of spinocerebellar ataxia type-12 associated with only 43
CAG repeats in PPP2R2B gene
A. Takkar, M. Faruq, S. Shakya, A. Garg, A.K. Srivastava (New
Delhi, India)
Objective: To report a patient with SCA12 phenotype and posi-
tive family history with 43 number of CAG repeats.
Background: Spinocerebellar ataxia type 12 (SCA12) is an auto-
somal dominant cerebellar ataxia associated with the expansion of an
unstable CAG repeats in the 5UTR region of the PPP2R2B gene on
chromosome 5q3133 . SCA 12 is a commoner subtype in the north-
ern part of India and till now expansion to 47 repeats has been found
to be responsible for occurrence of disease.
Methods: DNA was isolated from peripheral blood using salting
out method with due consent. CAG expansion in concerned gene
was measured using fluorescent labelled primers. Numbers of repeats
were confirmed by Sanger Sequencing. Patient and her sibling were
clinically evaluated in ataxia clinic at AIIMS.
Results: A 74 year old women presented with progressive hand
and jaw tremor, dysarthria and gait ataxia from the past 2 years.
Family history was positive as her sister was also affected with
SCA12. Mother and brother also suffered from similar illness but
were not available for DNA testing. Neurological examination dem-
onstrated abnormal finger nose test, impaired tandem walking, mild
bradykinesia, reduced deep tendon reflexes, normal eye signs and no
motor or sensory deficits. MRI brain showed cerebral and cerebellar
atrophy. Motor and sensory nerve conduction studies were normal.
Conclusions: We consider this a case of interest because it low-
ers down the number of CAG repeats from 47 to 43 considered to be
responsible for SCA12 phenotype in a patient.
948
Sympathetically induced sudomotor and cold pressor test in
patients of spinocerebellar ataxia 2: A preliminary study
D. Tamuli, M. Faruq, A.K. Jaryal, A.K. Srivastava, K.K. Deepak
(New Delhi, India)
Objective: To evaluate the sympathetic reactivity by cold pressor
test (CPT) and quantitative sudomotor axon reflex test (QSART) in
patients of spinocerebellar ataxia (SCA) 2.
Background: SCA is a progressive neurodegenerative disorder
associated with sympathetic autonomic dysfunction. QSART and
CPT are two commonly used tests of sympathetic reactivity. There is
a paucity of information regarding comparison of sympathetic
responses in QSART and CPT in SCA 2 patients. The present study
was designed to correlate the sympathetic reactivities in SCA 2.
Methods: We assessed sympathetic reactivity by QSART and
CPT in 17 patients of genetically confirmed SCA 2 (age 33 6 9
years) by Q-sweat testing (WR Medical Electronics) and continuous
beat-to-beat blood pressure monitoring (Finapres) respectively.
Results: The latency and sweat volume values of QSART in
SCA 2 patients obtained from four different sites were: forearm
(144.8 6 61.45 sec, 0.308 6 0.224 lL), proximal leg (168; 116.5-193
sec, 0.327 6 0.247 lL), distal leg (136.7 6 86.74 sec, 0.364 6 0.359
lL) and foot (162.7 6 62.32 sec, 0.290 6 0.149 lL). During CPT,
patients showed peak latency of DBP as 43.24 6 14.69 sec and DBP
as 16 67 mmHg. Significant but weak correlation was found
between foot volume and DDBP (R2 5 0.259, p50.04,) during
QSART and CPT in SCA 2 patients.
Conclusions: The sympathetic reactivity involving QSART and
CPT were found to be weakly correlated. Both tests are based on
integrity of sympathetic nervous system and thus it is likely that
these are mediated by common sympathetic mechanism.
S367
949
Distal hereditary motor neuropathy with HSJ1 chaperone
mutation, presenting with peripheral motor neuropathy,
associated to Parkinsonism, and cerebellar ataxia. Case report
H.A.G. Teive, W.O. Arruda, R.H. Scola, L.C. Werneck, F. Kok
(Curitiba, Brazil)
Objective: To describe a new phenotype of a rare recessive distal
hereditary motor neuropathy with HSJ1 chaperone mutation, in a
Brazilian patient.
Background: A homozygous HSJ1 chaperone mutation is related
to a rare lower motor neuron disease, characterized by distal heredi-
tary motor neuropathy and was described in a Jewish family originat-
ing from Morocco.
Methods: A case report about a rare disease: Distal Hereditary
Motor Neuropathy with HSJ1 Chperone mutation, with diferente
phenotype.
Results: A 45 years-old male patient presented progressive gait
disorder, with lower limb weakness, associated to bradykinesia, fol-
lowed by gait ataxia and falls since age 30 y.o. Family history dem-
onstrated 3 affected siblings (a sister, with cerebellar ataxia and
peripheral neuropathy, a maternal cousin, with early-onset Parkinson-
ism, and a maternal uncle, with a diagnosis of spinal muscular atro-
phy). Neurological examination showed an asymmetric tetraparesis,
with muscle atrophy, predominantly in the lower limbs, associated to
profound global arreflexia, bradykinesia, muscle rigidity, with cog-
wheeling, rest tremor (right hand), postural instability and cerebellar
gait ataxia. Extensive work-up showed a CSF protein increased,
EMG with signs of peripheral axonal motor neuropathy, muscle
biopsy with denervation findings, peripheral nerve biopsy disclosed
hypertrophic neuritis. Brain and spinal cord MRI were normal.
Genetic tests for Friedreichs ataxia, ataxia and ocular apraxia type 1
and 2, POLG mutation, SCAs (1,2,3,6,7,8,10,12,14 and 17), park 2,
and survival motor neuron gene were negative. Whole-exome
sequencing demonstrated the presence of homozygous mutation in
the gene DNAJB2(DNAJ/HSP40 homolog, subfamily B, member)
(Chr2: 220.146.784, Variant: c.352 1 1G>A(IVS5 1 1G>A).
Conclusions: A homozygous HSJ1 chaperone mutation is related
to a rare lower motor neuron disease, characterized by distal heredi-
tary motor neuropathy and was described in a Jewish family originat-
ing from Morocco. In this Brazilian case report, we described the
same mutation but with a new phenotype of this disease, which
includes Parkinsonism and cerebellar ataxia.
950
Estimation of skeletal muscle mass in patients with
spinocerebellar ataxia
H.G. Teive, C.A. Leite, M.E. Schieferdecker, R.M. Vilela, D.S.
Macedo (Curitiba, Brazil)
Objective: To estimate skeletal muscle mass (SMM) in a group
of patients with Spinocerebellar Ataxia (SCA), by anthropometric
and bioelectrical impedance methods (BIA).
Background: SCAs are part of a group of neurodegenerative dis-
orders that affect balance and gait. Over time, these disorders can
affect the muscle tone and may influence its trophism. Body compo-
sition assessment is necessary for promoting therapeutic strategies to
mitigate the loss and muscle weakness, and to improve its structure
and function. Methods of imaging evaluation enable a more detailed
analysis of the body compartments. However, there are some limita-
tions of applying this technology to determine body composition,
mainly due to its high cost and the individuals exposure to radiation
doses. BIA is simple to operate, safe, non-invasive, and relatively
inexpensive for evaluating body composition as compared to image
equipments.
Methods: The SMM of seventy-six patients with SCA was quan-
tified. Individuals of both genders with several types of SCA in vari-
ous stages of the disease were assessed. BIA analysis was used
Movement Disorders, Vol. 30, Suppl. 1, 2015
S368 POSTER SESSION
according Heyward (2000). Muscle mass was predicted by Janssen
(2000) equation.
Results: To our knowledge, until this moment, there are no stud-
ies that have evaluated SMM of patients with SCA in this manner.
The mean age was 45.3 years (SD 10.5), ranging from 22 to 72,
with 54% women. The average of weight and height was 64.2 kg
(SD 13.9) and 161.2 cm (SD 8.7), respectively. According to the
Body Mass Index, 43.4% of patients were eutrophic, 39.5% were
overweight, 10.5% were obese, and 6.6% were underweight. SCA 3
was the most common (41%) and SARA scores ranged from 1 to
36.5.
Men presented higher SMM than women: 28.4 kg (SD 4,1) com-
pared with 18.1kg (SD 2.6) respectively. SMM was approximately
13% smaller than reference values in both genders, independent of
age group.
Conclusions: These data demonstrate that although the studied
patients presented high prevalence of obesity and overweight, there
was SMM loss, which may result in a devastating impairement on
their ability to remain independent. Considering the importance of
evaluating the SMM to identify risk of deterioration in functional
capacity of patients, the use of BIA can be a low-cost, simple han-
dling and low risk alternative to be used for this purpose. Further
studies comparing images methods with BIA in SCA patients are
required.
951
Anthropometric profile of patients with spinocerebellar ataxia
H.G. Teive, C.A. Leite, M.E. Schieferdecker, R.M. Vilela, D.S.
Macedo (Curitiba, Brazil)
Objective: To assess the nutritional status of a group of patients
with Spinocerebellar Ataxia (SCA) by using anthropometric
methods.
Background: Patients with SCA may have symptoms, like dys-
phagia, loss of taste perception, tremors, loss of coordination, depres-
sion and others that affect the nutritional status. To estimate body
composition and correlate it to potential nutritional disorders, allow
appropriate interventions for the recovery and/or maintenance of the
individuals health status. Anthropometry is a simple, not expensive,
non-invasive and reproducible method used to determine FFM and
FM.
Methods: It was evaluated the nutritional status of seventy-six
individuals of both genders with several types of SCA, in various
stages of the disease, using anthropometric measurements such as
weight, height, body mass index (BMI), biceps, triceps, subscapular
and suprailiac skinfolds thickness, body fat mass and fat free mass.
Anthropometric data were collected according to Lohman (1988).
Results: This study offers the first data on body composition of
patients with several types of SCA. The mean age was 45.3 years
(SD 10.5), ranging from 22 to 72, with 54% women. The average of
weight and height was 64.2kg (SD 13.9) and 161.2cm (SD 8.7),
respectively. SCA 3 was the most common (41%) and SARA scores
ranged from 1 to 36.5. According to the BMI, 43.4% of patients
were eutrophic, 39.5% were overweight, 10.5% were obese, and
6.6% were underweight, and among of these one 2.6% were classi-
fied as severe thinness. Mean body fat mass was above 75th percen-
tile in both genders, independent of age, with 25.6% (SD 6.8) in
male and 35.9% (SD 8.9) in female group. As expected, significant
differences in FFM (P<0.001) were noted for all age groups between
men and women. The male group presented 50.7kg (SD 7.5) com-
pared with 37.6kg (SD 5.1) in female. Even so, according to these
data, male group was below to 10th percentile.
Conclusions: These results suggested that patients with SCA tend
to develop sarcopenic-obesity, worsening their movement disabilities,
accelerating functional decline and increasing the risk of diseases
and mortality. That is why nutritional care is an important part of
treatment to early identify nutritional status and to correct them with
appropriated diet therapy.
Movement Disorders, Vol. 30, Suppl. 1, 2015
952
Deep brain stimulation of the dentate nucleus improves
cerebellar ataxia: A double-blind n51 study
M.J. Teixeira, R.G. Cury, R. Galhardoni, V.R. Barboza, E. Alho,
C.M. Seixas, G. Lepski, D. Ciampi de Andrade (S~
ao Paulo, Brazil)
Objective: To assess tremor, ataxia and dystonic changes after
short-term dentate nucleus (DN) deep brain stimulation (DBS) after
unilateral cerebellar infarction.
Background: Cerebellar projections modulate activity in the contralat-
eral primary motor cortex (M1) through dentothalamocortical projections.
Acute ischemic damage to the deep cerebellar nuclei is known to result in
ataxia and loss of excitatory input to the contralateral M1 cortex. However,
chronic cerebellar ischemic lesions have recently been associated with ree-
merging increase in local inhibition in the contralesional M1, leading to
inter-hemispheric asymmetry in cortical excitability, which could account
for part of the functional impairment seen after stroke. We hypothesized
that DBS of DN would balance the functional asymmetry seen between
both M1 after chronic cerebellar and attenuate clinical symptoms.
Methods: We report a case of post-surgical right cerebellar hemi-
sphere infarction in a fifty-year-old female after a resection of the right
acoustic neuroma leading to dystonia and ataxia with significant impair-
ment in her daily activities. Based on the refractoriness of symptoms to
medical treatment and a good response to neuronavigated low-frequency
transmagnetic stimulation(TMS) to the healthy dentate nucleus, deep
brain stimulation to the left dentate nucleus was performed. A blind
Movement Disorder specialist evaluated the patient under on-stimulation
and off-stimulation. Cortical excitability was evaluated by TMS. Clinical
assessment was performed using validated tools.
Results: There was improvement in tremor and in cerebellar ataxia
scales[table1] during on-stimulation. The Patient Global Impression of
Change (ranging from 1 to 7) was 6 after the active session (i.e. mod-
erately improved) and 3 after the sham procedure (i.e. no change).
There were no changes in dystonia after active treatment.
Evaluation of dystonia, tremor and ataxia after deep brain stim-
ulation of the dentate nucleus
Before on- sham-
Scales surgery stimulation stimulation % change*
UDRS 09/112 09/112 09/112 None
SARA 25,5/40 17/40 25,5/40 33%
FTMTRS 38/144 24/144 38/144 37%
UDRS: Unified Dystonia Rating Scale; SARA: Scale for the assess-
ment and rating of ataxia; FTMTRS: Fahn, Tolosa, Marin Tremor
Rating Scale. * % Change after on-stim deep brain stimulation
During on-stimulation the cortical excitability has been normalized.
Conclusions: This is the first controlled, neuronavigation-guided
deep-rTMS and DBS study aiming at ataxia and tremor control. Sin-
gle sessions of rTMS usually provide short-lasting clinical effects,
commonly lasting for a few days after stimulation. In our patient, the
clinical improvement after DBS remained until the last evaluation
(two months). The study protocol was safe and well tolerated, and it
provides evidence for studies using DBS in this patient population.
953
SCA2 presenting as a focal dystonia
H.M. Wied, J.J. Gaul, L.E. Doyle, S.G. Reich (Baltimore, MD, USA)
Objective: To demonstrate that SCA2 may present as a focal dystonia.
Background: SCA2 is due to an expansion of CAG repeats in
the ataxin-2 gene on chromosome 12q24. Patients typically present
in adulthood with gait and limb ataxia, slow saccades and neuropa-
thy. Extrapyramidal signs are not uncommon and including
 POSTER SESSION
Parkinsonism, which may be responsive to levodopa; dystonia has
been observed in at least 14% of patients (van Gaalen J, et al. Mov
Disord 2011) but is usually not the presenting sign. When SCA2
begins with a Movement Disorder with little or no ataxia, the diag-
nosis may not be considered.
Methods: Case report and video.
Results: At age 41y an African American woman noticed difficulty
manipulating a pencil with her right hand. On examination there was dys-
tonic writers cramp of the right hand as well as mild dystonia with other
tasks. There was slight dysmetria of both upper limbs and mild difficulty
tandem walking but neither of these findings was symptomatic. An MRI
demonstrated cerebellar and brainstem atrophy. Her mother was reported
to have a progressive gait disorder and her maternal grandmother was sim-
ilarly affected; two of three siblings were affected as well as maternal
uncles and cousins. A total of ten individuals were reported as sympto-
matic in a three-generation pedigree (Fig). It was subsequently learned
that her mother presented with a cerebellar syndrome and was found to
have SCA2 (37 CAG repeats); as her disease progressed, she was
observed to have a rest tremor and mild cervical dystonia. Our patients
cerebellar signs have been minimally progressive during follow-up of 8
years, in contrast to the dystonia which has worsened to the extent that she
can barely use the right hand due to flexion of the thumb and fingers which
exacerbates during attempted use. She did not improve with botulinum
toxin or levodopa but has had some improvement with trihexyphenidyl.
Conclusions: This case demonstrates that SCA2 may present as a
focal dystonia with minimal cerebellar signs and that throughout the
course, the dystonia may remain the predominant symptom.
954
Withdrawn by Author
Fig. 1. (954).
S369
955
Recurrent episodic isolated nystagmus associated with GAD
antibody positivity
Z. Xu, P.X. Koh, N.K. Loh, T. Umapathi, J.Y.H. Chia (Singapore,
Singapore)
Objective: To present a patient with recurrent episodes of iso-
lated eye movement abnormalities in the absence of other cerebellar
signs associated with GAD (Glutamate Decarboxylase)-antibodies.
Background: Retrospective reviews of patients with spinocere-
bellar ataxia suggest that episodic vertigo may precede the develop-
ment of cerebellar ataxia by many years . Nystagmus is a feature of
GAD-positive cerebellar ataxia but this has always been reported as
a persistent feature occurring in conjunction with progressive and
persistent limb or gait ataxia. We present the first known case of
recurrent episodic isolated eye movement abnormalities associated
with GAD antibody positivity in the absence of axial or appendicular
ataxia.
Methods: Case report.
Results: A 64 year old female presented with recurrent episodes
of vertigo over a period of 4 years, with each episode lasting up to 5
days. There was no family history. During each episode, examination
revealed pronounced horizontal gaze evoked nystagmus and down-
beating nystagmus but this was never associated with other cerebellar
signs. She was well in between episodes.
Investigations that were normal include: MRI Brain, MRI Cervi-
cal Spine and tumour markers. However, serum GAD antibodies
were strongly positive (216.4 U/ml). A Thoracic CT showed an
irregular hyperdense lesion measuring 2.5cm x 2.4cm x 2.0cm in the
chest for which histopathology was inconclusive and showed mainly
degenerate material.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S370 POSTER SESSION

Fig. 2. (954).

She was treated with 1g intravenous methylprednisolone for 5 Conclusions: Oculomotor abnormalities associated with GAD
days resulting in marked resolution of nystagmus, for which she antibodies include: gaze evoked, downbeating and periodic alternat-
remained asymptomatic at discharge. ing nystagmus, opsoclonus-myoclonus and oculomotor apraxia.

Clinical characterstics of patients with paraneoplastic cerebellar degeneration

Patient/ Age of Presenting Brain Time to wheelchair

Gender onset symptoms and signs Cancer Autoantibody imaging CSF analysis bound state
1/F 56 Gait, limb ataxia, Elevated Ca 125, Anti-Yo Normal 133 WCC 3 months
diplopia and new stage 3B (94% lymphocytes),
peripheral ovarian serous 363 RCC, elevated
neuropathy papillary carcinoma oligoclonal bands
2/M 70 Gait, truncal and New metastatic None Normal 7 WCC 3 months
limb ataxia, small cell (78% Lymphocytes),
nystagmus, lung carcinoma 0 RC, protein 0.9
dysarthria and and Prostate
weight loss Intraepithelial
Neoplasia
3/F 64 Gait, truncal and Existing stage Anti-Yo Normal WCC 68, Lost to follow up
limb ataxia, 4 ovarian RCC <1,
nystagus cancer, protein 0.53
diagnosed
2 years ago

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
However, these occurred in conjunction with progressive limb or gait
ataxia. The association of GAD with nystagmus in the absence of
other features of ataxia has not been previously reported.
It is currently unknown whether episodic nystagmus such as that
described in our patient is a prodromal symptom that would lead to
the development of overt appendicular ataxia in GAD-associated
ataxia. Our case could also represent a previously unrecognized phe-
notype of GAD-associated neurological disorders. We recommend
GAD antibody testing in patients who present with unusual oculomo-
tor abnormalities even when there are no overt cerebellar features to
be found.
956
Clinical characteristics of patients with paraneoplastic cerebellar
degeneration
Z. Xu, L.C. Tan (Singapore, Singapore)
Objective: To identify the initial clinical, immunological and
radiological features of patients presenting with a cerebellar syn-
drome who were ultimately diagnosed with Paraneoplastic Cerebellar
Degeneration.
Background: The initial presentation of an adult patient with a
cerebellar syndrome presents a diagnostic challenge due to the wide
differentials involved. Paraneoplastic cerebellar degeneration,
although extremely rare, is one important diagnosis not to miss.
However, the diagnosis of this rare entity is further complicated by
the existence of seronegative paraneoplastic cerebellar degeneration,
which is estimated to account for 50% of cases of paraneoplastic cer-
ebellar degeneration, the delayed appearance and detection of occult
malignancies and the high proportion of Multiple System Atrophy-
Cerebellar (MSA-C) in the Asian population, for which its diagnosis
at an early stage of the disease is difficult.
Methods: Retrospective case note analysis.
Results: 3 patients with paraneoplastic cerebellar degeneration
were identified in 2010 and 2011 from a large tertiary centre in Sin-
gapore: 1 had a prior malignancy, the remaining 2 patients were
diagnosed with malignancies during the initial presentation through
routine investigations. The anti-Yo antibody was detected in the 2
patients with ovarian carcinoma. All patients had abnormal CSF
analysis with lymphocytic predominance, normal brain imaging find-
ings, poor response of the underlying cerebellar syndrome to a com-
bination to immunosuppression and chemotherapy. Patients not
included in this analysis who were initially thought to have a proba-
ble paraneoplastic cerebellar degeneration had MSA-C as the most
common diagnosis.
Conclusions: Paraneoplastic cerebellar degeneration remains a
rare diagnosis amongst adult patients presenting with a cerebellar
syndrome. In our series of patients, malignancies were readily identi-
fied using routine investigations during their initial presentation with
a cerebellar syndrome. Most of our patients who were initially
thought to have probable paraneoplastic cerebellar degeneration were
ultimately diagnosed with MSA-C. All our patients with paraneoplas-
tic cerebellar degeneration had rapid progression to a wheelchair
bound state, normal brain imaging, abnormal CSF analysis with a
predominance of lymphocytes. In such cases, the clinical suspicion
for paraneoplastic cerebellar degeneration should be high.
957
Neurotological findings prevalent in ataxias hereditary
B.S. Zeigelboim, H.A.G. Teive, E.S. Abdulmassih, R.C. Cardoso, G.
Santos, M.I. Severiano, R. Sampaio (Curitiba, Brazil)
Objective: To examine vestibular disorders in patients with reces-
sive and dominat cerebellar ataxia.
Background: Spinocerebellar ataxia is a disease that belongs to a
heterogeneous group of neurodegenerative diseases that are charac-
terized by the presence of progressive cerebellar ataxia.
S371
Methods: A retrospective cross-sectional study was conducted.
76 patients were evaluated ranging from six to 63 years of age
(mean age of 41.2) and underwent the following procedures: case
history, ENT and vestibular evaluations.
Results: Clinically, the patients commonly had symptoms of gait
disturbances (67.1%), dizziness (47.3%), dysarthria (46.0%) and dys-
phagia (36.8%). In vestibular testing, alterations were predominantly
evident under caloric testing (77.6%), dismetric saccades (50.0%),
rotational chair testing (46.0%) and testing for gaze nystagmus
(43.4%). The presence of alterations occurred under examination in
85.5% of these patients, 63.1% occurred in subjects with dominant
ataxia and 22.4% occurred in subjects with Friedreichs ataxia and
14.5% examination showed normal. The majority occurring in those
with central vestibular dysfunction, 68.4% of the examinations.
Conclusions: The most evident neurotological symptoms were
gait disturbances, dizziness, dysarthria and dysphagia. Alterations in
vestibular examinations occurred in 85.5% of patients, mostly in the
caloric test, with a predominance of deficient central vestibular sys-
tem dysfunction. This underscores the importance of the contribution
of topodiagnostic labyrinthine evaluations for neurodegenerative dis-
eases since, in most cases, the initial symptoms are neurotological,
and these evaluations should also be included in the choice of proce-
dures to be performed in clinical and therapeutic monitoring.
958
Vestibular disease in patients with Friedreich ataxia
B.S. Zeigelboim, H.A.G. Teive, R.C. Cardoso, G. Santos, M.I.
Severiano, J.H. Faryniuk (Curitiba, Brazil)
Objective: To examine vestibular disorders in patients with Frie-
dreich ataxia.
Background: The Friedreich ataxia is a neurodegenerative dis-
ease and progressive by nature, it has autosomal recessive inheri-
tance and early onset in most cases. The affected gene plays the role
of encoding mitochondrial protein frataxin that is involved in the
iron metabolism. The deficit of this protein compromises mitochon-
drial respiratory chain.
Methods: A retrospective cross-sectional study was conducted.
Thirty patients were evaluated ranging from age 6 to 72 (mean age
of 38.6) and underwent the following procedures: case history, ENT
and vestibular evaluations.
Results: Clinically, the patients commonly had symptoms of
incoordination of movement (66.7%), gait disturbances (56.7%) and
dizziness (50.0%). In vestibular testing, alterations were predomi-
nantly evident under caloric testing (73.4%), testing for gaze nystag-
mus (50.1%), rotational chair testing (36.7%) and optokinetic
nystagmus (33.4%). The presence of alterations occurred under
examination in 90.0%, with the majority occurring in those with cen-
tral vestibular dysfunction, 70.0% of the examinations.
Conclusions: The most evident neurotological symptoms were
incoordination of movement, gait disturbances and dizziness. Altera-
tions in vestibular examinations occurred in 90.0% of patients,
mostly in the caloric test, with a predominance of deficient central
vestibular system dysfunction. This underscores the importance of
the contribution of topodiagnostic labyrinthine evaluations for neuro-
degenerative diseases since, in most cases, the initial symptoms are
neurotological, and these evaluations should also be included in the
choice of procedures to be performed in clinical and therapeutic
monitoring.
959
Vestibular rehabilitation with virtual reality in spinocerebellar
ataxia
B.S. Zeigelboim, H.A.G. Teive, R.C. Cardoso, G. Santos, M.I.
Severiano, P.B.N. Liberalesso, J.H. Faryniuk, V.R. Fonseca
(Curitiba, Brazil)
Movement Disorders, Vol. 30, Suppl. 1, 2015
S372 POSTER SESSION
Objective: To verify the benefits of the vestibular rehabilitation
(VR) with virtual reality through the assessment before and after the
application of the Berg Balance Scale (BBS) in four cases of spino-
cerebellar ataxia (SCA).
Background: The spinocerebellar ataxias (SCA) are a heteroge-
neous group of neurodegenerative diseases that are characterized by
progressive cerebellar ataxia and their first clinical manifestations are
balance and coordination deterioration besides eye disorders.
Methods: The cases were underwent the following procedures:
anamnesis, ear inspection, vestibular assessment and application of
the BBS before and after VR with virtual reality using games from
Wii Fit device. The cases describe four patients that were diagnosed
with genetically inherited SCA (two type 2, one type 3 and one still
under investigation), three of them were female and one was male,
with ages ranging from 30 to 62 years.
Results: The patients presented otoneurological symptoms and
the vestibular test showed the presence of semi-spontaneous nystag-
mus, absence of post-rotational nystagmus, hyporeflexia, and asym-
metric directional preponderance of the nystagmus in the caloric test.
Patients from cases 1 and 2 have showed an improvement in motor
coordination and in body balance, even though the score presented
by the BBS had demonstrated medium risk for falling before and
after the exercises. In case 3, the patients loss of balance and BBS
score have improved, presenting low risk of falling; whereas the
patient in case 4 did not show any improvement in the assessment
after the exercises.
Conclusions: This case study shows the applicability of VR exer-
cises with virtual stimuli in SCA with improved motor coordination
and postural balance.
POSTER SESSION 6
Wednesday, June 17, 2015
12:0013:30
Coronado Ballroom
Education in Movement Disorders
960
First Middle East camp for Parkinsons disease, Movement
Disorders and neuromodulation: Review of outcomes and
implications for future directions
J.A. Bajwa, H. Khalil (Riyadh, Saudi Arabia)
Objective: To review the outcomes of the first Middle East camp
for Parkinsons disease (PD), Movement Disorders and Neuromodu-
lation and its implications in the region.
Background: Middle East and the Arabian world includes
numerous developing countries with an estimated population of over
400 million. The prevalence of PD in the region is believed to be
similar to the prevalence reported worldwide. The fields of PD and
Movement Disorders are however underdeveloped and underserved
in the region. While the characteristics of the disease and the needs
of these patients are potentially comparable between the Middle East
and other regions of the world, significant barriers to achieving opti-
mal care for PD and Movement Disorders exist in these developing
nations.
Methods: The first Middle East camp was held in Dubai on April
12-13, 2014 to create a dialogue between all regional stakeholders
from researchers, clinician, private practitioners and industry; thus
delivering evidence-base education in the field of PD and Movement
Disorders for the 1st time. The meeting lasted for two days and cov-
ered all major educational themes with special emphasis on up- to-
date discussion regarding medical and surgical management for PD
as well as other Movement Disorders.
Movement Disorders, Vol. 30, Suppl. 1, 2015
Results: Over one hundred and fifty participants attended the
meeting from over 25 countries. Diversity in audience was noted;
neurologists, nurse-specialist, occupational therapists, physiothera-
pists, researchers and academicians were in attendance. Educational
sessions were provided by distinguished faculty members from seven
different countries. The meeting achieved its goal by providing up-
to-date discussion in the field to a very underserved region. It helped
to bridge group of experts from the region to collaborate and charac-
terize various unmet educational, clinical and research needs with in
the field. This initial breakthrough meeting has yielded to the 2nd
Middle East camp scheduled for April 2-4, 2015 in Amman, Jordan.
Conclusions: There is a clear need to optimize the care of PD in
the Middle East and Arabian world. The first Middle East camp pro-
vided a platform to initiate a structured educational process to
deliver teaching and provide skills for the treatment of PD and
Movement Disorders in this underserved region.
961
Movement Disorders and the media
B.R. Barton, K. Kompoliti (Chicago, IL, USA)
Objective: To explore the diversity and impact of prominent
depictions of Movement Disorders in the media.
Background: Movement Disorders have not been commonly por-
trayed in the media until recently. Given their relatively rare inci-
dence, prominent depictions of these diseases in the media have the
potential to educate or misinform the general public. Little attention
is given to the overall impact in some forms of media including the
internet and news outlets.
Methods: Using internet resources (e.g. Google Search, Internet
Movie Database), publications, and personal recollections we
assembled a list of movies (feature length, non-documentary) and crit-
ical internet/news references for portrayals of Parkinsonism, dystonia,
tremor, Huntingtons disease, ataxia and tics. Movies were categorized
by first: disease being the main driving force to move the plot or not;
second: a) disease portrayed but not specifically diagnosed; b) por-
trayed by actual patients; c) fictional portrayal; d) mentioned but not
depicted. Internet/news was categorized by: a) use of disease state to
further a political agenda; b) attempts to overdramatize the consequen-
ces of the diagnosis and assign depression/suicide to the diagnosis; c)
feeding into mass hysteria; d) Jumping to publicizing consequences of
medical interventions before checking the medical facts.
Results: For movies: Most references were of tics (n523) and
Parkinsonism (n516), with few other disease portrayals, most fic-
tional. Movies with the main character suffering from a Movement
Disorder and being responsible for plot advancement were infre-
quent. Overall disease depiction was in most instances inaccurate,
particularly with tic disorders. For internet/news: the number of
references is not quantifiable based on a large amount of archived
footage, but in many instances disease depiction is exploited to either
advance a specific agenda and/or sensationalize the story.
Conclusions: A limited number of movies, albeit some highly
viewed, have featured Movement Disorders, mainly depicting fic-
tional portrayals of tics and Parkinsonism. A vast number of internet/
news archives can be classified into key categories according to pos-
sible influence on public perception. The number of films and inter-
net resources available to the public in the last 15 years is
increasingly extensive, and disease depiction is not always accurate;
thus, more scrutiny is required by experts to examine the accuracy
and knowledge disseminated by these media.
962
How can we better educate study participants for an improved
informed consent? Taking a look at Parkinsons disease
transplant trials
N. Hellmers, I. de Melo-Martin, C. Henchcliffe (New York, NY, USA)
 POSTER SESSION
Objective: To describe key challenges in ensuring patient under-
standing during the informed consent process.
Background: A fundamental requirement of the informed consent
process is that study participants have a genuine understanding of
relevant aspects of the study so as to make an autonomous decision.
This presents multiple challenges for first-in-human clinical trials
involving cell or tissue transplantation in Parkinsons disease.
Researchers must ensure that participants understand complex
research methodology and that they avoid the therapeutic
misconception.
Methods: As a first step to developing an improved informed
consent process and determine barriers to understanding, we per-
formed a systematic review of the literature using search terms:
informed consent, Parkinsons disease, bioethics, stem cell people with Parkinsons is organised.
therapy, cell transplant, education.
Results: 1. No prior rigorous studies have compared effective
strategies for distilling complex science to provide adequate informa-
tion on risks and benefits. Current guidelines encourage educating
research volunteers but how best to achieve this is unclear. 2. Bar-
riers to understanding clinical research methods and goals. Subjects
often have difficulties understanding relevant concepts in clinical
research and can fail to understand that research involves testing a
hypothesis. 3. Limits of one time consent and the need for long
term assessments of comprehension. Consent needs to be an ongoing
process. Researchers must ensure ongoing understanding from partic-
ipants. In a neurodegenerative condition, this will likely require dif-
ferent tools over time.
Conclusions: Attention to what information to provide, how best
to provide it, and how to ensure understanding is critical. There is
little published evidence of demonstratably effective education to
facilitate genuinely informed consent for first-in-human cell trans-
plant trials in Parkinsons disease. Establishing teaching strategies
during the informed consent process will be necessary, and given
progressive cognitive impairment in Parkinsons disease, external
guidance to understand complex concepts may be helpful. Possible
solutions to consider are use of diverse educational materials, includ-
ing tablet-based or web-based information, and involving patient
research advocates in their development.
963
Evidence-based, patient-centered physiotherapy for people with
Parkinsons: A pilot implementation of the Dutch ParkinsonNet
concept in Germany
S.H.J. Keus, M. Munneke, M.J. Nijkrake, K. Krebber, C. Schaffelder,
H. Woltjer, F. Radefeld, A. Schniederjan, H. Grehl, B.R. Bloem
(Nijmegen, Netherlands)
Objective: We aim to evaluate the feasibility and benefits of
implementing the Dutch ParkinsonNet concept in Germany.
Background: Through implementation of the ParkinsonNet con-
cept, over the past 10 years, care for people with Parkinsons in the
Netherlands has improved, at lower costs (Bloem & Munneke, BMJ
2014). Through ParkinsonNet, Parkinson-expert health professionals
are continuously trained to deliver evidence-based, patient-centered
care; to increase their treatment volumes; to collaborate in commu-
nity networks; and are visible to clinicians and people with Parkin-
sons. Started with a small group of physiotherapists and
neurologists in 2004, ParkinsonNet has now trained and connected
over 2,000 health professionals, across 19 disciplines, in 69 commu-
nity networks throughout the Netherlands. With financial support of
the INTERREG IV program EURegio, Gelderland Province and the
German Parkinsons disease Association, a first international imple-
mentation of ParkinsonNet is piloted.
Methods: In collaboration with the neurology department of a
general hospital (EVKLN, Duisburg, 50km from the nearest Dutch
ParkinsonNet), all physiotherapists working in their adherence region
were informed in writing about the development of a ParkinsonNet
in their region and invited to a information event. At this event, the
S373
structure, benefits and requirements of participation to a Parkinson-
Net were discussed, a brief summary of the European Physiotherapy
Guideline for Parkinsons disease (2014, www.Parkinsonnet.info)
was presented and participants were invited to a 3-day ParkinsonNet
entry-level course. This course was adapted to the German needs
through discussion within the local head of physiotherapy, the Physi-
oDeutschland representative of the European Guideline development,
and a survey amongst the physiotherapists registered for the course.
All required materials were translated into German. Participants were
offered ParkinsonNet membership, including access to the secured,
web-based platform ParkinsonNet Connect for information and com-
munication, ongoing education and visibility in the Parkinsons care
finder. For March coming, a first event for involve neurologists and
Results: A first German ParkinsonNet has been installed. Results
of the first evaluations on feasibility and benefits will be presented at
the International Parkinson and Movement Disorder Society (MDS)
congress.
964
The contributions of continuing education in dysphagia for
pediatric nursing care in a teaching hospital
V.D. Leonor, R.S. Santos, R.G. Senff, B.S. Zeigelboim, H.G. Teive
(Curitiba, Brazil)
Objective: Propose educational action in dysphagia for the nurs-
ing team of the pediatric in a teaching hospital.
Methods: Study of cross delineation quantitative approach. The
study was performed in a tertiary reference hospital, entailed to the
Unified Health System (SUS). The sample consisted of 62 professio-
nals including nurses, technicians and nursing assistants who work in
the care of pediatric patients. We applied a questionnaire for verifica-
tion of knowledge about dysphagia later an educational activity and
its immediate evaluation was performed.
Results: Knowledge of nursing dysphagia was evidenced as posi-
tive, especially regarding the concept with 96.77% of hits, symptoms
with 83.87% of hits, causes with 74.19% of hits, consequences with
70.97% of hits, identification of a qualified professional for rehabili-
tation with 85.48% accuracy and importance of rehabilitation with
87.10% of hits. Research participants were receptive to educational
action taken individually through folder and then posters. In the
immediate evaluation after they reported that the intervention had
augmented knowledge about dysphagia, recognized the importance
of these and would like to receive more information about this and
other pathologies.
Conclusions: The study demonstrated the fragmented nursing
knowledge about dysphagia, but with interest and disposition to learn
if content available through continuing education.
965
Efficacy of an education and exercise group on understanding of
Parkinsons and uptake of exercise in people with Parkinsons
disease
F.A. Lindop, R.H. Skelly (Derby, United Kingdom)
Objective: To evaluate effectiveness of a multidisciplinary Par-
kinsons education & exercise group on (1) improving understanding
of symptoms, interventions and management, (2) uptake of regular
exercise and (3) understanding how to manage difficulties with
transfers.
Background: Education in understanding and management can
empower patients to take a greater role in monitoring & management
of their condition (Iansek and Morris 2013). The multidisciplinary
team can provide education enabling Parkinsons patients to have
more autonomy, improving exercise participation & management of
transfer difficulties.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S374 POSTER SESSION
Methods: Recently diagnosed patients had a programme of group
exercise and education comprising six 90 minute sessions over six
weeks. Maximum group size was 10. Sessions included discussions
on signs & symptoms, medication, bladder/bowel, speech & swallow,
importance of exercise, sleep, and a practical transfers session. Evi-
dence for the benefits of exercise in Parkinsons was shared in order
to encourage home exercise, and group exercise (e.g. chair hockey)
formed part of each session. Sixty-seven participants attended, 40
male and 27 female. A questionnaire was completed by participants
on starting the group, and another on completion, determining their
understanding of 12 aspects of Parkinsons and whether they exer-
cised regularly.
Results: Pre-group questionnaires were completed by 67 patients
and post-group by 61. Pre-group, 44% reported a good understand-
ing of Parkinsons, 99% reported a better understanding after-
wards. Understanding of medications was reported as good by
44% pre-group but better by 94% after. Understanding the impor-
tance of exercise was reported as good by 74% pre-group, but
99% after. Self reported participation in regular exercise was 44/67
(65%) pre-group and 56/61 (96%) after group education (p<0.001,
Chi Square test). Knowledge of how to manage difficulties getting
on/off chair, bed and floor was reported as good by 49% pre-group
but improved to 97% after. End of group comments were added by
54% of participants who reported feeling supported, informed and
more confident.
Conclusions: Our data suggests that an education and exercise
group improves patient understanding of Parkinsons, confidence in
transfer ability and increases uptake of regular exercise. This may
enable patients to have better autonomy in condition management.
966
Medication errors prolong length of stay in hospitalized
Parkinsons disease patients
D. Martinez-Ramirez, J.C. Giugni, C. Little, J.P. Chapman, B.
Ahmed, E. Monari, M.S. Okun (Gainesville, FL, USA)
Objective: We aimed to investigate potential medical errors that
may occur during PD hospitalization.
Background: Parkinsons disease (PD) patients are more likely
to be hospitalized, have higher rates of hospital based complications,
and are known to have a substantial increased risk of deterioration
during hospitalization.
Methods: An IRB approved protocol used a retrospective cross-
sectional chart review of 339 consecutive hospital encounters from
212 PD patients. The review included the period from January 2011
to March 2013. Medical errors were defined as delayed or missed
administration of dopaminergic drugs or the administration of contra-
indicated dopamine blocking agents. A univariate ANCOVA was run
to examine whether missed dosages of levodopa and/or the use of a
dopamine blocker could be related to increased length of PD hospital
stays.
Results: Characteristics of population are described in table 1.
Characteristics of population (n5339).
No. (SD) Minimum Maximum
Age, y 74.1 610.1 34 97
Female, no. 206 (60.8%) - -
Charlson index, no. 5.9 61.5 2 11
Disease duration, y 6.4 66.3 0 30
Hoehn & Yahr, no. 1.3 60.7 0 2
LED, no. 502.4 6487.9 0 3285
The analysis revealed a significant effect for missed dosages of
levodopa (p5<0.01). Subjects, who missed at least one dose stayed
in the hospital longer (8.6 60.8) days compared to those who did
Movement Disorders, Vol. 30, Suppl. 1, 2015
Fig. 1. (966).
not miss any dosages (3.5 61.1) days. The results also revealed a
significant effect for contraindicated dopamine blocking agents and
the length of hospital stay (p5<0.05). Administration of a dopamine
blocking agent resulted in a hospital stay of 7.5 61.2 days compared
to 4.6 60.71 days. [figure1] Neurologists were consulted in around
25% of encounters.
Conclusions: Frequent preventable medication administration
errors occur in hospitalized PD patients. These medication errors are
potentially modifiable factors that could be improved by education
and the introduction of better hospital protocols.
967
Knowledge and awareness regarding Parkinsons disease in
general population Truth and prejudice
I. Telarovic, S. Telarovic (Zagreb, Croatia)
Objective: To investigate knowledge and awareness regarding
Parkinsons disease (PD) in general population.
Background: Except for their primary tasks of diagnostics, treat-
ment and prevention, modern healthcare providers are to educate the
population, work on de-stigmatization of patients and popularization
of medicine and science.
Methods: We used our own specially designed questionnaire
about PD that was distributed via SurveyMonkey online and individ-
ually in a printed form for the population that does not use a com-
puter. The study group (N 5 234) was defined according to different
variables (age, gender, education). Subjects (not PD patients nor
family members) answered questions about nature of the disease,
symptoms, treatment, famous people suffering from PD, age of
onset, risk factors and survival in PD.
Results: Data was analyzed using SPSS. Results of study pre-
sented varying degrees of knowledge of PD, especially answers
regarding famous people suffering from PD (64% incorrect) and risk
factors (79% incorrect). Correct answers correlated with the level of
education.
Conclusions: Knowledge and awareness regarding PD in general
population varies depending on many variables. It is necessary for
experts to provide better education using all available resources and
levels, with multidisciplinary approach. A majority of participants
requested the correct answers upon finishing the survey wanting to
gain a better knowledge of the PD, thus confirming the need to make
additional efforts in educating and informing the population about
PD and other neurological disorders through public forums, lectures,
using media, brochures, etc. This would benefit the early recognition
of PD, correct the prejudice and help de-stigmatization of people suf-
fering from PD.
 POSTER SESSION
Neuroimaging
968
Parkinsons progression markers initiative (PPMI) prodromal
cohort of REM behavior disorder (RBD) with DAT deficit
Parkinsons Progression Markers Initiative (PPMI) RBD
Investigators (New Haven, CT, USA)
Objective: To enroll and follow a cohort of prodromal subjects
within the Parkinsons Progression Markers Initiative (PPMI), with
REM behavior disorder (RBD) and a dopamine transporter (DAT)
binding deficit to examine progression biomarkers during prodromal
PD and establish the time course for phenoconversion to motor Par-
kinsons disease (PD).
Background: Several studies have demonstrated that enriching a
population for PD risk by combining non-motor symptoms with
DAT deficit may successfully identify individuals at high risk to phe-
noconvert to manifest PD. Several studies have shown that RBD is a
substantial risk factor for the development of synucelinopathies
including PD and MSA.
Methods: PPMI is longitudinal study to identify clinical, imaging
and biospecimen biomarkers of PD onset and progression. PPMI has
established standardized methods of acquisition and analysis of bio-
marker data in a multi-center study. PPMI sites with a collaborative
relationship with a local sleep centers recruited patients with poly-
somnograms (PSG) from recent sleep studies. Patients with evidence
for RBD based on their PSG as determined by REM sleep without
atonia (RSWA), using the Montplaisir 2010 or Frauscher 2012 crite-
ria assessed by a central reading lab and who also had a DAT deficit
(compared to healthy subjects) as determined by the PPMI imaging
core lab using standardized visual and quantitative outcomes were
enrolled and will be assessed longitudinally on a schedule similar to
existing PPMI cohorts.
Results: 108 RBD subjects with PSGs where recruited, 90 (83%)
met evidence of RBD by central reading lab 16 (15%) did not meet
Fig. 1. (969).
S375
criteria (2; 1.9% not readable). DaTSCAN imaging was completed
on 70 (65%) subjects with 36 (51%) meeting criteria of DAT deficit,
The mean lowest Putamen in RBD compared to healthy subjects;
1.01 1/-0.33 vs.1.66 1/- 0.34, with 30 male/6 female. Enrollment
and subject follow-up is ongoing.
Conclusions: PPMI has established the feasibility of utilizing a
central PSG read as eligibility criteria for a multi-center PD prodro-
mal RBD cohort. Approximately 50% of subjects identified by PSG
and clinical criteria as RBD who underwent DAT imaging showed a
DAT deficit. Continued follow-up of this cohort is required to under-
stand the prodromal PD biomarker signature for RBD subjects.
969
Rat brain basal ganglia imaged with optical coherence
tomography: Feasibility and future perspectives
^
J.S. dos Angelos, W.O.C. Lopez, R.C.R. Martinez, P.R. Reis, C.K.
Takimura, M.J. Teixeira, P.A. Lemos Neto, E.T. Fonoff (Sao Paulo, Brazil)
Objective: To evaluate (1) feasibility of optical coherence tomog-
raphy in acquiring rat brain basal ganglia images and (2) compare
images with known rat brain histological sections.
Background: Optical coherence tomography (OCT) is a promis-
sory imaging method that renders in vivo and real-time cross section-
als views of tissues, using near-infrared light. High-resolution images
can be obtained in different clinical settings with such technology,
including basal ganglia tomograms during stereotactic procedures.
This last application remains to be well defined, tested in humans
and relevant to electrodes implant.
Methods: Two male Rattus novergicus (230-250g) were anesthe-
tized and placed in a stereotactic frame (David-Kopf instruments)
following current ethical guidelines of experimental animal practice.
Targets coordinates of caudate-putamen (CPU) and globus palidus
internus posterolateral (GPi) were determined using histological sli-
ces from Paxinos e Watson atlas (2005). A stainless metal cannula
was adjusted to the stereotactic frame guiding the fiber optic OCT
Movement Disorders, Vol. 30, Suppl. 1, 2015
S376 POSTER SESSION
catheter (DragonflyTM, St Jude Medical) that was connected to a
mobile console (C7-XRTM, St Jude Medical) for OCT image acquis-
itions. Structures in a diameter of 2 3 mm lateral to the target
were scanned. Images were processed and then compared with rat
brain slices of the same studied nucleus available in Teaching and
Research Institute from Sirio Liban^es Hospital, S~ao Paulo, Brazil.
Results: OCT was able to determine with precision the striatum
appearance and its transition to GPi, rendering images similar to a
histological view. [figure1]
Conclusions: Our preliminary results show that OCT application
in rat brain basal ganglia was useful and suitable for identifying
deep gray matter nucleus. More studies are required because such
technology would improve so much deep brain stimulation surgery
in humans, provided that safeness and benefits are ensured.
970
Arterial spin labelling (ASL) reveals an abnormal cerebral
perfusion pattern in Parkinsons disease
K. Abe, T. Hayashi, M. Yamamoto, N. Akiyama, M. Fujita
(Nishinomiya, Japan)
Objective: To determine whether arterial spin labeling (ASL) can
be used to evaluate regional cerebral blood flow (CBF) patterns in
Parkinsons disease (PD).
Methods: Thirty-one PD patients who met a Japanese PD diagno-
sis criteria and 31 age and sex normal controls were scanned by
using a pseudo-continuous arterial spin labeling (PCASL) method
with a 1.5 Tesla MRI unit.
Clinical signs were evaluated by Hoehn-Yahr stage, unified Par-
kinsons disease rating scale (UPDRS), minimental state exmination
(MMSE), frontal assessment batery (FAB), the Montral cognitive
assessment (MOCA).
Regional cerebral blood volume (CBV) was compared in the
frontal, the parietoposterial, and the posterior cortex using region-of-
interest analysis.
Results: PD patients showed three regional CBV patterns. The
first group had normal regional CBV patterns comparing with those
of normal controls. The second group had reduced frontal cortex
regional CBV patterns comparing with those of normal controls. The
third group had reduced parietoposterial cortex regional CBV pat-
terns comparing with those of normal controls.
Conclusions: This is a study to detect three patterns of hypoper-
fusion in the cortex in PD patients using ASL perfusion MRI.
Because ASL perfusion MRI is completely noninvasive and can,
therefore, safely be used for repeated assessments, this method can
be used to monitor treatment effects or disease progression in PD.
971
Brain amyloid-b content is associated with cognitive decline in
Parkinsons disease: A cross sectional study using [F18] FDDNP
PET and CSF Ab levels
F. Antonelli, M.T. Buongiorno, Y. Compta, Y. Fernandez, J. Pavia,
F. Lomena, J. Garcia, I. Ramirez, A. Camara, M. Fernandez, M.
Soler, X. Perez, J. Barrio, M.J. Marti (Barcelona, Spain)
Objective: The aim of this study was to assess the associations
of [18F] FDDNP-PET and cerebrospinal fluid (CSF) levels of tau
and Ab with clinically defined PD-dementia (PDD) and neuropsy-
chological performance in PD patients.
Background: More than 50% of patients with Parkinsons disease
(PD) develop dementia in the advanced stage. Neuropathological
substrate of dementia in PD appears to be heterogeneous, with a role
of tau and Ab proteins having been suggested. CSF analysis of these
proteins and positron emission tomography (PET) with different
ligands are used as biomarkers of brain deposition of these proteins.
2-(1-{6-[(2-[18F]Fluoro-ethyl)(methyl) amino]-2-naphthyl}ethylide-
ne)malononitrile ([18F] FDDNP) is a PET ligand which has been
Movement Disorders, Vol. 30, Suppl. 1, 2015
shown to be sensitive in the in-vivo visualization of the accumulation
of both tau and Ab proteins in the brain.
Methods: We evaluated a sample of 16 patients with PD without
dementia (PDND), 8 patients with PDD and 8 healthy controls. All sub-
jects underwent comprehensive neuropsychological assessment, [18F]
FDDNP PET, and CSF analysis of Ab and Tau levels. The primary
outcome was to evaluate if there were differences in the [18F] FDDNP
binding and in CSF Ab or tau levels between PDND and PDD patients.
As secondary endpoint we evaluated possible correlations of cognitive
scores with [18F] FDDNP binding and CSF Ab and tau levels.
Results: We found that PDD patients had higher [18F] FDDNP
binding in the lateral temporal region and lower CSF Ab levels com-
pared to PDND patients and healthy controls with an inverse associa-
tion between FDDNP PET and CSF Ab (the higher the former, the
lower the latter). Several correlations between cognitive dysfunction
measures and both [18F] FDDNP binding and CSF Ab were found.
In particular patients having worst cognitive performances showed
higher binding of [18F] FDDNP and lower level of Ab in CSF.
Conclusions: In summary we showed that dementia and neuro-
psychological performance in PD are related to higher burden of Ab
in the brain as measured by [18F] FDDNP PET and CSF Ab. Thus,
these biomarkers findings support the role of underlying Ab as a
substrate of cognitive impairment in PD, which might eventually be
considered a target for future therapeutic approaches.
972
Brain connectivity changes associated with t-DCS and cognitive
training plus cognitive training in Parkinsons disease with mild
cognitive impairment
R. Biundo, L. Weis, E. Fiorenzato, G. Gentile, M. Giglio, M. Campo,
R. Schifano, A. Antonini (Venice-Lido, Italy)
Objective: The aim of this study is to investigate whether cogni-
tive changes are associated with discrete regional modifications of
brain perfusion and cortical excitability.
Background: Data were collected in the context of a double-
blind randomized study where we found long-term benefit of anodal
left DLPFC trascranial direct current stimulation (t-DCS) in long
term memory and visuo-spatial skills in Parkinsons patients with
mild cognitive impairment (PD-MCI) despite a temporary break
down of executive/attentional abilities during treatment.
Methods: Twenty matched PD patients (10 real and 10 sham t-
DCS condition) participated at the treatment (4 weeks) and follow
up session (16 weeks). Treatment consisted of online t-DCS (sham
or real) with structured 30 minutes cognitive training (CT) adminis-
tered 4 times a week. Each patient underwent clinical, neuropsycho-
logical evaluation and MRI at baseline, 4-week and study end.
Results: At 4 weeks, real t-DCS group showed increased frac-
tional amplitude of low frequency fluctuation (fALFF) activity in
bilateral frontal areas, right temporal and left cerebellum areas and
decreased fALFF activity in left precentral, temporal areas, and in
the right frontal-orbital areas, together with decreased performance
in attentional and motor speed abilities. At 16 weeks follow-up we
observed a wider increase of fALFF activity in parietal, temporal
region and cerebellum and a focal reduction in the frontal middle
and orbital areas bilaterally and right cerebellum together with
increased performance in visuo-spatial abilities and long term mem-
ory. At 4 weeks the sham group showed broad increase in whole
brain activity and focal decreased activity in temporal, angular and
cerebellum areas together with increased long term memory index.
At 16 weeks a brain activity similar to baseline was observed with
reduced frontal, rolandic, cingulated and cerebellum areas fALFF
activity and focal increase in occipital, temporal areas together with
a cognitive performance similar to baseline.
Conclusions: We found brain connectivity modifications associ-
ated with cognitive performance changes during rehabilitation treat-
ment both at 4 and at 16-week follow up. These results are
promising and should help clarifying how the brain is endowed with
 POSTER SESSION
intrinsic functional reorganization to support and maintain cognitive
changes over time.
973
Substantia nigra echogenicity and odor discrimination in REM-
sleep behavior disorder and Parkinsons disease
J. Carlos, V. Pablo, U.S. Reinaldo, N. Cristobal, S. Julia, G. Jaime
(Santiago, Chile)
Objective: To compare the differences in olfactory function and
substantia nigra echogenicity in patients with REM Sleep Behavior
Disorder (RBD) with and without Parkinsons disease (PD) and in
PD patients without RBD.
Background: There is a great interest for deciphering the rela-
tionship between sleep disorders and synucleinopathies. In particular
REM sleep behavior disorder (RBD) has been described as a prodro-
mal manifestation of Parkinsons disease (PD), preceding even by
years the onset of motor manifestations.
Methods: Patients with RBD with PD (n510) and without PD
(n515), PD patients without RBD (n511) and healthy subjects
(n515) were included. Olfaction was evaluated using the Sniffin
Sticks test and Substantia nigra (SN) hyperechogenicity was assessed
using transcranial ultrasonography (TCS). RBD dignostic was con-
firmed by nocturnal polysomnography in the majority of patients. PD
diagnostic was established using London Brain Bank Criteria.
Results: Transcranial sonography showed an increased echogenic-
ity (biggest area found) in substantia nigra in patients with RBD
compared to control (mean1/-SD) 0,27 1/- 0,15 vs 0,14 1/-0,08,
but no difference was found between those with and without PD
(0,30 1/-0,18 vs 0,25 1/- 0,12) neither between those with PD with
or without RBD. Olfactory evaluation (score) showed a reduced
olfaction in both RBD groups as compared with healthy controls
(6,16 1/- 3,14 vs 9,23 1/- 2,39). However, for this test RBD
patients with PD performed significantly worse than those without
PD (4,4 1/- 3,44 vs 7,33 1/- 2,38, p<0.001).
[figure1]: Distribution of odor discrimination and SN echogenicity
in the groups. Results expressed as percentages.
Conclusions: RBD Patients show abnormalities in both substantia
nigra echogenicity and odor discrimination. Olfactory dysfunction seems
to be more related to the presence of PD in subjects with RBD. Prospec-
tive studies are needed to establish whether Olfactory function is also a
better predictor than TCS to predict conversion from iRBD to PD.
974
Comparison between odor discrimination, substantia nigra
echogenicity and nigrostriatal dopaminergic activity measured by
18F.PR04 PET in Parkinsons disease
J. Carlos, V. Pablo, C. Pedro, K. Vasko, P. Rosana, A. Horacio
(Santiago, Chile)
Fig. 1. (973).
S377
Objective: To evaluate the relationship between odor discrimina-
tion, substantia nigra echogenicity and nigrostriatal dopaminergic
activity in patients with Parkinso
ns disease.
Background: Positron emission tomography for imaging dopami-
nergic pathways is considered to be a valuable tool for differential
diagnosis and early detection of Parkinsons disease. During last dec-
ade transcranial substantia nigra echogenicity and odor discrimina-
tion has been also used as complimentary tools for the diagnosis of
PD. However there is a lack of information about the relationship
between these three diagnostic methods to support the diagnosis of
PD.
Methods: Twelve patients with PD according to established crite-
ria were prospectively included. All subjects underwent a static PET
scan (Siemens mCT) for a duration of 30 min, 60 min after bolus
injection of 165 6 15 MBq (mean 6 SD) [18F]PR04.MZ. Data analy-
sis was performed calculating standard uptake ratios with cerebellum
as reference. Normalization of brain images and delineation of VOIs
was performed using PMOD imaging software and CT- and VOI-
templates were created for this study. Odor discrimination was eval-
uated by using sniffing stick test (hyposmia was considered as less
than 7 detections) and transcranial sonography of the substantia niga
(SN) was also conducted. Pathological echogenicity was considered
as SN area more than 0.20 cm2.
Study was approved by local and governmental authorities and
participants signed informed consent prior to study begin.
Results: Age (mean 1/- SD) was 56.8 1/- 13,9 years. Substantia
nigra hyperechogenicity was found in 10 patients (SN area: 28,81/-
14,2) Hyposmia was observed in 6 cases (7.5 1/-3 oddors). PET
analyses showed dopaminergic depletion in 11 patients. Percentage
of posterior putamen depletion was 66.01/-29.2. Nine subjects with
Dopaminergic depletion also exhibited SN hyperechogenicity. There
was no relationship between SN area nor olfaction detection and
magnitude of dopaminergic depletion.
Conclusions: Evaluation of SN ecogenicity and dopaminergic
activity by 18FPR04.MZ PET are valuable tools in the diagnosis of
PD. Larger studies are required to confirm these findings. FONDE-
CYT No. 11130534.
975
Functional connectivity in Parkinsons disease is differentially
impacted by alpha-synuclein and amyloid
D.O. Claassen, S. Rane (Nashville, TN, USA)
Objective: To examine the relationship between CSF a-synuclein
and Ab-Amyloid levels with brain functional connectivity in Parkin-
sons disease patients.
Background: While abnormal a-synuclein accumulation is a
well-described pathologic finding in Parkinsons disease (PD), the
role of Ab-Amyloid deposition in the clinical progression of PD is
unclear. Cerebrospinal fluid (CSF) levels of neurodegenerative pro-
teins and resting state MRI are well described disease biomarkers.
Here, we assessed how reductions in cerebrospinal fluid (CSF) levels
of a-synuclein and Ab-Amyloid correlate with changes to functional
connectivity in key neuronal networks affected in PD.
Methods: Data from patients (n534) in the the Progressive Par-
kinsons Markers Initiative database, who underwent both functional
MRI (fMRI) and CSF analysis for a-synuclein and Ab-Amyloid,
were evaluated. fMRI data were analyzed using established seed
voxel connectivity approaches following component based noise cor-
rection (CompCor). Seed regions-of-interest (ROI) included orbito-
frontal, lateral and medial prefrontal, parietal, and posterior
cingulate. Voxel-wise synchrony for each seed ROI was calculated
and compared within different established brain networks to total
CSF-a-synuclein and CSF-Ab after correcting for age and gray-
matter volume.
Results: Mean CSF-a-synuclein and CSF-Ab levels were
1698 6 790 and 387 6 96 pg/ml. Overall, reductions in CSF-a-
synuclein, not CSF-Ab, related to changes in connectivity of frontal
Movement Disorders, Vol. 30, Suppl. 1, 2015
S378 POSTER SESSION
regions. Distinct connectivity patterns in regions of the default mode
network were evident between CSF-a-synuclein and CSF-Ab. Low
CSF-a-synuclein was associated with enhanced connectivity
(p<0.05) in the frontal regions. Low CSF-Ab was associated with
reduced connectivity (p<0.05) in temporal and posterior regions.
Conclusions: We show distinct differences in brain connectivity
associated with CSF a-synuclein and CSF-Ab levels. CSF-a-
synuclein appears to impact frontal networks, previously linked to
executive control, and unlike Ab, is associated with enhanced con-
nectivity in frontal and default networks. Ab appears to reduce con-
nectivity in regions associated with advanced disease duration and
severity, namely the posterior and temporal cortex. These findings
support the hypothesis that disease characteristics of PD may be
linked to differing pathologic processes.
976
White matter microstructure in idiopathic craniocervical
dystonia
A. DAbreu, G.L. Pinheiro, R.P. Guimar~ aes, B.M. Campos, F.
Cendes (Campinas, Brazil)
Objective: Our goal is to evaluate the white matter microstruc-
ture in subjects with craniocervical dystonia using DTI (diffusion
tensor imaging).
Background: Dystonia is a syndrome characterized by involun-
tary muscle contractions, causing twisting movements and abnormal
postures, which are often painful.
Craniocervical dystonia involves the contraction of the head and
neck muscles. It is the most frequent dystonia in adults, and it can
be focal or segmental. Botulinum toxin is the best treatment for cra-
niocervical dystonia, although the effect is temporary. Classically
considered being secondary to a dysfunction or lesion in the basal
ganglia circuit, recent studies have shown the involvement of the
sensorimotor areas and the cerebellum.
Methods: In the present study, we evaluated structural brain
changes in 40 patients comparing them to 40 healthy controls. Sec-
ondarily, we divided the patients into 4 groups based on dystonia
localization: blepharospasm, blepharospasm 1 oromandibular, ble-
pharospasm 1 oromandibular 1 cervical and cervical. Patients and
controls underwent the same MRI acquisition protocol in a 3T Phi-
lips Achieva MRI scanner. All patients were assessed by an experi-
enced neurologist specialized in Movement Disorders.
We performed DTI analyzes with TBSS and we evaluated the
fractional anisotropy and the mean diffusivity. We performed two
confirmatory analysis using a ROI based approach and tractography.
Results: We did not find microstructure alteration in the white
matter of subjects with craniocervical dystonia.
Conclusions: These results suggest that white matter tracts are
not primarily affected in craniocervical dystonia. Further studies
should evaluate the presence of functional and connectivity abnor-
malities in these subjects.
977
Pattern of regional cortical thickness in patients with
Parkinsons disease and impulse control disorders
R. De Micco, G. Santangelo, C. Vitale, A. Tessitore, M. Amboni, D.
Corbo, A. Giordano, P. Barone, G. Tedeschi (Naples, Italy)
Objective: To investigate the pattern of gray matter (GM) atro-
phy and cortical thickness (CTh) in patients with Parkinsons disease
(PD) with and without impulse control disorders (ICD).
Background: Previous PET and fMRI studies have shown an
abnormal activation pattern in PD patients with ICD in multiple
regions linked with impulse control, like orbitofrontal cortex, anterior
cingulate cortex, nucleus accumbens. Using standard neuropsycho-
logical tests, PD patients with ICD demonstrated impairment in a
Movement Disorders, Vol. 30, Suppl. 1, 2015
range of cognitive domains, including frontal lobe abilities and spa-
tial planning.
Methods: 15 patients with PD with ICD (ICD1), 15 patients
with PD without ICD (ICD-) and 24 age and sex-matched healthy
controls (HCs) were enrolled in the study. PD was defined according
to the UKBB clinical criteria; patients were screened for ICDs by
the Minnesota Impulsive Disorders Interview (MIDI). Whole brain
structural imaging was performed on a 3T GE MR scanner. Surface-
based investigation of CTh was carried out by using Freesurfer Soft-
ware. We also used voxel-based morphometry (VBM-SPM8) to
investigate the pattern of GM atrophy. We considered cortical areas
with the p value less than 0.05 corrected for multiple comparisons as
statistically significant.
Results: No significant differences were detected between the
groups in any of the clinical variables. The voxel-wise analysis of
the regional differences in CTh revealed a specific abnormal pattern
involving the limbic system in the comparisons between: a) ICD-
and ICD1 patients and b) ICD1 patients and HCs. In particular,
ICD1 patients showed a statistically significant (p<0.05) cortical
thickening when compared to both ICD- patients and HCs in the
anterior cingulate (ACC) and orbitofrontal (OFC) cortices. Moreover,
cortical thickening in these areas is correlated (p<0.05) to MIDI
score. VBM data did not reveal any statistically significant differen-
ces in local GM between ICD1 and ICD- patients and between
patients and controls.
Conclusions: Our results demonstrated that ICD1 patients have a
stronger pattern of CTh in limbic regions compared with ICD-.
Thus, aberrant anatomical and cytoarchitectural features in OFC and
ACC, involved in reward-related decision making, may play a role
in the lack of inhibition of compulsive behaviors. We also confirm
that CTh may be more sensitive than VBM in revealing cortical
structural abnormalities in neurodegenerative disorders.
978
Lead location for subthalamic nucleus deep brain stimulation
using a 3d visualization tool

M. Del Alamo, I. Avil
es, F. Estella, L. Caba~
nes, I. Regidor (Madrid,
Spain)
Objective: To compare three visualization tools used to measure
the location of the implanted deep brain stimulation (DBS) leads rel-
ative to the subthalamic nucleus (STN) target.
Background: 3D visualization system could be a reliable tool to
facilitate programming in PD patients implanted with a DBS system.
Methods: A total of 10 DBS leads implanted in five Parkinso ns
disease (PD) patients with different DBS systems were studied.
Implanted leads were located in a post-op CT. Three different techni-
ques were used to locate the target; post-op CT was fused with either
(1) pre-op T2 MRI imaging, (2) the Schaltenbrand atlas, or (3) a 3D
visualization tool using the Morel atlas.
Results: Of the ten leads studied, 80% using the Schaltenbrand
atlas (2) and the 3D visualization tool (3) showed the same relative
target-lead position as the gold standard(direct visualization of target
with T2 MRI) (1). Within the eight leads where the relative location
measured with the three systems was equal, the lead-target distance
differed: three leads were implanted directly in the desired target
(lead-target distance 0 mm); five leads were implanted with a devia-
tion from the target (lead-target distance [0.7-3.1] mm the same
distance deviation was observed when the actual T2 (1) and lead
position image was compared with the atlas (2) and 3D visualization
tool (3).
In the 20% of cases with a lead-target distance mismatch using
method (1) vs. methods (2) and (3), a clear deviation within the anat-
omy of the patient and the normalized atlas was shown. This location
misalignment within procedures for the atlas-related positioning and
the 3D visualization tool was linearly related to the deviation in the
patient-specific anatomy compared to the standardized anatomical
atlas. For these error cases, the deviation in the position of the
 POSTER SESSION S379

actual target compared with the atlas targets used in the two groups
to validate was the same as the deviation of the lead location com-
pared to the reality of the lead position.
Conclusions: This method will allow us to validate systems such
as the 3D visualization tool (GuideTM, Boston Scientific) and enable
its use as a trusted tool to obtain optimal programming options.

979
MRI findings in a rare case of sporadic Creutzfeldt-Jacob
disease presenting as progressive supranuclear palsy
A. Duffy, B. Koo, K. Park, M. Bobinski, L. Zhang (Sacramento, CA,
USA)
Objective: Report MRI findings in a rare case of sporadic
Creutzfeldt-Jacob disease (sCJD) presenting as Progressive Supranu-
clear Palsy (PSP).
Background: sCJD classically presents as a rapidly progressive
dementia, ataxia, and myoclonus. There are rare reports of sCJD pre-
senting as PSP with typical features of early falls, Parkinsonism, and
vertical gaze palsy. MRI characteristically demonstrates bilateral
symmetric hyperintensities within the striatum and to a lesser extent
with thalamic and cortical involvement (Zerr et al, 2009). Amongst
case reports of sCJD presenting as PSP, we found only one report
with supportive MRI findings to suggest a diagnosis of sCJD (Shi-
maura et al, 2003).
Methods: Case report. Fig. 2. (979).
Results: A 67-year-old male with a 7-month history of ataxia,
falls, and tremors that developed rapidly over the course of one
month. Subsequently, he became severely dysarthric. At 6 months he
was wheelchair bound requiring full care, anarthric, and dysphagic. revealed presence of 14-3-3 and RT-QuIC supporting a diagnosis of
He remained cognitively intact communicating with an iPad. Exami- CJD.
nation revealed eyelid apraxia, spasmodic dysphonia with a barely [figure1] [figure2]
audible whisper, axial rigidity, bradykinesia, ataxia, intention tremor, Conclusions: We report a case of sCJD presenting as PSP with
and postural instability with inability to walk. The initial diagnosis hyperintensity on DWI greater than on FLAIR sequences in a corti-
was PSP; however, a rapid course and MRI findings were highly cal distribution supporting a diagnosis of sCJD. Additionally, we
suggestive of sCJD. The latter included restricted diffusion and were able to observe the evolution of MRI findings in our patient
abnormal high FLAIR signal in the cortex of bilateral frontal, poste- over his 7-month course in a classic neocortical pattern of sCJD. Our
rior temporal, occipital and parietal lobes (Figs 1-2). An MRI 7 case emphasizes the importance of imaging as an aide to the clinical
months prior showed subtle restricted diffusion with FLAIR signal diagnosis of sCJD, especially in challenging atypical presentations,
hyperintensity involving left frontal and parietal cortices. CSF and adds to the growing literature on MRI findings in sCJD.

980
Comparison of baseline 123-I Ioflupane SPECT striatal binding
ratios with diffusion tensor images from the Parkinsons
progression marker initiative
C.L. Gallagher, J. Sojkova, B.B. Bendlin, O. Okonkwo, A. Alexander,
I.W. Wu, N. Schuff (Madison, WI, USA)
Objective: To compare fractional anisotropy (FA), an MRI-based
index of white matter microstructural integrity, to striatal binding
ratio (SBR), a SPECT-based index of nigrostriatal dopaminergic pro-
jections, in Parkinsons disease (PD) and control subjects.
Background: Several studies have shown diffusion tensor MRI
(DTI) differences in cerebral white matter in PD patients when com-
pared with healthy controls. Whether these differences are a consist-
ent finding in large datasets, and whether they reflect pathological
changes related to PD, is not known. The Parkinsons Progression
marker initiative (PPMI) is a multicenter, longitudinal study that col-
lects both DTI and 123-I Ioflupane SPECT. We hypothesized that
this dataset would show lower SBR to be associated with lower FA
in major white matter tracts.
Methods: Data from 162 PPMI subjects (92 PD, 52 HC, 18
SWEDDs) with both SPECT and DTI (mean intra-scan interval 1.6
months) available as of January 2014 were analyzed. Using a voxel-
wise approach, we compared FA within major white matter tracts
(FA .15 or higher) to mean hemispheric SBR for caudate nucleus
Fig. 1. (979). and putamen. FA maps were first normalized in tract-based spatial

Movement Disorders, Vol. 30, Suppl. 1, 2015

S380 POSTER SESSION

and scanner model (Siemens TrioTrim or Verio, both 3T). We also

compared FA between PD and control groups and with SBR in the
PD group. Reported clusters included at least 20 voxels at P < .001.
Results: Greater age was associated with diffusely lower FA
throughout hemispheric white mater (T=3.2-7.0). [figure1] With the
exception of a small parietal-occipital cluster (T=5.2; MNI 35, -70,
6), the relationship between FA and either putamen or caudate
nucleus SBR was opposite that expected; higher FA was associated
with lower SBR in several clusters (T=3.5-4.9). [figure2] Within the
PD group, higher FA was associated with lower SBR; PD subjects
had clusters of higher FA than controls.
Conclusions: In comparison to age, dopamine deficiency (based
on SBR) was a weak predictor of FA variations, and furthermore
yielded an effect opposite that hypothesized. Several factors, includ-
ing laterality of PD onset, may have influenced this outcome and
require further investigations.

Fig. 1. (980).
Fig. 2. (980).
statistics (TBSS; Smith, NeuroImage 2006); voxel-wise analyses
were then conducted in SPM12 (http://www.fil.ion.ucl.ac.uk) using a
regression design with covariates of age, gender, years of education,
981
HemiParkinsonism leading to the discovery of a large
epidermoid tumor
R. Garcia-Santibanez, H. Sarva, A. Khorsandi, R.K. Shrivastava,
W.L. Severt, D. MacGowan (New York, NY, USA)
Objective: To describe a patient, with hemiParkinsonism, found
to have a large contralateral temporal lobe epidermoid tumor.
Background: Epidermoid cysts account for 0.3 to 1.8% of brain
tumors. Although classically arising from the skull base, 19 cases
had temporal lobe origin. Most were asymptomatic. None presented
with hemiParkinsonism.
Methods: Case report.
Results: A 30-year-old left-handed man had three-months of
progressive, debilitating, left arm resting tremor. He later developed
a postural left leg tremor and left hand weakness and dexterity loss.
He denied difficulty walking, falls, or autonomic or cognitive symp-
toms. His general neurological exam demonstrated a central left
facial droop, left pronator drift, 4/5 strength of the extensor muscles
of the left arm, and left sided hyperreflexia. The Movement Disor-
ders exam demonstrated a high frequency left arm resting tremor,
which reemerged with postural changes and had a mild action com-
ponent. There was a postural, low frequency left leg tremor. He had
rigidity and bradykinesia disproportionate to the arm weakness.
Handwriting was micrographic. He stood up easily. Posture, stance,
base, and heel strike were normal. Left arm swing was decreased.
Brain MRI showed a nonenhancing right temporal lesion, which
was hyperintense on diffusion weighted imaging, causing mass
effect upon the right ventral midbrain. The lesion measured
5.3x5.0x5.0 centimeters. [figure1] Pathology confirmed it as an epi-
dermoid cyst. Tremor resolved hours after emergent near total
resection. At one month follow up, all findings completely resolved.
[figure2]

Fig. 1. (981).

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
Fig. 2. (981).
Conclusions: Our patients report stresses the need for neuroi-
maging in patients presenting with Parkinsonism who are young or
have the following: atypical features; poor levodopa response; pos-
tural instability without rigidity; and other unexplained neurological
symptoms. Masses can cause Parkinsonism by basal ganglia com-
pression; midbrain distortion; nigral invasion; and damage to fiber
tracts connecting the basal ganglia with higher order regions. Our
patient likely had distortion and compression of the basal ganglia
without significant destruction of dopaminergic neurons as suggested
by his excellent postsurgical recovery. Although less than one per-
cent of tumors cause Parkinsonism in large retrospective series, they
should be considered in the differential as early, aggressive treatment
may improve Parkinsonism and quality of life, as in our patient.
982
Longitudinal evaluation of brain atrophy in Parkinsons disease
and Parkinsons plus syndromes
C. Guevara (Providencia, Chile)
Objective: To quantify annualized whole-brain atrophy rate
(aWBAR) in patients with PPS and Parkinsons disease (PD) using
SIENA (Structural Imaging Evaluation using Normalisation of
Atrophy).
Background: Parkinsons Plus Syndromes (PPS) comprise multi-
ple system atrophy (MSA), Progressive Supranuclear Palsy (PSP),
corticobasal degeneration (CBD) and non vascular lower body Par-
kinsonism (LBP), all incurable and progressive illnesses which
require marker of disease progression for clinical trials. Quantitative
magnetic resonance imaging offers the possibility to assess brain
atrophy longitudinally.
Methods: Prospective study in PD (n:12), MSA (n:4), PSP (n: 4),
CBD (n:2) and LBP (n:2).
Results: aWBAR in MSA was 1.32% (0.22-2.75), in PSP 1.22%
(0.6-2.67), in CBD 1.39% (0.73-2.05) and in LBP 0.9% (0.9 to
0.98).
Comparing PD (aWBAR: 0.47% (0.02-1.40)) vs. PPS (aWBAR:
1.23% (0.22-2.75)), p: 0.01.
Conclusions: Patients with PPS have accelerated brain atrophy
compared with PD who hold similar values to healthy population.
Whole-brain atrophy rates from magnetic resonance imaging data
may be an informative way to quantify disease progression in an
unbiased fashion.
983
Metabolic changes associated with slow dopaminergic depletion:
A longitudinal PET study in the MPTP primate model of
Parkinsons disease
L.F. Hernandez, F. Molinet-Dronda, J. Blesa, C. Juri, M. Collantes,
E. Iglesias, I. Pe~
nuelas, J.A. Obeso (Pamplona, Spain)
S381
Objective: Analyze the metabolic pattern associated with pro-
gressive nigro-striatal DA depletion in the MPTP monkey model
with the aim to identify the changes that occur during different states
of striatal dopamine depletion.
Background: Parkinsons disease (PD) is mainly characterized
by striatal dopamine (DA) depletion due to loss of dopaminergic
neurons in the Substantia Nigra pars compacta (SNpc). Progressive
cell loss and greater nigro-striatal denervation are associated with
increased motor deficits. During this initial process, there is a succes-
sion of compensatory mechanisms that delay the appearance of
motor manifestations, leading to a prolonged and unnoticed pre-
motor period of disease evolution.
Methods: In this work we used twenty-four monkeys (Macaca
fascicularis) that received MPTP treatment (0.5 mg/kg, i.v.) on a
weekly basis to obtain different groups based on different degrees of
DA depletion: Baseline, asymptomatic, recovered, mild, and severe
Parkinsonian, according to Kurlan scale assesments. An additional
group (n56) was studied at baseline, severe Parkinsonian and after
L-Dopa treatment for 14 weeks. PET imaging was performed using
monoaminergic (11C-DTBZ) and metabolic (18F-FDG) radiotracers.
ROI analysis were done for 11C-DTBZ PET (striatum) and Statisti-
cal Parametric Mapping (SPM) analysis for 18F-FDG studies (whole
brain).
Results: 11C-DTBZ PET images showed a progressive decrease
of Binding Potential (BP) values in the striatum throughout MPTP
administration and the ensuing of Parkinsonian signs. 18F-FDG PET
in the Parkinsonian state was characterized by reductions in posterior
parietal, temporal lobe, lateral premotor and frontal cortex, as well
as increases in the thalamus, globus palidus and cerebellum. 18F-
FDG PET after L-Dopa administration revealed a metabolic pattern
recognized by hypometabolism in posterior parietal-occipital region
and hypermetabolism in post-comisural putamen, thalamus and
midbrain.
Conclusions: From these results, we can conclude that progres-
sive DA striatal depletion in this MPTP monkey model led to recog-
nizable Parkinsonian metabolic patterns that are homologous to the
clinical changes observed on patients. Moreover, we report for the
first time, a demonstration of metabolic brain networks at different
DA depletion stages in a nonhuman primate model of Parkinsonism.
984
Assessment of outcomes in Parkinsons disease subjects
randomized to SPECT imaging of the dopamine transporter
P.T. Hickey, M. Kuchibhatla, B.L. Scott, L. Gauger, M.A. Stacy
(Durham, NC, USA)
Objective: To evaluate the impact of presynaptic dopamine trans-
porter (DAT) imaging on functional outcomes in patients with Par-
kinsons disease (PD).
Background: PD is the second most common neurodegenerative
disorder and marked by the progressive degeneration of nigrostriatal
Movement Disorders, Vol. 30, Suppl. 1, 2015
S382 POSTER SESSION
dopaminergic neurons. Although diagnosis is based on clinical
grounds, new imaging techniques have been developed to assess the
integrity of the nigrostriatal system. DAT imaging enables in vivo
demonstration of striatal dopamine activity and has shown to
improve diagnostic confidence and influence treatment decisions in
Parkinsonian patients. Imaging has become a clinically useful tool
and is increasingly utilized in early PD trials, including those investi-
gating disease-modifying therapies. Thus, the impact of DAT imag-
ing on patient outcomes is important to understand and has not been
explored.
Methods: In this novel prospective imaging study, 20 subjects
with de novo Parkinsons disease were randomly assigned to undergo
[123I]-FP-CIT SPECT (DaTscan) either at diagnosis, 6, and 12
months or delayed to 6 and 12 months. Patient optimism was investi-
gated using the Life Orientation Test Revised (LOT-R) at baseline
and following each imaging session. Disease severity was evaluated
with the Unified Parkinsons disease Rating Scale part III (UPDRS
III) and prescribing practices were recorded.
Results: Patients were equally matched for age of PD onset (57
years (10.97) vs 64.8 years (10.64), p50.13) and disease severity
(UPDRS III at study entry 19.6 (7.26) vs 24.8 (8.87), p50.3057).
Despite added time of diagnostic confidence in the initial imaging
group, there was no difference in patient optimism as measured by
LOT-R between groups (Wilcoxon Scores (Rank Sums) p5.3025).
At the end of 12 months there was no difference in UPDRS III
scores (17.5 (9.35) vs 19.1 (9.07) p50.9082) nor dopaminergic treat-
ment (average LEDD 211(204.96) vs 172 (176.43) p50.7314).
Conclusions: Presynaptic DAT imaging does not alter functional
outcomes in PD patients when incorporated into the diagnostic algo-
rithm. As the utility of in vivo imaging increases, these results sug-
gest no impact on potential planned interventions in de novo PD
patients.
985
The decreasing of dopamine-transporter uptake on the right
ipsilateral side of tremor in a patient with Parkinsons disease
E. Hoshiyama, T. Kadowaki, A. Nakamura, K. Suzuki, K. Hashimoto,
K. Hirata (Tochigi, Japan)
Objective: To report a case of the decreasing of dopamine-
transporter uptake on the right ipsilateral side of tremor in a patient
with Parkinsons disease.
Background: The dopamine transporter (DaT) imaging is useful
to diagnose for presynaptic dopaminergic neuron degeneration. When
Case summaries
Suspected
Diagnosis on offending
Gender Age presentation drug
Female 81 IPD Prochlorperazine
(by GP)
Male 87 IPD Sodium valproate
Female 80 DIP Aripiprazole/lithium
Female 79 DIP Olanzapine
Female 77 DIP Amisulpride
Movement Disorders, Vol. 30, Suppl. 1, 2015
a diagnosis is difficult to define about tremor patients, DaTSCAN
can find the diagnosis such as the dopamine neuron inspection.
Methods: A 85-year-old man came our hospital with a chief
complaint of the right arm tremor. For neurological findings were the
right arm resting tremor and slightly rigidity of bilateral arms. We
suspected tremor-dominant Parkinsons disease. Because he has
slightly bilateral rigidity to consideration of aging, the DaTSCAN
was done for the inspection of the tremor.
Results: Although brain MRI was normal findings, DaT-SPECT
of brain showed decreasing in the right basal ganglia. Results of the
DaTSCAN were Striatum-Right=3.982, Striatum-Left=4.421. Inter-
estingly, the dopamine-transporter uptake reduced on the right ipsi-
lateral side of tremor. We diagnosed Parkinsons disease. His
symptom of the tremor was improved when we started to administer
L-dopa.
Conclusions: This case suggests that a tremor symptom and the
decrease of the dopamine nervous system do not have relevance.We
think it is an important case to consider about a patient of scans
without evidence of dopaminergic defict (SWEED).
986
The role of DaT scan in drug induced Parkinsonism
R. Irons, B.M. Joanna, C.K. Apurba (Reading, United Kingdom)
Objective: To describe and evaluate the use of the DaT scan in
suspected drug induced Parkinsonism (DIP) in our elderly care
Movement Disorders service.
Background: The DaT scan has been available in clinical prac-
tice for a decade, and has been a useful tool for differentiating idio-
pathic Parkinsons disease (IPD) due to dopaminergic synaptic loss
from essential tremor. It is difficult to exclude underlying IPD in
patients with DIP as drugs may unmask IPD. Whilst there is evi-
dence that DaT scan has good sensitivity and specificity in distin-
guishing IPD and PID, there is currently no consensus on the timing
for DaT scan when DIP is suspected.
Methods: In a two year period five patients with suspected possi-
ble DIP underwent a DaT scan. Case notes were obtained and we
reviewed their clinic letters and DaT scan results, and summarised
the salient features of the cases. The cases are presented as a series
of individual case studies.
Results:
Of our five patients, two were suspected IPD at presentation and
three were suspected DIP. One patient in each group returned a posi-
tive scan, both of which were showed severe synaptic loss bilater-
ally. The result led to a revised diagnosis in three out of five cases,
Indication for DaT DaTscan result Revised diagnosis
No benefit from - DIP
levodopa
Little benefit from 1 MSA
levodopa
No benefit from - DIP
levodopa
Risk of neuro-psychiatric 1 Idiopathic
disturbance secondary Parkinsonism
to levodopa
Risk of neuro-psychiatric - DIP
disturbance secondary
to levodopa
 POSTER SESSION
with consequent withdrawal or initiation of levodopa. The decision
to proceed to DaTscan was mainly based on lack of benefit from
previous dopamine therapy, or the perceived risk of inducing seri-
ous neuro-psychiatric symptoms in those on anti-psychotics.
Conclusions: DaTscan is a useful tool to rule out underlying
IPD in DIP where there may be an unmasking effect by the
drugs. In addition to omitting the offending drug, dopamine
replacement is required in such cases. The timing of the DaTscan
is based on clinical judgement as there are no clinical guidelines.
Managing such patients, particularly when anti-psychotics are
implicated, must be done jointly between Movement Disorder and
psychiatric services.
987
Longitudinal imaging and phenoconversion in the PARS
prodromal cohort
D. Jennings, M. Stern, A. Siderowf, S. Eberly, D. Oakes, K. Marek,
PARS Investigators (New Haven, CT, USA)
Objective: The objective of the Parkinsons Associated Risk Syn-
drome (PARS) study is to develop a strategy to identify a large-scale
cohort at risk for Parkinsons disease (PD) using sequential olfac-
tory testing and DAT imaging.
Background: The PARS cohort consists of 203 hyposmic and
100 normosmic subjects without a diagnosis of PD at baseline. Base-
line DAT imaging indicates 11% of hyposmic subjects have DAT
deficit (<65% of age expected putamen binding ratio) indicating
they may be at increased risk for developing PD. We report longitu-
dinal imaging and phenoconversion data at 4 years follow-up for the
PARS cohort.
Methods: Subjects completed baseline, 2-yr and 4-yr clinical and
123I--CIT/SPECT evaluations. Clinical evaluations (UPDRS, cogni-
tive testing, diagnosis assignment) were performed blind to imaging
and olfactory data. Change in striatal binding ratio (SBR) between
baseline, 2-yr and 4-yr imaging was compared based on olfactory
and DAT imaging status. Phenoconversion to PD, defined by the
clinical investigators best current diagnosis, was examined at 2-yr
and 4-yr visits.
Results: 203 hyposmics and 100 normosmics completed baseline
assessments, 262 completed 2-yr, 173 completed 4-yr visits. Among
hyposmics with a DAT deficit at baseline 35% (8/23) phenocon-
verted by year 2 and 13/23 (56%) phenoconverted by year 4. Mean
percent change in striatal SBR among hyposmic phenoconverters
was -16.9 (68.8) at yr 2 and -29.2 (614.7) at yr 4 compared to -2.0
(616.8) at yr 2 and 4.8 (616.6) at yr 4 for hyposmic non-
converters.
Conclusions: Longitudinal follow-up of the PARS cohort demon-
strates 56% phenoconversion among hyposmics with a baseline DAT
deficit within the 4-year follow-up period. Longitudinal DAT imag-
ing indicates that phenoconverters demonstrate an increased reduc-
tion in DAT compared to hyposmic non-converters. Additional
follow-up will allow for more precise estimation of the phenoconver-
sion rate and identification of markers that may predict the rate of
progression in the pre-diagnostic phase of PD.
988
Quantitative assessment of iron deposition in Parkinsons disease
using enhanced T2 star weighted angiography (ESWAN)
Q.S. Ji, S. Zhang, J.Z. Mao, Y.H. Han, M.Q. Yang, Z.W. Zhu, Q.S.
Zhu, Z. Xue (Wuhan, Peoples Republic of China)
Objective: Investigate the diagnostic value of ESWAN for Par-
kinsons disease(PD). Quantitative assessment of iron deposition in
Parkinsons disease using enhanced T2 star weighted angiography
(ESWAN).
S383
Background: Enhanced T2 star weighted angiography (ESWAN)
can be used for quantitative analysis of iron, and iron concentrations
in these regions in the brain may be represent the severity of PD.
Methods: We obtained ESWAN images from 48 primary PD
patients and 12 healthy individuals and the Unified Parkinsons dis-
ease Rating Scale (UPDRS) III assessment, Non-Motor Symptoms
Scale (NMSS)and the Mini Mental State Examination (MMSE) were
used to rate all the patients. The R* signal values can show the iron
deposition in the brain and the region of interests (ROI) included:-
substantia nigra, red nuclei, globus pallidus, putamina, caudate
nuclei, and thalami .
Results: The comparison of the R* signal values between the
ROI on the same side of the PD patients and in the control group
revealed significant differences in substantia nigra, red nuclei, and
putamina.There was significant difference between HY1 and HY2-4
patients in terms of the signal values of the substantia nigra. There
was a slight correlation between the R* signal values of the substan-
tia nigra of the PD patients (HY 1) and the UPDRS III ratings. No
correlation between the R* signal values in the PD patients and the
NMSS and MMSE scales have been found.
Conclusions: Iron concentrations in ROI may be represent the
severity of the motor symptom of PD, whether iron deposition at
some locations are related to the non-motor symptom remains a
problem for further investigation. ESWAN has special advantages in
determining iron deposition in the brain and allow for sensitive diag-
nosis of PD.
989
Longitudinal [11C]BF-227 PET study in MSA-C patients
A. Kikuchi, N. Okamura, M. Tashiro, S. Furumoto, T. Hasegawa, S.
Watanuki, K. Hiraoka, Y. Funaki, T. Baba, M. Kobayashi, N.
Sugeno, M. Konno, E. Miura, R. Oshima, S. Yoshida, R. Iwata, S.
Takahashi, H. Fukuda, Y. Itoyama, H. Arai, Y. Kudo, K. Yanai, M.
Aoki, A. Takeda (Sendai, Japan)
Objective: We aimed to study whether [11C] 2-(2-[2-dimethyla-
minothiazol-5-yl]ethenyl)-6-(2-[fluoro]ethoxy) benzoxazole (BF-227)
positron emission tomography (PET) can show time-dependent
changes of a-synuclein deposits in brain lesions in multiple system
atrophy (MSA) patients.
Background: The histopathological hallmark of MSA is the
appearance of glial cytoplasmic inclusions, which are mainly com-
posed of a-synuclein fibrils. Monitoring time-dependent changes of
in vivo a-synuclein will have a key role for the assessment of sever-
ity of pathological progression and therapy in MSA.
Methods: Four patients with probable MSA with predominant
cerebellar ataxia (MSA-C) without dementia and 15 aged normal
subjects were studied to examine the distribution of [11C]-BF-227 in
the brain. A Z-score map of individual PET images was created for
comparison between the mean and SD of the PET images of aged
normal controls for each voxel. A software program named the Easy
Z-Score Imaging System (e-ZIS) was used for this analysis.
Results: [11C]BF-227 PET showed time-dependent increases of
tracer uptake in brain resions such as the subcortical white matter
and from frontal to parietal cortex in all four MSA-C patients. These
distributions were consistent with the GCI-rich brain regions in post-
mortem patients.
Conclusions: Our data suggest that [11C]BF-227 PET might be a
suitable surrogate marker for monitoring intracellular a-synuclein
deposition in living brains with MSA-C.
990
Cognitive impairment and its structural correlates in the
Parkinsonian subtype of multiple system atrophy
J.S. Kim, J.J. Yang, D.K. Lee, J.M. Lee, J. Youn, Y.E. Huh, J.W. Cho
(Seoul, Korea)
Movement Disorders, Vol. 30, Suppl. 1, 2015
S384 POSTER SESSION
Objective: This study aimed to identify the existence of cognitive
impairments, different topographic patterns of morphological changes
in Parkinsonian subtype of multiple system atrophy (MSA-P) using
imaging analysis, and whether these morphological changes could be
associated with cognitive dysfunctions in MSA-P.
Background: Basically the DSM-IV criterion of dementia is a
not supporting feature for MSA diagnosis. However, recent stud-
ies indicate that patients with MSA-P experience cognitive
impairment.
Methods: We recruited 15 non-demented probable MSA-P
patients and 32 normal control (NC) subjects and they underwent
detailed neuropsychological testing and magnetic resonance imaging.
We analyzed morphological changes using cortical thickness analy-
sis, voxel-based morphometry (VBM), and cerebellar volumetry.
Multiple linear regression analysis was performed to evaluate the
correlation of each cognitive score with the mean thickness of signif-
icant cortical thinning clusters, mean gray matter density of VBM
clusters, and cerebellar volume.
Results: The scores on the digit span test, Seoul Verbal Learning
Test (immediate and delayed), phonemic Controlled Oral Word
Association test, and Stroop-color test were significantly lower in
MSA-P group than those in the NC group. We found two clusters
exhibiting significant cortical thinning in the right paracentral lobule
and parahippocampal gyrus. VBM analysis revealed significant gray
matter atrophy in the MSA-P group in the bilateral basal ganglia,
cerebellum, and temporal and frontal cortical areas. There were no
associations among cortical thinning, subcortical gray matter loss,
and cerebellar volume. Multiple linear regression analysis demon-
strated that cognitive dysfunction correlated significantly with thin-
ning in the neocortex, cerebellum, and striatum.
Conclusions: Our data demonstrate that cortical and cerebellar
atrophy and striatal degeneration are associated with cognitive
impairment in patients with MSA-P.
991
Diagnosis of Parkinsonism with 3T MR image of nigrosome-1:
Correlation between susceptibility-weighted imaging and 123I-FP-
CIT-SPECT findings
K.J. Kim, J.M. Kim (Seongnam, Korea)
Objective: To evaluate the diagnostic performance of nigrosome-
1 susceptibility-weighted MR imaging(SWI) in the diagnosis of
Parkinsonism.
Background: Nigrostriatal dopaminergic degeneration in Parkin-
sonism results in the loss of nigrosome-1, and this can be visualized
by SWI. However, how helpful is this imaging technique in diagnos-
ing Parkinsonism is not well known to date.
Methods: We evaluated the loss of nigrosome-1 in the patients
with Parkinsonism using SWI at 3.0 tesla. And the diagnostic per-
formance of this method was compared with 123I-FP-CIT-SPECT.
We recruited 34 controls and 122 patients with Parkinsonism, all of
whom underwent both imaging. Initially, clinical diagnosis of Parkin-
sonism, including Parkinsons disease, multiple system atrophy, and
progressive supranuclear palsy was made, and nigrostriatal dopami-
nergic degeneration was confirmed with 123I-FP-CIT-SPECT. Two
blinded observers interpreted the presence of nigrosome-1 on SWI,
and nigrostriatal dopaminergic degeneration was indicated if
nigrosome-1 was absent on SWI on at least either side. Comparing
with 123I-FP-CIT-SPECT, diagnostic accuracy of SWI detecting
nigrostriatal degeneration was evaluated. Chi-square test with SPSS
20 were used for statistical analysis, and p value < 0.05 was regarded
as statistically significant.
Results: Among 122 patients with Parkinsonism, 115 showed
bilateral nigrostriatal degeneration on 123I-FP-CIT-SPECT. And, 108
(99 with bilateral, and 9 with unilateral side) showed loss of
nigrosome-1 on SWI. Among 34 controls, 21 showed no loss of
nigrosome-1, while 13 showed loss of nigrosome-1 in either side.
Diagnostic sensitivity and specificity of SWI were 88.5% and 61.8%.
Movement Disorders, Vol. 30, Suppl. 1, 2015
Chi-square test revealed statistically significant correlation between
loss of nigrosome-1 on SWI and nigrostriatal degeneration on 123I-
FP-CIT-SPECT. (p < 0.001).
Conclusions: The loss of nigrosome-1 in 3T SWI reflects well
the nigrostriatal degeneration in Parkinsonism, and SWI can comple-
ment 123I-FP-CIT SPECT in the diagnosis of Parkinsonism. How-
ever, 123I-FP-CIT SPECT seems to detect the nigrostriatal
degeneration earlier than SWI.
992
Diagnosis of Parkinsonism by 7 Tesla MRI
J.M. Kim, K.J. Kim, Y.J. Bae, E. Kim, S.Y. Kang, E.S. Oh, H.J.
Jeong, S.E. Kim, Z.H. Cho, B.S. Jeon (Seongnam, Korea)
Objective: To evaluate the diagnostic performance of detecting
nigrosome-1 in the patients with Parkinsonism, and to assess the fea-
sibility of 7 T MRI in the clinical setting.
Background: High-field 7 T T2*-weighted imaging can visualize
the alteration of the nigrosome-1 in Parkinsonism.
Methods: Between December, 2011 and March, 2013, 7 T T2*-
weighted imaging was performed in normal control subjects and
patients (n 5 26) with Parkinsonism including idiopathic Parkinsons
disease (IPD, n 5 30), multiple system atrophy with predominant
Parkinsonism (MSA-P, n 5 5), multiple system atrophy with predom-
inant cerebellar ataxia (MSA-C, n 5 2), and progressive nuclear palsy
(PSP, n 5 3). Two blinded readers independently interpreted the pres-
ence of the nigrosome-1 on 7 T MRI. Readers agreement and diag-
nostic accuracy was calculated.
Results: Bilateral nigrosome-1 was intact in all normal control
subjects. The nigrosome-1 was bilaterally missing in all of the
patients with IPD, MSA-P, and PSP. Sensitivity and specificity for
the diagnosis of IPD, MSA-P, and PSP by the detection of the
nigrosome-1 was 100%, respectively. Intra- and inter-observer agree-
ment was excellent (j 5 1). As for the patients with MSA-C, both 2
patients had intact nigrosome-1.
Conclusions: The loss of nigrosome-1 on 7 T T2*-weighted
imaging provides excellent diagnostic performance for Parkinsonism.
The diagnosis of MSA-C using the nigrosome-1 should be cautious,
since the nigrosome-1 can be intact in the patients with MSA-C.
993
A functional neuroradiological study in an adult case of beta-
propeller protein-associated neurodegeneration
S. Kumada, I. Hayakawa, Y. Nakata, E. Yoshida-Kasai, S. Uchino, Y.
Hachiya, E. Kurihara, F. Yokochi (Tokyo, Japan)
Objective: To determine the pathophysiological basis of
dystonia-Parkinsonism in an adult patient with beta-propeller protein-
associated neurodegeneration (BPAN).
Background: BPAN is a recently established subtype of neurode-
generation with brain iron accumulation, caused by mutations in the
autophagy gene WDR45. While patients show nonprogressive intel-
lectual impairment during childhood, dystonia-Parkinsonism and
dementia rapidly progress in adulthood.
Methods: Our patient is a 35-year-old woman with genetically
confirmed BPAN. She presented with mental retardation in early
childhood, which was static until age 26, when she developed
dystonia-Parkinsonism and cognitive decline. She was treated with
levodopa from age 27, which improved both her motor function and
mental activity. However, peak-dose dyskinesia appeared at age
32, progressing over the following years, necessitating reduction of
levodopa. At present she is bedridden with generalized rigidity. Lev-
odopa still shows partial efficacy in reducing her rigidity, but causes
severe dyskinesia. Brain MRI and dopamine transporter single-
photon emission computed tomography (DAT-SPECT) was
performed.
 POSTER SESSION
Results: Brain MRI showed severe cerebral and cerebellar atro-
phy, and iron accumulation in the bilateral globus pallidus (GP), sub-
stantia nigra (SN), and thalamus. T1-weighted images revealed
regions of hyperintensity in the SN with a central band of hypointen-
sity. Hypointense lesions were also noted in the GP. High-resolution
neuromelanin images obtained by a 3-T scanner demonstrated loss of
high signal intensity, which is normally seen in the locus coeruleus
(LC). DAT-SPECT revealed significant reduction in striatal uptake
of the tracer.
Conclusions: Our study showed severe impairment of the nigro-
striatal dopaminergic pathway in a patient with advanced BPAN.
This may be the principal cause of dystonia-Parkinsonism, including
levodopa-induced dyskinesia, in this patient. Loss of noradrenergic
LC neurons may also be involved in the pathogenesis.
994
The usefulness of magnetic resonance imaging on Parkinsonian
multiple system atrophy before the occurrence of autonomic
dysfunction
W.W. Lee, J. Shin, H.J. Kim, H. Park, C.W. Shin, B.S. Jeon (Seoul,
Korea)
Objective: To examine the usefulness of brain MRI as an early
diagnostic tool of multiple system atrophy with predominant Parkin-
sonism (MSA-p) before the clinical diagnostic criteria are met.
Background: MSA-p can be difficult to be differentiated from
Parkinsons disease (PD), especially in early phase. Most studies on
magnetic resonance image (MRI) as a tool to diagnose MSA have
been done in an advanced stage, virtually when there is no need to
perform MRI to make a diagnosis. Recent MRI developments such
as 3.0T MRI and susceptibility-weighted image have provided a
more sensitive tool to detect iron deposits.
Methods: We included subjects by the following criteria: Parkin-
sonian patients who did not meet the criteria of probable MSA-p at
the time of MRI evaluation, but later met the criteria of MSA-p dur-
ing the follow-up. Thirty-two PD patients served as control. Two
neurologists, blinded to clinical information, reviewed the brain
MRI.
Results: Forty-four cases of probable MSA-p were included (28
with 1.5T MRI, and 16 with 3.0T MRI). Of 44 cases, 29 (64.4%)
had any putaminal changes. Brainstem or cerebellar abnormalities
were found in 10 patients (22.2%), among whom 9 patients (20%)
had putaminal changes also. Among 32 PD patients, there were 4
putaminal abnormalities (1 with putaminal atrophy, and 3 with low
signal intensities in the posterolateral putamen). When 3.0T MRI
(n 5 16) was analyzed, sensitivity and specificity against PD con-
trols were as follows; 93.8% vs 87.5% for putaminal changes,
31.3% vs 100% for brainstem/cerebellar changes, and 93.8% vs
87.5% for the combination of putaminal changes and brainstem/cer-
ebellar changes.
Conclusions: MRI is helpful in making the diagnosis of MSA-p
even when a diagnostic criteria is not met. 3.0T MRI raised the sen-
sitivity and specificity in our study.
995
Longitudinal assessment of subcortical volume and iron content
in two variants of multiple system atrophy
J.H. Lee, T.H. Kim, T.H. Kim (Yangsan-si, Gyeongsangnamdo,
Korea)
Objective: This study aimed to investigate whether there are dif-
ferences in progression of subcortical atrophy and iron deposition
between the two variants of multiple system atrophy (MSA).
Background: Longitudinal assessment using quantitative MRI
may help to increase accuracy of diagnosis and characterize the time
course of the degenerative process.
S385
Methods: Two serial MRI including T1-weighted and R2*
images were analyzed in 8 patients with Parkinsonian variant MSA
(MSA-p), 9 patients with cerebellar variant MSA (MSA-c), and 15
patients with Parkinsons disease (PD). The time interval between
baseline and follow-up investigations was 18.1 6 3.0 SD months in
MSA-p, 17.9 6 2.7 SD months in MSA-c, and 24.1 6 1.8 SD months
in PD patients, respectively. The R2* values and volumes were cal-
culated for the selected subcortical structures (caudate nucleus, puta-
men, globus pallidus, and thalamus) using an automated region
based analysis. Annual change rate (ACR, %) estimates were calcu-
lated from baseline and follow-up parameters.
Results: In MSA-p patients compared with PD, significant higher
atrophy rates were observed in all subcortical structures. In MSA-c,
there was greater volume loss in the globus pallidus and thalamus
over time compared to PD. Direct comparison of two variants
showed significantly more rapid progression of putaminal atrophy in
MSA-p than in MSA-c. With regard to R2* changes, a significant
increase at follow-up, and a higher rate of progression was identified
in the putamen of MSA-p group. There was no subcortical region
with significant differences in R2* values between MSA-c and PD.
Conclusions: This longitudinal study revealed different progres-
sion rates of MRI markers between MSA-p and MSA-c. Putaminal
iron accumulation may be a more specific for MSA-p.
996
DaTscan: Correlation of clinical phenotype and and scan
concordance: A retrospective study
K.H. Longfellow, G. Hu, S. Minoshima, S. Elman, D. Lewis (Seattle,
WA, USA)
Objective: To investigate how clinical phenotype correlates with
objective visualization of dopaminergic dysfunction through DaTscan
on diagnostically challenging patients, and the concordance between
neuroimaging abnormalities and clinical symptoms. We quantified
clinical symptoms in patients who undergo DaTscan, and analyzed
concordance between clinical observation and scan result.
Background: Although there is an abundance of research on the
sensitivity and specificity of DaTscan in diagnosing Parkinsons dis-
ease, much less is known about how DaTscan technology mirrors
clinical impression. Additionally, there is a paucity of literature
regarding the discrepancies that can arise between asymmetry on
clinical exam and expected side of greatest disease burden visualized
through Datscan (Concordance or Discordance).
Methods: In this retrospective study, patients who underwent
DaTscan at the University of Washington Medical center, Harborview
Medical Center, and Veterans Administration (Puget Sound) will be
identified. We aim to quantify demographic features of those under-
going DaTscan, including the most common clinical symptoms at
scan request, the the concordance between clinical phenotype and
Datscan results.
Results: [figure1]
When the Dominant side was effected symptomatically, DaTscan
was concordant 78% of the time. Conversely when the non-dominant
hemi-body was clinically symptomatic, DaTscan was concordant
only 22% of the time.
Currently in collection: Neuroradiographic quantification of
degree of asymmetry.
Conclusions: 67% of the time when the scan was discordant
symptoms manifest on the non-dominant hemi-body.
Perhaps the non-dominant side has a lower ability to cope with
disease burden and symptoms display despite less observable dopa-
minergic loss.
With regard to clinical features and correlation (When reported
positive) with Datscan results, postural instability was reported rela-
tively less then other cardinal features, however, when positive
did correlate highly (73%) to and abnormal Datscan. Postural insta-
bility may be a relatively good clinical indicator of dopaminergic
dysfunction.
Movement Disorders, Vol. 30, Suppl. 1, 2015
Fig. 1. (996).

Fig. 2. (996).
 POSTER SESSION
997
The role of the frontal lobe in complex walking tasks in healthy
older adults and patients with Parkinsons disease: An fNIRS
study
I. Maidan, H. Bernad-Elazari, F. Nieuwhof, M. Reelick, N. Giladi, J.
Deutsch, J. Hausdorff, A. Mirelman (Tel Aviv, Israel)
Objective: To investigate changes in frontal activation during
dual tasking (DT) and obstacle negotiation between healthy older
adults and subjects with PD.
Background: Gait is influenced by higher order cognitive and
cortical control mechanisms. Recent studies used functional near
infrared spectroscopy (fNIRS) to examine frontal lobe activity during
walking, reporting increased oxygenated hemoglobin (HbO2) levels
during walking while DT, compared to usual walking. Previous work
also showed that motor-cognitive deficits are exaggerated with aging
and Parkinsons disease (PD). Nonetheless, the role of frontal activa-
tion during complex walking tasks is largely unknown.
Methods: 20 healthy older adults (69.7 6 1.3 yrs) and 47 patients
with PD (71.7 6 1.1 yrs) were studied. Frontal brain activation of
Brodmans Area 10 was assessed using an fNIRS system and gait
was assessed using an electronic walkway. Assessments included:
walking in a self-selected speed; walking while serially subtracting
3s (SS3s); walking while stepping over 5 obstacles; and standing
while SS3s. Data was collected from 5 walks of 30 meters in each
condition. Repeated Measures Analysis of Variance tested changes
between conditions and groups. Post hoc analysis was used to assess
changes between walking conditions.
Results: Significant differences were observed in HbO2 levels
between all conditions (p[thinsp]<0.001). No differences were seen
between groups (p50.79), however, interaction between group and
condition in HbO2 was significant (p50.004). Both groups tended to
increase frontal activation during walking while stepping over obstacles
(p<0.051), however, only older adults increased frontal activation dur-
ing walking while SS3s (p50.016). The older adults had a lower DT
cost for gait speed (p<0.001) and better performance of SS3s
(p50.034) than the subjects with PD. The HbO2 level during walking
while SS3s was correlated with the performance of SS3s in subjects
with PD (r=0.332, p50.031), but not in older adults (p50.408).
Conclusions: This study provides evidence that walking while
stepping over obstacles is associated with frontal brain activation in
both healthy older adults and subjects with PD, while walking while
SS3s increased frontal activation only in healthy older adults. It is
unclear whether the absence of a change in HbO2 during DT in sub-
jects with PD is the cause or effect of lower DT performance.
998
Midbrain MR planimetry in neurodegenerative Parkinsonism:
Comparison between 1.5 and 3 Tesla MRI
S. Mangesius, A. Hussl, B. Heim, C. M
uller, B. Pinter, E. Reiter, M.
Schocke, W. Poewe, K. Seppi (Innsbruck, Austria)
Objective: To compare m/p-ratio and MRPI(1,2) obtained by 1.5
versus 3 Tesla scanners and to determine the diagnostic accuracy of
m/p-ratio and MRPI to differentiate between PSP, PD, MSA and HC
in both, 1.5 vs. 3T MRI.
Background: The midbrain-to-pons-area-ratio (m/p-ratio) and the
magnetic resonance Parkinsonism index (MRPI) using MR planime-
try on routine 1.5 Tesla MRI have been successfully applied to dif-
ferentiate Progressive Supranuclear Palsy (PSP) from Parkinsons
disease (PD), Multiple- System-Atrophy (MSA) and healthy controls
(HC). In the differential diagnosis of Parkinsonism 3 Tesla MRI has
the potential of enhanced spatial resolution, but the use of MR
planimetry in 3T MRI has not been evaluated yet.
Methods: Blinded MR planimetry to determine MRPI and m/p-
ratio in patients with neurodegenerative Parkinsonism (PD: n542,
age: 65 6 9, female/male ratio: 38/62%, H&Y: 3 6 0.6; MSA: n522,
age: 62 6 9, female/male ratio: 46/55%, H&Y: 3 6 0.9; PSP: n521,
S387
age: 67 6 6; female/male ratio: 29/71%, H&Y 3 6 0.7) and healthy
controls (n539, age: 61 6 9, female/male ratio: 61/39%) using scan-
ners with 2 different strength fields (1.5 and 3 Tesla). According to a
previously published paper of our group(2), abnormal MRPI was
considered as equal to or higher than 14.38 and abnormal m/p-ratio
as lower than 0.18.
Results: The intraclass correlation coefficients (two-way mixed
effects model) of both MRPI and m/p-ratio between 1.5 and 3 Tesla were
high (MRPI: 0.97, 95%CI:0.95-0.98; m/p-ratio: 0.98, 95%CI:0.97-0.99).
There were significant group differences between PSP and the
non-PSP group for both MRPI and m/p-ratio in both 1.5 and 3T (all:
p<0.001). PSP patients had a MRPI of 22.9 and 21.6 with 1.5 and
3T, respectively, whereas the non-PSP group showed a MRPI of
12.4 and 12.5. The m/p-ratio in the PSP group was 0.125 for both,
1.5 and 3T, and 0.233 and 0.232 for the non-PSP group, respectively.
The sensitivity to detect PSP for an abnormal MRPI was 95% and
specificity 79% on 3T MRI and 95% and 77% on 1.5T, respectively.
Also, the m/p-ratio showed similar diagnostic accuracy in detecting
PSP for both 1.5 and 3T MRI (1.5T: sensitivity 86%, specificity
90%; 3T: sensitivity 91%, specificity 88%).
Conclusions: MRPI and m/p-ratio have similar diagnostic accura-
cies when obtained by MRI using 3 Tesla and 1.5 Tesla MR
machines.
(1)Quattrone A, et al., Radiology 2008;246:214-221. (2)Hussl A,
et al., Mov Disord 2010;25(14):2444-2449.
999
Automatic and non-automatic gait: Identifying two different
networks using functional MRI
V. Marchal, J. Sellers, C. Gallea, E. Bertasi, R. Valabregue, P.
Leboucher, B. Lau, M.L. Welter, E. Bardinet, C. Karachi (Paris,
France)
Objective: To identify which brain areas are involved in auto-
matic gait and in gait with obstacles in healthy volunteers using
fMRI.
Background: Gait is an automatic motor program involving the
cortex, basal ganglia, brainstem and spinal cord. The mesencephalic
locomotor region (MLR) of the brainstem, which contains the pedon-
culopontine (PPN) and cuneiform (CN) nuclei, receives cortical
inputs and drives spinal cord patterns. The MLR is thought to control
gait programs, and recent evidence has implicated an MLR dysfunc-
tion in gait disorders, especially in freezing of gait, which is often
provoked by obstacles that interrupt the automatic gait program.
Methods: We used a virtual reality task mimicking walking
down a hallway. We presented virtual gait trials without and with a
doorway, each at two different speeds. We trained 20 healthy volun-
teers to first walk down a real hallway and second to use the virtual
environment. As a control, we used a virtual task mimicking the sub-
ject standing on a moving treadmill, without and with a doorway at
the same two speeds. We used a questionnaire to score each sub-
jects impression of walking during the virtual reality.
Results: Subjects rated their impression of walking on average
6,38/10 (r=0,08). 4/20 subjects did not exhibit any cerebral activa-
tion and their reaction times showed peaks corresponding to episodes
of drowsiness during the task. Thus, we performed second level anal-
yses in 16/20 subjects. A speed contrast did not yield any significant
brain activations (p<0,001 uncorrected for multiple comparisons).
Thus, we conducted an ANOVA (task x obstacle) ignoring speed. A
contrast of virtual gait versus moving walkway yielded activation of
a motor/premotor network including bilateral primary motor and pre-
motor cortices of the limbs, supplemental motor area, cerebellum,
motor putamen, thalamus and the reticular formation of the brain-
stem including the left PPN. The same contrast in the presence of a
doorway yielded the same network at the cortical and basal ganglia
levels, with the addition of right STN activation. In the MLR, the
activation was located bilaterally in the CN and not in the PPN.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S388 POSTER SESSION
Conclusions: These data support the hypothesis that automatic
gait involves mainly motor and premotor cortices, cerebellum, basal
ganglia and the PPN, whereas gait with obstacles activates the sub-
thalamic and CN nuclei, which may encode environmental cues for
adaptive locomotion.
1000
Mechanisms underlying impaired self-agency in functional
Movement Disorders: A resting state fMRI study
C.W. Maurer, S. Horovitz, K. LaFaver, M. Hallett (Bethesda, MD, USA)
Objective: To assess the neural mechanisms underlying lack of
self-agency in patients with functional Movement Disorders (FMD).
Background: The abnormal movements produced by patients with
FMD are generated by normal voluntary motor pathways, but are per-
ceived by patients as being involuntary. This lack of self-agency is
one of the key features of FMD. The right temporo-parietal junction
(TPJ) has been proposed to play an important role in self-agency by
comparing internal predictions of movement with actual external
events, acting as a mismatch detector. Although task-based fMRI
studies have previously demonstrated hypoactivity of the right TPJ in
FMD patients, this region has not been examined in the resting state.
Methods: Resting state multi-echo BOLD fMRI and MP-RAGE
images were obtained in 35 patients with clinically definite FMD
and 35 age- and sex-matched healthy controls using a 3T Skyra Sie-
mens scanner. Pre-processing was performed using the AFNI tool
meica.py. Group-wise comparison between FMD patients and healthy
controls was performed using AFNI GroupInstaCorr with the right
TPJ as seed region-of-interest. Age, sex, BDI depression scores and
childhood trauma scores were included as potential covariates.
Results: As compared to controls, FMD patients demonstrated
decreased functional connectivity (p<0.05 corrected) between the
right TPJ and the bilateral precentral gyri, left declive, bilateral
insula, left middle cingulate, bilateral middle temporal gyri, right
posterior cingulate, and left superior frontal gyrus. There was no
effect of age, sex, or BDI score. Patients exhibited increased func-
tional connectivity between the right TPJ and the left inferior parietal
region with increasing levels of childhood emotional trauma.
Conclusions: We propose that the diminished functional connec-
tivity between the right TPJ and the above-mentioned motor regions
reflects impaired feedforward with the brains mismatch detector.
Furthermore, diminished functional connectivity between the right
TPJ and the bilateral insula may reflect impaired intentional binding.
We suggest that these mechanisms may contribute to the reduced
sense of agency in FMD patients.
1001
Longitudinal functional MRI studies of Parkinsons disease
patients with and without mild cognitive impairment
O. Monchi, M. Al-Azzawi, A. Nagano-Saito, B. Mejia-Constain, C.
Degroot, A. Hanganu, A.L. Lafontaine (Calgary, AB, Canada)
Objective: To (1) compare the evolution of patterns of neural
activity observed with functional Magnetic Resonance Imaging
(fMRI) in Parkinsons disease (PD) patients with and without mild
cognitive impairment (MCI), and (2) find out which patterns of activ-
ity are associated with future cognitive decline.
Background: Compared to PD-nonMCI, PD-MCI has been
linked with greater structural and functional neural decline. Using
fMRI, we reported previously deceased activation in the lateral pre-
forontal cortex (PFC) and the caudate nucleus in PD-MCI compared
with PD-nonMCI patients at the same stage of the disease (Nagano-
Saito et al., 2014). However, we had not investigated the longitudinal
effect of the early presence of MCI in PD with fMRI, and the pat-
terns of activity associated with subsequent cognitive decline.
Methods: 24 non-demented patients with PD underwent a neuro-
psychological assessment according with level II MDS recommenda-
Movement Disorders, Vol. 30, Suppl. 1, 2015
tion, and were separated in two groups: twelve with and twelve
without MCI and also performed the Montreal Cognitive Assessment
(MoCA). During the following week they underwent an fMRI ses-
sion performing the Wisconsin Card Sorting Task. They were invited
for a second assessment (neuropsychological and fMRI) 19 months
after. In a first analysis the patterns of neural activity between the
two time points for each of the 2 groups was compared. In another
analysis, all patients were combined and the patterns of neural activ-
ity in the initial session was correlated with the evolution of the
MoCA score between the two time points.
Results: When planning the set shift, PD-nonMCI patients
recruited the regions associated with this process (PFC and caudate
nucleus), but activity in these regions reduced over time. In contrast,
activity in different cortical areas of the PD-MCI patients increased
over time. Finally, for all patients, lower activity at time 1 in the hip-
pocampus and the thalamus during planning the set-shift, correlated
significantly with MoCA decline.
Conclusions: These results might reflect the possibility that patients
with PD-MCI have reached the limit of their neural resources associ-
ated with executive processes, and that neural reorganization occurs
with time. Importantly, our results support the possibility that the lack
of hippocampal compensation in PD may be reflective of subsequent
cognitive decline as had been suggested by Carbon et al., (2010).
1002
Anatomical differences in white matter integrity between
idiopathic normal pressure hydrocephalus and secondary
obstructive hydrocephalus: Diffusion tensor study
N. Nishida, H. Toda, R. Okumura, H. Hashikata, N. Ikeda, Y. Kang,
M. Ishikawa, K. Iwasaki (Osaka, Japan)
Objective: The aim of this study was to determine the distribu-
tion of white-matter-integrity modification in chronic hydrocephalus
that manifest higher order gait disturbance.
Background: Gait disturbance in chronic hydrocephalus is most
treatment-responsive symptoms yet its precise mechanism is
unknown. Moreover, gait disturbance appears in different types of
chronic hydrocephalus.
Methods: We assessed consecutive 13 patients (age 75.8 6 4.2)
with idiopathic normal pressure hydrocephalus and 11 patients (age
53.9 6 18.6) with secondary obstructive hydrocephalus revealed by
gait symptoms. They underwent 3.0 T MR imaging including a DTI
protocol (32 gradient directions with a b value of 1000s/mm2).
Image pre-processing was performed using FSL, following the TBSS
protocol, and threshold-free cluster enhancement was used to assess
significant differences between the two groups.
Results: In patients with idiopathic normal pressure hydrocepha-
lus compared with secondary obstructive hydrocephalus, the FA val-
ues were significantly decreased in anterior thalamic radiation in the
periventricular white matter while significantly increased in unci-
nated fasciculus and superior cerebellar peduncle.
Conclusions: Similarly manifesting with gait disturbance and
radiological ventriculomegaly, idiopathic normal pressure hydroceph-
alus and secondary obstructive hydrocephalus are morphologically
dissimilar. Idiopathic normal pressure hydrocephalus was character-
ized with high-convexity tightness, whereas secondary obstructive
hydrocephalus shows third ventricular ballooning. Though prelimi-
nary, our data shows the complexity of anatomical substrate underly-
ing the higher-order gait disturbance.
1003
GABA (gamma-aminobutyric acid) in essential tremor: An MR
spectroscopy study
P. Panyakaew, H.J. Cho, S. Horovits, M. Hallett (Bethesda, MD, USA)
Objective: To explore the role of GABA in the pathophysiology
of ET by using MR spectroscopy.
 POSTER SESSION S389

Background: Evidence from pathology, electrophysiology, imag- position. The GABA1/Cre, Glx/Cre ratios, corrected for tissue compo-
ing and drug therapies lead to the hypothesis of disturbances of sition, were compared between two groups by using t-test.
GABA in the cerebellum in ET. Data from GABA-based neuroimag- Results: The demographic data are shown in table1.
ing are limited.
Methods: In an ongoing study, seven ET patients and 4 controls
were scanned on a 3T GE MRI scanner with a 32-channel coil. High- Demographic data of ET and controls
resolution T1-weighted images obtained with a magnetization-prepared
Characteristics ET (N=7) Controls (N=4) p values
gradient-echo sequence (MPRAGE) were used for localization and tis-
sue composition estimation. Two voxels of interest (30x30x20mm) Age 61.00 6 9.69 62.75 6 6.24 0.76
were centered over the right cerebellar hemisphere and the mid frontal Female (%) 2 (20%) 2 (50%) 0.48
lobe, as control. [figure1] We measured metabolites using the point-
Disease duration 30.00 6 21.04
resolved spectroscopy (PRESS) pulse sequence and the J-edited method
Age of onset 31.00 6 24.39
(TR/TE 1500/68ms, 768 acquisitions, 20 min scanning time). GABA TETRAS ADL score 22.43 6 4.76
peak, including macromolecules (GABA1) at 3 ppm and Glx (gluta- TETRAS performance 17.14 6 4.67
mate and glutamine) at 3.8 ppm were fitted using in-house software
score
written in IDL by JWvdV. Both peaks were referenced to Creatine
TETRAS total score 39.57 6 8.16
(Cre) as it has steady concentration in the brain. Using FMRIB and
AFNI software libraries, we calculated the percentage of CSF, grey and ET 5 essential tremor, TETRAS 5 TRG essential tremor rating
white matter in each voxel to control for difference in voxel tissue com- assessment scale

Fig. 1. (1003).

The results of GABA spectroscopy parameters in ET and controls.

Parameters ET (N=7) Controls (N=4) P values

Cerebellum (CB)
GABA1/Cre 0.0889 6 0.02 0.0887 6 0.01 0.99
Corrected GABA1/Cre with WM 0.1325 6 0.04 0.1387 6 0.03 0.77
Corrected GABA1/Cre with GM 0.3065 6 0.13 0.2583 6 0.07 0.52
Glx/Cre 0.0467 6 0.03 0.0520 6 0.01 0.70
%WM 0.67 6 0.11 0.63 6 0.07 0.51
%GM 0.316 0.09 0.34 6 0.09 0.55
%CSF 0.02 6 0.01 0.03 6 0.01 0.47
Mid frontal lobe (MF)
GABA1/Cre 0.1055 6 0.01 0.1158 6 0.05 0.30
Corrected GABA1/Cre with WM 0.2056 6 0.02 0.2249 6 0.05 0.37
Corrected GABA1/Cre with GM 0.2173 6 0.03 0.2389 6 0.04 0.28
Glx/Cre 0.0791 6 0.01 0.0888 6 0.02 0.28
%WM 0.41 6 0.03 0.39 6 0.03 0.56
%GM 0.386 0.02 0.37 6 0.03 0.24
%CSF 0.21 6 0.04 0.24 6 0.05 0.33
Ratio of corrected GABA with WM in CB/MF 0.65 6 0.21 0.62 6 0.09 0.76
Ratio of corrected GABA with GM in CB/MF 1.43 6 0.68 1.11 6 0.35 0.41
GABA (gamma-aminobutyric acid), Glx (Glutamine and glutamate), Cre (Creatine), WM (White matter), GM (Grey matter)

Movement Disorders, Vol. 30, Suppl. 1, 2015

S390 POSTER SESSION
Fig. 2. (1003).
There were no significant differences in GABA1/Cre, GABA1/
Cre corrected for tissue composition (GM and WM) and Glx/Cre in
both cerebellum (CB) and mid frontal lobe (MF).
Percentages of GM, WM and CSF in each voxel were not differ-
ent between ET and controls. There was a trend of higher corrected
GABA1/Cre with GM in cerebellum in ET than controls. A ratio of
corrected GABA1 with GM in CB/MF was also higher in ET than
controls. For all subjects, GABA1/Cre, corrected GABA1/Cre with
GM and a ratio of GABA1 in CB/MF negatively correlated with
age. [figure2] For the ET group, there were no correlation between
any GABA spectroscopy parameters with age, disease duration and
TETRAS score.
Conclusions: Our pilot study suggests that there might be no differ-
ences in GABA composition in cerebellum between ET and controls
using MR spectroscopy. This would indicate either no loss of GABA in
CB in ET or the method is just not sensitive enough to identify differ-
ences. However, a decline with age may be demonstrable.
1004
First Latin American experience in the assessment of striatal
dopaminergic uptake in patients with Parkinsons disease by
means of co-registered 18F-DOPA PET/CT and MRI images
M.C. Peralta, D. Menna, M. Aguilar, H. Corradini, A. Perez, A.
Valda, F. Biafore, J.A. Gili, M.J. Bastianello (Caba, Argentina)
Objective: To evaluate the striatal dopaminergic function using
18F-DOPA PET/CT scan along with MRI.
To quantify the dopaminergic deficit at the caudate and putamen
nucleus in patients with moderate to severe Parkinsons disease (PD)
compared to control subjects.
Background: The differential diagnosis of PD in cases of neuro-
degenerative or basal ganglia disorders with similar clinical features
constitutes a diagnostic challenge.
Movement Disorders, Vol. 30, Suppl. 1, 2015
A recent study showed the novel finding of only 26% accu-
racy for a clinical diagnosis of PD in untreated or not clearly
responsive subjects, highlighting the low diagnostic accuracy of
early PD (1).
Methods: Control subjects and PD patients matched for age and
H&Y stage III-IV were evaluated at day 1 at the Neurology depart-
ment of CEMIC University Hospital. On day 2 PET scan and MRI
were performed at the Imaging Department.
PD patients stopped their antiParkinsonian medications 12 hours
before scanning. All subjects received 150 mg carbidopa before
administration of 18F-DOPA (0.05- 0.07 mCi/kg). Acquisition was
performed 75 minutes postinjection in a PET/CT Philips Gemini 64
TF. All participants received volumetric MRI; images were seg-
mented in caudate, putamen and cerebellum. The resulting segmen-
tation was applied to a co-registered PET-MRI for quantification of
volume and total number of counts/structure. Concentration uptakes
in caudate and putamen were normalized to the cerebellum. A rela-
tive loss index was calculated as the percentage of patient uptake
decrease compared to controls.
Results: There were 12 patients, mean age=65 ys old (41-80);
male/female=9/3; mean PD duration=9.2 y (6-14): H&Y stage III
(n510), IV (n52), UPDRS III=32 ON (21-48) and 7 control sub-
jects, mean age=55 ys old (37-81); male/female=4/3.
The mean normalized uptake in left/right caudate/putamen in
PD patients was 1.24 6 0.30, 1.28 6 0.28, 1.34 6 0.12 and
1.33 6 0.11 respectively and 1.70 6 0.27, 1.71 6 0.27, 2.20 6 0.22
and 2.27 6 0.20 in the control group, p<0.0001. The loss index in
PD patients for left and right caudate/putamen was 27% and 22%
and 39% and 41%.
Conclusions: This is the first study on PET-CT/MRI biomarker
for PD in Argentina. PD patients showed significant lower uptake
values of 18F-DOPA in striatal structures compared to controls.
18F-DOPA PET-CT/MRI is a useful biomarker to reliably deter-
mine dopamine deficient Parkinsonism.
 POSTER SESSION S391

1005
Withdrawn by Author

1006
Transcranial sonography of the substantia nigra in Parkinsons
disease (PD) and controls: Distinguishing PD and controls by two
different measurement strategies
M. Pondal, A.E. Lang, C. Marras (Toronto, ON, Canada)
Objective: To establish a cut-off of SNs area and define the per-
formance of this cut-off for distinguishing PD patients from controls
in our practice using two different measurement strategies.
To investigate relationship between SN hyperechogenicity and
their demographic and clinical features.
Background: The characteristic finding in TCS in Parkinsons
disease (PD) patients is a hyperechogenic substantia nigra (SN). It is
recommended that each laboratory determines its cut-off value for
SNs hyperechogenicity. Techniques for encircling the hyperecho-
genic area are not precisely defined.
Methods: Consecutive PD patients attending the Movement Dis-
orders clinic and their accompanying persons were invited to partici-
pate. Measurements of SN area were performed at the time of the
study (live) on each subject by one or both neurologists
independently. Fig. 2. (1006).
The larger side or unilateral measurement of each case was used
in the analysis.
Two different SNs measurement techniques were performed to
find a strategy that provided the best discriminating ability between from controls for a SNs area of 0.14 cm 2 [figure1] and measure-
PD and controls: ments technique 2 a sensitivity of 59% and a specificity of 80% in
1. SN encircled following closely the edges of the hyperechoge- discriminating PD from controls for a SNs area of 0.19 cm 2 [fig-
nicity, summing the cross-sectional area of any regions encircled. ure2]. SN hyperechogenicity was not associated with side more
2. SN encircled including all the hyperechogenicity in a single affected, age at PD onset, age at examination, gender or handedness.
region. A positive trend between SN hyperechogenicity and duration of
Results: SNs echogenic area (cm2) was larger in PD than in con- symptoms was observed.
trols with both measurements techniques. 1: PD mean 0.16 6 0.06, Conclusions: SN hyperechogenicity is greater in PD than con-
controls 0.09 6 0.04, p<0.0001 and technique 2: PD 0.21 6 0.07, trols. However, at cut-offs that provide adequate specificity, the sen-
controls 0.14 6 0.06, p<0.0001. Measurement technique 1 showed a sitivity of this technique is relatively low in our experience. We did
sensitivity of 59% and a specificity of 87% in discriminating PD not find associations between SN echogenicity and major demo-
graphic or clinical features.

1007
Neural substrates for head movements in cervical dystonia: A
functional magnetic resonance imaging study
C.N. Prudente, R. Stilla, S. Singh, C. Buetefisch, X. Hu, E.J. Hess, K.
Sathian, H.A. Jinnah (Atlanta, GA, USA)
Objective: To delineate the neural basis for abnormal head move-
ments in individuals with cervical dystonia (CD).
Background: CD is characterized by excessive involuntary con-
tractions of neck muscles. Current understanding of the neuroana-
tomical basis of CD is extremely limited. Previous brain imaging
studies of CD have been restricted to investigating brain activity dur-
ing tasks unrelated to head movements because scans cannot be con-
ducted when the head is moving. For similar reasons, the ability to
study the neural controls of head movements in normal individuals is
also limited. By using a novel approach to examine the patterns of
brain activity associated with isometric head movements in healthy
controls and individuals with CD, this study addressed the much
needed knowledge of the neural controls of normal and abnormal
head movements.
Methods: Functional magnetic resonance imaging scans were
performed during isometric head rotation against an immobile sup-
port. During isometric tasks, muscle contractions are maintained for
a few seconds without an actual movement. This protocol has been
Fig. 1. (1006). previously used to delineate active brain regions in other types of

Movement Disorders, Vol. 30, Suppl. 1, 2015

S392 POSTER SESSION
movements, such as those involving the hands. Our experiments
included isometric head and hand tasks. Isometric hand tasks were
examined as a positive control and to establish relative locations of
head and hand regions under isometric conditions.
Results: Sixteen CD individuals and 17 controls participated in
the study. All subjects were able to complete the tasks without elicit-
ing head movements above accepted thresholds. Regions showing
significant changes during isometric hand tasks in both groups
included the contralateral primary motor cortex (M1), somatosensory
cortex (S1) and basal ganglia, bilateral SMA and ipsilateral cerebel-
lum. Isometric head tasks in controls showed significant activation of
contralateral medial M1, bilateral SMA and basal ganglia, and ipsi-
lateral cerebellum. A similar activation pattern was observed in CDs,
except that no significant activation in M1 was detected. Whole-
brain and regions of interest analysis for between group comparisons
are currently ongoing.
Conclusions: The findings will delineate brain regions involved
in normal control of head movements, as well reveal abnormalities
associated with CD. Furthermore, findings will point to target brain
areas for developing potential treatment strategies.
1008
Region-of-interest analysis of multimodal MR imaging at 3 Tesla
differentiating between Parkinso ns disease (PD) and atypical
Parkinsonian syndromes (APS)
E. Reiter, C. Mueller, B. Pinter, R. Esterhammer, W. Poewe, C.
Scherfler, K. Seppi, M. Schocke (Innsbruck, Austria)
Objective: To differentiate between PD and APS based on
region-of-interest (ROI) analysis of diffusion tensor imaging (DTI)
and relaxometry.
Background: Several previous studies indicated that diffusion
tensor imaging (DTI) detects micro-structural damages and relaxom-
etry quantifies iron overload in PD and APS. We performed DTI
analysis and relaxometry on different brain regions including caudate
nucleus (NC), putamen (PU), thalamus (TH), globus pallidus (GP),
corpus callosum (CC), dentate nucleus (ND), middle cerebellar
peduncle (MC) and substantia nigra (SN).
Methods: 51 healthy controls (HC) as well as 54 PD (disease
duration  5 years), 23 multiple system atrophy (MSA) and 24 pro-
gressive supranuclear palsy (PSP) patients were prospectively
recruited to undergo 3.0 Tesla magnetic resonance imaging. The ROI
analysis was performed by manual delineation of the areas on co-
registered parameter maps of mean diffusivity (MD), fractional ani-
sotropy (FA), R2 and R2*. Overall significant effects between the
different groups were performed with the KruskalWallis test fol-
lowed by post hoc, unpaired Wilcoxon Rank tests with Bonferroni
correction (significance level <0.05). 35 HC, 35 PD, 14 MSA and
14 PSP were randomized for flexible discriminant analysis (FDA) as
a training set.
Results: PSP patients showed significantly increased MD within
TH, GP, ND, MC and SN, significantly increased FA within NC and
PU, significantly increased R2 within NC and PU, significantly
increased R2* within the SN. MSA patients had significantly
increased MD within PU and MC, significantly increased FA within
MC, significantly increased R2* within PU, respectively. PD patients
exhibited significantly increased MD within PU, TH, ND, MC, SN
and one subregion of SN, significantly increased FA within MC, sig-
nificantly increased R2* within PU, SN and one subregion of the
SN. FDA in the test set revealed correct classification in 6/8 MSA
and 7/9 PSP patients, while 3/19 PD patients were predicted as APS.
Conclusions: Region-of-interest analysis detected micro-structural
damages at highfield MRI with the help of multimodal neuroimaging
including relaxometry and DTI scalars. Furthermore, we revealed dif-
ferent patterns of iron accumulation. Using FDA, we obtained a
good differentiation not only between PD and APS, but also between
MSA and PSP.
Movement Disorders, Vol. 30, Suppl. 1, 2015
1009
Motor and non-motor features of Parkinsons disease in
idiopathic REM sleep behaviour disorder
M. Rolinski, L. Griffanti, K. Szewczyk-Krolikowski, R.A. Menke, T.
Quinnell, Z. Zaiwalla, C.E. Mackay, M.T.M. Hu (Oxford, United
Kingdom)
Objective: To evaluate both structural and functional imaging
changes in patients with idiopathic REM sleep behavior disorder
(RBD).
Background: Resting-state functional MRI (rs-fMRI) has been
shown by our group as a promising tool for the diagnosis of early
Parkinsons disease (PD). As REM sleep behavior disorder (RBD) is
strongly associated with alpha- synucleinopathy, we aimed to investi-
gate potential resting-state connectivity and structural changes in this
promising prodromal group.
Methods: Twenty-six patients with polysomnography-proven idi-
opathic RBD and 22 age and sex-matched healthy controls were
recruited. All subjects underwent a structural MRI protocol, includ-
ing T1-weighted and diffusion imaging. Blood-oxygen level depend-
ent (BOLD) sequences were acquired during resting conditions, with
the subject awake and their eyes open. Based on a priori hypotheses,
rs-fMRI analysis was confined to three networks of interest (the basal
ganglia network (BGN), the sensorimotor network (SMN) and the
default mode network (DMN)), and one control network (the primary
visual network (PVN)).
Results: There were no significant volumetric differences
between patients with RBD and healthy controls. Voxel-based mor-
phometry analysis did not yield any significant grey matter differen-
ces between the two groups. Similarly, no significant differences of
fractional anisotropy were found using white matter tract analysis.
Rs-fMRI revealed decreased coactivation within the BGN
(involving the caudate, putamen, globus pallidus and the dorsolateral
prefrontal cortex) and the SMN (precentral gyrus) of patients with
RBD. No increased coactivation within these networks was seen in
the RBD group, and no between-group differences were seen in the
DMN and PVN.
Conclusions: Rs-fMRI demonstrates significantly reduced coacti-
vation within the BGN and SMN of patients with RBD. These
results are similar to those found in early PD and are likely to repre-
sent pre-clinical basal ganglia dysfunction. This approach shows
great promise as a potential biomarker for prodromal alpha-
synucleinopathy.
1010
Dopamine transporter scan (DaTscan) and clinical global
impression of severity of Parkinsons disease: Data from a non
motor natural history study
A. Sauerbier, P. Martinez-Martin, M. Politis, A. Rizos, N. Troja, N.
Mulholland, G. Vivian, B. Cocoran, D. Trivedi, L. Perkins, R. Inniss,
M. Parry, A. Martin, R. Brown, K. Ray Chaudhuri (London, United
Kingdom)
Objective: To analyse and compare the association between
DaTscan ratios and duration of disease and the clinical global
impression of severity of Parkinso
ns disease (PD).
Background: The Clinical impression of severity index of PD
(CISI-PD) is a valid tool to assess the severity of PD in a compre-
hensive (motor and cognitive) manner in clinical practice.
Methods: Clinical and CISI data related to PD as well as caudate
and putamen uptake ratios with DATScan were analysed. Cross sec-
tional data is presented.
Results: 62 patients (70.97% male, mean age 61.55 6 12.71
years, mean duration of disease 3.7 6 3.6 years, age at PD onset
67.84 6 12.76 years, mean Scopa Motor Score 17.65 6 9.77, Levo-
dopa equivalent dose 441.86 6 470.84 mg) showed a low mean
uptake caudate (right 1.42 6 0.59, left 1.45 6 0.57), putamen (right
 POSTER SESSION
0.86 6 0.47, left 0.93 6 0.39) and striatum (right 1.14 6 0.52, left
1.20 6 0.47) in this ongoing study.
A moderate association between the caudate uptake and the
duration of disease (right caudate r 5 -0.49, left caudate r 5 -0.41)
and CISI-PD total score (right caudate r 5 -0.46, left caudate r 5 -
0.45) was noted while there was a strong association between the
duration of disease and putamen uptake (r= -0.56/-0.51). Association
between putamen uptake and CISI (r 5 -0.48/-0.48) was moderate.
Overall, a moderate to strong association between the striatum
uptake and the duration of disease (right striatum r 5 -0.54, left
striatum r 5 -0.48) and the total score of the CISI-PD (right striatum
r= -0.48, left striatum r= -0.47) was noted. Furthermore, cognitive
impairment as indicated by Mini Mental State Examination and
CISI-PD correlated significantly with putaminal and caudate uptake
ratios.
Conclusions: This first study addressing CISI-PD and DaTscan
suggests that CISI-PD could function as a marker of disease severity
and progression as indicated by striatal and putaminal DaT uptake
values in PD. In addition, striatal DaTscan uptake could be a marker
for aspects of cognitive impairment in PD.
1011
Imaging neurodegeneration in Movement Disorders: A VBM
study
M. Saxena, B. Rana, A. Juneja, S.S. Kumaran, R. Agrawal, M.
Behari (New Delhi, India)
Objective: To observe any differences in the tissue architecture
of the brain.
Background: Voxel based morphometry (VBM) is useful in early
differentiation of Parkinsons disease (PD) from the other Parkinson-
Fig. 1. (1011).
S393
plus syndromes (PPS), including multiple system atrophy (MSA) and
Progressive Supranuclear Palsy (PSP).
Methods: T1-weighted magnetization prepared rapid gradient
echo (MPRAGE) images were acquired on a 1.5T Siemens
(Avanto) clinical MR scanner, using an 8-channel head coil. Each
volume consisted of 176 slices in sagittal orientation with echo
time (TE) 3.37ms, repetition time (TR) 1900ms, inversion time
(TI) 1100ms, field of view (FOV) 256mm, matrix 256 3 256, in
phase resolution 100%, slice thickness 1mm. The study involved
32 PD, 17 MSA, 20 PSP and 42 age and gender matched controls.
VBM analysis was performed with SPM8. 3 dimensional T1-
images Magnetization prepared rapid gradient echo (MPRAGE)
images were normalized to standard space (MNI) smoothed and
segmented into grey matter (GM), white matter (WM), and cere-
brospinal fluid (CSF) volumes. These were DARTEL normalized
to a common stereotactic space with thorough cleanup and de-
noising using SANLM filter using12-parameter affine transforma-
tion. Significance was tested using 2-sample t-test between the
controls and each patient groups using both the segmented images
as well as the GM,WM, CSF volumes.
Results: In general significant grey matter loss was observed in
patients. [figure1]WM was significantly higher in patients as com-
pared to controls.[figure2] This may be attributed to the greater brain
volumes in patients. Significant GM loss was observed in bihemi-
spheric Caudate, and medial frontal gyrus PSP, caudate, cerebellum,
thalamus and parts of frontal, temporal, and limbic lobes in PD and
cerebellum, caudate, frontal, temporal, parietal and occipital lobes in
MSA. White matter loss was significant for brain stem and cerebel-
lum in PSP, cingulated gyrus and cerebellum in MSA and fusiform
gyrus in PD.
Fig. 2. (1011).
Movement Disorders, Vol. 30, Suppl. 1, 2015
S394 POSTER SESSION
The GM/WM/CSF and ICV values in Subjects of Parklinsonism
Grey
Subject N Matter
Controls 42 548.0 6 55.7
PD 32 544.7 6 73.6
MSA 17 531.5 6 109.9
PSP 20 507.1 6 59.1
Values are in cubic mm
Conclusions: This differential loss in GM/WM/CSF may be
important in defining the pattern of neurodegeneration in Movement
Disorders.
1012
Resting state fMRI differentiates essential tremor patients from
controls
Q. Shen, P. Pattany, S. Sargolzaei, A. Sarou, B. Fortes, H. Islam, P.
Kundu, A. Avila, F.B. Nahab (La Jolla, CA, USA)
Objective: To identify differences in blood flow responses during
resting state fMRI between Essential Tremor (ET) and healthy volun-
teers (HV).
Background: The clinical hallmarks of ET are action tremors,
noted during posture and/or movement (kinetic). Studies looking to
identify the neural correlates of ET have provided little new informa-
tion, as the brain regions that are active in ET are similar to those
seen in HV mimicking tremor. If the abnormalities associated with
ET are presumed to be omnipresent, then changes in blood flow
responses measured with fMRI should be noted even when no trem-
ors are present in subjects with ET. Regions showing greater connec-
tivity have previously been shown to have lower BOLD response
standard deviations. We hypothesize that subjects with ET vs. HV
will show differentially reduced standard deviations in brain regions
involved in tremor generation at rest, despite the absence of tremors.
Methods: We carried out a resting state (rs-fMRI) study in sub-
jects with ET (n518) and healthy controls (n518) on a 3-Tesla GE
MR-750 scanner. Subjects were instructed to lie still with eyes open
during a 5-minute rs-fMRI acquisition. To ensure subjects had no
tremors during the course of the scan, MR-compatible tri-axial accel-
erometers were placed over the dorsum of the hands. 3D-T1 volumes
Fig. 1. (1012).
Movement Disorders, Vol. 30, Suppl. 1, 2015
White Intra cranial
Matter CSF Volume
498.7 6 65.9 225.2 636.2 1271.9 6126.3
544.5 6 72.0 259.2 6 44.4 1348.4 6 152.6
547.5 6 114.6 302.3 6 114.1 1381.3 6 300.2
512.2 6 76.8 277.3 6 40.1 1296.7 6 151.0
were collected for spatial normalization and overlay. Voxel-wise
standard deviations were calculated for each subject. AFNI neuroi-
maging package (Cox 1999) was used for statistical analysis using
3DDeconvolve with voxel-wise T-tests performed with family-wise
error rates calculated to correct for multiple comparisons. The raw
values from the regions identified were also used to calculate
descriptive statistics.
Results: Four regions showed significantly reduced standard devi-
ations within our ET group compared with HV. [figure1] The ET
group as a whole should the least variability in red nucleus>anterior
cingulate>SMA>L cuneus.
Conclusions: The use of rs-fMRI standard deviation maps may
serve as a biomarker of ET. Further studies are needed to determine
whether the degree of reduction in SD correlates with tremor severity
and the sensitivity and specificity of using such a methodology for
diagnostic purposes.
1013
Unilateral blepharospasm associated with invasive lacrimal gland
tumor
H.A.G. Teive, G. Fabiani (Curitiba, Brazil)
Objective: To report a case of unilateral blepharospasm second-
ary to an invasive lacrimal gland tumor, most likely a lymphoma.
Background: Malignant tumors of lacrimal glands are relatively
rare. Most of them are lymphomas and affects more elderly women.
Results: Case Report: We report a 48-year-old man with who
developed right unilateral blepharospasm eyes in a short period of
two months, associated with right abducens nerve paresis, excessive
tearing and redness in the right eye. Brain MRI showed an invasive
tumor of right lacrimal gland (25mm X 22mm X 10 mm) extending
 POSTER SESSION
Fig. 1. (1013).
to the lateral rectus muscle and orbital regions. The aspect is highly
suggestive of lymphoma [figure1] and [figure2]
Conclusions: Malignant tumors of lacrimal glands are relatively
rare. Most of them are lymphomas and affects more elderly women.
Essential blepharospasm, usually are bilateral and idiopathic.
Fig. 2. (1013).
S395
To the best of our knowledge this is the firs case report of sec-
ondary and unilateral blepharospasm caused by a lacrimal gland
tumor.
1014
Altered response to reward in non-manifesting carriers of the
G2019S LRRK2 mutation
A. Thaler, A. Mirelman, R.C. Helmich, B.F.L. Van Nuenen, T.
Gurevich, A. Orr-Urtreger, K. Marder, S. Bressman, B.R. Bloem, T.
Hendler, N. Giladi (Tel-Aviv, Israel)
Objective: To assess both anticipation of reward and response to
rewarding outcomes, in a cohort of non-manifesting carriers (NMC)
of the G2019S mutation in the LRRK2 gene.
Background: The G2019S mutation in the LRRK2 gene has
been previously implicated in the pathogenesis of Parkinsons disease
(PD), healthy NMC of the mutation are considered an at risk popu-
lation for the future development of PD. Disturbances in reward
processing are common in late stage PD and include pathological
gambling, hoarding, hypersexuality and compulsive drug taking.
However, it is yet not clear whether this disturbance is drug related
or part of the degenerative process. We used an fMRI forced choice
gambling task to address this issue.
Methods: Sixty-eight healthy first-degree relatives of PD patients
who carry the G2019S mutation participated in this study (34 NMC).
A 15 minute event related fMRI forced-choice domino task that has
been previously used by our group in order to assess both anticipa-
tion and response to reward outcomes was utilized. [figure1]
Movement Disorders, Vol. 30, Suppl. 1, 2015
Fig. 1. (1014).

Fig. 2. (1014).
 POSTER SESSION S397

Results: Subjects behavior on standard questionnaires was well

matched. NMC demonstrated a trend for higher risk index scores
(p50.06). No whole brain or region of interest (ROI), between-group
differences were noted on reward anticipation for either positive or
negative rewards. However, NMC had higher activations in the left
nucleus accumbens (p50.03), left inferior parietal (p50.04), left per-
cuneus (p50.01), bilateral medial orbito-frontal cortex (right
p50.03, left p50.05) and right insula (p50.05) in an ROI analysis
of response to rewarding outcomes compared with non-manifesting
non-carriers of the mutation. [figure2]
Conclusions: While anticipation to rewarding outcomes was not
affected in NMC of the G2019S mutation, a higher response to
rewarding outcomes was noted in different structures of the reward
system including the ventral striatum. This finding indicates that the
disturbance in reward processing that can be identified in PD
patients, is part of the disease process and is not related solely to the
use of medications.

1015
The dynamic change in substantia nigra hyperechogenicity in
Parkinsons disease is associated with age and disease duration Fig. 1. (1016).
T. Toomsoo, A.H. Pool, I. Liepelt-Scarfone, L. Kadastik-Eerme, T.
Asser, D. Berg, P. Taba (Tallinn, Estonia)
Objective: To evaluate does substantia nigra hypereechogenicity
dle reconstruction according to underlying anatomy in CBS
stable or not stable marker course of Parkinsons disease?
patients.
Background: Substantia nigra hyperechogenicity (SN1) is used
Methods: We recruited 11 CBS patients and 11 age- and gender-
as a proxy for Parkinsons disease (PD) diagnosis. Although there is
matched HS. The diagnosis of CBS was made according to consen-
considerable variation in SN1 values across patients, previous work
sus criteria (Armstrong et al., 2013) and motor/non-motor features
suggests that SN1 is a stable marker throughout the course of the
were scored by standardized clinical scales. Diffusion and T1 images
disease. We analyzed SN1 values seprately in both side, according
were acquired using a 3T MRI scanner (Siemens Verio). T1 images
to the side of initial clinical symptoms caused by PD and assessed
were registered, segmented, parcellated and labeled on the basis of
relations of SN1 values in both sides and association with PD
DKT40 atlas in 34 cortical regions in each of the individual hemi-
duration.
sphere to calculate the cortical thickness changes using surface-based
Methods: The study was conducted on 266 PD patients and 166
morphometry tools in FREESURFER. Streamline tracts were recon-
healthy controls. SN1 was measured by transcranial sonography
structed in individual diffusion space using the TRACULA toolbox.
with three replicate measurements on both sides. We correlated SN1
Average and voxel-wise fractional anisotropy (FA), axial diffusivity
with a range of clinical parameters. The relation between the SN1
(AD) and radial diffusivity (RD) values were calculated within eight
in the side of initial signs and clinical parameters was demonstrated
major WM tracts in each hemisphere. Group comparison for thick-
in linear regression analysis.
ness changes was performed by GLM-based analysis and for diffu-
Results: We analyzed SN1 corresponding to the side of initial
sion changes by SPSS toolbox; results were corrected for multiple
signs. We found that SN1 is on average 17.6% higher at PD start
comparisons.
side. Furthermore, we demonstrated a significant association between
Results: Compared to HS, CBS patients had significant thinning
start side SN1 and PD duration in a late stage PD patients showing
in the precentral gyrus and superior temporal gyrus bilaterally [fig-
a 15% reduction in SN1 as compared to early and mid stage PD
ure1]. In all the WM tracts examined in CBS patients, AD was more
patients. We also found that contrary to the control group, increase
altered than FA and RD. We found increased AD bilaterally in the
in patient age is associated with a decrease in initial side SN1. Our
superior longitudinal fasciculus, corpus callosum, cingulum and unci-
data suggest that SN1 is not a stable biomarker for PD but it is sig-
nate. In addition, we found increased AD in the corticospinal tract
nificantly different in different PD duration stages.
and anterior thalamic radiations only on the left side.
Conclusions: The present study demonstrates that SN1 is not a
Conclusions: Our results show a circumscribed cortical thinning
stable biomarker and warrants a longitudinal follow-up study in the
affecting the precentral and superior temporal areas in CBS patients.
same clinical cohort.
In addition, the increased axial diffusivity, an expression of axonal
loss, involved most WM tracts suggesting a widespread WM damage
1016 in CBS. Overall these abnormalities likely represent the anatomical
substrate of motor and non-motor impairment in CBS.
Brain microstructural grey and white matter alterations in
patients with cortico-basal syndrome
N. Upadhyay, A. Suppa, F. Di Stasio, M.C. Piattella, N. Petsas, G. 1017
Fabbrini, C. Colosimo, P. Pantano, A. Berardelli (Roma, Italy)
Structural assessment in craniocervical dystonia: global and
Objective: To evaluate possible changes in cortical thickness and differential analyses
anatomically constrained tractography in patients with cortico-basal
L. Vilany, T.J. Rezende, L.G. Piovesana, L.S. Campos, F.R. Torres,
syndrome (CBS) compared to healthy subjects (HS).
M.C. Franca, Jr., A.C. Amato-Filho, I. Lopes-Cendes, F. Cendes, A.
Background: CBS is an atypical Parkinsonian disorder charac- DAbreu (Campinas, Brazil)
terized by neurodegeneration involving the cerebral cortex and
basal ganglia. Although previous neuroimaging studies have Objective: To investigate in craniocervical dystonia (CCD): (1)
reported both gray matter (GM) and white matter (WM) changes in cortical thickness and subcortical volume, (2) clinical correlations
CBS, no studies have investigated cortical thickness and WM bun- between structural changes, (3) steps (1) and (2) in cervical dystonia

Movement Disorders, Vol. 30, Suppl. 1, 2015

S398 POSTER SESSION

TABLE 1. Exploratory Analyses

2
Cortical Area Cluster size (mm ) TalX TalY TalZ Patients mean (mm) Controls mean (mm) p-value
CCD
Right Hemisphere
Lateral occipital 151.93 16.7 -98.0 -10.4 1.963 6 0.162 1.990 6 0.137 0.000
Precuneus 13.89 9.8 -56.5 15.5 2.114 6 0.156 2.193 6 0.123 0.001
CD
Right Hemisphere
Lateral occipital 97.88 18.5 -99.8 -10.8 1.959 6 0.174 1.990 6 0.136 0.001
Precentral 7.79 40.8 -10.5 32.5 2.252 6 0.156 2.355 6 0.133 0.001
Left Hemisphere
Cuneus 211.52 -5.1 -94.5 10.4 2.149 6 0.183 2.232 6 0.141 0.000
Paracentral 31.62 -16.6 -41.4 57.0 1.687 6 0.150 1.703 6 0.129 0.001
B&O
Right Hemisphere
Lateral orbitofrontal 34.89 26.5 19.6 -12.2 2.388 6 0.117 2.483 6 0.140 0.000
Inferior parietal 62.72 42.3 -72.8 19.0 2.144 6 0.133 2.212 6 0.121 0.001
Lateral occipital 36.75 43.9 -63.0 4.6 1.896 6 0.135 1.990 6 0.136 0.001
Superior temporal 14.39 57.8 -31.6 9.8 2.545 6 0.131 2.664 6 0.157 0.001
Isthmus of cingulate 11.87 7.8 -36.7 34.0 2.263 6 0.254 2.379 6 0.212 0.001
Left Hemisphere
Postcentral 104.93 -57.9 -16.1 34.2 1.793 6 0.130 1.857 6 0.102 0.000
Supramarginal 19.32 -57.2 -47.8 33.9 2.209 6 0.116 2.320 6 0.113 0.001
Pars opercularis 36.49 -33.2 10.3 13.6 2.284 6 0.123 2.365 6 0.145 0.001
Superior temporal 69.25 -48.9 -13.9 -5.5 2.472 6 0.138 2.617 6 0.164 0.001
Bankssts 8.92 -50.7 -44.7 -0.1 2.198 6 0.136 2.318 6 0.151 0.001
Superior parietal 13.19 -35.1 -49.7 50.8 1.874 6 0.146 1.965 6 0.107 0.001
Bankssts: posterior portion of superior temporal sulcus

alone (CD) and blepharospasm/oromandibular dystonia isolated or in subcortical structures. We did not observe any significant clinical
combined (B&O). correlation with structural abnormalities.
Background: Previous voxel based morphometry (VBM)
analyses in CCD showed controversial findings. Recently, dysto-
nia has been associated with circuit alterations instead of a Final Primary and Secondary Analyses
mainly basal ganglial disturbance. Freesurfer (FS) has presented Cotical Atrophy - ANCOVA
better results than VBM when applied to cortical thickness. Areas Patients Mean6SdControls Mean6Sdp-value
Therefore, it is relevant to perform a new investigation with CCD
this new tool. Right Hemisphere
Methods: Our primary analysis sample consisted in 49 CCD paracentral cortex 2.252 6 0.156 2.355 6 0.133 0.001
patients and 79 healthy controls (HC). Our secondary analysis, precentral gyrus 2.137 6 0.159 2.233 6 0.130 0.000
had a sample of 18 CD versus 79 HC, and 18 B&O versus 79 Left Hemisphere
HC. We acquired T1 weighted scans at a 3T scanner. We used fusiform gyrus 2.596 6 0.209 2.639 6 0.158 0.001
FS to obtain cortical thickness, subcortical volume of groups middle temporal gyrus 2.548 6 0.166 2.660 6 0.159 0.001
and perform an exploratory analysis. We performed an precentral gyrus 2.262 6 0.158 2.357 6 0.134 0.001
ANCOVA (dependable variables: age, gender, estimated intra- rostral anterior cingulate2.679 6 0.229 2.825 6 0.235 0.001
cranial volume) at Systat, corrected by Dunn-Sidak (p0.001). superior temporal 2.488 6 0.216 2.617 6 0.164 0.000
We then performed a general linear model (GLM) to investigate CD
the relationship between affected areas and clinical variables Right Hemisphere
(onset age, score at MARSDEN-FAHN, time of botulinum fusiform gyrus 2.547 6 0.229 2.646 6 0.150 0.001
toxin), corrected by Bonferroni. frontal pole 2.461 6 0.171 2.611 6 0.206 0.001
Results: The exploratory analyses demontrated atrophy in the B&O
right precuneus and lateral occipital gyrus in CCD; atrophy in the Left Hemisphere
left cuneus, paracentral, right lateral occipital and precentral gyri in precentral 2.187 6 0.168 2.346 6 0.167 0.001
CD; atrophy in the right lateral orbitofrontal, inferior parietal, lateral supramarginal 2.209 6 0.109 2.254 6 0.127 0.001
occipital, superior temporal, isthmus cingulate, left postcentral, Subcortical Analyses
supramarginal, pars opercularis, superior parietal gyri, superior tem- No significant differences were observed
poral gyrus and sulcus in B&O. Clinical Analyses
In CCD versus HC, we found cortical atrophy in the left fusi- No relationships were observed.
form, middle temporal, precentral, rostral anterior cingulate and
superior temporal gyri, right paracentral cortex and precentral gyrus.
CD versus HC showed atrophy in the right fusiform gyrus and fron-
tal pole, and B&O versus HC demonstrated atrophy in the left pre- Conclusions: We detected the involvement of areas in the motor,
central and supramarginal gyri. No significant differences were found somatosensory and visual processing in CCD, with a possible differ-
ential pattern of involvement in CD and B&O.

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
1018
Amyloid-b imaging in Parkinsons disease: Comparison of
analytic techniques
D. Weintraub, J. Dubroff, I. Nasrallah, R. Goldmann Gross, J. Rick,
R.S. Akhtar, H. Hurtig, A. Chen-Plotkin, L.M. Chahine, N. Dahod-
wala, J.E. Duda, J.F. Morley, J.Q. Trojanowski (Philadelphia, PA,
USA)
Objective: To compare qualitative and quantitative analysis of
positron emission tomography (PET) amyloid-b (Ab) imaging scans
in non-demented Parkinsons disease (PD) patients with normal
global cognition.
Background: There is evidence for increased Alzheimer disease
(AD) biomarkers in patients with PD, especially in those patients
with dementia (PDD). One such biomarker is Ab PET imaging. Ab
amyloid scans can be read qualitatively (by a radiologist) and quanti-
tatively (by software analysis), but the inter-rater reliability for quali-
tative reads or agreement between qualitative and quantitative reads
in PD is unknown.
Methods: 40 patients (67.5% male; mean age=65.7 years) with
idiopathic PD (mean disease duration=4.1 years) without dementia
and normal global cognition on average (mean DRS-2 score=139.4)
underwent florbetapir(18F) PET/CT brain imaging. Each study was
qualitatively interpreted by two experienced nuclear medicine physi-
cians as either positive or negative for the presence of abnormal cer-
ebral Ab amyloid, then consensus was reached. Cerebral Ab
amyloid was quantified by calculating standardized uptake value
ratios (SUVrs) in six regions of interest (anterior and posterior cingu-
late gyrus, precuneus, and frontal, temporal and parietal cortices) rel-
ative to the cerebellum using a commercially available 510K
approved program (Siemens Scenium).
Results: Seven patients (17.5%) were positive for cerebral Ab
amyloid based on qualitative consensus read, and five (10.0%) were
positive using a previously published SUVr cut-off value of 1.17.
Cohens kappa for the initial qualitative read comparing raters was
0.84 (38/40 cases). Positive qualitative cases read had a higher global
SUVr (1.28 vs. 0.98, p50.04 [t test]) and higher SUVrs for the pari-
etal, posterior cingulate and temporal cortices; positive quantitative
cases showed significantly increased amyloid levels in all measured
regions. Using the aforementioned SUVr cut-off value as the quanti-
tative gold standard for a positive scan, there was good sensitivity
(75%) and specificity (89%) for the consensus qualitative read.
Conclusions: Qualitative reads appear to show good agreement
with quantified reads for Ab scans in PD patients. Approximately
15% of non-demented PD patients with normal global cognitive per-
formance have positive Ab scans and evidence for increased Ab in
multiple cortical regions.
Parkinsons disease: Genetics
1019
Comprehensive evaluation of immune mediated inflammation
biomarker and IL-10 promoter DNA polymorphisms in sporadic
PD patients
K.K. Alagamuthu, A. Meyyazhagan, M.A. Shafi Ahammed Khan, P.
Krishnan, S. Keshavaroa, B. Vellingiri (Coimbatore, India)
Objective: The main objective was to identify the Immunological
Factors (IL-1beta and IL-6) and IL-10 promoter DNA polymor-
phisms in sporadic PD patients.
Background: Parkinsons disease (PD) is the second most com-
mon neurodegenerative disease, after Alzheimers disease (AD). The
potential causes of PD remain elusive but studies have revealed that
inflammatory processes play a vital role in the pathogenesis. Immune
mediated inflammations play an important role in the pathogenesis of
PD.
S399
Methods: The study enrolled 16 patients with diagnosed idio-
pathic PD. Control samples were 16 randomly selected healthy indi-
viduals from the same geographical region. Immunological Factors
(IL-1beta and IL-6) were analysed using ELISA. PCR-RFLP meth-
ods were used for genotyping.
Results: Compared to healthy controls, significant increase in the
levels of IL-1beta and IL-6 was observed. Statistically significant
(p<0.001) differences between PD patients and controls were found.
Conclusions: Results from our study revealed that the IL-10
polymorphism might be a risk factor of sporadic Parkinsons disease
in a South Indian population. Screening of genetic variants in innate
immune and inflammatory response genes may further reveal for the
development of PD. In addition, associations between these parame-
ters is a clinically relevant endeavour, and these associations will
assist in identifying susceptibility biomarkers for this challenging
disease.
1020
Case of a man with early Parkinsons disease with a history of
essential tremor running in the family
G. Avagyan, A. Sahakyan, I. Gabrielyan, S. Khachaturyan, K.
Harutyunyan, H. Manvelyan, A. Voskanyan, A. Nazaryan (Yerevan,
Armenia)
Objective: To demonstrate a case of possible genetic linkage of
Parkinsons disease and essential tremor.
Background: Parkinsons disease is a neurodegenerative disease
affecting millions worldwide. Tremor, rigidity, and bradykinezia and
other signs are a result of progressive degeneration of dopaminergic
neurons, primarily in a part of the mid-brain called the substantia
nigra. As for the essential tremor, recent evidence indicates a neuro-
degenerative pathophysiology and even an overlap with Parkinsons
disease taking into consideration the facts that essential tremor is
clinically progressive and several signs, such as bradykinezia, rest
tremor can also be observed.
Methods: 49 year old male with tremor was seen in the clinic.
According to the patient the symptoms started 2 years ago after see-
ing a street fight. For some period of time he had delusions and
nightmares for which he did not seek medical care. Then he started
to develop mild tremor of the right hand which during two years
involved also right leg. The patient mentioned essential tremor in the
family history from his mother side. The patient also recalls that his
grandfather had shaky hands and was using alcohol as a treatment.
Results: Neurological examination was remarkable with rest
tremor on right extremities, rigidity in all extremities and the neck
area, slurred speech with low voice, pseudo bulbar palsy, mask like
face, marked bradykinezia and postural instability. The laboratory
tests on Wilsons disease and MRI were unremarkable. The patients
tremor improved markedly on b-blocker (propranolol) and bradykine-
zia was improved on dopamine agonists (piribedil).
Conclusions: The relationship in terms of common pathophysio-
logical mechanisms between essential tremor and Parkinsons disease
has been a topic for discussions for years and whether the relation-
ship is coincidental still remains unclear. Whether this two Move-
ment Disorders also share same genetic base also is debated.
Multicenter studies with large number of patients and long history of
diseases, genetic analyses should be performed to confirm or to reject
the relationship between these two conditions.
1021
TOMM40 SNPs and multiple types of dementia
L. Bekris, D. Tsuang, J. Leverenz, C.E. Yu, O. Lopez, R. Hamilton,
D. Bennett, J. Schneider, A. Buchman, E. Larson, P. Crane, J. Kaye,
P. Kramer, R. Woltjer, J. Trojanowski, D. Weintraub, A. Chen-
Plotkin, D. Irwin, J. Rick, G. Schellenberg, S. Watson, W. Kukull, P.
Nelson, G. Jicha, J. Neltner, D. Galasko, E. Masliah, J. Quinn, K.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S400 POSTER SESSION
Chung, D. Yearout, I. Mata, K. Edwards, T. Montine, C. Zabetian
(Cleveland, OH, USA)
Objective: The aim of this exploratory investigation was to test
for an association between dementia type and 2 SNPs located in the
APOE gene region within the TOMM40 gene, rs2075650 and
rs59007384.
Background: Recently, our group reported that the APOE e4
allele is an important risk factor for cognitive impairment across the
spectrum of Lewy body disease (LBD). APOE e4 carrier status is a
well known risk factor for Alzheimers disease (AD), although many
non-carriers also develop AD. Genome wide association studies
(GWAS) in AD have found a strong association between quantitative
traits, such as age-at-onset, and single nucleotide polymorphisms
(SNPs) within the APOE region that include not only APOE, but
also the TOMM40 gene. Thus, we examined the association between
SNPs in the TOMM40 gene and dementia subtypes, with a particular
focus on APOE e4 non-carriers to avoid issues of linkage
disequilibrium.
Methods: Subjects were classified into 5 categories based on neu-
ropathologic findings: dementia with high-levels of AD pathology
and no LBD (AD; n5253); dementia with high-levels of both AD
and LBD pathology (LBD-AD; n5252); dementia with LBD and no
or low levels of AD (pure DLB (pDLB; n599), Parkinsons dis-
ease dementia with high-levels of AD pathology (PDD-AD; n525);
Parkinsons disease dementia with LBD and no or low levels of AD
pathology (PDD; n547); Parkinsons disease without dementia and
with no or low levels of AD pathology (PD; n527); controls with no
or low levels of AD pathology and no LBD (controls; n5278). All
subjects were tested for associations between APOE locus SNPs and
disease.
Results: As expected, preliminary results show that the propor-
tion of APOE e4 and TOMM40 SNPs are significantly higher in the
AD, LBD-AD, DLB, and PD groups compared with the control
group. Among the APOE e4 non-carriers (APOE e3/3 only) the
TOMM40 rs2075650 G allele is associated with disease for AD,
LBD-AD and marginally with pDLB, but not PDD-AD, PDD or PD,
compared to controls.
Conclusions: Our findings with TOMM40 SNPs in APOE e4
non-carriers suggests that multiple sites within the APOE gene
region may contribute to dementia risk in some but not all
synucleinopathies.
1022
Expanding the phenotype of PLA2G6 related Parkinsons
subtypes
S. Bohlega, B. Tawil, L. Al-Jomaa, A. Magrashi, T. Alkhairallah, N.
Al Tassan (Riyadh, Saudi Arabia)
Objective: The aim of this study is to screen Saudi PD patients
for PLA2G6 gene.
Background: Genetic studies in familial Parkinsons disease
cases have identified a number of genes involved in the etiology of
PD. Park14 or PLA2G6 gene related dystonia Parkinsonism recently
described in atypical young onset Parkinsons with dystonia.
Methods: One hundred twenty (120) PD patients (11 with autoso-
mal dominant inheritance, 17 with autosomal recessive inheritance
and the remaining are sporadic cases) were screened by direct
sequencing for mutations in PLA2G6.
Results: Three (3) unrelated native Saudi families with eight (8)
affected individuals were identified with adult onset levodopa-
responsive Parkinsonism, pyramidal signs and cognitive and psychi-
atric features. There was no evidence of iron accumulation or cere-
bral atrophy. The psychiatric features were very severe and
disabling. Levodopa response was transient, partial with bizarre and
strange motor and behavioral side effects. Disease progressed relent-
lessly leading to death or total dependence within 3-4 years. We
identified a homozygous 2222G-A transition in the PLA2G6 gene,
Movement Disorders, Vol. 30, Suppl. 1, 2015
resulting in an arg741-to-gln (R741Q) substitution in a conserved
residue.
Conclusions: PLA2G6 related Parkinsonism or PARK14 consti-
tutes 6% of Autosomal Recessive Parkinsons disease in Saudi Ara-
bian PD cohort, dystonia and brain iron deposition was not noted in
our cases, otherwise the phenotype is consistent with previously
reported cases.
1023
Clinical and genetic analysis of a large pedigree with Parkinsons
disease from an isolated Trentino valley
L. Borellini, M.C. Malaguti, E. Monfrini, V. Melzi, R. Di Giacopo,
G. Franco, I. Trezzi, D. Ottaviani, M. Pellegrini, S. Ferrari, G.P.
Comi, A. Di Fonzo (Milan, Italy)
Objective: To describe the clinical and genetic findings of a large
kindred with Parkinsons disease (PD) coming from a geographically
isolated region.
Background: The identification of a substantial number of Men-
delian genes involved in rare monogenic forms of PD has signifi-
cantly improved the comprehension of the disease pathogenesis.
Most of those genes have been identified by linkage studies. A possi-
ble alternative approach is to identify disease genes studying isolated
populations. One of the advantage of isolates is the existence of
well-ascertained multi-generational pedigrees, descended from fewer
founders and spanning fewer generations [Arcos-Burgos et al.,
2002]. For this purpose, we aim to search for a PD causative gene
mutation in patients from Trentino valleys, where communities were
isolated for centuries due to geographical barriers and demographic
history.
Methods: Detailed neurological examination and neuroradiologi-
cal studies were collected for each patient. We extracted DNA from
blood of all patients and performed genetic analysis by direct
sequencing of exons and intron-exons boundaries of LRRK2 (exons
29, 30, 31, 34, 35, 41), SNCA, PRKN, PINK1 and DJ-1. Quantita-
tive PCR of all exons of PRKN and SNCA were assessed. A haplo-
type analysis of the entire LRRK2 locus was performed.
Results: We identified a six-generation kindred with several sub-
jects affected by PD originating all from the same small village of a
geographically isolated valley of Trentino. All patients fulfill the
diagnostic criteria for PD, with an age of onset ranging between 35-
57. Haplotype analysis of LRRK2 showed no allele sharing between
affected. Neither point mutations nor genomic rearrangements were
identified in known PD genes.
Conclusions: The identification of a novel large family with
hereditary PD and no mutations in the known PD genes opens the
possibility to search for a novel causative gene for the disease.
1024
Investigating prodromal markers of Parkinsons disease in adults
with hemizygous 22q11.2 deletions
N.J. Butcher, C. Marras, M. Pondal, P. Rusjan, L. Christopher, A.P.
Strafella, A.E. Lang, A.S. Bassett (Toronto, ON, Canada)
Objective: To examine prodromal markers of Parkinsons disease
(PD) in adults with 22q11.2 deletions at high genetic risk of early-
onset PD.
Background: The hemizygous 22q11.2 deletion and the associ-
ated multisystem syndrome, 22q11.2 deletion syndrome
(22q11.2DS), has recently been identified as a novel genetic risk fac-
tor for early-onset Parkinsons disease. Adults with 22q11.2DS may
exhibit early markers of PD including pre-diagnostic motor signs,
non-motor symptoms, and neuroimaging biomarkers of PD that could
help identify those at highest risk.
Methods: Motor and non-motor functioning was examined in
adults (n513) molecularly confirmed with 22q11.2DS (median age
39 years, range 30-54 years; eight treated for psychosis) using
 POSTER SESSION
standard measures and compared with healthy matched controls
(n510). Transcranial sonography was used to investigate substantia
nigra echogenicity. Positron emission tomography (PET) using 11C-
dihydrotetrabenazine, a vesicular monoamine transporter (VMAT2)
radioligand, was used to investigate striatal dopamine neuron
density.
Results: Patients with 22q11.2DS were rated significantly higher
than controls on the MDS-UPDRS III (p<0.0001), with bradykinesia
of varying severity observed in 12 of the 13 cases. There were five
with postural/action tremor, and three with rigidity. Nine were
assessed to have a Movement Disorder, including Parkinsonism
(n55), drug-induced Parkinsonism (n52), and postural/kinetic
tremor with and without Parkinsonism (n52). The majority (n510)
of patients with 22q11.2DS were hyposmic, and showed colour dis-
crimination defects relative to controls (p50.02). Substantia nigra
echogenicity was similar between groups (p50.3). Surprisingly,
patients with 22q11.2DS showed 35% higher striatal VMAT2 bind-
ing than controls (p<0.01). Lower levels of binding showed a corre-
lation trend with higher bradykinesia subscores (r=-0.53, p50.08).
Conclusions: These preliminary results show that adults with
22q11.2DS demonstrate motor and non-motor features possibly con-
sistent with pre-diagnostic and pre-motor stages of PD. The presyn-
aptic dopaminergic abnormality identified using PET imaging
suggests a novel pathway to Parkinsonism and/or PD in 22q11.2DS.
Larger, longitudinal studies are needed to determine if the observed
imaging, motor, and other phenotypes are prodromal markers of PD
in this genetic syndrome.
1025
Genetic variants of SNCA are associated with the susceptibility
of Parkinsons disease but not for amyotrophic lateral sclerosis
and multiple system atrophy in a Chinese population
Y. Chen, Q. Wei, R. Ou, B. Cao, X. Chen, B. Zhao, K. Chen, W.
Song, H. Shang (Chengdu, Peoples Republic of China)
Objective: To elucidate the role of polymorphisms of alpha-
synuclein (SNCA) among different ethnic backgrounds, three poly-
morphisms, rs3775444, rs3822086 and rs11931074, which were
strongly associated with PD in Caucasian population, were studied in
this study.
Background: In consideration of the overlapping of clinical man-
ifestations and pathologic characteristics among PD, amyotrophic lat-
eral sclerosis (ALS), and multiple system atrophy (MSA), the
possible associations of aforementioned three polymorphisms and
these three neurodegenerative diseases were studied in a Chinese
population.
Methods: A total of 1276 PD, 885 sporadic ALS (SALS), 364
MSA patients, and 846 health controls (HCs) were included. All sub-
jects were genotyped for the three polymorphisms using Sequenom
iPLEX Assay technology.
Results: Significant differences in the genotype distributions
(p55.99E-06 and p54.98E-06, respectively) and the minor allele fre-
quency (MAF) (p52.16E-06 and p52.15E-06, respectively) of
SNCA rs3822086 and rs11931074 were observed between PD and
HCs. However, no differences were found in the genotype distribu-
tions and MAF of SNCA rs3775444 between PD and HCs. Haplo-
type incorporating the three SNPs strengthened the association with
PD further (best haplotype, p59.62E-005). No significant differences
in the genotype distributions and MAF of the SNPs were found
between SALS and HCs, between MSA and HCs, and between sub-
groups of PD and SALS. However, the MAF of SNCA rs3775444
was significantly higher in MSA patients with frontal lobe dysfunc-
tion than those without (OR 2.53, 95%CI: 1.55-4.15).
Conclusions: Our results suggest the rs3822086 and rs11931074
in SNCA decrease the risk for PD, and SNCA rs11931074 may
affect frontal lobe dysfunction of MSA, in the Chinese population.
These polymorphisms in SNCA are unlikely to be a common cause
of SALS and MSA.
S401
1026
Mitochondria-related genes and the risk of Parkinsons disease
and Alzheimers disease: Gene-gene interaction analysis
S.J. Chung, J. Kim, Y.J. Kim, K. Kim, S. You, M.J. Kim, H.S. Ryu,
S.Y. Kim, J.H. Lee (Seoul, Korea)
Objective: To investigate the role of genetic interaction among
mitochondria-related genes in the development of Parkinsons dis-
ease (PD) and Alzheimers disease (AD).
Background: Mitochondrial dysfunction in the substantia nigra
has been documented in patients with PD. It is also recognized as
major contributor in amyloid beta-mediated neurotoxicity in AD.
The importance of mitochondria to the cause and pathogenesis of PD
and AD has been reinforced by the identification of specific muta-
tions in the mitochondria-linked genes.
Methods: The mortalin (HSPA9), parkin, PINK1, DJ1, and
COQ2 genes were selected. For HSPA9, direct sequencing using an
automated DNA sequencer (ABI 3730, Applied Biosystems, CA,
USA) for the entire coding region (17 exons) and exon-intron bound-
ary of 50 bp was performed in 24 PD patients, 24 AD patients, and
24 controls. The genetic variants with minor allele frequency
(MAF) > 1% from sequencing data were selected for the second-
stage genotyping. Common (MAF > 5%) and low-frequency
(MAF 5 1 5%) genetic variants were also selected using the Hap-
Map and 1000 Genomes Project JPT and CHB samples to select var-
iants in the HSPA9, parkin, PINK1, DJ1, and COQ2 genes. We
genotyped genetic variants (8 in HSPA9, 10 in parkin, 4 in PINK1, 6
in DJ1, and 2 in COQ2) in 500 PD cases, 400 AD cases, and 500
controls, using the Fluidigm high-throughput platform. Logistic
regression analysis with additive coding schemes as a primary analy-
sis was performed.
Results: The high-risk group carrying more than 4 risk alleles in
the HSPA9 SNP rs41295739, parkin SNP rs9356040, PINK1 SNP
rs76795760, DJ1 SNP rs2235733, and COQ2 variant M128V had
significantly increased risk of PD compared with the low-risk group
carrying 0-2 risk alleles (v2 5 0.01 for 4 vs 0-2 risk alleles). The
high-risk group carrying more than 3 risk alleles in the HSPA9 SNP
rs41295739, parkin SNP rs1784590, PINK1 SNP rs1043424, DJ1
SNP rs34124834, and COQ2 SNP rs148156462 had significantly
increased risk of AD compared with the low-risk group carrying 0-2
risk alleles (v2 5 0.039 for 4 vs 0-2 risk alleles).
Conclusions: Our results suggest that genetic interaction among
mitochondria-linked genes may play a role in the development of PD
and AD.
1027
Polymorphisms of dopamine receptor genes are associated to
increased risk of visual hallucinations in Italian Parkinsons
disease patients
C. Comi, M. Ferrari, F. Marino, G. Riboldazzi, S. Rosa, R. Cantello,
G. Bono, M. Cosentino (Novara, Italy)
Objective: To determine whether single nucleotide polymor-
phisms (SNPs) of dopamine receptor (DRD) genes are associated
with visual hallucinations (VHs) in Italian Parkinsons disease (PD)
patients.
Background: VHs are a frequent and important non-motor com-
plication of PD. VHs are associated to a negative prognosis, in terms
of both morbidity and mortality. Variations in DRD genes may have
a role in predisposing to VHs, since previous studies showed an
association between DRD variations and Alzheimers disease with
psychosis, as well as schizophrenia and bipolar disorder. There is
only one published study on DRD variations in PD subjects with and
without VHs, in which no statistically significant association was
found.
Methods: Case-control study of 84 PD subjects, 42 with and 42
without VHs matched for age, gender, disease duration and dopami-
nergic medication. Genomic DNA was analyzed by polymerase chain
Movement Disorders, Vol. 30, Suppl. 1, 2015
S402 POSTER SESSION

reaction for SNPs in both D1 (DRD1 A48G and C62T, DRD5 T798C)
and D2-like receptor genes (DRD2 G2137A and C957T, DRD3 G25A
and G712C, DRD4 C616G and nR VNTR 48 bp). Genotype distribu-
tions and allele frequencies were compared between groups.
Results: Allelic frequencies did not deviate from Hardy-Weinberg
equilibrium. We found that patients with, compared to those without VHs,
had a statistically increased frequency of the following alleles: allele G at
DRD1 A48G (OR 3.7; P 5 0.0075), allele T at DRD1 C62T (OR 10.7;
P 5 0.0001) and allele T at DRD2 C957T (OR 3.4, P 5 0.0286). No sig-
nificant association with VHs was found for the other DRD SNPs. On a
functional level, D1 and D2 receptor systems have opposite effects on
cAMP, with the former increasing and the latter decreasing its production.
Notably, DRD1 62T is known to increase gene expression, whereas
DRD2 957T decreases mRNA stability, and those two effects point to a
synergistic over-activation of the D1 signalling pathway.
Conclusions: Our study shows that PD patients with VHs display
higher frequency of DRD SNPs that are known to increase cAMP
intercellular levels. Our data are in line with robust associations pub-
lished in psychiatric conditions, such as nicotine and alcohol depend-
ence, bipolar disorder and psychoses. On a clinical level, our Fig. 1. (1028).
findings may provide valuable information for personalizing pharma-
cological therapy in PD patients.

Met/Val 9.1(1/-3.3), Val/Val 8.8(1/-3.3), p50.005). This difference

1028
was mainly due to higher dyskinesia subscores, in Met allele carriers
Effect of catecho-O-metyltransferase (COMT) genotype on the (p50.006). Patients with the Val/Val genotype had higher global
response to bilateral subthalamic deep brain stimulation (DBS- cognitive efficiency scores (MDRS) when adjusted for age, gender
STN) in Parkinsons disease (PD) and disease duration (139.0(1/-4.8) vs 137.6(1/-10.1), p50.03).
F. Cormier-Dequaire, S. Bureau, K. Tahiri, G. Mangone, J. After surgery, we observed a difference between groups for UPDRS
Kraemmer, A. Welaratne, C. Karachi, A. Birce, M.L. Welter, J.C. IV (p50.003) and dyskinesia subscores (p50.0002) with a greater
Corvol (Paris Cedex 13, France) decrease in Met allele carriers, an allele dose effect (Met/Met -
7.6(1/-4.6), Met/Val -7.0(1/-4.0), Val/Val -6.1(1/-4.2), p50.005),
Objective: To evaluate the influence of COMT genotype on and an interaction between the effects of DBS and COMT genotype
DBS-STN response in PD patients. on dyskinesia (p50.03). [figure1]
Background: Bilateral DBS-STN is proposed to PD patients at Conclusions: Our study confirms the influence of COMT geno-
motor fluctuation stage and has been shown to dramatically alleviate type on dyskinesia and cognition in PD patients. We did not found
motor symptoms. However, some patients have poor outcome with any influence of COMT genotype on neither motor effect nor cogni-
low effect on motor symptoms and non-motor side effects. COMT tive outcome under DBS-STN. A greater diminution of dyskinesia
genotype modifies dopa biodisponibility, dyskinesia and working under DBS-STN in Met/Met PD patients was observed, suggesting
memory in PD patients so we hypothesised that it may influence an interaction of COMT genotype with DBS STN response on
DBS response and contribute to explain heterogeneous outcomes. dyskinesia.
Methods: We compared motor (UPDRS) and cognitive (MDRS)
assessments preoperative and 12 months after DBS-STN in PD
patients at the Pitie-Salpetriere Hospital. . The COMT Valine(- 1029
Val)158Methionine(Met) polymorphism was analyzed by allelic dis-
crimination Taqman assay. All statistical analyses were performed Using a GBA deficient drosophila model to understand
with Statistica software. pathogenic mechanisms in PD
Results: Between 1996 and 2009, 309 PD patients underwent M.Y. Davis, K. Trinh, R. Thomas, B. Whittley, T. Montine, L.
DBS-STN surgery. Among them, 257 were genotyped for the COMT Pallanck (Seattle, WA, USA)
Val158Met polymorphism and included in the analysis. Sixty-three Objective: To understand how glucocerebrosidase (GBA) muta-
(25%) had Met/Met genotype, 124 (48%) Val/Met, and 70 (27%) tions increase susceptibility to Parkinsons disease (PD).
Val/Val, which respected Hardy Weinberg equilibrium. Background: PD is a common neurodegerative disorder charac-
terized by progressive motor symptoms and cognitive decline. Our
understanding of its pathogenesis is limited, and currently no
Patient characteristics disease-modifying therapies exist. GBA mutations are the strongest
Met/Met Val/Met Val/Val genetic risk factor for PD. GBA encodes the lysosomal enzyme glu-
(n563) (n5124) (n570) cocerebrosidase and biallelic GBA mutations cause Gauchers dis-
ease, the most common lysosomal storage disease. Unlike rare
Age, years 54,2 (9,5) 55,5 (8,8) 55,0 (10,2) Mendelian forms of PD, GBA carriers with PD have similar clinical
Sex ratio, M/F 39/24 72/52 48/22 and neuropathological features to sporadic PD, making GBA loss of
Age at onset, years 43,9 (7,1) 42,7 (9,3) 43,0 (9,3) function models attractive for investigating mechanisms underlying
Disease duration, years 12,1 (4,7) 13,2 (6,4) 12,0 (4,5) PD.
Dopa equivalent dose 1159 (475) 1120 (537) 1136 (469) Methods: A Drosophila mutant (referred to as GBA1del) was
created that deletes coding sequences of GBA1a and GBA1b, the
two homologs of human GBA1 in flies.
Values are mean (standard deviation) Results: GBA1del homozygotes have reduced glucocerebrosidase
(GCase) enzyme activity compared to controls and accumulate glu-
At baseline, we observed higher scores of UPDRS IV in cosylceramide, the substrate of GCase. GBA1del homozygotes have
Met allele carriers and an allele dose effect (Met/Met 10.0(1/-3.8), shorter lifespan compared to controls, age-dependent decreased

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
climbing ability, delayed recovery from heat-induced paralysis, and
delayed recovery from mechanical stress (bang sensitivity). Histopa-
thology of 30 day old GBA1del homozygote brains revealed multiple
vacuoles suggestive of neurodegeneration that was not present in
age-matched control brains. Since GBA is also associated with
increased risk of cognitive symptoms in PD, we used a simple court-
ship assay to test learning and memory. This assay did not reveal a
difference in learning between control and GBA1del homozygotes,
however GBA1del homozygotes and heterozygotes had decreased
latency to initiate courtship compared to controls by 24 hours after
training, consistent with a memory defect. Western blot analysis
revealed accelerated insoluble protein aggregation in GBA1del
homozygotes and was rescued by disruption of the enzyme ceramide
glucosyl transferase.
Conclusions: We have developed a GBA deficient Drosophila
model that manifests motor and memory deficits similar to PD. Our
results suggest that GBA deficiency causes glucosylceramide accu-
mulation, disruption of lysosomal function and protein turnover. Fur-
ther studies using this model will elucidate the pathogenic
mechanisms causing PD and may reveal potential new targets for
disease-modifying therapies.
1030
DNA methylation as an epigenetic biomarker for Parkinsons
and Alzheimers diseases
E. Driver-Dunckley, B. Meechoovet, R. Caselli, C. Adler, T. Beach,
T. Dunckley (Scottsdale, AZ, USA)
Objective: Biomarkers that aid in earlier diagnoses of Alzhei-
mers (AD) or Parkinsons disease (PD) could facilitate earlier diag-
nosis and treatment of these diseases. Here we characterize the
global methylation profiles from patients with post-mortem neuropa-
thologic confirmation of either AD or PD and confirm specific meth-
ylation changes in a prospective cohorts of patients.
Background: Many complex sporadic neurodegenerative disor-
ders are the phenotypic expression of interactions between environ-
mental influences and an individuals inherent genetic risk. Specific
molecular mechanisms mediating the differential impact of environ-
mental factors on susceptible individuals leading to the development
(and prevention) of neurodegenerative disease remain unclear. Epige-
netic changes to DNA methylation patterns at specific genomic loci
have been found in individuals with AD and PD. A more complete
genome-wide characterization of the methylation events in AD and
PD could add new insights into the etiology of these disorders.
Methods: Genome-wide methylation profiles were obtained on
blood samples from 19 neurologically normal controls, 20 AD and
19 non-demented PD patients using the Illumina Infinium 450K
Methylation BeadChip. Consented subjects gave blood samples and
subsequently followed through end of life. Neuropathology analyses
confirmed the respective clinical diagnoses. A second validation
cohort of 15 controls, 10 AD, and 15 PD patients was prospectively
recruited based purely on clinical criteria.
Results: We obtained robust data on over 480,000 CpG methyla-
tion sites in the form of beta values, which represent the ratio of
methylated CpG to the sum of methylated plus nonmethylated CpG
at a given site. Thus, these values range from 0 (unmethylated) to 1
(fully methylated). Significant methylation differences in the discov-
ery cohort of neuropathological-confirmed cases and controls were
then confirmed in the second prospectively recruited cohort.
Conclusions: Methylation profiles in the blood of individuals
with AD or PD and healthy controls show distinct differences. Fur-
ther validation efforts on larger sample sets, and characterization of
methylation status in patients at varying stages of disease, will help
to establish whether methylation status at specific loci could be
leveraged as a biomarker to track disease progression or aid in dis-
ease diagnosis.
S403
1031
Substantia nigra hyperechogenicity in LRRK2 G2019S mutation
carriers
A. Drobnis, J. Hagenah, R.A. Ortega, A. Glickman, C. Wang, A.
Deik, J. Soto-Valencia, B. Johannes, M. Barrett, D. Raymond, L.J.
Ozelius, K. Marder, N. Giladi, S.B. Bressman, R. Saunders-Pullman
(New York, NY, USA)
Objective: To determine whether G2019S mutations in the
LRRK2 gene are associated with substantia nigra hyperechogenicity.
Background: Enlarged areas of hyperechogenicity in the substan-
tia nigra (aSN) are a promising pre-clinical marker of LRRK2 Par-
kinsons disease (PD). As greater aSN may precede onset of PD
motor symptoms, TCS is a non-invasive method with the potential to
identify individuals at high risk for development of PD.
Methods: We previously reported hyperechogenicity in LRRK2
PD and LRRK2 non-manifesting carriers (NMC). To further explore
the association between hyperechogenicity and LRRK2 mutation car-
riage, we assessed maximum area of hyperechogenicity in the sub-
stantia nigra (aSNmax) with transcranial sonography (TCS) in an
expanded cohort at Mt Sinai Beth Israel. 60 LRRK2 and GBA muta-
tion negative PD (IPD), 55 PD with LRRK2 mutations(LRRK2-PD),
47 NMC, 28 non-LRRK2 mutation family members without PD
(NC-F), and 74 healthy control subjects, from 52 LRRK2 families
were scanned (52% LRRK2-PD and 23% IPD previously reported).
A rater blinded to gene status identified and measured areas of
hyperechogenicity. Differences between groups were compared using
rank sum tests and generalized linear models (GLM) adjusting for
age and gender (and duration in PD).
Results: Both IPD and LRRK2-PD were significantly older than
NMC, NC-F, and controls (p<0.01 for all comparisons). The IPD
and LRRK2-PD groups were not different from one another in age
or duration of disease. aSNmax compared with controls was greater
in IPD (IPD: 0.27cm260.12, vs controls: 0.20 6 0.10; p<0.01), as
well as in LRRK2-PD (0.30 6 0.10), NC-F (0.26 6 0.11), and NMC
(0.26 6 0.14) compared with controls (p<0.01, p<0.01, and p50.01
respectively), and was greater in LRRK2-PD vs NMC (p50.05), but
LRRK2-PD was not different than IPD. In GLM, all differences
remained significant except for LRRK2-PD vs NMC (p50.14).
Conclusions: In this larger sample we demonstrate that harboring
a LRRK2 mutation is associated with nigral hyperechogenicity, and
is present in carriers without PD as well. Of note, NC-F also demon-
strated hyperechogenicity, further raising the question as to whether
additional factors that might predispose to PD are more frequent in
this group. Longitudinal study is warranted to determine whether
NMC with more hyperechogenicity are at higher risk for
phenoconversion.
1032
Withdrawn by Author
1033
Genetic loci of Parkinsons disease in rapid eye movement sleep
behavior disorder
Z. Gan-Or, S.L. Girard, A. Noreau, C.S. Leblond, J.F. Gagnon, I.
Arnulf, Y. Dauvilliers, A. Desautels, V. Cochen De Cock, B.
Frauscher, C. Monaca, B. Hogl, P.A. Dion, R.B. Postuma, J.Y.
Montplaisir, G.A. Rouleau (Montreal, QC, Canada)
Objective: We aimed to examine whether known genetic markers
of Parkinsons disease (PD) are also associated with Rapid eye
movement (REM) sleep behavior disorder (RBD), and with progres-
sion from RBD to synucleinopathies.
Background: Parkinsons disease (PD) and other synucleinopa-
thies often occur after a prodromal stage of RBD. While the genetic
background of PD has been extensively studied, the contribution of
Movement Disorders, Vol. 30, Suppl. 1, 2015
S404 POSTER SESSION
genetic factors to RBD and to progression from RBD to PD is still
unknown.
Methods: 261 RBD patients and 379 controls were analyzed for
nine SNPs previously associated with PD, and their effects on RBD
risk were examined, as well as their effects on the eventual progres-
sion to synucleinopathies, which was examined in a prospective
follow-up in a subset of patients.
Results: Two known PD SNPs, rs6812193 (annotated to the
SCARB2 gene, OR=0.67, 95% CI=0.51-0.88, p50.004) and
rs12185268 (annotated to the MAPT gene, OR=0.43, 95% CI=0.26-
0.72, p50.001) were associated with RBD. Kaplan-Meier survival
analysis in a sub-set of RBD patients who underwent prospective
clinical follow-up (n556, clinicians were blinded to the genetic sta-
tus), demonstrated that homozygous carriers of the USP25 rs2823357
SNP had progressed to synucleinopathies faster than others (Log-
rank p50.003, Breslow p50.005, Tarone-Ware p50.004).
Conclusions: Our results demonstrate that RBD is associated
with at least a subset of PD-associated genes, and suggest that com-
bining genetic and prodromal clinical data may facilitate the identifi-
cation of individuals that are either susceptible or have reduced risk
to develop synucleinopathies.
1034
Postural control alterations in healthy LRRK2 G2019S mutation
carriers
N. Giladi, Y. Beck, K. Brockmann, D. Berg, B.J. War, J. Aasly, C.
Pont Sunyer, D. Vilas, A.K. Rao, K.S. Marder, R. Sunders-Pullman,
S.B. Bressman, A. Orr-Urtreger, J.M. Hausdorff, A. Mirelman (Tel
Aviv-Yafo, Israel)
Objective: Identify associations between sway kinematics and the
LRRK2 G2019S mutation.
Background: Studies in healthy adults have shown that gait vari-
ability in LRRK2 G2019S mutation carriers was worse than in non-
carriers and balance deficits were identified in individuals with a
high risk for developing Parkinsons disease (PD) during challenging
conditions. The present work extends these earlier studies to investi-
gate sway in healthy asymptomatic LRRK2 G2019S mutation car-
riers, a group of adults with an increased risk of developing PD.
Methods: The study was conducted as part of the gait Consortium
LRRK2 study funded by the Michael J Fox foundation. Sway measure-
ments were collected using a 3D accelerometer worn on the lower back.
Sixty-one non-manifesting LRRK2 G2019S mutation carriers (NMC)
and 61 non-manifesting non-carriers (NMNC) were studied. Subjects
stood quietly for 30 seconds with a comfortable base of support and eyes
open. Sixty-four different parameters were calculated from the acceler-
ometer signals: 22 in the time domain, 10 in the frequency domain, and
32 in phase space. To account for multiple comparisons, a threshold of
0.05/64 5 0.0008 was used as the level of significance.
Results: The groups were similar with respect to age, gender,
height, weight, and cognitive function. Differences between groups
were observed in the time domain, frequency domain and phase space.
For example, mean velocity of the COM in the medio-lateral (ML)
direction (NMC: 0.01 6 0.008 m/sec, NMNC: 0.026 6 0.019 m/sec,
p<0.0001) and path length in the anterior-posterior (AP) direction
were higher in the non-carriers (NMC: 28.52 6 0.726 m/sec2, NMNC:
29.37 6 1.134 m/sec2, p50.0002). The mean length of the diagonal
lines in the recurrence plot in the AP direction, a reflection of the
average length of a recurring state, was larger in the carriers (NMC:
5.52 6 1.29, NMNC: 4.63 6 0.70, p50.0003).
Conclusions: These results support the existence of subtle motor
changes in postural control among asymptomatic G2019S mutation
carriers. Time, frequency and phase space measures demonstrate
more constrained movements among carriers which reflect decreased
sway. Larger scale longitudinal studies are needed to further investi-
gate sway kinematics as a predictor of disease and as a marker for
disease progression.
Movement Disorders, Vol. 30, Suppl. 1, 2015
1035
The SNP rs11868035 may not confer genetic risk toward
Parkinsons disease in central China
C. Han, J. Huang, N. Xiong, L. Liu, G. Zhang, H. Jiang, J. Yang, J.
Li, X. Xu, Y. Shen, T. Wang (Wuhan, Peoples Republic of China)
Objective: To evaluate whether or not the rs11868035 correlates
with Parkinsons disease (PD) in central China.
Background: Genotype-environment interaction is now approved
to be a significant mechanism contributing to PD, people with some
genes are more susceptible to Parkinsons disease. Among which, the
novel single nucleotide polymorphim (SNP) rs11868035 was previ-
ously reported to be associated with PD in a Web-Based Genome
Wide Association Study, however, when referring to the central
China, there is still no definite relationship.
Methods: We conducted a case-control study on patients from
central China, including 376 PD patients and 320 controls to deter-
mine the distribution of rs11868035.
Results: Our data indicates no significant difference in either
genotype frequencies or allele frequencies. Simultaneously, no
detectable difference is observed between EOPD patients and con-
trols, as is the same for LOPD. Besides, the genotype seems to have
less to do with age.
Conclusions: We conclude that maybe no association exists
between rs11868035 and PD in central China. A study evolving
larger samples is recommended.
1036
CSF derived exosomal microRNA profile in patients with
Parkinsons disease
T. Hasegawa, N. Sugeno, A. Kikuchi, R. Oshima, S. Yoshida, A.
Takeda, M. Aoki (Sendai, Japan)
Objective: The aim of this study is to characterize the CSF
derived, exosomal microRNA (miRNA) profiles in PD patients and
healthy controls, to determine its usefulness as biomarkers for PD.
Background: The clinical diagnosis of Parkinsons disease (PD)
entirely relies on medical history, neurological findings and the
response to dopamine-replacement therapy. However, for develop-
ment of disease-modifying therapy, early diagnosis by objective lab-
oratory test is urgently needed.
Methods: The study cohort consisted on sex and age matched
healthy controls (n53; mean age 67.6; 2 males and 1 female) and
patients (n55; mean age 63.9; 3 males and 2 females) who fulfilled
the clinical diagnostic criteria of PD. Exosome was isolated from
freshly corrected CSF using ExoMir kit (Bioo Scientific). After puri-
fication of miRNA from exosome, Agilent Human microRNA Micro-
array v2.0 (Agilent Technologies) was used to identify miRNAs
expressed at high level in CSF derived exosome in PD patients ver-
sus controls. Total RNA (100 ng per sample) was hybridized to the
microarrays. Predicted miRNA-mRNA interactions were taken from
TargetScan 4.1 and miRDB ver.5 and DIANA LAB.
Results: We identified that the expression of hsa-miR-X miRNA,
which specifically binds the mRNA of polo-like kinase (PLK)2, a
known a-synuclein kinase, was significantly higher in PD patients
compared to controls.
Conclusions: CSF derived, exosomal miRNA expression profiles
may provide supplemental biomarkers for diagnosing PD.
1037
Association between PARK16 variants and Parkinsons disease
in central China: A case-control study
H. Jiang, J. Huang, N. Xiong, L. Liu, G. Zhang, C. Han, J. Yang, X.
Xu, J. Li, Y. Shen, T. Wang (Wuhan, Peoples Republic of China)
 POSTER SESSION
Objective: To investigate whether or not three single-nucleotide
polymorphisms (SNPs) within PARK16 locus contribute to the risk
of Parkinsons disease (PD) in central China.
Background: Several PARK16 variants have been reported to be
associated with PD worldwide. However, published data in different
regions were inconsistent and there was little information for popula-
tion in central China.
Methods: We genotyped three SNPs within the PARK16 locus
(rs823114, rs823156, and rs947211) among 401 PD patients and 393
control subjects in central China. Then we analyzed allelic and geno-
typic associations between PD patients and controls.
Results: Our results showed that the minor allele of rs823156
(OR=1.355, P=0.028) was associated with risk for PD, and G carriers
of rs823156 conferred higher risk than A carriers (OR=2.313,
P=0.027). While the minor allele of rs823114 (OR=0.794, P=0.028)
seemed to be a protective factor, and A carriers of rs823114 con-
ferred lower risk for PD than G carriers (OR=0.642, P=0.013). How-
ever, there was no statistically significant association of rs947211
with PD for both allelic and genotypic analyses in our study.
Conclusions: Our observations indicated that rs823156 variant
within PARK16 might confer genetic risk for PD among the popula-
tion in central China while rs823114 might be a protective factor.
1038
The tyrosine hydroxylase Val81Met polymorphism is associated
with motor symptom severity in de novo patients with
Parkinsons disease
J. Kraemmer, F. Cormier-Dequaire, A. Brice, J.C. Corvol, PPMI
Genetic Working Group (Paris, France)
Objective: We aimed to investigate the relationship between the
Tyrosine hydroxylase (TH) Val81Met polymorphism, dopamine
denervation and motor severity in subjects with de novo Parkinsons
disease (PD).
Background: TH is the rate-limiting enzyme in dopamine bio-
synthesis and has been functionally implicated in compensatory
mechanisms in the presymptomatic and early symptomatic stage of
PD. The individual compensatory potential may be altered by genetic
variation. A previous study has suggested the TH Val81Met poly-
morphism (rs6356, MAF 0.419) to be associated with the Unified
Parkinsons disease Rating Scale (UPDRS) motor score in patients
with early PD.
Methods: All data used for this analysis were obtained from the
Parkinsons Progression Markers Initiative (PPMI) database (www.
ppmi-info.org/data). Patients were included in the analysis if they
were caucasian, drug-nave at screening, and underwent dopamine
transporter (DAT) imaging within one month of clinical evaluation.
Genotype of the rs6356 TH polymorphism was extracted from Neu-
roX single nucleotide polymorphism (SNP) arrays using plink
software.
Results: Among the 656 subjects enrolled in PPMI, 293 PD
patients matched all criteria and were selected for further analysis.
Genotype distribution was in Hardy-Weinberg equilibrium (p50.27):
121 GG (homozygous for the ancestral allele), 127 GA, 45 AA. A
allele carrier status was found to be associated with significantly
higher MDS-UPDRS III scores (t-test, p50.012) and remained sig-
nificant when taking into account gender, center effect, age and dis-
ease duration at the time of evaluation, as well as striatal DAT
Characteristics of the study population
N Males Age at Data, years Age at Disease Onset, years
77 43 (55.8%) 63.5 (11.0) 56.1 (10.6)
S405
binding averaged for both sides (multivariate analysis, p50.01). An
even stronger association with MDS-UPDRS III scores was found in
the allele-dosage model (ANOVA, p50.007; multivariate analysis,
p50.001). No association was found between the TH rs6356 poly-
morphism and DAT scan measures.
Conclusions: Our results suggest that the TH rs6356 polymor-
phism influences motor symptom compensation at onset of PD. The
functional relevance of this finding remains to be understood.
1039
Whole-exome sequencing for mutation discovery in an African-
American pedigree with Parkinsons disease
M.S. LeDoux, S.R. Vemula, J. Xiao, O.A. Ross, Z.W. Wszolek
(Memphis, TN, USA)
Objective: Genetically and phenotypically characterize a large
African-American pedigree with familial Parkinsons disease (PD).
Background: Some studies suggest that Parkinsons disease (PD)
is less prevalent in African than European Americans, perhaps due to
ascertainment bias. Moreover, most pedigree-based gene mapping
and genome-wide association studies in PD have been limited to
Caucasians of European descent. Therefore, the role of genetics in
the pathogenesis of PD in African-Americans has been understudied.
Methods: Sanger and whole-exome sequencing.
Results: Among 5 affected family members, age of onset ranged
from 54 to over 65 yrs of age. Characteristic features of this pedigree
include early hyposmia, asymmetric tremor, positive responses to
levodopa, prominent rigidity, hypophonia and palilalia. After exclu-
sion of SNCA multiplications and common mutations in PD-
associated genes with Sanger sequencing, whole exome sequencing
in the proband exposed missense variants in LRRK2 (c.3784C>G)
and PINK1 (c.1502G>A) that are predicted to be deleterious via in
silico analyses and show marked differences in population frequen-
cies between Caucasians and African-Americans. In particular,
LRRK2 rs4640000 (c.3784C>G) is rare to absent in Caucasians, rela-
tively common in African-Americans, and has a CADD C-score of
21.6. The proband was also found to harbor an additional 28 novel
variants predicted to be definitely pathogenic by PolyPhen-2, Muta-
tionTaster, SIFT and LRT.
Conclusions: Race/ethnicity and the limitations of in silico analy-
ses must be taken into account when interpreting data derived from
whole-exome sequencing. Familial PD does occur in African-
Americans and may be genetic in origin.
1040
Genetic variation and cognitive impairment in Parkinsons
disease patients from Uruguay
A. Lescano, V. Raggio, E. Dieguez, B. Aguiar, L. Bocos, N.
Gonzalez, F. Salda~ na, J. Sburlati, J.M. Carrasco, F. Brunet, I.
Amorn, R. Aljanati, M. Martinovic, L. Roche, R. Buzo, S. Dansilio,
M. Inca-Martinez, B.A. Cholerton, C.P. Zabetian, I. F. Mata (Monte-
video, Uruguay)
Objective: To determine whether common variation in the APOE
and MAPT genes is associated with cognitive performance in patients
with Parkinsons disease (PD) from Uruguay.
Background: Cognitive impairment (CI) commonly occurs in PD
and has a major impact on quality of life and mortality. Available
Mean (SD)
Disease Duration, years Education, years MoCA
7.4 (5.6) 8.8 (5.0) 22.3 (5.5)
Movement Disorders, Vol. 30, Suppl. 1, 2015
S406 POSTER SESSION
evidence suggests that genetic variants in several genes, including
APOE and MAPT, might play a role in determining susceptibility to
CI in PD, yet this has not been examined extensively in Latin Amer-
ican populations.
Methods: We studied 77 PD patients with a mean level of educa-
tion of 8.8 years from the Polyclinic of Parkinsons and Movement
Disorders at the Institute of Neurology, School of Medicine in Mon-
tevideo, Uruguay.
All study participants, followed as part of the Latin American
Research consortium on the Genetics of PD (LARGEPD), underwent
assessment of global cognitive abilities using the Montreal Cognitive
Assessment (MoCA). Subjects were genotyped for APOE rs429358
and rs7412 (which define the e2, e3, and e4 alleles) and MAPT
rs1800547 (which differentiates the H1 and H2 haplotypes) using
TaqMan assays on an ABI7900. We performed linear regression to
test for association between genotype and cognitive performance
with adjustment for age, sex, years of education and disease
duration.
Results: The APOE e4 allele was associated with lower perform-
ance on the MoCA (P=0.02, b coefficient 5 2.76 [5.11 to 0.42]),
while MAPT H1/H2 was not associated with MoCA scores (P=0.75).
Conclusions: Our data indicate that in a Uruguayan sample of
PD patients the APOE e4 allele, but not MAPT H1/H2, predicts
lower global cognitive function as indicated by performance on the
MoCA. Our results extend findings from a recent multicenter study
of highly educated PD patients in the US to a Latin American popu-
lation with lower mean levels of education, and suggest that the
MoCA may be a useful tool for cross-cultural cognitive genetic
studies.
1041
Leucine-rich repeat kinase 2 (LRRK2) interacts with vacuolar
protein sorting 35 (Vps35) to regulate autophagy
R. Linhart, Y.J. Ho, D. Kaing, E. Hou, D. Sohal, R. Eismati, J.
Rosales, R. Fedrizzi, A. Tsang, D. Fong, A. Dawson, K. Venderova
(Stockton, CA, USA)
Objective: The goal of this work is to determine how two autoso-
mal dominant Parkinsons disease genes, LRRK2 and VPS35, inter-
act to regulate neuronal function.
Background: VPS35 codes for the core component of the retro-
mer complex known to be responsible for sorting and trafficking of
select cargo proteins from endosomes to the trans-Golgi network or
plasma membrane. However, how VPS35 contributes to Parkinsons
disease pathology is unknown.
Methods: We employed our LRRK2 overexpressing Drosophila
lines generated previously (Venderova K et al Hum Mol Genet
2009) and other transgenic lines available from the Bloomington
Drosophila Stock Center, and from the Exelixis Collection at the
Harvard Medical School.
Results: We demonstrate that overexpressing Vps35 greatly exa-
cerbated the eye phenotype of flies overexpressing Atg1 a kinase
necessary for autophagy initiation. Conversely, knocking-down
expression of Vps35 rescued the Atg1 phenotype. These data suggest
that Vps35 positively regulates autophagy. Next, we analyzed this
interaction in dopaminergic neurons that control movement. We pre-
viously demonstrated that reducing expression of Vps35 in Drosoph-
ila dopaminergic neurons causes locomotor deficits. While
overexpressing Atg1 alone had no effect on locomotor activity, it
failed to rescue phenotype of the Vps35 knock-down flies. Finally,
we observed that similarly to Vps35, overexpressing LRRK2 also
exacerbated the Atg1 eye phenotype. Strikingly however, LRRK2
significantly suppressed the Vps35 phenotype, which is consistent
with our recently published data (Linhart R, Mol Neurodeg 2014).
Conclusions: Altogether, our data suggest that LRRK2 and
VPS35 interact in the autophagy pathway, and that retromer is acting
downstream of Atg1 to positively regulate autophagy.
Movement Disorders, Vol. 30, Suppl. 1, 2015
1042
Genetic variation in GAPDH confers susceptibility to sporadic
Parkinsons disease in central Chinese population
L. Liu, J. Huang, N. Xiong, G. Zhang, X. Xu, C. Han, J. Li, H. Jiang,
J. Yang, Y. Shen, T. Wang (Wuhan, Peoples Republic of China)
Objective: To evaluate the possible association between
glyceraldehyde-3-phosphate dehydrogenase (GAPDH) variation and
Parkinsons disease (PD) in central Chinese population.
Background: Recent studies have demonstrated that GAPDH is
the composition of Lewy body inclusions and involved in the patho-
genesis of PD. It remains unknown whether or not potential genetic
variation in the GAPDH gene confers susceptibility to sporadic PD.
Methods: A total of 302 sporadic PD patients and 377 healthy
control subjects were recruited in our study for assessing four single
nucleotide polymorphisms (rs3741918, rs1060621, rs1060620 and
rs1060619) in the GAPDH gene. Single-locus and haplotype-based
tests of association were employed in this study.
Results: In the multivariate logistic regression analysis, all these
four polymorphisms were significantly associated with increased risk for
sporadic PD, even after a strict Bonferroni correction analysis
(OR=1.55, 95% CI=1.14-2.09, corrected P=0.018; OR=1.59, 95%
CI=1.17-2.15, corrected P=0.012; OR=1.75, 95% CI=1.29-2.36, cor-
rected P=0.001 and OR=1.71, 95% CI=1.27-2.31, corrected P=0.002
under additive model, respectively). In addition, two haplotype blocks
were observed as Block 1 (rs3741918 and rs1060621, TT) and Block
2 (rs1060620 and rs1060619, AT) conferring risk for sporadic PD.
Conclusions: Our study indicates that GAPDH variants influence
susceptibility to sporadic PD, which is consistent with the role of
GAPDH protein in neuronal apoptosis. To our knowledge, this is the
first study to explore the genetic association between GAPDH poly-
morphisms and the risk of sporadic PD.
1043
Olfaction in Parkin compound and single heterozygotes in young
onset United Kingdom PD patients
N. Malek, K.A. Grosset, M.A. Lawton, C.R. Smith, N. Bajaj, R.A.
Barker, Y. Ben-Shlomo, C. Bresner, D.J. Burn, T. Foltynie, H.R.
Morris, N. Williams, N.W. Wood, D.G. Grosset, On Behalf of PRo-
BaND Collaborators (Glasgow, United Kingdom)
Objective: To compare olfaction results according to Parkin
genotype status. To compare the prevalence of Parkin single hetero-
zygosity in Parkinsons disease (PD) cases to the 3.7% rate in
healthy controls [1].
Background: Parkin positive (homozygote or compound hetero-
zygote) PD is differentiated from idiopathic PD by absent or sparse
Lewy bodies at autopsy and preserved olfaction during life. The sig-
nificance of single Parkin mutations (single heterozygosity) is
debated, but impaired olfaction suggested that their PD was unrelated
to the heterozygous state [2].
Methods: Comprehensive analysis of the Parkin gene (Sanger
sequencing, multiplex ligation-dependent probe amplification analy-
sis) was performed in early onset PD patients (diagnosed <50 years
old in the Tracking Parkinsons study) to identify three PD patient
groups: compound heterozygotes (bi-allelic Parkin mutation carriers),
single heterozygote Parkin mutation carriers, and PD patients with
normal Parkin analysis. Olfaction was tested using the 40-item
United Kingdom version of the University of Pennsylvania Smell
Identification Test. Cases positive for LRRK2, GBA, and PINK1 were
excluded from olfaction analysis.
Results: Of 326 early onset PD cases, 7 (2.1%) were Parkin
compound heterozygotes, and 13 (3.9%) were Parkin single hetero-
zygotes. Olfaction results were available in 242 cases (7 compound,
9 single, and 226 PD gene test negative cases). In compound hetero-
zygotes, the median olfaction score was 30, inter-quartile range
(IQR) 28-36, which was significantly better than in single heterozy-
gotes (median 19, IQR 18-28) and gene test negative PD cases
 POSTER SESSION S407

(median score 23, IQR 16-28)(Kruskal Wallis p50.0062). These dif-

ferences persisted after adjusting for age, disease duration and gender
(Tukey, 95% confidence intervals). There was no significant differ- Conclusions: We have established the infrastructure and com-
ence in olfaction scores between single Parkin cases and gene test pleted patient entry for a large cohort study in PD, with support for
negative PD cases (Mann Whitney p50.9912). biomarker studies, in both recent and young onset cases.
Conclusions: Olfaction is normal in Parkin compound heterozy-
gotes, but abnormal in Parkin single heterozygotes and idiopathic
PD, which matches findings in a US study [1]. The prevalence of 1045
Parkin single heterozygotes was similar to healthy European subjects Association of GBA mutations with tau pathology in dementia
[2], suggesting that it is not a significant risk factor for the develop- with Lewy bodies
ment of early onset PD. K.S. Marder, L.N. Clark, R.N. Alcalay, J.P. Vonsattel, L.S. Honig
References: (New York, NY, USA)
1. Alcalay RN et al. Neurology 2011; 76(4): 319-26.
2. Bruggemann N et al. Parkinsonism & Related Disorders 2009; Objective: To determine whether GBA mutations are independ-
15(6): 425-9. ently associated with tau tangle pathology in autopsied brains with
Lewy Body (LB) disorders, with or without AD pathology.
Background: Dementia with LB may relate to synuclein or Alz-
1044
heimer pathology, and has been suggested to more often relate to Ab
Tracking Parkinsons: A United Kingdom cohort study in than tau tangle pathology. GBA mutations are associated with the
Parkinsons disease presence of cortical LB (OR 6.48 95%CI 2.45-17.16, p<0.001) and
N. Malek, K.A. Grosset, M.A. Lawton, N. Bajaj, R.A. Barker, Y. Ben- lesser likelihood of meeting NIA-Reagan Institute intermediate or
Shlomo, D.J. Burn, T. Foltynie, H.R. Morris, N.M. Williams, N.W. high criteria for AD (OR 0.35; 95%CI 0.15-0.79, p50.01) after
Wood, D.G. Grosset, On Behalf of the ProBaND Collaborators adjustment for sex, age-at-death and ApoE4 (Clark 2009). Here we
(Glasgow, United Kingdom) examine relationship of GBA to tau deposition.
Methods: Brain tissue was obtained from the Columbia Univer-
Objective: To explore, in young onset (diagnosed <50 years sity Brain Bank and included 187 cases: 95 with LB disorders with
old) and recent onset Parkinsons disease (PD) (diagnosis < 3 years) or without AD, 60 AD without LB, and 32 controls without AD or
the variation in phenotypic expression across 4 main domains: LB. LB were assessed according to the third report for the DLB con-
motor, non-motor, quality of life and response to drug therapy, in sortium. Neuropathological rating included Braak and CERAD scores
relation to demographic factors, environmental influences and as per National Alzheimer Coordinating Center Neuropathology
genetic traits. Manual Version 9.1. Braak staging of tau deposition was dichotom-
Background: There is wide variation in the phenotypic expression ized as low (Braak 0-IV) vs. high (V-VI). GBA exons were fully
of PD. Large cohort studies are underway to examine the factors influ- sequenced and 32 cases were found to have nonsynonymous coding
encing the phenotypic heterogeneity of PD. Tracking Parkinsons is a sequence mutations (GBAmut).
large prospective, observational, multicentre (n570) project in the Results: GBAmut (n532) were more frequent with low Braak
United Kingdom, also known as the Parkinsons Repository of Bio- stage 23/89 (25.8%) than high Braak stage 9/98 (9.2%), p =0.003. In
samples and Networked Datasets (PRoBaND) study. a logistic regression model, GBAmut (OR 4.17 95%CI 1.63-10.69;
Methods: Standard questionnaires and clinical assessments p50.009), absence of an ApoE4 (ApoE4-)(OR 2.64 95%CI 1.30-5.34
using validated scales are employed. Follow up visits are every 6 p50.007), male gender (OR 2.17 95%CI 1.03-4.23 p50.04), no
months for up to 4.5 years for recent onset PD, and for 1 year for dementia OR 6.96 (3.10-15.76 p<0.001), but not age at death or
young onset PD. All participants have LRRK2 (G2019S) and GBA presence of LB pathology (OR 2.11 p50.07) were associated with
mutation carrier status assessed; early onset cases are also low Braak stage. When analysis was restricted to 108 LB cases (28
screened for mutations in PARK2 and PINK1. Serum samples are GBAmut) both ApoE4- (OR 2.76; 95%CI 1.16-6.56 p50.022) and
collected and stored at -80 degrees centigrade for exploratory bio- GBAmut (OR 4.69 95% CI 1.66-13.28 p50.004) remained signifi-
marker analysis. cant. In a separate model with the addition of CERAD plaque score,
Results: 2239 PD patients have been recruited; their demographic, low Braak (outcome) was associated with GBAmut OR 3.97 (95%CI
motor and non-motor characteristics are summarized in the table. 1.11-14.28; p50.035) and with low amyloid plaque score (CERAD)
(p<0.001) but not with ApoE4, gender, or age-at-death. These results
remained significant when GBA E326K and T369M variants were
Demographics and Clinical scoring in 2239 PD patients excluded from the model.
Young onset Recent Conclusions: GBAmut, with and without dementia, is associated
Variable n5255 onset n51984 with more pure Lewy Body pathology characterized by low tangle
burden, even in the presence of neuritic amyloid plaques.
Age at diagnosis (years) 43.4 (5.5) 66.2 (9.5)
Male sex 66.3% 65.7%
Handedness (right: left: 88.0: 8.4: 3.6% 85.4: 9.6: 5.0% 1046
mixed) A missense mutation in RAB39b causes X-linked dominant
Disease duration (years) 10.1 (6.6) 1.3 (0.9) Parkinsons disease
Ethnicity: White 95.2% 98.2% I.F. Mata, Y. Jang, C.H. Kim, D. Hanna, M.O. Dorschner, J. Witt,
Hoehn and Yahr stage 2.1 (0.8) 1.7 (0.7) A. Samii, K.A. Chung, D.R. Shprecher, A.J. Espay, F.J. Revilla, S.A.
MDS-UPDRS Part 3 score 28 (15) 29 (12) Factor, O. Klepitskaya, D.S. Higgings, I. Litvan, J.B. Leverenz, J.W.
Non-motor symptom severity 57.6 (42.6) 32.7 (26.2) Roberts, P. Agarwal, D. Yearout, M. Inca-Martinez, E. Martinez,
Montreal cognitive assessment 25.2 (3.6) 24.9 (3.6) T.R. Thompson, B.A. Cholerton, S.C. Hu, K.L. Edwards, K.S. Kim,
Levodopa equivalent daily dose 858 (545) 290 (209) C.P. Zabetian (Seattle, WA, USA)
Objective: To identify the causal gene in a multi-incident family
All data are mean (standard deviation) except where indicated, with Parkinsons disease (PD).
MDS-UPDRS 5 Movement Disorder Society Unified Parkinsons Background: Genes underlying several Mendelian forms of PD
disease rating Scale. have been discovered which have substantially improved our

Movement Disorders, Vol. 30, Suppl. 1, 2015

S408 POSTER SESSION
understanding of the molecular pathogenesis of the disease. The
causative genes in other large PD kindreds remain to be found.
Methods: We studied a large multigenerational pedigree with 7
individuals (5 males, 2 females) affected with clinically typical PD
(mean age at onset, 46.1 years; range, 29-57 years). We performed
exome sequencing on 4 affected and 1 unaffected family members.
A custom analysis pipeline was used to generate a list of coding
mutations that were shared among affected individuals. These candi-
date variants were then Sanger-sequenced in all members of the ped-
igree for whom DNA was available (n516) to assess segregation
with disease. The frequency of selected mutations was assessed in a
multicenter cohort of PD patients enrolled in the Parkinsons Genetic
Research Study (PaGeR) (n51,448). PC12 cells transfected with
wild-type or mutant constructs were used to characterize the corre-
sponding proteins.
Results: We identified a missense mutation in RAB39B (G192R)
that closely segregated with disease and exhibited X-linked dominant
inheritance with reduced penetrance in females. The mutation occurs
at a highly conserved amino acid residue within the hypervariable C-
terminal domain of the protein. RAB39B G192R appears to be rare
as it was not detected in any other PD patients in the PaGeR cohort.
In PC12 cells there was no difference in protein expression levels
between mutant and wild-type, but the mutant protein failed to
migrate into the terminal regions of neurites.
Conclusions: Our data indicate that disruption of normal traffick-
ing of Rab39b results in clinically typical PD. Rab39b is a member
of the Rab GTPase family, a group of small proteins that act as
molecular switches and regulate vesicular transport. Further charac-
terization of normal and aberrant Rab39b function promises to eluci-
date important mechanisms underlying neurodegeneration in PD and
related disorders.
1047
A pilot study in chromosomal alteration and association study of
HTRA2 gene mutations in Parkinsons patients (PD)
A. Meyyazhagan, M. Subramaniam, B. Subramanian, P. Krishnan, G.
Changrathil, S. Keshavarao, B. Vellingiri (Coimbatore, India)
Objective: The study aims to analyze the chromosome alterations
and rare mutations in HTRA2 and its association in PD patients.
Background: Parkinsons disease (PD) is a neurodegenerative
disorder which causes dopaminergic neuronal loss in the nigro stria-
tal pathway. It is a heterogeneous disease, is described as a genetic
psychiatry disorder. Multiple lines of evidence support the notion
that most cases of PD likely have an underlying genetic cause or
predisposition. Recently, association of High temperature require-
ment protein A2 (HTRA2) with Parkinsons disease is discussed in
the context of a Parkinsons disease. Rare mutations and copy num-
ber variation (CNV) evidence suggested HTRA2 as a strong candi-
date gene for the pathogenesis of PD.
Methods: In the present study, in order to investigate the possible
cytogenetic damage using peripheral blood lymphocyte culture (PBLC),
and rare mutations of HTRA2 that have been reported to be associated
with PD patients using PCR SSCP method, and was carried out in
the 18 PD patient samples, and equal number of controls were selected.
Results: In our study chromosomal alterations were frequently
observed in chromosomes 1, 5q, 6p, 17p and X (1p32, 5q31- q35,
6q16.2, 17p13, Xp22, and Xq13). In the present study, chromosomal
aberrations showed higher degree in experimentals compared to con-
trols (P<0.001). We analysed the association between three single
nucleotide polymorphisms (SNPs) of the HTRA2 gene. No significant
evidence between any SNPs of HTRA2 gene in PD was observed.
Conclusions: In conclusion, in this pilot study, we observed that
the identification of cytogenetic abnormalities is not only important
for providing a cause for the PD in a single individual but is also
critical for accurate counselling regarding recurrence risks to parents
and family members. We suggest that HTRA2 gene not represent a
major susceptibility gene for HTRA2 in Coimbatore population.
Movement Disorders, Vol. 30, Suppl. 1, 2015
1048
Four copies of SNCA responsible of autosomal dominant
Parkinsons disease in two Italian siblings
N. Modugno, R. Ferese, R. Campopiano, S. Zampatti, E. Giardina,
M. Santilli, A. Nardone, D. Postorivo, S. Ruggieri, F. Fornai, G.
Novelli, S. Gambardella (Pozzilli, Italy)
Objective: In this study, we screened two Italian siblings with
PD with a family history compatible with dominant inheritance in
order to detect the presence of variations in genes responsible for
dominant PD. We describe the first Italian family with four copies of
SNCA (the eighth worldwide), probably caused by a triplication
inside a duplicated region of SNCA.
Background: The a-synuclein gene (SNCA) multiplication has
been implicated in autosomal dominant forms of Parkinsons disease
(PD).
Methods: We performed genetic testing on two PD siblings with
a family history compatible with dominant inheritance of PD.
Results: Molecular analysis together with anamnestic interview
showed an in-cis mechanism with a 351 Kb triplication containing
SNCA and 5 exons of MMRN1 gene in 4q22.1 (90,500 Mb-
90,851Mb), inside a duplicated region of 1,29 Mb (90,013Mb-
91,310Mb). Clinical phenotype is characterized in the male by early-
onset, 8 years of disease history, rapid progression, levodopa respon-
siveness rapidly deteriorating with motor complications. Several non
motor symptoms progressively appeared such as cognitive impair-
ment, sleep and speech disturbances without dysautonomia. The sis-
ter shows a later age at onset, 4 years of history, responsiveness to
dopaminergic treatments without evidence of motor complications or
other significant and disabling non motor symptoms.
Conclusions: The identification of another family with SNCA multi-
plication confirm a genomic instability in this region and add information
to the complex genotype-phenotype correlation of PD patients.
1049
Identification of neurotransmitter levels and vitamin D receptor
gene (VDR) polymorphism in sporadic Parkinsons disease in
South Indian region
M. Subramaniam, A. Meyyazhagan, S.K. Shanmugam, M. Iyer, K.
Inho, B. Vellingiri (Coimbatore, India)
Objective: Vitamin D plays an important role in neurodegenerative
disorders and plays a vital role as crucial neuro-immunomodulator, can-
didate gene for susceptibility to Parkinsons disease (PD).
Background: In this study, we performed a case-control study
that GABA levels and VDR gene polymorphisms influenced the risk
for the development of onset of sporadic Parkinsons disease (PD) in
South India.
Methods: 22 PD patients with equal number of controls were
genotyped by amplification of VDR coding exons performed using
primers. We also determined GABA levels in blood and vitamin D
were measured in plasma in PD and controls.
Results: GABA level and Vitamin D was significantly (p<0.001)
higher in PD patients when compared to controls. Results from our
study revealed that the frequency of VDR gene was significantly
increased in PD group compared to the control groups respectively,
and found significant difference (p<0.001) in genotypic distribution
between PD patients and controls.
Results: GABA level and Vitamin D was significantly (p<0.001)
higher in PD patients when compared to controls. Results from our
study revealed that the frequency of VDR gene was significantly
increased in PD group compared to the control groups respectively,
and found significant difference (p<0.001) in genotypic distribution
between PD patients and controls.
Conclusions: This study shown to have valuable diagnostic and
prognostic tool and possible association of GABA and Vitamin D levels
with VDR polymorphism in genetic susceptibility to sporadic PD in
South Indian population. Our study was an important addition to the
 POSTER SESSION S409

small number of previously published reports on VDR gene variants in
PD and shows the need for further studies in different populations to
elucidate the role of these polymorphisms in Movement Disorders.
1050
Parkinsons disease variant database
K. Nuytemans, L. Wang, G.W. Beecham, C. Van Broeckhoven, J.M.
Vance (Miami, FL, USA)
Objective: Create a database with each variant ranked for signifi-
cant contribution to Parkinsons disease (PD).
Background: Next generation sequencing (NGS) has significantly
increased the rate of rare sequence variants (SVs) reported in PD.
But interpretation of the functional significance of SVs can be diffi-
cult, with information scattered in many sources. Current databases
do not address actual contribution of variant to PD pathogenesis and/
or do not accommodate NGS data in this format.
Methods: SVs will be extracted from the literature and existing NGS
databases. In addition, current plans are to include summary reports of indi-
vidual SV from the NINDS Whole Exome consortium on PD. SVs are
ranked in each of three evidence levels: 1) Genetic evidence (e.g. popula-
tion frequency, family segregation) and 2) functional evidence extracted
from literature and data repositories (e.g. binding specificity assays, expres-
sion analyses) and 3) in-silico analyses for all variants to determine poten-
tial functional effect of the variants (in-silico evidence) (e.g. PolyPhen2
for nonsynonymous, RegulomeDB and GWAVA for non-coding variants).
Results: Each variant is placed in one of six ranks, based on the
strength of evidence from the three evidence-levels. The database will be
available to the user through a website (proposed launch mid-2015, also
accessible through the Miami Udall website) and detailed description of
the ranks will be provided to simplify interpretation of the ranks. Summary
(quality control) data for each dataset and summary frequency data for
each SV will be linked to the NGS laboratorys info or publication, to facil-
itate collaborative efforts.
Objective: Characterize the PARK10 locus for single nucleotide
variants (SNVs) that could contribute to the PD association.
Background: A recent genome wide association study (GWAS)
using autopsy-confirmed Parkinsons disease (PD) cases and controls
(Beecham et al, Neurology 2014, in press) replicated the previously
identified PARK10 locus. This risk association has not been seen in
GWAS studies using only clinically-diagnosed patients, strongly sup-
porting that significant genetic and pathological heterogeneity exists
in the PD phenotype. To characterize the PARK10 region identified
by Beecham et al. we examined a dataset of clinically-diagnosed PD
cases and controls in an ongoing next generation sequencing project.
Methods: The 160 kb region spanning PARK10 (Beecham et al)
was included in a custom capture design for sequencing in 333 PD
cases and 167 controls. Variant positions were annotated using Seat-
tleSeq, GWAVA, CADD and RegulomeDB for functionality (relating
to transcription factor binding, miRNA binding, enhancer/silencing
potential), and analyzed for association.
Results: As expected, the top autopsy-confirmed GWAS hits
were not associated in this smaller clinical dataset. 99% of variants
in this region are noncoding, including 77 annotated with potential
effect on functionality. One (rs11206279; eQTL) showed a trend for
association with PD, but was not replicated in the autopsy-confirmed
dataset. Interestingly, we observed a small region of Hardy-
Weinberg disequilibrium (HWD) in cases, but not controls, within
the region near the highest association peak of Beecham et al. Evalu-
ation of this region is currently underway.
Conclusions: No obvious functional SNVs potentially contribut-
ing to PD were seen in the clinically-diagnosed dataset, though the
additional heterogeneity compared to the autopsy-confirmed data
could be problematic. The preliminary data suggest noncoding var-
iants - potentially a CNV- contribute to the GWAS signal. The iden-
tification of noncoding variant(s) contributing to PD in this locus
would not only signify the unraveling of a potential new mechanism
in PD pathogenesis but also one of the early examples of functional
noncoding variability detection in neurodegenerative disorders.

Rankings for SVs 1052

Rank 1 Rank 2 Rank 3 Development of biomarker battery to discriminate LRRK2
Genetic Highest High High mutation carriers
support R.A. Ortega, R. Alcalay, A. Mirelman, C. Pont Sunyer, C. Wang, Q. Yu,
In-silico High High or High or J. Hagenah, D. Raymond, A. Glickman, M. Pullman, B. Johannes, N.
support Intermediate Intermediate Doan, L.J. Ozelius, S. Pullman, K. Marder, N. Giladi, E. Tolosa, S.B.
Functional Any High Intermediate Bressman, R. Saunders-Pullman (New York, NY, USA)
support or Low Objective: To develop a battery of non-invasive markers with opti-
Rank 4 Rank 5 Rank 6 mal predictive determination for G2019S LRRK2 mutation carriers.
Genetic Intermediate Low Low Background: For motor and non-motor features to discern pre-
support clinical LRRK2 carriers at risk for phenoconversion, they should be
In-silico Any High Intermediate present in early Parkinsons disease (PD), specifically early LRRK2-
support or Low PD, and may be present and increased in unaffected carriers com-
Functional Any Intermediate Low pared with controls.
support or Low Methods: We developed a parsimonious set of motor and non-
motor measures by evaluating 244 early LRRK2 and 576 idiopathic
PD (IPD), 195 unaffected carriers (NMC), 180 non-carrying family
members (NC-F) and 71 unrelated neurologically normal controls
from the LRRK2 AJ Consortium and the Hospital Clinic of Barce-
Conclusions: The PD variant database will allow users to quickly eval- lona. We examined non-motor features: PD non-motor scale (PD-
uate variants when interpreting sequence data, leading to a more focused NMS), olfaction (UPSIT), neuropsychological function (MoCA,
follow-up in a research or clinical setting. The summary data format avoids Color Trails, Stroop), depression/anxiety (BDI, GDS, STAI), auto-
the presence of individual identifiers, facilitating rapid availability of NGS nomic function (SCOPA-AUT), RBD (RBDSQ), sleepiness (Epworth
data to the PD research community and thus potential collaborative efforts. Sleepiness Scale), neuroimaging (transcranial sonography, BI) and
This work is funded by the US Department of Defense. motor features: UPDRS-III, finger tapping, and digitized spiral analy-
sis measures (spiral). Not all measures were available for partici-
1051 pants, especially spiral (161 IPD, 68 LRRK2-PD, 79 NMC, 55 NC-
F, 35 controls). Battery derivation used logistic regression, with PD
Noncoding variants contributing to the PARK10 locus as the outcome, and was restricted to early disease ( 3 years).
K. Nuytemans, G.W. Beecham, W.K. Scott, E.R. Martin, L. Wang, Measures meeting p<0.05 were retained and evaluated in NMC vs.
J.M. Vance (Miami, FL, USA) NC-F and NMC vs. control using ROC analyses, and the AUC of

Movement Disorders, Vol. 30, Suppl. 1, 2015

S410 POSTER SESSION
the full and reduced models compared. Batteries were chosen to
maximize the number of individuals with selected measures.
Results: An optimal battery included the combination of UPDRS-
III; UPSIT; spiral measures; age; and gender. This combined model
distinguished NMC from NC-F (AUC, 95% CI) (0.77, 0.67-0.87) and
control (0.95, 0.91-1.00) when compared to the reduced model
(UPDRS-III, age, gender) (NMC vs. NC-F: 0.61, 0.49-0.75) (p<0.01),
(NMC vs. control: 0.86, 0.78-0.94) (p50.03). In a model without spiral,
PD-NMS, UPSIT, UPDRS-III, age and gender better discriminated
NMC from NC-F (0.65, 0.56-0.73) compared to the reduced model
(0.63, 0.54-0.72) (p50.04), but not NMC from control.
Conclusions: A battery of combined markers better distinguishes
NMC from other groups when compared to the reduced battery. Lon-
gitudinal assessment is warranted to determine the utility of the com-
bined model in predicting eventual phenoconversion.
1053
Increased oligomeric alpha-synuclein in Gaucher disease:
Possible explanation for the link with Parkinsons disease
S.N. Pchelina, A.K. Emelyanov, E.P. Nuzhnyi, T.S. Usenko, T.M.
Boukina, M.A. Nikolaev, A.F. Yakimovskii, E.Y. Zakharova (St.
Petersburg, Russia)
Objective: To assess whether the link between Parkinsons dis-
ease (PD) and Gaucher disease (GD) could be explain by increased
oligomerization of alpha-synuclein.
Background: GD is caused by mutations in the GBA gene,
encoding glucocerebrosidase, a lysosomal enzyme. Today enzyme-
replacement therapy (ERT) is the standard treatment for GD. GD
patients and carriers of GBA mutations are at increased risk of PD.
However, it remains unclear whether this link is due to oligomeriza-
tion of neuronal protein alpha-synuclein.
Methods: We examined oligomeric alpha-synuclein levels in plasma
of 41 GD patients (median age 15, range 1-71, 17 males) and 40 healthy
individuals (median age 16, range 3-70, 17 males) using ELISA with
mab 5G4 antibodies special for oligomeric alpha-synuclein species
(Human Synuclein OLIGO kit Roboscreen, Germany). 32 GD patients
received ERT. Leucocytes GBA activity was measured in GD patients
before treatment using fluorescent enzyme substrate (4-methylumbelli-
feryl-b-D-glucopyranoside (4MU-b-glc), Sigma-Aldrich).
Results: Plasma alpha-synuclein levels were increased in GD patients
compared to controls (GD: median 5 22,9 pg/ml, range1,57 444,58 pg/
ml; controls: median=6,02 pg/ml, range 1,05 103,14 pg/ml, p<0.0001).
This difference was absent if subgroup of GD patients receiving ERT for
more than 5 years was compared to controls. Negative correlation
between plasma oligomeric alpha-synuclein levels and leucocyte GBA
activity was observed in patients with GD without ERT or receiving ERT
less than 5 years (N=21, R2=0,487, p<0,001).
Conclusions: Our results suggested that decreased GBA activity
may influence alpha-synuclein oligomerization that may explain high
risk of PD development in GD patients and supplied further evidence
that lysosomal dysfunction may play a role in accumulation and oli-
gomerization of alpha-synuclein. Therapeutic strategies augmenting
GBA activity might be potentially helpful for treatment of GBA-
associated PD.
1054
Clinical and genetic features of an early-onset Parkinsons
disease Peruvian cohort
E.H. Sarapura, C. Cosentino, M.A. Inca-Martinez, M.R. Cornejo-
Olivas, L. Torres, V. Marca, O. Ortega, D.M. Velit-Otani, K.A.
Espinoza-Huertas, D. Yearout, H. Huston, C. Zabetian, I.F. Mata, P.
Mazzetti (Lima, Peru)
Objective: To describe the clinical and molecular characteristics
of patients with Early Onset Parkinsons disease in Peru.
Movement Disorders, Vol. 30, Suppl. 1, 2015
Background: Parkinsons disease (PD) is a multifactorial pro-
gressive neurodegenerative disorder; characterized by resting tremor,
rigidity, and bradykinesia, as well as non-motor symptoms, such as
cognitive impairment or autonomic dysfunction. Early onset Parkin-
sons disease (EOPD) is defined by the development of the symp-
toms before the age of 40, representing up to 10% of the PD patients
. Mutations in three autosomal recessive genes have been related to
EOPD: PARK2, PINK1, and DJ-1; however, frequencies of mutations
in these genes vary across studies and populations. Here we show a
preliminary report of the clinical features observed in our Peruvian
EOPD cohort, as well as the genetic findings to date.
Methods: We selected from the Latin American research consortium
on the Genetics of PD (LARGE-PD) all the EOPD cases followed up at the
Instituto Nacional de Ciencias Neurologicas (N=68); and gathered standar-
dized clinical evaluation, cognitive assessment based on MoCA, UPDRS
motor score and Hoehn &Yahr score for all participants. We screened 40
of them for point mutations and dosage in the PARK2, LRRK2 and SNCA
genes. IRB Approval from INCN was obtained for this study.
Results: Our EOPD patients presented with a mean age of 40.9 [1-]
8.2 years and a mean age at onset of 31.5 [1-] 8.3 years; 37 were males
and 24 had positive family history (second degree). The mean education
was 12.5 years. Rigid-akinetic syndrome was the predominant phenotype
in this group, but tremor was the principal symptom at onset (61%).
Mean cognitive performance based on MoCA scored: 23.2 610 [range
9-28]. Fifty cases had good response to levodopa, with 30% presenting
dyskinesias. Genetic information was available for 40 individuals: 3
showed one pathogenic variant (2 point mutation and one dosage
change), while 1 was compound heterozygous for the PARK2 gene. We
also found a LRRK2 -R1441G carrier with dominant family history. No
changes were observed for SNCA dosage.
Conclusions: EOPD patients in our Peruvian cohort appear clini-
cally similar to the ones described in other populations. As expected,
Parkin mutations were the most common mutations associated with
EOPD in our cohort.
1055
Screening of spontaneous genomic alterations and P53 gene
polymorphism in new onset of Parkinsons disease
M.A. Shafi Ahammed Khan, K.K. Alagamuthu, A. Meyyazhagan, Y.
Mohd, M. Iyer, S. Keshavarao, B. Vellingiri (Coimbatore, India)
Objective: To evaluate the presence of spontaneous chromosomal
alterations and p53 polymorphism at codon 72 in peripheral blood
leukocytes in newly diagnosed Parkinsons patients.
Background: Parkinsons disease (PD) is a progressive neurolog-
ical disorder characterised by a large number of motor and non-
motor features that can impact on function to a variable degree.
Methods: Patients with Parkinsons disease (16) and control sub-
jects (16), was recruited and matched for age, sex, and smoking hab-
its. Cytogenetic analysis was performed using the human lymphocyte
for finding chromosomal alterations. Restriction Fragment Length
Polymorphism was done for genotype analysis of P53 gene.
Results: Patients with Parkinsons disease showed an increase in
the incidence of spontaneous Chromosomal alterations (p < 0.05)
compared to controls. Moreover, there was no statistically significant
between p53 gene was found in Parkinsons disease.
Conclusions: Understanding of the broad spectrum of clinical man-
ifestations of Parkinsons disease is essential to the proper diagnosis of
the disease. Genetic mutations or variants, chromosomal abnormalities
are potential biomarkers that may improve diagnosis and allow the
identification of persons at risk and better treatment options.
1056
Cognitive deficit and neuropsychiatric features in early
Parkinsonism due to homozygous PINK1 mutation: A case
report
C. Siri, E. Reali, G. Sacilotto, S. Goldwurm, E. Scarpini, G. Pezzoli
(Milan, Italy)
 POSTER SESSION S411

Objective: To report extensive cognitive and behavioral charac-

terization of a PD patient homozygous for PINK1 mutation.
Background: Knowledge on behavioral and cognitive aspects of Behavioral profile was characterized by increased impulsivity,
PD patients homozygous for PINK1 mutations is still poor. moderate depression and anxiety, irritability, sleep disturbances.
Methods: Extensive neuropsychological assessment evaluated: DATscan was severely pathological in both striata, RMN revealed a
global functioning (MMSE, CDT, BIT), attentive-executive abilities fronto-temporal cortico-subcortical atrophy; FDG-PET was normal.
(FAB, CPM-Raven, Weigl Sorting Test, Elithorn Perceptual Maze CSF analysis did not show any alteration in progranulin, tau and
Test, Cognitive Estimation Task and Tower of London, Attentive Mat- amyloid protein values.
rices, Stroop Color-Word Test and Trail Making Test), memory abil- Conclusions: We describe a case of early onset PD patient homo-
ities (incidental memories, digit and Corsi span, Story Recall, RAVLT, zygous for PINK1 mutation with selective and severe memory and
FCSRT, ROCF recall), language (verbal fluencies and Boston naming), visuo-constructive deficits which are not related to mental retardation
visual-spatial abilities (Judgment of Line Orientation), praxis abilities and not attributable to other common neurodegenerative processes.
(ROCF learning, ideomotor apraxia and visual-constructive apraxia) Considering the heterogeneity of the few reports on cognitive and
and behavioral profile (BDI-II, BIS, FBI, NPI). behavioral status of patients with this mutation, it is important to fur-
Results: We evaluated a male patient homozygous for PINK1 ther explore the relationship between PINK1 mutations, behavior and
Q456X mutation (age 45 yy; 6-year PD duration; 13 years education; cognition.
UPDRS III: on 10/108, off 23/118). One year after diagnosis he devel-
oped dopamine dysregulation syndrome and impulse control disorders
in association to ropinirole ER 12mg/day and rasagiline 1mg/day. 1057
Two years later, therapy was changed into 400mg/day levodopa and Methylomic analysis in A53T transgenic PD mouse model
quetiapine 25 mg/day, behavioral addictions ended. Premorbid esti- C. Song, Q. Xu, Y. Hu, B. Tang (Changsha, Peoples Republic of
mated IQ score was 100 (BIT). At neuropsychological assessment, China)
pathological performances were recorded in tests of incidental, short
and long term memory functions and visual-constructive performances Objective: To study global DNA methylation changes in
while general cognition and other explored abilities were normal. Parkinsons disease (PD) and to find possible PD pre-diagnosis
biomarkers.
Background: DNA methylation is associated with gene expres-
Cognitive assessment scores sion. Recent studies highlight the existence of aberrant DNA methyl-
GLOBAL FUNCTIONS ation levels in PD; however, there is insufficient research to explore
MMSE 30/30 genomic methylation alterations.
Clock Drawing test 8.5/10 Methods: 5-methylcytosine antibody immunoprecipitation
ATTENTIVE-EXECUTIVE ABILITIES method combined with high-density microarray hybridization
Strop coloured word (time) 20 sec (MeDIP-Chip) was used to depict the global changes in DNA
Strop coloured word (error) 0 methylation. Bisulfite sequencing PCR (BSP) technique was con-
Trail Making A 36 sec ducted for further quantitative examination of CpG island methyl-
Trail Making B 91 sec ation of PARK5 and PARK15. mRNA level was also detected in
Trail Making B-A 55 sec substantianigra.
Attentive Matrices 46/60 Results: MeDIP-Chip analysis revealed over 3,000 genes with an
Frontal Assessment Battery 16/18 altered methylation status and involved 36 pathways. Among them,
CPM Raven 24/36* PARK5 (Uchl1) and PARK15 (Fbxo7) had decreased methylation
Weigl Colour-Form sorting test 13/15 level. BSP technique confirmed the Uchl1 and Fbxo7 hypomethy-
Elithorns perceptual maze test 12.5/16 lated significantly. Among the 26 CpG sites of Uchl1, 6th, 10th, 14th
Cognitive Estimation Task (errors) 13/42 and 21st sites were significantly hypomethylated in transgenic mice,
Tower of London 17.72 and among the 50 CpG sites of Fbxo7, 9th, 10th, 14th, 15th, 27th,
MEMORY 29th, and 32nd sites were significantly hypomethylated. Accordingly,
Category Incidental memory 7/20** higher levels of Uchl1 mRNA were expressed, but Fbxo7 mRNA
Phonologic Incidental Memory 5/20** expression had no significant increase.
Digit Span 4/9** Conclusions: Our study indicated that Uchl1 and Fbxo7 had
Corsi Block Tappinng test 3/9** lower methylation level in transgenic mice and might be potential
Story Recall Test 9.9/16 biomarkers for the molecular screening of PD. Additionally, MeDIP-
Rey Auditory Verbal Learning Test (immediate) 33/75** Chip seems to be a robust approach to exploring global methylation
Rey Auditory Verbal Learning Test (delayed) 5/15** changes.
Free and Cued Selective Reminding Test (immediate) 29/36
Free and Cued Selective Reminding Test (delayed) 8/12*
Rey Osterrieth Complex Figure (recall) 7/36** 1058
LANGUAGE Withdrawn by Author
Boston Naming Test 14/15
Cathegory Fluencies 38
Phonological Fluencies 33
1059
VISUAL-SPATIAL ABILITIES
Bentons Judjment Lines Orientation Tests 23/30 Oxidative stress and cytogenetic analysis compared with PARK8
PRAXIS gene in Parkinsons disease patients
Rey Osterrieth Complex Figure (copy) 29/36** B. Vellingiri, A. Meyyazhagan, K.K. Alagamuthu, K. Siva, M. Iyer,
Visual-constructive apraxia test 11/16* S.N. Dharwadkar, S. Keshavarao (Coimbatore, India)
Ideomotor Apraxia 72/72
Objective: This study aims to identify the genetic alterations of
PD by using the conventional cytogenetic techniques Trypsin G-
** Pathological and *borderline score according to normative banding with PARK8 genotype. To estimate the role of selected ions
data on Italian population related to energy metabolism as a consequence of oxidative stress.

Movement Disorders, Vol. 30, Suppl. 1, 2015

S412 POSTER SESSION
Background: Parkinsons disease (PD) is a neurodegenerative
disease affecting at least 1% of the population over age of 45. Oxi-
dative stress contributes to the cascade, leading to dopamine cell
degeneration in PD. Carrying a PARK8 allele is the major genetic
risk factor for PD.
Methods: The present study includes 26 PD patients, and equal
number of subjects were analysed. In order to investigate the possi-
ble cytogenetic damage using PBLC (peripheral blood lymphocyte
culture), the analysis of the PARK8 genotype was performed on lym-
phocytes by PCR. Oxidative stress was assessed by estimating lipid
peroxidation product in the form of thiobarbituric acid reactive sub-
stances, nitric oxide in the form of nitrite & nitrate.
Results: The PD patient shows higher total chromosomal abbera-
tion (CA) level when compared to control patients. The observed
chromosomes are (2q36-q37, 5q31- q35, 10q11-q13, Xp22, and
Xq13). Plasma thiobarbituric acid reactive substances and nitric
oxide levels were significantly high but superoxide dismutase and
ceruloplasmin, were significantly low in PD when compared with
control subjects. A comparison of the frequencies for PARK8 geno-
types among the PD subjects and control subjects demonstrated a
significant difference between the two groups.
Conclusions: The strong association of PARK8 with PD patients
called attention to the importance of genetic studies in PD. Alteration
of the selected measured ions confirms that oxidative stress and
defective mitochondrial energy production could represent the pri-
mary causative factor in the pathogenesis of PD patients.
1060
Leucine-rich repeat kinase 2 (LRRK2) impairs function of the
retromer-associated WASH complex
K. Venderova, D. Kaing, R. Eismati, R. Joseph, L. Radek, H. Yu-Ju,
H. Emily, T. Ariel, F. Ryan, F. Derek (Stockton, CA, USA)
Objective: The goal of this work is to determine how pathogenic
mutant LRRK2 affects the endolysosomal pathway.
Background: LRRK2 is the most common causative gene of Par-
kinsons disease. We have recently presented evidence that overex-
pression of another Parkinsons disease gene, Vacuolar protein
sorting 35 (VPS35), completely rescues several LRRK2 phenotypes
(Linhart R et al, Mol Neurodeg 2014). VPS35 is a component of
the retromer complex essential for endosomal sorting and trafficking
of specific cargo proteins to the Golgi or to the plasma membrane;
however, how exactly LRRK2 interacts with the retromer complex
is not clear.
Methods: We employed our LRRK2 overexpressing Drosophila
lines generated previously (Venderova K et al Hum Mol Genet
2009) and other transgenic lines available from the Bloomington
Drosophila Stock Center, and from the Exelixis Collection at the
Harvard Medical School.
Results: Our targeted screen in vivo showed that knocking-down
expression of FAM21, a component of the WASH complex associ-
ated with retromer, in dopaminergic neurons caused a significant
impairment of locomotor activity similar to that seen in pathogenic
mutant LRRK2 flies. Furthermore, overexpressing WASH1 com-
pletely rescued this LRRK2 phenotype.
Conclusions: These results strongly suggest that LRRK2 regu-
lates retromer function by interfering with the function of the WASH
complex.
1061
Parkinsonism with early disautonomic symptoms and normal
MIBG scintigraphy related to LRRK2 mutation
 Mux, E. Tolosa, Y. Compta (Barcelona, Spain)
D. Vilas, A.
Objective: To report a patient with LRRK2-related Parkinsonism
with early dysautonomic symptoms and normal 123I-metaiodobenzyl-
guanidine (MIBG) cardiac scintigraphy.
Movement Disorders, Vol. 30, Suppl. 1, 2015
Background: Dysautonomic symptoms are common in idiopathic
Parkinsons disease (IPD), even in early stages, but are also present
in other degenerative Parkinsonisms, most prominently in multiple
system atrophy (MSA), making the differential diagnosis challenging
especially in initial disease stages.
Methods: Single case report.
Results: A 48-year-old man without family history of Parkinson-
ism presented to our clinic with a nine-month history of slowness
and pain in his left arm. He also complained of urinary urgency and
lightheadedness and coat hanger pain when standing up. On neuro-
logical evaluation he had intermittent rest and action tremor in his
left hand along with mild bradykinesia in the left upper extremity
and in both lower extremities. His systolic blood pressure decreased
30 mmHg from lying to standing. A brain MRI was normal and a
[123I] FP-CIT SPECT showed decreased striatal uptake. Due to the
combination of Parkinsonism and early dysautonomic symptoms,
MSA was considered in the differential diagnosis. A cardiac 123I-
metaiodobenzylguanidine (MIBG) scintigraphy showed a normal late
myocardial/mediastinal uptake ratio (2.28), being thus suggestive of
MSA rather than IPD. Still, MSA was considered unlikely due to
lack of progression from baseline visit to follow-up and the lack of
other red flags suggestive of MSA. As monogenic PD, particularly
the LRRK2-related one, can resemble IPD but have less involvement
of the peripheral nervous system, this diagnostic possibility was also
considered and indeed the patient happened to be positive for the
G2019S mutation.
Conclusions: In a young-adult patient with Parkinsonism, dysau-
tonomic symptoms and normal MIBG heart SPECT but no other
clinical red flags of MSA, LRRK2-related Parkinsonim might be con-
sidered in the differential diagnosis.
1062
Genome wide pleiotropic study in 144,701 subjects reveals
shared genetic variants between Parkinsons disease and
immune-mediated diseases
A.W. Witoelar, Y. Wang, R. Desikan, W. Thompson, A.J. Schork, V.
Zuber, E. Ellinghaus, A. Franke, B.A. Lie, L.K. McEvoy, T.H.
Karlsen, IPDGC, S. Djurovic, A. Brice, N. Wood, P. Heutink, J.
Hardy, A. Singleton, A.M. Dale, T. Gasser, O.A. Andreassen, M.
Sharma (Oslo, Norway)
Objective: Identifying novel shared genetic factors between Par-
kinsons disease and immune-related disorders.
Background: Post genome-wide association studies (GWAS) era
provides an unprecedented opportunity to perform cross-phenotype
analyses to identify novel shared genetic factors between different
complex phenotypes. Recently published GWAS and subsequent
GWAS based pathway analyses provided unequivocal support
regarding the involvement of immune mediated pathways in Parkin-
sons disease (PD).
Methods: We analyzed GWAS data from a selection of arche-
typal immune-mediated diseases comprising a total of 144,701 sub-
jects of Caucasian ancestry to systemically investigate whether
shared genetic factors are present between PD and common immune-
mediated diseases.
Results: Using recently developed False Discovery Rate (FDR)
methods, we identified 30 risk loci (conditional FDR < 0.01, after
pruning) for PD conditioned on Crohns disease (CD), ulcerative
colitis (UC), rheumatoid arthritis (RA), type 1 diabetes (T1D), celiac
disease(CeD) and psoriasis (PSOR), out of which several are novel.
After removing MHC related markers from the analyses, 28 loci
remained significant. Furthermore conjunctional analyses of CD, UC,
RA, T1D, CeD and PSOR with PD identified 17 loci with overlap
between PD and immune related disorders (conjunctional
FDR < 0.05, after pruning), and thus provided genetic link between
these phenotypes.
 POSTER SESSION
1063
Genetic variants of TOR1A gene are not associated with
sporadic PD susceptibility: A replication study in a central Han
Chinese study
X. Xu, N. Xiong, J. Huang, L. Liu, G. Zhang, H. Jiang, C. Han, J.
Yang, J. Li, Y. Shen, T. Wang (Wuhan, Peoples Republic of China)
Objective: To evaluate the correlation between Genotype of
TOR1A rs1801968 and Parkinsons disease (PD).
Background: The protein encoded by TOR1A(torsin family 1,
member A) is expressed prominently in substantia nigra compact,
and plays an important role in the control of protein folding, process-
ing, stability, and the reduction of misfolded protein aggregates.
Mutations of TOR1A can result in the autosomal dominant disorder,
torsin dystonia 1. However, whether or not there is any association
between the TOR1A gene alteration and PD remains unexplored in
Chinese population, especially in central Chinese population.
Methods: In this project, we conducted a case-control association
study in a cohort of 390 central Chinese PD patients and 325 con-
trols for the Genotype of TOR1A rs1801968.
Results: Here, we aimed at studying the effect of TOR1A
rs1801968 on the risk of PD by performing a case-control association
study in central China. Genotype of TOR1A rs1801968 showed no
difference between PD patients and controls.
Conclusions: We conclude that Genotype of TOR1A rs1801968
showed no difference between PD patients and controls.
1064
HLA polymorphisms may be one of the susceptibility genes in
Chinese sporadic PD
J. Yang, J. Huang, N. Xiong, L. Liu, C. Han, G. Zhang, H. Jiang, X.
Xu, J. Li, Y. Shen, T. Wang (Wuhan, Peoples Republic of China)
Objective: To evaluate the relationship of HLA gene (HLA)
polymorphisms and Parkinsons disease (PD) in Chinese population.
Background: Parkinsons disease (PD) is a progressive neurode-
generative Movement Disorder which can be caused by the interac-
tion of multiple susceptibility genes and environmental factors. We
here searched for DNA variants at the HLA 3UTR through single
strand conformation analysis and direct sequencing in a cohort of
Chinese PD patients and controls to explore the function of the gene
in PD pathogenesis.
Methods: 2 Single Nucleotide Polymorphisms (SNPs) markers
located within HLA gene were chosen for genotyping and evaluated
their haplotype structure in a cohort of sporadic PD patients and con-
trol individuals.
Results: 558 individuals including 319 PD patients and 239 nor-
mal persons were collected to analyze their clinical and molecular
data in total. We identified two HLA 3 UTR variants. But only one
SNP rs3129882 was significantly associated with PD risk
(p 5 0.0001; odd ratio =1.36, 95%CI 5 1.1 9 21.58).And we found
this SNP was independent of early age at onset of PD.
Conclusions: In conclusion, we found the association between
the HLA rs3129882 SNP and PD in Chinese population. But there
was no evidence for a significant effect of this SNP on the age at
onset. Our study suggests that the variants could have a direct role
on PD; however, more functional studies should be implemented to
determine its effect on HLA expression.
1065
Genetic variants of SNCA gene are associated with sporadic PD
susceptibility: A replication study in a central Han Chinese study
G. Zhang, N. Xiong, J. Huang, L. Liu, C. Han, H. Jiang, J. Yang, X.
Xu, J. Li, Y. Shen, T. Wang (Wuhan, Peoples Republic of China)
S413
Objective: To validate whether multiple genetic variants in
SNCA gene could predispose to sporadic, late-onset form of Parkin-
sons disease (PD) in central Chinese population.
Background: PD is the second prevalent age-related neurodege-
nerative disease and usually refers to multiple genetic and environ-
mental factors influencing disease risk. Many polymorphisms in
SNCA gene have recently been confirmed as risk factors for PD.
Methods: Four Single Nucleotide Polymorphisms (SNPs) markers
located within SNCA gene were chosen for genotyping and evaluat-
ing their haplotype structure in a cohort of 393 sporadic PD patients
and 392 control individuals.
Results: With regard to allele, two SNPs showed the greatest
association with PD (rs11931074, OR 1.29, 95%CI 1.03-1.63,
p50.032 and rs356221, OR 1.33, 95%CI 1.04-1.71, p50.025), but
the remaining two SNPs (rs7687945, OR 1.22, 95%CI 0.91-1.62,
p50.19 and rs2736990, OR 1.16, 95%CI 0.91-1.49, p50.24) were
found to be no statistical association with PD. Based on the co-
dominant model, significantly increased risks were found in subjects
of rs11931074 with TT genotype (OR 1.71, 95%CI 1.07-2.74,
P=0.03) and rs7687945 with CC genotype (OR 2.59, 95%CI 1.02-
6.59, P=0.042). Similar results were detected in rs11931074 and
rs356221 with regard to dominant model, and SNPs rs7687945 in
recessive model. No statistically significant relationship between
rs2736990 and PD risk in any genetic models was observed. More-
over, no difference was found in four SNPs between EOPD patients
and all of the controls. Nevertheless, TT and GT genotype of
rs11931074 seemed to be more statistically frequent in LOPD, and
AT genotype of rs356221 in female PD patients. No block existed in
our analysis.
Conclusions: We conclude that genetic variants of SNCA gene
confer susceptibility to sporadic PD but in a different distribution.
1066
Multiple LRRK2 variants modulate risk of sporadic Parkinsons
disease susceptibility: A replication study in a central Han
Chinese case-control study
G. Zhang, N. Xiong, J. Huang, L. Liu, C. Han, H. Jiang, J. Yang, X.
Xu, J. Li, Y. Shen, T. Wang (Wuhan, Peoples Republic of China)
Objective: To validate whether multiple genetic variants in
LRRK2 gene could predispose to sporadic, late-onset form of Parkin-
sons disease (PD) in central Chinese population.
Background: PD is the second most prevalent age-related neuro-
degenerative diseases that multiple genetic and environmental factors
contribute to disease occurrence. We here performed a gene-based
case-control association study to validate multiple LRRK2 risk var-
iants in a central Han Chinese case-control study.
Methods: Six Single Nucleotide Polymorphisms (SNPs) markers
located within LRRK2 gene were chosen for genotyping and evaluat-
ing their haplotype structure in a cohort of 393 sporadic PD patients
and 392 control individuals.
Results: No allele of G2019S was detected in either PD or
health control groups. Minor alleles of rs1994090 (OR 1.824,
95%CI 1.26-2.65, p50.002), rs2046932 (OR 1.74, 95%CI 1.15-
2.80, p50.011) and rs34778348 (OR 2.94, 95%CI 1.54-5.62,
p50.001) were found to be more common in cases than in controls
with significant evidence for an association with PD. Moreover,
risk of PD development was increased via a dominant model at
SNP rs1994090 (OR 1.89, 95%CI 1.25-2.84, p50.003), rs34778348
(OR 2.86, 95%CI 1.48-5.55, P=0.0014) or a co-dominant model at
SNP rs1994090 with TG genotype (OR 1.81, 95%CI 1.18-2.78,
P=0.0069), and rs2046932 with CT genotype (OR 1.65, 95%CI
1.02-2.68, P=0.045). No statistically significant relationships
between rest SNP rs7304279, rs34594498 and the risk of sporadic
PD in any genetic models were observed. No haplotype block was
constructed.
Conclusions: We conclude that genetic variants of LRRK2 gene
confer susceptibility to sporadic PD but in a different distribution.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S414 POSTER SESSION
1067
ALDH2 genetic variation is associated with the risk for
Parkinsons disease
X. Zhang, Y.L. Ye, Y.N. Wang, F.F. Liu, X.S. Zhuang, X.X. Liu, B.L.
Hu, J.H. Zhu (Wenzhou, Peoples Republic of China)
Objective: To evaluate the association between aldehyde
dehydrogenase-2 (ALDH2) polymorphisms and Parkinsons disease
(PD) in a Chinese cohort.
Background: Genetic variation of ALDH2, which encodes a key
enzyme involved in aldehyde oxidation in the brain, has been recently
suggested to enhance pesticide association with PD. However, whether
ALDH2 polymorphism is associated with PD remains elusive.
Methods: Tag-single nucleotide polymorphisms of ALDH2,
that is, rs4767944, rs441 and rs671, were extracted and analyzed
in a Chinese cohort consisting of 521 PD patients and 504
controls.
Results: The results showed that rs4767944 (p 5 0.012), but not
rs441 and rs671, were associated with PD. The C allele of
rs4767944 served a risk factor toward PD. Further analysis presented
a significant association between haplotype frequencies and risk for
PD, which was primarily driven by the preponderance of the C-T-G
haplotype of rs4767944, rs441 and rs671 in PD patients (p 5 0.003).
Conclusions: Our data provide novel insight that ALDH2 genetic
variation is associated with PD susceptibility.
1068
MicroRNA-mediated DNA methyltransferase 1 deregulates
SNCA methylation in Parkinsons disease
J.H. Zhu, X. Zhang, J.Y. Wang, X. Cheng, B.L. Hu (Wenzhou,
Peoples Republic of China)
Objective: To understand the changes of DNA methyltransferase
1 (DNMT1) in association with Parkinsons disease (PD) and to
investigate the underlying mechanisms.
Background: Recent studies in SNCA hypomethylation and its
subsequent regulation on a-synuclein expression suggest an impor-
tance of DNA methylation in PD. In accordance, decreased expres-
sion of DNMT1 was detected in postmortem brains of PD patients,
suggesting DNMT1 may be the key mediator for the deregulation of
DNA methylation in PD.
Methods: The 1-methyl-4-phenylpyridinium (MPP1), 6-
hydroxydopamine, lactacystin, rotenone and paraquat were used to
treat SH-SY5Y cells to induce cellular PD model.
Results: Following the treatment of MPP1 in SH-SY5Y cells, the
expression of DNMT1 protein displayed a time- and dose- dependent
decrease, whereas the mRNA level of DNMT1 was surprisingly ele-
vated. As the decrease of DNMT1 protein was not resulted from
altered lysosomal or proteosomal degradation, we screened a set of
microRNAs (miRNA) which may potentially regulate the translation
of DNMT1 mRNA, and measured their abundances in SH-SY5Y cells
and substantia nigra of C57BL/6J mice. The miRNA-17 and -19a
were selected as potential regulators of DNMT1 and were confirmed
by overexpression of their respective mimics or inhibitors. The expres-
sion levels of both miRNA -17 and -19a were elevated following
MPP1 treatment. Overexpression of the miRNA inhibitors rescued
the MPP1-induced reduction of DNMT1 protein, and thereby blocked
MPP1-induced SNCA intron 1 hypomethylation and subsequent
increase of its mRNA level. At last, we applied another four cellular
PD inducers, that is, 6-hydroxydopamine, lactacystin, rotenone and
paraquat, all of which were shown leading to a decrease in DNMT1
protein level, and an increase in miRNA -17 and -19a levels.
Conclusions: Our results underscored the deregulation of
DNMT1 in association with PD, and demonstrated that derange-
ment of miRNAs contributed to the decrease of DNMT1 protein
and subsequent DNA hypomethylation. Our study indicates that a
complex epigenetic regulation may be involved in PD
pathogenesis.
Movement Disorders, Vol. 30, Suppl. 1, 2015
Rating scales
1069
Determining the reliability of performing the modified unified
Parkinsons disease rating scale (UPDRS) remotely in a pilot
virtual visit study in the home
K.L. Andrzejewski, M.T. Bull, P. Auinger, V. Venkataraman, M.J.
Grana, B.P. George, C.M. Boyd, C. Beck, B. Rajan, E.R. Dorsey, K.
Biglan (Rochester, NY, USA)
Objective: To evaluate the reliability of the modified (excluding
rigidity and postural instability) Unified Parkinsons disease Rating
Scale (mUPDRS) conducted remotely versus the gold standard
mUPDRS conducted in person.
Background: We have previously demonstrated the reliability of
the mUPDRS conducted via telemedicine with patients seen in a
nursing home. We recently demonstrated the feasibility of virtual
house calls conducted via telemedicine using video software directly
into the home but have not previously reported on the reliability of
mUPDRS assessed remotely in the home.
Methods: In the context of a pilot study of virtual house calls,
participants (n59) had the mUPDRS conducted in-person at baseline
and one month later via telemedicine directly into their homes. The
intraclass correlation coefficient (ICC) for the total mUPDRS score
was calculated to determine agreement between in-person and remote
exams and Cohens kappa (j) coefficients were used to assess agree-
ment between scores for in person and remote virtual exams for indi-
vidual items of the mUPDRS.
Results: Reliability of total mUPDRS score completed in-person
versus remotely was excellent (ICC=0.78). Facial expression and
arising from a chair had good agreement (0.40  j < 0.75), speech,
rest tremor, posture, and bradykinesia had fair agreement
(0.20  j < 0.40), and action tremor, finger taps, hand and rapid
alternating movements, leg agility, and gait had less than fair agree-
ment (j <0.20). Removal of participants who had fluctuations in
response to dopaminergic therapy (n52) did not significantly change
agreement.
Conclusions: The mUPDRS conducted remotely has excellent
reliability compared with in-person assessment. Similar to previous
studies, individual items have varying levels of agreement when con-
ducted remotely suggesting new methods may be needed to accu-
rately assess aspects of motor function remotely.
1070
Evaluating the use of the online bradykinesia-akinesia
Incoordination (BRAIN) test in Parkinsons disease in on and
off states
D.S. Athauda, H. Hasan, A. Noyce, T. Foltynie (London, United
Kingdom)
Objective: To evaluate the use of the BRAIN test as a test of
upper limb motor function in individuals with Parkinsons disease in
the On and Off states.
Background: The BRAIN test is an online computer tapping task
that has previously been validated and can differentiate individuals
with Parkinsons disease from healthy controls and also correlate
with PD severity measured by disease-specific rating scales(Noyce
ref).
Motor fluctuations and wearing off symptoms develop in 40% of
patients after 4-6 years and around 70% of patient after 9 years of
dopaminergic therapy [1]. This is often a source of frustration for
patients and can contribute to poor quality of life. Identification of
these symptoms through careful history taking and various patient
diaries can be time-consuming and may be unreliable due to poor
compliance.
 POSTER SESSION
Using a patient led, convenient, reliable tool to objectively iden-
tify motor fluctuation may be of benefit to clinicians when i) making
treatment decisions, and ii) may help objectively quantify bradykine-
sia in clinical trials.
Methods: Validation of the online BRAIN test was undertaken in
60 patients with moderate stage Parkinsons disease (Hohn and Yahr
<2.5) in the On state and the Off state (following a period of
drug withdrawal). Kinesia scores (KS30, number of key taps in 30
seconds), akinesia times (AT30, mean dwell time on each key in
milliseconds), incoordination scores (IS30, variance of travelling
time between key presses) and dysmetria scores (DS30, accuracy of
key presses) were compared between the On and Off states.
These parameters were also correlated against total motor scores and
sub-scores from the MDS-UPDRS in the ON and OFF states.
Results: Mean BRAIN test subscores were significantly different
between patients in their On and Off states. There was also a
significant correlation between these subscores and the MDS-UPDRS
Part III scores in the On and Off states.
Conclusions: Our data suggest the BRAIN test can be a reliable
test of upper limb function and can reliably differentiate between the
On and Off state in Parkinsons disease. This test may be used ity was assessed by correlating IRT-derived PDAQ scores with meas-
by patients in outpatient clinics or home settings to aid clinicians
help identify motor fluctuations which may be used to guide future
management, or by extrapolation, may help measure severity of bra-
dykinesia for use in clinical trials.
1071
Correlation between the functional independence measure (FIM)
and the scale for assessment and rating of ataxia (SARA) for the
evaluation of spinocerebellar ataxia
F.M. Branco Germiniani, T.V. Canelossi Rosa, R. Nickel, P.B.N.
Liberalesso, H.A.G. Teive (Curitiba, Brazil)
Objective: The aim of this study was to identify the correlation
between the assessment of the Functional Independence Measure
(FIM) and the Scale for Assessment and Rating of Ataxia (SARA)
used to evaluate patients with Spinocerebellar Ataxia.
Background: The spinocerebellar ataxias are a group of neurode-
generative diseases that have in common the involvement of the cer-
ebellum and its connections, resulting in impairment of planning and
execution of voluntary movements, which can lead to functional
dependency.
Methods: Patients with Spinocerebellar Ataxia from de Move-
ment Disorders Outpatient group of the Hospital de Clnicas da
UFPR were evaluated with both the Rating Scale and Classification
of Ataxia and the Functional Independence Measure. Pearsons cor-
relation coefficient was used for statistical inference.
Results: The SARA scale has higher ratings in more severely
compromised subjects, whereas, the FIM has greater rates for more
independent patients. Thus, we found a negative correlation between
magnitude and moderate disease compromise on the severity sub-
scales and both the total and motor components of the FIM. The
results showed that the level of functional independence is directly
related to the severity of spinocerebellar ataxia. A level of 5% (p
0.05) for statistical significance was used for all tests.
Conclusions: In our study we found that the higher the functional
independency of the patients, the greater the measured values of the
FIM and lower scores on the SARA scale.
1072
The Pennsylvania daily activities questionnaire: Development,
reliability and validity of a new item bank for cognitive
instrumental activities of daily living in Parkinsons disease
L. Brennan, J.D. Rubright, J. Rick, N. Dahodwala, J.E. Duda, H.
Hurtig, M. Stern, S.X. Xie, L. Rennert, J. Karlawish, J.A. Shea, J.Q.
Trojanowski, D. Weintraub (Philadelphia, PA, USA)
S415
Objective: To describe the development and psychometric analy-
sis of the Pennsylvania Daily Activities Questionnaire (PDAQ).
Background: Cognitive impairment in Parkinsons disease (PD)
and PD dementia (PDD) are major sources of disability, caregiver
burden and mortality. While cognitive impairment predominantly
affects ability to perform instrumental activities of daily living
(IADLs), the majority of scales used in PD research were specifically
designed for Alzheimers disease (AD), such as the AD Cooperative
Study Activities of Daily Living scale (ADCS-ADL). A PD-specific
IADL scale would be useful both clinically and in cognitive treat-
ment trials. The PDAQ is an item-response theory (IRT)-based tool
for rating cognitive IADLs in PD.
Methods: Candidate items for the PDAQ were developed through
literature review and comments from focus groups of patients and
caregivers. Item selection and calibration of IRT parameters was per-
formed using responses from a cohort of PD patients and knowledge-
able informants (KIs: spouses, other family members, or close
friends; n5388). In independent cohorts of PD patients and KIs,
assessments of test-retest reliability (n550) and construct validity
(n568) of the PDAQ were subsequently performed. Construct valid-
ures of motor function, cognition, the ADCS-ADL, and directly
observed daily function.
Results: Fifty items were retained in the final PDAQ item bank.
Items were excluded due to redundancy, difficult reading level, and
when IRT parameters could not be calculated. Test re-test reliability
was high (ICC= 0.97; p<0.001). In adjusted analysis, the PDAQ
score correlated strongly with cognitive function (r=0.68; p<0.001),
but not with motor impairment (r=0.08; p 5 0.53). There was also a
strong correlation with directly observed daily function (r= 0.87;
p<0.001). Finally, the PDAQ score accurately discriminated between
PD patients with and without dementia (ROC area 5 0.91; 95% CI
0.85-0.97).
Conclusions: Scores obtained from the PDAQ, a new measure of
daily function that can be implemented to assess IADLs in patients
with PD, show strong evidence of reliability and validity. IRT-based
psychometric analysis suggests this new item bank can discriminate
across a range of functional ability.
1073
UPDRS motor subscales provide a measure of key locomotor
function
C. Curtze, J.G. Nutt, P. Carlson-Kuhta, M. Mancini, F.B. Horak
(Portland, OR, USA)
Objective: We determined the association of objective measures
of locomotor function and clinical measures of motor symptoms in
people with idiopathic Parkinsons disease (PD).
Background: The motor UPDRS and its related subscales are
the most common clinical measures of motor functioning in people
with PD. However, its association with objective measures of key
locomotor function is unknown.
Methods: One hundred and four subjects with idiopathic PD
were tested in the morning in their practical OFF state, i.e. at least
12 h after last dose of levodopa. Clinical outcome measures included
(1) UPDRS motor, (2) PIGD, (3) Bradykinesia, (4) Tremor, and (5)
Rigidity. Subjects performed three trials of the instrumented stand
and walk test (ISAW) consisting of: standing quietly for 30 sec, ini-
tiating gait with the most affected leg, walking 7 m, turning 180 deg,
and walking back 7 m. The subjects wore six inertial sensors (MTX
Xsens or Opals, APDM) attached to ankles, wrists, the sternum and
the lumbar region. A total of 34 measures of locomotor function
were computed using Mobility Lab. These measures were catego-
rized into six domains: (1) postural sway, (2) initiation of gait, (3)
gait-pace, (4) gait - arm & trunk movement, (5) gait dynamic sta-
bility, and (6) turning.
Results: Absolute strength of association (Spearmans rho) of the
UPDRS motor subscales and objective measures of locomotor
Movement Disorders, Vol. 30, Suppl. 1, 2015
S416 POSTER SESSION
Fig. 1. (1073).
function is given in the figure. The motor UPDRS was most related
to measures of the turning, gaitpace, and initiation of gait domains.
The PIGD had the strongest association with the domains of turning,
and gaitpace. In addition, the PIGD had the largest overall surface
in plot showing its relatedness to a spectrum of locomotor domains.
Bradykinesia and rigidity were both related to the turning domain,
whereas tremor showed a strong association with postural sway in
the medio-lateral direction.
[figure1]
Fig. 1: Association of UPDRS motor subscales and objective
domains of locomotor function using a spider graph.
Conclusions: Turning measures from body-worn inertial sensors
predicted the motor UPDRS, PIGD, bradykinesia subscale and rigid-
ity subscale.
1074
Development of the Parkinsons disease medication beliefs scale
(PD-Rx)
J.E. Fleisher, N.A. Dahodwala, S.X. Xie, J.A. Shea (New York, NY,
USA)
Objective: To create an instrument assessing the medication
beliefs of patients with Parkinsons disease (PD) and their caregivers
that motivate dopaminergic therapy adherence.
Background: Studies have found that suboptimal medication
adherence is common and associated with worse outcomes and
higher costs. Beliefs regarding treatment develop from an interplay
of numerous factors, including education, social support, and rela-
tionships with healthcare providers. These beliefs ultimately shape
medication adherence. While instruments exist to measure patients
general beliefs about medications, no such tool exists for PD and the
unique concerns that surround PD and its treatments.
Methods: We conducted 6 focus groups of patients and caregivers
living with PD. Participants were drawn from PD support groups,
including early-stage, young-onset, women, caregivers, and minority
groups. In the initial round of 3 focus groups, nominal group technique
was employed to generate potential items. The transcripts were
reviewed and analyzed using a grounded theory approach to create a
draft instrument (PD-Rx). This draft was presented to experts for their
review (Movement Disorder neurologists, psychiatrists, nurses, and
social workers.) Next, the PD-Rx was reevaluated for readability, com-
Movement Disorders, Vol. 30, Suppl. 1, 2015
prehensiveness, and applicability by a second round of 3 focus groups
drawn from the same pool of patient and caregiver participants.
Results: Thirty-eight subjects, of whom 71% were individuals
with PD, participated in the focus groups. Participants generated 24
initial topics that were pared down to 17 items by expert review, and
agreed upon by the second round of focus groups. Items are rated on
a 5-point scale and include impact on current symptoms (e.g.,
tremor, dystonia, mood), impact on current adverse effects (e.g., dys-
kinesia, impulse control disorders), impact on daily living (e.g.,
affordability, daily burden of regimen), and future concerns (e.g.,
neuroprotection, tachyphylaxis). The PD-Rx is currently being
assessed in two cohorts of PD patients and caregivers to assess its
psychometric properties.
Conclusions: By elucidating common medication beliefs held by
individuals with PD and their caregivers, we can begin to address
the relationship between such beliefs and medication adherence. This
scale will enable the development of interventions to address inaccu-
rate or harmful beliefs, with the objective of improving adherence
and, potentially, disease outcomes.
1075
Handling missing values in the MDS-UPDRS
C.G. Goetz, S. Luo, L. Wang, B.C. Tilley, N.R. LaPelle, G.T.
Stebbins (Chicago, IL, USA)
Objective: Define the number of missing values permissible to
render valid total scores for each MDS-UPDRS Part.
Background: To handle missing values, imputation strategies
serve as guidelines to reject an incomplete rating or create a surro-
gate score. We tested a rigorous, scale-specific, data-based approach
to handling missing values for the MDS-UPDRS.
Methods: From two large MDS-UPDRS datasets, we sequentially
deleted item scores, either consistently (same items) or randomly
(different items) across all subjects. Lins Concordance Correlation
Coefficient (CCC) compared scores calculated without missing val-
ues with prorated scores based on sequentially increasing missing
values. The maximal number of missing values retaining CCC>0.95
determined the threshold for rendering a valid prorated score. A sec-
ond confirmatory sample was selected from the MDS-UPDRS inter-
national translation program.
Results: To provide valid Part scores applicable across all HY
stages when the same items are consistently missing, one missing item
from Part I, one from Part II, three from Part III, but none from Part IV
can be allowed. To provide valid Part scores applicable across all HY
stages when random item entries are missing, one missing item from
Part I, two from Part II, seven from Part III, but none from Part IV can
be allowed. All cutoff values were confirmed in the validation sample.
Conclusions: These analyses are useful for constructing valid sur-
rogate Part scores for MDS-UPDRS when missing items fall within
the identified threshold and give scientific justification for rejecting
partially completed ratings that fall below the threshold.
1076
Predictive validity of facial masking for experienced stigma in
Parkinsons disease
S.D. Gunnery, M. Saint-Hilaire, C.A. Thomas, L. Tickle-Degnen
(Medford, MA, USA)
Objective: To evaluate the ability of a clinician administered
measure of facial expressivity and behavioral ratings administered by
trained coders to predict experienced enacted stigma in people with
Parkinsons disease (PD).
Background: Studies show that practitioners and peers percep-
tions of people with PD with masked facies are negatively biased,
yet little is known about the relationship between facial masking and
the social experience of people with PD. The clinical standard for
measuring facial masking is the MDS-UPDRS face motor item
 POSTER SESSION
(UFace) in which clinicians judge expressivity in real time. UFace is
sufficient to show loss of facial activation but is not typically used in
a socially expressive context. Social psychology can offer methods
to measure facial expression that may be better suited for research
on PD social outcomes such as stigma.
Methods: Facial masking was measured in 23 participants with
PD using the UFace, and two social psychological facial coding sys-
tems independently. Clips of participants conversing about an enjoy-
able activity were coded using the Interpersonal Communications
Rating Protocol (ICRP) and Facial Action Coding System (FACS).
ICRP uses a composite of trained coders ratings of active facial
expressivity, blinks, and mouth closure. FACS involves a certified
rater coding activation of face muscles, with the current unit of anal-
ysis being number of simultaneously grouped muscle activations.
Enacted stigma (experiencing unfavorable attitudes expressed by
others) was measured with the Stigma Scale for Chronic Illness.
Results: The three facial expressivity measures showed conver-
gent validity (a 5 .81). Enacted stigma was correlated with ICRP rat-
ings (r(21) 5 .44, p 5 .04) and FACS coding (r(20) 5 .50, p 5 .02)
but not with UFace (r(21) 5 .22, ns).
Conclusions: The three measures showed good convergence, but
only the ICRP and FACS were predictive of participant stigma. The
correlation between facial masking and enacted stigma is evidence
that people with decreased expressivity experience negative social
outcomes. More research is needed to study the mechanisms driving
this relationship and to develop clinically valid measures of PD
facial action. Due to time constraints, the MDS-UPDRS face item
may be the most practical clinical measure of facial expressivity, but
for research purposes, methods that allow for detailed rating of stim-
uli collected in social contexts should be considered.
1077
Minimal clinically important difference on the Parkinsons
disease sleep scale 2nd version (PDSS-2)
N. Kov  G. Deli, J. Janszky, S. Komoly,
acs, Z. Aschermann, P. Acs,
B. Faludi, K. Horvath (P
ecs, Hungary)
Objective: The aim of the present study was to determine the
estimates of minimal clinically important difference for the Parkin-
sons disease Sleep Scale 2nd version (PDSS-2) total score and
dimensions.
Background: Sleep-related problems are one of the most frequent
non-motor symptoms. Severity of sleep-quality may be judged by the
recently developed PDSS-2 scale.
Methods: The subject population consisted of 250 PD patients.
At baseline, MDS-UPDRS, Hoehn-Yahr Scale, Mattis Dementia Rat-
ing Scale and PDSS-2 were assessed. Six months later the PDSS-2
was re-evaluated with the Patient-reported Global Impression
Improvement scale. Both anchor-based techniques (within patients
score change method and sensitivity- and specificity-based method
by receiver operating characteristic analysis) and distribution-based
approaches (effect size calculations) were utilized to determine the
magnitude of minimal clinically important difference.
Results: According to our results, any improvements larger than -
3.56 points or worsenings larger than 1.96 points can represent clini-
cally important changes for the patients. These thresholds have the
effect size of 0.21 and -0.21, respectively.
Conclusions: Minimal clinically important differences are the
smallest change of scores that are subjectively meaningful to
patients. Studies using the PDSS-2 as outcome measure should uti-
lize the threshold of -3.56 points for detecting improvement or the
threshold of 1.96 points for observing worsening.
1078
Health and aging in Parkinsons disease: Management of self-
care like social responsibility factor
L.A. Leandro, H.G. Teive (Curitiba, Brazil)
S417
Objective: To know self-care standards in a Parkinsonian elderly
population and its relationship with the functionality.
Background: The management of old age has long been regarded
as an appropriate action for private and family life, in the mid-
twentieth century gained expression and legitimacy in the social con-
cerns and has become a matter of public health. But recently, the
advance of age suffered a privatization process, which replaces the
older and their destinations on the social responsibility to make space
for aging is seen as a worldwide phenomenon, with regard to the
care that also involve the government and its various forms of atten-
tion, including communities and families.
Methods: Cross-sectional study with a descriptive approach was
evaluated 44 patients of both sexes diagnosed with Parkinsons dis-
ease (PD), HY II/III, aged between 65 and 83 years. The self-care
pattern was evaluated by applying the Appraisal of Self-Care Agency
Scale (ASA-A) and the degree of functionality evaluation by the
Unified Parkinsons disease rating scale (UPDRS III).
Results: The sample consisted of 82% women; 43% of them are
widows. As to education, 60% of seniors had an educational level
considered low. Half of the population had more than 60 years, 44%
about 70 years and 6%, 80 years or more. It was shown an impaired
functional performance through the UPDRS III and there were a rel-
ative knowledge among patients regarding their self-care ability
(94,53, sd 12,86).
Conclusions: The results showed that the capacity was decreased
self-care for patients over 75 years of age. As the age increases
decreases the functional independence and the ability for self-care.
1079
Parkinsons disease impact on frailty and physical vulnerability
of the octagenarian elderly people
L.A. Leandro, H.G. Teive (Curitiba, Brazil)
Objective: Identify physically vulnerable older people, their liv-
ing conditions and health and associate with various outcomes such
as functional decline, frailty, hospitalization and death .
Background: Fragility can be defined as a biological syndrome
of impaired homeostatic reserve capacity of the organism and resist-
ance to stressors, resulting in declines in multiple physiological sys-
tems, causing vulnerability and adverse clinical outcome.
Vulnerability is a present condition in aging that can manifest in dif-
ferent dimensions.
Methods: A total of 27 elderly Parkinsonian octogenarians, HY
II/III, followed by a period of six months at the geriatric outpatient
clinic of the city of Curitiba, Brazil. Patients were evaluated for Vul-
nerable Elders Survey - VES 13 to analyze whether they were vul-
nerable and the UPDRS III and Schwab England to know the level
motor and functional.
Results: Of the total sample, 15 (55.56%) were women; 19
(70.37%) widows; 22 (81,48%) lived with relatives. Presented a
compromised engine performance by UPDRS III and committed by
Schwab England Activities of Daily Living. The outcomes were
functional decline and frailty associated with physical vulnerability.
Conclusions: The physical vulnerability is associated with weak-
ness, reduced functional ability and death. A vulnerable elderly are
more fragile and this leads to a situation of dependence in their
activities often providing death as final outcome.
1080
Inter-rater reliability of the hemifacial spasm severity scale
(HFS-SS)
E.C. Lim, A.M. Quek, L.L. Yeo, L. Shen, A.W. Chow, R.C. Seet
(Singapore, Singapore)
Objective: To assess the inter-rater agreement of the HFS-SS, in
patients with hemifacial spasm of varying severity, before and after
provocative maneuvers.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S418 POSTER SESSION
Background: Hemifacial spasm (HFS), characterized by involun-
tary contractions of muscles innervated by the facial nerve, affects
9.8 per 100,000 persons and may be embarrassing, or even disabling.
HFS is usually unilateral, but may rarely be bilateral. Until the
development of the SMC grading system (1), there was no rating
scale to assess the severity of hemifacial spasm. We developed a
novel hemifacial spasm severity scale (HFS-SS), and assessed inter-
rater agreement.
References:
1. Lee JA, Jo KW, Kong DS, Park K. Using the new clinical
grading scale for quantification of the severity of hemifacial spasm:
correlations with a quality of life scale. Stereotact Funct Neurosurg.
2012;90:16-9.
Methods: We videotaped 60 Asian patients with hemifacial
spasm (25 female, 35 male; 51 Chinese, 4 Indian, 4 Malay and 1
Burmese; Ages 28 95 years, Mean 58.8 years) at rest and after pro-
vocative maneuvers, for 1 minute each. The HFS-SS requires the
assessor to quantify the severity of twitching (on a scale of 0 to 4) in
the forehead, eye, nasal & maxillary region, mouth & chin region,
and neck. Whether HFS was unilateral or bilateral, and the presence/
absence of facial weakness, were also determined. Four qualified
neurologists independently reviewed videotaped assessments and
scored patients using the HFS-SS and the Facial and Oral Move-
ments component of the Abnormal Involuntary Movement Scale
(AIMS). Intraclass correlation between the 4 raters was assessed, and
the internal consistency of the HFS-SS was estimated using Cron-
bachs a.
Results: Intraclass correlation (ICC) between the 4 raters was
consistently high for both HFS-SS and AIMS (complete HFS-SS rat-
ing: 0.935; Assessment at rest (AAR) only: 0.931; Assessment after
provocative manoeuvres (AAPM) only: 0.931; AIMS: 0.853). Aver-
age Cronbachs a for HFS-SS was 0.916 (range 0.887 0.944),
compared to 0.620 (range 0.572 0.679) for AIMS. Kappa statistics
for multiple raters showed good inter-rater agreement for individual
items within the HFS-SS, (AAR 0.523, range 0,473-0.629; AAPM
0.493, range 0.382-0.550).
Conclusions: The HFS-SS is internally consistent and reliable for
the assessment of the severity of hemifacial spasm.
1081
Spatial and temporal variability during spirography
M. Memedi, J. Westin (Borl
ange, Sweden)
Objective: To investigate variability of spatial and temporal per-
formance of Parkinsons disease (PD) patients and healthy elderly
subjects during spirography tasks.
Background: A total of 105 subjects were recruited, comprising
of 65 patients with advanced PD (mean 6 sd age; 65 6 11), 15
patients intermediate stage patients experiencing motor fluctuations
(65 6 6), 15 clinically stable patients (65 6 6) and 10 healthy elderly
subjects (61 6 7). Thirty of the 65 advanced patients switched from
oral to continuous administration of treatment via pump. The sub-
jects used a telemetry touch screen device in their home environment
settings. On each test occasion, they were asked to trace pre-drawn
Archimedes spirals as accurately and fast as possible.
Methods: Spatial and temporal variability were measured by
computing four intra-individual measures of drawing displacement
and speed, respectively. Combined scores were derived by applying
principal component analysis on these measures and retaining the
first component. One-way ANOVA test followed by Tukey multiple
comparisons test was used to assess differences between the groups.
Results: Patients with advanced PD had slower drawing speed
and more spatial variability than moderate patients, stable patients
and healthy elderly subjects with a mean increase of 76%, 89% and
90% (p<0.001), respectively. The spatial variability of stable patients
did not differ from healthy elderly subjects. In contrast, the mean
temporal variability did not differ between healthy subjects, stable
Movement Disorders, Vol. 30, Suppl. 1, 2015
patients and advanced patients. Moderate patients had higher tempo-
ral variability than other groups.
Conclusions: The findings suggest that patients with PD can be
best discriminated from healthy subjects on measures of spatial vari-
ability rather than temporal variability. Spatial variability measures
are not useful for diagnosing PD but can be used for measuring the
severity of symptoms.
1082
Automatic spiral analysis for objective assessment of motor
symptoms in Parkinsons disease
M. Memedi, A. Johansson, F. Bergquist, D. Nyholm (Borl ange,
Sweden)
Objective: To develop and evaluate a computer-based method to
quantify Parkinsons disease (PD) motor symptoms related to Off
episodes and peak dose dyskinesias from spirals drawn on a touch
screen device.
Background: A total of 75 subjects were recruited, comprising
65 patients (mean 6 IQR age; 65 6 11) with advanced PD and 10
healthy elderly (HE) subjects (61 6 7). The subjects repeatedly per-
formed spirography tasks in their home environments using a touch
screen telemetry device.
Methods: Three clinicians used a web interface that animated the
spirals and allowed them to rate task performance. Initially, a num-
ber of motor features were assessed including impairment on a
scale from 1 (normal) to 10 (extremely severe), speed, irregularity
and hesitation on a scale from 0 (normal) to 4 (extremely severe).
Finally, cause of impairment was marked on a two-category scale
including Off and dyskinesia. The raw spiral data was processed and
thirteen quantitative measures were calculated and used in a logistic
regression classifier to automate the processing of scoring the cause.
Results: Intra-class correlation coefficients of the motor features
for the three raters were as follows: impairment, 0.7; speed, 0.73;
irregularity, 0.78; and hesitation, 0.45. The raters interpreted the
cause of impairment differently with Weighted Kappa coefficients of
0.27, 0.23 and 0.53 (p<0.001). The mean scores of the quantitative
measures were significantly different across spirals rated as Off, a
random sample of spirals drawn by HE subjects and spirals rated as
dyskinetic. The internal consistency of the measures was good with
Cronbachs Alpha coefficient of 0.64. The agreements between the
cause ratings of the logistic classifier and the three raters were good
with Weighted Kappa coefficient of 0.55 (p<0.001, Table 1).
Conclusions: The computer method automatically assesses the
severity of unwanted symptoms and can discriminate between PD-
specific and/or treatment-specific motor symptoms. The objective
assessments may improve decision-making during symptom evalua-
tion of individualized treatment when the goal is to maximize func-
tional On time for patients while minimizing their Off episodes and
troublesome dyskinesias.
TABLE 1. Assessments of cause of impairment in animated
spiral drawings for the raters and computer method. Cor-
rectly classified instances are highlidhted in bold.
Computer
Off Dyskinesia Total
Raters Off 28 13 41
Dyskinesia 10 59 69
Total 38 72 110
Weighted Kappa 0.55 (p<0.001)
 POSTER SESSION
1083
Vowel production deficit in cases of dysarthria due to
Parkinsons disease
D. Misra, M. Behari, V. Narang (New Delhi, India)
Objective: The present study proposes to examine the specific
correlation, if any between the score on H&Y scale and the first
formant, F1 of the vowels which corresponds to the high-low mov-
ment of the tongue on the other hand, and between H&Y score and
the F2 or F2-F1 of the vowels which correspond to the front-back
movement of the tongue in the articulation of vowels.
Background: One of the previous studies on acoustic space in
cases of PD by the authors (Misra, 2010)shows how acoustic space
gets reduced to nearly 50% of the control even when the score on
H&Y scale is 1.5 indicating early stages of PD.
Methods: 160 subjects, 24 to 30 score in MMSE; 1.5 to 4 H&Y
score in UPDRS, 46 male speakers of Hindi selected; 46 age and
gender, language matched control subjects also selected; 92 subjects
divided into 5 groups (5M15C); and (5F15C).Words chosen with
seven peripheral vowels i, e, E, a, o,O and u in the same CVC posi-
tion. Software used: PRAAT for analysis.
Results: The acoustic space gets considerably reduced in PD
cases with an average of 72% and 74% reduction for males and
females respectively. It also indicates the gradual decline in acoustic
space corresponding to progressive neuro- motor degeneration in PD
as shown in the following results. Minimal deficit with H&Y score
of 1.5: speech generally comprehensible but acoustic space reduced
to less than 50%. With the deterioration of the condition as indicated
by the scores 2, 2.5 and 3.0 on H&Y scale, there is further reduction
of acoustic space by about 10 to 15%. H&Y score 4 shows the other
extreme with a maximal deficit of 84% in male and 86% in fema-
le.The two parameters F1 and F2-F1 were examined separately to
see which one was relatively more stable and which one was worse
affected by neuro-motor degeneration in PD. F1 range which corre-
sponds to vowel height, high- low movement of the tongue in vowel
production shows a steep decline of 37.6% in cases of H&Y 1.5 and
then it continues to stay in the range of 65% i.e. 35% 1/-5% less
than normal for all groups. The cumulative effect of F1 and F2-F1
on acoustic space is remarkable.
Conclusions: Acoustic space can thus be used as an indicator of
early onset of PD with marked deficit of 55 to 60% and further grad-
ual decline and reduction in acoustic space corresponding to H&Y 2,
2.5 and 3, culminating in cases of H&Y 4 with the severity of motor
control deficit showing in acoustic space reduced by 85 to 90%.
1084
Comparing the psychometric properties of the paper and e-based
versions of the 39-item Parkinsons disease questionnaire (PDQ-
39)
D. Morley, S. Dummett, L. Kelly, J. Dawson, C. Jenkinson (Oxford,
United Kingdom)
Objective: To compare the psychometric properties of the paper
and e-based versions of the 39-item Parkinsons disease Question-
naire (PDQ-39).
Background: The PDQ-39 is the most extensively used self-report
instrument for the assessment of health-related quality of life in people
with Parkinsons (PwP). It demonstrates sound psychometric proper-
ties, has been incorporated in over 350 studies, including clinical tri-
als, with its use being widely recommended. The measure totals 39
items assessing eight dimensions of health; Mobility, Activities of
Daily Living, Emotional Well-Being, Stigma, Social Support, Cogni-
tions, Communication, and Bodily Discomfort. Given its level of
uptake and the increasing emphasis on electronic data capture, an e-
based version of the PDQ-39, the ePDQ, has recently been developed.
Methods: Psychometric data from the initial PDQ-39 validation
survey (n5359) was compared with that from the validation survey
of the ePDQ (n5118). Analyses included inspection of item-total
S419
correlations, internal reliability via Cronbachs alpha and construct
validity through higher order factor analysis.
Results: Item-total correlations ranged from 0.67-0.91 for the
PDQ-39 and 0.38-0.90 for the ePDQ. For the eight dimensions of
health, internal reliability ranged between 0.69 and 0.94 for the
PDQ-39 and 0.64 and 0.95 for the ePDQ. Higher order factor analy-
sis resulted in eigenvalues of 4.5 and 4.4 for the PDQ-39 and ePDQ
respectively. Explained variance was calculated as 56.80 for the
PDQ-39 and 55.38 for the ePDQ, with alpha values of 0.89 and 0.88
respectively.
Conclusions: Results indicate that the ePDQ largely mirrors the
properties of the paper-based version, the PDQ-39, in terms of reli-
ability and validity. Potential users can therefore incorporate the
ePDQ into computer-based data capture systems with confidence.
1085
Pretesting the Oxford participation and activities questionnaire:
Results from an expert review
D. Morley, S. Dummett, L. Kelly, J. Dawson, R. Fitzpatrick, C.
Jenkinson (Oxford, United Kingdom)
Objective: To pretest a new measure, the Oxford Participation
and Activities Questionnaire (Ox-PAQ), through views gained from
an expert panel on a preliminary 24-item draft.
Background: There is growing interest in the management of
long term conditions and maximising the cost effectiveness of treat-
ment, in part by keeping people active and participating in daily life.
The Ox-PAQ initiative aims to develop and validate a PROM to
assess participation and activity in people experiencing a range of
health conditions including Parkinsons disease, multiple sclerosis,
motor neurone disease, cancer, diabetes, osteoarthritis, spinal cord
injury and chronic back pain.
Methods: The Ox-PAQ was reviewed by an expert panel of 11
participants with a broad range of expertise, including clinical prac-
tice, academia, health economics and health technology assessment.
Panel responses were analysed and adjustments based on relevance,
concurrence between participants and methodological appropriateness
were subsequently made.
Results: The review resulted in minor changes to the format and
wording of six items. Two new items relating to pain and close rela-
tionships (e.g. with parents, carers, spouse, children) were added.
One item relating to personal care (washing and dressing) was sepa-
rated into two items. These adjustments resulted in a 27-item draft
questionnaire.
Conclusions: Expert review of the Ox-PAQ constitutes an impor-
tant first phase in pretesting the new measure. This will now be fol-
lowed by a series of cognitive interviews to further pretest the
instrument prior to a large scale validation survey.
1086
PDSS-2 cut-off scores for the severity of sleep disturbances in PD
Patients
M.L. Muntean, H. Benes, F. Sixel-D oring, C. Trenkwalder (Kassel,
Germany)
Objective: We aimed to determine PDSS-2 cut-off values defin-
ing a sleep disturbance severe enough for referring the patient to a
sleep center or initiation of specific treatment.
Background: Parkinsons disease Sleep Scale-2 (PDSS-2)
assesses a wide spectrum of disease specific sleep problems in Par-
kinsons disease (PD) and is easy to administer as a patient self-
rating scale. The validation study showed that the scale is reliable,
valid and precise. Until now, however, only one Japanese study
assessed cut-off scores to define poor sleepers.
Methods: We enrolled 93 inpatients with idiopathic PD consecu-
tively admitted to our hospital. Patients completed the PDSS-2. The
attending physician, who was blinded to the PDSS-2 results, but
Movement Disorders, Vol. 30, Suppl. 1, 2015
S420 POSTER SESSION

familiar with the patients history and current disease status com-
pleted a questionnaire consisting of two general questions regarding
the presence of PD specific and non-PD related sleep problems. Sta-
tistical analysis was performed to determine cut-off values for the
PDSS-2 in correlation to the physicians evaluation of sleep disturb-
ance severity.
Results: The study population consisted of 52(56%) men and
41(44%) women with an average age of 69.22 6 8.74 years. 18
(19%) patients had Hoehn& Yahr Stage 1-2,5, 55 (59%) patients
Stage 3-4 and 20 (25%) patients Hoehn& Yahr Stage 5 (during off).
PDSS-2 showed a sensitivity of 77.6% and a specificity of 74.3% in
relation to physician evaluation of PD specific sleep problems.
According to the physicians evaluation, PD specific sleep disturban-
ces occurred in 62% of the patients. 83% patients with PDSS-2
scores higher than 17 had clinical relevant sleep disturbances com-
pared to only 33% of the PD patients with scores equal or lower 17.
A PDDS-2 score of 17 is proposed as cut-off value for PD specific
sleep problems. The non-PD related sleep problems were not corre-
lated with PDSS-2 scores. Data are similar to those published by
Suzuki et co (2014), who defined patients with PDSS-2 scores higher
than 15 as poor sleepers.
Conclusions: To our knowledge this is the first study to define
PDSS-2 cut-off values for the severity of sleep disturbances in a
European PD population. Our study shows that scores higher than 17
define clinical relevant PD related sleep disturbances.
1087
1088
A multicentre study of the patients perspective: The first
Parkinsons disease pain questionnaire (Kings PD pain quest)
A.M. Rizos, P. Martinez-Martin, S. Pal, C. Carroll, D. Martino, C.
Falup-Pecurariu, B. Kessel, A. Sauerbier, A. Martin, M. Parry, R.
Inniss, L. Perkins, D. Trivedi, P. Odin, A. Antonini, K. Ray Chaud-
huri (London, United Kingdom)
Objective: To develop and validate an easy to use novel clini-
cal self-completed Parkinsons specific pain questionnaire (comple-
mentary to the Kings PD Pain Scale).
Background: Pain is a poorly characterised non-motor symptom
of Parkinsons disease (PD) and a determinant of quality of life
(Wasner, Deuschl. 2012). We have recently validated the first pain
scale specific to PD (Kings PD Pain Scale), but there are no patient
completed tools to empower patients to self-declare pain related
symptoms.
Methods: In a cross-sectional, open, multicentre pilot validation
study of the novel PD pain questionnaire (Kings PD Pain Quest),
which is complementary to the Kings PD Pain Scale (Figure 1) we
collected data from PD patients with otherwise unexplained pain and
controls without PD using the Kings PD Pain Quest, addressing the
same 14 items as the Kings PD Pain Scale in lay English under-
standable and completed by patients.
Results: 191 patients (mean age 64.2 6 11.8 years, duration of
disease 5.4 6 4.9 years, median H&Y 2 [range 1-5], 62.8% male)
and 174 non PD controls (mean age 56.7 6 16.0, 55.5% male) were
studied. Most patient-reported types of pain were musculoskeletal

Continuous motion sensor assessment of Parkinsons disease

during activities of daily living
C.L. Pulliam, D.A. Heldman, M.A. Burack, T.O. Mera (Cleveland,
OH, USA)
Objective: To use motion sensors to capture tremor, mobility,
and dyskinesia in patients with Parkinsons disease (PD) and motor
fluctuations during activities of daily living.
Background: Tremor, bradykinesia, mobility, and dyskinesia
have been measured previously using body worn motion sensors.
However, quantification during unconstrained activities poses a
unique challenge since dyskinesias can be difficult to distinguish
from voluntary movement.
Methods: Eight subjects with PD and a history of levodopa-
induced dyskinesias were instrumented with six degree-of-freedom
motion sensors on the wrist and ankle. Data were recorded as sub-
jects completed a series of activities of daily living (ADL) at stations
set up in a simulated home environment for approximately two
hours. Subjects first performed the activities in the OFF medication
state and then took their usual prescribed dose of medication and
continued to rotate through the ADL stations. Data recording ses-
sions were videotaped for subsequent evaluation. Time and fre-
quency domain algorithms based on previous clinical data processed
the kinematic data to generate severity scores for tremor and dyski-
nesia every 12 seconds. Moving average filters were applied to iden-
tify transitions in medication state. Dyskinetic periods were those for
which dyskinesia score exceeded an empirically-determined
threshold.
Results: Algorithm scores for tremor and dyskinesia showed a
high level of agreement with annotations based on visual inspection
of the video recordings and changed in concert with medication
state. Tremor and dyskinesia scores were predictive of the presence
or absence of tremor and dyskinesia, with average sensitivity and
specificity greater than 90%.
Conclusions: A system with two motion sensors can provide
accurate measures of overall tremor and dyskinesia as patients com-
plete complex movements associated with typical activities. Such a
system could provide valuable insight on motor fluctuations in the
context of daily life and aid in the development and evaluation of
new therapies. Fig. 1. (1088).

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION S421

Fig. 2. (1088).

pain (80.1%), nocturnal (pain while turning in bed, 46.6%), dystonic puted for the detection of noticeable OD, or the risk of aspiration,
(46.1%) or radicular pain (39.8%), as shown in Figure 2. and proved by cross-validation.
Controls also reported mostly musculoskeletal pain (63.8%)%), Results: The 26-item questionnaire MDT-PD showed high inter-
followed by radicular pain (25.3%), generalized whole body pain nal consistency (Cronbachs Alpha 0.91). Patients of the validation
(23.0%) and nocturnal pain (22.4%). Differences reached significance
level for musculoskeletal, dystonic radicular and nocturnal pain, as
well as RLS related pain (p<0.05, chi-square test).
Conclusions: Interim results suggest the Kings PD Pain Quest is
an useful and the first self completed tool complimentary to the PD
pain scale for assessment of patient reported pain, a key unmet need,
in PD.

1089
How to screen for dysphagia in Parkinsons disease? The
Munich dysphagia test (MDT-PD) A patient reported outcome
questionnaire
J.A. Simons, A. Waldmann, U.M. Fietzek (L
ubeck, Germany)
Objective: To evaluate the diagnostic performance of a new
dysphagia-screening questionnaire specified for patients with Parkin-
sons disease (PD).
Background: Oropharyngeal dysphagia as well as manifested
aspiration frequently occur in patients with PD. Especially symptoms
of the early clinical syndrome are still widely underdiagnosed, lead-
ing to significant threats to health, such as pneumonia, malnutrition,
or reduced quality of life. There are no disease-specific and suffi-
ciently validated screening procedures available.
Methods: The project comprised the development (N=105) and
validation phases (N=82) of the Munich Dysphagia Test (MDT-PD).
Patients were recruited at a German center for Movement Disorders
from 2009/3 to 2011/3. Enrollment of PD patients for validation pur-
pose was consecutively. Patients were assessed by clinical swallow-
ing tests and fiberoptic endoscopic evaluation. They were assigned to
the groups no dysphagia (N), oropharyngeal dysphagia (OD), and
dysphagia with penetration/aspiration (P/A) along their severity
grades of underlying rating-scales. These criteria sum scores were
compared against the results of the priorily answered MDT-PD. The
internal consistency was evaluated and the diagnostic quality com- Fig. 1. (1089).

Movement Disorders, Vol. 30, Suppl. 1, 2015

S422 POSTER SESSION
study aged 70.9 6 8.7 (mean 6 SD), were Hoehn & Yahr stage of 3
in median and scored 29.5 6 13.3 in the UPDRS motor part. Dyspha-
gia prevalence was 73% (44% with OD, 29% with P/A). A positive
correlation was found between the criteria sum score and weighted
MDT-PD sum score (r= 0.70, p<0.001). Discrimination between N
and P/A resulted in a sensitivity/specificity of 90%/86%, positive/
negative predictive values of 86%/90%, and likelihood ratios1/- of
6.3/0.1 (N vs. OD: sens/spec 82%/71%, ppv/npV 82%/71%, LR1/-
2.9/0.2), and similar results in cross-validation.
Conclusions: In medical practice the MDT-PD can be used for a
valid detection and initial graduation of dysphagia severity. The
questionnaire is available in German and English language. The
patients answers can be easily evaluated using a web application
[figure1].
1090
High-risk defining clinical parameters for dysphagia in
Parkinsons disease
J.A. Simons, N. Eisemann, U.M. Fietzek, A. Katalinic (Lubeck,
Germany)
Fig. 1. (1090).
Movement Disorders, Vol. 30, Suppl. 1, 2015
Objective: To define high-risk groups for oropharyngeal dyspha-
gia and laryngeal aspiration using clinical parameters reported to
have positive correlation with dysphagia severity in Parkinsons dis-
ease (PD).
Background: Dysphagia is a highly relevant symptom in Parkin-
sons disease (PD), occurring in 50-100% of patients. Clinical identi-
fication is complex, and therefore occurs too late with presentation
of life-threatening complications, such as aspiration pneumonia or
malnutrition/dehydration.
Methods: Consecutively enrolled PD patients of a German Move-
ment Disorders center underwent neurological examinations as well
as clinical and fiberoptic endoscopic swallowing evaluations. Along
the severity grades of underlying rating-scales they were allocated to
3 groups: no dysphagia(A), oropharyngeal dysphagia(B), and dyspha-
gia with penetration/aspiration(C). Cut-off values for high-risk
groups (A vs C, or A vs B1C) were determined from ROC curves
for mod. Hoehn & Yahr scale (HY), UPDRS motor part, disease
duration, age, drooling score scale, dysarthria score, and body mass
index. Relative risks (RR) and 95%-confidence intervals (CI) were
calculated.
Results: The 77 patients (mean age 70.5 6 8.4, median HY 3)
were classified to group A (21 patients), B (34), and C (22). Identi-
fied cutoffs were identical for both outcome groups (C; B1C).
 POSTER SESSION
[figure1] Dysphagia risk was significantly increased for almost all
parameters. Highest clinical relevance was ascertained for UPDRS
III and HY. Particularly at UPDRS III >=26 the risk for laryngeal
aspiration was found to be 6.23 times greater (CI 1.5525.02); and
also the risk for oropharyngeal dysphagia symptoms was 2.35 times
higher at this value (1.374.05). At HY >=4 was a 4.29 times
greater risk associated with aspiration (1.909.73), and an additive
risk for higher probability of oropharyngeal symptoms (RR 1.62;
1.242.12).
Conclusions: Motor performance and the disease stage were
closely associated with swallowing performance. In clinical practice
patients presenting risk factors of UPDRSIII >=26 or HY >= 4
should be screened for dysphagia with a validated disease-specific
questionnaire1 or undergo additional diagnostics, if necessary. Deter-
mined cutoffs need further confirmation, due to possible overfitting.
1. Simons JA, et al. Development and validation of a new screen-
ing questionnaire for dysphagia in early stages of Parkinsons dis-
ease. Parkinsonism Relat Disord 2014; 20(9):992998
1091
The PowerGlove: Assessment of hand and finger movements in
Parkinsons disease patients
K.J. van Dijk, R. Verhagen, J.C. van den Noort, L.J. Bour, P.H.
Veltink, C. Heida (Enschede, Netherlands)
Objective: The aim of the study is to test whether the Power-
Glove (PG), an instrumented glove which consists of inertial (accel-
erometers and gyroscopes) and magnetic sensors, is a valid and
reliable instrument to measure different degrees of hand motor
impairments in patients with Parkinsons disease (PD).
Fig. 1. (1091).
S423
Background: Assessment of hand movements is an important
part of the motor function section of the Unified PD Rating Scale
(UPDRS). Unfortunately, the assessment often varies per physician
and is highly dependent on experience. This subjective nature some-
times makes it hard to interpret the UPDRS correctly. Recently, the
University of Twente developed the PG which enables accurate and
ambulant measurement of hand and finger movements (Fig. 1A)[1].
Application of the PG during the clinical scoring will enable more
accurate observation of hand function and quantification of the PD
motor symptoms.
Methods: We plan to include 35 PD patients. We will assess the
hand movements of the patients in medication on/off state with the
PG during 7 UPDRS items, i.e. tremor at rest, action and postural
tremor, finger tapping, rapid opening/closing of the hand, pro/supina-
tion of the hand, and wrist rigidity. Sensor units of the PG are
attached to the dorsal side of the left hand and on the finger seg-
ments of the thumb, index and middle finger. One additional PG sen-
sor is attached to the forearm to measure the wrist angle. A force
sensor is used to measure the force which is applied to passively flex
the wrist of the patient. Prior to measurement, an anatomical calibra-
tion procedure is performed to determine the sensor-to-segment coor-
dinate systems.
Results: Visual inspection of preliminary results showed there
were notable differences in the recorded data within a patient in
medication on/off state (Fig 1B-D). [figure1]
Figure 1, (A) the PG, (B) an example of the power spectrum
from acceleration data during the postural tremor task, (C-D) the
joint angles of the index finger during rapid opening/closing of the
hand (on/off medication).
Conclusions: The results indicate that the PG enables to quantita-
tively detect differences in the clinical state of the patient. In the
Movement Disorders, Vol. 30, Suppl. 1, 2015
S424 POSTER SESSION
next phase of this study, parameters need to be found which describe
the performance of UPDRS tasks and include these in the group
analyses of the 35 PD patients.
[1]Noort, J. et al. Applications of the PowerGlove for measure-
ment of finger kinematics. BSN Workshops IEEE, 2014
Therapy in Movement Disorders: Medical
1092
Clinical outcomes of step synchronized vibration training in
Parkinsons disease patients
R. Aggarwal, M. Behari, S. Agrawal, I. Pretzer-Aboff, K. Winfree, G.
Dhankar, T. Shiva, V. Vashista (Delhi, India)
Objective: To evaluate effect of step synchronized vibration
intervention on those with Parkinsons disease (PD).
Background: Gait and balance disorders cause significant disabil-
ity and handicap in PD patients. Sensory cues and vibration therapy
have been used to improve gait abnormalities in PD patients. We
have developed PD shoe that provides step-synchronized vibration as
tactile cue while walking.
Methods: Seventeen PD patients with history of freezing of gait
volunteered for a step synchronized vibration intervention using the
PD Shoe device. Training involved 10 sessions of gait training over
two weeks. Each session included three 6-minute bouts of walking
with step-synchronized vibration applied to the distal end of the sec-
ond metatarsal head and the medial surface of the calcaneus, pre-
ceded and followed by 2-minute walking bouts with no vibration
present. Subjects were assessed on performance based clinical meas-
ures of the Unified Parkinsons disease Rating Scale part three
(UPDRS III), Timed Up and Go test (TUG), Berg Balance Scale
(BBS), and the 10 meter walk test. Subjects were also assessed on
the questionnaire based clinical measures of Freezing of Gait Ques-
tionnaire (FOG-Q), Falls Efficacy Scale- International (FES-I), and
the Parkinsons disease Questionnaire (PDQ39). All measures were
made pre intervention, post intervention, and at a two-week post
intervention follow up. Friedman test followed by Wilcoxon signed
rank test was used.
Results: The mean age was 55 (SD 10.1) years and the mean dis-
ease duration was 8.9 (SD 5.4) years. All patients completed the
training without any adverse effects. Sixteen patients reported for a
follow up evaluation two weeks after the intervention. There was a
significant improvement in measures of the UPDRS III (p50.044),
TUG (p50.005), BBS (p50.003), FES-I (p50.041), and PDQ-39
(p50.021). Changes were not significant on the measures of FOG-Q
or 10 meter walk test from pre to follow up evaluations.
Conclusions: Step synchronized vibration is a safe and effec-
tive intervention for persons with PD. It was shown to improve
balance as illustrated by the change in BBS, gait as reflected
with the improved TUG and FES-I, motor features as demon-
strated by UPDRS III, and quality of life as shown in PDQ-39
scores.
1093
Carrier mediated delivery system bearing dopamine for effective
management of Parkinsonism
S. Bhargava, V. Bhargava (Kanpur, India)
Objective: In the present investigation, amino acid coupled lipo-
somes bearing dopamine-HCl were prepared to deliver drug to the
brain utilizing receptor-mediated transcytosis for effective manage-
ment of Parkinsonism.
Background: Parkinsons is a Neurodegenerative disease in
which there is dopamine deficiency in Basal ganglia. The delivery of
Movement Disorders, Vol. 30, Suppl. 1, 2015
drug and sustaining it in effective concentration in brain is challeng-
ing due to blood brain barrier (BBB).
Methods: L-lysine stearylamine conjugate (LSC) was synthesized
& LSC coupled liposomes bearing dopamine HCl was prepared by
lipid cast film method. Formulations were analyzed for average vesi-
cle size measured through Laser diffraction particle analyser (CILAS
1064 L, France), shape through Transmission Electron Microscopy,
drug entrapment determined using Sephadex G- 75 minicolumn cen-
trifugation method, in-vitro drug release and in-vivo efficacy of the
formulations was assessed by measuring the reduction in the degree
of drug induced catatonia in albino rats.
Results: Average particle size was found in the range of 1.92-
0.80 mm. There was increase in the size for coupled liposomes due
to the inclusion of LSC in liposomal bilayers. The percent encapsula-
tion efficiency decreased from 46.82 6 2.17% in uncoupled to
38.13 6 1.18% in coupled liposomes. The in-vitro drug release after
24hrs was 58.9 6 2.94% with uncoupled while the coupled liposomes
showed 43.7 6 2.18% drug release. The lower value for coupled for-
mulation could be due to the retardation of drug release caused due
to the incorporation of LSC in the liposomal bilayers, which
enhanced the structural integrity of the bilayer. In-vivo study reveals
that the animals receiving uncoupled liposomes showed partial
reduction and animals that received coupled liposomes showed
almost complete reduction in catatonia.6
Conclusions: Fluoresence study clearly indicates the uptake of 6-
CF in blood vessels and accumulated in brain. This could be due to
enhanced uptake of Lysine coupled liposomes through amino acid
transporters present at BBB surface.
1094
Decreased OFF time and improved Parkinsons disease
symptoms with the gastroprokinetic camicinal as an adjunct to
L-DOPA based treatment; a pilot study
D.J. Burn, S.L. Marrinan, T. Otiker, L.S. Vasist, R.A. Gibson, B.K.
Sarai, M.E. Barton, D.B. Richards, P.M. Hellstr
om, D. Nyholm, G.E.
Dukes (Newcastle upon Tyne, United Kingdom)
Objective: To evaluate L-DOPA (LD) adjunctive treatment with
camicinal (C) on: symptoms of motor impairment (MDS-UPDRS
part 3) and Parkinsons disease (PD) symptoms (total MDS-UPDRS),
amount of awake time spent OFF, pharmacokinetics (PK) of LD,
gastric emptying (GE), safety/tolerability.
Background: LD absorption occurs in the small intestine and is
rate-limited by GE. GE is slowed in up to 90% of PD patients. C is
an oral motilin receptor agonist, which enhanced GE in healthy vol-
unteers (50 mg QD) for 14 days.
Methods: We conducted a Phase II randomized, double-blind,
placebo (P)-controlled study in 56 (36 male, 20 female) PD patients
who had slow GE and suboptimal motor control while taking LD-
based therapy. Subjects were randomized in a 2:1 ratio to either C
50 mg (n537) or P (n519) once daily for 8 days. Total MDS-
UPDRS score was assessed at baseline and on Day 8, prior to the
LD dose; part 3 score was assessed at baseline and on Day 8, post
LD dose. OFF time was assessed by daily diaries during the base-
line and treatment periods. GE and LD PK were assessed at baseline
and on Day 8.
Results: Subjects receiving C had a significantly greater mean
reduction from baseline in OFF time versus those receiving P (-
2.31 hrs; 95% CI -3.71, -0.90), with a corresponding mean improve-
ment of 13 points (95% CI 5, 20) in the total MDS-UPDRS score
and 9 points (95% CI 3, 15) improvement in 4 hour post-dose part 3
score. There was no evidence of a significant increase in LD expo-
sure, although there was a reduction in median Tmax (60 min; Day
8 vs. placebo). Reduction in Tmax correlated with improvements in
OFF times (on average, 60 min Tmax decrease 5 48 min decrease
in OFF time). Modest non-significant GE enhancement occurred
on C. Non-serious adverse events (AE) were reported by 24 (63%)
in C group, (most frequent: headache, fatigue) and by 17 (89%) in P
 POSTER SESSION
group (most frequent: headache, nausea). Two subjects receiving C
had AE of increased dyskinesias. Four serious AEs occurred (C: pru-
ritus, circulatory collapse; P: rib fracture and ankle fracture, worsen-
ing PD). Only worsening of PD was considered treatment-related by
the investigator.
Conclusions: Adjunct treatment to LD with C in poorly con-
trolled PD patients may result in symptom improvement and
decreased waking OFF time. Larger/longer clinical trials are neces-
sary to confirm these findings.
1095
Mucuna pruriens for the treatment of Parkinsons disease in low
income countries: Very low cost seed preparation without
pharmaceutical technology
E. Cassani, M. Barichella, R. Cilia, J. Laguna, F. Sparvoli, A.
Akpalu, K. Ofosu Budu, M.T. Scarpa, E. Cereda, L. Iorio, G. Pezzoli
(Milan, Italy)
Objective: To develop a safe, simple, low-cost, standardizable
method for Mucuna Pruriens (MP) seed preparation. To quantify the
dose of MP required to treat PD patients (according to the literature,
the efficacy of levodopa with dopa-decarboxylase inhibitor (DDCI)
vs levodopa DDCI-free is 1:4-5).
Background: In low income areas, such as Africa, about 0.2% of
the population is believed to be affected by Parkinsons disease
(PD). Most patients (87.5%) cannot afford pharmacological therapy.
A therapeutic option for them is the use of a legume called Mucuna
Pruriens (MP), which grows spontaneously in the tropics and has
seeds with a fairly high levodopa content (4-6%). It is known as
Ayurvedic remedy for PD.
Methods: We collected 29 different kinds of MP seeds, from
Africa (Ghana, Togo, Zambia, Mozambique, Zimbabwe) and Latin
America (Bolivia, Brazil, Costa Rica) and we measured:
- The content in levodopa and in alkaloids in the dried seeds.
- The change in levodopa content after standard boiling and after
roasting (seeds were roasted in a pan for 15, peeled, ground and
passed through a sieve).
Then, we estimated the quantity of levodopa required for each
patient; we weighed the corresponding dose of roasted powder, dis-
persed it in water and administered it to patients.
Results: - The mean content in levodopa in the dried seeds was
5.1%. Alkaloids were not found.
- The mean concentration of levodopa after boiling was 2.7%. A
healthy volunteer, after ingestion of 11 g of boiled MP, experienced
some mild side effects (hyposalivation, nausea, hypotension).
Instead, roasting seems to be safe and does not significantly
reduce the content in levodopa (still 5%). In the tropics the cost of
the roasted powder prepared at home is negligible. The roasted pow-
der is easy to take and to be stored.
- In an open-label study, MP roasted powder was similar to phar-
maceutical preparations levodopa/DDCI in terms of clinical antiPar-
kinsonian effects and side effects. 100 1 25 mg tablet of levodopa/
DDCI corresponds to about 7.5-8 g of roasted powder (containing
about 400 mg of DDCI-free levodopa).
Conclusions: MP is safe, effective, easy to prepare and very
cheap (total annual cost for a PD patient: 10-15 US $). MP is a sus-
tainable alternative treatment for PD patients in low income
countries.
1096
Mucuna pruriens therapy in Parkinsons disease: A double-blind,
placebo-controlled, randomized, crossover study
R. Cilia, J. Laguna, E. Cassani, E. Cereda, G. Pezzoli (Milano,
Italy)
Objective: To investigate safety and efficacy of Mucuna pruriens
(MP) challenge in comparison to levodopa(LD)1DDCI. Primary effi-
S425
cacy outcomes: (1a) change in UPDRSIII at 90 and 180 from OFF;
(1b) latency to ON; (1c) duration of full ON. Primary safety out-
comes: (2a) frequency of adverse events; (2b) severity of
dyskinesias.
Background: MP is a legominous plant whose seeds contain
high-concentrations of levodopa.
Methods: This double-blind, placebo-controlled, randomized,
crossover study was conducted in Santa Cruz (Bolivia) where the
local neurologist (J.L.) has long-standing experience on MP therapy
in PD. The LD content in MP collected here was 5.7% (after roast-
ing and grinding).
Eighteen patients with advanced PD (eight on MP therapy since a
median of 3.5 ys) underwent six treatments:
(1) Dispersible LD1Benserazide (BZ) at 3.5 6 0.2mg/kg;
(2) MP at 3.5-fold higher dose than LD/BZ (17g: LD
13.1 6 1.1mg/kg);
(3) MP at 5-fold higher dose than LD/BD (24g: LD
18.5 6 1.1mg/kg);
(4) LD without DDCI at the same dose of high-dose MP
(18.3 6 1.0mg/kg);
(5) MP1BZ at the same dose of LD/BZ (5g: LD 3.8 6 0.2mg/
kg);
(6) Placebo.
UPDRS III scores were collected in OFF, at 90 and 180. Dyski-
nesias were rated using the AIMS at 90 and 180. We recorded all
AEs, supine/standing blood pressure and heart rate.
Results: Compared to LD1BZ, treatment with high-dose MP
induced larger improvement of UPDRSIII at 90 (p50.037) and 180
(p50.001). Latency to ON was shorter (p50.008), full ON was lon-
ger (p<0.001) and dyskinesias were milder (p50.021) after MP than
LD1BZ. The frequency of overall adverse events after MP tended to
be lower than after LD1BZ (11% vs. 39%; P=0.121) and was signif-
icantly lower after the same dose of LD without DDCI (66.7%;
P=0.002). No differences were found in cardiovascular response.
Lower dose of MP had similar effects on motor symptoms and ON
duration than LD1BZ, but with lower AEs and dyskinesias. Before
this study, patients on chronic MP therapy reported neither major
side effects nor worsening of motor complications compared to
LD1DDCI.
Conclusions: MP is a safe and effective treatment in PD with
motor fluctuations and dyskinesias. A longitudinal 16-week crossover
study is ongoing to investigate safety and efficacy of chronic MP
therapy compared to LD1DDCI. If safe and effective in the long-
term, MP could be a sustainable alternative to standard medical ther-
apy for PD in low-income countries.
1097
Pilot study to evaluate transcranial direct current stimulation
(tDCS) during sleep for the treatment of Parkinsons disease
D.A. Heldman, C.L. Pulliam, L.M. Blassucci, J.P. Giuffrida, C.L.
Comella (Cleveland, OH, USA)
Objective: This pilot study is designed to determine feasibility,
efficacy, and adverse effects of transcranial direct current stimulation
(tDCS) applied during sleep in Parkinsons disease (PD).
Background: Recent studies have demonstrated that noninvasive
anodal tDCS applied to the scalp over motor cortex can improve PD
symptoms. Applying tDCS during sleep could provide a feasible
method for providing therapy for an extended period when the brain
may be more susceptible to tDCS-related modulation.
Methods: This study used a placebo controlled, crossover design
and included subjects with idiopathic PD who are currently treated
with levodopa therapy with morning akinesia. Each subject under-
went two pairs of consecutive night polysomnograms (PSG), an
adaptation night and a study night, separated by 1-4 weeks. During
the adaptation night, subjects were studied using a standard PSG pro-
tocol. During each study night, tDCS electrodes were applied with
the anode at C3 or C4 on the 10-20 system contralateral to the more
Movement Disorders, Vol. 30, Suppl. 1, 2015
S426 POSTER SESSION
affected limb and cathodes consisting of four linked electrodes in
ring fashion. Subjects were randomized to receive either active or
sham tDCS on the study night of the first pair and then crossed over
to active or sham tDCS for the study night of the second pair. Begin-
ning 1 hour after sleep onset on study nights, three 20 minute tDCS
sessions were applied for 20 minutes separated by 1 hour intervals.
In the morning following both adaptation and study PSGs, prior to
the first dose of levodopa, subjects were evaluated by a rater blinded
to treatment status using the Unified Parkinsons disease Rating
Scale (MDS-UPDRS) and by a motion-sensor-based automated
motor assessment.
Results: Six subjects (3 male, 3 female; age 52-70 years; baseline
MDS-UPDRS-III scores 30.2 6 8.5) participated in the study. Morn-
ing UPDRS bradykinesia scores showed a trend toward improved
following active tDCS compared to sham (24.7% versus -0.1%,
respectively, p50.13). Objective measures of motor performance
also tended to improve following active tDCS (10.1% versus -0.8%,
respectively, p50.18). The only adverse effect was mild burning sen-
sation reported by 1 subject.
Conclusions: In this pilot study, tDCS administered during sleep
tended to improve morning severity of PD prior to first levodopa
dose with minimal side effects. Based on these results, additional
investigations are warranted.
1098
Rapid titration impact on length of stay for Parkinsons disease
patients with orthostatic hypotension
A.D. Hohler, M.C. Ponce de Leon, T. DePiero, D. Katz, A. Deb
(Boston, USA)
Objective: The purpose of this project was to develop a rapid
titration protocol to optimize the treatment of orthostatic hypotension
in Parkinsons disease.
Background: Orthostatic hypotension is seen in over 40% of our
moderate and advanced patients with Parkinsons disease. It contrib-
utes to difficulties with cognition, gait and ambulation. Reduction in
orthostatic hypotension causes improvement in these areas. Ortho-
static hypotension is defined as a drop in systolic blood pressure of
at least 20 points, or diastolic blood pressure of at least 10 points
within 3 minutes when moving from sitting to standing position.
Methods: We developed a rapid titration schedule using a tiered
approach to aggressively manage orthostatic hypotension. Step 1:
antihypertensive medication adjustment, hydration, and compression
stockings. If orthostatic hypotension continued Step 2 saw the initia-
tion of salt tablets three times a day and initiation of fludrocortisone
0.1 mg in the am. Step three involved increasing fludrocortisone and
initiation of midodrine. Step 4 involved increasing midodrine and
initiation of pyridostigmine.
Results: There was a significant reduction in the length of stay in
our patients. Prior to the initiation of our rapid titration program the
average length of stay of our patients was 20.67 days. After the ini-
tiation of this program the length of stay was reduced to 12.38 days.
This 40% reduction in inpatient time allowed patients to return to
their lives in a more expedited fashion.
Conclusions: A rapid titration step program was useful at our
institution to reduce length of stay in our patients with Parkinsons
disease and orthostatic hypotension. This protocol is safe and well
tolerated.
1099
Psychometric validation of the Polish version Parkinsons disease
questionnaire-39 (PDQ-39) and its short form (PDQ-8)
A.T. Krygowska-Wajs, A. Gorecka-Mazur, K.A. Tomaszewski, K.
Potasz, A. Furgala (Cracow, Korea)
Objective: The aim of this work was to validate the Polish ver-
sion of the PDQ-39 and its short form (PDQ-8).
Movement Disorders, Vol. 30, Suppl. 1, 2015
Background: The PDQ-39 is a disease - specific measure for
health related quality of life (HRQoL) assessment in Parkinsons dis-
ease (PD). Tracking changes in a patients HRQoL becomes increas-
ingly important in clinical practice, as well as in international
clinical trials. This calls for validated and acceptable tools for
HRQoL assessment to facilitate inter-population comparisons.
Methods: Patients with the diagnosis of idiopathic PD according
to UK Parkinsons disease Society Brain Bank Criteria were included
in the study. All patients filled out the Polish version of the PDQ-39,
the PDQ-8, and a demographic questionnaire. The severity of PD
symptoms was assessed using the Hoehn & Yahr scale. Standard
validity and reliability analyses were performed. The re-test took
place 2 weeks after the initial assessment.
Results: One-hundred-and-nineteen patients (47 women 39.5%;
72 men 60.5%) aged 63.0 6 10.5 years with disease duration of
9.0 6 5.4 years were enrolled into the study group. The mean study
group scores of the PDQ-39, PDQ-8, and of the Hoehn & Yahr scale
were 34.5 6 20.6; 34.6 6 20.2 and 2.6 6 0.73, respectively. There
was a strong positive correlation between the total scores of the
PDQ-39, and the PDQ-8 (r=0.72; p<0.0001). Cronbachs alpha coef-
ficients ranged 0.81-0.94 for the PDQ-39 and 0.79 for the PDQ-8,
showing positive internal consistency of both questionnaires. Re-test
was undertaken with 78 patients (39.2%). The interclass correlation
for the PDQ-8 was 0.84 (95%CI 0.75-0.90) and proved appropriate
test-retest reliability. Satisfactory convergent and discriminant valid-
ity in multi-trait scaling analyses was seen.
Conclusions: The Polish version of the PDQ-39 and the PDQ-8
proved to be reliable and valid tools for measuring health-related
quality of life in PD patients. Both can be recommended for use in
the clinical setting in the Polish population. The PDQ-8 seems to be
a good substitute for the PDQ-39 in situations requiring question-
naire brevity.
1100
Dalfampridine extended release in patients with Parkinsons
disease related gait dysfunction: A randomized double blind trial
C.C. Luca, G. Nadayil, C. Dong, E. Field-Fotte, C. Singer (Miami,
FL, USA)
Objective: To evaluate the effect of dalfampridine extended
release (D-ER) 10 mg tablets twice daily on different domains of
walking in patients with Parkinsons disease (PD).
Background: Gait related disability is the most troublesome fea-
ture of PD and effective treatment options are lacking.
Dalfampridine-ER improves walking in patients with Multiple Scle-
rosis and was reported to be beneficial in PD patients as well.
Methods: 22 patients with PD and gait dysfunction were random-
ized to receive D-ER 10 mg twice daily or placebo for 4 weeks in a
crossover design with a 2 week washout period. The primary out-
comes were change in the stride length and velocity, measured by
3D movement analysis system. Secondary outcome measures
included: United Parkinsons disease Rating Scale (UPDRS part III)
and Freezing of Gait Questionnaire (FOGQ). Safety and Tolerability
were assessed.
Results: 18 PD patients completed the study; mean age,
67.5 6 8.7. Baseline scores for motor UPDRS and FOGQ were
36.6 6 14.1 and 14.1 6 5.3, respectively. At 4 weeks, velocity was
not significantly different between D-ER (0.89 m/s 60.33) and pla-
cebo (0.93 m/s 60.27) conditions. The stride length was also similar
between conditions: 0.96m 60.38 for D-ER versus 1.06m 60.33 for
placebo. A trend for improvement in the motor UPDRS (1.8,
p50.34) and FOGQ (0.9 p50.19) after 4 weeks of D-ER was identi-
fied. Responder analysis showed significant improvements with D-
ER in 10 patients in UPDRS (6.6 62.7, p50.02), PIGD sub-score
(gait score; 3.2 6 1.02, p50.004) and FOGQ (-2.1 6 0.8, p50.01).
D-ER was generally well tolerated with the most frequent side
effects being dizziness, nausea and balance problems.
 POSTER SESSION
Conclusions: D-ER is well tolerated in PD patients. The patient-
reported beneficial effects seen in UPDRS, PIGD and FOG scores
suggest that D-ER may potentially have favorable effects in certain
aspects of walking in patients with PD. Larger studies are necessary
to establish the effects of D-ER in patients with PD and gait
dysfunction.
Study sponsored by AAN CRTF and ACORDA.
1101
A novel levodopa dry powder inhaler for treatment of off
periods in Parkinsons disease patients
M. Luinstra, F. Grasmeijer, P. Hagedoorn, H.W. Frijlink, A.H. de
Boer (Groningen, Netherlands)
Objective: The aim of our study was to develop a dry powder
inhaler with levodopa which is adapted to the inspiratory perform-
ance of Parkinsons patients during their off periods.
Background: The treatment of Parkinsons patients in off periods
with orally administered levodopa is hindered by a poor bioavailabil-
ity and a a resulting slow onset of effect. Therefore, there is a need
for levodopa formulations with a more rapid onset of effect, like a
pulmonary formulation of levodopa.
Methods: Based on the inspiratory capacities of Parkinsons
patients, we developed and screened various levodopa powder for-
mulations in order to study the in vitro deposition. After screening,
we selected the most suitable levodopa dry powder formulation,
which was studied in detail for different pressure drops across the
inhaler as well as for different dose levels.
Results: Levodopa that is co-micronised with only 2% l-leucine
and dispersed with the Cyclops high dose dry powder inhaler showed
to be a promising candidate for the treatment of Parkinsons disease
patients in an off period. A created pressure drop of at least 3 kPa,
but preferably 4 kPa across the Cyclops during at least 3 seconds is
needed for acceptable dispersion and emission of the powder
formulation.
Conclusions: The combination of this particular formulation and
the Cyclops inhaler meets the basic in vitro requirements regarding
delivered fine particle dose for satisfactory deposition in the periph-
eral airways and dose reproducibility. This is partly caused by the
high resistance of the inhaler, which limits the flow rate and, there-
fore, oropharyngeal deposition, but this was shown to be well
handled and tolerated by Parkinsons disease patients in an off period
in a separate study. Future clinical trials have to show if the devel-
oped levodopa inhalation product has the desired therapeutic effect.
1102
Mapping the availability, price and affordability of drugs used to
treat Parkinsons disease in Kenya
J. Mokaya, W.K. Gray, R.W. Walker (Nairobi, Kenya)
Objective: To determine the availability, price and affordability
of drugs for treating Parkinsons disease (PD) in Kenya.
Background: The demographic transition and ageing of the Afri-
can population are contributing to an increase in the burden of non-
communicable disease, including PD. However, there is a dearth of
knowledge about the availability and affordability of different drug
treatment for PD in Africa.
Methods: A facility based survey was conducted in selected pub-
lic, private and other sector, medicine outlets in former headquarter
towns of Kenyas 8 provinces. We used the World Health Organiza-
tion/Health Action International methodology to obtain data for PD
drugs. Unit price for each drug was obtained and the amount per
month set aside by the lowest paid government worker to purchase a
months supply of drugs, after deducting an average amount of basic
monthly expenses, was calculated to determine affordability.
Approval to conduct this survey was obtained from the Kenyatta
S427
National Hospital/University of Nairobi Ethics Research Committee
and the Ministry of Health.
Results: 48 outlets were visited, 6 in each of the 8 provinces. 50%
of the sampled outlets experienced irregular supply of medicines,
while 44% highlighted lack of awareness as a limitation in the man-
agement of PD in Kenya. The average availability of PD drugs in the
public sector was less than 20% for all medicines whereas in the pri-
vate and other sector outlets, PD drug availability was 63% for Ergot
derived dopamine agonists, 55% for anticholinergics, 48% for Levo-
dopa, and less than 10% for MAOIBs, non-ergot derived dopamine
agonists and COMT inhibitors. The average cost of levodopa and car-
bidopa 100/10 mg for a month (100mg thrice a day regimen) is about
37 US Dollars (USD), while 9 USD per month could be set aside by
the lowest paid government worker to purchase PD medication, after
deducting an average amount for basic monthly expenses. 79% of the
outlets considered anticholinergics (Trihexyphenidyl) affordable at an
approximate monthly cost of 4 USD for a 5mg thrice daily regimen.
Conclusions: Availability and affordability of drugs used to treat
PD in Kenya are poor and pose a challenge for managing PD. In
addition to creating awareness, ensuring a consistent supply of PD
drugs at an affordable price is key to the successful management of
PD in Kenya.
1103
Zonisamide improves Parkinsonism in patients with DLB: A
double-blind randomized placebo-controlled study
M. Murata, T. Odawara, K. Hasegawa, Y. Tamai, M. Nakamura, R.
Shimazu, K. Kosaka (Tokyo, Japan)
Objective: To evaluate the efficacy of zonisamide (ZNS) for Par-
kinsonism in patients with dementia with Lewy bodies (DLB).
Background: Previously we showed ZNS improves motor symp-
toms in patients with Parkinsons disease with rare occurrence or
exacerbation of hallucination.
Methods: Patients diagnosed with probable DLB, who had a
UPDRS Part 3 total score 10 and a Mini-Mental state examination
(MMSE) score 10-26, and had received L-dopa/DCI therapy for 12
weeks were included. They received placebo (P) for 4 weeks in a
single-blind manner, then were randomized into 3 groups and
received P, ZNS 25 or 50 mg/day for 12 weeks in a double-blind
manner. The primary endpoint was the UPDRS Part 3 total score.
The MMSE, Neuropsychiatric inventory (NPI), Zarit caregiver bur-
den interview (ZBI), adverse events (AEs), clinical laboratory tests,
ECG was also evaluated.
Results: Of 159 patients (58 [P], 51 [ZNS 25 mg], 50 [ZNS
50 mg]) randomized, 153 (55, 48, 50, respectively) were included in
the modified intention-to-treat (mITT) analysis (the primary), and
159 in the safety analysis. At baseline, mean age (6 SD) was
75.1 6 6.3 years, mean duration of dementia and motor dysfunction
was 3.8 6 2.5 and 3.6 6 2.9 years, respectively. The frequency of
fluctuating cognition and visual hallucination were both 67.3%.
Approximately 10% of the patients received quetiapine for their psy-
chiatric problems. The mean levodopa equivalent daily dose was
318.7 6 191.3 mg and mean levodopa daily dose was
278.9 6 148.6mg. The mean UPDRS Part 3 total score was
32.4 6 11.4, mean MMSE score was 21.4 6 4.8.The UPDRS part 3
total score reduced in all the 3 groups at Week 12 (change from
baseline [LS Mean 6 SE]; -2.1 6 0.9 [P], -4.4 6 1.0 [ZNS 25 mg], -
6.2 6 1.0 [ZNS 50 mg]), and the reduction was greater for ZNS
50 mg than for P (difference, -4.1 [95% confidence interval; -6.8, -
1.4]; p50.003, ANCOVA [Fishers LSD]). The score of MMSE,
NPI-10, or ZBI did not significantly change. The incidence of AEs
was 50.0% (P), 43.1% (ZNS 25 mg), and 64.0% (ZNS 50 mg). The
reported AEs were similar to those in patients with Parkinsons dis-
ease. No notable differences in incidences of somnolence, hallucina-
tion, or cognitive disorder were found between ZNS and P.
Conclusions: ZNS significantly improved Parkinsonism accompa-
nying DLB without exaggerating psychiatric symptoms.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S428 POSTER SESSION
1104
Impact of therapeutic area specific data standards for
Parkinsons disease
J. Neville, S. Kopko, J. Odenkirchen, W. Galpern, K. Marek, D.
Burn, Y. Ben Shlomo, D.G. Grosset, M. Farrer, K. Romero, E.
Aviles, S. Dubman, M.F. Gordon, A. Roach, D. Stephenson (Tucson,
AZ, USA)
Objective: The objective of this work is to convey the applica-
tion and utility of clinical data standards developed for Parkinsons
disease (PD).
Background: Critical Path Institute (C-Path) has played a leader-
ship role in developing consensus data standards and fostering pre-
competitive data sharing. The Coalition Against Major Diseases
(CAMD), one of C-Paths consortia, in partnership with the Clinical
Data Interchange Standards Consortium (CDISC) and the National
Institute of Neurological Disorders and Stroke (NINDS), have suc-
cessfully developed consensus data standards for PD. These thera-
peutic area specific standards represent the preferred format by
regulatory agencies for submitting new drug applications.
Methods: The CAMD coalition of academic experts, NINDS,
industry members, regulatory agencies, and patient advocacy groups
collectively developed data standards in partnership with CDISC. With
input from clinical subject matter experts (SMEs) and NINDS, working
groups of data standards experts mapped clinical concepts relevant to
PD to the CDISC Study Data Tabulation Model (SDTM) and devel-
oped controlled terminology to support the construction of standardized
databases for research and regulatory submission in PD clinical trials.
Results: A CDISC therapeutic-area data standards user guide
(TAUG) was developed for PD based on the CDISC SDTM founda-
tional standards. The PD TAUG originated from the comprehensive
common data elements (CDEs) developed by the PD Common Data
Elements (CDE) Work Group (http://www.commondataelements.
ninds.nih.gov/pd.aspx#tab=Data_Standards). Concepts covered by the
PD TAUG include family history, deep brain stimulation, micro-
scopic findings (neuropathology), biospecimens (tissue sample han-
dling/tracking), and neuroimaging (MRI, PET/SPECT,
Spectroscopy). Clinical outcome assessments include UPDRS, MDS-
UPDRS and a variety of additional endpoints.
Conclusions: The use of consensus data standards maximizes
efficiency in regulatory review and facilitates analyses across diverse
studies. Importantly, CDISC standards will be required by FDA for
regulatory submission as early as fiscal year 2017. These standards
foster the collection of clinical trial data and the integration and
analysis of existing or anticipated data across various stakeholders
systems. The PD CDISC TAUG is readily available to sponsors, data
scientists and researchers for widespread use and implementation
(http://www.cdisc.org/therapeutic).
1105
Helicobacter pylori infection in Parkinsons disease patients
detected by 14C urea breath test, a new nucleer medicine test
E.E. Okuyucu, H. Yalcin, B. Ozer, S. Yilmazer, M. Demirci, I. Melek,
T. Duman (Hatay, Turkey)
Objective: The aim of this study is to observe the Helicobacter
Pylori positivity by a non-invasive new nucleer medicine test and
efficacity of HP eradication on clinical response to levodopa treat-
ment at PD patients.
Background: Peptic ulcus, Helicobacter pylori (HP) infections
seem to be more frequent in Parkinsons disease (PD) patients than
normal population. Also, existance of Helicobacter Pylori in stomach
reduces levo dopa absorpsion.
Methods: 32 patients coming to Mustafa Kemal University Hos-
pital Neurology out patient clinic with idiopathic PD who were
receiving levodopa and having any gastric problems, were included
the study. The existence of HP were made by 14C -urea breath test
and anti-CagA antibody.
Movement Disorders, Vol. 30, Suppl. 1, 2015
After screening of HP, eradication were made. Before and after
eradication UPDRS and Hoehn-Yahr scale were performed.
Results: The mean age of patients were 67.6 6 8.1 years, duration
of Parkinsons disease were 4.8 6 4.2. Among 32 patients with PD,
22 (68.8%) had positive result on 14C-urea breath test. After eradica-
tion only 1 (3.1%) patient had a positive result(McNemar Test,
p<0.001). Twenty (%63,5) patients had pozitive anti-CagA antibody,
after eradication there were 5 (%15,6) patients still having anti-CagA
antibody (p<0.001). The mean value of total UPDRS scores before
and after eradication were 34,3 6 18,5 and 25,3 6 15,2 sequentially
(p<0.001). The mean value of Hoehn-Yahr scale scores before and
after eradication were also 1,9 6 0,8 and 1,75 6 0,7 sequentially and
significantly beter after eradication (p<0.001).
Conclusions: 14C-urea breath test is a new and effective, non-
invasive test for detecting HP positivity. This non-invasive simple
test can let us to eradicate of HP that will help clinical outcome by
arranging the absorpsion of levodopa in PD patients with HP
infection.
1106
Treatment of secondary freezing of gait with rivastigmine
P. Paiva, E.H. Molho, A. Ramirez-Zamora (Albany, NY, USA)
Objective: To report the marked improvement in freezing of gait
(FoG) with rivastigmine in a patient with secondary freezing of gait
due to osmotic demyelination.
Background: FoG is a disabling motor block that is associated
with Parkinsons disease and atypical Parkinsonism. The pedunculo-
pontine nucleus (PPN) and laterodorsal tegmental nucleus (LTN)
contain predominantly cholinergic neurons and has connections to
the thalamus, basal ganglia, and cerebellar nuclei. It is thought that
the PPN plays a role in FoG in Parkinsons disease and atypical Par-
kinsonism. Rivastigmine is an acetylcholinesterase inhibitor that can
ameliorate in cognitive decline from Parkinsons disease and has
also been noted to improve gait dysfunction.
Methods: A case report from a tertiary medical center.
Results: A 51-year-old right-handed woman with bipolar disorder
and history of alcohol abuse suffered a fall and was found to have
hyponatremia complicated by central pontine myelinolysis. She had
resultant pseudobulbar affect, dysarthria, ataxia, and FoG. She was
in a rehabilitation facility for a year before she presented to our
clinic. At that time, she did not have cerebellar ataxia. She was
noted to have gait abnormalities including FoG upon initiation of
ambulation and with turning as well as mild asymmetric Parkinson-
ism, spastic dysarthria, and intermittent leg spasms. Brain MRI done
a year after injury showed a hyperintensity in the central pons on T2
sequence consistent with central pontine myelinolysis. The area
likely also affected the LTN. A variety of treatments failed to pro-
vide improvement in FoG inlcuding pramipexole,
dextroamphetamine-amphetamine XR, and high dose carbidopa-
levodopa. She was then started on transdermal rivastigmine with
slow titration up to 9.5mg. She was noted to have decreased fre-
quency of FoG at her 2 month follow up. The dose was titrated up
to 13.3 mg. She was noted to have a profound improvement in FoG
after a 3 month follow up.
Conclusions: This case report suggests a role for rivastigmine in
treatment of gait disorders and secondary FoG, presumably through
increased cholinergic transmission. Further studies are warranted to
evaluate use of rivastigmine in other disorders presenting with FoG.
1107
The Parkinsons progression marker initiative (PPMI)
Developing a sample size estimate for Parkinsons disease
therapeutic trials
Parkinsons Progression Marker Initiative (New Haven, CT, USA)
 POSTER SESSION
Objective: The goal of the Parkinsons Progression Marker Initia-
tive (PPMI) is to identify clinical, imaging and biospecimen bio-
markers of PD progression to provide tools for studies of disease
modifying therapeutics.
Background: Clinical MDS-UPDRS, imaging and biospecimen
biomarker longitudinal data are essential to inform planning of sam-
ple size and study duration for PD therapeutic trials. The PPMI has
enrolled 423 untreated PD patients with baseline clinical, DAT imag-
ing and biospecimen data already reported.
Methods: PPMI PD subjects have been evaluated longitudinally
with MDS-UPDRS at baseline and at 3 month intervals, CSF at
baseline, 6 months and 12 months and DAT imaging at baseline and
12 months. All PPMI subjects have reached their 12-month assess-
ment. All study data is integrated into the PPMI study database.
Access to PPMI data and biospecimen is available at www.ppmi-
info.org.
Results: The 12 month PPMI longitudinal clinical, imaging and
CSF were used to establish sample size estimates for potential thera-
peutic PD trials. At baseline MDS-UPDRS mean (SD) in the PPMI-
PD cohort was 32.36 (13.1) with a mean change of 5.31 (12.0) for
PD subjects at 12 months. The baseline mean putamen binding ratio
for PD subjects was 0.83 (0.30) with mean change of 0.13 (0.16) at
12 months. The baseline mean CSF alpha synuclein pg/ml for PD
subjects was 1844.68 (786.13) with mean change of 13.15 (612.1) at
12 months. Estimates of the total sample size required to detect a
reduction in MDS-UPDRS of 50% was 654 and 866 for 80% and
90% power and to detect a change in mean putamen DAT binding
by 50% was 216 and 288 for 80% and 90% power. While the small
interval change in alpha synuclein during a 12-month follow-up sug-
gests that it will not be a useful biomarker of longitudinal change, it
can be estimated that 50 subjects would be required to detect a
change in synuclein from baseline of 40% and 46% with 80% and
90% power.
Conclusions: Longitudinal PPMI data acquired during 12 months
follow-up can provide estimates of sample size required to detect
change in these PPMI outcomes in potential PD therapeutic trials.
Additional longitudinal data is required to refine these sample size
estimates. In addition combining PPMI biomarker outcomes to define
subsets of PD subjects may further reduce sample size requirements
for future studies.
1108
Continuous delivery of ropinirole by subdermal ProNeuraTM
implants
S. Sreedharan, K. Bankiewicz, R. Patel (South San Francisco, CA,
USA)
Objective: A subcutaneous implantable product that can continu-
ously release dopamine replacement therapy (DRT) for 6-12 months
from a single application.
Background: The cornerstone of symptomatic treatment for Par-
kinsons disease (PD) is DRT. Frequent dosing with oral DRT medi-
cation, however, is associated with the pulsatile stimulation of
dopamine receptors (DR) due to peak-trough fluctuations in drug
plasma concentrations. This non-physiologic stimulation of brain DR
contributes to development of serious motor complications and dys-
kinesias, thus limiting treatment effectiveness. New treatments that
provide continuous DRT appear to be more effective, but current
approaches are surgically invasive and associated with potentially
serious adverse effects. ProNeuraTM is a proprietary subdermal
implantable drug delivery system that provides continuous, non-
fluctuating therapeutic drug levels for several months from a single
application. Efficacious and well-tolerated continuous delivery of
buprenorphine using this platform has been demonstrated in a Phase
3 clinical program (ProbuphineV R ) on opioid addiction.
Methods: ProNeura-based implants containing the dopamine ago-
nist, ropinirole, were tested for pharmacokinetics (PK) of release in
rats and in non-human primates, and motor functions and onset of
S429
dyskinesias in MPTP-induced Parkinsonian monkeys were evaluated
in a dose-escalating study with ropinirole implants.
Results: Continuous non-fluctuating release of ropinirole was
observed for a period of several months following implantation and
PK studies in rats have been extended to determine the full duration
of release. The dose-escalating study with implants in Parkinsonian
monkeys demonstrated that motor functions could be significantly
improved following treatment, and no onset of dyskinesias was seen.
There were also no signs of skin irritation, inflammation or fibrotic
capsule formation detected at the implant site in monkeys at study
termination.
Conclusions: The feasibility of continuous long-term non-fluctu-
ating delivery of ropinirole using the ProNeura implant platform has
been demonstrated. The novel matchstick-sized subdermal ropinirole
implants could significantly improve PD pharmacotherapy and
patient compliance, lower caregiver expense, and enhance the
quality-of-life in patients by providing CDS without the side effects
and inconvenience associated with chronic dosing with oral DRT or
from infusion by external mechanical pumps.
1109
Effects of amantadine on postural instability in Parkinsons
disease
B. Topcular, A. Altinkaya, A. Kaymaz, A. Yabalak, B. Altunrende, Z.
Matur, O. Gungor Tuncer, E. Altindag, D. Orken, G. Akman-Demir
(Istanbul, Turkey)
Objective: To evaluate the effects of amantadine therapy on pos-
tural instability in Parkinsons disease.
Background: Amantadine is a NMDA antagonist that has anti-
Parkinsons properties. Although it is widely used for treatment of l-
dopa related dyskinesias some case reports also mention its effect on
postural instability in Parkinsons disease.
Methods: Parkinsons disease patients treated with amantadine
for postural instability in 2013 in our Movement Disorders Clinic
were evaluated retrospectively. Patients were evaluated with UPDRS
motor score. Only patients under steady dopaminergic treatment
were included in the analysis. Amantadine was started as 2x50 per
day and increased up to 500 per day when needed.
Results: There were 21 patients. Male to female ratio was 16/5.
Mean age of the group was 72.5. Mean disease duration was 6.4
years. Mean Amantadine dose was 390.48/day. Mean UPDRS motor
score were 34.2. All except two patients reported benefit from aman-
tadine. The mean fall score of the UPDRS motor scale was 2.48
before amantadine and 2.00 under amantadine treatment.
Conclusions: Our study results show that amandatine might have
a modest effect on postural instability in Parkinsons disease.
1110
Anticholinergics are still effective in early stage of male PD
patients
Y. Tsuboi, S. Fujioka, T. Mishima, R. Onozawa, J. Fukae, Y.
Yamaguchi (Fukuoka, Japan)
Objective: To assess efficacy of trihexyphenidyl for PD patients,
we conducted clinical study with adding and withdrawing design.
Background: Anticholinergic agents were recommended no lon-
ger using as treatment with Parkinsons disease (PD) because of the
adverse effect, especially for fear of cognitive decline. However,
withdrawing trihexyphenidyl in patients with PD often shows unfav-
orable results.
Methods: Observational study with adding and withdrawing
design was conducted in trihexyphenidyl used patients with PD in
Fukuoka University Hospital. The primary outcome measure was the
changes of clinical symptoms after adding or withdrawing trihexy-
phenidyl. We divided subjects into two groups; responders and non-
responders. Responders are defined as cases showed significant
Movement Disorders, Vol. 30, Suppl. 1, 2015
S430 POSTER SESSION
symptomatic deterioration after withdrawing trihexyphenidyl or
improvement after adding trihexyphenidyl. Non-responders are
defined as cases showed no changes after withdrawing trihexyphe-
nidyl or no effect after adding trihexyphenidyl. Cases, which needed
to be withdrawn due to adverse effect, were also included in non-
responders. We compared the characteristic of clinical manifestations
between two groups. This study was approved by IRB in Fukuoka
University Hospital.
Results: Responders included 27 cases (male: 17, female: 10),
while non-responders included 30 cases (male: 10, female: 20). Res-
ponders was male dominant (p50.035). Disease duration and age at
evaluation was not different between responders and non-respon-
ders(disease duration; 7.11 6 6.02 years vs. 8.67 6 6.69 years,
p50.362, n.s.)(age; 67.5 6 9.59 vs. 69.2 6 7.26 years, p50.456, n.s.),
however, there is significant difference in H&Y staging between the
two groups, revealing responders keeping earlier staging of PD
severity (2.56 6 1.00 vs. 3.26 6 0.92, p50.015).
Conclusions: Adding and withdrawing study of trihexyphenidyl
revealed significantly symptomatic effect beyond levodopa in
patients with early stage of male PD. No significant adverse effect
was observed in responders. Exploratory outcomes suggested that tri-
hexyphenidyl might improve motor symptoms in such patients.
1111
Drug candidates promoting O-linked glycosylation of tau for the
treatment of tauopathies
C. Wiessner, A. Quattropani, M. Neny, S. Ousson, J. Hantson, A.
Sand, B. Permanne, D. Beher (Lausanne, Switzerland)
Objective: The aim is to develop novel brain-penetrable inhibi-
tors of the enzyme O-linked beta-N-acetylglucosaminidase (OGA)
that reduce the formation of toxic tau aggregates.
Background: The presence of neurofibrillary tangles (NFTs) is a
characteristic hallmark of tauopathies which include amongst others
progressive supranuclear palsy (PSP) and Alzheimers disease (AD).
NFTs are composed of aggregates of the microtubule associated tau
protein and NFT pathology can be modified by inhibition the glyco-
side hydrolase, O-linked beta-N-acetylglucosaminidase (OGA).
Mechanistically, OGA inhibition blocks the removal of O linked N-
acetylglucosamine (O-GlcNAc) moieties from serine and threonine
residues. This leads to an accumulation of O-GlcNAcylated tau pro-
tein that is less prone to aggregation. Following this rationale we
sought to develop novel OGA inhibitors with the final aim to test the
tau hypothesis in the clinic using PSP as initial indication.
Methods: A focused medicinal chemistry lead optimization cam-
paign was performed starting from a series of novel OGA inhibitors.
Candidate molecules with improved potency, drug-like pharmacoki-
netic and pharmacodynamic profiles were identified using a stringent
assay cascade. Sensitive methods to measure enzyme inhibition and
tau O-GlcNAcylation in the brain and peripheral tissue have been
developed.
Results: The OGA inhibitor ASN-561 has been identified as a
preclinical development candidate. ASN-561 has good potencies for
inhibition of the recombinant and cellular O-GlcNAcase enzymes
combined with excellent brain penetration. ASN-561 demonstrated
pharmacodynamic efficacy in wild-type mice upon single, oral dose
utilizing O-GlcNAcylation of protein as readout for CNS target
engagement. In JNPL3 tau transgenic mice ASN-561 increased O-tau
levels up to 12-fold compared to vehicle at the highest dose.
Increased overall O-GlcNAcylation in blood-borne cells by ASN-561
correlated well with brain O-GlcNAcylation and is currently devel-
oped as a target engagement biomarker for Phase 1 studies.
The preclinical package supporting the investigation of the mole-
cule in human clinical trials is currently being collected.
Conclusions: ASN-561 is an advanced preclinical OGA inhibitor
with the potential to enter human Phase I safety and tolerability stud-
ies in 2015.
Movement Disorders, Vol. 30, Suppl. 1, 2015
1112
Moving health care to the patients home: An innovative
approach to introduce levodopa-carbidopa intestinal gel (LCIG)
treatment
T. Willows, K. Groth, J. Bjorkehag, M. Andersson, J. Larsson, J.
Permert (Stockholm, Sweden)
Objective: To explore the possibilities and challenges with letting
patients with Parkinsons disease (PD) obtain advanced treatment
with LCIG without being hospitalized.
Background: PD is often complicated by motor fluctuations.
This is often due to variations in gastrointestinal absorption. To
diminish these fluctuations, various methods can be used for instant
the introduction of LCIG. The most common way to do this is by
introducing a naso-jejunal (NJ) tube and having the patient hospital-
ized in order to evaluate the motor fluctuations and to titrate the dos-
age of LCIG infusion. If the titration is satisfactory the patient will
receive percutaneous endoscopic gastrostomi (PEG) in order to
obtain a permanent system.
Methods: Using video-communication system (VCS) to perform
the titration of LCIG in the patients home.
The VCS used included three systems, one for the neurologist,
one for the nurse and one for the patient.
Two criterions were used for the VCS: the quality should be
good enough for the neurologist to judge the patients movements
and easy to use.
A high resolution VCS was selected with touch screens.
One week prior to receiving the NJ-tube the VCS was set up at
the patients home and the patient was educated in handling the
pump for the LCIG.
Three consecutive patients that met the criteria for advanced
treatment with LCIG in accordance with the Swedish summary of
product characteristic were recruited.
The patient received the NJ-tube at day 1, returned home and met
the nurse who helped the patient connecting the pump to the NJ-
tube. The patient, nurse and doctor thereafter met through the VCS
on irregular basis depending of the need and when convenient for
the patient or doctor.
Follow-up structured interviews were conducted with each
patient.
Results: Time to decision, of a permanent LCIG system, variated
between 2 and 4 days.
Numbers of VCS contacts; 2-4 in a day, duration between 7-13
minutes.
The VCS provided an accurate perception of the patients
movements.
All three home titrations were considered successful by all
participants.
Conclusions: Faster titration, compared with when hospitalized,
2-4 days instead of 5-14 days.
Potential gains, less stress for the patient, lower health care costs
and possibly higher clinical results.
The patients felt secure and appreciated not to be hospitalized.
1113
Clinical efficacy of istradefylline on psychiatric symptoms in
Parkinsons disease
T. Yamamoto, T. Furuya, K. Ikeda, A. Miyake, T. Mitsufuji, T.
Kimura, A. Tanaka, K. Takahashi, N. Tamura, N. Araki (Iruma-gun,
Japan)
Objective: To evaluate the effects of istradefylline on motor
impairment and psychiatric symptoms after 3 months of therapy in
Parkinsons disease (PD) patients with motor complications.
Background: Istradefylline; a non-dopaminergic selective adeno-
sine A2A receptor antagonist, has been reported to improve motor
function in PD patients. However, the efficacy of istradefylline on
psychiatric symptoms has not been clarified yet.
 POSTER SESSION
Methods: Open administration of istradefylline for 3 months (first
two months; 20 mg/day, further one months; 40mg/day) was con-
ducted in 9 patients with PD(Age; 67.4 6 7.4 YO; mean6SD, dura-
tion; 6.9 6 3.6 Y). Changes of motor function were evaluated
monthly by the Unified PD Rating Scale (UPDRS) part III before
and after treatment. Psychiatric symptoms were assessed by the Zung
Self-Rating Scale (SDS), apathy evaluation score (AS) and the 16-
item fatigue scale for PD (PFS-16). Subjects were divided into two
groups with or without abnormal score assessed by each evaluation
scale. Two cases could not complete this study due to the side
effects of istradefylline.
Results: I. Motor function: Score in UPDRS III baseline and 1
month, 2 months, 3 months after treatment was 38, 34, 31 and 27,
respectively. Motor performance was judged as improved. II. Psychi-
atric symptoms: 1. [circ1] apathy group (Three cases): Score on AS
was 24 at baseline, 19, 12,10 at 1 to 3 months after treatment and
the score was normalized within 2 months after treatment (Cutoff
value 16). [circ2] Non-apathy group (Four cases): The score was
6,5,5,5 at each period. 2. [circ1] Depression group (Two cases):
Score on SDS was 52, 45, 41, 39 at baseline and 1 to 3 months after
treatment (Cutoff value 50). The depression was relieved after first 1
month. [circ2] Non-depression group (Five cases): The score was 39,
37, 32 and 32 at each period. 3. [circ1] Fatigue group (Four cases):
The Score on PFS-16 was 4.2, 3.9, 3.7, 3.4 at each period and these
scores lowered as passage of time (Cutoff value 3.3). However,
fatigue was continuously observed during this study. [circ2] Non-
fatigue group (Three cases): The score was 1.9, 2.2, 2.0, 1.9 at each
observation.
Conclusions: 1. Istradefylline was effective to improve apathy
and depression, but not effective for fatigue in patients with PD. 2.
Improvements of apathy and depression with istradefylline may be
induced by activation of Nucleus accumbens, where adenosine A2A
receptor are enriched.
POSTER SESSION 7
Thursday, June 18, 2015
12:0013:30
Grand Hall
Epidemiology
1114
Pattern of Movement Disorders in a general neurology practice
in Southwestern Nigeria: A 6 month review
A.M. Adebiyi, M.A. Komolafe, M.B. Fawale, A.A. Adebowale (Ile-Ife,
Nigeria)
Objective: To determine (1) the spectrum of Movement Disor-
ders in a Nigerian general neurology practice and (2) the variations
of Movement Disorders with age and gender in a Nigerian general
neurology practice.
Background: Movement Disorders have been reported among
Africans for several decades, but there is insufficient data regarding
the spectrum of these Movement Disorders. The frequency of Move-
ment Disorders is known to be lower in Africans than other popula-
tions with the exception of the North African nations where
prevalence figures approximate those of European countries. The
most commonly diagnosed Movement Disorder in Africa is Parkin-
sons disease.
Methods: The clinic register of the general neurology unit at a
tertiary hospital facility in South-western Nigeria was searched for
information pertaining to newly diagnosed Movement Disorder cases
over a six-month period from July-December 2014. Data such as
S431
age, gender and diagnoses of patients were obtained and analyzed
using descriptive statistics.
Results: A total of 33 cases were identified of which 26 (78.8%)
were male and 7 (21.2%) were female. The male to female ratio was
3.7:1. The ages of the patients ranged from 25-92 years, with a mean
of 64.21 6 12.23 years. The majority-27(81.8%) of the 33 patients-
of the patients had diagnoses of Parkinsons disease. Of the remain-
ing cases, there were 2 (6.1%) cases of dystonia and 4 (12.1%) cases
of essential tremors. All the patients with Parkinsons disease were
above 50 years of age at diagnosis, of whom 21 (77.8%) were male
and 6 (22.2%) were female. The mean age at diagnosis in patients
with PD was 66.04 6 8.51 years, higher in male (67.09 6 9.15 years)
than female (62.00 64.05 years) patients (P-value 0.059, t-test statis-
tic 2.003).
Conclusions: The most common Movement Disorder in our prac-
tice is Parkinsons disease. Majority of the patients with PD are male
and are above 50 years of age. Males are slightly older than females
at PD diagnosis. Non-PD cases are infrequent in our practice. Com-
munity based studies are however needed to unearth the true magni-
tude, spectrum and other epidemiological aspects of Movement
Disorders in our practice environment.
1115
Frequency and pattern of Parkinsons disease in Obafemi
Awolowo University Teaching Hospitals, Ile-Ife, Nigeria
O.I. Agunbiade, M.A. Komolafe, O.E. Popoola (Ile-Ife, Nigeria)
Objective: To describe the Frequency and Pattern of Parkinsons
disease among Neurology outpatients in the Obafemi Awolowo Uni-
versity Teaching Hospital, Ile- Ife, Western Nigeria.
Background: PD is the most common Movement Disorder char-
acterized by paucity of voluntary and autonomic activities or exces-
sive movements unrelated to muscle weakness. In a previous study,
Lang opined a lifetime risk of developing PD as 2% for men and
1.3% for women. Though may not be life-threatening initially, PD
can seriously impair daily functions while the involuntary nature of
the disorder may be embarrassing, causing emotional distress or
depression in most individuals.
Methods: This is a retrospective study of the case records of
patients that presented at the Neurology clinic with PD between
October 2010 and October 2013. A register of all neurology outpa-
tients was used to retrieve all PD cases seen. Details such as the age,
sex, social class, diagnosis, investigation done, and treatment
received were recorded. Diagnosis was clinical.
Results: Total neurology clinic consultation during the study
period was 728, of which 93 (12.8%) were Movement Disorders.
Forty-three patients presented with PD (46.2% of the Movement Dis-
order cases) comprising thirty-four males and nine females with a
mean age of 65. Most of the patients (86.1%) had idiopathic PD
while most (62.8%) of the patients presented the Hoehn and Yahr
Stage II of the disease. Majority (79.1%) presented after 6 months of
onset of first symptom. Analysis of the type of PD showed that 32%
had cognition impairments on first initial presentation. Most (94%)
of the patients were on Levodopa-Carbidopa and anticholinergic
medications while deep brain stimulation (DBS) had never been
tried. Poor clinic compliance and default were challenges as a signif-
icant 41% were found either to have missed a clinic appointment (of
three) or defaulted.
Conclusions: PD is the most common Movement Disorder cases
seen in our neurological practice and idiopathic PD was the com-
monest type seen. Late presentation and early defaults are common.
There was a male preponderance while DBS not yet available
explains that there remains a great room for improvement. There
should be general education at community level on early presentation
while General practitioners should also be educated to refer cases of
PD to the Neurologist promptly.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S432 POSTER SESSION
1116
Trends and pattern of Parkinsons disease in Obafemi Awolowo
University Teaching Hospitals, Ile-Ife, Nigeria between 1984-2004
and 2010-2013
O.I. Agunbiade, M.A. Komolafe, T.T. Lekan-Agunbiade (Ile-Ife,
Nigeria)
Objective: To compare the trends in the Pattern of PD among
Neurology outpatients in the Obafemi Awolowo University Teaching
Hospital, Ile- Ife, Western Nigeria between 1984-2004 and 2010-
2013.
Background: PD is the most common Movement Disorder char-
acterized by paucity of voluntary and autonomic activities or exces-
sive movements unrelated to muscle weakness. In a previous study,
Akinyemi reported an age-adjusted prevalence of 67 per 100,000 in
Southwest Nigeria. Though may not be life-threatening initially, PD
can seriously impair daily functions while the involuntary nature of
the disorder may be embarrassing, causing emotional distress or
depression in most individuals.
Methods: This is a retrospective study of the case records of
patients that presented at the Neurology clinic with PD between
1984-2004 and 2010-2013. A register of all neurology outpatients
was used to retrieve all cases of PD seen. Details such as the age,
sex, social class, diagnosis, investigation done, and treatment
received were recorded. The diagnosis of PD was clinical.
Results: Thirty two patients presented with PD between 1984 and
2004 while forty three patients (46.2% of the Movement Disorder
cases) were seen between 2010 and 2013. Over both periods, more
males presented with a male-female ratio of 20:12 between 1984 and
2004, and 34:9 between 2010 and 2013. Mean ages were 63.7 and
65 respectively. 68.4% of cases between 1984 and 2004 were late
onset while it was 79.1% between 2010 and 2013. Analysis of the
type of PD showed that 34.4% of cases seen between 1984 and 2004
had cognition impairments on first initial presentation whereas 32%
of cases seen between 2010 and 2013 presented with cognitive
impairment on first contact. Over both periods, L-Carbidopa and
anticholinergic were treatment options while deep brain stimulation
is yet to be available.
Conclusions: Over both periods of study, PD was the commonest
Movement Disorders and idiopathic PD was the most common form
seen. PD was also found to be commoner among males and most of
the cases we see were late onset. There was a male preponderance
over both periods while DBS not yet available explains that there
remains a great room for improvement to help the patients. However,
availability of a Neurology specialist has brought about a significant
increase in the number of cases seen as more patients presented in
our neurology clinics.
1117
Comparing symptoms and patterns of Parkinsons disease
between leading teaching hospitals from Eastern and Western
Nigeria
O.I. Agunbiade, T.T. Lekan-Agunbiade, P. Henry John, A.O. Ade-
bambo (Ile-Ife, Nigeria)
Objective: To compare the trends in the Pattern of PD among
Neurology outpatients in the University of Uyo Teaching Hospital,
Uyo, Eastern Nigeria and Obafemi Awolowo University Teaching
Hospital, Ile- Ife in Western Nigeria.
Background: PD is the most common Movement Disorder char-
acterized by paucity of voluntary and autonomic activities or exces-
sive movements unrelated to muscle weakness. National Parkinsons
Foundation reported that majority of PD cases are over age 65 with
men, women and all socioeconomic as well as geographical groups
in the United States being affected.
Methods: This is a comparative study of the PD cases seen in Uni-
versity of Uyo Teaching Hospital, Uyo, Eastern Nigeria between Octo-
ber 2013 and October 2014 and the cases seen in Obafemi Awolowo
Movement Disorders, Vol. 30, Suppl. 1, 2015
University Teaching Hospital, Ile- Ife in Western Nigeria between
October 2010 and October 2013. The registers of all neurology outpa-
tients were used to retrieve all cases of PD seen in both regions. Details
such as the age, sex, social class, diagnosis, investigation done, and
treatment received were recorded. The diagnosis of PD was clinical.
Results: Twelve patients presented with PD in University of Uyo
Teaching Hospital between October 2013 and October 2014 while
forty three patients were seen in Obafemi Awolowo University
Teaching Hospital, Ile-Ife between 2010 and 2013. In both regions,
more males presented with a male-female ratio of 8:4 in Uyo and
34:9 in Ile-Ife. Mean ages were 68 and 65 respectively. 67% of cases
seen in Uyo were late onset while same applied to 79.1% of cases
seen in Ile-Ife. While 58.3% and 62.8% of cases presented the
Hoehn and Yahr Stage II of the disease respectively, 25% of patients
seen in Uyo had cognitive impairments on first presentation whereas
32% of cases seen in Ile-Ife presented with cognitive impairment on
first contact. Just as Levodopa-Carbidopa and anticholinergic medica-
tions were treatments of choice in both regions, early default was
equally established.
Conclusions: In both regions of study, PD was the commonest of
Movement Disorders cases seen, with mean ages 68 and 65 in Uyo
and Ile-Ife respectively while late presentation is a common chal-
lenge. PD was also found to be commoner among males and default
remains a major threat to the outcome of care. Unavailability of
DBS in both regions explains that there is a great need for improve-
ment in PD care in Nigeria.
1118
Factors determining wearing-off in Thai Parkinsons disease
patients: The report of the Thai PD registry database involving
6,623 patients
R. Bhidayasiri, O. Jitkritsadakul, N. Wannachai, K. Boonpang, J.
Sringean, L. Kaewwilai, P. Jagota, P. Panyakaew, S.
Singmaneesakulchai, S. Petchrutchatachart (Bangkok, Thailand)
Objective: The objective of our study was to evaluate the factors
contributing to wearing-off in Thai PD patients who were registered
in Thai PD registry database.
Background: Wearing-off (WO) represents a common manage-
ment challenge for physicians who take care of PD patients.
Although the frequencies of WO from published studies ranged from
40 to 85% after 9 years of levodopa therapy, the variability was
likely to reflect the differences in study designs, populations, and
instruments used to detect WO.
Methods: The data on PD patients who received the clinician
assessment from physicians for WO was retrieved from the Thai PD
registry database (www.chulapd.org) as described in the previous lit-
erature. The following factors were considered as independent varia-
bles to predict WO, including the specialty of physicians
(neurologists vs. non-neurologists), young-onset, sex, long disease
duration (>15 years), cardinal symptoms of PD at onset, patterns of
medications usage, and current predominant phenotype. The logistic
regression using forward stepwise was applied to all variables.
Results: 6,623 PD patients from the registry database were
included in the analysis. 42 patients (0.6%) were excluded from the
analysis. Clinical demographics were described in [table1]
Clinical characteristics of Parkinsons disease patients who
received clinician assessment of wearing-off
Clincal demographics Number (%) Mean (SD)
Gender
Male 3324 (50.2)
Female 3299 (49.8)
Age (year) 71.2 (11.9)
(Continued)
 POSTER SESSION S433

Table (Continued)
Clinical characteristics of Parkinsons disease patients who
received clinician assessment of wearing-off
Clincal demographics Number (%) Mean (SD)

Onset of PD
Young-onset 404 (6.1)
Typical-onset 3310 (50.0)
Late-onset 2383 (36.0)
PD duration (years) 10.8 (5.3)
Motor symptoms at onset
Tremor 4541 (68.6)
Postural instability 3809 (57.5)
Rigidity 3201 (48.3)
Bradykinesia 4757 (41.8)
Antiparkinsonian usage
Levodopa 4828 (72.9)
Dopamine agonists 1550 (23.4)
COMT inhibitor 1023 (15.4)
MAO-B inhibitor 398 (6.0)
Anticholinergics 1709 (25.8)

Among 6,623 patients, 2,042 patients (31%) received clinician

assessment of having WO. Neurologists were significantly more likely
to diagnose WO compared to non-neurologists (52.8 vs. 47.2%,
p<0.01). The following predictors significantly contributed to WO,
including rigidity, young-onset, postural instability, long disease dura-
tion, and levodopa usage (OR: 5.21, 1.78, 1.76, 1.63, and 1.37 respec-
tively, p<0.01). Tremor predominant phenotype was significantly less
likely to contribute to WO (OR: 0.84, p<0.05). Patients with WO were
significantly more likely to use COMT inhibitor (OR: 1.61, p<0.01).
Logistic regression analysis showing each independent variables
contributing to wearing off
Independent variables Odd ratio (95% CI) p-value
Rigidity 5.21 (4.51-6.03) <0.001
Young-onset 1.78 (1.41-2.25) <0.001
Postural instability 1.76 (1.52-2.04) <0.001
Long disease duration (>15 years) 1.63 (1.39-1.91) <0.001
Levodopa usage 1.37 (1.11-1.7) <0.01
Tremor predominant 0.84 (0.71-0.98) <0.05
Conclusions: Consistent with previously published literature,
rigidity, postural instability, young-onset, long disease duration and
levodopa usage were risk factors of WO. In Thailand, neurologists
were more likely to detect WO based on their clinician assessment
than non-neurologists. Patients with WO were more likely to receive
COMT inhibitor as the treatment as indicated in the Thai PD guide-
line. This information will be useful to expand the awareness of WO
among non-neurologists, particularly in high-risk patients.
1119
Risk factors for pneumonia development in Parkinsons disease
A nationwide population-based study
Y.P. Chang, J.H. Tsai (Kaohsiung, Taiwan)
Objective: To evaluate the risk factors for pneumonia develop-
ment among patients with Parkinsons disease (PD).
Background: Pneumonia is the most common infectious disease
and is one of the ten leading causes of death in the world. Further-
more, there has been no nationwide population-based study exploring
the risk factors for pneumonia in the PD population.
Fig. 1. (1119).
Methods: Participants diagnosed with new onset PD between
2000 and 2009 were enrolled from the 20002010 National Health
Insurance Research Database in Taiwan. The comparison cohort was
comprised of PD patients with an incidence of pneumonia and those
without pneumonia. Cox proportional hazard models were used to
estimate the risk of pneumonia among patients with PD. [figure1]
Results: Of the 2,001 enrolled patients with PD, 381 (19.0%) had
an incidence of pneumonia during the study period. Multivariate Cox
proportional hazards analysis identified older age group (80 years-
old, hazard ratio [HR] 3.15 [95% confidence interval 2.324.28]),
male gender (HR 1.59 [1.291.96]), geographic region of Taiwan
(northern, HR 1.36 [1.041.78], southern and eastern, HR 1.40
[1.051.88]), rural areas (HR 1.34 [1.051.72]), chronic heart failure
(HR 1.53 [1.022.29]), and chronic kidney disease (HR 1.39 [1.03
1.90]) as risk factors for pneumonia in PD patients. Of interest, we
found that PD patients who had received treatment for dental caries
suffered less from pneumonia (HR 0.80 [0.640.99]).
Conclusions: The risk factors for pneumonia among PD patients
in Taiwan included older age, male, geographic region of Taiwan,
living in rural areas and comorbidity with chronic heart failure and/
or chronic kidney disease, but treating dental caries may diminish
the risk. Clinicians need to recognize the risk factors as early as pos-
sible and try to correct these comorbidities in PD patients before
they progress to potentially fatal pneumonia.
1120
Military service and Agent Orange exposure in PSP: A case-
control study
T. de la Riestra, P. Lees, C. Cunningham, E.A. Carl, S.D. Edland, I.
Litvan (La Jolla, CA, USA)

Movement Disorders, Vol. 30, Suppl. 1, 2015

S434 POSTER SESSION

Objective: We evaluated whether there was an association 1121

between PSP and exposure to Agent Orange (TCDD [2,3,7,8
tetracholorodibenzodioxin]).
Background: Progressive Supranuclear Palsy (PSP), the most fre-
quent atypical Parkinsonian disorder, is a primary tauopathy which
pathogenesis remains unclear. Since Agent Orange (TCDD [2,3,7,8
tetracholorodibenzodioxin]) was reported to increase tau
phosphorylation.
Methods: A total of 300 incident PSP cases meeting the
NINDS-SPSP clinical criteria and 300 age- and gender-matched
healthy controls were recruited throughout North America as part
of a case-control study to determine environmental risk factors for
PSP. We evaluated demographics, education, years of service, loca-
tion, service during the Vietnam era (1961-1975), in Vietnam or
South East Asia and reported exposure to Agent Orange and smok-
ing. In addition, a pharmacologist and an industrial hygienist blind
to the case status assigned exposure as none, possible, probable and
definite, according to the years of service, service during the Viet-
nam era, location, and reported exposure to agent orange. Condi-
tional logistic regression controlling for matching variables (age,
gender, and military service) and exposure to Agent Orange,
obtaining a college diploma, ever living within one mile of a farm,
smoking pack-years, serving in the military, and serving during the
Vietnam era was performed to assess the association between serv-
ice exposure history and PSP.
Results: 73 cases and 73 matched controls reported military
service, 12 cases and 7 controls during the Vietnam era. 14 of the
cases and 12 of the controls were judged to have potential exposure
to Agent Orange. After controlling for covariates, neither military
service during the Vietnam era or potential exposure to agent
orange was associated with case status (odds ratio for military serv-
ice during the Vietnam era 3.3044 (95% CI 0.6788-16.0869) p-
0.13883; odds ratio for exposure 0.4991 (95% CI 0.1267 - 1.9667)
p-value: 0.32062.
Conclusions: In this case-control study, we couldnt find a rele-
vant relationship between military and Agent Orange exposure and
PSP. Small sample size may have limited our ability to detect a rela-
tionship. Further studies will be necessary to for definite conclusion.
Clinical and epidemiological factors associated with mortality in
Parkinsons disease in a Brazilian cohort
G.C. Fernandes, M. Socal, C.R.M. Rieder, A.F.S. Schuh, M.D.B.
Londero (Porto Alegre, Brazil)
Objective: We aimed to identify clinical and epidemiological fac-
tors influencing mortality hazards in a Brazilian cohort of PD
patients.
Background: Prognosis of Parkinsons disease (PD) is variable.
Most studies show a higher mortality rate in patients with PD com-
pared to the general population. However, clinical and epidemiologic
factors predicting mortality are still poorly understood and heteroge-
neous in the current literature.
Methods: Clinical and epidemiologic features including patient
history and physical, functional and cognitive scores were collected
from a hospital-based cohort of PD patients using a standardized pro-
tocol and clinical scales on the first evaluation. Data on comorbid-
ities and mortality were collected on follow-up. Descriptive statistics
and Cox proportional hazards models were employed to identify fac-
tors associated with decreased survival.
Results: During a mean follow-up of 4.71 years (range 1-10), 43
(20.9%) of the 206 patients reassessed died. Those who died had
higher mean age at disease onset than those still alive at the last
follow-up (67.7 years vs 56.3 years; p < 0.01). In the univariate anal-
ysis, age at baseline was associated with decreased survival. In the
adjusted Cox proportional hazards model, age at disease onset and
race/ethnicity were predictors of mortality.
Conclusions: Late age at disease onset and advanced chronologi-
cal age are associated with decreased survival. Clinical comorbidities
and PD characteristics were not associated with decreased survival in
our sample, probably because of the small sample size as well as
their association with advanced age. Race/ethnicity, an inconsistent
predictor of mortality in the literature, was found in our study to be
associated with increased hazard of mortality. Taken together, our
findings indicate the importance of studying survival among different
populations of PD patients.

Clinical characteristics of Parkinsons disease patients at first evaluation

Patients alive
at last Patients
Characteristic All patients follow-up who died
N 206 163 43
Age at onset, mean(sd) years 57.9 (11.5) 56.3 (0.89) 63.7 (1.54)**
Age at onset, n(%)
<60 years 113 (55%) 99 (61%) 14 (33%)**
60 years 93 (45%) 64 (39%) 29 (67%)**
Disease duration, mean(sd) years 8.32 (4.99) 8.36 (4.97) 8.16 (5.16)
Range 1-29 1-29 1-25
Gender, n(%)
Female 105 (51%) 88 (54%) 17 (40%)
Male 101 (49%) 75 (46%) 26 (60%)
Race, n(%)
White 182 (89%) 148 (91%) 34 (79%)**
Non-white 23 (11%) 14 (9%) 9 (21%)**
Clinical Subtype, n(%)
PIGD 108 (55%) 85 (56%) 23 (56%)
Mixed 22 (11%) 18 (12%) 4 (9%)
Tremor 65 (33%) 49 (32%) 16 (37%)
Cognitive impairment, n(%) 51 (29%) 35 (25%) 16 (47%)*
Depression 64 (31%) 51 (31%) 13 (30%)
Hoehn-Yahr, mean(sd) 2.7 (0.81) 2.7 (0.82) 2.7 (0.78)
Schwab & Englands ADL, mean(sd) 73 (22.8) 73.5 (22.3) 71.9 (24.9)
Notes: *p<0.05; **p<0.01; PIGD: postural instability-gait disorder phenotype; Cognitive Impairment defined as mini-mental state examination
score lower than or equal to 23 (maximum score: 30). ADL: activities of daily living. Percentages calculated out of those with information.

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION S435

Association between baseline characteristics and mortality, expressed as mortality hazard ratio with 95% confidence interval (CI)

Univariate Models Adjusted Model

HR (95% CI) p-value HR (95% CI) p-value

Age of onset, per year increase 1.06 (1.03-1.09) <0.001 1.06 (1.02-1.10) 0.004
Age at onset < 60 years 0.32 (0.16-0.64) 0.001
Age at first visit, per year increase 1.05 (1.02-1.08) 0.001
Disease duration 0.87 (0.74-1.02) 0.093 0.86 (0.70-1.07) NS
Female* 11.2 (0.89-140.9) 0.062 76.5 (2.03-2886) 0.019
Race** 2.11 (1.00-4.43) 0.049 3.41 (1.21-9.58) 0.021
Subtype PIGD*** 0.82 (0.43-1.56) NS 0.83 (0.22-3.17) NS
Mixed 0.67 (0.22-2.02) NS 1.31 (0.47-3.67) NS
Cognitive Impairment 1.99 (1.01-3.92) 0.046 1.8 (0.80-4.01) NS
Depression 1.00 (0.52-1.94) NS 0.88 (0.36-2.14) NS
Hoehn-Yahr 0.90 (0.62-1.32) NS 1.05 (0.53-2.06) NS
ADL 1.00 (0.99-1.01) NS 1.00 (0.98-1.02) NS
Any major comorbidity 1.00 (0.54-1.89) NS 1.62 (0.63-4.16) NS
Notes: Univariate models include only one variable at a time. The adjusted model included all listed covariates simultaneously. Indicator variable
for age of onset lower than 60 years and age of first visit not included in the adjusted model because of collinearity.*Female: time-varying com-
ponent estimated because of violation of proportional hazards assumption. **Race: non-whites as compared to whites. *** Subtype: reference
group: tremor. PIGD: Postural-instability-gait disorder subtype. ADL: activities of daily living. NS: non-statistically significant, p>0.10.

1122
Remote TBI is a risk factor for recent falls among older veterans
R.C. Gardner, C.B. Peltz, K. Kenney, R. Diaz-Arrastia, K. Yaffe (San
Francisco, CA, USA)
Objective: To determine whether older adults with remote trau-
matic brain injury (TBI) are more likely to fall or to have Parkinson-
ism compared to those without TBI history.
Background: TBI is thought to be a risk factor for Parkinsons
disease (PD). Parkinsonism and resultant falls may develop insidi-
ously over years and may represent pre-clinical PD. Yet, few studies
have investigated motor function of older adults with remote TBI.
Methods: We recruited 62 U.S military veterans (ages 55
years) who reported a prior history of TBI  1 year ago necessitating
medical attention (assessed with Ohio State TBI interview) and who
did not have a PD diagnosis and 72 control veterans with no history
of TBI or PD diagnosis. We assessed motor function with self-
reported history of falls within the past year and the Unified PD Rat-
ing Scale (UPDRS; higher score indicates more Parkinsonism). Falls
and UPDRS score were compared between TBI subjects and controls
using linear regression for continuous outcomes and logistic regres-
sion for dichotomous outcomes while adjusting for age, gender, and
race. Analyses were repeated after excluding subjects with TBI
within 30 years of assessment.
Results: TBI subjects and controls did not differ significantly on
age (mean age 76 vs. 79 years, p50.08), gender (95% male vs. 88%
male, p50.12), or race (97% white vs. 88% white, p50.11). Mean
time since most recent TBI was 39 years (range 2-77 years; most
had TBI >30 years ago). 27% of TBI subjects reported falls in the
past year compared to 14% of controls (OR 3.5, 95% CI 1.3-9.3).
This association persisted even after excluding TBI subjects with
TBI within 30 years of assessment (OR 3.5, 95% CI 1.2-10.4). 46/62
TBI subjects and 56/72 controls had undergone UPDRS. While total
UPDRS score was greater but not statistically significantly different
among those with TBI vs. controls (9.9 vs. 7.9, p50.10), TBI sub-
jects had significantly higher postural instability (p50.04) and body
bradykinesia (p50.03) scores compared to controls.
Conclusions: Among older veterans, remote TBI is a significant
risk factor for falls within the past year. Further research is
warranted to determine whether early motor features of PD or Par-
kinsonism due to non-PD neuropathologies may be contributing to
this risk.
1123
Genetic and gene-environment associations with Parkinsons
disease (PD) in an Alaska native population
S.M. Goldman, C.M. Tanner, B. Trimble, M. Korell, G.W. Ross, A.B.
Singleton, C. Meng, D. Guest, R.D. Abbott (San Francisco, CA,
USA)
Objective: To determine the association of variants in the xenobi-
otic efflux membrane transporter p-glycoprotein (ABCB1, p-gp,
MDR1) and PD in Alaska Native people, and whether variants mod-
ify associations with persistent organochlorine pesticides (OCs).
Background: Variants in xenobiotic metabolizing genes are
inconsistently associated with PD risk. The OC pesticides hexachlor-
obenzene (HCB) and 4,4-DDE (a DDT metabolite) are associated
with PD in our study of Alaska Native people. Genetic modification
of the association of OCs and PD by a xenobiotic membrane trans-
porter is biologically plausible, but has rarely been tested.
Methods: Alaska Native people with PD and controls matched
for age, gender and region were identified within the Alaska Tribal
Health System and invited to participate. Peripheral blood was
obtained, and DNA extracted. Single nucleotide polymorphic variants
(SNPs) in ABCB1 were tested using an Affymetrix DMET array.
OCs were measured in serum using gas chromatography with mass
OR (95%CI) for PD associated with 1/- SNP and </>
median OC level
-variant, 1variant, -variant, 1variant,
SNP*OC < median < median > median > median
rs10276036 * 1 (ref) 1.6 (0.6-4.3) 1.4 (0.6-3.2) 4.5 (2.0-10.0)
HCB
rs2032582 * 1 1.5 (0.6-3.9) 1.6 (0.7-3.5) 6.2 (2.5-15.5)
HCB
rs2235040 * 1 1.2 (0.3-3.9) 0.8 (0.2-3.6) 3.0 (0.9-9.8)
HCB
rs2032582 * 1 2.4 (0.9-6.2) 1.1 (0.5-2.5) 3.1 (1.3-7.4)
4,4-DDE
rs2235040 * 1 2.3 (0.7-7.4) 1.4 (0.3-6.4) 3.1 (0.97-10)
4,4-DDE

Movement Disorders, Vol. 30, Suppl. 1, 2015

S436 POSTER SESSION
selective detection (GC-MS), and were dichotomized based on
median levels in controls. Minor allele dominant associations were
tested in logistic regression models adjusted for age and gender.
Multiplicative interaction was tested by including a product term for
SNP by OC.
Results: 69 PD and 179 controls participated in the study, and 65
PD and 168 controls provided blood samples. Seven of 9 ABCB1
SNPs with a minor allele frequency >5% were significantly associ-
ated with PD, among them rs10276036 (OR 2.7, 95%CI 1.5-4.9,
p50.001), rs2032582 (G2677A/T)(OR 2.4, 95%CI 1.3-4.5, p50.004)
and rs2235040 (OR 2.3, 95%CI 1.02-5.3, p50.04). ABCB1 SNPs
modified associations of OCs and PD (Table). Effect measure modifi-
cation was greatest for HCB.
Conclusions: Variants in the p-glycoprotein gene are associated
with PD in Alaska Native people, a population exposed to environ-
mentally persistent OCs. Associations of OCs and PD were modified
by ABCB1 genotype. Persons with altered activity of xenobiotic
efflux pumps may be more susceptible to PD, especially in combina-
tion with OC exposure.
1124
Brain magnetic resonance imaging measures are associated with
progression of mild Parkinsonian signs in community-dwelling
older adults
J. Han, S. Jain, A.L. Metti, K. Yaffe, A.L. Rosso, L.J. Launer, S.B.
Kritchevsky, R.M. Boudreau, H.J. Aizenstein, A.B. Newman, C.
Rosano (Pittsburgh, PA, USA)
Objective: To evaluate associations between magnetic resonance
imaging (MRI) measures of brain structure and progression of mild
Parkinsonian signs (MPS) in older adults, using the Unified Parkin-
sons disease Rating Scale Part 3 motor examination (UPDRS-III).
Background: MPS, consisting of bradykinesia, tremor, rigidity
and gait/postural abnormalities, are commonly found in older adults
without known neurologic disease and are associated with cognitive
decline, disability and mortality. As the origin of these signs remains
unclear, imaging studies may help elucidate the underlying neuro-
logic mechanisms.
Methods: We included 205 participants from a longitudinal study
(Health Aging and Body Composition) who had an MRI in 2007-
2009 concurrent with UPDRS evaluation, a follow-up UPDRS after
a minimum of 2 years, and were not on anti-Parkinsonian or
Parkinsonism-inducing medications. MRI measures included whole
brain volumes of white matter hyperintensities and gray matter
(GM), and diffusion tensor imaging measures of fractional anisotropy
(FA) in normal appearing white matter and mean diffusivity (MD) in
gray matter. MPS was defined using the following minimum criteria
on UPDRS-III: (1) 2 items with score of 1, (2) 1 item with score
of 2, or (3) rest tremor score of 1. MPS progression was measured
by UPDRS-III change over time. Pearson or Spearman correlations
were used to evaluate associations, as appropriate. Partial correla-
tions were used to adjust for age.
Results: At time of MRI, mean age was 82.7 6 2.6 years old,
UPDRS-III was 1.5 6 2.8, and MPS was present in 29.8%. Rate of
UPDRS-III change was 0.6 6 0.9 points per year over mean follow-
up of 3.8 6 0.8 years. Faster increases in UPDRS-III were associated
with older age (r=.17, p5.017), lower GM volume (r=-.17, p5.018),
and higher gray matter MD (r=.18, p5.011). The association
between rate of UPDRS increase and MD was stronger, and inde-
pendent of age, for subjects with no MPS at study entry (partial q
=.20, p5.017) relative to those with MPS, and trended towards sig-
nificance for GM volume (partial q =-.15, p5.074).
Conclusions: In this study, worsening of Parkinsonian signs was
predicted by smaller GM volumes and increased MD. Our results
suggest that GM integrity, both at the macro- and microstructural
level, may impact development of MPS, especially in those older
adults living in the community initially free from these signs.
Movement Disorders, Vol. 30, Suppl. 1, 2015
1125
Accuracy of death certification in the Denbighshire cohort at 16
years
P.J. Hobson, J.R. Meara (Rhyl, United Kingdom)
Objective: The aim of the present investigation is to examine the
reported causes of death in a community cohort of Parkinsons dis-
ease (PD) patients.
Background: In this investigation in North Wales, Denbighshire
United Kingdom (UK). Review of hospital and primary care records
were employed to ascertain the number of individuals who died dur-
ing the investigation period.
Methods: A total of 166 PD patients were followed for 16 years.
Death certificates were obtained from the UK national Births,
Deaths, and Marriages record office for the cohort. Primary and
underlying cause of death, along with the age of the subject and the
age of death recorded on all certificates coded using the ICD-10 sys-
tem were extracted.
Results: During the period of investigation from 1997-2013, 158/
166 (95%) of the cohort died. The Standard Mortality Rate (SMR)
compared to the England & Wales 2012 population was 1.82 (95%
CI: 1.55 2.13). Controlling for incident PD cases at baseline (n
=80), the SMR was 1.89 (95% CI: 1.49 2.37), indicating that there
was no excess mortality between the prevalent and incident cases
(p < 0.186). The main cause of death reported in the PD cohort was
pneumonia (52%), followed by cardiac related deaths (21%). PD as
the primary cause of death (Part 1a on UK death certificates) was
recorded in just over 4%. In section 1b of the death certificate (con-
ditions substantially contributing to death), PD was reported 24% of
cases. In section II of the death certificates (co-morbid conditions
substantially contributing to death); PD was reported in 19% of
cases. In 75/158 (47%) of the patient cohort, PD as significant con-
tributing factor in the cause of death was not reported. Although 144
of the cohort had a diagnosis of dementia at the time of death, this
was reported in less than 10% (n514) of certificates.
Conclusions: The current investigation serves to highlight the
increased mortality risk of over 1.5 (95% CI: 1.55 2.13) times that
of the general population. However the diagnostic accuracy of the
cause of death recorded on certificates is suboptimal. This evidenced
by the fact that PD was not recorded at all on 75 of our cohorts
death certificates. Furthermore, in spite of the findings here that over
90% of the PD cases at death had a diagnosis of dementia; it was
recorded in less than 10% certificates, further emphasising the weak-
ness of death certification in this population as an accurate means of
data capture.
1126
Mild cognitive impairment in Parkinsons disease and its
progression onto dementia; a 16-year outcome evaluation of the
Denbighshire cohort
P.J. Hobson, J.R. Meara (Rhyl, United Kingdom)
Objective: The current investigations aim is to explore the inci-
dence and possible neuropsychological domain differences between
Parkinsons disease (PD) patients with Mild Cognitive Impairment
(PD-MCI) and no cognitive impairment (PD-NCI), based upon the
International Parkinson and Movement Disorder Society Task Force
Guidelines for PD-MCI.
Background: Mild Cognitive Impairment in Parkinsons disease
has been suggested to be a predictor for the development of PD
dementia (PDD).
Methods: At baseline (T1), four years (T2) and six years (T3),
166 patients with PD were administered global neuropsychological
assessments. At 16-years case note and neuropsychological assess-
ment review was employed calculate the number of patients who had
progressed to PDD.
Results: Sixty eight patients at T1 were classified as PD-NCI, 18
with PD-MCI and 80 with PDD. At T2, 12 of the PD-MCI cohort at
 POSTER SESSION S437

T1 had progressed to PDD and there were 15 incident cases of PD- Among 2 patients, having multiple Movement Disorders, one
MCI. At T3, 9 PD-MCI cases at T2 had progressed to PDD. There patient had Parkinsonism, Writers dystonia, Blepherospam, includ-
were 10 incident cases of PD-MCI at T3.The incidence of progres- ing some Frontal lobe apathy features.
sion from PD-MCI to PDD was 98.0 per 1000 person years, with an Another patient had Essential Tremor with Hemifacial spasm.
annual conversion rate to PDD of 11%. Neuropsychological predic- Conclusions: In my short duration observational studies as
tors for conversion from PD MCI to PDD were semantic language, freshly started General Neurology OPD, Idiopathic Parkinsons dis-
praxis (figure drawing/copying), and visuospatial deficits. At 16- ease (12) has the highest incidences, followed by Essential
years, 91% of the PD-MCI cohort had progressed to PDD. Tremor(4), as expected from other epidemiological studies.
Conclusions: PD-MCI is an important predictor for the progres- Limitations of my study are a short duration and single person
sion to PDD. This investigation also confirmed that if PD patients observational study, but Im likely to continue this pilot project for a
live long enough, they will develop cognitive impairment or demen- longer duration with more conclusive data.
tia. Early detection of cognitive impairment in these individuals is References;
possible with existing standardised global cognitive assessments 1.Epidemiology of Parkinsons disease and Movement Disorders
which include semantic language assessment. in India: Problems and Possibilities,UB Muthane, Mona Ragothaman,
G Gururaj, JAPI, Vol. 55, October 2007
1127
1128
Incidence of Parkinsons disease and various Movement
Disorders in a general neurology OPD clinic in a South Indian Prevalence, incidence and risk factors associations of Parkinsons
superspeciality private hospital by a fresh general neurologist disease in an elderly population in Cuba
S.K. Jaiswal (Hyderabad, India) J.J. Llibre Guerra, J.C. Llibre Guerra, J.J. Llibre Rodriguez, M.
Guerra Hernandez, L. Garcia Arjona (La Habana, Cuba)
Objective: To highlight the recent trends of incidences and prev-
alences of Parkinsons disease and various Movement Disorders in a Objective: To estimate the prevalence, incidence, and risk factors
Private Hospital in India. of Parkinsons disease among older Cubans and assess the effects of
Background: India as a second populous country in the world apolipoprotein E genotype on the incidence of PD.
has a high burden of Movement Disorders patients, as highlighted by Background: Population-based registries of Parkinsons disease
previous studies from government institutes from India 1. But a good (PD) are not common in developing countries, and voluntary regis-
data collection from private institutes with recent trends will help in tries cannot be assumed to be representative, as a result a
defining characteristics of Movement Disorders in Asian population, population-based study door to door could clarified the pevalence
especially in Indian population, which in turn will help in the better and incidence and correlates of Parkinsons disease in older Cubans
management of Movement Disorders. populations.
Methods: In my General Neurology OPD, Ive collected data of Methods: A one phase survey (baseline) of all over 65 year old
all patients visited to me. It is a prominent private Superspeciality residents of seven catchment areas in Cuba (n52944) during 2003 to
Hospital in South India, having total 4 general neurologists, working 2005. Diagnosis of PD was established according to the Brain Bank
as a team with 3 neurologists have recently started their General Society criteria. In order to make a definitive diagnosis of Parkin-
Neurology OPD, including me and one neurologist with 30 years of sons disease every subject that received such a diagnosis during the
experience, with equal distribution of new patients, coming to neu- first phase was re-evaluated by two experienced neurologists. Base-
rology OPD. line data was used to estimate prevalence and the effect of apolipo-
From 1st May,2014 to 31st Dec,2014, during 8 months of dura- protein E genotype on PD prevalence. An incidence wave was
tion, total 950 neurology patients consulted to me in my General conducted 4.5 years after cohort inception in order to estimate inci-
Neurology OPD. All patients underwent necessary investigations, dence and risk factors associations.
including neuroimaging, preferrably MRI Brain(1.5 T). Results: The adjusted prevalence of PD was 1.1%. PD was asso-
Results: Total 32 patients of Parkinsons disease and various ciated with older age, less education, and a family history of PD.
Movement Disorders consulted to me during 8 months of duration The incidence rate of PD was 0.3 per 1000/pyear (95% CI, 0.17-
among 950 OPD patients . 0.45). APOE genotype was associated cross-sectionally with PD and
Details of all these patients are shown in Table 1. Dementia prevalence, but the effect on the incidence was much atte-
nuated, and only apparent among those in the youngest age group.
Conclusions: The prevalence and incidence of PD in the older
Cuban population is similar to that of developed countries, and the
Total No. of
rate increases with age. These findings underscore the need to
Types of disorders Patients(32) Sex(M/F) Age
improve our understanding of risk factors associated with PD in spe-
Idiopathic PD 12 10/02 55-76 cific populations, as well as the need for public health programs for
ET 04 03/01 21-62 population that is currently undergoing rapid demographic ageing
PSP 02 02/00 65-70 and epidemiological transition.
Parkinsonism 02 01/01 66-71
Vascular Parkinsons 02 01/01 67-72
HFS 02 02/00 29-42 1129
Writers Cramp 01 01/00 42 Priorities in Movement Disorder research
Blepherospasm 01 00/01 50 M.M. Macas, C.L. Go, J.C. Navarro (Manila, Philippines)
Tics 01 00/01 10
MyoclonicTwitch 01 01/00 33 Objective: To analyze the patterns of Movement Disorders pro-
RLS 01 00/01 49 spectively using the registry of Movement Disorders in our institu-
MSA 01 01/00 72 tion and to identify some research priorities.
Multiple 02 02/00 62-81 Background: Movement Disorders are common reasons for con-
sultation and referrals in our hospital. They are often thought to
ET 5 Essential Tremor, PSP 5 Progressive Supranuclear Palsy, affect movement only. However, most patients also experience psy-
HFS 5 Hemifacial Spasm,RLS 5 Restless Leg Syndrome,MSA=Mul- chiatric, cognitive, and other non-motor symptoms, either from the
tiple System Atrophy disease itself, or as a side-effect of medications. No data has been

Movement Disorders, Vol. 30, Suppl. 1, 2015

S438 POSTER SESSION

obtained regarding Movement Disorders in our institution. With the below one: 0.6 (0.40.7). In PD, median survival was lower than life
use of our registry, we aim to document findings prospectively, for expectancy across all ages, but, proportionally, was reduced more in
use as data mining to support a variety of researches in the future, under 65s.
and to guide us as to priorities in services, teaching and research.
Methods: Starting April 2014, all adult patients seen at the
Department of Neurology and the Department of Behavioral Medi- Median survival versus expected survival in PD by age strata
cine both inpatients and outpatients, presenting with Movement Dis-
Median Expected
orders, were included in this registry. With signed consent from
Deaths, survival in survival
these patients, the motor manifestations were documented by record-
Age stratum N (%) years (95% CI) in years
ing with a video camera. All verified Movement Disorders were
included in our IRB-approved Movement Disorder Registry. These
Under 65 9 (21) 11.4 (8.2n/a) 25.6
patients were then characterized as to their demographic and clinical
64 to 74 25 (36) 8.6 (7.8n/a) 13.7
profile, and were reviewed as to the pattern of Movement Disorders. 75 to 79 17 (45) 7.3 (6.910.2) 9.6
Results: Since April 2014, we have registered about 41 patients, 80 and above 39 (80) 4.1 (3.35.6) 6.4
with a mean age of 51 years for male and 67 years for female. The
most commonly seen Movement Disorder was Parkinsons disease
(70%). Other Movement Disorders were dystonia, hemichorea, hemi-
facial spasm, tardive dyskinesia, and tic disorder. This was in keep-
ing with other studies in Asian countries. As a national health
institution, and the second institution locally with a registry of
Movement Disorders, we hope to continue this registry so that we
could obtain a substantial data for future researches, to establish a
hospital prevalence and incidence of common Movement Disorders,
and to be able to answer the possible natural course of Movement
Disorders.
Conclusions: Creating a registry of Movement Disorders is bene-
ficial to be able to document findings from a prospective analysis the
patterns of Movement Disorders in our institution and to help us con-
struct research questions following research priorities in Movement
Disorders. Among patients registered, Parkinsons disease remains
the most common disease seen in our institution.

1130
Mortality in Parkinsons disease and atypical Parkinsonian
disorders
A.D. Macleod, C.E. Counsell (Aberdeen, United Kingdom)
Objective: To evaluate the excess mortality associated with Par-
kinsons disease (PD), Lewy body dementia (LBD), progressive
supranuclear palsy (PSP), multiple system atrophy (MSA), and vas-
cular Parkinsonism (VP).
Background: There is major heterogeneity in previous mortality
estimates in PD and few studies have reported mortality in other Par-
kinsonian syndromes. The optimal way to study mortality is long-
term follow-up of community-based incident cohorts.
Methods: All incident Parkinsonism cases were identified over
4.5 years (2002-4, 2006-9) in the Aberdeen area using multiple,
community-based ascertainment strategies (PINE study). Diagnoses
of syndromes were guided by research criteria. Age-sex matched
community-based controls were also recruited. Participants were
tagged to the NHS central register for regular death notifications.
Kaplan-Meier survival probabilities were plotted and age-sex
adjusted hazard ratios (HRs) for each syndrome versus controls were
calculated. Standardised mortality ratios (SMRs) were calculated
using regional mortality data, adjusted for age, sex and calendar
year. Age-sex adjusted life expectancies were calculated from
regional actuarial data.
Results: By June 2014, 90 deaths occurred in 198 PD patients,
107 deaths in 117 patients with other syndromes and 66 deaths in
260 controls (mean 5.3 years follow-up).[figure1] Only one control
was lost to follow-up. Median survivals in PD, LBD, PSP, MSA,
and VP were 7.8 (95% confidence interval 6.79.4), 3.3 (2.34.1),
2.6 (1.13.8), 5.1 (1.3N/A), and 2.1 (1.53.4) years, respectively.
HRs comparing these syndromes with controls were 2.8 (2.03.9),
8.0 (5.212.4), 6.3 (3.810.3), 3.6 (1.96.9), and 7.9 (5.012.4)
respectively. SMRs were all lower than HRs, but significantly greater
than one (1.5 [1.21.9], 4.2 [3.05.9], 3.8 [2.65.5], 1.8 [0.93.4],
and 4.2 [3.06.0] respectively). SMR for controls was significantly
Fig. 1. (1130).
Conclusions: Recruitment bias caused better control survival than
expected mortality, biasing hazard ratios. The SMR showed a 50%
increase in mortality in PD, consistent with previous inception stud-
ies. In terms of mortality, younger people with PD appear to have
proportionally more to lose. Survival was much poorer in other Par-
kinsonian syndromes.
1131
Predictors of institutionalisation in an incidence-based cohort of
Parkinsons disease
A.D. Macleod, C.E. Counsell (Aberdeen, United Kingdom)
Objective: To investigate frequency of, and baseline predictors
of, institutionalisation in Parkinsons disease (PD).
Background: The optimal study design for studying prognosis is
long-term follow-up of an incident cohort. There are few data on the
frequency or predictors of institutionalisation (i.e. entry to nursing
home, or other place of residential care) in PD and no data on pre-
dictors from incident cohorts. The only previous prospective
prevalence-based study found older age, impairment, dementia, and
hallucinations were independent predictors of nursing home
placement.
Methods: We attempted to identify all new cases of PD (diagno-
ses guided by UK PD Brain Bank criteria) in Aberdeen, UK, over
4.5 years (2002-4, 2006-9) using multiple, community-based ascer-
tainment methods. Age-sex matched community-based controls were
also recruited. Consenting patients were seen annually and place of
residence at each follow-up or before death were ascertained,
together with date of entry to an institution. Those institutionalised

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
Fig. 1. (1131).
at baseline were excluded from analyses. Kaplan-Meier probabilities
of institution-free survival comparing PD with controls were plotted.
Baseline variables were investigated as potential predictors of institu-
tionalisation using Cox regression. Individuals who died or were lost
to follow-up were censored.
Results: 198 patients with PD and 260 controls were recruited.
One patient and one control were institutionalised before diagnosis.
One patient and four controls were lost to follow-up. 44 (22%) PD
patients and 19 (7%) controls were institutionalised during mean 6.1
years follow-up.[figure1] At 5 years, 15.3% (95% CI 10.121.7) of
patients and 5.2% (2.98.9) of controls were institutionalized. Haz-
ards of institutionalisation were higher in PD than controls (HR 3.72
[2.166.39]). In univariable analyses, baseline age, dependence
(Schwab & England <80%), UPDRS motor score, timed walk,
MMSE and CIRS co-morbidity score, but not sex or living alone
were associated with institutionalisation. In multivariable analysis,
older age (HR 1.05 [1.011.09]), lower MMSE score (HR 0.88
[0.790.98]), and dependence (HR 2.48 [1.185.25]) were independ-
ently associated with greater hazards of institutionalisation.
Conclusions: Institutionalisation was higher in PD than controls.
Older age, poorer cognition and being dependent at diagnosis led to
increased institutionalisation.
1132
Movement Disorders in non-Wilsonian cirrhotic patients; the
report of prevalence and risk factors from the medical school in
agricultural-based community
K. Methawasin, C. Wongjitrat, P. Chonmaitree, S.
Rattanamongkolgul, T. Asawavichienjinda (Ongkharak, Thailand)
Objective: To investigate the prevalence of Movement Disorders
in non-Wilsonian cirrhotic patients and their significant risk factors.
Background: The acquired hepatocerebral degeneration associ-
ated with portosystemic shunting was documented in 1965. Parkin-
sonism and other Movement Disorders were reported. However,
there is no study about their prevalence in general practice.
Methods: One hundred and forty-three patients with hepatic cir-
rhosis of the gastroenterology clinic and internal medicine wards of
HRH Princess Maha Chakri Sirindhorn Medical Center, Nakorn
Nayok, were invited to participate in this study between February
2013 and February 2014. Two gastroenterologists were responsible
for the diagnosis, etiologies, complications and treatments of liver
cirrhosis. One neurologist included volunteers regarding the inclusion
criteria. The hepatic encephalopathy was classified regards to West
Haven criteria for semiquantitative grading of mental status . Neuro-
logical examination results and abnormal involuntary movements
S439
were recorded as primary outcomes. Neuroradiology was for the
detection of severe brain lesions.
Results: Alcoholism is the most common cause of liver cirrhosis.
Hyposmia was detected in 35 cirrhotic patients with statistical signif-
icance related to the hepatocellular carcinoma and hepatic encephal-
opathy (P<0.05, RR 5 2.958, 95%CI 1.108-7.899 and P<0.05,
RR 5 2.667, 95% CI 1.219-5.834). Eighty-three patients (58%) pres-
ent Movement Disorders. The negative myoclonus was found in one
case. The commonest Movement Disorder is an intention tremor at
37.1%, which orderly followed by bradykinesia, Parkinsonism, and
postural tremor at 29.4%, 10.5%, and 6.3%. The prevalence of
Movement Disorders simultaneously increased with the high Child-
Turcotte-Pugh (CTP) score. With age-range adjustment, the alcoholic
cirrhosis and hepatic encephalopathy are statistically significant fac-
tors (P<0.05, RR=5.998, 95%CI 1.315-27-358, and P<0.001,
RR=10.996, 95%CI 4.034-29.974) for the development of Movement
Disorders in non-Wilsonian cirrhotic patients.
Conclusions: Intention tremor is common in cirrhotic patients.
The alcoholic cirrhosis and the hepatic encephalopathy are significant
risk factors of the development of hyposmia and Movement Disor-
ders in non-Wilsonian cirrhotic patients after age adjustment.
1133
Movement Disorders in non-Wilsonian hepatic cirrhosis patients
at HRH Princess Maha Chakri Sirindhorn Medical Center,
Srinakharinwirot University, Ongkharak campus; the subgroup
analysis of various phenotypes of Movement Disorders and
associated risk factors
K. Methawasin, C. Wongjitrat, P. Chonmaitree, S.
Rattanamongkolgul, T. Asawavichienjinda (Ongkharak, Thailand)
Objective: According to data from the Movement Disorders in
non-Wilsonian cirrhotic patients; the report of prevalence and risk
factors from the medical school in agricultural-based community, the
research team aims to identify risk factors associated with the devel-
opment of various phenotypes of Movement Disorders detected in
the study.
Background: Some etiologies such as hepatic encephalopathy,
and accumulations of toxins/waste products due to impaired hepatic
function were proposed to cause abnormal movements in cirrhotic
patients. However, other etiologies are needed to clarify their
significance.
Methods: Cirrhotic patients in the group of intention tremor, Par-
kinsonism, bradykinesia, postural tremor, abnormal ocular move-
ments and gait ataxia were analyzed by the statistical analysis; Chi-
square or Fisher-Exact tests, and logistic regression. Patients in the
bradykinesia group were sub-grouped to be the bradykinesia with or
without rigidity and the bradykinesia without rigidity group.
Results: For intention tremor, alcoholic cirrhosis is a significant
risk factor related to it (P<0.05, RR 5 10.060, 95%CI 1.557-65.000).
The Parkinsonism of our study was influenced by confounders,
hyperlipidemia (P 5 0.044, RR 5 0.105, 95%CI 0.012-0.943) and
motor and sensory deficits (P<0.05, RR 5 5.125, 95%CI 1.224-
21.471). For bradykinesia, the prevalence of bradykinesia with or
without rigidity associated to the hepatic encephalopathy, DM,
hyperlipidemia, and motor or sensory deficits. Contrarily, only the
hepatic encephalopathy shows statistical significance on the preva-
lence of bradykinesia without rigidity either before or after age-range
adjustment (P<0.001, RR 5 39.981, 95%CI 8.794-181.760 and
P<0.001, RR 5 40.207, 95%CI 8.815-183.385). An abnormal ocular
movement detected is the jerky pursuit while performing horizontal
gaze. It significantly related to the hepatic encephalopathy (P<0.05,
RR 5 4.789, 95%CI 1.826-12.558) both before and after age-range
adjustment. Ataxic gait in this study shows no significant association
to all risk factors.
Conclusions: Alcoholic cirrhosis strongly associated to the devel-
opment of intention tremor. Interestingly and significantly, patients
with hepatic encephalopathy showed the purely fine motor slowness.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S440 POSTER SESSION
1134
Frequency and pattern of Movement Disorders at a tertiary care
hospital in Enugu, Southeast Nigeria
O.A. Molokwu, B.A. Ezeala, I.O. Onwuekwe, O.S. Ekenze, A.C.
Nwabueze (Enugu, Nigeria)
Objective: To study the frequency and spectrum of Movement
Disorder cases presenting to the adult neurology clinic of the Univer-
sity of Nigeria Teaching Hospital (UNTH) Enugu, southeast Nigeria
and to compare with observations in other regions.
Background: Movement Disorders are not uncommon in neurol-
ogy clinics. The epidemiology of Movement Disorders has been well
studied in developed countries. However, paucity of data exists in
most developing nations including Nigeria. Literature has shown Par-
kinsonism,benign essential tremor and dystonia as the first, second
and third most common forms of Movement Disorder presenting to
most neurology clinic.
Methods: We did a chart review of all patients presenting to the
neurology clinic of UNTH Enugu between January 1, 2012 to
December 31 2013. Demographic and clinical data were documented
and the frequency of Movement Disorders was determined.Data was
analyzed using SPSS version 19.
Results: A total of 2315 neurological cases were seen over the
study period.211cases were Movement Disorders giving a frequency
of 9.11%. 146 cases (69.19%) were cases of Parkinsonism.Idiopathic
Parkinsons disease accounted for 111cases (76.03%) of the cases of
Parkinsonism.Benign essential tremor,dystonia,cerebellar ataxia,
myoclonus and others accounted for 10.9%,6.7%,5.7% 2.8% and
1,4% respectively of the Movement Disorder cases.
Conclusions: Parkinsonism still remains the commonest Move-
ment Disorder presenting to the neurology clinic of UNTH Enugu,
southeast Nigeria.
1135
New onset Movement Disorders in type 2 diabetes mellitus
patients presenting in hyperglycemic crisis at a tertiary hospital
in Enugu, South East Nigeria
O.A. Molokwu, I.O. Onwuekwe, B.A. Ezeala, O.S. Ekenze, A.C.
Nwabueze (Enugu, Nigeria)
Objective: This study analyzed the spectrum, clinical, demo-
graphic and neuroimaging correlates. of new-onset Movement Disor-
ders seen in type 2 diabetic patients admitted in hyperglycemic
crisis.
Background: Hyperglycemic crisis in patients with diabetes mel-
litus (DM) has been shown to be associated with various Movement
Disorders such as chorea, ballism, athetosis etc. either singularly or
in combination (hemichorea-hemiballism (HCHB), choreoathetosis)
and showing either a generalized or lateralized distribution pattern.
These Movement Disorders occur more commonly in those present-
ing with hyperglycemic hyperosmolar state than diabetic ketoacido-
sis. HCHB has a localizing value and points to the contra-lateral
putamen and/or subthalamic nucleus affectation.Many of what we
know about Movement Disorders in patients presenting in hypergly-
cemic crisis come from case reports and case series of predominantly
Asian or Caucasian subjects. Little is known about African subjects.
Methods: Patients with a history of type 2 DM or new onset type
2 DM admitted into our medical wards with new onset Movement
Disorders between January 1st, 2010 and December 31st, 2014 were
evaluated. Data on demographics, clinical presentation, Movement
Disorder characteristics and neuroimaging findings (where available)
were analyzed.
Results: A total of six patients (3 males and 3 females) with type
2 DM presented with hyperglycemic crisis and new onset Movement
Disorder. 3 had HCHB, 2 had hemichorea and a contra-lateral hemi-
paresis, and the last had choreoathetosis. The ages of the patients
ranged from 55-82 years. All but one presented in a hyperglycemic
hyperosmolar state. 1/3 had complete resolution of the Movement
Movement Disorders, Vol. 30, Suppl. 1, 2015
Disorder with therapy for DM alone while the remaining 2/3 had
additional therapy for the Movement Disorder. 50% of those treated
additionally for the Movement Disorder achieved complete resolution
while the other half had persistence of the abnormal movements. CT
scan was done only in the 2 patients who had hemichorea and
contra-lateral hemiparesis though it did not show the classic hyper-
density of the putamen.
Conclusions: Prompt recognition, prompt glycemic control and in
some cases, addition of specific therapy for the Movement Disorder
will help improve the resolution and outcome of abnormal move-
ments seen in diabetic hyperglycemic crisis.
1136
Prevalence and treatment pattern of Parkinsons disease
dementia in Korea
Y.S. Oh, J.S. Kim, I.S. Park, Y.S. Shim, I.U. Song, J.W. Park, P.H.
Lee, C.H. Lyoo, T.B. Ahn, H.I. Ma, Y.D. Kim, S.B. Koh, S.J. Lee,
K.S. Lee (Seoul, Korea)
Objective: The aim of the present study was to investigate the
point prevalence of dementia and mild cognitive impairment (MCI)
in patients with PD.
Background: Cognitive impairment is one of the most common
non-motor symptoms of PD and is associated with reduced quality of
life for the patient and increased caregiver burden and distress.
Patients with PD had a three- to six-fold higher risk of developing
dementia compared with individuals without PD, and nearly 80% of
patients with PD eventually develop dememtia. However, reports on
the prevalence of cognitive impairment in PD have been insufficient
in Korea.
Methods: A total of 1200 patients with PD from 12 hospitals
were included in the study. All patients were grouped into normal
cognition, MCI, and dementia subgroups. General cognitive status
and dementia severity were assessed by the Korean version of the
Mini-Mental Status Examination, Clinical Dementia Rating, and
Global Deterioration Scale, and Parkinsonian motor status was
assessed by the Hoehn and Yahr staging score. Associated sleep
behaviors and other medical conditions were checked. Prescribing
patterns of antidementia medications were analyzed.
Results: Cognitive impairment was frequent in patients with PD;
MCI was found in 38.9% of patients while dementia was in 38.3%
of patients. The prevalence of cognitive impairment was increased
with increasing age and longer disease duration and the symptoms of
postural instability were associated with cognitive impairment. Many
dementia patients (94.2%) and 23.8% of MCI patients were treated
with anti-dementia drugs, with rivastigmine the most frequently
used.
Conclusions: The point prevalence of cognitive impairment in
patients with PD was 77.3%. Cognitive impairment was associated
with age, disease duration, and specific Parkinsonian motor symp-
toms. Over 90% of the patients with dementia were treated with
anti-dementia medication and rivastigmine was the most frequently
used for the management of dementia.
1137
Comparing patterns of presentation and appropriateness of
diagnosis of Movement Disorders between the teaching hospitals
in Osun State, Western Nigeria
O.J. Ojo, O.I. Agunbiade, T.T. Lekan Agunbiade (Osogbo, Nigeria)
Objective: To examine and compare the patterns of presentation
and diagnosis of Movement Disorder cases in the Teaching Hospitals
within Osun State viz; Ladoke Akintola University of Technology
Teaching Hospital,Osogbo and Obafemi Awolowo University Teach-
ing Hospital, Ile-Ife.
Background: Movement Disorders are common presentations in
neurological practices; however there have been few studies on how
 POSTER SESSION
they present in Nigeria and if they were appropriately diagnosed.
Though often not life-threatening,MDs can cause serious behavioral
abnormalities, impaired daily functions while its involuntary nature
may be embarrassing, causing emotional distress or depression in
some individuals.
Methods: A descriptive-comparative study of the neurological
cases seen in the two Teaching Hospitals in Osun State, Western
Nigeria between 2010 and 2014 to examine the pattern of presenta-
tion and diagnosis of MDs in both facilities. The record of patients
that presented at the Neurology clinics of OAUTH, Ile-Ife and LTH,
Osogbo between October 2010 and October 2014 (A register of all
neurology outpatients) was used to review all cases of MDs seen.
Results: Over the period of study, total neurology clinic consulta-
tion in OAUTH, Ile-Ife was 910, of which 118 (13%) were Move-
ment Disorders while clients seen in LTH, Osogbo, were 1170 of
which 15 (1.28%) were Movement Disorder cases. Seventy-two of
the clients seen in OAUTH, Ile-Ife were males and forty-six were
females while eleven males and four females were seen in LTH,
Osogbo. Mean ages were 61 and 54 respectively. Presentation after
Six months of initial symptom was common to both centers.
Conclusions: In both facilities of study, MDs had male prepon-
derance and was commoner among clients 50 and above.With the
presence of neurologist in both,one in eight clients in OAUTH had
MDs compared to one in every seventy-eight cases in LTH.Some
assumptions can be explained as affecting the presentation and
appropriateness of diagnosis of MDs; they are taken within the com-
munities as either spiritual attack or early signs of aging thus, poor
presentation in the health facility; inadequate knowledge of General
practitioners on MDs thus, inappropriate diagnosis and poor or
delayed referral to neurologist.Unavailability of DBS in both facili-
ties explains that there is a great need for improvement in MDs care
in Nigeria.
1138
Parkinsons and pesticides: A study on gene-environment
interactions in Egypt
T.W. Rosler, M.M. Salama, A. Eltantawy, A. Shalash, G. Fawe, E.
Khedr, A. Elmotayam, E. Elsaeedy, G.U. H oglinger (Munich,
Germany)
Objective: We aim to explore the synergistic interactions
between environmental pesticide exposure and polymorphisms in
specific genes in the etiology of Parkinsons disease (PD).
Background: Pesticide exposure and related environmental fac-
tors such as well water drinking or farming are associated with an
increased risk for PD. But not solely the environment, also the indi-
vidual genetic make-up contributes to the susceptibility for sporadic
PD. These two conditions may play a role in Egypt, extensive and
unprotected use of pesticides on the one hand and genetic factors
e.g. high frequencies of LRRK2 mutations, which have been found
in North African countries, on the other hand. Today, Egypt has one
of the highest prevalence rates of PD worldwide and still only little
is known about possible interactions of defined environmental and
genetic risk factors.
Methods: The study is carried out within the Egyptian Network
for Neurodegenerative Diseases (www.ennd.org), comprising N=16
neurological university hospitals from all over Egypt. PD patients are
recruited from rural areas with high pesticide exposure and from
urban areas with low exposure. Equal numbers of controls are
recruited from patients attending outpatient clinics who are not suf-
fering of any neurodegenerative disorder, and from healthy persons
accompanying patients; controls are classified into low and high pes-
ticide exposure. All participants are assessed with a standardized
questionnaire to evaluate past exposure to pesticides and other PD-
related environmental factors. PD patients are examined to verify
presence of PD (UK brain bank criteria) and to quantify disease
severity (Hoehn & Yahr stage, UPDRS motor part). DNA of each
S441
participant was collected to analyze polymorphisms in PD-associated
genes or defined genes encoding detoxification enzymes.
Results: We developed functional infrastructures and standard
operating procedures to collect biological samples and clinical data
from within the entire country of Egypt. So far, we collected epide-
miological data and analyzed DNA from N= 243 PD cases and
N=217 controls. We will present first data on genetic and environ-
mental associations and on gene-environment interactions in PD in
Egypt.
Conclusions: The present study provides further insights into spe-
cific risk factors that contribute to the increased prevalence of PD in
Egypt and more generally into mechanisms of the gene-environment
interplay in the etiology of PD.
1139
Accuracy of clinical diagnosis of Parkinsons disease: A
systematic review and Bayesian meta-analysis
G. Rizzo, D. Martino, S. Arcuti, M. Copetti, A. Fontana, G.
Logroscino (Tricase, Italy)
Objective: To evaluate diagnostic accuracy of the clinical diag-
nosis of Parkinsons disease (PD) reported in the last 25 years by a
systematic review and meta-analysis.
Background: A correct diagnosis of PD is important for clinical
management and pharmacological and epidemiological studies.
Methods: We performed electronic searches of PUBMED and
EMBASE database from 1988 to 31th August 2014 to identify all
relevant studies reporting diagnostic parameters regarding the clinical
diagnosis of PD, as sensitivity, specificity, positive predictive value
(PPV), negative predictive value (NPV) and accuracy, or crude data.
Two authors independently extracted data from the eligible studies.
We sub-classified the selected studies based on the different study
setting, type of test diagnosis and gold standard, and performed
meta-analyses of the available data using a Bayesian approach.
Results: We selected 21 studies reporting on 23 populations and
5260 patients. The pooled diagnostic accuracy was 79.8% [95%
credible interval (CrI), 75.7% - 83.5%]. Looking at the different type
of test diagnosis, the pooled diagnostic accuracy was 76.2% [95%
CrI, 69.7% - 81.8%] for clinical diagnosis performed mainly by non-
experts. Clinical diagnosis performed by Movement Disorders
experts rising from 76.4% [95% CrI, 71.4% - 80.7%] of initial
assessment to 84.9% [95% CrI, 73.5% - 92.3%] of refined diagnosis
after follow-up. Using UKPDSBRC criteria the pooled diagnostic
accuracy was 82.7% [95% CrI, 62% - 93%].
Conclusions: The overall validity of clinical diagnosis of PD is
not satisfying. The accuracy did not significantly improve in the last
25 years, particularly in the early stages of disease. Misclassification
rate should be considered to calculate the sample size both in obser-
vational studies and RCT. Imaging and biomarkers are needed to
support the diagnosis in vivo.
1140
The impact of hospital Parkinsons disease volume on patient
safety events: Should we regionalize PD inpatient care?
D. Safarpour, D. Thibault, A. Willis (Philadelphia, PA, USA)
Objective: To describe patient safety events for hospitalized indi-
viduals with Parkinsons disease, using the AHRQ Patient Safety
Indicators (PSIs), and examine the impact of hospital PD volume on
patient safety.
Background: Individuals with PD are hospitalized more often
than the general population. Avoidable safety events (such as post-
operative fall with hip fracture) may signify lower hospital quality,
but may also indicate personnel inexperience with certain disease
populations, and therefore may respond to intervention.
Methods: We used the National Inpatient Sample (NIS) database
from 2000-2010 to calculate the performance of NIS hospitals on
Movement Disorders, Vol. 30, Suppl. 1, 2015
S442 POSTER SESSION

medical (skin pressure ulcers, unexpected death) and post-operative
(hip fracture, hemorrhage, metabolic derangement, respiratory failure,
sepsis, DVT/PE) PSIs. Hospitals were designated as high or low
PD volume based on the annual proportion of inpatients diagnosed
with PD. We calculated overall/PD PSI rates, adjusting for age, sex
and comorbid illnesses. Logistic regression models compared the
odds of having any/each PSI between 1) PD and the general popula-
tion, and 2) PD patients in high vs. low PD volume hospitals, adjust-
ing for patient race, sex, age, length of stay.
Results: PD patients suffered inpatient falls with hip fracture
more than twice as often as the general population (adjusted rate per
1000 admissions- general: 0.80, 0.73-0.87; PD: 2.15, 1.52-2.88). PD
patients had greater odds of 11 PSI (AOR 1.35, 1.33-1.37), post-
operative hip fracture (AOR 2.33, 1.76-3.08) pressure ulcers (AOR
1.87, 1.83-1.90), and unexpected death (AOR 1.14, 0.94-1.38). PD
patients treated in high PD volume hospitals had lower odds of 11
PSI (AOR 0.94, 0.90-0.98), post-operative hemorrhage/hematoma
(AOR 0.76, 0.59-0.99) and PE/DVT (AOR 0.74, 0.63-0.87). We
found lower odds of the other PSIs in high volume hospitals as well,
but the 95% CIs crossed unity. Stratification by admission type
(elective/emergent) or hospital teaching status did not change the
direction of our findings.
Conclusions: Parkinsons disease patients are more vulnerable to
specific safety events, even during elective admissions. Treatment at
hospitals with great PD population experience reduces the likelihood
of these harms. Future studies are needed to determine the extent to
which staff education or regionalization of PD inpatient care can
improve patient safety for this population.
1141
COPPADIS-2015 (COhort of Patients with PArkinso ns DIsease
in Spain, 2015): A global Parkinsons disease project underway
D. Santos Garca, T. de Deus Fonticoba, P. Mir, E. Cubo, L. Vela,
M.C. Rodrguez-Oroz, J.M. Arbelo (Ferrol, Spain)
Objective: To describe a Spanish ongoing global Parkinsons dis-
ease (PD) Project based on four pillars: (1) PD as a global disease;
2) Quality of life (QoL) and caregiver issues; 3) Biomarkers; 4) Dis-
ease progression.

TABLE 1. Centers participating in Project COPPADIS-2015.

Control Complementary
Principal Investigator (PI) and Institution name City Patients (n) subjects (n) studies
1. Diego Santos Garca; Secci on de Neurologa, Hospital Arqui- Ferrol 60 10 YES
tecto Marcide, Complejo Hospitalario Universitario de Ferrol (A Coru~
na)
(CHUF).
2. (1) Oriol de Fabregues-Boixar Nebot and (2) Jorge Hernandez Barcelona 60 (40/20) 20 (10/10) unknown
Vara; Unidad de Trastornos del Movimiento, Servicio de Neu-
rologa, Hospital Universitario Vall dHebron.
3. Carmen Borrue Fernandez; Unidad de Trastornos del Movi- Madrid 50 10 YES
miento, Servicio de Neurologa, Hospital Infanta Sofa.
4. Pablo Mir Rivera; Unidad de Trastornos del Movimiento, Ser- Sevilla 40 10 YES
vicio de Neurologa y Neurofisiologa Clnica, Instituto de Bio-
medicina de Sevilla, Hospital Universitario Virgen del Roco,
CSIC y Universidad de Sevilla.
5. Fina Mart Domenech; Unidad de Parkinson y Trastornos del Barcelona 40 10 NO
Movimiento, Servicio de Neurologa, Instituto Clnico de Neu-
rociencias, Hospital Clnic.
6. Beatriz Tijero Merino; Unidad de Neurologa Funcional y Bilbao 35-40 10 YES
Enfermedad de Parkinson, Hospital de Cruces.
7. Jose Chacon Pe~na; Unidad de Neurologa, Hospital Infanta Sevilla 30-25 10 NO
Luisa.
8. (1) Manuel Seijo Martnez and (2) Iria Cabo L opez; Seccion Pontevedra 30 (15/15) 20 (10/10) unknown
de Neurologa, Hospital de Pontevedra.
9. Vctor Puente Periz; Unidad de Trastornos del Movimiento, Barcelona 25-30 10 YES
Servicio de Neurologa, Hospital del Mar.
10. Ines Legarda Ramirez; Servicio de Neurologa, Hospital Uni- Palma de 25 10 YES
versitario Son Espases. Mallorca
11. Francisco Carrillo Padilla; Servicio de Neurologa, Hospital Santa Cruz 25 10 YES
Universitario de Canarias, San Crist obal de la Laguna. de Tenerife
12. Lydia Lopez Manzanares; Unidad de Trastornos del Movi- Madrid 25 10 YES
miento, Servicio de Neurologa, Hospital La Princesa.
13. Caridad Valero Merino; Unidad de Neurologa, Hospital Valencia 20-25 10 NO
Arnau de Vilanova.
14. Jaime Kulisevsky Bojarski; Unidad de Trastornos del Movi- Barcelona 20 10 NO
miento, Servicio de Neurologa, Hospital de Sant Pau.
15. Jose Manuel Garca Moreno; Unidad de Trastornos del Movi- Sevilla 20 10 YES
miento, Hospital Universitario Virgen Macarena.
16. Benito Galeano Bilbao; Secci on de Neurologa, Hospital Uni- Ceuta 20-25 10 YES
versitario de Ceuta.
17. Nuria Caballol Pons; Unidad de Trastornos del Movimiento, Sant Joan 20 10 YES
Consorci Sanitari Integral, Hospital Moises Broggi. Desp
(Barcelona)

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION S443

TABLE 1. Continued

Control Complementary
Principal Investigator (PI) and Institution name City Patients (n) subjects (n) studies
18. Pilar Sanchez Alonso; Servicio de Neurologa, Hospital Madrid 15-25 10 YES
Puerta de Hierro.
19. Mari Cruz Rodrguez Oroz; Hospital Universitario Donostia, San Sebastian 20 10 YES
Instituto de Investigacion Biodonostia.
20. Esther Cubo Delgado; Servicio de Neurologa, Complejo Burgos 15 10 YES
Asistencial Universitario de Burgos.
21. Lydia Vela Desojo; Unidad de Neurologa, Fundaci on Hospi- Alcorc
on 15 10 YES
tal de Alcorcon. (Madrid)
22. Maria Jose Catalan Alonso; Unidad de Trastornos del Movi- Madrid 15 10 YES
miento, Servicio de Neurologa, Hospital Clnico San Carlos.
23. Luis Manuel L opez Daz; Seccion de Neurologa, Hospital de Burela (Lugo) 15 10 NO
Burela.
24. Maria Gema Alonso Losada; Servicio de Neurologa, Hospi- Vigo 15 10 YES
tal Meixoeiro, Complejo Hospitalario Universitario de Vigo
(CHUV).
25. Nuria Lopez Ariztegui; Unidad de Trastornos del Movi- Toledo 15 10 YES
miento, Complejo Hospitalario de Toledo.
26. Monica Kurtis Urra; Unidad de Trastornos del Movimiento, Madrid 15 10 YES
Servicio de Neurologa, Hospital Ruber Internacional.
27. Jon Infante Ceberio; Unidad de Trastornos del Movimiento, Santander 15 10 YES
Servicio de Neurologa, Hospital Universitario Marques de
Valdecilla.
28. Sonia Escalante Arroyo; Servicio de Neurologa, Hospital de Tortosa 15 10 YES
Tortosa Verge de la Cinta (HTVC). (Tarragona)
29. Juan Carlos Martnez Castrillo; Unidad de Trastornos del Madrid 15 10 YES
Movimiento, Servicio de Neurologa, Hospital Ram on y Cajal.
30. Jose Matas Arbelo Gonzalez; Unidad de Trastornos del Las Palmas de 15 10 YES
Movimiento y enfermedad de Parkinson, Servicio de Neuro- Gran Canaria
loga, Hospital Universitario Insular de Gran Canaria.
31. Rene Ribacoba Montero; Unidad de Trastornos del Movi- Oviedo unknown 10 unknown
miento, Servicio de Neurologa, Hospital Central de Asturias.
32. Jessica Gonzalez Ardura; Servicio de Neurologa, Hospital Lugo 15 10 YES
Universitario Lucus Augusti (HULA).
33. Javier Lopez del Val; Unidad de Trastornos del Movimiento, Zaragoza 15 10 YES
Servicio de Neurologa, Hospital Clnico Universitario Lozano
Blesa.

34. Mara Asuncion Avila Rivera; Unidad de Trastornos del LHospitalet 15 10 YES
Movimiento, Consorci Sanitari Integral, Hospital General de de Llobregat

LHospitalet. (Barcelona)
35. Hortensia Alonso Navarro; Secci on de Neurologa, Hospital Madrid 15 10 YES
Universitario del Sureste, Madrid.
36. Carlos Garca Sancho; Servicio de Neurologa, Complejo A Coru~
na unknown 10 unknown
Hospitalario Universitario de A Coru~ na (CHUAC).
37. Josefina Martnez Sim on; Unidad de Trastornos del Movi- Granada 15 10 unknown
miento, Servicio de Neurologa, Complejo Hospitalario Uni-
versitario de Granada.
38. Pilar Quilez Ferrer; Unidad de Trastornos del Movimiento, Barcelona unknown 10 unknown
Hospital Universitario Mutua de Terrasa.
39. Olga Carmona Codina; Servicio de Neurologa, Hospital Girona 15 10 unknown
Josep Trueta y Parc Mart i Julia.
40. Juan Garca Caldentey; Unidad de Neurologa, Hospital Palma de 15 10 NO
Quiron Palmaplanas. Mallorca
41. Ana Rojo Sebastian; Unidad de Parkinson y Movimientos Alcala de 15 10 YES
Anormales, Servicio de Neurologa, Hospital Universitario Henares
Prncipe de Asturias. (Madrid)
42. Silvia Mart Martnez; Servicio de Neurologa, Hospital Gen- Alicante 15 10 NO
eral de Alicante.
43. Jose Andres Domnguez Moran; Unidad de Neurologa, Hos- Alcira 15 10 YES
pital de la Rivera. (Valencia)
925 450 29 YES

Movement Disorders, Vol. 30, Suppl. 1, 2015

S444 POSTER SESSION

Fig. 1. (1141).

Background: PD is a progressive neurodegenerative disorder designed to find PD diagnosis and/or progression biomarkers and
causing motor and non-motor symptoms that can affect independ- know the natural progression of the disease are needed.
ence, outcomes and the QoL of both patients and caregivers. Studies Methods: Observational, descriptive, non-interventional, cross-
sectional, 5-year follow-up, national (Spain), multicenter, and

Fig. 2. (1141).

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
evaluation study. Specific goals: (1) Detailed study (clinical, serum
biomarkers, genetic and neuroimaging) of a population of PD
patients from different areas of Spain (COPPADIS), (2) comparison
with a control group and (3) follow-up for 5 years. COPPADIS-2015
has been specifically designed to assess 17 proposed objectives.
Study population: Approximately 800 non-demented PD patients,
600 caregivers and 400 control subjects. Study evaluations: (1) Base-
line [figure1]; (2) Follow-up [figure2]. Serum biomarkers (S-100b
protein, TNF-a, IL-1, IL-2, IL-6, vitamin B12, methylmalonic acid,
homocysteine, uric acid, C-reactive protein, ferritin, iron) and brain
MRI (volumetry and MTAi [Medial Temporal Atrophy Index]) at
baseline and at the end of follow-up and genetic studies (DNA and
RNA) at baseline will be performed in a subgroup of subjects (300
PD patients and 100 control subjects).
Results: There are no results at this time. Study periods: (1)
Recruitment period, from May 1, 2015 to August 31, 2016 (basal
assessment); (2) Follow-up period, 5 years; (3) Closing date of clini-
cal follow-up, November 30, 2021. At present (December 2014), 43
centers of Spain have confirmed their participation.
Conclusions: COPPADIS-2015 is an ambitious initiative. This
project will provide important information of the natural history of
PD and the value of various biomarkers.
1142
Familial aggregation of Parkinsons disease in Utah: A
population-based analysis
R. Savica, S. Pulst, L.A. Cannon-Albright (Salt Lake City, UT, USA)
Objective: To describe the familial clustering of Parkinsons dis-
ease in the largest population-based study of the USA.
Methods: We took advantage of the multiple record-linked data
sources of the Utah Population Database (UPDB), which includes
genealogy data for more than 2.5 million individuals. Among the
493,175 individuals with a valid Utah death certificate (DC), we
identified cases of PD using ICD. Among probands whose DCs listed
PD, the relative risk (RR) of death with PD was determined among
first- through third-degree relatives, using birthyear-, sex-, and
birthplace-matched cohorts.
Results: We identified 3,625 individuals with a DC indicating
PD. Among 16,560 deceased first-degree relatives of probands, the
RR of dying with PD was increased compared with the population
(RR 5 1.86, 95% confidence interval 1.64, 2.11). The RR of dying
with PD was also increased among 37,393 deceased second-degree
relatives (RR 5 1.45, 95% CI 1.29, 1.63) and third-degree relatives
(RR 5 1.16, 95% CI 1.08, 1.24). The offspring of the probands had
the strongest risk of dying with PD (RR 5 2.86, 95% CI 2.03, 3.91).
Conclusions: Our results confirm and further expand the results
of prior studies of PD. Furthermore, this work expands on previous
studies by quantifying the RR of PD among more distant relatives.
Finally, the excess relatedness and the elevated RRs for PD among
first, second and third-degree relatives strongly supports a genetic
contribution to PD mortality.
1143
The decline of the amyotrophic lateral sclerosis/Parkinsonism-
dementia complex (ALS/PDC) of Guam and the recent
identification of Huntingtons chorea in the families of Umatac
village
J.C. Steele, C.G. Quinata, L.Q. Cruz, R. Carlos, M. Farrer (Covina,
CA, USA)
Objective: To report the epidemiology of neurodegenerative syn-
dromes in Umatac village, the epicenter of ALS/PDC for 2 centuries.
Background: Neurological diseases on Guam are likely to pro-
vide understanding of universal neurodegenerations.
Methods: During 2014, volunteers assisted JCS to identify disor-
ders of movement, memory impairment and paralysis among the
S445
1,000 residents of Umatac. 90% were Chamorros in six principal,
intermarried families. Most had lived all their lives in this small and
isolated village of southern Guam where foreign sailors and traders
introduced western ways and diseases after Magellans historic land-
ing in 1521.
Results: 3 patients ages 74 to 84 were already known to have
had symptoms of PDC for 9 to 15 years.
3 other patients with PDC, ages 52, 69 and 73 were newly
identified.
No one was identified with ALS.
We identified 2 cases with chorea and dementia, ages 48 and 60
whose disease had begun when ages 39 and 53. They were from dif-
ferent families and both had first degree relatives who suffered ALS/
PDC.
The father of the younger patient, born in 1935 developed chorea
at age 61 and died 8 years later. Genomic sequencing of his DNA
by Farrer in 2013 identified a trinucleotide repeat expansion of the
Huntington gene HTT (42 CAG repeats) and we concluded he had
suffered Huntingtons chorea.
Subsequent inquiries revealed 4 additional cases of probable HC.
Conclusions: The current pattern of ALS/PDC in Umatac is simi-
lar to that reported by Plato (1) in other villages on Guam, but PDC
remains most prevalent in Umatac and includes a young case born in
1964.
This is the first report of Huntingtons chorea on Guam during 70
years of surveillance (2). The 7 cases we suspect were all born in
Umatac and are from 3 families who suffer high rates of ALS/PDC.
1. Plato CC, Garruto RM, Galasko D, et al. Amyotrophic lateral
sclerosis and Parkinsonism-dementia complex of Guam: changing
incidence rates during the past 60 years. Am J Epidemiol 2003;
157:149 2157.
2. Steele J, Guella I, Szu-Tu, Lin M, Thompson C, Evans D,
Sherman, Vilarino Guell C, Gwinn K, Morris H, Dickson D, Farrer
M. Defining neurodegeneration on Guam by targeted genomic
sequencing. Accepted by Annals of Neurology for publication in
2015.
1144
Vagotomy and subsequent risk of Parkinsons disease
E. Svensson, E. Horv
ath-Puho, R.W. Thomsen, J.C. Djurhuus, L.
Pedersen, P. Borghammer, H.T. Srensen (Aarhus N, Denmark)
Objective: We aim to examine the long-term risk of Parkinsons
disease in patients who have undergone vagotomy compared with a
matched population cohort.
Background: It has been hypothesized that Parkinsons disease is
caused by an enteric neurotropic pathogen entering the brain through
the vagal nerve, a process thought to take over 20 years. Vagotomy,
a surgical procedure in which the vagus nerve is resected, was previ-
ously a common treatment for peptic ulcer. Two primary types of
vagotomy were performed: full truncal vagotomy, in which both
vagal trunks were severed, and super-selective vagotomy, in which
only the nerves supplying the fundus and body of the stomach were
resected.
Methods: We used data from the Danish National Patient Regis-
try, covering all Danish hospitals, to gather a cohort of patients who
underwent either full truncal vagotomy or super-selective gastric
nerve vagotomy between 1977 and 1995, and a matched general pop-
ulation cohort. We used Cox regression to compute hazard ratios for
Parkinsons disease, comparing the risk among vagotomy operated
patients and the matched general population cohort, and correspond-
ing 95% confidence intervals [CI], adjusting for potential
confounders.
Results: The risk of Parkinsons disease was decreased in patients
who underwent truncal vagotomy (incidence rate 5 0.65 per 1,000
person-years) compared to the general population cohort [incidence
rate 5 0.86 per 1,000 person-years; overall adjusted hazard
ratio 5 0.84; 95% confidence interval [CI]: 0.63-1.14; after follow-
Movement Disorders, Vol. 30, Suppl. 1, 2015
S446 POSTER SESSION
up > 20 years, adjusted hazard ratio 5 0.53; 95% CI: 0.28-0.99]. In
patients who underwent super-selective vagotomy (incidence rate-
5 0.57 per 1,000 person-years), risk of Parkinsons disease was simi-
lar to that in matched general population cohort members (incidence
rate 5 0.56 per 1,000 person-years) [overall adjusted hazard
ratio 5 1.09; 95% CI: 0.84-1.43; after follow-up of >20 years,
adjusted hazard ratio 5 1.16; 95% CI: 0.80-1.70]. Results were con-
sistent after external adjustment for unmeasured confounding by
smoking.
Conclusions: Our study supports the hypothesis of a vagal
entry point in the putative ascending pathogenesis of Parkinsons
disease.
1145
Persistent organic pollutants (POPs) and Parkinsons disease
(PD) in an Alaska native population
C.M. Tanner, S.M. Goldman, B. Trimble, M. Korell, G.W. Ross, C.
Meng, D. Guest, R.D. Abbott (San Francisco, CA, USA)
Objective: To determine the association of POPs and PD in
Alaska Native people.
Background: POPs (e.g., polychlorinated biphenyls (PCBs),
organochlorine pesticides (OCs)) have been associated with PD risk.
Alaska Native people may have high exposures to POPs.
Methods: Lifelong occupational, residential and dietary risk fac-
tor data were collected by structured interview and compared in
Alaska Native people with PD and controls matched for age, gender
and region. Diagnosis was by expert consensus. Serum levels of
POPs were measured by gas chromatography-mass spectroscopy.
Analyses used geometric means and log-transformed values. Asso-
ciations with PD were tested using logistic regression models
adjusted for age and gender. For determination of odds ratios (ORs)
and trends, we constructed quartiles based on distributions in
controls.
Results: 69 PD (mean age: 65.7 6 11.6 years; 51% men) and
179 controls (mean age: 62.7 6 12.1 years; 45% men) participated;
65 PD (50% men) and 168 controls (45% men) provided serum.
Cigarette smoking was associated with lower PD risk (OR 0.41,
95% CI 0.23, 0.74, p < 0.002). The most common POPs detected
were 4,4-DDE, hexachlorobenzene (HCB), and PCB congener
138. Geometric means and odds ratios (ORs) were higher in PD
(Table).
Conclusions: Higher serum HCB levels are associated with
increased PD risk and an association with higher PCB levels is sug-
gested in this Alaska Native population. In Swedish elders, PCB-138
and HCB are associated with increased markers of oxidative stress
(Kumar et al, Chemosphere 2014). PCB-138 concentrates in brain,
causing reduced striatal dopamine and impaired DAT and VMAT
(Caudel, 2006). These POPs may initiate mechanisms associated
with PD pathogenesis.
Distribution and Statistical tests of Common POPs
Case
Geometric
POP % Detected Mean
4,4-DDE 92.3 2.1
HCB 82.0 0.32
PCB-138 89.2 0.34
Sum of all PCBs 0.59
Count of any PCB 89.2
*Highest vs. lowest quartile, adjusted for age & gender; **4 PCB congeners vs. none
Movement Disorders, Vol. 30, Suppl. 1, 2015
1146
Utility of electronic medical record databases using ICD-9
criteria for recruitment in clinical research: From rare to
common disease
T. Thacker, A.R. Wegele, S. Pirio Richardson (Albuquerque, NM,
USA)
Objective: To evaluate in the electronic medical record, the accu-
racy of ICD-9 codes for cervical dystonia (CD) and Parkinsons dis-
ease (PD), which are clinical diagnoses. Then to compare these
accuracy rates with the rates for a common medical disorder with
laboratory confirmation, diabetes mellitus type 2 (DM-2).
Background: Recruitment of subjects for clinical trials is a major
challenge. The utility of electronic-medical record database ICD-9
diagnoses for clinical trials recruitment remains unclear due to accu-
racy concerns. Movement Disorders, which do not have associated
diagnostic laboratory or imaging tests, may be especially prone to
inaccuracy in coding.
Methods: We performed a retrospective chart review to confirm
the ICD-9 diagnoses of PD, CD and DM-2. UK Parkinsons disease
Society Brain Bank Clinical Diagnostic Criteria, the clinical criteria
for dystonia proposed by Albanese et al.1 and hemoglobin A1c  6
were used to confirm the diagnoses of PD, CD and DM-2, respec-
tively. The statistical analysis of the accuracy rates for ICD-9 codes
were performed using a Fishers exact test.
Results: We reviewed a total of 421 charts (n5129, n5142,
n5150 for PD, CD and DM-2, respectively). The accuracy rate of
diagnosis was different between all diseases examined with an over-
all p<0.001. In post hoc pairwise comparisons, the accuracy of DM-
2 diagnosis by ICD-9 (96.6%) was greater than CD (88.0%) and
both greater than PD (55.0%) (p0.003).
Conclusions: ICD-9 diagnoses for disorders like DM-2 with
clearly defined laboratory criteria are more accurate compared to
Movement Disorders, like CD & PD. CD had a high rate of ICD-9
accuracy, possibly due to predominant use of this diagnosis by
Movement Disorders specialist as seen in our study. The ICD-9 code
for PD includes the diagnosis of Parkinsonism, and this ambiguity in
the coding may lead to the lower accuracy rate found in this study.
Based on our results, ICD-9 based screening of clinically diagnosed
diseases such as CD may be more accurate than previously thought.
Use of ICD-9 diagnoses as a screening tool for recruitment purposes
for clinical trials remains an area of study.
1
Albanese & Lalli. Is this Dystonia? Movement Disorders. 2009;
24:1725-1731.
1147
Prevalence of Parkinsons disease in Ukraine in 2013
Y.O. Trufanov, N.K. Svyrydova, A.I. Galusha, O.V. Popov (Kyiv,
Ukraine)
Control
% Geometric
Detected Mean OR* 95%CI P for trend
92.3 1.5 2.0 0.84, 4.6 0.17
67.9 0.26 2.9 1.3, 6.5 0.015
78.0 0.26 2.2 1.0, 5.0 0.062
0.41 2.5 1.1, 5.7 0.053
81.0 3.2** 1.01, 9.9 0.057
 POSTER SESSION S447

with PD per 100,000 in 2013 was registered in the Vinnytsya, Lviv

The number of registered patients with PD per 100,000 and Kyiv regions (122.4/103.4/102.9) and in the city of Kyiv
of population all over Ukraine and in different regions of (109.6). In 14 regions of Ukraine and in the city of Sevastopol, the
Ukraine (modified from Hobzei M.K., Zinchenko O.M., number of the registered patients was 50-100 per 100,000. In 8
Golubchikov M.V., Mishenko T.S. The state of neurological regions of Ukraine, only 30-50 per 100,000 was seen.
service in Ukraine in 2010 and 2013. Conclusions: The number of registered patients with PD in
Parkinsons disease) Ukraine increased in 2013 by 9.06% as compared to 2010. An
increasing number of registered patients with PD by 1.22% - 45.77%
The number were seen in 21 regions of Ukraine and Sevastopol. A decreasing
of PD number of registered patients with PD by 0.08% - 4.18% were seen
patients per only in 4 regions of Ukraine and Kyiv.
100,000 Dynamics The prevalence of PD in Ukraine appears to be lower than in
Oblast (Region) other countries. As well, the number of the registered cases of PD
per varies significantly among regions.
2010 2013 100,000 % The low prevalence of PD in Ukraine (65.0 PD patients per
100,000 of population) as well as a wide spectrum of values of the
Ukraine 59.6 65.0 1 5.4 1 9.06% registered cases among Ukrainian regions (from 33.3 to 122.4 PD
100 and more patients per 100,000 patients per 100,000 of population) may be connected with the
1. Vinnytsya 122.5 122.4 - 0.1 - 0.08% underdiagnosis of PD.
2. Kyiv city 111.3 109.6 - 1.7 - 1.53%
3. Lviv 91.9 103.4 1 11.5 1 12.51%
4. Kyiv region 85.8 102.9 1 17.1 1 19.93%
50-100 patients per 100,000 1148
5. Cherkasy 90.9 87.1 - 3.8 - 4.18%
6. Khmelnytskyi 81.8 82.8 1 1.0 1 1.22% Longitudinal study of mild Parkinsonian signs in elderly people
7. Sevastopol city 61.1 77.0 1 15.9 1 26.02% in Japan
8. Chernihiv 63.2 75.3 1 12.1 1 19.15% K. Wada-Isoe, K. Tanaka, M. Kishi, S. Nakashita, Y. Tajiri, S. Taga-
9. Volhynia 64.8 73.8 1 9.0 1 13.89% shira, M. Yamamoto, K. Nakashima (Yonago, Japan)
10. Poltava 68.7 72.6 1 3.9 1 5.68%
11. Zakarpattia 65.8 69.8 1 4.0 1 6.08% Objective: To clarify the longitudinal clinical course of Mild Par-
12. Kharkiv 71.3 69.5 - 1.8 - 2.52% kinsonian signs (MPS) in elderly people, and to identify predictors
13. Zaporizhia 69.3 68.1 - 1.2 - 1.73% of its evolution, focusing on cognition, sleep, mood, and cerebrovas-
14. Ivano-Frankivsk 46.1 67.2 1 21.1 1 45.77% cular lesions on MRI. The evolution of MPS.
15. Mykolaiv 46.2 59.1 1 12.9 1 27.92% Background: MPS are thought to represent the end of a disease
16. Rivne 45.0 55.9 1 10.9 1 24.22% spectrum that spans from normal aging to neurodegenerative dis-
17. Zhytomyr 52.2 54.9 1 2.7 1 5.17% eases. MPS have been reported to be associated with dementia,
18. Luhansk 47.0 51.7 1 4.7 1 10.00% depression, mortality, and with functional disability. However, the
19. Ternopil 43.5 50.2 1 6.7 1 15.4% longitudinal clinical course of MPS has remained unclear.
30-50 patients per 100,000 Methods: One hundred sixty-eight participants (80.0 6 7.6 years,
20. Kirovohrad 42.8 47.5 1 4.7 1 10.98% 65% women) were diagnosed as having MPS at baseline (in 2008
21. Sumy 38.8 45.4 1 6.6 1 17.01% 2009). A follow-up study was performed in 20122013. Motor func-
22. Autonomous 38.7 42.5 1 3.8 1 9.82% tion was assessed according to a modified Unified Parkinsons Dis-
Republic of Crimea ease Rating Scale (mUPDRS) score. MPS was determined to be
23. Dnipropetrovsk 31.8 41.6 1 9.8 1 30.82% present if any of the following conditions were met: (1) two or more
24. Kherson 39.2 40.6 1 1.4 1 3.57% mUPDRS ratings 5 1; (2) one mUPDRS rating 5 2; or (3) a
25. Chernivtsi 38.8 39.8 1 1.0 1 2.58% mUPDRS rest tremor rating 5 1. Those who had two or more cardi-
26. Odesa 31.1 37.6 1 6.5 1 20.90% nal signs (UPDRS rating 2) were classified as having parkinsonism.
27. Donetsk 30.6 33.3 1 2.7 1 8.82% The Mini-Mental State Examination (MMSE) for global cognitive
function, the Geriatric Depression Scale with 15 questions (GDS-15)
for depressive symptoms, and the Pittsburgh Sleep Quality Index
(PSQI) for sleep disturbance were administered at baseline. Brain
MRI scans were also performed and the Fazekas scale was used to
assess white matter hyperintensities.
Objective: To compare the prevalence of Parkinsons disease
Results: Of 168 participants with MPS, 23 subjects were
(PD) in Ukraine in 2010 and 2013; to compare the prevalence of PD
deceased or had moved from the town. One hundred four participants
in Ukraine with other countries.
completed a follow-up study (response rate; 73.2%). Non-responders
Background: Previous research has shown that the number of
were older than responders (mean=81.6 years vs 78.4 years). At
registered cases of PD in the USA, Canada, countries of the Euro-
follow-up, 43 participants had MPS (Stable group), 22 participants
pean Union (Italy, Spain, Bulgaria, the UK, Estonia, Sweden), Aus-
had Parkinsonism (Progressive group), and 39 participants were diag-
tralia and Asia countries (South Korea, Japan, China) ranges from
nosed as normal (Revert group). There were no significant differen-
104 to 374 per 100,000 population.
ces in mUPDRS or GDS-15 scores at baseline between the groups.
Methods: Statistical data of the Ministry of Health Protection of
The mean age, frequency of sleep disturbance, and the Fazekas PVH
Ukraine was obtained to determine prevalence of PD.
score at baseline were significantly lower in the Revert group com-
Ukraine is divided into 25 regions (oblasts), with separate data
pared with the Stable and Progressive groups. The MMSE score at
for the cities of Kiev and Sevastopol.
baseline was significantly lower in the Progressive group compared
Results: Table 1 presents systematized data of reported cases of
with the Stable and Revert groups.
PD in all Ukrainian regions.
Conclusions: MPS can be reversible in elderly people. Age, cog-
As seen in table 1, the number of the registered patients with PD
nitive function, sleep disturbance, and white matter lesions might be
in Ukraine is 65.0 per 100,000. The largest number of the patients
associated with the evolution of MPS.

Movement Disorders, Vol. 30, Suppl. 1, 2015

S448 POSTER SESSION

1149
Mortality of Parkinsons disease from a five-year follow up study
in Shanghai
G. Wang, S. Chen (Shanghai, Peoples Republic of China)
Objective: Our study was aimed to identify the mortality rates
and predictors of death in PD patients in China.
Background: The mortality of Parkinsons disease (PD) and its
associated risk factors among clinically definite PD patients in China
have been rarely investigated.
Methods: 157 consecutive clinically definite PD patients from
the urban area of Shanghai were recruited from a central hospital
based Movement Disorder clinic in 2006. All patients were regularly
followed up at the clinic until December 31, 2011, or death. Mortal-
ity and associations with baseline demographics, health and medical
factors were then determined within the cohort.
Results: After 5 years, 11(7%) patients died. The standardised
mortality rati was 0.62 (CI 0.32 to 1.07, P=0.104). The main causes
of death were pneumonia (54.5%, 6/11) and digestive disorders
(18.2%, 2/11), respectively. Age at onset, independent living, the
MMSE score, the PDSS score and the ESS score at baseline were
statistically significantly different between the survival group and the
deceased group (P<0.05). Across all participants, risk factors for
death included low MMSE score, and high ESS score according to a
binary variable logistic regression analysis . Fig. 1. (1150).
Conclusions: This study confirms the similar survival of patients
with PD to the control population up to a follow-up of 5 years. Inter-
ventions tailored to potential risk factors associated with death may (P=0.94), and rapid eye movement sleep behavior disorder (P=0.71)
offer further benefits. between ET patients and controls.
Conclusions: The prevalence of ET in people50 years old in
rural area of Shanghai China is low. Prevalence of certain NMSs
1150 was higher in participants with ET relative to health controls.
Prevalence of non-motor symptoms of essential tremor in a rural
area, Shanghai, China: A population-based, door-to-door survey
Y.W. Wu, X. Wang, W. Cheng, Q. Sun, N. Song, Y. Zhou, Q. Jiang, Genetics
Y. Qiao, J. Xu, L. Liang, H. Tang, J. Ma, X. Gao, S. Chen
(Shanghai, Peoples Republic of China)
Objective: Few studies regarding the epidemiology of essential 1151
tremor (ET) and its non-motor symptoms (NMS) have been con- Glucocerebrosidase mutations and atypical Parkinsonism: A
ducted to date. Wethus conducted a door-to-door survey to investi- multi-centre exploratory study
gate the ETand its NMS and clinical manifestations in a rural area 
R. Alvarez Velasco, P. Giraldo, P. Ir
un, E. Viedma Guiard, J. L opez
inShanghai, China.
Sendon, I. Avil
es Olmos, G. Garca Ribas, P.J. Garca-Ruiz, L. Vela
Background: The traditional view that ET is a mono- Desojo, J.C. Martnez Castrillo, A. Alonso C
anovas (Madrid, Spain)
symptomatic tremorgenic disorder has been challenged. Emerging
evidences in recent years suggest that ET is possibly associated with Objective: To determine the frequency of glucocerebrosidase
several non-motor symptoms (NMS), including cognitive impair- (GBA) mutations in patients with atypical Parkinsonian syndromes
ment, anxiety, depression and olfactory dysfunction. However, upon (APS) with features of tauopathy (progressive supranuclear palsy-
reviewing the literature to date, there are few epidemiological studies PSP and corticobasal syndrome-CBS).
covering the natural spectrum of NMS featured in ET. Background: GBA mutations cause autosomal recessive Gauch-
Methods: We recruited 24,464 residents (50 years old),living in ers disease (GD). A strong association between heterozygous GBA
Malu town, Shanghai, in the study. Investigations were divided into mutations and Parkinsons disease has been demonstrated. Although
two stages, screening questionnaire followed by clinical diag- this link has not been demonstrated so far in APS, genetic studies
nosis. In stage one, trained physicians conducted door-to-door sur- were based only in common mutations screening, when a higher reli-
veys using our screening questionnaire for Movement Disorders, ability would be expected from GBA gene sequencing studies. In
including ET. In stage two, participants with suspected ET had their addition, adult onset GD has been reported to present with atypical
diagnosis confirmed by Movement Disorder specialists. We further Parkinsonian features, specifically tauopathy phenotypes (PSP, CBS),
randomly selected 123 subjects from those adults screened negative with mild or absent systemic features of GD.
for neurological conditions in our research for the study of NMS, Methods: Ongoing cross-sectional multicentre study of PSP and
including cognitive impairment, depression, rapid eye movement CBS patients, including demographic and clinical variables, beta-
sleep behavior disorder, olfactory function etc. [figure1] glucosidase and chitotriosidase serum activity and complete GBA
Results: The prevalence of ET in individuals (50 years old) gene sequencing. Our aim is to complete a sample of at least 40
was 0.245% (PR=2.45 per 1000).The minimental state examination patients.
(MMSE) scores were lower in ET patients than in controls Results: 6 patients (67% male, mean age 74, range 60-80) with
(25.81 6 4.20 vs. 26.63 6 3.14,P=0.024) .Complaints of restless legs PSP diagnosis have been included so far. In all cases, beta-
reported by ET patients were significantly higher than those in con- glucosidase and chitotriosidase serum activity have been within nor-
trols (P<0.05). In contrast, we did not observe significant difference mal range and complete GBA gene sequencing has shown no
for other NMS, including olfactory function (P=0.82), depression abnormalities.

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
Conclusions: Our ongoing study does not support so far an asso-
ciation among tauopathies and GBA mutations. The larger expected
sample will help further clarify this possible link.
1152
C9ORF72 expansion in neurodegenerative disorders
characterized by Parkinsonism and chorea
N.Y. Abramycheva, E.Y. Fedotova, M.S. Stepanova, S.A.
Klyushnikov, Y.A. Seliverstov, S.N. Illarioshkin (Moscow, Russia)
Objective: To estimate the prevalence of the C9ORF72 expan-
sion among patients with Parkinsons disease (PD), atypical Parkin-
sonism (AP) and phenocopies of Huntingtons disease (HDP).
Background: The hexanucleotide repeat expansion in C9ORF72
gene has been identified as a cause of a significant proportion of
cases of frontotemporal dementia and amyotrophic lateral sclerosis.
Recently, several studies have shown the association of the
C9ORF72 expansion with PD and HDP.
Methods: We screened for this mutation a large cohort of Rus-
sian patients, including 175 patients with PD, 54 with AP (progres-
sive supranuclear palsy, corticobasal syndrome and multiple system
atrophy) and 31 with HDP, and 223 healthy controls, using a fluores-
cence fragment length analysis of PCR fragments and repeat primed
PCR.
Results: In PD group, we found 4 patients (2.3%) with an inter-
mediate expansion of 19-20 repeats, including one familial case. In
this group, however, none carried a pathogenic C9ORF72 expansion
of >30 repeats. Among patients with HDP, we identified 3 cases
with the intermediate expansion of 18-20 repeats (9.6%) and no
cases with the pathogenic mutation. In AP and controls, we did not
find persons carrying the intermediate or pathogenic copy number of
repeats in C9ORF72 gene. The difference between controls and
groups with PD and HDP in terms of prevalence of the intermediate
expansion in C9ORF72 was significant (p<0.05).
Conclusions: Our results demonstrate that the C9ORF72 expan-
sion, especially lying within the intermediate copy number of hexa-
nucleotide repeats, could be associated with neurodegenerative
disorders characterized by Parkinsonism and chorea.
This study was supported by the Russian Foundation for Basic
Research (grant # 13-04-01718a).
1153
Phosphorylated pS1292 LRRK2 to total LRRK2 concentration
ratio in urine exosomes distinguishes LRRK2-PD and idiopathic
PD
R.N. Alcalay, K.B. Fraser, A. West (New York, NY, USA)
Objective: To measure total LRRK2 and phosphorylated pS1292-
LRRK2 levels in urine exosomes of LRRK2 G2019S carriers with
PD (LRRK21/PD1), and non-carriers with (LRRK2-/PD1), and
without PD (LRRK2-/PD-).
Background: LRRK2 G2019S mutations may increase Parkin-
sons disease (PD) risk through a gain of kinase function including
autophosphorylation at the serine-1292 residue near the LRRK2
GTPase domain. Phosphorylated pS1292-LRRK2 may reflect
LRRK2 kinase activity.
Methods: 14 Male participants included LRRK21/PD1 (n57),
LRRK2-/PD1 (n54), and LRRK2-/PD- (n53). Fresh urine was col-
lected and frozen in a -80oC freezer. Urinary exosomes were purified
from 40 ml samples. Monoclonal anti-LRRK2/Dardarin clone
acquired from NeuroMab were used to measure total LRRK2, and
novel polyclonal antibodies generated in rabbits against pS1292-
LRRK2 were used to quantify total-LRRK2 and pS1292-LRRK2 in
Western blots. Total LRRK2, pS1292-LRRK2 and the ratio between
total LRRK2 and pS1292-LRRK2 were compared between G2019S
carriers with PD and non-carriers with and without PD.
S449
Fig. 1. (1153).
Results: All three groups were similar in age (mean=67.0;
SD=7.5). The ratio of pS1292-LRRK2 to total LRRK2 was signifi-
cantly different between LRRK21/PD1 (mean=0.90; SD=0.28;
range 0.60-1.46) and both LRRK2-/PD1 (mean=0.20; SD=0.03;
range 0.16-0.24, p<0.001) and LRRK2-/PD- (mean=0.19; SD=0.09;
range 0.10-0.29; p<0.001). The values did not overlap. [figure1]
Conclusions: A ratio of phosphorylated pS1292-LRRK2 to total
LRRK2 in urine may distinguish between LRRK21/PD1 and non-
carriers with and without PD. Future studies are required to confirm
that this ratio signifies LRRK2 autophosphorylation activity in the
brain and to test if the elevated ratio is associated with disease char-
acteristics in men and women.
1154
Glucocerebrosidase activity in Parkinsons disease with and
without GBA mutations
R.N. Alcalay, O.A. Levy, C. Waters, S. Fahn, B. Ford, S.H. Kuo, P.
Mazzoni, M.W. Pauciulo, W. Nichols, Z. Gan-Or, G.A. Rouleau,
W.K. Chung, P. Wolf, P. Oliva, J. Kreutzer, K.S. Marder, X.K. Zhang
(New York, NY, USA)
Objective: Glucocerebrosidase (GBA) mutations are associated
with Parkinsons disease (PD). We measured glucocerebrosidase
enzymatic (GCase) activity in dried blood spots in PD patients and
controls with and without GBA mutations.
Methods: PD patients (n5517) and controls (n5252) were
recruited from Columbia University, and fully sequenced for GBA
mutations. GCase activity in dried blood spots was measured by
mass spectrometry-based assay. GCase activity was compared among
participants with two GBA mutations/variants (homozygotes/com-
pound heterozygotes), GBA heterozygotes and non-carriers. The
association between GCase activity and PD status was measured in
adjusted regression models excluding GBA and LRRK2 G2019S
mutation carriers. In non-GBA non-LRKK2 PD patients, the associa-
tion between GCase activity and disease characteristics was
examined.
Results: GBA homozygotes/compound heterozygotes had lower
GCase activity than GBA heterozygotes (0.85mmol/l/h versus
7.88mmol/l/h, p<0.001), and GBA heterozygotes had lower GCase
activity than GBA and LRRK2 non-carriers (7.88mmol/l/h versus
11.93mmol/l/h, p<0.001). [figure1] PD patients had slightly lower
mean GCase activity than controls (11.14mmol/l/h versus 11.85mmol/
l/h, p50.011). Differences persisted even after exclusion of all GBA
and LRRK2 carriers (11.53mmol/l/h, versus 12.11mmol/l/h, p50.036)
and adjustment for age and gender (p50.012). However,
Movement Disorders, Vol. 30, Suppl. 1, 2015
S450 POSTER SESSION
Fig. 1. (1154).
LRRK2 G2019S carriers (n536) had higher enzymatic activity than
non-carriers (13.7mmol/l/h versus 11.93mmol/l/h, p50.002). Among
PD non-GBA non-LRRK2 carriers, higher GCase activity was asso-
ciated with longer disease duration (p50.002) in adjusted models,
possibly indicating a milder disease course.
Conclusions: Lower GCase activity is strongly associated with
GBA mutations, and modestly with PD after excluding all carriers.
High GCase activity in LRRK2 G2019S carriers may reflect a dis-
tinct pathogenic mechanism.
1155
Double homozygous mutations (R275W and M432V) in the
Parkin gene associated with late onset PD
J. Carr, B. Sihaam, T. Chris, B. Soraya, F. Matt (Cape Town, South
Africa)
Objective: To describe pathogenic mutations in a consanguineous
South African family, where family members presented with mild
features of PD at ages ranging from 47 to 68 years.
Background: Parkin mutations are typically associated with early
onset Parkinsons disease (PD) and dystonia. We identified a family
with three affected members with PD and a history of consanguinity.
Methods: Whole exome sequencing validated with Sanger
sequencing was performed.
Results: Double homozygous mutations (R275W and M432V)
were identified in the Parkin gene, falling within the RING1 and
RING2 domains respectively. The affected patients had typical fea-
tures of PD, were mildly affected, and their ages of presentation
were 47, 58, and 68 years.
Conclusions: Double homozygous mutations in the RING1 and
RING2 domains were identified. Despite the predicted effects of dou-
ble mutations, the three patients presented late with typical PD. In
selected families, it may be appropriate not to limit screening for
parkin mutations only to those patients presenting with early-onset
PD. Currently, there is no clear genotype-phenotype correlation
shown for mutations affecting the ubiquitin or RBR
domains(Grunewald A, Kasten M, Ziegler A, Klein C. Next-
generation phenotyping using the parkin example: time to catch up
with genetics. JAMA Neurol. 2013;70(9):1186-91), and this finding
of double homozygous mutations in a family who tended to present
at an older age than is typically seen contributes to a broadening of
the understanding of the spectrum of Parkin gene related PD.
The presence of mutations in both RING1 and RING2 domains
suggests that there should be significant loss of Parkin function, and
Movement Disorders, Vol. 30, Suppl. 1, 2015
Fig. 1. (1155).
there is pathological evidence that the RW275 mutation in the
RING1 domain is sufficient to give rise to widespread Lewy bodies
(Ruffmann C, Zini M, Goldwurm S, Bramerio M, Spinello S, Rus-
coni D, et al. Lewy body pathology and typical Parkinsons disease
in a patient with a heterozygous (R275W) mutation in the Parkin
gene (PARK2). Acta Neuropathol 2012;123:9013). Pathogenic
mutations in RING2 abolish the E3 ligase activity of Parkin, and
mutations at G429E, G430D, and C431F are all reported to lead to
loss of E3 Ligase activity. The M432V mutation is novel, but is
highly conserved, and may affect E3 Ligase activity, given its prox-
imity to three sequential mutations which are known to affect this
function.
1156
Establishment and validation of the first stable human ATP7B
knockout hepatoma cell line: A Wilson[apos]s disease cell model
G. Chandhok, V. Sauer, A. Aggarwal, M. Bhatt, A. Zibert, H.H.J.
Schmidt (M
unster, Germany)
Objective: To establish and validate a stable human ATP7B
knockout (KO) cell line to study copper (Cu) metabolism and drug
response in Wilson[apos]s disease (WD).
Background: Human hepatocytes are most ideal for studying Cu
metabolism and toxicity in liver; however, short survival remains a
limitation. While lower eukaryotic models and mammalian cell lines
have provided insights in studying functional properties of ATP7B
mutants, the difference in species and organ source make extrapola-
tion of results to humans difficult. Human hepatoma cell lines pro-
vide excellent cellular platforms for studying copper toxicity,
however; expression of endogenous ATP7B makes analysis difficult.
Methods: HepG2 (human hepatocellular carcinoma) cells were
transfected with Zinc Finger Nucleases (ZFN) targeted to exon 8 of
the ATP7B gene for generation of KO cells. Single cell cloning was
performed in 96 well plates and individual clones were screened for
the targeted mutation. KO cells derived were subjected to qPCR and
western blot analysis to study the ATP7B gene and protein expres-
sion. Cell viability, oxidative stress and apoptosis in presence of Cu
were determined in HepG2 and KO cells. In addition, viability was
determined following Cu exposure and treatment with zinc (Zn), D-
penicillamine (DPA) or both.
Results: The genotype of KO cells showed small deletions adja-
cent to the putative ZFN cutting site indicating the presence of a tar-
geted KO. Analysis of ATP7B cDNA and protein confirmed the
deleterious aberration. KO cells showed normal cell growth, Cu
uptake and release and gene expression as compared to HepG2.
Addition of Cu provoked oxidative stress and apoptosis in KO cells
with significantly lower viability as compared to HepG2. The induc-
tion of metallothionein was significantly reduced in KO cells as
 POSTER SESSION
compared to HepG2 in presence of Cu. Zn and DPA were effective
in rescuing cells against Cu toxicity. DPA alone was more effective
in HepG2 and a synergistic effect of both drugs was observed in the
KO cell line.
Conclusions: We have generated for the first time a stable human
hepatoma ATP7B KO cell line. This cell line represents a human
cell model for WD and will help provide insights on functional anal-
ysis and treatment of ATP7B mutants.
1157
Phenotypic characterization of patients with p.C271*
Wilson[apos]s disease mutation; the most frequent ATP7B
mutation in India
G. Chandhok, A. Zibert, H.H.J. Schmidt, M. Bhatt, A. Aggarwal
(M
unster, Germany)
Objective: To study the phenotype and treatment response in
Indian patients with homozygous p.C271* Wilson[apos]s disease
(WD) mutation.
Background: Phenotypic studies in WD are limited by genetic
heterogeneity. Characterization of high frequency mutation helps
provide insights into disease mechanism and treatment efficacy.
p.C271* mutation, of the ATP7B gene has emerged to be widely dis-
tributed in India.
Methods: 61 patients with WD were screened for ATP7B muta-
tions. WD-related disability was graded by the Global Assessment
Scale for Wilson[apos]s Disease (GAS for WD). All patients
received decoppering treatment and were tracked longitudinally. The
clinical characteristics of patients homozygous for p.C271* mutation
were compared with that of the overall cohort and the known pheno-
type of p.H1069Q.
Results: p.C271* mutation was the most frequent mutation in our
cohort seen in 14/61 patients. Of the 8 patients with homozygous
p.C271*, 5 were men. Mean age of disease onset was 8 years (range
3-14). At onset, 3 patients had liver and 4 had neurological symp-
toms, while 1 was asymptomatic. All 7 symptomatic patients had
compensated cirrhosis and relatively high neurological disability with
elevated GAS for WD tier 1 cognition and/or motor scores and high
total tier 2 scores (mean 22.3 6 9.9). Zinc therapy (alone or with D-
penicillamine/trientine) was used in 4/8 patients and in all led to neu-
rological worsening. All 8 patients tolerated decoppering well. At
follow up, the 1 asymptomatic patient remains symptom free, 6 have
normalized after decoppering for 27 months (range 21-48) and 1
continues to improve. The p.C271* phenotype was comparable to
the phenotype associated with p.E122fs, p.M573fs and p.T977M. In
comparison to common European mutation p.H1069Q, the p.C271*
mutation was associated with earlier disease onset and a more severe
phenotype.
Conclusions: We characterized the phenotype and treatment
response in patients with p.C271*, the major WD genotype in India.
p.C271* mutation was associated with early onset (first decade) of
WD and severe liver and neurological disease. Decoppering treat-
ment was tolerated well and reversed the severe WD-related disabil-
ity. Response to zinc therapy was poor. Clinical data were matched
to in vitro functional analysis of WD hepatic cells as reported else-
where (see other abstracts by Chandhok et al.).
1158
No association of GPNMB rs156429 polymorphism with
Parkinsons disease, amyotrophic lateral sclerosis and multiple
system atrophy in Chinese population
Y. Chen, R. Ou, Q. Wei, B. Cao, X. Chen, K. Chen, B. Zhao, H.
Shang (Chengdu, Peoples Republic of China)
Objective: Analysis the associations between the polymorphism
GPNMB rs156429 and the three neurodegenerative diseases (PD,
ALS and MSA) in a Chinese population.
S451
Background: The rs156429 polymorphism in the glycoprotein
nonmetastatic melanoma protein B (GPNMB) gene was found to be
associated with the risk for PD in caucasian population by genome-
wide association studies (GWAS). Recently, encoded protein,
GPNMB, was identified as a novel neuro-protective factor in amyo-
trophic lateral sclerosis (ALS). In consideration of the overlapping of
clinical manifestations and pathologic characteristics among PD,
ALS, and multiple system atrophy (MSA), the possible associations
of the polymorphism and the three neurodegenerative diseases were
studied in a Chinese population.
Methods: All of the subjects, including PD (n51096), sporadic
ALS (SALS) (n5876) and MSA (n5356) patients, and 829 health
controls (HCs) were included. All subjects were genotyped for this
polymorphism using Sequenom iPLEX Assay technology.
Results: No differences were found in the genotype distributions
and minor allele frequency of GPNMB rs156429 between PD
patients and HCs, between SALS patients and HCs, between MSA
patients and HCs, and between subgroups of PD, ALS and MSA
patients with regard to clinical features such as sex, age of onset,
presence or absence of cognitive abnormality, depression and
anxiety.
Conclusions: Lack of association identified in our study suggests
that GPNMB rs156429 was unlikely to be the cause of ALS, PD and
MSA in Chinese population.
1159
LRRK2 and GBA variants influence rate of motor progression in
Parkinsons disease
M.Y. Davis, C. Johnson, J.B. Leverenz, D. Weintraub, J.Q.
Trojanowski, A. Chen-Plotkin, V.M. Van Deerlin, S. Factor, C.
Wood-Siverio, J.F. Quinn, K.A. Chung, A.L. Peterson-Hiller, L.S.
Rosenthal, T.M. Dawson, M.S. Albert, J.G. Goldman, G.T. Stebbins,
B. Bernard, D. Yearout, S. Hu, B.A. Cholerton, T.J. Montine, K.L.
Edwards, C.P. Zabetian (Seattle, WA, USA)
Objective: To investigate whether genetic variants associated
with Parkinsons disease (PD) susceptibility also influence the rate of
motor symptom progression in PD.
Background: PD is heterogeneous in rate of progression of
symptoms. Genome-wide association studies have identified variants
in multiple loci associated with increased susceptibility to PD. We
investigated whether these variants may also be associated with rate
of motor progression in PD and account for heterogeneity in disease
course.
Methods: Longitudinal data on motor performance (UPDRS and
MDS-UPDRS part III) were obtained from 799 patients enrolled at 6
sites in the US. UPDRS scores were converted to MDS-UPDRS
scores using the calibration method of Goetz et al., 2012. Subjects
were genotyped for 16 variants in 14 susceptibility loci (LRRK2
[G2019S and rs11564273], HIP1R, GAK, TMEM163, HLA, BST1,
MAPT, MCCC1, SLC41A1, RIT2, STK39, RAB25, and SNCA
[REP1 and rs356219]) and complete sequencing of the GBA coding
region was performed. GBA carriers were analyzed as a single group
that included individuals with either pathogenic mutations or the
functional polymorphism E326K. Generalized estimating equations
were used to test for association between genotype and change in
MDS-UPDRS part III score, adjusting for sex, age at examination,
disease duration, and site. Bonferroni correction was used to adjust
for 17 comparisons.
Results: The mean disease duration in the cohort was 8.5 6 5.6
years, the mean duration of follow-up was 3.0 6 1.8 years, and the
mean age at the baseline visit was 67.5 6 9.0 years. LRRK2 G2019S
was associated with a significantly lower annual decline in MDS-
UPDRS III score (p50.001, corrected p [pc]=0.017), while GBA var-
iants were associated with a higher annual decline (p50.0026,
pc=0.044). There was no significant association between change in
MDS-UPDRS III score and any of the other variants examined after
correction for multiple testing.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S452 POSTER SESSION
Conclusions: Our data suggest that motor symptoms progress
more rapidly in PD patients who carry GBA variants, but more
slowly in patients with LRRK2 G2019S. These findings provide evi-
dence that genetic variation influences the heterogeneity in motor
progression observed in PD and serve as a strong rationale for con-
ducting large-scale genetic studies on this topic in the future.
1160
Novel GNAL variant in a Brazilian patient with sporadic
dystonia
P.M. de Carvalho Aguiar, C. Oliveira dos Santos, F.P. da Silva-
Junior, S.C. Azevedo Silva, E.R. Barbosa, V. Borges, M.S.G. Rocha,
H.B. Ferraz (Sao Paulo, Brazil)
Objective: To investigate GNAL variants in Brazilian patients
with dystonia.
Background: GNAL variants have been associated with adult-
onset predominantly cervical dystonia in different ethnical groups. The
protein plays a role in coupling dopamine D1 and adenosine A2A
receptors to adenylyl cyclase, and in histone H3 phosphorylation.
Since mutations in GNAL were first identified as a cause of dystonia,
several works confirmed its role in the development of the dystonia in
distinct ethnic groups, with different prevalences. The role of this
gene in Brazilian dystonia patients has not been determined.
Methods: Peripheral blood DNA was extracted from fifty- one
unrelated Brazilian patients with idiopathic isolated dystonia who
were negative for TOR1A and THAP1 mutations. The two major
GNAL isoforms (NM_182978.3 and NM_001142339) were screened
through Sanger sequencing of all 12 exons and exon- intron bounda-
ries. Non- synonymous variants were also screened in 160 chromo-
somes from healthy Brazilian subjects.
Results: An exon 5 heterozygous variant c.C630A/p.Phe211Leu
(corresponding to c.C443A DT09/p. A148E in isoform
NM_001142339) was identified in a 59 year-old female patient, of Ital-
ian and Portuguese ethnicity, with a history of cervical and laryngeal
dystonia since age 23 and no family history. This variant is highly con-
served, it was not identified in 160 Brazilian control chromosomes or in
the 63000 exomes from the Exome Aggregation Consortium. It is pre-
dicted to be deleterious by three in silico analysis algorithms. We also
identified a novel exon 1 heterozygous variant (isoform NM_182978.3)
in several patients and controls: c.119Cdelins TGGTCCC which substi-
tutes a Proline at position 40 for a Leucine and creates two additional
codons for a Valine and a Proline (p.Pro40delinsLeuValProl), but stays
in frame. Since this variant is frequent, is also present in normal con-
trols and does not cause a frame shift, it is unlikely to be pathogenic.
Conclusions: We identified a novel potential dystonia causative
GNAL variant and this is the first report in the Brazilian population.
Further studies will be carried out in a larger sample to determine
the prevalence and importance of this gene as a dystonia cause in
our population.
Funding sources: Sao Paulo Research Foundation (FAPESP)
grants #2010/19206-0 and 2014/17128-2 (PCA).
1161
Novel compound heterozygous mutations in PRKRA cause pure
dystonia
P. de Carvalho Aguiar, V. Borges, H.B. Ferraz, L.J. Ozelius (Sao
Paulo, Brazil)
Objective: To describe novel PRKRA variants in familial
dystonia.
Background: PRKRA mutations were first described in two Bra-
zilian families with autosomal recessive young- onset dystonia- Par-
kinsonism. Since then, only two other cases have been identified
and, recently, the homozygous p.Pro222Leu variant, originaly
described in two Brazilian families, was identified in a Polish kin-
dred sharing same disease haplotype as the original families. To con-
Movement Disorders, Vol. 30, Suppl. 1, 2015
firm PRKRA as a dystonia cause, it is important to identify different
variants in different ethnical backgrounds who do not carry the origi-
nal disease haplotype.
Methods: Patients: The proband is a 37- year-old Brazilian
woman of Portuguese ancestry, the fifth child of non-consanguineous
parents, diagnosed with a history of focal dystonia since age 4 which
generalized in four years. No Parkinsonian or pyramidal signs were
observed. At first, family history of dystonia was negative. Screen-
ings for TOR1A and THAP1 were negative. Parents and siblings
were examined. Her younger sister, aged 19, had a very subtle dys-
tonic posture in the third and fourth fingers of the left hand and was
rated as possible dystonia. She was not aware of the age of onset. At
age 28 she developed cervical dystonia and marked dysphonia.
When the sibling became affected, the family history was consistent
with possible recessive inheritance, which in turn, led us to screen
PRKRA by sequencing.
Results: In both affected patients, we identified highly conserved
novel variants in exon 2, c.G230C (p.Cys77Ser), and in exon 7,
c.G638T (p.Cys213Phe). A variant affecting the same amino acid
c.T637C (p.Cys213Arg), together with c.C665T (p.Pro222Leu) has
been previously described in a patient with dystonia, whose symptoms
developed after a febrile illness and who had volume loss in the basal
ganglia. All unaffected family members carry a single variant. The
father and two siblings carry the c.G230C variant, the mother carries
c.G638T. None of these variants were found in 240 Brazilian control
chromosomes and only p.Cys213Phe was reported at an extremely
low frequency (7.916e-06) in the Exome Aggregation Consortium.
Three in silico predictions support these variants as disease causing.
Conclusions: Herein we report two novel mutations in siblings
with isolated dystonia confirming PRKRA as a causative disease
gene.
Funding: Sao Paulo Research Foundation (FAPESP) grant #2010/
19206-0 (PA) and NS037409 (LJO).
1162
Novel recruitment strategy to enrich for LRRK2 mutation
carriers
T. Foroud, D. Smith, J. Jackson, J. Verbrugge, C. Halter, L.
Wetherill, K. Sims, W. Xin, V. Arnedo, S. Lasch, K. Marek
(Indianapolis, IN, USA)
Objective: This study was designed to test whether an internet
based approach could be an effective approach to screen and identify
mutation carriers.
Background: The LRRK2 G2019S mutation is found at higher
frequency among Parkinsons disease (PD) patients of Ashkenazi
Jewish (AJ) ancestry. This study was designed to test whether an
internet based approach could be an effective approach to screen and
identify mutation carriers.
Methods: Individuals with and without PD of AJ ancestry were
recruited and consented through an internet based study website
developed as part of the Parkinsons Progression Markers Initiative
(PPMI) study. An algorithm was applied to a series of screening
questions to identify individuals at increased risk to carry the
LRRK2 G2019S mutation.
Results: 1,000 individuals completed the initial screening. 741
qualified for mutation testing and 650 were tested. 72 individuals
carried at least one LRRK2 G2019S mutation; 38 with PD (12.5%)
and 34 without (10.1%). Among the AJ PD participants, each
affected first-degree relative increased the likelihood the individual
was LRRK21 (OR= 4.7; 95% confidence interval 5 (2.4 9.0)). The
same was not observed among the unaffected AJ subjects (p50.11).
Conclusions: An internet-based successfully screened large num-
bers of individuals to identify those with risk factors increasing the
likelihood that they carried a LRRK2 G2019S mutation. A similar
approach could be implemented in other disorders to identify individ-
uals for clinical trials, biomarker analyses and other types of research
studies.
 POSTER SESSION
1163
Association study of GWAS top hits in late-onset Alzheimers
disease with the susceptibility to Parkinsons disease in a Chinese
population
J.F. Guo, Y. Wang, X.X. Yan, B. Tang (Changsha, Peoples Republic
of China)
Objective: The aim of this study was to investigate the AD
GWAS top hits with PD susceptibility in a Chinese han population.
Background: Alzheimers disease (AD) and Parkinsons disease
(PD) are common age-related neurodegenerative disorders. The two
diseases share several clinical and pathologic characteristics; we
therefore explored whether they have overlapping genetic risks.
Methods: 442 PD patients and 454 matched controls were
included in our cohort. We selected 15 single nucleotide polymor-
phisms (SNPs) in 11 genes (APOE, BIN1, CLU, ABCA7, CR1, PIC-
ALM, MS4A6A, CD33, MS4A4E, CD2AP and EPHA1) that were
genotyped using MALDI-TOF mass spectrometry.
Results: 442 PD patients and 454 matched controls were included
in our cohort. We selected 15 single nucleotide polymorphisms
(SNPs) in 11 genes (APOE, BIN1, CLU, ABCA7, CR1, PICALM,
MS4A6A, CD33, MS4A4E, CD2AP and EPHA1) that were geno-
typed using MALDI-TOF mass spectrometry.
Conclusions: These findings implicate that AD GWAS top hits
might not play a major role in the genetic predisposition to PD and
the two diseases may not share a common genetic risk.
1164
Exon dosage analysis of parkin gene in Chinese sporadic
Parkinsons disease
J.F. Guo, X. Dong, X.X. Yan, B. Tang (Changsha, Peoples Republic
of China)
Objective: To clarify the role of parkin exon dosage mutation in
Chinese sporadic Parkinsons disease.
Background: Parkin gene mutations are by far the most common
mutations in both familial Parkinsons disease (PD) and sporadic PD.
Approximately 50% of parkin mutations are exon dosage mutations (i.e.,
deletions and duplications of entire exons). Multiple ligation-dependent
probe amplification(MLPA) is a robust, easy and accurate technique for
detecting gene rearrangements for more than 40 loci in one assay.
Methods: We firstly established a MLPA assay for quick detec-
tion of parkin exon rearrangements. Then, we studied parkin exon
dosage mutations in 755 Chinese sporadic Parkinsons disease
patients using the established MLPA assay.
Results: We designed 16 pairs of probes to detect the parkin exon
rearrangement and optimized the PCR conditions. Using this MLPA
assay, we found there were 25 (3.3%) patients with exon dosage alter-
ations including deletions and duplications, 20 (11.4%) patients with
exon rearrangements in 178 early-onset patients, and 5 (0.86%)
patients with exon rearrangement mutations in 579 later-onset patients.
The percentage of individuals with parkin dosage mutations is more
than 33% when the age at onset is less 30 years old, but less than 7%
when the age at onset is more than 30. In these mutations, deletion is
the main mutation style, especially in exon 25.
Conclusions: We successfully constructed a MLPA assay to
detect exon rearrangement in parkin gene. Our result indicated that
exon dosage mutations in parkin gene may be a main reason for spo-
radic PD, especially in EOP.
1165
Secondary paroxysmal kinesigenic dyskinesia associated with
CLCN2 gene mutation
H.A. Hanagasi, B. Bilgic, T.E.M. Abbink, F. Hanagasi, Z.
Tufekcioglu, H. Gurvit, N. Basak, M.S. van der Knaap, M. Emre
(Istanbul, Turkey)
S453
Objective: To present the clinical features and genetic analysis of
a Turkish patient with paroxysmal kinesigenic dyskinesia with
CLCN2 gene mutation.
Background: Paroxysmal kinesigenic dyskinesia (PKD) is parox-
ysmal involuntary movements which consist of any mixture of dys-
tonic, choreic, and ballistic movements without loss of
consciousness. More recently homozygous or compound-
heterozygous CLCN2 gene mutations have been reported unique pat-
terns of MRI abnormalities in patients with leukoencephalopathies of
unknown origin.
Methods: The patient was a 22-year-old woman with onset of
paroxysmal dyskinesias at the age of 21. Her gestational and perina-
tal history, developmental milestones and motor functions were nor-
mal until the age of 7, at which age she developed mild bilateral
hand tremor. At the age of 21, paroxysmal neck movements emerged
provoked by exercise, consisting of forward leaning and turning of
head, associated with tremor on the left hand and forced closure of
eyes; there was no associated pain. The attacks occurred 3-4 times
per hour and lasted for ten seconds.
Results: Because of the suggestive cranial MR findings, the
analysis involved exons and flanking intronic regions of the
CLCN2 gene by sequence analysis in the patient. The molecular
analysis revealed that the patient is homozygous for the
c.1113delinsACTGCTCAT, p.Ser375CysfsX6 mutation. Both
parents carried the heterozygous c1113delinsACTGCTCAT,
p.Ser375CysfsX6 mutation. This mutation causes a deletion with a
shift in the reading frame, resulting in a premature stop at protein
level.
Conclusions: CLCN2 mutations can present with a PKD syn-
drome. CLCN2 mutations should be added to the list of secondary
causes of PKD.
1166
A novel mutation for McLeod neuroacanthocytosis
V.N. Holiday, A. Hiller (Portland, OR, USA)
Objective: To describe a case of McLeod neuroacanthocytosis
syndrome with a novel gene mutation.
Background: McLeod neuroacanthocytosis syndrome is an X-
linked multisystem disorder characterized by dementia, psychiatric
abnormalities, chorea, seizures, neuromuscular, cardiac, and hema-
tologic abnormalities. The clinical findings and basic lab tests can
lead to the diagnosis, however, immunohematologic and molecular
genetic testing are available for confirmation. The XK gene is the
only gene in which a mutation is known to cause the phenotype of
McLeod syndrome. The majority of mutations are deletions, non-
sense mutations, or splice-site mutations, resulting in an absent or
truncated membrane transport protein XK, suggesting a loss of
function, though the exact function of the XK protein is not
known.
Methods: JP is a 67 year old man with a history of epilepsy
that presented for evaluation of abnormal involuntary movements.
At presentation, the patient reported 2-3 years of chorea involving
the trunk and all extremities. His history was also remarkable for a
gradually progressive personality change, dementia, and long stand-
ing seizure disorder. His neuropsychiatric testing revealed progres-
sive deficits in learning, memory, executive, and psychomotor
functioning. A brain MRI from one year prior to the Movement
Disorder evaluation showed focal atrophy of bilateral caudate
nuclei. The patient had an elevated CK of 1394 and an axonal
motor and sensory neuropathy on nerve conduction study and
EMG. CBC showed acanthocytes. The patient also has atrial fibril-
lation and mild dilated cardiomyopathy. He had no family history
of neurologic disease. Based on history and examination, the
patient was tested for multiple causes of chorea, including genetic
testing for Huntingtons disease, but was ultimately tested for
McLeod neuroacanthocytosis.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S454 POSTER SESSION

Results: Immunohematologic testing revealed RBC type Kx and 1167

weakened expression of the Kell blood group antigens when com-
pared to normal controls, indicating the McLeod phenotype. Exon
sequencing of the XK gene showed normal exons 1 and 3. Exon 2
was homozygous for a deletion of A at position c.475, predicted to
result in a frameshift and premature stop codon. This mutation, at
the time it was detected on September 12, 2014, had not been previ-
ously reported.
Conclusions: This case reports a patient with the characteristic
phenotype for McLeod neuroacanthocytosis syndrome and a newly
described mutation within the XK gene.
The impact of rare variants in FUS and HTR2A in essential
tremor
F. Hopfner, G. Stevanin, S.H. M
uller, E. Mundwiller, M. Bungeroth,
A. Durr, M. Pendziwiat, M. Anheim, S.A. Schneider, L. Tittmann, S.
Klebe, D. Lorenz, G. Deuschl, A. Brice, G. Kuhlenb aumer (Kiel,
Germany)
Objective: We resequenced the coding region of recently
reported genes (FUS, HTR2A) found by exome sequencing in fami-
lial essential tremor (ET). By means of our own studies, several

TABLE 1. Fused in sarcoma (FUS) mutation analysis

AA altering AA altering Poly
Number of ET Number variants in variants in Phen-2 Mutation
Study patients of Controls ET patients controls score SIFT Taster 2
Merner et al. 2012 23 (7 def., 3 450 18 x p. 0 NA NA disease causing
prob., 13 poss.) (Q290 Stop)
Merner et al. 2012 270 single patients 450 1 x p.(R216C) 1 x p. probably tolerated polymorphism
1 x p.(P431L) (Arg216Cys) damaging
Parmalee et al. 2013 116 single patients 262 0 0 NA NA NA
Zheng et al. 2013 180 single patients 273 1 x p.(M392I) 0 benign tolerated disease causing
Labbe et al. 2013 152 familial patients 0 0 NA NA NA NA
Rajput et al. 2013 216 single patients 219 1 x p.(R377W) 0 probably damaging disease
damaging causing
Hedera et al. 2013 52 independent patients 0 0 NA NA NA NA
Ortega-Cubero 178 single patients 0 0 NA NA NA NA
et al. 2013 and familial patients
Hopfner and 85 familial patients 0 0 NA NA NA NA
Stevanin et al. 2014
Mutations in the fused in sarcoma (FUS) gene in eight genetic studies of ET.

TABLE 2. Rare variants in FUS annotated in the exome variant server.

Number of Variants in
general general
Number of population Variants in population
Study ET patients individuals*1 ET patients individuals*2 PolyPhen-2 score SIFT MutationTaster 2
EVS 0 4297 NA 1 x p.(Y25S) probably damaging tolerated disease causing
EVS 0 4297 NA 1 x p.(G40A) possibly damaging tolerated disease causing
EVS 0 4297 NA 1 x p.(S89T) benign polymorphism polymorphism
EVS 0 4297 NA 1 x p.(Q102E) probably damaging damaging disease causing
EVS 0 4297 NA 1 x p.(P106L) probably damaging tolerated disease causing
EVS 0 4297 NA 1 x p.(S110L) benign tolerated polymorphism
EVS 0 4297 NA 1 x p.(S135N) benign tolerated polymorphism
EVS 0 4297 NA 1 x p.(P151L) possibly damaging damaging disease causing
EVS 0 4297 NA 1 x p.(S182F) possibly damaging tolerated polymorphism
EVS 0 4297 NA 1 x p.(G187S) benign tolerated polymorphism
EVS 0 4297 NA 1 x p.(G191S) benign tolerated polymorphism
EVS 0 4297 NA 1 x p.(N263S) probably damaging tolerated disease causing
EVS 0 4297 NA 1 x p.(E278A) possibly damaging tolerated disease causing
EVS 0 4297 NA 1 x p.(G414S) probably damaging tolerated disease causing
EVS 0 4297 NA 1 x p.(P431L) probably damaging damaging disease causing
EVS 0 4297 NA 1 x p.(P450S) probably damaging damaging disease causing
EVS 0 4297 NA 1 x p.(G465E) probably damaging tolerated disease causing
EVS 0 4297 NA 1 x p.(R485W) benig tolerated disease causing
EVS 0 4297 NA 1 x p.(G515S) possibly damaging damaging disease causing
EVS 0 4297 NA 2 x p.(P18S) possibly damaging tolerated disease causing
EVS 0 4297 NA 2 x p.(N63S) benign tolerated polymorphism
*1: The actual number of individuals of European/American descent sequenced for each variant in the EVS varies slightly. Therefore the mean
of all entries was used. *2: these variants were found twice in the EVS data. To avoid overestimation of the mutation frequency in general popu-
lation individuals we performed statistics with one allele only.

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
Fig. 1. (1167).
other studies analysing rare variants in ET and information given in
the exome variant server we estimated the frequency of rare variants
in large patient samples as well as control samples.
Background: ET is often a familial disorder with an autosomal
dominant inheritance pattern. Potentially causative variants in FUS
and HTRA2 have been identified both in a single ET family. Subse-
quent studies assessed the frequency of rare variants in independent
samples and described further putatively causal variants.
Methods: We performed DNA sequencing of FUS in 85 unre-
lated, familial German and French definite ET patients and DNA
sequencing of HTRA2 in 29 familial German ET cases. We critically
analyzed the role of rare variants in ET on the basis of our studies
and previous ones. Fishers exact test was used to test for association
S455
between two categorical variables.The effects of amino acid substitu-
tions on protein function were predicted using the programs
PolyPhen-2, SIFT and MutationTaster 2. Multiple species protein
sequence alignment of FUS was performed using Clustal Omega.
Results: We did not find novel variants affecting the protein
sequence in FUS. We found one exonic missense SNP in HTRA2
(rs72470544, A141S, NM_013247) in a single sample. This SNP had
been mentioned as potentially associated with Parkinsons disease
but was predicted to be benign by softwares assessing functional
SNP effects and has a frequency of 5% in population based controls.
Seven previously published studies and data from the exome variant
server (EVS) showed that rare exonic variants in FUS are most likely
not more frequent in ET than in the general population.
Multiple species amino acid sequence alignment of the FUS gene
shows that both, the variants found in ET patients and the variants
found in general population individuals affect well conserved amino
acids, approximately evenly distributed over the protein. [figure1]
Conclusions: Our findings provide no evidence for a role of rare
genetic variants in the pathogenesis of ET, apart from the initially
published FUS and HTRA2 mutations segregating large tremor fami-
lies. Rare variants known up to date do not play a major role as sus-
ceptibility factors in ET both, for familial ET as well as genetically
complex ET.
1168
Association of MAPT single nucleotide polymorphism with
corticobasal syndrome
C.L. Huang, S.C. Lai, Y.W. Lin, Y.H. Wu-Chou, C.S. Lu, T.H. Yeh
(Taoyuan, Taiwan)
Objective: To examine the association of MAPT single nucleo-
tide polymorphism (SNP) with corticobasal syndrome.
Background: Corticobasal syndrome (CBS) is a rare, progressive
neurodegenerative disorder characterized with asymmetric progres-
sive rigidity, apraxia, limb dystonia and myoclonus, as well as
behavioral and cognitive symptoms. The etiology of CBS is
unknown; however, neuropathological and genetic evidence supports
a pathogenetic role for microtubule-associated protein tau.
Methods: Genetic analysis of eight SNPs within the MAPT
genomic region in 24 patients with CBS and 96 age-matched
controls.
Results: Among the eight SNPs, the rs1800547 polymorphism
which is associated with H2 haplotype is not present in patients or
controls. Two SNPs, rs2435207 and rs2471738, are associated with
CBS with an odd ratio of 2.224 (p50.0301; 95%CI=1.067 to 4.634)
and 2.242 (p50.0331; 95%CI=1.053 to 4.774), respectively. The AT
haplotype of these two SNPs which localized between intron 5 and
intron 11 revealed a significant association with CBS (odd
ratio=2.371; p50.0222; 95%CI=1.11 to 5.066).
Conclusions: Although the sample size was small, our data may
suggest that the MAPT genetic variants are associated with the
increased risk of CBS. The association of rs2435207 and rs2471738
with CBS indicates the important genomic region within exon 6 to
11 of MAPT gene and may support the pathologic finding of 4R tau-
opathy in CBS.
1169
Systematic mutational analysis of glucocerebrosidase gene in a
Parkinsons disease population from Southern Spain
S. Jesus, P. Gomez-Garre, I. Huertas-Fernandez, I. Bernal-Bernal,
M. Bonilla-Toribio, M.T. Caceres-Redondo, F. Carrillo, L. Vargas-
Gonzalez, M. Gomez-Llamas, E. Calderon, M. Carballo, P. Mir (Sev-
ille, Spain)
Objective: Our aim was to determine the involvement of varia-
tions in GBA related to PD and to assess if there are specific clinical
Movement Disorders, Vol. 30, Suppl. 1, 2015
S456 POSTER SESSION
features in PD patients carriers of GBA variations compared to non-
carriers.
Background: Homozygous mutations in glucocerebrosidase gene
(GBA) cause Gaucher disease. It has been showed that heterozygous
patients with GBA mutations have an increased risk to suffer Parkin-
sons disease (PD).
Methods: We included a caucasian cohort of 532 PD patients
and 542 control subject. The genetic assessment was performed by
High Resolution Melting analysis and sequencing for samples which
showed abnormal melting profiles. We analized the found variations
using in-silico analysis. We compared the clinical features between
GBA-carriers and non-carriers in the PD group. We also made the
same analysis in the group carrier of potential pathogenic variants
compared to carriers of potential benign variants based on in-silico
study.
Results: We obtained 39 variations across GBA gene. Fourteen
of them were novel and 12 polymorphisms. The bioinformatic analy-
sis showed a potential deleterious change of function in 9 novel var-
iants. PD patients with variations in GBA were younger at disease
onset and required higher dose of LDOPA equivalent dose. They
also showed more frequently visual hallucinations, dyskinesias,
motor fluctuations, REM sleep behaviour disorders and constipation.
Additionally, the group carrier of potential deleterious variations,
showed more anxiety and cognitive impairment and a trend in
impulse control disorders.
Conclusions: Variations in GBA establish a risk factor in the
development of PD and influence the clinical spectrum of the
disease.
1170
Phenotypic and molecular characterisation of autosomal
recessive spastic paraplegias
E. Kara, J. Hardy, H. Houlden, For the Institute of Neurology HSP
Collaboration (London, United Kingdom)
Objective: 1) To study the frequency and phenotype-genotype
correlations of genetic forms of spastic paraplegia assessed at a large
tertiary reference centre over the course of a decade. 2) To assess
whether mutations in genes causing other Movement Disorders such
as Parkinsons disease are also related with spastic paraplegias. 3)
To functionally characterise SPATACSIN, encoded by SPG11 in
which mutations are the most common cause of autosomal recessive
spastic paraplegia.
Background: Spastic paraplegias are a heterogeneous group of
neurodegenerative diseases with mutations in over 40 genes identi-
fied to date. However, there are still several genes awaiting discov-
ery, and the majority of proteins encoded by genes mutated in
spastic paraplegias have not undergone comprehensive functional
characterisation.
Methods: 1) Screening of a cohort of 80 patients with spastic
paraplegia through Sanger sequencing, Multiplex ligation-dependent
probe amplification (MLPA), whole exome sequencing, targeted
resequencing through the Illumina Trusight exome chemistry panel,
and homozygosity mapping. 2) Biochemistry studies on fibroblasts
derived from 8 patients with mutations in SPG11 and 9 controls. 3)
Functional characterisation of spastic paraplegia genes through
weighted gene co-expression network analysis (WGCNA) that was
applied on an in-house gene expression dataset derived from 101
healthy human brains.
Results: We identified the probable cause of disease in 47
patients (59%). The majority carried biallelic mutations in SPG11
(36%), followed by FA2H (5%), SPG7 (3%), SPG15 (1%), ATL1
(1%), DNMT1 (1%) and SPTBN2 (1%). Several patients carried
mutations in genes previously associated with Parkinsons disease
(DJ-1, ATP13A2), lipofuscinoses (PSAP, TPP1, ATP13A2) and
NBIA (FBXO7, PANK2). Variants of unknown significance were
identified within LRRK2 and GCH1. Autophagy analysis on patient-
derived fibroblasts with SPG11 mutations did not show alterations in
Movement Disorders, Vol. 30, Suppl. 1, 2015
autophagy, contrary to previous findings. WGCNA results corrobo-
rated this finding and suggested a role for SPATACSIN (encoded by
SPG11) in the nucleus, with possible functional links with ALS pro-
teins FUS and TARDBP, spastic paraplegia proteins KIAA0196 and
SPG20, and ATM and POLG.
Conclusions: These findings widen the clinical and genetic spec-
trum of spastic paraplegias and suggest genetic and functional links
with numerous neurodegenerative diseases.
1171
Dopamine receptor (DRD3 rs6280) polymorphism and the risk of
impulse control disorders in an Indian Parkinsons disease
cohort
A. Kishore, S. Moorthy, S. Krishnan, G. Sarma, S. Sarma, M.
Banerjee (Trivandrum, India)
Objective: To test whether allelic variants of dopamine (DRD3),
glutamate (GRIN2B) and serotonin (HTR2A) receptors increase the
risk for impulse control disorder and related behaviors (ICDRB) in
Parkinsons disease (PD).
Background: We previously reported a frequency of 31% of
ICDRB among 305 PD patients on dopamine replacement therapy
(DRT, using standard diagnostic criteria and direct interview. Use of
pramipexole or ropinirole was the sole independent clinical risk fac-
tor (Sarath chandran et al., 2013) for developing ICDRB. Genetic
risk factors are suspected to enhance the risk of ICDRB.
Methods: Two hundred Indian PD patients on DRT (100 ICDRB-
positive and 100 ICDRB- negative) and 118 healthy controls partici-
pated. Genotyping of functionally and pharmacologically relevant
SNP variants of DRD3 rs6280, GRIN2B rs1806201 and HTR2A
rs6280 were carried out in both groups.
Results: Among the 100 ICDRB-positive PD, compulsive buying
was present in 31%, hyper sexuality in 25%, compulsive eating in
20%, punding in 7% and pathological gambling in 6%. More than
one ICDRB occurred in 10%. 5% of healthy controls tested were
ICDRB- positive. The frequency of allelic variants of the glutamate,
serotonin and DRD3 receptors tested in this study did not differ
between PD patients and healthy controls. There was a significant
association of only the DRD3 rs6280 variant (P 5 0.03) with ICDRB.
In DRD3 rs6280 variant, the C allele and CT genotype were
increased in ICDRB- positive PD while T allele and TT genotype
were increased in ICDRB- negative PD. Multivariate analysis con-
trolling for clinical variables showed that pramipexole or ropinirole
use, but not dose or duration of exposure, was a clear independent
risk factor (OR 2.2, P 5 0.02) for ICDRB, while there was a trend
for CT genotype of DRD3 (rs6280) (OR 1.8, P 5 0.06) to increase
the risk.
Conclusions: Use of pramipexole or ropinirole as DRT is a stron-
ger risk factor for developing ICDRB. Contrasting allelic presence in
ICDRB positive and negative patients may suggest variation in intra-
cellular signaling in response to dopamine agonists in the mesolimbic
system in the genetically vulnerable group, thus leading to maladap-
tive reward learning in them.
1172
C9orf72 mutation in a patient with a Movement Disorder
presentation
N. Licking, R. Woltjer, T. Bird, J. Quinn (Portland, OR, USA)
Objective: To present a case of C9orf72 mutation in a patient
with a Movement Disorder presentation.
Background: In late 2011, a repeat mutation of C9orf72 was
found to be the most common genetic cause of fALS and FTD.
While typically patients with this mutation present with motor neu-
ron disease and/or dementia, atypical presentations have recently
been described, including Movement Disorders.
 POSTER SESSION
Methods: Case record review, videotaping, and review of brain
pathology in affected relatives.
Results: The patient is a 63y/o female that presents for evaluation
of involuntary movements. She has a PMHx significant for depres-
sion and ADHD. She has a family history significant for dementia in
her mother and several female maternal relatives in middle age as
well as ALS in two male maternal relatives. The patient did not
have dementia, as she manages her own money and affairs. She was
living alone until a recent shoulder surgery when her daughter
moved in for assistance. Following surgery, the patient was referred
by her physical therapist for evaluation due to the movements. Exam
indicated an animated and tangential female with choreiform move-
ments in the hands and feet. She scored 28/30 on MMSE. MRI brain
in 2008 was read as normal. Initial concern was for Huntingtons
Disease, but genetic testing was negative. C9orf72 was evaluated
and returned positive in this huntington-like presentation.
Brain autopsy results in relatives with FTD were reviewed and
showed tau-negative, ubiquitin-positive, TDP43-positive inclusions in
the hippocampus and cortex. Family members were tested for pro-
granulin mutations and were negative but they had not been tested
for C9ORF72.
Testing for C9orf72 in the patient presenting with chorea was
positive, with greater than 44 repeats.
Conclusions: This patient demonstrates that C9ORF72 mutations
may present as a choreiform disorder, without clinical or radiologic
evidence of FTD. C9ORF72 mutations should be considered in
patients presenting with chorea and negative HD testing, especially
if there is a family history of dementia.
1173
SPG11 mutations cause autosomal recessive axonal Charcot-
Marie-Tooth disease
T. Lo Giudice, C. Montecchiani, M. Di Lullo, M. Mearini, A.
Casella, F. Gaudiello, C. Terracciano, R. Massa, E. Rogaeva, P.H.
St George-Hyslop, J.L. Pedroso, O.G.P. Barsottini, T. Kawarai, A.
Orlacchio (Rome, Italy)
Objective: To perform clinical-genetic analysis in families with
autosomal recessive axonal Charcot-Marie-Tooth disease defined by
clinical, electrophysiological, and pathological assessments.
Background: Mutations in the SPG11/KIAA1840 gene are com-
mon cause of autosomal recessive hereditary spastic paraplegia with
thin corpus callosum and peripheral axonal neuropathy and accounts
for about 40% of autosomal recessive juvenile amyotrophic lateral
sclerosis. The overlap between axonal Charcot-Marie-Tooth disease
and both these disease, as well as the common autosomal recessive
inherited findings of thin corpus callosum and axonal Charcot-Marie-
Tooth in three related patients, prompted us to sequence the SPG11
gene in affected individuals of 28 unrelated families with autosomal
recessive axonal Charcot-Marie-Tooth disease.
Methods: DNA extraction, linkage study, Sanger sequencing,
RFLP analysis, bioinformatics, neurological assessment, diagnostic
imaging, electroneurographic assay, and sural nerve biopsy.
Results: We identified 15 SPG11 mutations in 12 families (two
sequence changes never reported before, p.Gln198X and
p.Pro2212fs). The mutations seemed to be pathogenic since they co-
segregated with the disease in all pedigree and were absent in con-
trols. All known axonal Charcot-Marie-Tooth autosomal recessive
genes (COX6A1, GDAP1, HSPB1, KIAA1985, LMNA, LRSAM1,
MED25, MFN2, NEFL, POLG, and TYMP), genes causing autosomal
recessive hereditary spastic paraplegia with thin corpus callosum and
axonal peripheral neuropathy (SPG7, SPG15, and SPG21), as well as
the causative gene of peripheral neuropathy with or without agenesis
of the corpus callosum (SLC12A6) were screened out. An additional
locus for autosomal recessive Charcot-Marie-Tooth disease type 2H
on chromosome 8q13-21.1 was excluded by linkage analysis. Pedi-
grees originated in Italy, Brazil, Canada, England, Iran, and Japan.
In addition to axonal Charcot-Marie-Tooth disease, affected individu-
S457
als of one Italian family showed thin corpus callosum with mental
retardation.
Conclusions: Our results indicate that SPG11 is the causative
gene of a wide spectrum of clinical features, including autosomal
recessive axonal Charcot-Marie-Tooth disease.
1174
Exome sequencing in 25 index cases of congenital mirror
movements
A. Meneret, E.A. Franz, O. Trouillard, R.J.M. Gardner, C. Depienne,
S.P. Robertson, E. Roze, D. Markie (Paris, France)
Objective: To identify new causative genes of congenital mirror
movements.
Background: Congenital mirror movements constitute a rare dis-
order characterized by isolated involuntary movements of one side of
the body that mirror intentional movements on the opposite side.
Two causative genes, DCC and RAD51 (and one unconfirmed gene,
DNAL4) have been found so far, but they only account for 35% of
the 48 reported cases.
Methods: International cases were collected over a period of 5
years in France and New Zealand. Exome sequencing was carried
out in 25 index cases of congenital mirror movements (8 familial
and 17 sporadic) without mutations in either DCC or RAD51. Fur-
thermore, rearrangements of these genes were excluded in 14 of the
cases.
Results: Rare variants were found in several good functional can-
didate genes, and selected for statistical analyses and functional stud-
ies. In addition, genetic heterogeneity of congenital mirror
movements was further confirmed by the lack of a common candi-
date gene for all non-DCC non-RAD51 cases.
Conclusions: Our data suggests the involvement of several prom-
ising candidate genes in congenital mirror movements. Confirmation
of one or more of these genes will further our understanding of the
processes involved in the lateralization of motor control.
1175
A missense mutation in the KCTD17 gene causes autosomal
dominant myoclonus-dystonia
N.E. Mencacci, I. Rubio-Augusti, A. Zdebik, F. Asmus, M. Ludtmann,
A.K. Hauser, V. Plagnol, A. Pittman, S. Bandres-Ciga, M. Soutar, K.
Peall, H. Morris, D. Trabzuni, M. Ryten, M. Tekman, H. Stanescu,
R. Kleta, M. Carecchio, N. Nardocci, B. Garavaglia, E. Lohmann, A.
Weissbach, C. Klein, J. Hardy, A.Y. Abramov, T. Foltynie, T. Gasser,
K.P. Bhatia, N.W. Wood (London, United Kingdom)
Objective: To identify the genetic cause in a four-generation
British kindred with multiple individuals affected with myoclonus-
dystonia (MD), in which mutations in the e-sarcoglycan (SGCE)
gene had been excluded.
Background: MD is a rare Movement Disorder characterized by
a variable combination of non-epileptic myoclonus and dystonia.
Mutations in SGCE are the most common genetic cause of familial
MD, however they are detected in only 30-50% of cases.
Methods: We performed genome-wide linkage analysis in 7
affected individuals, 5 unaffected and 4 spouses. The two most dis-
tantly related affected individuals underwent exome sequencing.
Sanger sequencing of the entire KCTD17 coding region was subse-
quently performed in other 76 unrelated SGCE negative familial MD
cases. Screening of exon 4 of the KCTD17 gene was performed in
another 400 sporadic cases.
Results: Seven individuals in the index pedigree displayed signs
of MD. Age of onset ranged from 5 to 20 years and all cases initially
presented with myoclonic jerks. Dystonia showed a progressive
course with aging, with increasing severity of symptoms and spread-
ing from the cranio-cervical district to other sites.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S458 POSTER SESSION
Parametric multipoint linkage analysis and haplotype reconstruc-
tion identified a single peak on chromosome 22 segregating with the
disease (maximum LOD score 2.4). Exome sequencing revealed the
novel change c.434 G>A; p.R145H as the only possibly pathogenic
variant in the linked chromosome interval. Screening of a large
cohort of SGCE negative MD cases revealed the same mutation in
the index case of a dominant German family. The variant is absent
in 2,000 internal controls and in further 61,000 exomes reported
in the Exome Aggregation Consortium database.
KCTD17 is abundantly expressed in all brain regions with the
highest expression observed in the putamen and thalamus. Functional
studies using calcium imaging in case and control fibroblasts demon-
strated abnormalities in the endoplasmic-reticulum-dependent cal-
cium signalling.
Conclusions: We demonstrate that a missense mutation in the
KCTD17 gene is a novel cause for autosomal dominant MD. This
finding broadens the spectrum of human diseases associated with
mutations in the members of the KCTD gene family. Functional
insight into the role of KCTD17 and the pathogenic effects of the
R145H mutation will shed light onto the mechanisms leading to the
abnormal neuronal activity underlying MD.
1176
Methodology for assessment of genetic-environmental interaction
in epigenesis of early onset Parkinsons disease in Arab ancestry
A.A. Peer Zada, S. Nahrir, J.A. Bajwa (Riyadh, Saudi Arabia)
Objective: Comprehensive PD genetic analyses in Saudi Arabia
are lacking and we therefore, aim to assess the genetic-
environmental interaction interplay of early onset Parkinsons disease
(EOPD) among PD cohort of Arab ethnicity registered in Movement
Disorders database at King Fahad Medical City, Riyadh, Saudi
Arabia.
Background: Background and results: Parkinsons disease (PD)
is a neurodegenerative disorder that is recognized to have genetic
and epigenetic etiology linked to either familial forms of the disease
or to a majority sporadic idiopathic forms. Our epidemiological data
revealed a higher trend of EOPD with a prevalence of 30%. In
EOPD group (age <50y) low vitamin D (<50mmol/L) was seen in
16 out of 34 patients (66.7%). 20% of the PD patients had first
degree relative with the same disease, supporting the interplay of
consanguinity and genetic predisposition as risk factors for the dis-
ease. Molecular analyses in Saudi patients presenting with different
clinical phenotypes have revealed a number of novel variants of
known or unknown clinical significance. For example, whole exome
sequencing of a patient presented with delayed motor milestones,
delayed speech and intellectual disability with neurological deteriora-
tion detected a homozygous novel variant in the RRM2B gene and
in the PDSS2 gene, and heterozygous novel variants in the KRITI
and in the MTFMT. Other patients with Joubert syndrome, methyl-
malonic acidemia, multiple epiphyseal dysplasia revealed known and
novel variants in the CC2D2A gene, in the MMAA gene and in the
COL2A1 gene.
Methods: Whole exome sequencing will be performed for the
identification of rare and novel causal variants in the Saudi patients
presenting with EOPD. For EOPD and epigenetic studies, a combina-
torial approach utilizing next generation sequencing technology on
selected cases of PD fulfilling the inclusion criteria, quantitative real-
time and bisulfite PCR, bioinformatics and biostatistics pipeline will
be employed. This data will be analyzed in reference to multidimen-
sional epidemiological data to generate clinical epigenetic relevance.
Results: It is our expectation and an educated-guess hypothesis to
find novel variants in EOPD based on above observations.
Conclusions: In summary, our study will pave the way forward
in advancing our knowledge and open a new era of genetic and epi-
genetic research in PD of the Arab ancestry.
Movement Disorders, Vol. 30, Suppl. 1, 2015
1177
The Contursi family 20 years later: Intrafamilial variability in a
kindred with A53T mutation of SCNA gene
L. Ricciardi, S. Petrucci, D. Di Giuda, M.C. Sensi, F. Cocciolillo,
M. Ginevrino, E.M. Valente, A. Fasano (London, United Kingdom)
Objective: We here describe intrafamiliar variability of a branch
of the Contursi kindred.
Background: A53T mutation of SNCA gene was the first muta-
tion described in genetically inherited Parkinsons disease (PD). It
was initially discovered in an Italian family (the Contursi kindred)
and was subsequently identified in families of other origins.
Methods: We systematically assessed 17 family members belong-
ing to a four-generation family segregating the A53T mutation.
Motor, non-motor (cognitive, psychiatric and behavioural) and instru-
mental (olfaction assessment and DAT SPECT) profiles were
evaluated.
Results: We identified 6 carriers of SNCA A53T mutation. Four
were affected by PD (1 female; mean age: 42 6 9.8 years) and 2
were clinically unaffected (1 female, mean age 29.5 6 2.1 years). PD
patients had a mean age at disease onset of 32.7 6 10.5 years and
mean disease duration of 9.2 6 8.5 years. Although they all presented
typical PD with an initial good response to dopaminergic therapy
and early motor complications, they showed a marked intra-familial
variability of the clinical phenotype. Two of them were siblings; at
the study time, 19 and 14 years respectively after disease onset, they
presented with severe motor symptoms, mainly akinesia, gait disor-
ders and postural instability partially responding to levodopa and
deep brain stimulation of subthalamus (one case). They were
demented, depressed, apathetic and totally dependent. One had ortho-
static hypotension and urinary dysfunction.
The remaining 2 patients were mother and son; they both had 2
years of disease duration. She had moderate motor symptoms, mainly
bradykinesia with a good response to therapy and mild motor fluctu-
ations. The mother showed moderate cognitive impairment and
depression. Her son had moderate motor symptoms, he showed a
mild, isolated executive dysfunction and behavioural disorders
(punding).
The two unaffected carriers did not present any sign nor refer any
symptom of PD; they had neither neuropsychological nor psychiatric
alterations. Interestingly, olfaction was altered in all evaluated sub-
jects (patients and asymptomatic carriers).
Conclusions: We described the clinico-instrumental findings of a
branch of the Contursi kindred. This marked intra-familial expression
of A53T emphasizes the role of genetic modifiers also in familiar
PD linked to SCNA point mutations, as recently described for gene
duplications.
1178
Exome association study and 2nd SNP-GWAS of Japanese
Parkinsons disease
W. Satake, Y. Ando, M. Suzuki, H. Tomiyama, Y. Nagai, K.
Kashihara, S. Murayama, H. Mochizuki, K. Nakashima, K.
Hasegawa, A. Takeda, K. Wada, S. Tsuji, M. Yamamoto, M. Murata,
N. Hattori, T. Toda (Kobe, Japan)
Objective: To identify rare and common variants with sporadic
Parkinsons disease (PD)-risks.
Background: Sporadic PD is a complex disorder caused by mul-
tiple genetic variants. We previously reported a SNP-GWAS
(Genome-Wide Association Study) which detected 4 sporadic PD-
risk loci; PARK16, BST1, a-synuclein, and LRRK2 (Satake et al,
Nature Genet 2009). To identify further rare and common variants
with sporadic PD-risks, we performed 2 genomic studies; (A) Exome
Association Study and (B) 2nd SNP-GWAS.
Methods: (A) To search for rare-variant risks, we performed
whole exon (exome) sequencing of 755 sporadic PD patients using
HiSeq2500. (B) To identify further common-variant risks, we
 POSTER SESSION
performed Japanese 2nd SNP-GWAS (1,948 cases and 28,990 con-
trols), which expanded our previous one.
Results: (A) Average depth of our data was x 126, and 94.4% of
whole exon sequence was covered by >10 reads. Using data of 625
PD cases and 961 controls, we tested association between PD and
exonic variants within the 4 PD-loci (PARK16, BST1, a-synuclein,
and LRRK2). We detected 2 nonsynonymous variants with moderate
PD-risk (P=10-4) within LRRK2. But, within the other 3 PD-loci,
we detected no nonsynonymous variants with moderate PD-risk, sug-
gesting that these 3 PD-loci contribute to the disease as common var-
iants. (B) We identified a novel PD-risk locus with P < 5 3 10-8.
Expression level of a gene within the locus is reduced when the risk
SNP exists. In a fly model, knockdown of the gene worsen moter
function.
Conclusions: (A) We are now analyzing association between
whole exonic variants and PD to identify novel rare-variant risks for
PD. (B) Our genomic and in-vivo model data show that this gene is
a novel PD-risk.
1179
Association analysis of the GRN rs5848 and MAPT rs242557
polymorphisms in Chinese patients with PD, ALS and MSA
H. Shang, Y. Chen, B. Cao, X. Chen, B. Zhao, Q. Wei, R. Ou, X.
Guo (Chengdu, Peoples Republic of China)
Objective: Investgate the associations between polymorphisms
GRN rs5848 and MAPT rs242557 and these three neurodegenerative
diseases (PD, ALS and MSA) in a Chinese population.
Background: Recently, genome-wide association studies found
that granulin gene (GRN) rs5848 and microtubule-associated protein
tau gene (MAPT) rs242557 polymorphisms strongly increase the risk
of Alzheimer disease (AD). However, the results of association stud-
ies between the two polymorphisms and Parkinsons disease (PD)
were inconsistent. Considering that the clinical manifestations and
pathological characteristics overlap between AD, PD, amyotrophic
lateral sclerosis (ALS), and multiple system atrophy (MSA), the pos-
sible associations between the two polymorphisms and three neuro-
degenerative diseases (ALS, PD and MSA) were studied in a
Chinese population.
Methods: A total of 1270 PD patients, 887 sporadic ALS (SALS)
patients, 360 MSA patients and 830 healthy controls (HCs) were
studied in this study. All subjects were genotyped for the two poly-
morphisms using Sequenom iPLEX Assay technology.
Results: Minor allele T of GRN rs5848 diseased the risk for
PD in a dominant genetic model (OR: 0.81, 95%CI: 0.68-0.97,
P=0.0227). No differences were observed in the genotype distribution
and minor allele frequency (MAF) of MAPT rs242557 between PD
and HCs. In addition, no significant differences were found in the
genotype distributions and MAFs of the two polymorphisms between
SALS and HCs or between MSA and HCs. No significant differences
were found between subgroups with regard to the clinical presenta-
tion, such as sex, onset symptoms, absence or presence of cognition
impairment, anxiety or depression, in PD, SALS and MSA.
Conclusions: Our results show that GRN rs5458 may decrease
the risk for PD in Chinese population. These two AD susceptibility
locus discovered by GWAS contribute little to the observed epidemi-
ological association between the PD, ALS and MSA.
1180
A novel tau mutation, p.K317N, and globular glial tauopathy
P.M. Tacik, M. DeTure, W.L. Lin, M. Sanchez Contreras, A. Wojtas,
K.M. Hinkle, S. Fujioka, M.C. Baker, R. Walton, Y. Carlomagno, P.
Brown, A. Strongosky, N. Kouri, M.E. Murray, L. Petrucelli, K.A.
Josephs, R. Rademakers, O. Ross, Z. Wszolek, D.W. Dickson
(Jacksonville, FL, USA)
S459
Objective: To look for a genetic etiology of globular glial tauop-
athy (GGT) and to better characterize this entity.
Background: GGT is a group of 4-repeat tauopathies neuropatho-
logically characterized by tau-positive globular glial inclusions that
include globular oligodendroglial inclusions (GOI) and globular
astrocytic inclusions (GAI). GAI are mostly negative on Gallyas
sliver staining. To date 30 cases with GGT have been reported and
none has a known genetic etiology.
Methods: Six patients with GGT were screened for mutations in
microtubule-associated protein tau (MAPT) gene using Sanger
sequencing. Clinical, genealogical, neuropathological data were col-
lected. Biochemical and functional studies included Western blots,
microtubule and tau filament assembly.
Results: Three patients had a positive family history of dementia,
including one with a novel p.K317N variant. There were 4 men and
2 women with a mean age of death of 73 years (55-83 years), mean
age of onset of 66 years (50-77 years) and mean disease duration of
7.2 years (5-14 years). Early symptoms included frontotemporal
dementia (n54), corticobasal syndrome (n51) and short-term mem-
ory decline (n51). Later, all patients developed Parkinsonian fea-
tures, in 4 dopaminergic drugs were tried and were not beneficial.
All patients were homozygous for the MAPT H1 haplotype. Western
blots of detergent-insoluble brain fractions showed predominance of
4R tau isoforms. Recombinant p.K317N tau showed a reduced ability
to promote tubulin polymerization. When assessed using electron
microscopy, the mutation decreased 3R tau filament assembly and
increased 4R tau assembly.
Conclusions: The p.K317N variant is pathogenic. Sequencing of
MAPT should be considered in patients with GGT and a family his-
tory of dementia or atypical Parkinsonism. Since several individuals
in our series had a positive family history but no MAPT gene muta-
tion, other genetic factors may play a role in disease pathogenesis.
1181
Juvenile Parkinsonism and epilepsy due to homozygous
mutations in DNAJC6
P. Termsarasab, T.S. Pearson (New York, NY, USA)
Objective: To describe the seventh case of juvenile Parkinsonism
(JP) and epilepsy associated with mutations in DNAJC6 .
Background: DNAJC6 mutations have been reported as a cause
of autosomal recessive (AR) JP in six cases from two families.1, 2
Clinical features include JP with onset early in the second decade,
relatively rapid disease progression, epilepsy including absence and
generalized tonic-clonic seizures (GTCS), pyramidal signs, and cog-
nitive impairment. Parkinsonism was responsive to levodopa in
some2 but not all cases.
Methods: Case report and literature review.
Results: A daughter of consanguineous Puerto-Rican parents pre-
sented at age 14 with progressive gait disturbance. She had a history
of infantile motor developmental delay and hypotonia, and seizure
onset at 12 months. The first seizure was characterized by staring,
and she later developed GTCS at age 12 years. She had longstanding
intellectual disability, and at age 10, developed unsteady gait, falls,
stooped posture, slowness of movements, drooling and dysarthria.
Examination at age 14 revealed Parkinsonism with rest and postural
tremor in the upper limbs, left greater than right rigidity, and action
dystonia of both hands. MRI brain demonstrated subtle generalized
cerebral atrophy.
Whole exome sequencing revealed homozygous point mutations
in exon 16 in DNAJC6 (c.2116C>T, p.Arg806Stop). Both asymp-
tomatic parents had one allele with the same mutation, and a coinci-
dental heterozygous mutation (C1313X) in LRRK2 was identified in
the patient and her asymptomatic father.
Levodopa was started and increased to 150 mg/day with improve-
ment in tremor, sialorrhea and gait. She developed aggressive behav-
ior at 200 mg/day, which resolved with quetiapine 25 mg/day. Over
Movement Disorders, Vol. 30, Suppl. 1, 2015
S460 POSTER SESSION
the next 2 years, she developed restless limb movements and dyski-
nesias at peak-dose.
Conclusions: Mutations in DNAJC6 cause levodopa-responsive
AR-JP. Important phenotypic clues are co-existing mental retardation
and epilepsy.
References:
1. Edvardson S, Cinnamon Y, Ta-Shma A, et al. A deleterious
mutation in DNAJC6 encoding the neuronal-specific clathrin-uncoat-
ing co-chaperone auxilin, is associated with juvenile Parkinsonism.
PLoS One 2012;7:e36458.
2. Koroglu C, Baysal L, Cetinkaya M, Karasoy H, Tolun A.
DNAJC6 is responsible for juvenile Parkinsonism with phenotypic
variability. Parkinsonism Relat Disord 2013;19:320-324.
1182
Gene expression in rat brain by GSM900 MHz
N.K. Tiwari, V.P. Sharma, A. Pathak (Barabanki, India)
Objective: To examine the gene expression in rats brain, treated
by non-ionizing electromagnetic radiation from 900MHz-GSM
mobile phone was the main aim of this study.
Background: As studies supported electromagnetic radiation may
cause membrane leakage due to loss of calcium. Membrane leakage
of lysosomes release DNAase which explains the fragmentation of
DNA seen in cells exposed to mobile phone signals. Damage to
DNA is a fundamental mechanism for developing tumors and cancer.
The possibility of retaining mutations and cancer starting depends on
when DNA damage exceeds the rate of DNA repair. DNA damage
in brain cells can affect neurological functions and also possibly lead
to neurodegenerative diseases.
Methods: In this study, we investigated whether an exposure of
GSM-900 MHz irradiation from the Mobile Phone (3hours/day up to
28 days) could lead to the modulation of gene expression pattern in
the rat brain. All rats were habitualised for one week prior to start
the experiment in well designed circular mobile phone exposure
(CCPE) cage. CCPE cage was specially designed for EMR exposure
by mobile phone on the rats in the natural environment and it placed
inside the exposure room where other electric appliances were not
installed. In the cage, mobile phone was placed in the center and rats
were allowed to move around the device within 10 cm. radius. After
28 days, mRNA from the brain of control, sham and GSM-900 MHz
exposed rats were isolated and subjected to Quantitative Real time
Polymerase Chain Reaction (qRT-PCR) array analysis. Gene expres-
sion was measured and expressed in fold change as described by
Bandhyopadhay et.al. (2006). The qRT-PCR was performed by using
Sybr green chemistry on ABI 7900HT platform. The real time quan-
tification of amplification was done by measuring change in fluores-
cence by SDS2.3 software and further analyze by RQ manager.
Results: The results obtained from this study had shown that
there was no significant change in expressions of genes involved in
DNA damage and repair pathways such as chromatin assembly
(CHAF1A), DNA damage checkpoints (Chk1), DNA synthesis
(POLD1), post-transcriptional processes (RBM4), translation synthe-
sis (POLI) and stress signaling (Hsp90) as compared with controls.
Conclusions: Study concludes that mobile phones acute expo-
sure (GSM900MHz) does not support for genes expression involved
in DNA damage and repair pathways.
1183
C9orf 72 repeat expansions in a Canadian provincial cohort
A. Venkitachalam, S. Hume, S. Ashtiani, S. Christian, O.
Suchowersky (Edmonton, AB, Canada)
Objective: To determine the referral indication, family history
and clinical test sensitivity of C9orf72.
Background: The Chromosome 9 open reading frame 72
(C9orf72) gene, located on chromosome 9p21 contains a hexanucleo-
Movement Disorders, Vol. 30, Suppl. 1, 2015
tide GGGGCC repeat located in a non-coding region. Normal range
is 2 to 23 repeats, with repeats greater than 30 considered patho-
genic. These are inherited in an autosomal dominant fashion. Repeats
between 23 to 30 are of intermediate significance. Research has dem-
onstrated this repeat expansion as the most common cause of familial
Amyotrophic Lateral Sclerosis (ALS) and Fronto- Temporal Demen-
tia (FTD) with a worldwide incidence of 34% and 25% respectively.
Clinical testing for this expansion became available in Alberta in
January 2013. All testing for C9orf72 mutations in Alberta is per-
formed in one laboratory at the University of Alberta in Edmonton.
Methods: Using the Molecular Diagnostic laboratory database,
we identified all requests for C9orf72 testing and reviewed patient
data.
Results: To date, 59 patients (35 men, 24 women) have been
tested, 35 for ALS, 13 FTD, 4 Atypical Parkinsonism and 4 Late
onset ataxia (LOA). Family history was positive in 27 patients (14
ALS, 7 FTD, 3 Atypical Parkinsonism and 3 LOA). C9orf72 abnor-
malities were detected in 10 patients (7 ALS, 3 FTD); all had a posi-
tive family history. In the FTD phenotype, 1 pathogenic expansion, 1
homozygous expansion and 1 intermediate expansion were detected.
In the ALS phenotype, 1 deletion and 6 pathogenic expansions were
detected. No mutations were detected in the Atypical Parkinsonism,
LOA phenotypes and sporadic cases.
Conclusions: C9orf72 abnormalities were detected in 17% of
total cases, with 23% positive in ALS and 20% positive in FTD,
similar to rates seen in Western European populations. Lack of fam-
ily history significantly decreases the possibility of a positive result.
1184
Interaction between SNCA, LRRK2 and GAK increases
susceptibility to Parkinsons disease in a Chinese population
W. Yu, N. Li, L. Chen, L. Wang, E.K. Tan, R. Peng (Chengdu,
Peoples Republic of China)
Objective: To explore the gene-gene interaction between SNCA,
LRRK2 and GAK.
Background: Single nucleotide polymorphisms (SNPs) of SNCA,
LRRK2 and GAK have been identified as risk factors for Parkinsons
disease (PD). The expression of SNCA and neurotoxicity of alpha-
synuclein are affected by LRRK2 and GAK.
Methods: We conducted a gene-gene interaction analysis of 4
SNPs (rs356219, rs7304279, rs2046932 and rs1564282) of SNCA,
LRRK2 and GAK in a Chinese PD patient-control series (534
patients and 435 controls). Multifactor Dimensionality Reduction
(MDR) analysis was carried out.
Results: The MDR analysis showed a significant gene-gene inter-
action between the rs356219 of SNCA, rs2046932 of LRRK2 and
rs1564282 of GAK. This interaction showed a maximum consistency
(10/10) and high testing balanced accuracy (0.6059).The combination
of the three SNPs was associated with a 5 times increased risk of PD
TABLE 1. Comparison of best models, prediction
accuracies, cross-validation consistencies, and P values for
Parkinsons disease (PD) identified by multiple dimension
reduction (MDR)
Training Testing Cross-
balanced balanced Validation Testing
Model accuracy accuracy consistency P value
1 0.5954 0.5954 10/10 0.0541
12 0.6143 0.6091 10/10 0.0309
124 0.6208 0.6059 10/10 0.0366
1243 0.6227 0.5933 10/10 0.0648
SNCA-rs356219, LRRK2-rs2046932, LRRK2-rs7304279 and GAK-
rs1564282 are symbolized as 1-4, respectively.
 POSTER SESSION S461

TABLE 2. Associations between Parkinsons disease and acching the deeper stages of sleep. Still, when analyzing the pattern
different combinations of genotypes of muscle activity the morning soon after the nigh-sleep we found
that nearly 70% of patients had improvement of dystonic movements
LRRK2, tested either objectively (EMG traces) and subjectively (visual ana-
GAK, SNCA PD HC P value OR(95%CI) logue scale).
Conclusions: Patients with dystonia had important sleep disrup-
26 54 - 1(reference) tion with low sleep efficiency. Even if nocturnal sleep was impaired,
1 14 14 0.099 2.077(0.865 4.988) they did not report excessive daytime sleepiness. Dystonic spasms
1 6 3 0.043 4.154(0.962 17.935) persisted during all the sleep stages, although progressively decreas-
1 284 246 0.0004 2.938(1.457 3.945) ing while reaching slow-wave sleep. Dystonia improved after night-
11 99 64 0.00003 3.213(1.828 5.645) sleep.
11 1 0 0.155 1.038(0.964 1.118)
11 49 24 0.000019 4.240(2.156 8.339)
111 17 6 0.000386 5.885(2.076 16.677) 1186
One-risk genotype 304 263 0.000405 2.401(1.462 3.943)
Implementing a Delphi panel to improve understanding of
Two-risk genotype 149 88 0.000002 3.517(2.056 6.016)
patient characteristics of advanced Parkinsons disease
Key: PD, Parkinsons disease; HC, Healthy Controls; OR, odds ratio; A. Antonini, P. Odin, L. Kleinman, A. Skalicky, T. Marshall, K. Sail,
CI, confidence interval; 1,risk genotype; , non-risk genotype. K. Onuk (Venice, Italy)
Objective: To reach consensus among physicians treating patients
(OR=5.89, 95%CI: 2.08, 16.68; P<0.000), whereas a single risk with Parkinsons disease (PD) regarding key patient characteristics
genotype had only a 2.4 times increased risk (OR=2.40, 95%CI: that indicate transition to advanced PD (APD) and need for advanced
1.46, 3.94; P<0.000). therapy.
Conclusions: We demonstrated for the first time that SNPs in Background: There is a need for improved understanding around
SNCA, LRRK2 and GAK interacted with each other to confer an how physicians determine when a patient is transitioning or reaches
increased risk of PD. The risk alleles had a cumulative effect with advanced disease as there are no definitive diagnostic criteria to iden-
the highest risk associated with those who carry a 3-risk genotype tify APD.
and the lowest risk in those with a single risk genotype. Methods: A modified Delphi panel approach was utilized to syn-
thesize the opinions of PD clinical experts and build consensus by
means of a structured process using questionnaires and controlled
opinion feedback. The Delphi panel consisted of 17 neurological
Phenomenology and clinical assessment of experts located in Europe with experience treating patients with PD
Movement Disorders and experience with APD treatments. The panel was led by a steer-
ing committee of three key opinion leaders in PD. Two rounds of
data collection were obtained using open ended and close ended
questions by administering an online survey. Consensus was
1185 achieved if greater or equal to seventy percent of the panelists
Modulation of dystonia during sleep responded to a single response option or two or more ordinal scale
response options that could be aggregated.
E. Antelmi, R. Ferri, K. Bhatia, F. Mignani, C. Scaglione, F.
Results: Panelists represented different countries across Europe
Provini, P. Martinelli, R. Liguori (Bologna, Italy)
and had extensive years of experience treating PD patients (mean:
Objective: To record the activity on dystonic muscles during all 24.8 6 7.2 years). Consensus on definite indicators for transition to
the sleep stages. APD included moderate levels of troublesome motor fluctuations and
Background: There is the general belief that dystonia disappears dyskinesia and wearing off symptoms every two to three hours. Pan-
during sleep. However, polysomnographic (PSG) studies document- elists further agreed that 2-4 hours of off-time and 1-3 hours of dys-
ing this assumption clearly lack. kinesia are definite indicators of transition to APD. In addition, there
Methods: We prospectively recruited 20 patients affected by idio- was consensus regarding non-motor symptom indicators such as
pathic adult-onset cervical dystonia and 10 age-matched healthy vol- moderate levels of nighttime sleep disturbances, apathy, dementia,
untaries. Patients were investigated by means of history taking and hallucinations without insight and psychosis. Troublesome dyskine-
neurological examination. Both patients and subjects were investi- sias and wearing off periods were seen as important indicators for
gated by means of clinical interview and validated questionnaires for need for advanced therapy.
subjective sleep complains, excessive daytime sleepiness, sleep- Conclusions: Motor fluctuations, wearing off and specific non-
related movements disorders and mood complains. Both patients motor symptoms were definite indicators for transition to APD. Iden-
and subjects underwent PSG scheduled on individual habitual bed- tifying indicators for transition to APD will enable physicians to
time. Patients underwent PSG after 3 months from the last botulinum have earlier discussions with patients regarding APD and advanced
toxin injections. PSG montage included electroencephalogram, elec- treatment options.
trooculogram, submental electromyogram (EMG), surface EMG of
the anterior tibial muscles, thoracic and abdominal sensors, transcuta-
neous oximetry, electrocardiogram, and infra-red camera. Additional 1187
superficial EMG leads have been putted bilaterally on the muscles of Levodopa responsive Parkinsonism in a subject affected by
the cervical district. facioscapulohumeral muscular dystrophy 1
Results: Patients (10 females) had a mean age of 50 years 6 10, S. Beniaminov, M. Paucar, P. Svenningsson (Stockholm, Sweden)
a mean disease duration of 8 years 6 5 and a moderate diseases
severity. Questionnaire-based interviews cannot disclose any signifi- Objective: To characterize a subject affected by FSHD1 and
cant subjective sleep problems or mood disorders. When evaluating coexisting L-dopa responsive Parkinsonism.
PSG recordings we found a disrupted sleep pattern with reduced Background: Facioscapulohumeral muscular dystrophy (FSHD)
sleep efficiency. The analysis of the EMG traces from neck muscles is an autosomal dominant muscle disease. Two forms of this disease
discolsed that in the patients group EMG activity persisted throught are recognized: FSHD1 which constitutes almost 95% of cases and is
all the night, althought showing a progressive decrease while appro- caused by contractions of the D4Z4 allele in chromosome 4q35 and

Movement Disorders, Vol. 30, Suppl. 1, 2015

S462 POSTER SESSION
FSHD2 (5% of cases) caused by mutations in SMCHD1. The normal
D4Z4 allele spans between 11 and 100 repeat units while FSHD1
subjects have between 1 to 10 repeat units in this allele. Only one
FSHD case and cervical dystonia has been reported so far.
Methods: Clinical work-up and genotype of one FSHD subject.
Results: The subject is a 68 years old Swedish woman with a fam-
ily history of FSHD1 with debut of symptoms consistent with this
condition at the age of 55. A targeted mutation analysis revealed one
4 repeat units in the contracted D4Z4 allele in chromosome 4q35.
Seven years later the subject started to notice insidious resting tremor
predominantly on the left side, back pain, stiffness, walking difficul-
ties, freezing of gait, leg weakness, benign visual hallucinations and
RBD. Upon examination bradykinesia, mild rigidity and hypomimia
and anosmia were found besides FSHD features. MRI of her brain at
the age of 66 years was normal but dopamine transporter (DAT) imag-
ing revealed significant and presynaptic dopaminergic loss. Her Par-
kinsonism, incl tremor and back pain, responded to treatment with l-
dopa (current dosage 100 mg q.i.d.), ropinirol (4 mg o.i.d) was added
later. Her visual hallucinations receded after introducing quetiapine.
Conclusions: Whether the occurrence of l-dopa responsive Par-
kinsonism is coincidental in this case or an underdiagnosed feature
of FSHD1 remains to be determined. RBD may predict a synuclein-
opathy in this case. The predominant muscle weakness of FSHD
may overshadow the presence of Movement Disorders. Other neuro-
muscular diseases display a broad range of phenotype features that
include Movement Disorders, the multisystem proteinopathies are a
good example of it. However, in FSHD there is no pathological evi-
dence of protein aggregation in the muscle or in the brain. The
unique mechanism of disease proposed for FSHD states that a defec-
tive repression of the D4Z4 macrosatellite repeat array leads to
expression of the DUX4 retrogene in skeletal muscle (3,5,6). It is
still unknown whether this expression occurs in the brain.
1188
Assessment of dose failure and delayed-ON with the time-to-ON
questionaire (TOQ) and Parkinsons KinetiGraph in PD patients
with motor fluctuations
S. Brillman, S.H. Isaacson (Boca Raton, FL, USA)
Objective: To determine whether subjective and/or objective
assessments can reliably detect dose failures and Delayed-ON
responses to oral levodopa doses using the Time-to-on Questionaire
(TOQ) and the Parkinsons Kinetigraph (PKG).
Background: OFF periods are common as PD progresses. OFF
periods comprise end-of-dose wearing off and delayed time-to-ON.
Some doses may not have clinical effect, and result in dose failure
(no-ON). Recent studies have highlighted the high prevalence of
early morning OFF periods, morning akinesia, and dose failures.
Although the Wearing-OFF Questionairre can help detect end-of-
dose OFF, less attention has been directed to detection of Delayed-
On and to dose failures. Yet these motor fluctuations can signifi-
cantly affect daily activities and QOL.
Methods: Retrospective analysis of PD patients with motor fluc-
tuations who completed the Time-to-ON Questionairre (TOQ) at a
routine clinic visit, and who also had assessment with the Parkin-
sons Kinetigraph (PKG) bracelet for 7 days.
Results: Both the TOQ and the PKG provided subjective and
objective information, respectively, on the delayed time-to-ON after
an oral levodopa dose. Dose failures were also identified, more so on
PKG than on TOQ. Delayed-ON prolonged morning akinesia, and
also were common after meals (post-prandial akinesia).
Conclusions: Delayed-ON is common and significantly contrib-
utes to daily OFF time. Dose failures are also common, yet underre-
ported by patients. Both Delayed-ONand dose failure (no-ON)may
reflect impaired absorption of levodopa due to gastroparesis and/or
effects of competitive protein in the small intestine. Ongoing analy-
ses seek to evaluate the effect of these motor fluctuations on daily
activities and QOL.
Movement Disorders, Vol. 30, Suppl. 1, 2015
1189
Hyperkinetic prehension in patients with Parkinsons disease and
levodopa-induced dyskinesias
M.A. Burack, C. Geraci, J. Mink (Rochester, NY, USA)
Objective: To evaluate the impact of levodopa-induced dyskine-
sias on prehension in patients with Parkinsons disease.
Background: The effects of levodopa on arm kinematics in Par-
kinsons disease have been well-characterized for a variety of simple
and complex movements, including reach-to-grasp. Few studies have
specifically investigated the impact of levodopa-induced dyskinesias
on voluntary motor control.
Methods: We performed 3-D video based kinematic analysis of a
naturalistic reach-grasp-drink-return task in individuals with Parkin-
sons disease and levodopa-induced dyskinesias. Grip aperture and
transport-grasp coordination during the initial reach, and peak veloc-
ity during the 3 transport phases were compared before (OFF) and
after levodopa (dyskinetic), and to healthy controls.
Results: Dyskinetic state was associated with improved peak
velocity during all 3 transport phases compared to OFF state. There
was a significant phase-by-medication status interaction, with the
return phase demonstrating a significantly greater medication effect
than the initial reach. Peak grip aperture during the initial reach was
smaller than controls in the OFF state, and greater than controls in
the dyskinetic state. Timing of peak grip aperture during the trans-
port stage did not differ from controls in either medication state.
Conclusions: Basic coordination of transport and manipulation
were unaffected by the presence of dyskinesias. The task phase with
the greatest accuracy requirement (initial reach) demonstrated the
least improvement with levodopa. Scaling of hand shape was hypoki-
netic in the OFF state, and hyperkinetic relative to controls in the
dyskinetic state.
1190
A posturography analysis while dual task differentiates
Parkinsons disease patients from healthy controls
B. De la Casa-Fages, F. Alonso-Frech, F. Grandas (Madrid, Spain)
Objective: To gain insight into the pathophysiology of balance
disorders in PD.
Background: Postural instability and gait disorders (PIGD) are a
major problem for patients with PD. Subthalamic deep brain stimula-
tion (STN-DBS) alleviates the cardinal symptoms of PD such as
rigidity, tremor, and bradykinesia. However, its effects on PIGD are
debated. Few published studies assess the effect of STN-DBS on bal-
ance in PD using posturography.
Methods: We evaluated 12 PD patients who had undergone
STN-DBS (8 women and 4 men,age 46-70 years; median disease
duration, 15.6 years) and 13 healthy age-matched controls (6 women
and 7 men, age 47-73 years) using dynamic and static posturography.
Patients were evaluated under no medication or stimulation. The
clinical and demographic data for each patient included falls before
surgery, total dose of antiParkinsonian medication and stimulation
parameters. We assessed 20 paradigms (including eyes open/closed,
cognitive and motor dual task, different support surface width, sup-
porting a weight in one hand, pull test, performing a ballistic move-
ment, stepping down, and getting up from a chair).The displacement
of the center of pressure (CoP) was analyzed using 21 posturographic
parameters that offer information about displacement in the anterior-
posterior and lateral axes, including area, velocity, and radial dis-
placements. The Mann-Whitney test was used to compare patients
with controls. Receiver operating characteristic (ROC) curve analysis
was performed to assess the discriminative power of each paradigm
and posturographic parameter to differentiate controls from PD
patients. Statistical significance in all tests was set at p<0.05.
Results: Statistically significant differences were found between
controls and patients in 17 of the 20 paradigms of the protocol. Dual
task was the paradigm with most differences: 16 out of 21
 POSTER SESSION
parameters. ROC analysis revealed an area under the curve (AUC)
of up to 90% for nine parameters during dual task performance (the
highest being Area 95 [with an AUC of 97%]). It is also revealed
100% sensitivity, and 70.6% specificity, with a cut- off value of
4.5cm.
Conclusions: Determination of the area that involves 95% dis-
placement of the CoP while a subject is performing a dual task is
the most discriminative posturographic parameter to differentiate
healthy controls from PD patients.
1191
A simple approach to monitoring of Parkinsons disease state
using a Smart phone platform
J.M. Dean, M. Silverman (Boulder, CO, USA)
Objective: To outline a methodology for assessing the current
state of disability in individuals with Parkinsons disease using short
and simple assessments administered via a smart phone.
Background: There has been an influx of interesting devices for
monitoring various motor elements of Parkinsons disease including
tremor, FOG and gait instability among others (Goetz, et al., 2009,
Weiss, et al., 2011). Most of these devices are standalone appliances
that have been developed by a research and/or engineering team. As
a result, they can be sometimes costly to implement and impose an
additional burden by requiring subjects to wear, monitor and manage
an additional piece of equipment. Furthermore, introducing additional
technology into a signal chain invites additional opportunities for
equipment malfunction. Incorporating these tools into a smart phone
platform can be a cost-effective alternative approach for collecting
this type of data.
There is also a large amount of relevant information that can be
quantified via a smart phone without the use of complex sensor data.
For example, subjective input from a subject can provide excellent
quality information regarding any number of issues associated with Par-
kinsons disease such as depression or symptom frequency and severity.
It is also possible to perform quick assessments using tools designed for
a smart phone platform to provide performance related data.
Methods: The authors have produced tools available on an iOS
platform for assessing memory, balance, reaction time and time
perception.
Conclusions: With regular use, these tools can be to identify
changes in condition over time in a manner that can enhance personal
decision-making by the patient as well as clinical decision-making by
a physician, therapist or other healthcare professional. There continues
to be growing interest in technology for monitoring and assessing
many elements of Parkinsons disease. Although there are now a num-
ber of dedicated devices to obtain data for various Parkinsons-related
deficits, technology available in smart phones and consumer devices
are beginning to become a robust alternative. Although there is a
strong need for standardized data from such devices, this approach
could be a very promising opportunity to provide clinicians and
researchers with a significant amount of valuable data.
1192
The utilization of smartphone devices to enhance clinical
interventions
J.M. Dean, M. Silverman (Boulder, CO, USA)
Objective: To highlight the ability of currently available technol-
ogies to augment clinical judgment.
Background: A number of technologies currently available on
commercially available smartphones can serve to provide additional
data in both clinical and research settings. Although these technolo-
gies will neither supplant nor replace clinical judgment, they can
provide additional information that may not be readily recognized
during examinations or treatments.
S463
For example, researchers in Tel Aviv utilized accelerometry to
enhance a timed up and go (TUG) test. The device identified statisti-
cally significant differences in range and acceleration between controls
and subjects when examining sit to stand and stand to sit portions of
the activity (Weiss, et al, 2010). Other researchers have begun to repli-
cate this technology on an iPhone. Shaw and colleagues have made
use of the accelerometer available on iPhone to assess rigidity during
intraoperative testing during DBS surgeries (Shah, et al., 2014).
Methods: The authors have designed testing tools on the iOS
platform using instruments with an existing body of data for Parkin-
sons disease. These tools provide additional quantifiable data that is
not easily or readily available to clinicians without using additional
equipment.
A modified Stroop test performed on an iPhone utilizes speech
recognition for responses. While the program provides data regarding
accuracy, it is also able to provide data regarding reaction time,
which would be difficult to reliably collect without this tool. A
Flankers test incorporating the same assessment tools and speech rec-
ognition technology is available as well. Voice quality measures may
be collected from this input in future iterations.
Data about visual contrast sensitivity can be collected by another
tool that provides data regarding response time to gradually appear-
ing visual prompts. This provides relevant data regarding certain
types of visual impairment common in Parkinsons by identifying
when the subject is able to see the target object.
Conclusions: The ability to provide fast, quantifiable data sug-
gests that the incorporation of technologies into day-to-day practice
increasingly viable. Furthermore, the availability of smartphone tech-
nology makes them an increasingly natural companion in the clinic.
Validation of data from these instruments continues to be a barrier to
their more widespread implementation.
1193
Withdrawn by Author
1194
Physical activity correlates with disease severity among new
onset Parkinsons disease patients
P. Gonzalez-Latapi, J.D. Ciolino, T. Simuni (Boston, USA)
Objective: To describe the frequency and intensity of exercise in
a cohort of de novo PD patients versus matched healthy controls
(HC) and to analyze the association between exercise and motor
function, non-motor symptoms, cognition, and biomarkers of disease
among PD subjects.
Background: There is extensive data on the positive effect of
exercise on disability in Parkinsons disease (PD), however, there is
limited data on the impact of exercise on disease progression.
Methods: Data used in the preparation of this abstract were obtained
from the Parkinsons Progression Markers Initiative (PPMI) database
(www.ppmi-info.org/data), an international longitudinal observational
study of de novo, untreated (at enrollment) PD participants and HC. The
dataset includes demographics, a range of motor and non-motor scales
including the MDS-UPDRS, and biomarkers of disease. Exercise was
measured by the Physical Assessment Scale for the Elderly (PASE), a
validated self-reported scale. PASE ranges from 0 to 360, and a higher
score signifies greater exercise frequency and intensity.
Results: 239 PD and 76 HC subjects who had baseline data for
PASE were included. Overall, mean age was 63.2 (610.02, p50.6743),
69% were male (p50.2154) and 91% were Caucasian (p50.9988),
with no statistically significant differences between PD and HC. Overall
mean BMI was 27.5 (65.1, p50.2084). There was no significant differ-
ence in PASE score between HCs (186 6 90) and PD subjects
(175 6 110, p50.1458). Among PD subjects, PASE total score inver-
sely correlated with age (r=-0.221, p50.0005), HY stage (r=-0.171,
p50.0078), MDS-UPDRS total (r=-0.186, p50.0036) and Part III
Movement Disorders, Vol. 30, Suppl. 1, 2015
S464 POSTER SESSION
scores (r=-0.201, p50.0016). PASE was significantly correlated with T-
tau/A-Beta ratio (r=-0.134, p50.048) but not other biomarkers.
Conclusions: There was no significant difference in self-reported
exercise frequency and intensity between de novo PD and HCs.
Greater exercise correlated with decreased disease severity as well as
T-tau/A-beta ratio among PD patients. This pilot data should be vali-
dated once full dataset becomes available. Impact of exercise on
clinical and biological markers of PD progression will be studied
longitudinally.
1195
New observations in the Fragile-X associated tremor/ataxia
syndrome (FXTAS) phenotype
D.A. Hall, A.Y. Fraint, P. Vittal, A. Szewka, B. Bernard, E. Berry-
Kravis (Chicago, IL, USA)
Objective: To describe new phenotypic characteristics observed
in a series of patients with Fragile X-associated tremor/ataxia syn-
drome (FXTAS).
Background: FXTAS is caused by an expansion in the 5 trinu-
cleotide CGG repeat of the fragile X mental retardation 1 (FMR1)
gene. Clinical manifestations include kinetic tremor, cerebellar
ataxia, cognitive decline, psychiatric problems and Parkinsonism.
Methods: We conducted a retrospective chart review of patients
seen in the Fragile X Carrier clinic at Rush University in Chicago
between 2009-2014. Patients who had between 55-200 CGG repeats
and for whom clinical data was complete were included for analysis.
Data collected included age, sex, FMR1 premutation size, FXTAS
diagnosis (possible, probable, or definite), eye movement abnormal-
Fig. 1. (1196).
Movement Disorders, Vol. 30, Suppl. 1, 2015
ities, neuropathic signs, cognitive status, neuropsychiatric signs,
FXTAS Rating Scale (FXTAS-RS) score, MRI findings, and family
history of fragile X disorders.
Results: Nineteen patients with complete clinical data (38% of
whom were women) were included. For each category of FXTAS
diagnosis, FXTAS-RS and repeat sizes were as follows. Definite
FXTAS patients had FXTAS-RS scores between 30-75 and CGG
repeat sizes between 74-124. Probable FXTAS patients had
FXTAS-RS scores between 17-81 and CGG repeat sizes between 55-
120. Possible FXTAS patients had FXTAS-RS scores between 7-
41 and CGG repeat sizes between 85-120. Unexpectedly, five
patients had abnormal eye movements similar to those seen in pro-
gressive supranuclear palsy (PSP), and two patients met diagnostic
criteria for PSP. Two additional patients who suffered a rapidly pro-
gressive decline of their FXTAS signs were found to have focal spi-
nal cord disease.
Conclusions: This case series yields new information about the
FXTAS phenotype. Patients with FXTAS may present with a PSP-
like phenotype. Rapid progression of gait ataxia in FXTAS may war-
rant investigation for an additional spinal cord pathology. Addition-
ally, the FXTAS Rating Scale may not be informative regarding
diagnosis.
1196
4-year longitudinal changes in clinical rating, medication and
quantitative motor assessment in mild and moderate Parkinsons
disease: Results from the MODEP study
S. Heinzel, F. Bernhard, M. Maechtel, T. Heger, S. Nussbaum, W.
Maetzler, D. Berg (Tuebingen, Germany)
 POSTER SESSION
Fig. 2. (1196).
Objective: To study progression markers of disease severity
based on UPRDS-III, L-dopa equivalent dose and quantitative motor
tests in mild and moderate Parkinsons disease (PD) stages.
Background: Motor symptom severity of PD patients is commonly
quantified by semiquantitative clinical rating scales, such as the
UPDRS-III. However, heterogeneity and complexity of motor symp-
toms as well as changes in medication over time challenge reliable
trajectories of PD severity in individual PD patients and longitudinal
(pharmacological) studies with UPDRS-III changes as endpoints. Also,
it is still unknown, to which extent progression in UPDRS-III is com-
parable with longitudinal changes in quantitative motor assessments.
Methods: 27 PD patients (14 with 0 to 3 years disease duration
at baseline, early PD (mild PD stage); 13 with 5-10 years, late
PD (moderate PD stage)) were investigated bi-annually for 4 years
in the MODEP study (MODeling Epidemiological data to study Par-
kinsons disease progression). At each visit, UPDRS-III score as well
as axial, bradykinesia, hypokinesia and tremor subscores, daily L-
dopa equivalent dose (LED), and time to perform the Timed-up-and-
go (TUG) and the Purdue pegboard (PEG) test were assessed.
Annual and overall changes in these parameters were tested using t-
tests for all and early/late PD patients.
Results: The UPRDS-III change from year 1 to year 4 was sig-
nificant for the early PD group (8.4 6 9.6 points increase), but not
for the late (2.8 6 12.1 points decrease) nor the overall group
(3.0 6 12.1 points increase). UPDRS-III total scores, axial, bradyki-
nesia and hypokinesia subscores (Fig. 1a/b), and PEG (Fig. 1c)
showed a progression with inverted U-shaped characteristics. Tremor
subscores (Fig. 1b, 4-year change non-significant), LED (sign. in
early and late PD subgroups; Fig. 2) and TUG (sign. in the early PD
group; Fig. 1d) progressed rather linearly.
Conclusions: Our results from a small but thoroughly investigated
PD cohort seen longitudinally over 4 years indicate that some but not
all currently accepted progression parameters show continuous and lin-
ear changes. Particularly surprising is the inverted U-shaped progres-
sion of the UPDRS-III score, and those subscores that measure
symptoms sensitive to dopaminergic treatment. The TUG may have the
highest potential for detecting linear annual changes in such a cohort.
[figure1]
[figure2]
1197
Primary familial brain calcification (PFBC) with known gene
mutations A systematic review
M. Kasten, V. Tadic, A. Domingo, D. Alvarez Fischer, A.
Westenberger, C. Klein (L
ubeck, Germany)
Objective: To (i) provide a systematic literature review on the
neuroimaging and clinical phenotype of genetically confirmed PFBC;
S465
(ii) improve and harmonize future phenotype description and report-
ing by addressing data gaps; (iii) develop uniform definitions for
clinical characterization.
Background: In the past three years, it was determined that
mutations in three genes (SLC20A2, PDGFRB, and PDGFB) cause
primary familial brain calcification (PFBC), enabling genotype-
specific phenotyping.
Methods: We searched the MEDLINE database using the terms
PFBC, IBGC, brain calcification, Fahr disease OR Calcification
AND SLC20A2, PDGFRB, PDGFB from 2012 to May 2014. The
authors selected 25 articles from all records (n575) and manuscripts
from reference lists. Only genetically confirmed cases with individual
clinical information were included, leaving 15 manuscripts. Prede-
fined categories for data extraction were: Parkinsonism, dystonia,
cerebellar symptoms, epilepsy, headache, fatigue, other neurological
signs, dementia, depression, other psychiatric symptoms, imaging
results, and age at onset (AAO). We also assessed availability of
information to estimate possible bias.
Results: We included a total of 179 cases, 162 of which belong
to 25 families. Availability of information ranged from >90% for
ethnicity to 24% for AAO. All cases had calcifications upon cranial
computed tomography, most frequently located in the basal ganglia
(71%), subcortical white matter (41%), cerebellum (34%), or thala-
mus (29%). Mean AAO was 27.9 6 22.3 years and AAO was compa-
rable across genes (p50.768). The most frequently described signs
were Movement Disorders such as Parkinsonism (12%) and dystonia
(19%). Non-motor symptoms included headache or migraine (18%),
fatigue (6%), cognitive impairment (15%), depression (6%), and
other psychiatric disorders (15%). Penetrance of the imaging pheno-
type was 100% compared to 64% of the clinical phenotype. We pro-
pose a novel definition of disease status by specifying PFBC into
genetically/clinically/imaging-affected.
Conclusions: Especially in rare conditions, meta-analyses are the
most suitable tool to extract reliable information on the natural dis-
ease course. For this, we provide a minimal data set that can be used
for systematic clinical and imaging data collection in PFBC and will
improve informed patient counseling.
1198
Movement Disorder emergencies Experience of tertiary care
Neuropsychiatry Center in North India
S. Kushwaha, A. Anthony, S. Maheswari (Delhi, India)
Objective: To Study the patients presenting with Movement Dis-
order emergency and there management.
Background: Neurologists and General physicians manage the
Movement Disorders in day-to-day practice. The emergencies in
Movement Disorders are usually not recognized by treating physi-
cians. Movement Disorder emergencies are defined as a clinical pre-
sentation of neurological disorder dominated by variously defined
abnormal movements, evolving acutely and sub acutely. The rapidly
evolving Movement Disorder may be associated with significant
morbidity and mortality in absence of early recognition and
management.
Methods: Duration of study 2013 -14 - A cross sectional
Study.
Results: Total no of 18 patients of different Movement Disorders
were admitted in neurology ICU. These patients were categorized
into hyperkinetic (9 pts) and hypokinetic (9 pts) Movement Disorders
according to their presentations. In hypokinetic group, one patient
each of Wilsons disease, NBIA, Tardive and generalized dystonia
had presented with severe status dystonicus. Two patients of Parkin-
sons disease presented with severe freezing. Two patients of Neuro-
leptic malignant syndrome had severe rigidity. One patient presented
with chorea mollis. In Hyperkinetic group, the following patients
were presented with abnormal movements. Patients of serotonin syn-
drome (3pts), PD with severe dyskinesia (1pts), PD with psychosis
(1pt), Severe Chorea (2pts), Wilsons disease with tremors (2pts).
Movement Disorders, Vol. 30, Suppl. 1, 2015
S466 POSTER SESSION
Discussion - Movement Disorders generally have insidious onset.
The situation in which these disorders evolve rapidly or have acute
complications of the existing disorder constitute the Movement Dis-
order emergencies. All our patients of presented with exacerbation of
the abnormal movements, hypokinetic or hyperkinetic movements
due to different reasons in our emergency requiring admission in
ICU. The common causes leading to the emergencies besides pro-
gression of the disease are toxin and drug exposure or withdrawal,
metabolic derangement. Most of these emergencies are treatable.
Conclusions: The Movement Disorder emergencies are under rec-
ognized conditions seen in the course of usually insidiously progres-
sive Movement Disorders. It should be appropriately recognized and
treated to avoid the morbidity and mortality associated, as majority
of the causes are treatable.
1199
Dysphagia in PD: Response to continuous dopaminergic
stimulation
A. L an~ez, J. Olmedo, J. Vaamonde (Ciudad
opez, J.P. Cabello, R. Ib
Real, Spain)
Objective: To evaluate the clinical and manometrics changes in a
patient with Parkinso ns disease with severe off-dysphagia how was
treated with continuous dopaminergic stimulation with duodopa.
Background: Dysphagia is a frequent symptom in Parkinso ns
disease. Abnormalities included disturbances of oral and pharyngeal
phases of swallowing. The pathogenesis is multifactorial, involving
cognitive and psychological changes in addition to abnormalities of
the extrapyramidal and autonomic nervous systems. In general the
response to dopaminergic treatment is limited and not related to the
extent of motor function, witch is achieved by dopaminergic
stimulation.
Methods: We studied a Parkinsonian patient who suffered on-
off motor fluctuations, dyskinesias and severe off-dysphagia witch
improved during on period. Manometric changes of esophageal
body and lower esophageal sphinter have been documented during
the on and off periods.
Results: After starting treatment with duodopa we observe a dra-
matically ameliorate on-off fluctuations and an important improve
on the severe off-dysphagia. Esophageal manometry demonstrated an
improve in the delayed triggering of the swallowing reflex and a
reduction in the prolongation of the esophageal phase of swallowing
. Results: Of the 137 veterans evaluated, 10 (7.3%) had a diagno-
Conclusions: Esophageal motor abnormalities are frequent in PD.
Although treatment response is limited, some patients may benefit
from optimizing the dopaminergic replacement therapy, including the
use of continuous dopaminergic stimulation, specially when the
intake of food and medication is affected.
1200
Two patients with radiographic NPH and idiopathic Parkinsons
disease
H.S. Lee, M.F. Lew (Los Angeles, CA, USA)
Objective: To describe the diagnostic challenge of two patients
initially diagnosed with radiographic NPH that were referred for
Parkinsonism.
Background: We present two cases in which both patients ini-
tially presented with mild Parkinsonian symptoms and were found to
have normal pressure hydrocephalus on imaging. The diagnosis on
presentation was unclear based on clinical symptoms that did not fit
perfectly into either diagnostic category.
Methods: Two patients with an initial radiographic diagnosis of
NPH were followed clinically over 6 months time.
Results: Patient A was found to have mild asymmetric Parkinso-
nian symptoms. An MRI of the brain and flow study revealed normal
pressure hydrocephalus. Patient A was admitted for a lumbar drain
Movement Disorders, Vol. 30, Suppl. 1, 2015
but did not have clinical improvement. A DAT scan is pending. Car-
bidopa/Levodopa offered significant improvement in symptoms.
Patient B was diagnosed a decade ago with essential tremor. She
complained of 6 months of rest tremor and was found to have mild
asymmetric rest tremor and subtle Parkinsonian symptoms on exam.
MRI of the brain was consistent with normal pressure hydrocephalus.
Patient B was admitted for a lumbar drain. A DAT scan revealed
asymmetric abnormalities consistent with idiopathic Parkinsons
disease.
Conclusions: Patients who present with mild Parkinsonian symp-
toms can provide a diagnostic challenge. Patients with concurrent
normal pressure hydrocephalus offer further complexity in making a
proper clinical diagnosis. This case report highlights the difficulty in
properly addressing and diagnosing patients with these presentations
that can lead to multiple diagnoses being present unexpectedly.
1201
Psychogenic Movement Disorders in veterans: Phenomenology
and psychiatric comorbidity
J.D. Mack, J. Quinn, S. OConnor, B. Lobb, C. Murchison
(Portland, OR, USA)
Objective: To examine the frequency and phenomenology of psy-
chogenic Movement Disorders (PMD) in a Veterans Administration
Medical Center (VAMC) Movement Disorders clinic and compare
psychiatric comorbidity in veterans with PMD versus organic Move-
ment Disorder (OMD).
Background: PMD may present with the full range of Movement
Disorder phenomena and are often difficult to differentiate from
OMD. Studies of PMD in tertiary Movement Disorders centers have
shown a prevalence of 3-4%, although the frequency of PMD in vet-
erans has not been examined specifically. Recent work has found a
diagnosis of post-traumatic stress disorder to be predictive of psycho-
genic non-epileptic seizures in veterans. Likewise, a better under-
standing of relationships between psychiatric disorders and PMD in
veterans may aid in improved diagnosis and treatment of PMD.
Methods: We reviewed initial visit records of all new consulta-
tions in the Portland VAMC Movement Disorders Clinic from July
through December 2013. For those assessed to have PMD, further
record review was performed for Movement Disorder phenomenol-
ogy and psychiatric diagnoses, and comparisons were made to a
group of veterans diagnosed with OMD.
sis of psychogenic Movement Disorder. The most frequently
observed movement type in the PMD group was tremor (n56, 60%),
followed by stereotypy in 4 (40%), gait disturbance in 1 (10%),
other in 1 (10%) and 2 veterans displaying more than one type.
Veterans in the PMD group were significantly younger (mean 48.1,
range 21-69 years) than those in the comparison group (mean 70.4,
range 57-85 years, p50.005). There was no statistically significant
difference between PMD and OMD groups across psychiatric diag-
nostic categories. Veterans in the PMD group were more likely to
have an Axis I psychiatric diagnosis than OMD, although not statisti-
cally so (8 vs. 6, x2 p50.329).
Conclusions: The prevalence of PMD may be higher in veteran
than in civilian Movement Disorders clinics, and veterans with PMD
present at a younger age than those with OMD. No category of psy-
chiatric diagnosis is associated specifically with PMD compared to
those with OMD. Despite this, veterans with PMD have a high rate
of psychiatric comorbidity and studies are needed to further examine
psychiatric correlates of PMD in this population.
1202
Impact of different baseline motor features on prognosis in
Parkinsons disease
A.D. Macleod, C.E. Counsell (Aberdeen, United Kingdom)
 POSTER SESSION S467

Independent motor predictors of outcome in Cox regression analyses, adjusted for age

Motor features which independently Hazard ratio (95% CI)

Outcome predict outcome and p-value
Death (N=198) Total bradykinesia score (5-point increase) 1.44 (1.161.78), P=0.001
Ratio of mean axial score to mean limb score 2.09 (1.413.09), P<0.001
Dependence (Schwab & Mean axial score 2.89 (1.744.81), p<0.001
England <80%) (N=162)
Death or dependence (N=168) Total bradykinesia score (5-point increase) 1.50 (1.221.84), p<0.001
Ratio of mean axial score to mean limb score 1.74 (1.212.49), p50.003
Progression to Hoehn & Dopa-non-responsive symptoms total score (5-point increase) 2.57 (1.763.76), p<0.001
Yahr stage 3 (N=147)

Objective: To identify which motor features at diagnosis predict
prognosis.
Background: Other than tremor dominance (TD) or the postural
instability-gait disorder phenotype (PIGD), little is known about
what baseline motor characteristics influence prognosis in Parkin-
sons disease (PD).
Methods: We analysed data from the PINE study, a prospective
study of a community-based incident cohort of PD patients identified
in Aberdeen, Scotland, between 2002-4 and 2006-9, with long term
annual follow-up. Baseline motor features were derived from the
UPDRS part 3 scale: total tremor score, total bradykinesia score,
total rigidity score, mean score from axial items, mean score from
limb items, ratio of mean axial:mean limb items, dopa-responsive
signs, dopa-non-responsive signs, asymmetry of limb items, and the
TD/PIGD classification. We assessed four outcomes: death, depend-
ence (Schwab & England<80), death or dependence, and progres-
sion to Hoehn & Yahr stage 3 (H&Y3). Analysis were performed
using multivariable Cox regression using a backwards stepwise pro-
cess using variables which were significant in univariable analyses,
adjusted for age. Significance cut-off was 0.05.
Results: 198 patients were analysed (median 6.1 years follow-
up). In univariable analyses, bradykinesia score, axial score, limb
score, axial/limb ratio, dopa-responsive signs, and dopa-non-
reponsive signs were significant predictors of all outcomes. In uni-
variable analyses, asymmetry predicted dependency and death or
dependency and TD/PIGD only predicted H&Y3. In multivariable
analyses bradykinesia and axial/limb ratio were independent predic-
tors of death and death or dependency and axial score and dopa non-
responsive symptoms were predictors for dependency and H&Y3,
respectively.
Conclusions: Although univariable analyses were consistent
across these outcomes, different motor characteristics at diagnosis
were important for independent prediction of different prognostic
outcomes. However, a variable relating to severity of axial signs was
a common theme across three of these outcomes. Thus, axial motor
features appear to be an important predictor of prognosis, perhaps
stronger than the TD/PIGD classification, and deserve further study.
This analysis is limited by multiple comparisons, small number of
events per variable considered, correlations between variables and
not accounting for treatment effects so these findings require
replication.
1203
Voluntary control of facial musculature in Parkinsons disease
M. Marneweck, G. Hammond (New York, NY, USA)
Objective: To measure voluntary control of facial musculature in
Parkinsons disease.
Background: Aside from being measured in the context of pro-
ducing facial expressions of emotion, the ability to voluntarily con-
trol a range of facial muscles in Parkinsons disease (PD) has not
been systematically measured.
Methods: We used in three enrollment phases an adaptation of
the Upper and Lower Face Apraxia test, a measure of the ability to
make voluntary movements of the upper and lower face in PD
patients and healthy controls. Errors were scored due to (1) pauses
prior to movement initiation, (2) loss of individuation, (3) impover-
ished movement, (4) no movement at all, or (5) content errors (lik-
ened to ideational apraxia errors).
Results: The results show impaired voluntary control of facial
musculature in most but not all with PD (with large effect sizes)
which correlated positively and highly with disease severity. Errors
by PD patients were predominantly due to impoverished movement.
Conclusions: Similarly to spontaneous and voluntary emotional
expressions, voluntary non-emotional facial movements are impover-
ished in PD; impoverishment of all movement types will likely con-
tribute to the mask-like facial appearance that is seen with disease
progression. These findings also illustrate the utility of an adapted
Face Apraxia test as a practical and sensitive measure of voluntary
facial musculature control in PD. The test can be used to supplement
clinical observations and as a research tool.
1204
The Whack-a-Mole sign in functional Movement Disorders
J.E. Park, C.W. Maurer, M. Hallett (Bethesda, MD, USA)
Objective: We present a case series of three patients with func-
tional Movement Disorder who exhibit the whack-a-mole sign.
Background: Achieving and relaying the diagnosis of functional
Movement Disorders can be challenging. Identifying positive physi-
cal signs and diagnostic maneuvers is critical to this process. To
date, distractibility, entrainability and variability are recognized as
classic physical findings in patients with functional Movement Disor-
der. In this case series, we identify and characterize a novel phenom-
enon unique to these patients.
Methods: We present three patients as examples of the whack-
a-mole sign (see Video 1), characterized by movement suppression
of one body part being followed by the immediate appearance in
another body part. This name is derived from the arcade game
whack-a-mole, in which a mole, when hit, returns to its original
hole, only to re-emerge elsewhere. This phenomenon is not observed
in any organic Movement Disorder.
Results: Providing FMD patients with evidence of positive physi-
cal signs is considered critical for both arriving at and conveying the
diagnosis of functional Movement Disorder. An international com-
mittee of Movement Disorders specialists recently emphasized the
need to expand these positive signs. In this case series, we describe
an additional positive physical sign, unique to FMD patients, that
can serve as supporting evidence on examination, and can be
included as one of the positive criteria to share with the patient
when conveying the diagnosis of functional Movement Disorder.
The spread of a functional movement from one body part to
another has precedent in the phenomenon of causalgia-dystonia. The
spread of abnormal movements to different anatomical locations can

Movement Disorders, Vol. 30, Suppl. 1, 2015

S468 POSTER SESSION
Fig. 1. (1204).
be described to patients as evidence in support of a software prob-
lem involving broader networks as opposed to a hardware problem
affecting a particular anatomical location.
Conclusions: Previous studies have emphasized the importance of
incorporating multiple physical diagnostic maneuvers in order to accu-
rately diagnose functional Movement Disorders, given the limited sen-
sitivity and specificity of any particular measure. We propose that the
whack-a-mole sign, which we demonstrate to be present in a subset
of patients with functional Movement Disorders, is a valuable addition
to this inventory of positive physical signs and diagnostic maneuvers.
1205
Postural movement strategy for maintaing balance in early
Parkinsons disease with mild postural instability
J.H. Park, Y.J. Kang, T.K. Lee, K.B. Sung (Bucheon-si, Korea)
Objective: The aims of this study are (1) to examine postural
movement strategy for maintaining balance in patients with early PD
and (2) to compare the strategy pattern between early PD patients
with subtle or mild postural instability and those with normal pos-
tural stability.
Background: Postural instability is an important factor of falls
and fall-related injuries in PD. Under variably challenging sensory
conditions, selection of appropriate movement strategy can be neces-
sary for effective postural control. However, there are a few studies
assessing the ability to choose the right movement strategy in the
early stage of PD with subtle or mild postural instability.
Methods: Fifteen patients with PD (HY stage, 1-2.5) and 16 age-
matched control subjects participated in this study. Patients were
divided into two groups: PD with slight or mild postural instability
(MDS-UPDRS 3.12) and those without postural instability depending
on the results of Pull test. We examined an individual strategy and
equilibrium score obtained during a sensory organization test (SOT)
using the computerized dynamic posturography.
Movement Disorders, Vol. 30, Suppl. 1, 2015
Results: Correlation analysis between equilibrium and strategy
score showed strong positive associations in patient and control
groups (Spearmans rho=0.89 in patients; rho=0.89 in controls,
p<0.01). For patient groups, however, the strength of correlation was
lower in patients with mild postural instability (rho=0.873, p<0.01)
than patients without postural instability (rho=0.94, p<0.01), suggest-
ing that maladaptive hip strategy may be found in the patients with
postural instability and maladaptive ankle strategy in the patients
without postural instability.
Conclusions: These results suggest that early PD patients with
mild postural instability rely on hip dominant strategy, whereas those
without postural instability use ankle dominant strategy under condi-
tions disturbing visual, proprioceptive, and vestibular sensory inputs.
1206
Velopharyngeal dystonia: An unusual focal task-specific dystonia
A. Patel, L. Sulica, S. Frucht (New York, NY, USA)
Objective: To describe the clinical characteristics of two cases of
velopharyngeal dystonia.
Background: Velopharyngeal dysfunction produces a nasal
speech pattern due to an inability to close the nasal airway during
speech, most often associated with anatomical abnormalities of the
palate. We describe two cases of idiopathic velopharyngeal dystonia
causing a similar speech pattern.
Methods: Case report.
Results: Case 1: A 62-year-old man presented with a two year his-
tory of nasal speech, occuring six days after a dental procedure. There
were no chewing or swallowing difficulties. Previous treatment with anti-
biotics, oral corticosteroids, and pyridostigmine were ineffective. On
examination his voice was hypernasal and worsened when pronouncing
words with/k/,/g/, and/qu/sounds. Whispering and singing were normal.
Placement of a tongue depressor between his teeth improved his speech.
He had no abnormal laryngeal motion on fiber-optic exam. Treatment
with trihexyphenidyl 2mg TID resulted in a 50% subjective improve-
ment in his voice at one month follow-up, with 90% improvement on
4mg TID after 3 month follow-up. Case 2: A 41-year-old woman pre-
sented with a 16-month history of nasal speech. Previous treatment with
speech therapy, proton-pump inhibitors, and steroid injections to the
vocal cords had no benefit. On examination her speaking voice had a
simultaneously breathy and nasal quality. Talking in a high-pitched voice
or placing external pressure on the larynx improved her speech. Fiber-
optic exam noted velopharyngeal insufficiency in connected speech with-
out abnormal laryngeal motion in tasks meant to elicit spasms of focal
laryngeal dystonia. There was 75% subjective improvement in voice
clarity on trihexyphenidyl 2 mg TID at two month follow-up.
Conclusions: The two cases share salient features with more
common forms of dystonia. They expressed task-specificity to certain
phonemes of connected speech. This qualitative observation is simi-
lar to the objective findings of acoustic analysis in cases of adductor
spasmodic dysphonia, and may be a distinguishing characteristic of
dystonia from muscle tension dysphonia. Both cases displayed prom-
inent sensory gestes antagoniste, a well-reported feature of oroman-
dibular dystonia. Finally, both patients responded to anti-cholinergic
medication after previous multi-modal therapy failures.
1207
Learning more from finger tapping in Parkinsons disease: Up
and down from dyskinesia to bradykinesia
M. Picillo, G.B. Vincos, D.S. Kern, S.H. Fox, A.E. Lang, A. Fasano
(Toronto, ON, Canada)
Objective: The aim of the present study was to explore the clinical
meaning of a specific aspect of performance of the finger tapping item
of the UPDRS-III. We have observed that patients with PD tend to per-
form the finger tapping in the OFF condition with their arm and hand
closer to their lap, while they raise their arm at least to head level in
 POSTER SESSION S469

Table (Continued)
CDRS total score ON 4 (2 - 6)
CDRS upper limbs score 1 (0 - 2)
TAP OFF# 3 (3 - 4)
TAP ON# 4 (4 - 5)

* Except where otherwise specified 1 Significant difference

between UPDRS III OFF and UPDRS III ON (p<0.001).^ Sum
of the UPDRS III scores for finger tapping, pronation-supination
and hand grips tasks (items 23,24,25). # Significant difference
between TAP OFF and TAP ON (p<0.001). DUPDRS III: the
difference between the UPDRS-III in OFF and in ON conditions
evaluating the levodopa responsiveness.

Fig. 1. (1207).

the ON condition with levodopa-induced dyskinesia (LID). We sought

to use this phenomenon in developing a simple and easily adminis-
trated scale to score OFF/ON/ON with LID in patients with PD.
Background: Finger tapping is used to evaluate bradykinesia
focusing on amplitude, decrement, and speed of the movements.
However, vertical positioning of the hands when performing the task
may also be clinically relevant.
Methods: We developed a TAP score, measuring the vertical
level above the lap where the patient performs the finger tapping;
ranging from 1 (task performed with the hand close to the lap) to 5
(above the head) [figure1]. We retrospectively applied the TAP score Fig. 2. (1207).
in both the OFF and ON medication conditions of 100 PD patients
in addition to usual ratings of motor UPDRS and dyskinesia (Clinical
Dyskinesia Rating Scale, CDRS) during acute videotaped levodopa- TAP ON was significantly higher than TAP OFF [4 (4-5) versus
challenge. The following hypotheses were tested: 1) TAP score dur- 3 (3-4), p<0.001] [figure2]. Spearmans rank test showed a positive
ing the ON phases (TAP ON) is higher than during the OFF correlation between TAP ON and both CDRS total score (q =0.529,
phases (TAP OFF); 2) TAP ON is positively correlated with the p<0.001) and CDRS upper limbs score (q =0.576, p<0.001). Partial
severity of LID in the whole body and in the upper limbs; 3) TAP correlation confirmed the relationship between TAP ON and both
OFF is negatively correlated with the severity of bradykinesia in the CDRS total and upper limbs scores after controlling for the
whole body and in the upper limbs. DUPDRS-III (q =0.434, p<0.001 and q =0.510, p<0.001, respec-
Results: The demographic and clinical features of the 100 tively). Spearman rank test showed an inverse correlation between
patients included are shown in [table1]. TAP OFF and UPDRS-III OFF (q =-0.293, p<0.001) and UPDRS-
III OFF bradykinesia score (q =-0.256, p<0.001).
Conclusions: The TAP score maybe a measure of proximal
Demographic and clinical characteristics of the 100 PD patients movement amplitude and represents an easy and feasible method to
included evaluate defective or excessive motor output.
median (25th-75th percentiles)*
1208
Age at levodopa challenge, years 65 (58.25 - 70)
Clinical features of late-stage early-onset Parkinso
ns disease: 38
Disease duration, years 16.5 (12 - 23)
years of follow-up
Gender, Women/Men (%) 35/65
Side of onset, R/L (%) 54/56 B. Pinter, A. Diem-Zangerl, G.K. Wenning, W. Oberaigner, K. Seppi,
UPDRS III OFF1 38.5 (29.5 - 48.7) W. Poewe (Innsbruck, Austria)
Bradykinesia score OFF^ 6 (4 - 8) Objective: The objective of the present study was to describe the
UPDRS III ON1 21.5 (13 - 30) Parkinsons disease (PD) phenotype of advanced stages of up to 38
DUPDRS III1 15 (9.25 - 22.75) years of disease duration.
Background: Despite the growing disease prevalence, informa-
(Continued) tion on late-stage PD is scarce and hard to come by.

Movement Disorders, Vol. 30, Suppl. 1, 2015

S470 POSTER SESSION

TABLE 1. Clinical and demographic data of the surviving Objective: To determine the prevalence of falling in Parkinsons
seven patients disease (PD) patients, to assess generic and disease-specific clinical
and pharmacological factors, relationship with Health-related Quality
ID 1 2 3 4 5 6 7 of Life (HR-QoL), and changes in falls from OFF to ON in patients
with motor fluctuations.
Age (in years) 73 72 70 72 80 79 73 Background: Falls are a frequent feature of PD.
Gender (M/F) M M M M F M F Methods: 683 PD patients of the COPARK survey were eval-
Age of onset 39 38 36 38 48 48 45 uated (11 had missing data and were excluded from the analysis).
(in years) Patients with falls were identified as those with a UPDRS Item 13
Disease duration 34 34 34 34 32 31 28 1 in the ON condition. All patients were assessed in a standardized
Oral Levodopa - 1 1 1 1 1 1 manner [demographics, treatments, Unified PD Rating Scale
Duodopa - - - - 1 - 1 (UPDRS), Hospital Anxiety and Depression Scale, Pittsburg ques-
Dopaminagonists 1 - - - 1 - - tionnaire and HR-QoL scales (SF36, PDQ39)].
Amantadin 1 1 - - 1 1 1 Results: Falling was reported by 108/672 (16%) PD patients dur-
Surgical therapy 1 1 1 1 - 1 1 ing the ON-state and prevalence increased according to PD severity,
Fluctuations 1 1 1 1 1 1 1 from 5% in Hoehn & Yahr stage 1 to 60% in stage 4. Falling corre-
(disabling) (1) (1) (1) (NA) (-) (1) (1) lated with (1) generic factors such as female gender, age at the end
Dyskinesias - - - 1 1 1 1 of academic studies and diuretics consumption, (2) motor PD-
(disabling) (-) (-) (-) (NA) (1) (-) (1) specific factors including disease severity, frozen gait, difficulties
Dystonia 1 - 1 - - - 1 when arising from a chair, dyskinesia and higher levodopa daily
Falls 1 1 1 1 1 1 1 equivalent dose and (3) non-motor PD specific factors like orthostatic
Wheelchair 1 1 - 1 1 1 - hypotension and hallucinations. Falling was significantly related to
H&Y 4 5 4 4 5 5 4 lower HR-QoL. Falling was more frequent in OFF than ON in 48/74
MDS-UPDRS I 14 41 18 42 16 22 12 (64%) patients with motor fluctuations and remained unchanged in
MDS-UPDRS II 35 46 46 NA 42 44 19 27 patients (36%).
MDS-UPDRS III 60 65 87 NA 61 60 40 Conclusions: Falling affected a significant proportion of PD
MDS-UPDRS IV 10 12 12 NA 12 12 16 patients, especially in advanced stages. It was related to reduced HR-
NA not available QoL and was associated to a variety of generic and PD-specific
factors.

Methods: The present study includes PD patients with symptom

onset between 1974 and 1984 and age of onset older than 35 years.
All patients met Parkinso ns disease Society Brain Bank (PDSBB)
diagnostic criteria. By the censor date of this analysis (December 31,
2012) only 7 subjects of the initial cohort of 237 were still alive. All
surviving patients were contacted and invited to provide written
informed consent. Consenting subjects subsequently underwent a
standardised clinical in-person examination by one of the authors.
Results: All patients were in Hoehn and Yahr stages 4 or 5 when
on medication, and all suffered from freezing of gait and marked
postural instability with frequent falls. 5 of 7 patients were wheel-
chair bound. All patients were on Levodopa (LD) and had developed
motor complications with fluctuations and dyskinesias and had even-
tually required invasive therapies to control their LD-related motor
complications: 4 had received deep brain stimulation of the subthala-
mic nucleus, one patient had undergone thalamotomy and one sub-
thalamotomy and two were on chronic intrajejunal levodopa infusion
therapy (treatment duration of 3 and 5 years). At last follow-up, 4 of
7 patients still had L-Dopa induced dyskinesias, which were dis-
abling in two. Fluctuations were present in all patients and all but
one were classified as disabling. All except one patient had devel-
oped disabling degrees of dysphagia and dysarthria, 3 of 7 patients
were demented and recurrent visual hallucinations with loss of
insight were prominent in 6 of 7 patients. Bladder dysfunction was
present in most (5/7) and associated with urinary incontinence in 4
cases. Constipation was a complaint in all surviving patients while
symptomatic orthostatic hypotension was only present in one case.
Conclusions: At late-stages of up to 38 years of disease duration,
motor fluctuations are still disabling, the motor phenotype is akinetic
rigid and non-motor symptoms are present in almost all of them.
1209
Falls in ambulatory non-demented patients with Parkinsons
disease
O. Rascol, S. Perez-Lloret, P. Damier, A. Delval, P. Derkinderen, A.
Dest
ee, W.G. Meissner, F. Tison, L. Negre-Pages (Toulouse, France)
1210
Movement quantification for evaluation of gait in Parkinsons
disease using a RGB-D camera system
M.J. Rosas, J.P. Cunha, A. Rocha, H. Choupina, J.M. Fernandes, R.
Vaz (Porto, Portugal)
Objective: The main objective of this study was to evaluate the
suitability of an innovative RGB-D camera system to analyze gait in
Parkinsons disease (PD).
Background: Movement quantification can be valuable in the
assessment of Movement Disorders, such as PD, allowing quantita-
tive evaluation that may complement the physicians observations
towards a decision. This support can enable an improved diagnosis
procedure, leading to better treatment and therefore to increased
patients quality of life.
Methods: The experiment was performed in an 8x3 meters space
in 6 PD patients with an implanted DBS stimulator (5 males, 1
female; 60.5 1/- 5.6 years, 1.7 1/- 0.1 m, 83.3 1/- 9.5 kg) and 6
control subjects (3 males, 3 females; 55 1/- 10.9 years, 1.7 1/-
0.1 m, 81.3 1/- 13.9 kg). All patients provided written consent. An
innovative RGB-D camera system acquired computed 3D position of
20 body joints, as well as color and infrared radar depth images,
from the subjects while performing a 16 meters gait task. The task
was repeated 3 to 15 times by each subject, depending on gait diffi-
culties. The PD patients had their stimulator turned off. The acquired
data contained 133 gait cycles (41 from controls, 92 from patients),
totalizing 4,264 data frames. For each 3D joint data frame, we com-
puted 22 different spatial and temporal kinematic measures (velocity,
angle and distance between given joints). For each gait cycle, the
average and variance over all 22 measures were calculated, resulting
in 44 parameters. Additionally, 4 parameters commonly used in gait
analysis were analyzed. Statistical analysis was performed using a
Wilcoxon rank test.
Results: Both average and variance values for the velocity of all
joint types, and the distance between symmetrical limb joints were
lower for PD patients. The same is observed for the variance of all
considered angles. Considering a significance level of 0.1% (p-val-
ue</=0.001), 33 out of 48 explored parameters statistically

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
discriminate between PD and non-PD subjects. The highest discrimi-
native ones for each class (velocity, angle and distance) are pre-
sented in [table1] along with stride duration and length, average
stride velocity and cadence.
Average 6 SD values of the most discriminative parameters
(higher p values) and for commonly used parameters in gait
analysis literature (shaded rows)
Parameter Non-PD PD p-value
Average of velocity 1.3 1/- 0.2 0.9 1/- 0.4 p<0.001
of knee (m/s)
Average of angle 161.9 1/- 4.0 168.1 1/- 2.2 p<0.001
at knee ( )
Average of distance 0.6 1/- 0.1 0.5 1/- 0.1 p<0.001
between wrists (m)
Stride duration (s) 1.1 1/- 0.1 1.1 1/- 0.1 NS
Stride length (m) 1.2 1/- 0.2 0.8 1/- 0.4 p<0.001
Average stride 1.1 1/- 0.2 0.8 1/- 0.3 p<0.001
velocity (m/s)
Cadence (steps/min) 53.9 1/- 5.6 55.4 1/- 5.5 NS
Conclusions: The results suggest that the described innovative
system may provide additional information for management of PD
patients, namely for fall risk assessment and gait quality evaluation.
1211
Non-motor symptoms profiles of different ethnic groups with
Parkinsons disease: A study comparing the UK, Thailand,
Nigeria and Kuwait
A. Sauerbier, O. Jitkritsadakul, R. Bhidayasiri, J.Y. Al-Hashel, W.A.
Kamel, A. Kilany, T. Farombi, P. Martinez-Martin, R. Brown, M.
Parry, A. Martin, R. Inniss, L. Perkins, D. Trivedi, L. Klingelhofer,
A. Rizos, P. Zis, K. Ray Chaudhuri (London, United Kingdom)
Objective: To analyse and compare the non-motor symptoms
(NMS) profile and burden in people with Parkinsons (PwP) with dif-
ferent ethnic origins: Asian (Thailand), African (Nigeria), Arab
(Kuwait) and White Caucasian (UK).
Background: Previously, we reported that NMS profiles might be
different in White Caucasians (WC) PwP versus Indian PwP in the
UK (Sauerbier et al, 2014; Chaudhuri et al, 2000).
Methods: Clinical data related to Asian (Thai) PwP in Thailand,
African PwP in Nigeria, Arab PwP in Kuwait, Syria and Egypt and
White Caucasian PwP in UK as part of a NMS naturalistic longitudi-
nal study using the Non motor symptoms scale (NMSS) were ana-
lysed. Cross sectional data is presented.
Results: 60 Thai patients (45% male, mean age
60.49 6 11.24years, mean duration of disease (DoD) 10.75 6 5.43
years, age at PD onset 49.73 6 12.36 years, mean Scopa Motor Score
28.7 6 14.1), 46 Arab patients (53% male, mean age 63.16 6 10.80
years, mean DoD 10.3 6 5.6 years, age at PD onset 53.17 6 11.50
years, mean Scopa Motor Score 20.46 6 10.69), 30 African patients
(73% male, mean age 62.58 6 10.34 years, mean DoD 2.7 6 2.2
years, age at PD onset 59.88 6 9.73 years) and 59 WC (71% male,
mean age 67.95 6 10.20 years, mean DoD 7.55 6 6.15 years, age at
PD onset 60.32 6 11.19 years, mean Scopa Motor Score
16.85 6 9.29) have been compared in this ongoing study.
Applying the Kruskal-Wallis equality-of-populations rank test we
found a significant difference between the 4 different ethnic groups
in the domains sleep and fatigue (p<0.001), attention and memory
(p<0.01), gastrointestinal dysfunction (p<0.01), urinary dysfunction
(p<0.001), sexual dysfunction (p<0.001) and miscellaneous
(p<0.001). In addition, the NMSS total score was significantly dif-
ferent between the 4 ethnic groups (p<0.001).
S471
Conclusions: This is a first study of its kind and our preliminary
results support previous observations that NMS profiles might differ
between different ethnic groups. However, given that we present a
snapshot survey in non-matched populations, the study is expand-
ing to larger sample size to explore the range and nature of these
differences.
1212
Unawareness of hyposmia in elderly people with and without
Parkinsons disease
H.A. Shill, J.G. Hentz, J.N. Caviness, E. Driver-Dunckley, S. Jacob-
son, C. Belden, M.N. Sabbagh, T.G. Beach, C.H. Adler (Sun City,
AZ, USA)
Objective: To examine the frequency of unawareness of hypo-
smia in a cohort of subjects enrolled in a longitudinal aging study
and examine the relationship of unawareness to cognitive status.
Background: Hyposmia is common in Parkinsons disease and is
also seen with normal aging. It can be ascertained through objective
testing but it is unclear whether patients are aware of deficits and
whether this has implications for cognitive status.
Methods: Subjects in the Arizona Study of Aging and Neurode-
generative Disorders were studied with annual motor and cognitive
testing with objective smell testing (UPSIT) done every third year
beginning in 2002. Those with a baseline UPSIT <25 percentile
(hyposmia) were studied for presence of unawareness of hyposmia
and cognitive status.
Results: There were 75 subjects with Parkinsons disease (PD)
and 143 non-Parkinsonian controls with hyposmia. In the PD group,
9% had dementia and 16% had MCI, while in the control group,
27% had dementia and 16% had MCI. Lack of awareness of hypo-
smia was present in 16% of the PD subjects and 47% of those with-
out PD. In PD, there was no increase in unawareness in PD with
dementia. In non-PD controls, unawareness was correlated with pres-
ence of dementia. Unawareness of hyposmia correlated most strongly
with the neuropsychiatric tests of learning and memory. In controls
without dementia or PD, 48% were unaware.
Conclusions: Querying patients about anosmia might be useful in
Parkinsonian disorders without objective testing. However, in elderly
controls, it should be followed by objective testing and lack of
awareness has implications for worsened cognitive status.
1213
Variability of motor symptoms assessments in Parkinsons
disease and levodopas effect
L. Sid-Otmane, M. Panisset (Montreal, QC, Canada)
Objective: To observe the motor manifestations of non-
fluctuating patients with Parkinsons disease (PD) in the setting of
repetitive levodopa challenges with increasing doses.
Background: Motor assessments are common practice in PD for
either clinical or research purposes. However, symptoms severity
may vary from one day to the next and it is uncertain whether this
variation makes a difference in l-dopas effect.
Methods: In a study investigating the effect of levodopa on cog-
nition, five PD patients were evaluated using UPDRS-III and finger
tapping tests. Patients were tested weekly in technical OFF and again
one hour after increasing doses of levodopa, starting at 50mg and
increasing by 50mg at each subsequent visit until reaching a cogni-
tive endpoint. Symptom categories (PIGD, axial, bradykinesia, rigid-
ity and tremor) were derived from the UPDRS-III.
Results: Subjects showed variability between assessments in their
UPDRS-III OFF scores. Within subject variations were more stable
in the group for bradykinesia and PIGD compared to axial, tremor
and rigidity that differed from one subject to the other (Figure 1).
[figure1]
Movement Disorders, Vol. 30, Suppl. 1, 2015
S472 POSTER SESSION

Increasing doses of levodopa translated into variable scores, but
not respecting a linear dose-response profile. Also, doses that
induced the best ON scores in UPDRS-III (lowest UPDRS-III score)
were not the doses that induced the best improvement from the
patients OFF states (decrease from the OFF score) (Table 1 & 2).
change or the final ON score is more important to consider. Bradyki-
nesia and rigidity seem to be the symptoms that are more sensitive
to levodopa.

1214
Doses (mg) inducing the best ON state
The clinical spectrum of PARKIN disease (PARK2) and
PIGD Axial Rigidity Bradykinesia Tremor
heterozygous gene mutation carriers
S1 50 100 150 50 - R. Stark, J. Walch, B. Tettenborn, G. K
agi (St. Gallen, Switzerland)
S2 200 200 100 100 - Objective: To report the clinical variability of the affected sisters
S3 100 100 100 250 200 and to discuss the role of heterozygous gene mutation carriers in a
S4 150 150 100 150 - family with autosomal recessive Parkinsonism due to compound het-
S5 50 50 100 100 50 erozygous mutation in the parkin gene (PARK 2).
Results: #1: This 32 year old woman reported a three years his-
-: No score differences between the doses tory of progressive bilateral tremor of the hands. She presented with
a jerky tremor of both hands resembling myoclonus-dystonia pheno-
type. There were no clear cut signs of Parkinsonism, normal gait and
full eye movements. The Levodopa challenge test (200mg) was
Doses (mg) inducing the best improvement negative.
#2: This 23 years old sister reported a 4 years history of progres-
PIGD Axial Rigidity Bradykinesia Tremor sive gait problems. The clinical examination revealed dystonia with
tremor and bradykinesia pronounced on the left side with worsening
S1 200 150 200 150 50 of leg dystonia when walking.
S2 100 100 200 100 - Further investigations showed a negative Levodopa challenge test
S3 200 200 100 100 200 and severe bilateral pre-synaptic dopaminergic deficit in the DaTS-
S4 100 100 100 150 - CAN. Genetic testing was performed and revealed a compound het-
S5 50 50 100 100 100 erozygous mutation in the PARK-2 Gene: A point-mutation
c.714C>G; pC238W and a deletion in Exon 3.
-: No score improvements with the doses #3: At the age of 45 the father of case 1 1 2 developed tremor in
his left arm with only mild progression over the past years. At the
While bradykinesia and rigidity showed improvements with lower age of 62 he presents with mild left sided Parkinsonism with tremor
doses, higher doses were necessary to improve PIGD and axial and bradykinesia. His DaTSCAN shows a slightly asymmetric
symptoms. dopamine-transporter distribution in the putamen. He is likely either
Increasing doses of levodopa induced improvements with variable to be the carrier of the deletion or the point mutation. Respective
amplitudes in the finger tapping test. ON performances became better tests are currently performed.
as the doses increased until reaching a ceiling effect. Conclusions: Some points in this family with PARKIN disease
Conclusions: Variability is an important aspect to consider when merit attention:
evaluating patients in their OFF states. There is a variation in the -Dystonia is a common symptom in PARKIN disease but the
profiles across the different symptom/composite scores that we sur- myoclonus-dystonia phenotype of the older sister is unusual. The
veyed. Patients levodopa responses appear to be affected by their clue to the diagnosis was the younger sister, who presented with a
respective OFF state scores, questioning whether the amplitude of more classical young onset PD.

Fig. 1. (1213).

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
-Even though PARKIN disease is known to have an excellent
response to Levodopa, the Levodopa challenge test was negative in
both sisters. This underlines the lack of sensitivity of this test.
-It is an on-going discussion whether heterozygous carriers of one
parkin mutation develop subtle Parkinsonism. #3 presented here is a
good example favouring this hypothesis. Further support comes from
a F-Dopa PET study in parkin gene mutation carriers, which showed
that in these cases mean striatal uptake is lower than in healthy con-
trols. [Khan et al, Brain 2002]
1215
Clinical characteristics of Parkinsons disease with and without
family history of essential tremor
B. Tserensodnom (Ulaanbaatar, Mongolia)
Objective: To compare two groups of Parkinsons disease (PD)
patients with and without family history of Essential tremor (ET)
with regard to motor and non-motor symptoms.
Background: ET is a common Movement Disorder, characterized
with postural and action tremor. Recent reports have suggested that ET
and PD can coexist in the same patients and the higher frequency of PD
in patients with ET. We hypothesized that the presence of positive fam-
ily history of ET is clinically different from PD patients without ET.
Methods: Total 73 patients: 30 male (41.5%) and 43 female
(58.5%) patients with PD in according to UKBBPD criteria have
been enrolled. 11 PD patients had positive family history of ET (PD-
ET) in comparison to 62 patients without ET history (PD-nET) were
classified using retrospective analysis and questionnaire. We assessed
motor impairment using Hoehn and Yahr stage (HY), Unified Parkin-
sons disease Rating Scale (UPDRS) III parts. Non motor symptoms
were evaluated with (UPDRS) II parts, Shwab England daily activity
score, Mini Mental Status Examintaion (MMSE), de Boers quality
of life (QOL) questionnaire, and Beck Depression Inventory (BDI).
Results: 11 PD-ET (19%) patients (mean6SD age, 71.9 6 10.6
years; age at onset 68.4 6 10.3 years; mean duration of PD, 3.6 6 2.3
years) were matched with 62 PD-nET (81%) patients (mean6SD age
65.8 6 9.5 years; age at onset, 61.7 6 10.5 years; mean duration of
PD, 4.1 6 3.3 years).
Nonparametric Mann-Whitney test was done to elicit differences
in clinical characteristics among PD-ET vs PD-nET patients. PD-ET
patients had older aged (p50.004), later onset of disease (p50.003),
lower Hoehn and Yahr stage (p50.008), less severe motor symptoms
on UPDRS III (p50.02) and less akinesia (p50.002) and rigidity
subscore on UPDRS (p50.001) than PD-nET patients. In contrast,
there were no significant differences in tremor subscore on UPDRS,
cognitive function on MMSE score and depressive disorder in BDI
between two groups. PD-ET patients had higher score of QOL on
Boer (p50.02) and Shwab-England (p50.004) than PD-nET patients.
Conclusions: Our results suggest that positive family history of
ET in PD patient is related with old age, later and benign develop-
ment of PD and less severe motor symptoms. We could not find sig-
nificant differences in two groups concerning non-motor symptoms.
We suggest that more epidemiological and genetic studies are needed
to clarify this association.
1216
Stiff-limb syndrome affecting the arm; case report
E. Urrea-Mendoza, E. Dornoff, F.J. Revilla (Cincinati, OH, USA)
Objective: Describe an unusual clinical presentation of Stiff-
person syndrome and discuss the differential diagnosis.
Background: This disease is sporadic, it can be paraneoplastic or
idiopathic, affecting individuals of both genders, with a 2:1 male/
female ratio. In more than two thirds of patients the symptoms begin
with paroxysmal fear, easy startling, emotionally induced spasms, or
frequent falls. Two main sets of symptoms have been described: trun-
cal and proximal limb stiffness due to co-contraction of agonist and
S473
antagonist muscles, and superimposed episodic spasms. The spasms are
often caused by unexpected noise, tactile or visual stimuli, or strong
emotions. Stiffness is predominantly in the thoracolumbar paraspinal
muscles or abdominal muscles with progressive spread to proximal
limb muscles over time. Typically the lower extremities are affected.
Methods: Case report.
Results: We describe a 38-year-old woman who presented with a
3-year history of progressive stiffness and painful spasms limited to
the right upper extremity. Her deep tendon reflexes were increased
exclusively in right arm. Her plantar response was normal bilaterally.
Her serum and cerebrospinal fluid were positive for anti-glutamic acid
decarboxylase (anti-GAD) antibodies, titers were elevated (786.6
nmol/L); and negative for other antibodies, including anti-amphiphysin
antibody testing. She had extensive negative work-up for occult cancer
and paraneoplastic syndromes. Electromyography of antagonist muscle
pairs in the lower limbs was normal. There was a failure in reciprocal
inhibition in the right upper extremity. Her symptoms improved sub-
stantially with monthly IVIg treatment for 13 months.
Conclusions: To our knowledge this is the first report of symptoms
limited to one upper limb in a patient with stiff-person syndrome with
anti-GAD positive antibodies. Clinical and immunological findings
indicate that Stiff-person syndrome is a heterogeneous disease, sug-
gesting the need to redefine its diagnostic criteria.
1217
Identification of freezing of gait in Parkinsons disease using
waist mounted accelerometry
H. Zach, A.M. Janssen, A.H. Snijders, A. Delval, M.U. Ferraye, E.
Auff, V. Weerdesteyn, B.R. Bloem, J. Nonnekes (Vienna, Austria)
Objective: To investigate the sensitivity and specificity of the
freeze index to detect FOG episodes, especially during full rapid
turns and when walking with short steps rapidly with an accelerome-
ter attached to the lumbar region.
Background: Freezing of gait (FOG) is a common and debilitat-
ing phenomenon in Parkinsons disease (PD). Wearable accelerome-
ters can help to assess FOG in the research setting. Although FOG is
most often provoked during rapid full turns and when walking with
rapid short steps, it has not been evaluated whether accelerometry is
able to detect FOG while executing these tasks.
Methods: Twenty-three patients with Parkinso ns disease partici-
pated, who all had objective FOG. Participants performed several
walking tasks, including walking with short steps rapidly and rapid
full turns in both directions. Two experts identified FOG episodes
using off-line video-analysis, which acted as the gold standard. A
previously validated algorithm[1-3] that uses the ratio between nor-
mal locomotor (0.5 3 Hz) and pathological freezing frequencies (3
8 Hz) was applied on the accelerometer data to assess the
episodes.
Results: FOG was most often observed during full rapid turns
(81% of all episodes), followed by walking with short rapid steps
(12% of all episodes). During full rapid turns, accelerometry yielded
a sensitivity of 78% and specificity of 59%. A sensitivity of 64%
and specificity of 69% was observed during walking with small steps
rapidly. All tasks combined rendered a sensitivity of 75% and speci-
ficity of 76%.
Conclusions: Our results show that FOG can be detected from a
single lumbar attached accelerometer during several walking tasks,
including full rapid turns and walking with short steps rapidly. It holds
promise to be implemented in the research setting, but future studies
are first needed to further improve the sensitivity and specificity.
1218
Improving mobility assessment of Parkinsons patients using the
WIMuGPS system
L.F. Zhu, P. Boissy, C. Lavigne-Pelletier, M. Jog, R. Edwards, C.
Duval, M. Speechley (London, ON, Canada)
Movement Disorders, Vol. 30, Suppl. 1, 2015
S474 POSTER SESSION
Objective: 1. Provide comprehensive data on PwPs community
mobility. 2. To determine factors influencing the mobility of PwPs in
their natural setting.
Background: Common understanding of reduced life spaces of
people with Parkinsons disease (PwPs) is based on bias-prone self-
report measures. Wearable activity trackers are a promising alterna-
tive for objective mobility measurement, by adding data on distance
travelled and activity level in- and outside the home.
Methods: Over 14 days, 51 PwPs (Hoehn and Yahr stages I - III;
mean age: 68.6 6 6 years; mean disease duration: 6.6 6 6.4 years; 34
men) wore a GPS embedded with wireless inertial motion units
(WIMuGPS) during awake hours. PwPs also were assessed for: cogni-
tive status, comorbidity, social support, physical activity, quality of
life, disease duration and health status, residence setting and demo-
graphics. Simple linear regression was performed using these variables.
Results: 11.2 6 2.1 hours/day of data was collected from each PwP.
Daily time at home was 8.7 6 1.9 hours. PwPs made 1 6 0.8 trips out-
side the home/day. Cohabitation, place of residence and physical activity
were significant (p < 0.05) in models to predict number of trips outside
(r2 5 .25, .42, .26, respectively). Distance from home/day covered by
PwPs by car was 42.2 6 15.7 km, and on foot was 0.7 6 1.7 km. Partici-
pants occupied 4.3 6 2.1hotspots/day; each with an average distance of
6.1 6 4.7km from home. Time spent at home and hotspot number can
be predicted by disease duration, cohabitation and cognitive status
(r2 5 .34, .27, .44, respectively; p<0.05). Similar significant relationships
were not found for distance to hotspots. Daily area of mobility spanned
112.1 6 134.1 (range 5 2.1 326.5) km2 around the home, and was sig-
nificantly predicted by driving status, sex, cohabitation, place of resi-
dence and social support (r2 5 .15, .45, .54, .14, respectively; p < 0.05).
Conclusions: This is the biggest completed study measuring real
life mobility of PwPs over a long duration using non-invasive weara-
ble instruments. This study extends the existing literature by adding
variables to better describe and predict PwPs life space. It is shown
that PwPs maintained large life spaces, despite spending the majority
of waking hours at home. This approach has great potential to assess
how new treatments affect real life mobility.
1219
Comparing wearable activity sensors and self-report measures of
mobility
L.F. Zhu, P. Boissy, C. Lavigne-Pelletier, M. Jog, R. Edwards, C.
Duval, M. Speechley (London, ON, Canada)
Objective: To compare and contrast self-report vs instrumented
measures of real-life mobility.
Background: Mobility of people with Parkinsons disease (PwPs)
is typically assessed by self-report measures. They are cost efficient,
Comparison of co-existent myoclonus and dystonia in the same body region in SGCE mutation positive and negative cohorts
SGCE
SGCE positive
positive Probands
All (n519) only (n513)
Rest
Overall 10 8 15
Neck 10 8 13
Upper Limbs 0 0
Trunk 0 0
Lower Limbs 1 1
Action
Overall 8 5
Neck 6 5
Upper Limbs 5 4
Trunk 1 0
Lower Limbs 0 0
Movement Disorders, Vol. 30, Suppl. 1, 2015
but are prone to recall bias. Wearable sensors are increasingly being
used to gather large datasets that are free of recall bias.
Methods: Over 14 days, 43 PwPs (Hoehn and Yahr stages I - III;
mean age: 66.6 6 7.1 years; mean disease duration: 7.2 6 5.5 years;
27 men) wore a GPS embedded with wireless inertial motion units
(WIMuGPS) during hours awake. PwPs also completed standard
self-report measures such as the Life Space Assessment (LSA) and
daily mobility diaries. Only one common outcome was generated by
all three measures. Agreement between WIMuGPS and diary on
number of trips taken outside of own property/day were assessed
using % agreement and intraclass correlation (ICC). Agreement
between WIMuGPS and LSA on number of trips taken outside of
own property/2 weeks was measured by % agreement. Convergent
validity between WIMuGPS and self-report measures on the respec-
tive outcomes were assessed using mixed effects repeated measures
correlation.
Results: Moderate agreement between the WIMuGPS and diary
for daily number of trips outside was observed (%
agreement 5 66.9%; ICC 5 0.65). Convergent validity between the
two assessments was attained (r 5 0.67, p 5 0.04). WIMuGPS data
contained 11% data loss (65/602 total days), and 4.2% (25/602 total
days) of diary entries included missing or erroneous records. Reasons
included technical issues (WIMuGPS), difficulties with compliance
(both) and recall (diary). Moderate agreement and convergent valid-
ity between the WIMuGPS and the LSA also were observed on
biweekly trips outside the home (59.9% agreement; r 5 0.68,
p 5 0.03).
Conclusions: The LSA, daily diaries and WIMuGPS can be inter-
changeably used to capture basic measures such as number of trips
made by PwPs. However, quality of mobility or life spaces cannot
be inferred from trip frequency alone since it will generate huge
gaps in the understanding of mobility of patients. Wearable sensors
such as the WIMuGPS have the potential to go beyond estimating
the number of trips by calculating, for instance, distances traveled
between points of interests, the type of transport used (e.g., walking
or by car), area of life space, etc.
1220
Do distribution and co-existent myoclonus and dystonia aid in
the identification of SGCE mutations?
R. Zutt, J.M. Dijk, K. Peall, H. Speelman, Y.E.M. Dreissen, M.F.
Contarino, M.A.J. Tijssen (Groningen, Netherlands)
Objective: To evaluate discriminating motor characteristics of
Myoclonus Dystonia between SGCE mutation positive and mutation
negative patients.
Statistical
SGCE comparison All/ Statistical comparison
negative negative p-value Probands only/negative
(n520) (OR; 95% CI) p-value (OR; 95% CI)
0.19 (0.37;0.08, 1.73) 0.46 (0.53; 0.09,3.05)
0.74 (0.67;0.15, 3.01) 1.00 (0.86; 0.16,4.63)
2 NA NA
0 NA NA
1 1 .00 (1.50;0.04, 62.14) 1.00 (1.80; 0.04,75.80)
17 0.01 (0.13; 0.02,0.71) 0.01 (0.11; 0.01,0.73)
14 0.09 (0.26;0.05, 1.26) 0.15 (0.31; 0.05,1.71)
8 0.51 (0.58; 0.12, 2.74) 0.72 (0.67; 0.12,3.65)
4 0.34 (0.23; 0.01, 2.75) NA
0 NA NA
 POSTER SESSION
Background: Myoclonus Dystonia (M-D) is a young onset
Movement Disorder typically involving myoclonus and dystonia of
the upper body. A proportion of cases are caused by mutations to the
autosomal dominantly inherited, maternally imprinted, epsilon-
sarcoglycan gene (SGCE). Despite several sets of diagnostic criteria,
identification of those patients most likely to have an SGCE mutation
remains difficult.
Methods: Forty patients meeting pre-existing diagnostic clinical
criteria for M-D underwent a standardised clinical examination (20
SGCE-mutation positive and 20 negative). Each video was reviewed
and systematically scored (BFMDRS and UMRS) by two assessors
blinded to mutation status. A third novel tool was developed to allow
recording of co-existent myoclonus and dystonia in one or more of
four body regions (neck, arms, legs and trunk) at rest and with
action.
Results: Thirty-nine patients were included in the study (one
case was excluded owing to insufficient video footage), and subdi-
vided into 24 definite, 5 probable and 10 possible M-D. Myo- hydroxytryptophan and L-dopa is the current treatment. The use of
clonus and dystonia were most commonly observed in the neck and
upper limbs of both mutation positive and negative groups. In the
mutation negative group there was a significant excess of upper
limb myoclonus at rest and cervical and truncal dystonia with
action. Co-existence of myoclonus and dystonia in the same body
part was more commonly seen in the mutation negative cohort
(p50.008).
[figure1]
Conclusions: Overall, the absence of co-existence of myoclonus
and dystonia in the same body part, can serve as an additional pre-
dictive factor in determining the presence of an SGCE mutation in
patients with a M-D phenotype.
Fig. 1. (1220).
S475
Rare genetic and metabolic diseases
1221
Replacement therapy with rotigotine in tetrahydrobiopterin
deficiency: A case report
R. Alberto, P. Francesco, A. Serena, D.M. Francesca, A. Carlo
Alberto, B. Andrea, M. Aristide, Z. Maurizio, S. Marco, L. Leonardo,
R. Mario Giorgio (Torino, Italy)
Objective: To evaluate the efficacy and safety of rotigotine in a
patient with tetrahydrobiopterin (BH4) deficiency.
Background: BH4 is a fundamental cofactor of the enzymatic
hydroxylation of aromatic aminoacids. BH4 deficiency is a rare met-
abolic disorder, causing psychomotor development delay and Parkin-
sonian symptoms. Early replacement therapy with BH4, 5-
dopamine-agonists (DA) has been proposed to reduce L-dopa-
induced complications.
Methods: A 24-years-old male with BH4 deficiency came to our
attention with the following treatment: BH4, 5-hydroxytryptophan,
L-dopa/carbidopa 75/18.75 mg TID, entacapone 200 mg TID, selegi-
line 5 mg/day. Two years before, he underwent paramipexole therapy
(0.7 mg TID), withdrawn because of the occurrence of dyskinesias
and dystonias. Neurological examination showed mild postural/
kinetic tremor, mild bradikinesia, sporadic dyskinesias and early-
morning dystonia. MDS-UPDRS-III score was 12/8 (OFF/ON-condi-
tion). Brain [123I]FP-CIT SPECT was normal. In the attempt to
arrange a more feasible therapy we withdrawn entacapone and
Movement Disorders, Vol. 30, Suppl. 1, 2015
S476 POSTER SESSION
selegiline, starting rotigotine extended-release 6 mg/day and L-dopa/
carbidopa 50/12.5 mg BID.
Results: During the following six weeks the patient reported an
improvement of Parkinsonian symptoms (ON MDS-UPDRS-III
score: 3) with a reduction of early-morning dystonia.
However, three months later, he complained episodes of painful
dystonia of right foot and trunk. Rotigotine was withdrawn and pre-
vious therapy was restored, with resolution of side effects. Further-
more, the clinical condition returned to the previous state (ON MDS-
UPDRS-III score: 8).
Conclusions: This first description of a BH4-deficient patient
treated with rotigotine confirms previous efficacy data on pramipex-
ole. However, our patient developed dyskinesias as already experi-
enced with pramipexole.
The molecular mechanisms of dyskinesias in PD patients are still
unclear, involving aberrant synaptic plasticity and loss of dopamine
storage capacity. Nevertheless, our patient had an intact anatomical
substrate, as demonstrated by [123I]FP-CIT SPECT normality. Our
experience suggests as the mechanism at the basis of DA-induced
dyskinesias might be an overstimulation of dopaminergic striatal
receptors and the presence of an imbalance among different receptor
subtypes, stressing the relevance of post-synaptic mechanisms in the
dyskinesias onset.
1222
Dystonic symptoms in child with GNAO1 mutation respond to
bilateral GPi deep brain stimulation
R.D. Bhardwaj, J. Badhiwala, N. Remec, F. Shelley, S. Johan
(Phoenix, AZ, USA)
Objective: To describe the successful use of bilateral globus pal-
lidus interna (GPi) deep brain stimulation (DBS) for symptomatic
dystonia in a child with GNA01 mutation.
Background: A previously published report that used whole-
exome sequencing described four pediatric patients with a novel het-
erozygous mutation in GNA01, which codes a G Protein subunit;
causing epileptic encephalopathy. Two of these patients also demon-
strated involuntary movements. We report two additional brothers
with the same genetic mutation, also demonstrating severe dystonia
in addition to the epileptic encephalopathy. The elder brother, aged 7
years, underwent bilateral GPi deep brain stimulator implantation
recently, for treatment of primary dystonia. To our knowledge, this
is the first description of the use of DBS in a child with GNA01
mutation.
Methods: Objective findings such as dystonia rating scales [Fahn
Marsden Dystonia Rating Scale (FMDRS)], weight, and primary
caregiver quality of life data (from published and validated cerebral
palsy quality of life questionnaire for children) were serially noted
over the past five months since DBS implantation.
Results: The patients FMDRS score dropped from 65.5 pre-op
down to 35.0 after five months of continuous DBS therapy, demon-
strating a 46.6% reduction in score. Our patients weight increased
from 26.2 kg to 33 kg (a 26% increase) over 5 months, and his oral
anti-dystonic medications dropped from seven to three agents in total
over the five months. Significant gains were also noted within the
quality of life questionnaire across many domains of life, from the
parents perspective.
Conclusions: This is the first known report of a successful clini-
cal response to bilateral GPi DBS implantation therapy in a patient
with dystonia, from a GNA01 genetic mutation.
1223
Drug response to zinc and D-penicillamine in ATP7B mutant
hepatic cell lines
G. Chandhok, J. Horvath, A. Aggarwal, M. Bhatt, A. Zibert, H.H.J.
Schmidt (Munster, Germany)
Movement Disorders, Vol. 30, Suppl. 1, 2015
Objective: To evaluate functional characterization of most com-
mon disease-causing ATP7B mutations observed in Wilson[apos]s
disease (WD) patients following zinc (Zn) and D-penicillamine
(DPA) treatment.
Background: WD is an autosomal recessive disorder caused by
mutations in the ATP7B gene. Copper (Cu) chelation is commonly
used for reversal of toxicity either directly by chelators like DPA or
indirectly by metallothionein induction by Zn. The impact of these
drugs on the survival of hepatocytes carrying individual mutations is
unknown.
Methods: As an extension to our previous report on ATP7B
knockout hepatic cell line (PLoS ONE, 9: e98809, 2014), we gener-
ated stable cell lines expressing ATP7B mutations commonly
observed in Europe/US, Asia, and India. ATP7B gene and protein
expression were determined for all mutant cell lines. The effect of
Cu on viability, apoptosis, and intracellular trafficking was studied.
Cell survival and apoptosis were determined following Cu exposure
and treatment with Zn, DPA, or both.
Results: ATP7B mRNA was similar whereas protein expression
varied among the different mutant cell lines. Co-localization studies
suggested impaired trafficking in presence/absence of Cu in various
mutant cell lines. Cell viability studies showed different grades of
survival with p.H1069Q displaying moderate ATP7B activity. On
treatment with Zn, DPA, or both most cell lines showed individual
response to treatment. DPA was more effective than Zn in rescuing
cells against Cu toxicity. Only Zn/DPA combination treatment was
able to rescue the mutant cells similar to wild-type.
Conclusions: The study functionally characterized major disease
causing mutations observed in WD. ATP7B mutations showed a
genotype-specific response to treatment. Combination treatment with
Zn and DPA showed maximal survival of hepatic cells. Our data
suggest that efficacy of WD treatment may benefit from knowledge
of mutation-specific in vitro functional analysis and use of Zn/DPA
combination therapy.
1224
Rapidly progressive Parkinsonism in a patient with incontinentia
pigmenti
J.Y. Chen, V.S. Oza, R. Gopi, C.W. Christine (San Francisco, CA,
USA)
Objective: To describe a patient with Incontinentia Pigmenti (IP)
who developed rapidly progressive Parkinsonism.
Background: IP is a rare X-linked dominant disorder of ectoder-
mal development with a prevalence of 0.7/100,000. Besides skin it
may involve other ectodermal tissues including, teeth, hair, nails,
eyes as well as the central nervous system. About 30% of cases have
neurologic manifestations that vary from a single seizure to severe
motor and/or intellectual disabilities. All documented neurological
manifestations in the literature have developed in childhood, the
majority of which occur in the first year. About 80% of cases are
due to mutations in the NEMO/IKBKG gene. To our knowledge,
there have been no reports of Movement Disorder developing in a
patient with IP.
Methods: A single case report. Genetic testing was performed by
a commercial lab, (GeneDX).
Results: This woman was diagnosed with IP in infancy due to
skin abnormalities and later developed typical dental changes and
axillary hyperpigmentation. She completed high school and college
and then worked as a teacher. There was no family history of neuro-
degenerative diseases. At the age of 48 she developed asymmetric
bradykinesia, hypophonia, and gait changes. She had a good initial
response to levodopa but wearing-off developed requiring more fre-
quent dosing. By age 53 she had developed cognitive impairment
and moderate wearing-off. By age 54 she had become almost com-
pletely reliant on her husband for activities of daily living. A DAT
scan performed then showed nearly absent uptake of tracer in
 POSTER SESSION
caudate and putamen bilaterally. Genetic testing showed a novel
NEMO/IKBKG mutation predicted to cause loss of normal protein
function.
Conclusions: This relatively young woman with typical IP, devel-
oped rapidly progressive Parkinsonism. Although the co-occurrence
of these conditions could simply be due to chance, we speculate that
her genetic mutation makes her more susceptible to neurodegenera-
tion, perhaps due to alteration in NEMO/IKBKG function that nor-
mally provides neuronal anti-apoptotic signaling. This observation
may provide further insight into the cellular mechanisms underlying
neurodegeneration.
1225
Compound heterozygosity (c.352_353delAG and c.3517A>G) for
Niemann-Pick type C1 disease presenting as sporadic adult-onset
cerebellar ataxia, dystonia and supranuclear ocular paresis
M. Coelho, A.D. Magalh~ aes, L. Correia-Guedes (Lisbon, Portugal)
Objective: We report a case of Niemann-Pick type C1 disease.
Background: Niemann-Pick type C (NPC) disease is a rare auto-
somal recessive, probably underdiagnosed disorder, in which the
lysosomal accumulation of lipids causes a wide variety of symptoms
that difficult its diagnosis.
Results: A 41-year-old woman visited the department for imbal-
ance and difficulty swallowing, slurred speech and impairment in
memory and attention. On neurological examination there was execu-
tive dysfunction, mild short-term memory deficit, hypermetric sac-
cades and slowing of vertical ocular movements, facial dystonia,
scanning speech, limb ataxia and truncal ataxia, intention tremor,
inability to stand unaided with oscillations in every direction, wid-
ened base, unstable gait and inability to tandem walk. No evidence
of Parkinsonism or proprioceptive loss. Brain MRI showed pancere-
bellar atrophy. Inflammatory, vascular, toxic, endocrine and nutri-
tional, infectious and structural causes were excluded. Genetic
testing for SCA1,2,3,6,7 and 17, DRPLA and ataxia with oculomotor
apraxia type 1 and 2 was negative. Filipin test on skin biopsy was
positive and genetic testing for NPC1 showed compound hetero-
zygosity for c.352_353delAG (p.Q119fs*8) and c.3517A>G
(p.R1173G) mutations, the latter not previously reported.
Conclusions: NPC is a treatable disease that can manifest itself
in the adult as cerebellar ataxia, dystonia and abnormal ocular move-
ments even whithout family history. We report a case of a compound
heterozygosity and a new mutation not yet described.
1226
Neurologic manifestations of Lesch Nyhan syndrome improved
with bilateral deep brain stimulation, a case report
R.A. Falconer, S.L. Rogers, Y. Yaghi-Torres, K. Grajny, C. Kalhorn,
F. Amjad (Washington, DC, USA)
Objective: To evaluate the potential for a therapeutic approach of
bilateral deep brain stimulation to control movements associated with
Lesch Nyhan Syndrome.
Background: Lesch-Nyhan Syndrome (LNS) is a rare inherited
disorder caused by a deficiency of the enzyme hypoxanthine-guanine
phosphoribosyltransferase (HGPRT), which causes a buildup of uric
acid throughout the body and subsequent renal dysfunction and gout.
Neurological symptoms manifest early in life, including intellectual
disability, poor muscle control, facial grimacing, writhing and repeti-
tive movements of the arms and legs along with characteristic self-
mutilating behavior. Specifically, hyperkinetic movements consisting
of ballistic movements and dystonia are present. While the aforemen-
tioned symptoms due to the buildup of uric acid respond well to
treatment, the neurological symptoms typically do not respond to
medical treatment.
Methods: We present a case of a 29-year-old male with a history
of LNS, whose condition was characterized by early-onset self-muti-
S477
lating behaviors and late-onset debilitating dystonias and ballistic
movements. He was treated with deep brain stimulation (DBS) tar-
geting the bilateral globus pallidus interna, which led to considerable
improvement in these neurologic impairments.
Results: Our case shows that utilizing DBS in a patient with
LNS improved the extrapyramidal movements and speech impair-
ment. Objective evaluations over the 5-year period during which he
was followed at our institution demonstrate improvement in the fol-
lowing characteristics: articulation of speech, delayed speech initia-
tion, dystonias, and ballistic movements.
Conclusions: Deep brain stimulation is widely accepted as an
effective treatment for the symptoms of Parkinsons disease, but
reports that describe its use in LNS are limited. Our patients speech
became clearer and his extrapyramidal symptoms, such as dystonias
and writhing movements, were minimized after treatment, highlight-
ing the benefits of DBS treatments in such cases.
1227
Dystonia and seizures as first manifestations of primary
hypoparathyroidism in children: Report of two cases
J. Gonzalez Mujica, C. Cosentino Esquerre (Lima, Peru)
Objective: We present two pediatric patients who presented axial
dystonia and seizures as first manifestations of undiagnosed primary
hypoparathyroidism (PH).
Background: PH caused by parathyroid hormone deficiency and
characterized by hypocalcemia, is a rare condition, especially in the
pediatric population. Patients often present clinical manifestations
related to hypocalcemia such as tetany, muscle cramps, carpopedal
spasms and seizures. Neurological symptoms include behavioral and
cognitive abnormalities and Movement Disorders (tremor, Parkinson-
ism, chorea and ataxia). Dystonia has rarely been reported and might
be related to basal ganglia calcifications.
Methods: We present the clinical cases of two patients who, pre-
viously asymptomatic, presented axial dystonia followed by tonic-
clonic seizures with laboratory results and neuroimaging diagnosis of
PH.
Results: Two boys (7 and 12-y-o) with no personal or familial
medical history presented intense episodes of dystonia affecting
trunk, behavioral disorders and tonic-clonic seizures. Examination
did not revealed neurological deficit. Routine blood tests showed low
total and ionic calcium levels, elevated serum phosphate level,
slightly low magnesium level and low intact PTH level. MRI and
CT brain scan revealed bilateral calcifications involving basal ganglia
and subcortical white matter. With these findings diagnosis of PH
was made.
Conclusions: Metabolic disorders, especially hypoparathyroidism,
should be considered in children with seizures, Movement Disorders
and basal ganglia (and subcortical white matter) calcifications. Proper
identification of these conditions will allow early and appropriate
treatment and will prevent the emergence of possible long-term
sequelae.
1228
A novel PANK2 gene mutation in a patient with pantothenate
kinase-associated neurodegeneration
J.M. Hatcher-Martin, A.R. Rosen, S.A. Factor (Atlanta, GA, USA)
Objective: We report on a patient with pantothenate kinase-
associated neurodegeneration (PKAN) due to a novel mutation in the
PANK2 gene.
Background: Pantothenate kinase-associated neurodegeneration
(PKAN) is also known as neurodegeneration with brain iron accumu-
lation type 1, or NBIA1. It is an autosomal recessive disorder result-
ing from mutations in PANK2, the gene encoding pantothenate
kinase, a key regulatory enzyme in CoA synthesis. It is classically
Movement Disorders, Vol. 30, Suppl. 1, 2015
S478 POSTER SESSION

characterized by accumulation of iron in the basal ganglia resulting

in the classic eye-of-the-tiger sign on MRI.
Methods: Case Presentation.
Results: A 17-year-old male presented with worsening oroman-
dibular dystonia that began approximately six months prior to pre-
sentation. Upon further questioning, the patient was noted to always
be mildly clumsy and began showing some abnormal posturing in
his upper extremities around the age of 11. He has four older sisters
without any similar signs. Clinical exam showed severe jaw-opening
dystonia which significantly interfered with speech. He also had dys-
tonic posturing in his upper extremities, trunk, and left leg. Mild Par-
kinsonism was present as well as evidenced by moderate
bradykinesia and postural instability. MRI showed the classic PKAN
finding of the eye-of-the-tiger sign. Genetic testing revealed a
known pathogenic mutation in the PANK2 gene at c.460>T
(p.Arg154Trp) in exon 2 and a never-before reported mutation at
c.958A>G (p.Thr320Ala) in exon 4. Subsequent testing of his
parents confirmed that each mutation came from one parent. Thus
far, he has had mild-to-moderate response to botulinum toxin and
trihexyphenidyl.
Conclusions: This patient demonstrates the classic clinical and
radiographic presentation of PKAN due to compound heterozygous
PANK2 mutations, one of which has not previously been described. Fig. 1. (1229).

1229
Familial Creutzfeldt-Jakob disease: A novel phenotype associated
with E200K-129M mutation
D. Kaul, M. Feldman (Lebanon, NH, USA)
Objective: To present a unique phenotype of a pathologically
confirmed familial Creutzfeldt-Jakob Disease (fCJD) case, in whom
hemi-chorea was an initial presenting feature of the disease with
rapid onset and progression to death within 3 weeks.
Background: Creutzfeldt-Jakob disease (CJD) is the most com-
mon prion disease in humans and is associated with rapidly progres-
sive neurologic decline, cognitive dysfunction and Movement
Disorders. Familial CJD usually has a slower progression and is
caused by specific mutations in the gene encoding for the prion pro-
tein. Typical symptoms include cognitive impairment, ataxia, and
myoclonus. Hemi-chorea has not been previously been described as
an initial presenting symptom in familial CJD. Furthermore, rapid
progression of fCJD is atypical.
Methods: A 52 year old male presented with abnormal move-
ments for two weeks. He had an involuntary, slow writhing move-
ment of the right arm, hand, leg, and foot. The patients relatives
reported that his memory was intact and he was actively working.
They also observed that he was speaking slowly, and appeared nerv-
ous. There was no family history of abnormal movements. On exam-
ination, by a Movement Disorders trained neurologist, the patient
had right hemi-chorea, mild postural and kinetic tremors in his upper
extremities, brisk deep tendon reflexes, and a Mini Mental State
Examination of 25/30. He rapidly progressed to develop worsening
chorea, diffuse myoclonic jerks, ataxia, and had altered mental sta-
tus, and died in 3 weeks.
Results: MRI of his brain demonstrated cortical ribboning in the
left frontal and temporal regions and a pulvinar sign. [figure1]
Lumbar puncture had an elevated Tau protein and positive 14-3-3.
An EEG demonstrated left hemispheric periodic sharp waves. An
autopsy confirmed CJD through immune-staining with 3F4. Immune-
histochemical and histo-pathological studies was positive for E200K-
129M mutation in the Prion Protein (PRNP) Gene.
Conclusions: Patients with familial CJD have been reported to
have a clinical triad of dementia, ataxia and myoclonus. Hemi-
chorea has not been described as an initial symptom of familial CJD
in the setting of gene variant of E200K-129M mutation in the PRNP
gene. Hemi-chorea may be added to spectrum of initial presenting
symptoms in patients with familial CJD and a rapid disease
progression.
1230
Niemann-Pick type C presenting with psychosis
S.Y. Lee, H.J. Lee, S.M. Cheon, J.W. Kim (Busan, Korea)
Objective: We report Niemann-Pick type C in two siblings.
Background: Niemann-Pick type C is a rare, autosomal recessive
disease with visceral, psychiatric and neurological symptoms.
Methods: First case was 25-year-old male. He started to develop
delusions and limb clumsiness at the age of eighteen years. Halluci-
nation, cognitive impairment and gait disturbance followed within a
few years. On examination, He showed severe ataxic gait, limb dys-
tonia with ataxia, dysarthria, vertical gaze limitation, hyperreflexia,
and severe cognitive deficits. These progressive symptoms were
refractory to symptomatic medical treatment. The abdominal CT
scan revealed hepatosplenomegaly which was not detected on routine
physical examination. There was no definite abnormal finding in the
brain MR image, but widespread hypoperfusion was found in the
brain perfusion SPECT.
Second case was 23-year-old female, younger sister of the first
case. Her symptom was started with right hand clumsiness at the age
of nineteen years. And then psychosis, cognitive impairment and gait
disturbance developed during the next few years. On examination,
she had similar symptoms with her brother, but was milder than him.
She also had hepatosplenomegaly in the abdominal CT scan, and
mild diffuse brain atrophy was found in the brain MR image. NPC1
gene sequencing revealed compound heterozygote for p.R518W and
p.A927V mutations, already known as a genetic cause of Niemann-
Pick type C.
Results: This is the first case report of adolescent/adult form of
Niemann-Pick type C in Korea.
Conclusions: When a patient with generalized dystonia shows
either or both vertical supranuclear ophthalmoplegia and prominent
psychotic features which are unusually accompanied symptoms with
dystonia, hepatosplenomegaly should be searched for the diagnosis
of Niemann-Pick type C even though it is not noticeable on physical
examination.
1231
A Japanese family of hereditary geniospasm
R. Miyamoto, T. Kawarai, R. Oki, Y. Miyazaki, Y. Izumi, R. Kaji
(Tokushima, Japan)

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
Objective: To describe the clinical characteristics of a novel fam-
ily with geniospasm.
Background: Geniospasm is characterized by spontaneous inter-
mittent involuntary quivering or trembling of the chin that is intensi-
fied by stress or anxiety. To date, only about twenty families with
geniospasm have been reported.
Methods: We performed history taking and neurological exami-
nation on 4 symptomatic members in 4 generations of a Japanese
family with geniospasm.
Results: The proband developed intermittent involuntary trembling
in the chin in early infancy. He was otherwise healthy and neurologi-
cally normal. Although the involuntary movement was disappeared
spontaneously at age 8 months, it recurred at age 21 months. His
brother, mother and grandmother also showed an almost identical
involuntary movement; spontaneous and intermittent trembling in the
chin, neonatal or early infant onset, triggered by strong emotion,
absent during sleep. There were some differences in the degree of the
trembling among the affected patients. Spontaneous amelioration with
age was not confirmed in the grandmother. None of the affected
patients presented other neurological disturbances. Botulinum toxin
therapy or anticonvulsant drugs have never been tried.
Conclusions: To our knowledge, this is the first report describing
a Japanese family with geniospasm. The clinical features of the
patients were analogous to those of previously reported cases.
1232
Triheptanoin dramatically reduces the frequency of paroxysmal
Movement Disorders in GLUT1 deficiency
F. Mochel, E. Hainque, D. Gras, I. Adanyeguh, S. Caillet, D.
Rinaldi, B. Heron, E. Kaphan, J.Y. Hogrel, L. Servais, E. Roze
(Paris, France)
Objective: Based on our previous work with triheptanoin, a com-
pound that provides key substrates to the Krebs cycle in the brain,
we wished to obtain a proof-of-concept of its therapeutic benefit in
patients with glucose transporter type 1 deficiency syndrome
(GLUT1-DS).
Background: GLUT1-DS limits brain glucose availability leading
to cerebral energy deficiency. Ketogenic diet, which provides ketone
bodies to the brain and compensates for the lack of glucose, is effi-
cient on seizures control in GLUT1-DS but less on Movement Disor-
ders. Moreover, many patients especially adolescents and adults
have difficulties complying with the diet.
Methods: We performed an open-label study using triheptanoin
in 8 GLUT1-DS patients (7 to 48 years old) with non-epileptic par-
oxysmal manifestations. The study was divided in three phases of 2
months each baseline, treatment and withdrawal phases. We used a
comprehensive patient diary to record all motor and non-motor
events, as well as a clinical global impression scale. In patients older
Fig. 1. (1232).
S479
Fig. 2. (1232).
than 15 years (n55), we performed brain 31P-NMR spectroscopy to
measure the levels of phosphocreatine (PCr) and inorganic phosphate
(Pi) within the occipital cortex before (rest), during (activation) and
after (recovery) a visual stimulus.
Results: Triheptanoin was well-tolerated in all patients. Analyses
were performed on 6 patients as 2 patients were not compliant with the
study. During the baseline phase, GLUT1-DS patients experienced on
average 31 paroxysmal manifestations including 16 dystonic events.
When treated with triheptanoin, paroxysmal manifestations dropped to
an average of 3 per patient, including 2 dystonic events (p50.028).
After triheptanoin withdrawal, 24 paroxysmal manifestations were
recorded per patient including 12 dystonic events (p50.028).
[figure1]
Patients reported a clear improvement (CGI scale) when treated
and a clear worsening after drug withdrawal. This striking clinical
improvement was associated with the normalization of patients brain
energy profile, i.e. a significant increase of the Pi/PCr ratio during
brain activation compared to the rest and recovery phases (p50.021).
[figure2]
Upon study completion, all patients wished to continue treatment
with triheptanoin.
Conclusions: Triheptanoin dramatically reduced the number of
paroxysmal manifestations, especially dystonic episodes, and normal-
ized brain energy metabolism in GLUT1-DS patients.
1233
Niemann Pick C disease in a 20 year old female
V.K. Palmadottir, D. Pratt, K.L. Poston (Stanford, CA, USA)
Objective: To describe a case of Niemann Pick C (NPC) disease.
Background: NPC is a rare, systemic, recessively inherited lyso-
somal storage disease, characterized by abnormal accumulation of
free cholesterol and glycolipids, caused by mutations in NPC1 and 2
genes. Adult forms were thought to be rare, but likely
underdiagnosed.
Methods: Case report.
Results: A 20 year old Caucasian woman with history of devel-
opmental delay and motor problems since age 2, presumed cerebral
palsy (CP), presented for evaluation of 18 month history of progres-
sive motor and cognitive decline. At age 2 she was noted to have
hypotonia, hypermobility and clumsiness. As a child she could walk
and run and had mild cognitive deficits. Her course remained stable
until age 14 when fine motor skills and incoordination worsened
slightly. From age 18 she had more rapid motor and cognitive
decline with the addition of action tremor and odd postures of
hands, tripping and worsening imbalance, vision bobbing, bulbar
symptoms and worsening stuttering. On exam she had no dysmorphic
features, was cognitively impaired, but followed commands well.
Volitional vertical gaze was difficult, worse with inferior gaze with
Movement Disorders, Vol. 30, Suppl. 1, 2015
S480 POSTER SESSION
component of apraxia including blinking prior to initiation of upgaze.
She had mild hypotonia, hyperextensible joints but no bradykinesia,
spasticity or rigidity. Dystonic abnormal posturing of both hands
with action, L>R. Bilateral irregular, jerky, large amplitude tremor
of upper extremities with action was noted. Gait was normal with
exception of dystonic posturing of hands and unstable tandem gait.
Neuropsychology testing revealed average verbal skills but very low
performance on perceptual reasoning, working memory and process-
ing speed. MRI brain was normal, as were relevant serum and CSF
tests. Lysosomal testing of skin fibroblasts revealed cells positive for
filipin showing excess free cholesterol. Cholesterol esterification for
6 hours gave very low value confirming the diagnosis of NPC
disease.
Conclusions: A case series of 5 adult onset NPC disease showed
Movement Disorders were present (Anheim J Neurol 2014) as did
this case. The disease is partially treatable with miglustat and 2-
hydroxypropyl-g-cyclodextrin (HPGCD) is a potential new drug can-
didate under investigation. NPC is a potentially treatable disorder
that should be considered as a differential to CP and in patients with
new neurological impairments in teens or early adulthood.
1234
Dystonia-spasticity in a patient with a novel SLC25A12 mutation
M. Parnes, L. Robak, J.M. Shulman, A. Stocco, J. Jankovic
(Houston, TX, USA)
Objective: To describe a unique case of psychomotor regression,
dystonia and spasticity in a patient with a compound heterozygous
mutation in SLC25A12.
Background: Global cerebral hypomyelination, an autosomal
recessive disorder characterized by developmental arrest, hypotonia,
and seizures, has been found to be caused by deficiency of the neu-
ronal mitochondrial aspartate-glutamate carrier, ACG1 (Aralar),
encoded by the SLC25A12 gene. Mutations in this gene have also
been associated with autism spectrum disorder. Dystonia and spastic-
ity, however, have not been previously reported in patients with
mutations in this gene.
Methods: A 3 year-old girl was referred to our pediatric Move-
ment Disorder clinic for dystonia associated with a history of psy-
chomotor regression and epilepsy. Examination was notable for
ability to crawl but not walk, equinovarus deformity of the feet,
decreased truncal tone with spasticity of the extremities, brisk
reflexes, and dystonic posturing of the left arm. There was modest
improvement of tone with levodopa. Brain MRIs revealed hypomye-
lination and progressive nonspecific atrophy, and MR spectroscopy
was suggestive of neuronal cell loss.
Results: Whole exome sequencing revealed two novel mutations
in SLC25A12 in trans, including a frameshift mutation in exon 4
(c.2956C>T, p.K100fs) and a nonsynonymous variant [c.215T>C
(p.I72T)] within the conserved calcium-binding region that was pre-
dicted to be damaging. MRI results are consistent with a prior
reported case of global cerebral hypomyelination (Wibom et al,
NEJM 2009). There have been, however, no previous reported cases
of this disease presenting with dystonia or spasticity. This case likely
represents two novel pathogenic mutations, with additional symptoms
not previously described in this condition.
Conclusions: Whole exome sequencing has become a powerful
tool to accelerate genetic diagnosis in Mendelian disorders, as well
as for phenotypic expansion of associated clinical manifestations.
1235
How a flexible differential yielded an elusive diagnosis: A case
report
K. Ross, J. Axman, A. Harrington, S. Khurana (Miami, FL, USA)
Movement Disorders, Vol. 30, Suppl. 1, 2015
Objective: To present a classic case of stiff-person syndrome
(SPS) that was suggestive of other, more common pathologies, but
upon further investigation was characteristic for SPS.
Background: Stiff person syndrome is a rare neuromuscular dis-
ease characterized by baseline muscular rigidity with superimposed
episodes of spasms. Axial musculature is typically affected first with
extension to the proximal limbs resulting in impaired ambulation and
hyperlordosis. It has an estimated prevalence of 1:1,000,000,
although this estimation is likely the result of underdiagnosis. The
average age of symptom onset and diagnosis are 35 and 41.2 years,
respectively. Significant impairment due to disease progression may
be prevented with early diagnosis. Recognizing the signs and symp-
toms, as well as subsequently ordering appropriate laboratory studies
and neuromuscular analyses can help to solidify this elusive
diagnosis.
Methods: We present the case of a classic presentation of this
rare disorder. A 48 year-old Haitian female presented with three
years of worsening lower extremity pain, episodic spasms, and
increasing frequency of falls and a two week history of epigastric
and right flank pain. Her symptoms initially began with episodes of
sharp lumbar pain radiating down her legs and progressed to weak-
ness, spasticity, and immobility. On physical examination she had
increased tone and reflexes of the bilateral lower extremities. She
was in debilitating pain and was admitted to the hospital.
Results: Spine and brain MRI were grossly benign. She was
found to have abnormal uterine bleeding. Abdominal radiograph
revealed extensive uterine fibroids. Lack of significant radiographic
or laboratory findings suggested an autoimmune, paraneuoplasic,
myelopathic, or psychiatric etiology. She was given trials of gaba-
pentin, intravenous morphine, and baclofen without any significant
reduction in symptoms. The lack of response prompted a suspicion
of SPS. A trial of diazepam ultimately led to improvement of symp-
toms and increased mobility. She was found to be positive for anti-
GAD-65 antibodies, which is specific for SPS, helping to establish
the diagnosis.
Conclusions: It is important to be aware of and to consider rare
conditions in the differential diagnosis of neuromuscular disease.
Having SPS in the differential will help yield more timely diag-
nosis and treatment, and thus better prognosis and quality of life for
patients.
1236
Spectrum of Movement Disorders in mitochondrial cytopathy
patients
S.R. Schreglmann, G. Kaegi, F. Riederer, C.R. Baumann, D.
Waldvogel, H.H. Jung (St. Gallen, Switzerland)
Objective: To assess the prevalence, clinical presentation and
treatment response of Movement Disorders in a series of patients
with genetically confirmed mitochondrial cytopathy (MC).
Background: MCs are heterogeneous diseases of respiratory
chain dysfunction that may present with a variety of neurological
symptoms. Diagnostic confirmation may be difficult due to the low
sensitivity and specificity of standard tests including muscle biopsy,
making genetic testing the diagnostic gold standard. Movement Dis-
orders are known to occur in MCs, but their prevalence is not
known.
Methods: Retrospective analysis of case notes of all patients with
definitive MC, confirmed by genetic testing in either muscle tissue or
blood at our neuromuscular outpatient clinic.
Results:
8/59 patients (14%) with genetically confirmed MC in our cohort
either presented with, or developed relevant Movement Disorders
during the course of their disease - in 4 cases the Movement Disor-
der was the presenting symptom. In 3 of these genetically confirmed
8 MC a muscle biopsy was reported normal. The Movement Disor-
der phenotypes observed included Parkinsonism in 3 (two of them
with atypical features), chorea in two, dystonia in two and a mix of
 TABLE 1:. Clinical, biochemical, genetic and imaging features of mitochondrial cytopathy patients with Movement Disorders
age extrapyramidal
(yrs), involvement (age at age & symptoms at additional neurologi- laboratory/imaging
sex onset) onset cal symptoms biopsy finding genetic testing family history results
67, m right-sided Parkinson- 50 yrs, progressive slow horizontal sac- singular Cox-negative muscle: 7-9 kB dele- 1 sister with move- positive anti-Ri-Abs
ism (50 yrs) stiffness in right cades, decrased fibre: normal tion in mt2471.04 ment impairment and MRI: infratentorial
leg vertical eye move- (82%) panic attacks: mt- atrophy; brain
ments, neuro- genome deletions & PET: inhomogeni-
psychiatric (frontal POLG1-mutations ous parietal
lobe disorder, (p.Y831C, pattern;
insomnia, panic p.E1143G); 2 broth-
attacks, paradoxic ers died aged 30
benzodiazepine/ diagnosed with MS,
neuroleptics reac- 1 more sister right-
tion) REM-sleep sided walking diffi-
behaviour disorder, culties; many affected
restless legs family members with
restless-legs; mother
diabetes mellitus;
78, m axial & symmetrical 64 yrs, bradykinesia CPEO, swallowing ragged-red & ragged- muscle: 5kB-deletion not present CK: 207; Lactate: 1,7
atypical Parkinson- difficulties blue fibres, mito- in mt 2203.1 mmol/l; serial
ism (64yrs) early chondrial paracris- (>95%); POLG1/ MRIs: vascular
camptocormia, cer- tallinie inclusions 2, ANT1, Twinkle leukencephalop-
vical dystonia negative athy, multiple lacu-
nar infarcts, supra-
& infratentorial
atrophy;
73, f atypical parkisonism 61 yrs, stroke-like partial epileptic seiz- n.d. blood: A3243G muta- maternal grandmother normal serum lactate
(67 yrs) with early episodes ures, bilateral tion in tRNA Leu blind, mother and and CK; cranial
POSTER SESSION

backward falls, no vestibulo-cochlear gene; siblings diabetes MRI: periventricu-

gaze palsy, normal dysfunction with mellitus lar, microangio-
saccades sensori-neural pathic changes
hearing impari-
ment, retinopathy,
symmetrical distal
polyneuropathy,
psychotic episodes
48, m chorea (39 yrs) 34 yrs, CPEO CPEO, severe ragged-red fibres, muscle: 7-8kb dele- mother coeliac dis- CK: 296U/l; LDH:
sensori-motor poly- paracristallinic tion mtDNA (30- ease, no further 575U/l; serial
neuropathy, bilat- mitochondrial 40%) & further family history MRIs: infratento-
eral vestibulopathy, inclusions on elec- mutiple deletions; rial atrophy, pon-
myopathy with tet- tron microscopy tine/medullary
raparesis, ataxia, hyperintense
autoskopic lesions;
hallicinations;
69, f chorea (60yrs) childhood, limb polyneuropathy, cere- Cox-negative fibres, muscle: 7-13 kbp mother and maternal serial MRIs: progres-
weakness bellar dysarthria, mitochondrial deletion in aunt slow run- sive T2-
ataxia, saccadic accumulation & mt2492.01 (62%) ners, many cases hyperintense bilat-
intrusions, night paracristallinic of night blindness eral alterations
blindness, slowly in family centrum semiovale;

Movement Disorders, Vol. 30, Suppl. 1, 2015

S481
 TABLE 1:. Continued
S482

age extrapyramidal
(yrs), involvement (age at age & symptoms at additional neurologi- laboratory/imaging
sex onset) onset cal symptoms biopsy finding genetic testing family history results
progressive mitochondrial T2-hypointense
tetraparesis inclusions alterations (iron?)
in SN & Ncl.
Ruber; atrophy
fronto-parietal &
cerebellar/pontine;
ferritin accumula-
tions striatum &

Movement Disorders, Vol. 30, Suppl. 1, 2015

Gl. Pallidus;
38, m chorea, dystonia, 12 yrs, tremor and early childhood atten- normal muscle and blood: n.d. CSF lactate normal,
myoclonus (21 yrs) clumsiness tion deficit, pancer- mtDNA point serum lactate
ebellar syndrome mutation T7679C 3.3mmol/l; serial
with saccadic ocu- (F32L) MRIs: striato-
lar versions, sacca- nigral system
dic intrusions, gait changes, leucoen-
and extremity cephalopathy, cere-
ataxia, optic nerve bellar atrophy, thin
atrophy corpus callosum,
T2-hypointense
basal ganglia
43, m dystonic tremor, limb dystonic tremor, limb polyneuropathy, reduced COX- compund heterozy- 1 daughter died in anti-Ri-Abs positive,
rigor (32 yrs) rigor (32 yrs) hypometric complex enzyme gote deletion infancy due to Leigh serum Lactate
saccades, activity in skin (845delCT) and syndrome, 1 healthy 3.3mmol/l; brain
biopsy misssense mutation daughter, 1 daughter PET: reduced stria-
POSTER SESSION

(D202H) SURF1 with delayed devel- tal and cerebellar

gene opmental milesontes glucose
and raised serum metabolism;
lactate
56, m segmental dystonia 41 yrs, impaired retinitis pigmentosa, normal muscle: mtDNA one of two brothers CSF: lactate
(?) vision bilateral vestibular ATPase6 gene with delayed 3.3mmol/l; MRI:
dysfunction, sen- T8993G mutation developmental symmetrical cere-
sorineural hearing- (75%) milestones, bellar atrophy;
impairment, movement
shoulder girdle difficulties and
muscle atrophy progressive blind-
ness due to retinitis
pigmentosa (not
available for
examination)
 POSTER SESSION
chorea, myoclonus and dystonia in one. There was a response to lev-
odopa in 2 of 3 patients with Parkinsonism, while long-acting benzo-
diazepines were found useful in myoclonus and the single case of
mixed chorea/myoclonus and dystonia.
Conclusions: This series of genetically proven MC patients con-
firms that Movement Disorders have a high prevalence and can have
a variable phenotype in this patient population. Helpful clinical clues
to the diagnosis of MC in the described patients were a positive fam-
ily history, oculomotor abnormalities and/or cerebellar atrophy, while
the diagnostic sensitivity of muscle biopsy was low.
1237
Adult onset phenylketonuria with rapidly progressive dementia
and Parkinsonism
Z. Tufekcioglu, A. Cakar, B. Bilgic, H.A. Hanagasi, H.I. Gurvit, M.
Emre (Istanbul, Turkey)
Objective: To describe a patient with late onset phenylketonuria
presenting with rapidly progressive dementia, simultanagnosia, con-
structional apraxia and Parkinsonism which were reversible after
intervention.
Background: Phenylketonuria (PKU) is an autosomal recessive
metabolic disorder due to mutations in the gene for phenylalanine
hydroxlase (PAH) which converts phenylalanine (PHE) to tyrosine.
Eventhough it is a childhood disorder, in rare cases the first signs of
PKU may develop in late adulthood and may resemble other neuro-
logical diseases.
Methods: Case Report: A 59 year-old, previously normal func-
tioning man developed blurred vision, cognitive problems and gait
difficulty which progressed over 8 months. Neurological examination
revealed brisk reflexes, left side dominant Parkinsonism and slow
gait. Mini-mental state examination (MMSE) score was 25/30, in
neuropsychological testing he had a dysexecutive syndrome with
simultanagnosia and constructional apraxia. Cranial MRI revealed
bilateral diffuse hyperintense lesions in parietal and occipital white
matter with no significant atrophy. EEG showed diffuse slowing with
predominance of teta waves. In cerebrospinal fluid (CSF) examina-
tion protein level was found to be slightly elevated (61mg/dL) with
negative oligoclonal bands. EMG was normal. Routine diagnostic
work-up for rapidly progressive dementia and Parkinsonism were
negative. Serum aminoacid levels were determined to explore meta-
bolic leukodystrophies and PHE level was found to be highly ele-
vated (1075mmol/L) with normal tyrosine (61,20mmol/L) . His
cognitive dysfunction and signs of Parkinsonism improved after 3
months of phenylalanine restricted diet.
Conclusions: This case demonstrates that late onset PKU is a
rare, treatable cause of rapidly progressive dementia and Parkinson-
ism, it should be considered in the etiological work-up in patients
with certain constellations.
1238
Progressive myoclonic epilepsy in a case of adult-onset Leigh
syndrome due to T14487C mutation
M. Velez, C. Cosentino, M. Flores, J. Montoya, D. Segura, L. Torres
(Lima, Peru)
Objective: To report a case of adultonset Leigh syndrome with
progressive myoclonic epilepsy as the main neurological manifesta-
tion of an isolated mitochondrial complex I defect.
Background: Leigh syndrome (LS) includes three main aspects:
neurodegenerative disease with variable symptoms, mitochondrial
dysfunction caused by a hereditary genetic defect and bilateral CNS
lesions that can be associated with further abnormalities in diagnostic
imaging. Clinical presentation of LS is heterogeneous. Symptoms
appear in the majority of patients during the first two years of life
although they can be present in adulthood. Virtually all types of
S483
Movement Disorders have been reported. There are very few reports
of adult-onset progressive myoclonus.
Methods: We present a case report of a 34 year-old man who
presented since the age of 18 segmental repetitive myoclonus in the
proximal right arm initially well-controlled with clonazepam. Dysto-
nia of lower right limb appeared over the years disturbing gait. In
the last years, abnormal movements in the right arm reappeared reg-
ularly and gradually increased in frequency and intensity. At age 32,
he developed episodes of rhythmic clonic movements of that arm
and twitching of left facial muscles lasting around 30 s and recurring
frequently, which were clinically interpreted as epileptic seizures
although he never had epileptic generalized seizures. These facial
movements were notable increased during speech. It is worth men-
tioning that speech impairment initially improved with a geste antag-
onistique. Cranial nerves and cognition were normal for years.
Moderate ophthalmoplegia developed lately. His deceased mother
seemed to have had a similar neurological disorder.
Results: Cerebral MRI was normal at the beginning of the dis-
ease but others performed in the last years showed symmetrical
FLAIR and T2-weighted hyperintensities in putamen and the sub-
stantia nigra as well as cortical lesions.
A genetic study demonstrated the presence of the T14487C muta-
tion in the mtDNA-ND6 gene. Mutation heteroplasmy level in leuco-
cytes was less than 10%. Same mutation was detected in
asymptomatic maternal grandmother and two aunts but mutation load
data was not available. Poor control with high doses of levetiracetam
and carbamazepine.
Conclusions: This is the first reported peruvian patient with
adult-onset Leigh syndrome with predominant myoclonic epilepsy
and T14487C mutation.
1239
Investigation of factors affecting respiratory suppression in a
patient with Perry syndrome under mechanical ventilation
K. Yi, R. Kurisaki, K. Nakahara, H. Koide, T. Yamashita, K.
Uekawa, Y. Tsuboi (Uki, Japan)
Objective: To investigate the factors affecting respiratory sup-
pression in a patient with Perry syndrome (PS) under tracheostomy
positive pressure ventilation (TPPV).
Background: PS is a rare progressive hereditary disorder charac-
terized by cardinal signs of Parkinsonism, depression, weight loss,
and hypoventilation. Hypoventilation is a clinically important and
serious complication of PS, often leading to sudden death. However,
the mechanism of respiratory failure in PS remains still elusive.
Methods: A 45-year-old woman was diagnosed with PS based on
progressive Parkinsonism and hypoventilation, which were confirmed
by genetic analysis of DCTN1 G71A mutation in exon 2. The
descendants of an older sister of the patients paternal grandmother
had been previously diagnosed with PS. The patient was admitted to
our hospital for ventilatory support. At the time of evaluation, she
was taking L-dopa 825 mg daily with rotigotine patch 8 mg/24 h.
She showed motor fluctuations such as wearing-off and dyskinesia.
The settings of the respirator were as follows; Puritan BennettTM 840
ventilator, Volume-controlled Synchronized Intermittent Mandatory
Ventilation (SIMV) mode, tidal volume (TV): 460 ml, pressure sup-
port: 9 cmH2O, positive end expiratory pressure (PEEP): 3 cmH2O,
respiratory rate (RR): 12/min, and room air. We observed her condi-
tion for 24 h and recorded on, off, or sleep for 30 minutes daily. We
also recorded the end tidal CO2 (EtCO2), RR, TV, and minute venti-
lation (MV) at 1-min intervals. Statistical analysis of these parame-
ters was performed.
Results: On the evaluation day, the on-, off-, and sleep times
were 10, 6, and 8 h, respectively. Correlation analysis showed rela-
tively strong correlation between the average 30-minute TV and
EtCO2, and MV (correlation coefficient: 0.4879, 0.7933, respec-
tively). Wilcoxon signed-rank test revealed that EtCO2, TV, and MV
during sleep were significantly lower than those while the patient
Movement Disorders, Vol. 30, Suppl. 1, 2015
S484 POSTER SESSION

was awake (p < 0.05). Moreover, RR and MV during the off-time

were significantly lower than that during the on-time (p < 0.05).
Conclusions: Our result revealed that the present patient with PS
had respiratory fluctuations, which depend on different situations
such as awake/sleep and on/off. Respiration was particularly sup-
pressed during sleep and off time. These patterns of periodic respira-
tory suppression should be considered in patients with PS.

Restless legs syndrome and other sleep

disorders

1240
The prevalence of RLS and severity of symptoms in patients
with Idiopatic Parkinsons disease in the Republic of Macedonia
A. Doneva, S. Mancevska, V. Donev (Skopje, Macedonia)
Objective: The aim of the study was to evaluate the prevalence
and the severity of symptoms of the restless legs syndrome (RLS) in
patients with idiopathic Parkinsons disease in the Republic of
Macedonia.
Background: A sample of 80 patients with idiopathic Parkinsons
disease (53 men and 27 women, aged from 45 to 65 years and with
the duration of the IPD from 0 to 12 years) was estimated. Fig. 1. (1241).
Methods: For that purpose we used the following instruments:
structured questionnaire regarding demographic data of the patients
gin. The differential diagnosis considered a metabolic origin (severe
(age, gender, nationality), UPDRS Unified Parkinsons disease Rat-
hypomagnesemia) or less likely fat embolism. The following MRI
ing Scale (motor abilities), IRLSSGRS (International restless legs
exam demonstrated that most lesions vanished with cystic cavitations
syndrome study group rating scale) and IRLSSG (International Rest-
on lenticular nucleus and caudate. Brain SPECT with ECD-99m
less leg syndrome study group) questionnaire for the essential diag-
demonstrated hypoperfusion on frontal lobes, cingulated anterior and
nostic criteria for the restless legs syndrome. Analyzed parameters
basal ganglia. The brain tractography showed reduction on fractional
included: duration of the illness, severity of the clinical symptoms of
anisotropy [figure2] .
RLS and the severity of motor impairment within IPD.
As the patient fulfilled the diagnostic criteria for RLS we decided
Results: The prevalence of RLS in patients with IPD was 15%.
treating her with pramipexole 0.5 mg at night. The RLS vanished
There was no significant difference between the prevalence of RLS
with normalization of sleep. After 3 months of use she developed
among men and women. Severity of clinical symptoms was moderate
to severe. Motor impairment was significantly higher in RLS patients
compared to patients without RLS.
Conclusions: The presence of RLS in patients with IPD compli-
cates the clinical symptoms of Parkinsons disease. It is necessary
that the presence of RLS should not be ignored and the daily dose of
the medicaments should be properly adjusted in order to prevent its
negative effects.

1241
Acute restless legs syndrome and kleptomania after liposuction
surgery
G. Fabiani, H.A.G. Teive (Curitiba, Brazil)
Objective: To report a rare case of acute restless legs syndro-
me(RLS) and kleptomania after liposuction.
Background: Restless legs syndrome (RLS) is a Movement Dis-
order characterized by sensorimotor symptoms. RLS affects 5-10%
of European populations.
Results: Case Report: We report a 40-year-old woman submitted
to liposuction. Her past medical history included bariatric surgery.
After the liposuction she presented somnolence, mental confusion,
disorientation and memory deficits. After a week she started with
severe and unpleasant discomfort on lower limbs characterized by
pain and severe spasms on lower limbs at rest. The symptoms wors-
ened dramatically in the evening, preventing her to sleep and forcing
long walks and local massages to relieve the symptoms.
The brain MRI demonstrated [figure1] scattered and diffuse
lesions on brain, mainly in basal ganglia and cerebellum, almost
symmetrical. Signs of blood brain barrier breakdown were identified.
The radiologist suggested the lesions were of hypoxic ischemic ori- Fig. 2. (**).

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
kleptomania symptoms. We titrated the pramipexole to a lower dose
of 0,125 mg and these symptoms vanished. The patient has been
improving gradually since then but continues with moderate to
severe memory impairment and signs of defrontalisation.
Conclusions: Discussion: We report a unique case of acute RLS
associated with kleptomania, secondary to brain lesions after liposuc-
tion, most likely secondary to a hypoxic ischemic event. The RLS
symptoms are understood by the lesions on basal ganglia. In this
patient kleptomania arose by the failure of inhibitory control exer-
cised by caudate nucleus in limbic circuits and reduced fractional
anisotropy at tractography.
1242
Decision making in Parkinsons disease with and without REM
sleep behavior disorder
M.L. Fantini, P. Beudin, M. Figorilli, A.R. Marques, T. Vidal, B.
Debilly, P. Derost, U. Miguel, M. Puligheddu, F. Durif (Clermont-
Ferrand, France)
Objective: To compare decision making under ambiguity,
assessed by the Iowa Gambling Task (IGT), in Parkinsons disease
(PD) patients with and without REM sleep Behavior Disorder
(RBD).
Background: PD patients show poor performances in decision
making tasks, but results are not univocal.1 Impairment in decision
making is also observed in idiopathic REM sleep behavior disorder,
a condition that often predates PD.2 PD patients with RBD tend to
have more severe cognitive dysfunctions, as well as an increased fre-
quency of impulse control disorders, compared to PD without RBD.
However, no study has assessed decision making in PD patients with
RBD compared to PD without RBD.
Methods: Eighteen consecutive non-demented PD patients with
polysomnographically-confirmed RBD [10M; mean age: 63.7 6 9.6
yrs., Hohen &Yahr (H&Y):2.1 6 0.5] and 18 sex and age-matched
PD patients without RBD (PD-noRBD, mean age: 64.8 6 7.2 yrs,
H&Y: 2.4 6 0.1), performed an extensive test battery including exec-
utive functions as well as the Iowa Gambling Task. None of the
patients had a history of impulse control disorder or related
behaviors.
Results: No between-group differences were observed in PD
severity, duration, total levodopa dose and executive measures. No
difference was found in the Total IGT score in PD-RBD vs. PD-
noRBD patients (-1.4 6 9.5 vs. 9.4 6 20.6, p5 0.14). However, PD-
RBD patients performed significantly worse compared to PD-noRBD
at the final block (5.3 6 8.3 vs.-1.3 6 1.3; p50.015), showing that
they did not learn by feedback over task [figure1]. A higher propor-
Fig. 1. (**).
S485
tion of PD-RBD patients showed random or even worse performance
at the end of the task compared to PD-noRBD (100% vs 79%,
p50.05). Performance at the IGT final block did not correlate with
LEDD, PD duration, or measures of executive functions.
Conclusions: This study shows for the first time that decision
making under ambiguity is more severely impaired in PD-RBD
patients compared to PD-noRBD, despite no differences in executive
functions. Dysfunctional reward processing in PD-RBD may contrib-
ute to the reported increased risk to develop impulse control disor-
ders in this population.
1.Poletti M et al., Iowa Gambling Task in Parnson Disease. Jour-
nal of Clinic and Exp Neuropsychol 33:4, 395-409
2.Delazer M et al., Decision Making and Executive Functions in
REM Sleep Behavior Disorder. Sleep 2012;35:5, 667-673.
1243
Unilateral restless legs symptoms in neurosyphilis
E.B. George, P. Bansal (Detroit, MI, USA)
Objective: To present a case of unilateral restless legs (RLS)
symptoms in neurosyphilis with spinal involvement.
Background: Syphilis is called the great imitator due to the vari-
ety of possible symptoms.
Methods: Case report.
Results: A 51 y.o. right-handed man had been seen in neurology
clinic 4 years previously for gait instability, and diagnosed with neu-
rosyphilis (CSF VDRL 1:8, RPR 1:128). Brain MRI showed periven-
tricular white matter changes. He received penicillin IV 4x106 units
q 4 hrs for 14 days and another 10 days of IV penicillin outpatient.
His symptoms improved and his falls stopped. Repeat CSF VDRL
was 1:4 and RPR was 1:8. CSF IgG index decreased to 1.15 from
1.36. Infectious disease did not recommend further treatment. Over
the next 2 years he took desvenlafaxine, quetiapine and risperidone
from psychiatry with some drug-induced Parkinsonism. He devel-
oped orolingual dyskinesia and had been off antipsychotics for a
year when he came to the Movement Disorders Center, complaining
of 2 years progressive unpleasant feeling of internal movement, start-
ing in his left leg and extending up to his mouth on that side. The
sensation was worse in the evening and on lying down, and was
relieved by walking. He was on pregabalin and benztropine without
benefit. Ferritin, iron profile, creatinine and CBC were normal. He
had relief from ropinirole and later rotigitine. He did not tolerate clo-
nazepam but felt lorazepam helped, as did hydrocodone from his pri-
mary care physician for back pain. The RLS remained unilateral and
he did not report nocturnal leg movements. After 14 months he
developed acute bilateral leg weakness. Cervical spine MRI showed
a well-defined nonenhancing focal lesion of hyperintense T2 signal
in the left spinal cord at C4 and another lesion with faint ring
enhancement at C3-4. Brain MRI showed a crescent shaped lesion in
the splenium of the corpus callosum, with restricted diffusion and T2
hyperintensity but no enhancement. CSF VDRL was 1:2, with 10 oli-
goclonal bands, and IgG index was 1.03. He was re-treated with 4
x106units IV penicillin Q4 for 14 days, followed by benzathine peni-
cillin 2.4 x106units weekly for 3 weeks. His weakness and previous
left RLS symptoms resolved, with residual LHermittes sign.
Conclusions: The unilateral RLS symptoms appear related to the
spinal cord involvement in his incompletely treated neurosyphilis.
RLS symptoms have been reported with spinal multiple sclerosis and
spinal cord injury.
1244
Reflection impulsivity in patients with restless legs syndrome
B. Heim, L. Zamarian, A. Heidbreder, A. Stefani, M.T. Pertl, E.
Brandauer, K. Seppi, M. Delazer, W. Poewe, A. Djamshidian, B.
H
ogl (Innsbruck, Austria)
Movement Disorders, Vol. 30, Suppl. 1, 2015
S486 POSTER SESSION

Objective: To compare patients with restless legs syndrome TABLE 2. Mean scores on the IRLS and RLS QoL scores at
(RLS) to healthy controls using the beads task to assess reflection baseline, 6-months, 1-year and 2-year post-STN DBS
impulsivity.
Background: A subgroup of RLS patients treated with dopami- IRLS
nergic drugs develops impulse control disorders (ICDs) such as gam- IRLS IRLS impact RLS QoL
bling disorder, compulsive shopping and compulsive sexual disorder sum symptoms scores transformed
as well as augmentation. The aim of this study was to further charac- Timepoints scores scores (a) (b) scores (c) LE (d)
terise the neuropsychological profile of RLS patients using the beads
task. This is a test of reflection impulsivity which measures how Baseline
much evidence participants gather before making a decision. Patients No. of 22 22 22 22 22
also underwent a detailed neuropsychological assessment of execu- observations
tive functions including cognitive flexibility and response inhibition, Mean (SD) 19.59 12.91 4.45 68.29 1203.2
the Frontal Assessment Battery (FAB) and conceptualisation. (6.95) (4.33) (2.72) (20.26)
Methods: Only participants who scored more than 25 points on 6 Months
the Montreal Cognitive Assessment were included. We recruited 12 No. of 17 17 17 16 16
RLS patients without ICDs and 8 patients with at least one symptom observations
of an ICD or augmentation. Five of these 8 ICD patients had also Mean (SD) 14.53 9.53 3.41 72.26 370.8
augmentation. Results were compared to 18 age-matched controls. (12.27) (7.86) (3.61) (24.17)
Results: All RLS patients gathered less evidence and made more 1 Year
irrational choices than controls (p50.005). There was, however, no No. of 13 13 13 13 13
difference between the two RLS groups (p>0.1). Furthermore, observations
impulsive decisions on the beads task correlated with poorer concep- Mean (SD) 11.74 7.82 2.62 76.15 499.7
tualisation (p<0.05), which is a subtest of the Frontal Assessment (8.08) (5.39) (2.29) (20.07)
Battery. 2 Year
Conclusions: Our results show that RLS patients treated with No. of 10 10 10 10 10
dopaminergic medication make more impulsive choices than healthy observations
volunteers. Clinicia
ns vigilance is required to detect early behaviou- Mean (SD) 12.83 8.12 3.5 78.75 787.7
ral changes in RLS patients as these may be an early sign of ICDs. (11.26) (7.17) (3.47) (22.15)
P value 0.0109 0.0041 0.0003 0.3627
a: IRLS symptoms scores, 6 items, 1,2,4,6,7,8. Higher score=higher
1245
severity. b: IRLS impact scores, 3 items, 5,9,10. Higher score-
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) s 5 higher impact. c: RLS QoL transformed scores= [(Actual raw
improves restless leg syndrome (RLS) in patients with score lowest possible raw score)/Possible raw score range] X 100.
Parkinsons disease (PD) Higher score= better QoL. d: LE=[(levodopa1levodopa CR [0.7)
O.S. Klepitskaya, Y. Liu, S.H. Sillau, J. Tsai, A.S. Walters (Aurora, [1.1 if on COMT inhibitor]1pramipexole [1001ropinirole [33
CO, USA)
Objective: To study the effect of STN DBS in patients with PD
and RLS on their RLS symptoms and Quality of Life (QoL).
Background: RLS is highly prevalent in PD. DBS is an effective
treatment for dopamine-responsive symptoms of PD. It is reasonable after surgery. Patients with moderate to severe RLS at baseline
to postulate that because RLS responds well to dopaminergic therapy (IRLS sum scores>10) who completed questionnaires pre- and at
it would improve with DBS. Literature reports, however, have been least one time point post-operatively were included in the study.
inconclusive. The primary outcome measure was IRLS sum score and subscales
Methods: All patients undergoing STN DBS surgery for PD (severity and impact). The secondary outcome measures were
from 2008 to 2013 were asked to complete the International RLS RLS QoL scores, and rate of responders (>50% reduction in
Study Group rating scale (IRLS) and the RLS QoL questionnaires IRLS sum scores), remitters (IRLS sum score10, within mild
pre-operatively and post-operatively at 6 months, 1 and 2 years range), and complete remitters (IRLS=0). Differences among the
mean scores over time were analyzed using mixed model
regression.
Results: 22 patients met the inclusion criteria.
TABLE 1. Demographic Characteristic at baseline (before The preoperative IRLS sum scores were 19.59 6 6.95, severity
subscale 12.91 6 4.33, impact subscale 4.45 6 2.72, and the trans-
DBS operation)
formed RLS QoL score 68.29 6 20.26. The estimated differences
Variable No. Percentage % between pre- and averaged post-operative scores were: IRLS sum
score -7.80, severity subscale -5.43, impact subscale -1.20, and RLS
Age QoL 4.31. [figure1] The overall F tests demonstrated differences
Mean (SD) 58.3(7.4) among the times for the means of the IRLS scales: p-value for the
Median 59.5 sum score 0.0109, severity subscale 0.0041, and impact subscale
40-49 3 13.64% 0.0003. Mean Levodopa Equivalent (LE) was reduced at 6 m by
50-59 8 36.36% 69.2%, 1 y 58.5%, and 2 y 34.5%.
60-69 10 45.45% There was no statistical evidence of mean differences among the
70-79 1 4.55% times for the RLS QoL scale.[figure2] Rate of responders was 50%,
Total 22 100% remitters 50%, and complete remitters 27.3%.
Gender Conclusions: STN DBS significantly decreased the symptoms of
Female 12 54.55% moderate to severe RLS in patients with PD despite a decrease in
Male 10 45.45% dopaminergic treatment. This improvement was sustained over 2
Total 22 100% year period. These data suggest that STN DBS could be effective for
treatment of RLS.

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
Fig. 1. (1245).
Fig. 2. (1245).
1246
Optic nerve head, retinal nerve fiber layer and macular
thickness measurements in patients with restless legs syndrome
A. Koskderelioglu, T. Kusbeci, O. Kusbeci, M. Gedizlioglu (Izmir,
Turkey)
Objective: To evaluate the retinal changes in RLS patients.
Background: The human retina contains dopaminergic neurons
within the inner retinal layer. Restless legs syndrome (RLS) is
thought to have an underlying dopaminergic mechanism. Several
studies demonstrated dopaminergic neuronal loss in PD using optical
coherence tomography (OCT).
Methods: In this study we used spectral domain OCT examina-
tion to measure the peripapillary retinal nerve fiber layer (RNFL),
S487
the macular thickness, the thickness of all retinal layers in foveal
scans, ganglion cell complex (GCC, ganglion cell layer 1 internal
plexiform layer) thickness and optic nerve head parameters of 36
patients with idiopathic RLS and 36 age and sex matched controls
and compared the results with each other.
Results: The average peripapillary RNFL thickness was reduced
significantly in superior and inferior quadrants in RLS patients com-
pared with healthy controls(p50.032). The reduction of mean macu-
lar volume and total macular thickness were also significant in the
RLS patients. The most significant thickness differences were located
in the nasal inner, inferior inner, superior inner and inferior outer
quadrants (p<0.05). GCC thickness was reduced but the difference
was not statistically significant. Optic nerve head parameters (cup
volume, cup/disc area ratio, rim area and disc area) showed no sig-
nificant difference between patients and healthy controls.
Conclusions: Our study revealed significant RNFL loss and reti-
nal thinning detected by spectral domain OCT measurements in
RLS. Our results may support the dopaminergic dysfunction in the
pathogenesis of RLS. Prospective longitudinal studies with a larger
sample are needed to corroborate our results.
1247
Frequent causes of misdiagnosis of restless legs syndrome in
clinical practice
D.Y. Kwon, H.K. Yoon, M.H. Song (Ansan-city, Korea)
Objective: The aim of this study was to investigate common
causes of misdiagnosis of Restless legs syndrome/Willis-Ekbom Dis-
ease (RLS), diagnostic process in general clinics and the degree of
delay before receiving a final diagnosis of RLS.
Background: RLS is a common disorder, but easily under- and
misdiagnosed in routine clinical practice. Precise and accurate diag-
nosis of RLS is important as it has a significant impact on quality of
life of the patients. Diagnosis of RLS is simple when using clinical
questionnaire about core clinical symptoms, but can easily missed as
there are no confirmative laboratory tests as a biomarker and RLS is
still not well recognized even to the general clinicians.
Methods: We interviewed firstly diagnosed 37 drug-nave RLS
patients. All of the patients was not satisfied with the treatment
for the previous impression. Diagnosis of RLS was made accord-
ing to the revised diagnostic criteria by the international restless
legs syndrome study group. We asked a questionnaire at their first
visit which include age at onset, type of visited medical/paramedi-
cal facilities, time interval between first visit for that symptom
and final diagnosis, type of examination and diagnostic impres-
sion, and route of visit Movement Disorder clinic for RLS
diagnosis.
Results: All of the RLS patients were at least improved (p-CGI
score <3) after medical treatment for RLS. Average delayed time
before diagnosis of RLS was 3.4 years. For the medical facilities,
42% of the patients chose oriental medicine, 37% orthopedic sur-
geon, 21% neurosurgeon and 23% general physician and internal
medicine. 5 (13.5%) of the patients never been to the hospital as
they thought it was originally like that and was not a disease. Most
common misdiagnosis was the blood circulation problem (33.6%),
low back and disc problem (27%) and muscle cramps (17%), but
most frequent answer that the patients heard from a clinician was I
have no idea, no abnormal findings on test.
Conclusions: RLS is common disorder in general population
which could easily diagnose using simple questionnaire, but on the
other hands, can be easily misdiagnosed as a mimicking condi-
tions. Clinicians should know the core clinical features of RLS not
to miss the diagnosis, as the proper treatment improves quality of
life for the patients. More information about RLS should be given
to the physicians and the general public through various
approaches.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S488 POSTER SESSION
1248
Restless legs syndrome leads to reduced quality of life in patients
with multiple sclerosis
M. Minar, D. Petrlenicov
a, P. Valkovic (Bratislava, Slovakia)
Objective: To evaluate prevalence and characteristics of restless
legs syndrome and its impact on quality of life in patients with mul-
tiple sclerosis.
Background: Multiple sclerosis (MS) is a disabling neurological
disorder affecting people in productive age. A wide range of neuro-
psychiatric symptoms including dysesthesia, sleep disturbances and
fatigue, characterizes it. The same symptoms are typical also for rest-
less legs syndrome (RLS).
Methods: In a cross-sectional study, we examined random con-
secutive patients of MS outpatient clinic. After signing informed
consent, they filled questionnaire based on official International RLS
Study Group diagnostic criteria, followed by demographic data, as
well as MS and RLS specification. Blood for routine examination
was taken. Data were statistically analyzed.
Results: From overall 200 subjects, 26% (n552) fulfilled all essen-
tial criteria for RLS. Seventy seven percent of RLS sufferers were
women. Almost 60% positive subjects developed RLS symptoms after
MS onset. Attack of disease and MS treatment has no effect on RLS
symptoms changes in more than 2/3 of positive subjects, or 3=4 respec-
tively. In RLS positive group, sleep disturbances, fatigue/excessive
daytime sleepiness (EDTS) and reduced quality of life (QoL) were
more prevalent than in patients without RLS (p5.03, p5.04, and
p5.01, respectively). Intensity of RLS symptoms positively correlated
with sleep disturbances (rs=.421), sleep impairment correlated with
reduced QoL (rs=.545), as well as fatigue/EDTS did (rs=.681).
Conclusions: Restless Legs Syndrome is significantly prevalent
in MS patients, and has a negative impact on QoL. Since there is a
higher prevalence of somatosensory symptoms and fatigue in MS
patients, the RLS is often overlooked. Neurologists involved in MS
management must be aware of this condition and treat it if neces-
sary, to avoid further worsening of QoL of patients.
1249
Association between dementia and probable REM sleep behavior
disorder (RBD) using the Japanese version of the RBD screening
questionnaire in patients with Parkinsons disease
T. Nomura, Y. Tajiri, K. Wada, Y. Inoue, K. Nakashima (Yonago,
Japan)
Objective: In order to confirm associations between dementia
and probable REM sleep behavior disorder (pRBD), we used
RBDSQ in patients with PD.
Background: REM sleep behavior disorder (RBD) is not only a
preclinical symptom but also an aggravating factor of dementia in
patients with Parkinsons disease (PD). Polysomnographies (PSGs)
are necessary for the diagnosis of RBD, but it is difficult for individ-
uals to undergo PSG. The RBD screening questionnaire (RBDSQ)
has been developed as a screening tool for RBD.
Methods: Seventy patients with PD (age: 69.2 6 8.9 years old, 31
males and 49 females, length of PD morbidity: 7.4 6 6.4 years, Hoehn
& Yahr: 2.7 6 0.8) underwent examinations including RBDSQ-J and
Mini-mental examination (MMSE) in both 2011 and 2013. We assessed
changes in pRBD and associations between pRBD and dementia.
Results: Seventeen patients (24.3%) in 2011 and 27 patients
(38.6%) in 2013 were diagnosed as pRBD because they had scores
of 6 or higher on RBDSQ. Twelve patients continued to exhibit
pRBD, 15 developed pRBD, and 5 displayed improved pRBD over
the next 2 years. In 2013, PD patients with pRBD took higher
amounts of levodopa equivalents and had lower scores on the
MMSE. Four out of 12 patients (33.3%) with continuing pRBD and
4 out 15 patients (27%) developing pRBD also had dementia.
Conclusions: RBDSQ was useful for clinical estimation in patients
with PD, in whom we found that pRBD affected cognitive impairment.
Movement Disorders, Vol. 30, Suppl. 1, 2015
1250
Restless legs syndrome in end-stage renal disease patients in
Aracaju - Sergipe: Preliminary results
R.C.P. Prado, L.C. Ferreira, L.C.P. Prado (Aracaju, Brazil)
Objective: To characterize the population of chronic kidney dis-
ease in dialysis evaluated, and estimate the frequency of RLS in
selected dialysis clinic in Aracaju - Sergipe - Brazil.
Background: Restless Legs Syndrome (RLS) is a neurological
condition characterized by an irresistible urge to move the legs,
which occurs in about 3-15% of the general population. It is particu-
larly common in association with peripheral neuropathy, iron defi-
ciency, type 2 diabetes, multiple sclerosis and uremia. Patients
undergoing dialysis for chronic kidney disease have a high preva-
lence of sleep disorders, including RLS.
Methods: Dialysis patients undergoing peritoneal dialysis (PD)
and hemodialysis (HD), between march and june of 2014, were eval-
uated in Nefroclnica in Aracaju Sergipe Brazil, and obtained
demographic and laboratory data. The presence of RLS was investi-
gated using the diagnostic criteria of the International Restless Legs
Syndrome Study Group (IRLSSG), and then the Restless Legs Syn-
drome Rating Scale was also assessed.
Results: 146 patients were analyzed, mean age of 54.96 years
(23-88 years), 66% females. Sixty-three percent were married. As
frequent comorbidity, systemic arterial hypertension (SAH) was pres-
ent in 89% of patients. The etiology of chronic kidney disease was
multifactorial in 34% of cases, and SAH in 46% as isolated cause.
Of the 146 patients, 118 underwent HD (fistula 5 82; permcath 5 36)
and 28 PD. The mean duration of dialysis was 4.68 years (6 months
to 21 years). Analyzing laboratory results, pre-dialysis average creati-
nine was 9.5; Urea 150; hemoglobin 10 (all in use of erythropoietin);
TGP 20; serum iron 76; ferritin 461 and calcium 8.6. Regarding the
frequency of RLS, 12 patients (8%) were identified, only one in PD.
The mean scores obtained on the rating scale to RLS were 21 points
(13-26), being considered moderate in four patients and severe in
eight. The results of this analysis are preliminary, since the research
is still in progress.
Conclusions: Analyzing the results of this preliminary study, we
could characterize the selected end-stage renal disease patients, and
investigate the frequency and severity of RLS in the cohort.
1251
Comparative analysis of restless legs syndrome in end-stage renal
disease patients undergoing peritoneal dialysis and hemodialysis
in Aracaju - Sergipe: Preliminary results
R.C.P. Prado, L.C. Ferreira, L.C.P. Prado (Aracaju, Brazil)
Objective: To compare characteristics of patients undergoing
hemodialysis (HD) and peritoneal dialysis (PD) in a selected dialysis
clinic in Aracaju - Sergipe - Brazil, and estimate the frequency of
RLS in both groups.
Background: Restless Legs Syndrome (RLS) is a neurological
condition characterized by an irresistible urge to move the legs,
caused by an unpleasant feeling that is worse at rest and at night.
Can be idiopathic in about 3-15% of the general population, or sec-
ondary. As a result, patients may develop sleep disturbances and
excessive daytime sleepiness. RLS secondary to uremia is common,
underdiagnosed and treatable.
Methods: Dialysis patients undergoing PD and HD, between
March and June of 2014, were evaluated in Nefroclnica in Ara-
caju, Sergipe, Brazil, and obtained demographic and laboratory data.
The presence of RLS was investigated using the diagnostic criteria
of the International Restless Legs Syndrome Study Group, and then
the Restless Legs Syndrome Rating Scale was also assessed.
Results: A total of 146 patients were analyzed, 81% underwent
HD (fistula 5 82; permcath 5 36) and 19% PD. Comparing the HD
and PD groups, we could observe that the average age was similar
(HD 53.8 years, PD 55.2 years) as well as gender distribution (HD
 POSTER SESSION
32% X PD 39% female). Patients undergoing HD had higher average
time on dialysis (5.1 years) compared to PD group (2.9 years). Ana-
lyzing laboratory results, pre-dialysis average creatinine was 9.5;
Urea 150; Hemoglobin 10 (all in use erythropoietin); TGP 20; serum
iron 76; ferritin and calcium 461 8.6. Twelve patients were diag-
nosed with RLS. The frequency of RLS in patients undergoing HD
was of 9% (fistula 5 6 and permcath 5 5) and PD of 3.5%. The
mean scores obtained on the rating scale to RLS were 21 points (13-
26), considered moderate in four patients (one PD) and severe in
eight. These results are preliminary, since the research is still in
progress.
Conclusions: Analyzing the results of the preliminary study, we
could characterize the selected patients with End-Stage Renal Dis-
ease on dialysis, comparing patients undergoing HD and PD, and
investigate the frequency and severity of RLS in the sample.
1252
Familial impulse control disorders associated with dopaminergic
agonist therapy for RLS
M. Schonberger, C. Sidiropoulos, P. LeWitt (West Bloomfield, MI,
USA)
Objective: To report impulse control disorders (ICDs) experi-
enced by three first-degree relatives in association with their dopami-
nergic agonist (DA) therapy for restless leg syndrome (RLS).
Background: As occurs in Parkinsons disease patients treated
with DAs, this drug class also is associated with the emergence of
ICDs for RLS patients. Genetic factors have not been previously rec-
ognized to confer risk for this seemingly idiosyncratic behavioral dis-
order, whether occurring spontaneously or in the context of DA
therapy. Several risk factors have been proposed for the development
of DA-induced ICDs, including young age of RLS onset (Voon et al,
BMC Neurol, 2011).
Methods: Case report.
Results: A 62 year-old man, whose severe RLS began at age 19,
had a 5-generation family history of this disorder. His typical symp-
toms of RLS responded well to pramipexole (PPX) 2 mg/day, though
insomnia continued. Eventually, however, he began to frequent casi-
nos (leading to major financial losses) and he began, for the first
time, to smoke cigarettes. The probands health-conscious sister (also
affected with RLS) started treatment with PPX. Shortly afterwards,
she also began to smoke cigarettes, although she never had done so
before. The probands mother, whose RLS received PPX treatment,
began to shop compulsively (which was a novel behavior for her and
which required returning purchased items to stores). In each instance,
the aberrant behaviors ceased after discontinuation of PPX (which in
each instance had been highly effective for RLS relief). However,
the probands compulsive gambling persisted intermittently for >1
year after stopping PPX. In addition, he continued with occasional
smoking since this provided some relief of RLS symptoms. Mainte-
nance therapy for RLS has been effective with transdermal fentanyl
and diazepam.
Conclusions: Though prior research has not reported a genetic
contribution to the risk for DA-induced ICD, the apparent hereditary
involvement in this report is intriguing. Our findings suggest that
closely-related individuals affected with RLS and receiving DA treat-
ment should be considered at increased risk for ICDs if another DA-
treated family member has experienced this problem.
1253
Effects of comorbidities on the risk of restless legs syndrome
A. Tiltak, F. Genc, F. Kurtulus, N. Uzun, Y.B. G omceli, A. Yaman
(Antalya, Turkey)
Objective: In this study our aim is determine the comorbidities
of RLS patients on our follow-up by searching the files
retrospectively.
S489
Background: Restless legs syndrome (RLS) is a common cause
of insomnia and adversely affects the quality of life.
Methods: We searched the files of 67 RLS patients diagnosed
between 2010 and 2014 for the comorbidities like; cardiovascular,
hepatic and kidney diseases, malignancies, anemia, multiple sclero-
sis, thyroid disorders, migraine, anxiety and depression.
Results: There were 67 patients and 41 were female. The mean
age of the study population was 50 (21-82) years. The comorbid con-
ditions were like as; 42 patients had anemia and 37 of them had
severe iron deficiency, digestive disorders seen in 26 patients. Four
had migraine, seven had thyroid disorders, one had kobalamine defi-
ciency, one had stroke history, two were suffering from multiple
sclerosis, 15 of them were being treated for hypertension(HT), three
had epilepsy, two had chronic kidney disease (CKD), four had Dia-
betes Mellitus, there was one patient with hepatitis B, 20 of them
had anxiety and depression. Only eight patients were free from
comorbid conditions. 50 patients had normal electromyography
(EMG), eight had carpal tunnel syndrome, two had sensory, two had
sensorimotor polyneuropathy, one patient had L5-S1 radiculopathy
on EMG examinations. In overall assessment HT, iron deficiency,
digestive disorders and anxiety, depression were the major comorbid-
ities of RLS patients.
Conclusions: Iron deficiency, pregnancy, CKD were the best
known secondary causes of RLS like as we found in our study. RLS
is seen commonly with neurological and non-neurogical disorders.
Patients who have more than one comorbidities are associated with
increased risk of RLS.
1254
Periodic leg movements of sleep under general anesthesia
N. Vanegas, M. Hallett, K.A. Zaghloul, C. Lungu (Bethesda, MD,
USA)
Objective: To describe the occurrence of periodic leg movements
of sleep (PLMS) in a patient during general anesthesia.
Background: PLMS consists of periodic, myoclonic-like move-
ments of the lower extremities occurring in normal sleep. The patho-
physiology of this phenomenon is not entirely clear. Brainstem
hyperexcitability has been described, but most cases are thought to
originate at spinal level. A handful of cases have been described
with spinal anesthesia, but to our knowledge the phenomenon has
never been described under general anesthesia to date.
Methods: We report the case of a 56 year old man who devel-
oped PLMS under general anesthesia, before the implantation of
DBS electrodes for the treatment of Parkinsons disease. A video of
the phenomenology is included.
Results: The patient received 2mg of Midazolam, 100mcg of
Fentanyl and Propofol at an infusion rate of 125 mcg/Kg/min for
anesthesia induction during the initial stages of DBS placement.
Rhythmic movements of the legs were observed occurring at 5-20
second intervals. Some of the movements persisted briefly after the
anesthesia was discontinued.
Conclusions: We report a case of PLMS during general anesthe-
sia. The pathophysiology of the phenomenon is not entirely clear.
Based on previous reports of occurrence with spinal anesthesia, a
role for selective inhibition of spinal inhibitory interneurons has been
postulated. The observation that general anesthesia can also allow
the manifestation of PLMS suggests the possibility of alternative
subcortical origins of this phenomenon.
1255
Post-stroke restless legs syndrome and periodic limb Movement
Disorder
H.G. Woo, D. Lee, T.B. Ahn (Seoul, Korea)
Movement Disorders, Vol. 30, Suppl. 1, 2015
S490 POSTER SESSION
Objective: In this study, we planned to describe clinical and neu-
roimaging findings of 6 cases with post-stroke restless legs syndrome
(RLS) and periodic limb Movement Disorder (PLMD).
Background: Pathomechanisms of RLS and PLMD are difficult
to be separately tackled because RLS frequently coexists with
PLMD. There were some cases with RLS or PLMD after strokes
hinting different mechanisms.
Methods: The cases with post-stroke RLS or PLMD were
included from our database. To understand the different mechanisms,
we analyzed reported cases with post-stroke RLS or PLMD and
merged the clinical and neuroimaging data of our cases and the
reported cases. In all cases, RLS or PLMD occurred within 30 days
after stroke and had no history of RLS or PLMD prior to the stroke.
Results: Six cases with post-stroke RLS or PLMD were included
in our hospital. There were one patient with isolated RLS, three with
isolated PLMD and two with RLS and PLMD. In the literature, 25
cases of post-stroke RLS or PLMD were reported. Among them, 24
cases were presented with isolated RLS or PLMD. The clinical fea-
tures were compared between those with isolated RLS (20) and iso-
lated PLMD (8). Post-stroke PLMD developed later (p
value 5 0.025) and more frequently confined in the contralateral side
to the affected hemisphere with the stroke than post-stroke RLS (p
value 5 0.033).
Conclusions: In post-stroke RLS or PLMD, isolated cases were
very common (28/31). The difference in the clinical features may
suggest that RLS and PLMD develop via independent mechanisms.
Tics/Stereotypies
1256
Goal-directed and habitual behaviour systems in Gilles de la
Tourette syndrome
C. Delorme, A. Salvador, S. Palminteri, S. de Wit, E. Roze, A.
Hartmann, Y. Worbe (Paris, France)
Objective: To evaluate the balance between goal-directed and
habitual control systems in patients with Gilles de la Tourette Syn-
drome (GTS).
Background: Optimal behavioural performance results from a
balance between adaptive flexible and more rigid repetitive choices,
supported by goal-directed and habitual behavioural systems, respec-
tively. In GTS, this balance could be shifted towards the habitual
system, leading to a repetition of certain actions without the achieve-
ment of specific goals. As the habitual system is controlled by a
dopamine, use of dopamine antagonists in GTS could alleviate clini-
cal symptoms via the disruption of habit formation mechanism.
Methods: We employed a 3-stages instrumental learning para-
digm that included: (i) instrumental learning stage, (ii) outcome
devaluation stage and (iii) slip-of-action stage that directly tests the
balance between goal-directed and habitual systems. If a goal-
directed system exerts its control over behaviour, this results in a
selective responding towards valued as opposed to devalued out-
come. On the other hand, dominance of the habitual control system
leads to commission errors on trials associated with the devalued
outcomes. The task was tested on 3 groups of gender and age-
matched subjects: unmedicated and medicated (treated with neurolep-
tics) GTS patients and healthy controls (HC).
Results: Mixed-measures ANOVA showed that all groups suc-
cessfully learned from the instrumental learning stage (Main effect
of Learning: F(2,48) 5 161.00, p < 0.0001), with no difference
between groups. There was no difference in performance in the out-
come devaluation test, suggesting that all 3 groups learned the
action-outcome associations. By contrast, there was a significant dif-
ference (Main effect of Group: F(2,48) 5 4.47, p 5 0.024)) in the
slip-of-action stage. Unmedicated GTS patients had the highest rate
of response to the devalued stimuli on post-hoc comparisons
Movement Disorders, Vol. 30, Suppl. 1, 2015
(F(2,48) 5 4.86, p 5 0.020), whereas the performance of medicated
GTS patients was similar to those of HC.
Conclusions: These results suggest (i) the dominance of the
habitual system of behavioural control in unmediated GTS patients
that could play a key role in the formation and maintenance of GTS
symptoms, such as tics; (ii) use of dopamine blockers could re-adjust
the balance towards the goal-directed system. The findings are also
consistent with a previous data on functional hyperactivity of dopa-
mine system in GTS.
1257
Differential responsiveness of attention, OCD, and tics to
medications for Tourette syndrome
D.D. Duane, S. Leblang, M.A. Tokuyama (Scottsdale, AZ, USA)
Objective: To ascertain if the three major symptoms in Tourette
Syndrome (TS), inattention, OCD and tics, respond differentially to
medicinal therapy.
Background: To the best of our knowledge, no prior study has
evaluated the differential responsiveness of these TS symptoms to
medicinal treatment.
Methods: Retrospective chart analysis of 45 TS patients (35
male/10 female) with a mean age of 11.17 (range: 5.58 -16.75) in
which at least two evaluations were conducted with a change in
medication in which attention (attn) (both cognitive-CPT, TOVA,
LCT and behavioral measures-DSMIV Rating Scale, Achenbach
CBCL), OCD (Achenbach CBCL; Yale Brown Obsessive Compul-
sive Rating Scale) and tics (Yale Tic Rating Scale) were simultane-
ously assessed.
Results: Forty-seven medication trials: 29 atypical neuroleptic
(atyp) only, 4 SSRI only, 6 atyp and SSRI, 1 stimulant only, 1 Pimo-
zide only, 1 alpha blocker only; 1 SSRI and benzodiazepine; 1 SNRI
and AED; 1 SSRI, atyp, and AED; 1 SSRI, stimulant and atyp were
conducted. Of these trials, 15 patient trials showed improvement of
all three symptoms, most commonly when treated with an atyp 1/-
other medications (77%). Of 46 trials, 31 patients (67%) experienced
a positive effect on tics, 22 of the 31 (71%) also showed a positive
effect on attn; 17 of the 31 (55%) also experienced a positive effect
on OCD, in both most commonly with an atyp 1/- other medica-
tions. However, 6 of 12 with no benefit to tics had a positive effect
on attn. Of the 20 trials with a positive effect on OCD, 17 of 20
(85%) also exhibited a positive effect on tics, usually when treated
with an atyp, 1/- other medication. However, 12 of 21 (57%)
patients with no change or a negative effect on OCD experienced a
positive effect on attn, and 14 of the 21 (67%) experienced a positive
effect on tics.
Conclusions: Attn, tics and OCD often simultaneously improve
with use of an atyp with or without other medication classes. The
closest association is between a positive effect on tics and a positive
effect on attention. It is possible that tics and attn disorders share
similar mechanisms of responsiveness to medication, that a reduction
in tics benefits attention, or that there is a previously unrecognized
benefit to attention from atyp in TS not solely dependent on the ben-
efit to tics.
1258
Involuntary movements in adult patients with attention
hyperactivity deficit disorder (AHDH)
M. Farah, N.T. Mendes, M.M. Moscovich, A. Moro, R.P. Munhoz,
H.A.G. Teive (Curitiba, Brazil)
Objective: The objective of our study was to evaluate the corre-
lation of ADHD signs and presence of involuntary unmotivated
movements.
Background: The attention deficit hyperactivity disorder
(ADHD) is the most common mental disorder in children, but admit-
tedly also present in adulthood. It is known that one of the most
 POSTER SESSION
striking features of ADHD is the inability to keep in monotonous
activity. Patients with hyperactivity symptoms commonly experience
sense of unease presenting patterned excessive movement, often pur-
poseless. It is believed that the dysfunction is associated neural path-
ways that have not yet been elucidated.
Methods: 28 patients (8 male/20 female) with diagnosis of
AHDH according to the ASRS-18 criteria and without clinical diag-
noses were assessed. Mean age 28,14 (21-61) years. The same rater
evaluated all subjects. ASRS-18 was considered positive if there
were more than 4 answers often/very often in Part A (attention defi-
cit) and 4 in Part B (hyperactivity).We used a questionnaire that
addressed issues such as the presence of involuntary movements
unmotivated, frequency, type of movement and affected body site.-
This data was also compared to results in 59 healthy controls that do
not meet ASRS-18 criteria.
Results: The presence of unmotivated involuntary movements in
the group with criteria for ADHD was not significantly higher than
the control (78.58% vs 71.19%) . The most affected body site are
lower limbs (36,37%) both the ADHD group and in the control
(47,61%). The weekly frequency was also similar in both groups
(3.21 verses 3.85 in the control).
Conclusions: Our study shows increased presence of involuntary
movements in the group with ADHD, although discreet. The site of
the body most commonly involved are the lower limbs, especially
with repetitive motions to set the ground forefoot and heel hit. Addi-
tional studies are necessary to confirm the prevalence of involuntary
movements in patients with ADHD, since our dates have found little
difference in the control group.
1259
Premonitory urge to tic in Tourettes is associated with
interoceptive awareness
C. Ganos, A. Garrido, I. Navalpotro, L. Ricciardi, D. Martino, M.J.
Edwards, M. Tsakiris, P. Haggard, K.P. Bhatia (London, United
Kingdom)
Objective: To explore whether awareness of premonitory urges
to tic in adults with Gilles de la Tourette syndrome is associated
with interoceptive sensitivity.
Background: A contribution of aberrant interoceptive awareness
to the perception of premonitory urges in Gilles de la Tourette syn-
drome has been hypothesized but not experimentally studied.
Methods: We assessed interoceptive awareness in 19 adults with
Tourettes and 25 age-matched healthy controls using the heartbeat
counting task. We also used multiple regression to explore whether
the severity of premonitory urges was predicted by interoceptive
awareness or severity of tics and obsessive-compulsive symptoms.
Results: We observed a trend for lower interoceptive awareness
in adults with Tourettes compared to controls. Interoceptive aware-
ness was the strongest predictor of premonitory urges in Tourettes
patients, with greater interoceptive awareness being associated with
more urges. Greater tic severity was also associated with higher rates
of premonitory urges.
Conclusions: The observed relationship between severity of pre-
monitory urges and interoceptive awareness suggests that interocep-
tion might be involved in self-reported premonitory urges in
Tourettes. High levels of interoceptive awareness might reflect a
self-attentive capacity to perceive urges.
1260
The somatotopy of tic inhibition: Where and how much?
C. Ganos, J. Bongert, L. Asmuss, D. Martino, P. Haggard, A.
Munchau (London, United Kingdom)
Objective: To investigate the spatial distribution of tics in Tour-
ettes in a free ticcing and in a voluntary tic inhibition independent of anxiety and higher in subjects with tactile/any HS
condition.
S491
Background: Tics are the hallmark feature of Tourettes. The
basic phenomenological and neurophysiological characteristics of tics
have been widely investigated. Interestingly, the spatial distribution
of tics across different body parts has received little attention. No
previous study has investigated whether the capacity for voluntary
tic inhibition also varies across body parts.
Methods: We analysed video sequences of 26 adolescents with
Tourettes in a free ticcing condition, and in a voluntary tic inhib-
ition condition, to obtain absolute tic counts for different body
parts. Two measures of the spatial distribution of tics were then ana-
lysed. Linear regression analyses were employed to investigate the
relationship between the contribution of each body part to overall tic
behaviour and the ability to inhibit tics in that body part, averaged
over our patient group.
Results: Tic distribution across patients showed a characteristic
somatotopic pattern, with the face most strongly represented. A sig-
nificant negative relation was found between the ability to inhibit
tics and pooled tic frequency across body parts. The body parts that
exhibited fewest tics were the ones for which tic inhibition was most
effective.
Conclusions: Our data is consistent with the idea that tic recruit-
ment order reflects a tic generator spreading across a somatotopic
map in the brain. Voluntary tic inhibition did not simply cause a pro-
portional reduction of tics in each body part. Our findings suggest
that tic inhibition involves a voluntary shift of physiological signal
processing that suppresses motor noise by preferentially transmitting
only stronger signals within cortico-striato-thalamo-cortical motor
loops.
1261
Sensory phenomena in tic disorders: Dimensions and clinical
associations
D.G. Lichter, S.G. Finnegan (Buffalo, NY, USA)
Objective: To evaluate in subjects with Tourette syndrome (TS)
and chronic motor tic disorder (CMT): (1) The relationship between
stimulus hypersensitivity/overresponsivity (HS), generalized and
focal somatosensory urges (SU) and just-right/not just-right (JR/
NJR) phenomena; and (2) the contribution of these sensory symp-
toms to severity of tics and obsessive-compulsive disorder (OCD).
Background: In tic disorders, the clinical impact and inter-
relationship of HS and sensory/cognitive-sensory urges, which distin-
guish tics from other Movement Disorders, is incompletely
understood.
Methods: 75 subjects with TS (n570) or CMT (n55), aged
26.6 6 15.0 years, were evaluated for prodromal/associated sensory
symptoms using the University of Sao Paulo Sensory Phenomena
Scale (USP-SPS). HS was assessed by subject and/or parental inter-
view and, in a subset, by the Adult Sensory Profile and Sensory Gat-
ing Inventory. The Yale Global Tic Severity Scale (YGTSS), Yale-
Brown Obsessive Compulsive Scale (Y-BOCS/CY-BOCS), Dimen-
sional Y-BOCS (DY-BOCS) and CAMH-CDS were used to assess
tic and OCD severity, and mood. Predictors of OCD severity were
sought by stepwise regression analysis of total DY-BOCS scores.
Results: HS to tactile, auditory or visual/olfactory stimuli
occurred in 34 (45%) subjects and was more common at a younger
age (p 5 0.0003). HS was unrelated to SU or YGTSS score. Dystonic
but not clonic tic severity was associated with focal or generalized
SU and higher USP-SPS score (p 5 0.001) but not with JR/NJR phe-
nomena. JR/NJR behaviors occurred in 42 (56%) subjects and were
associated with Y-BOCS score and HS (p 5 0.014) but not with SU
or YGTSS score. JR behaviors and related symmetry/ordering com-
pulsions triggered by tactile/proprioceptive (31%), visual (21%) and
auditory (4%) stimuli accounted for the greatest percentage of var-
iance in total DY-BOCS scores, anxiety failing to contribute signifi-
cantly. The DY-BOCS cleaning/contamination score was also
(p 5 0.028).
Movement Disorders, Vol. 30, Suppl. 1, 2015
S492 POSTER SESSION
Conclusions: In TS: (1) Altered sensory processing is central to
both tics and OCD; (2) HS is more common in younger patients and
may increase expression of JR/NJR behaviors and washing/cleaning
obsessions and compulsions; (3) OCD is driven more by JR/NJR
phenomena than by anxiety; (4) HS and SU reflect orthogonal
dimensions of sensory experience; and (5) Heightened SU may pre-
dispose to more severe dystonic tics.
1262
Hand stereotypies in Wilsons disease
S.O. Mittal, A. Ranpura, A. Salardini, B. Jabbari (Cleveland, OH,
USA)
Objective: We present case study of young patient with diagnosis
of Wilsons disease (WD) presenting with stereotypies in both hands.
Background: Stereotypies are a phenomenological category of
hyperkinetic Movement Disorders. The exact definition of stereotypy
varies with different authors. It is described as coordinated, pat-
terned, repetitive, rhythmic, purposeless but seemingly purposeful or
ritualistic, movement, posture or utterance (Jankovic 1994). In an
attempt to distinguish stereotypies from tics and other repeated
Movement Disorders, described as a nongoal-directed movement
pattern that is repeated continuously for a period of time in the same
form and on multiple occasions, and which is typically distractible.
(Edwards et al 2013).
Wilsons disease is disorder of copper metabolism with excessive
accumulation of copper in basal ganglia. Hyperactive Movement Dis-
orders seen in WD includes dystonia (frequently evident in face,
jaw, neck, trunk, and limbs), tremor - postural, action-induced, inten-
tional, rest tremor or swinging involvement of the proximal upper
limb (wing-beating tremor). Yorio et al. (1994), have described ster-
eotypy of toes in both feet in a patient of WD.
Methods: This is a case study.
Results: 26 year right handed female presents with approximate 3
months history of decline in function with slowed information process-
ing, and dysarthirc speech. On exam she had purposeless, flexion-
extension movements of all fingers in both hands. They were involun-
tary, patterned, repetitive and rhythmic. The movements improved
slightly on distraction. Occasional dystonic movements of the lips and
jaw was present. Neurological exam was otherwise unremarkable.
Kayser-Fleisher rings was evident on slit-lamp exam. MRI brain
showed T2 hyper intensity in bilateral striatum. Laboratory investiga-
tions showed very low ceruloplasmin, high copper levels and abnor-
mal liver function, thus confirming WD and was initiated on trientine.
Conclusions: We believe, this is the first formal description of
hand stereotypy in Wilsons disease. It is important and challenging
to distinguish stereotypy from tremors, myoclonus, tics, dystonia,
chorea and athetosis. A videotape showing patients movements will
be presented in the conference.
1263
The clinical and morphometric features of tic hyperkinesis
S.E. Munasipova, Z.A. Zalyalova, S. Munasipova (Kazan, Russia)
Objective: To determine the clinical and morphometric character-
istics of patients with tics.
Methods: The morphometry of the cingulate gyrus, corpus cal-
losum, thalamus, globus pallidus, shell, caudate nucleus were per-
formed to 46 patients with tics associated by OCD (obsessive-
compulsive disorder) and ADHD (attention deficit hyperactivity dis-
order), 20 patients with chronic diseases of upper respiratory tract
and 20 healthy individuals.
Results: 1. in patients with tics the front third height of the cin-
gulate gyrus was less than that of the control group; the severity of
motor tics depends on the height of the middle third and vocal tics
of the height of the posterior third of the cingulate gyrus; dorsoven-
tral size of the caudate nucleus of the right hemisphere in the group
Movement Disorders, Vol. 30, Suppl. 1, 2015
of patients with tics was greater than that of the control group (p
<0.05).
2. The height of the middle third of the cingulate gyrus of
patients with OCD greater than in patients without OCD; the correla-
tion between the severity of OCD and the knees length of the cor-
pus callosum, the hemispheric asymmetry with left thalamic volumes
increase, the reduced the amount of the globus pallidus in the right
hemisphere, the flattened shape of the shell in the left hemisphere
and the elongated shape of the shell in the right hemisphere were
found (p <0.05).
3. The severity of ADHD depends on the distance from the fron-
tal pole of the brain to the knee of the corpus callosum which indi-
rectly indicates the interest of the frontal lobe.
Conclusions: The syndrome of tic hyperkinesis is the result of
the pancerebral dissociation involving the limbic system, the cortico-
striatal-thalamo-cortical circle. At the same time some phenotype has
topical dependency.
1264
Tic attacks: Panic disorder in Tourette syndrome?
S. Robinson, P. Hindley, T. Hedderly (London, United Kingdom)
Objective: To report a case study of Tourette syndrome (TS) and
tic attacks that challenges the view that tic attacks reflect extended
bouts of tics and provides a cognitive-behavioural framework to
guide assessment and treatment.
Background: TS is a neurological Movement Disorder character-
ized by tics - repetitive, involuntary movements and vocalizations
associated with a premonitory urge. Co-occurring anxiety disorders are
common. Tic attacks have been described as reflecting distinct bouts
of severe, continuous, nonsuppressible and disabling tics lasting from
15 minutes to several hours. To date, there are no clinical case reports
or studies exploring the assessment and management of tic attacks.
Methods: JT was a 15 year male who presented with florid tic-
like movements lasting 1-3 hours. Movements were preceded by a
swollen feeling in the spine, followed by uncontrollable limb jerking.
Onset of episodes was at 13 years, with 14 episodes reported and
managed by attending A&E. Medical investigations were normal
(EEG, MRI, toxicology, gastroenterology) and pharmacological man-
agement was unsuccessful (Aripirazole). JT reported a actively sup-
pressing a daily urge to twitch, with social anxieties and concern
about causing harm to self/others.
Results: JT was diagnosed with late onset TS with tic attacks,
social anxiety and OCD. Cognitive behavioural formulation indicated
a relationship between physiological sensations/tic urges, thoughts/
worries about tic attacks and behavioural responses (body scanning
for tics, planning escape routes). An internal focus of attention was
reported (80%), with the misinterpretation of anxiety symptoms (ele-
vated heart rate, sweating) triggering tic attacks. Behavioural experi-
ments, external attention training, thought challenging and image
restructuring contributed to a significant reduction in tic attacks.
Conclusions: JT presented with undiagnosed TS with tic attacks.
Cognitive-behavioural formulation indicated that his internal focus of
attention, social anxiety around tics, misinterpretation of anxiety
symptoms and engagement in safety behaviours triggered and main-
tained tic attacks. The episodes responded to psychological treatment
to manage anxiety (rather than the movements per se). This case
challenges the view that tic attacks reflect extended bouts of tics;
instead it is proposed that the tic-like movements of tic attacks may
be functional, with tic attacks reflecting episodes of panic in individ-
uals with TS.
1265
Neural correlates of Tourette syndrome within the centromedian
thalamus, premotor and primary motor cortices
J. Shute, P.J. Rossi, C. de Hemptinne, K. Foote, M. Okun, A.
Gunduz (Gainesville, FL, USA)
 POSTER SESSION
Objective: To further (1) the understanding of Tourette Syn-
drome through analysis of local field potentials collected from the
centromedian nucleus of the thalamus, premotor cortex, and primary
motor cortex and (2) the practice of deep brain stimulation by identi-
fying neural correlates of therapeutic outcomes and symptomology
that may be for development of closed loop stimulation paradigms.
Background: Tourette Syndrome (TS) is a neurological disorder
characterized by undesired motor and vocal tics. Treatment of TS
varies depending on symptom severity and individual therapy effec-
tiveness. Deep brain stimulation (DBS) is an emerging therapy for
the treatment of many neurological disorders, including severe TS
through the electrical stimulation of deep brain nuclei.
Methods: A patient with Tourettes Syndrome was implanted at
University of Florida (UF) Shands Hospital with two bilateral sub-
dural 4-contact cortical strip electrodes and two bilateral 4-contact
subcortical depth electrodes with the aim of capturing tic-related
physiology. All procedures were approved by the FDA and UF IRB.
The depth electrodes were placed bilaterally within the centromedian
nucleus of the thalamus (Cm) and the cortical subdural strips were
placed bilaterally over the premotor (PM) and primary motor (M1)
cortices. Local field potentials (LFP) from the depth electrodes, elec-
trocorticograms (ECoG) from the cortical electrodes, and electro-
myograms (EMG) from electrodes placed over the forearm and
cheeks were recorded intra-operatively while the patient was awake.
The patient was asked in interleaved trials to suppress tics (baseline),
make right and left hand movements, imitate tics, and tic freely.
Results: Initial results suggest that when compared to baseline,
Low Frequency activity in PM, M1 and Cm were correlated with
contralateral tic behavior compared to baseline. This observation was
different than what was observed in voluntary movements, which
were associated with contralateral cortical activity but not thalamic
activity. Local and subcortical-to-cortical phase amplitude coupling
(PAC) suggested regionally specific activation patterns across PM,
M1 and Cm.
Conclusions: Low frequency thalamic and cortical activity are
highly correlated with tics. A majority of tics (sensitivity: 70%, spec-
ificity 72%) were detected across 5 months of data using low fre-
quency activity from Cm and M1.
Therapy in Movement Disorders: Gene and
cell-based therapies
1266
Enhancement of lysosomal biogenesis reverse A53T mutant
a-synuclein induced toxicity
M. Bourdenx, S. Dovero, M. Bastide, G. Porras, N. Dutheil, Q. Li,
A. Ballabio, E. Bezard, B. Dehay (Bordeaux, France)
Objective: Enhancement or restoration of lysosomal-mediated
degradation may prove beneficial for PD.
Background: Increasing evidence indicates that impairment of
lysosomal function may contribute to the pathogenesis of Parkinsons
disease (PD). Autophagy-lysosome pathways alterations are observed
in sporadic and familial forms of PD as well as in toxic and genetic
rodent models of PD-related neurodegeneration. In this regard,
enhancement or restoration of lysosomal-mediated degradation may
prove beneficial for PD. Transcription factor EB (TFEB) has been
recently identified as a new master regulator of lysosomal biogenesis
and function and its activation has been shown to attenuate 1-
methyl-4-phenylpyridinium-induced cell death in an in vitro setting.
ZKSCAN3, a zinc finger family DNA-binding protein, has been
recently characterized as a master transcriptional repressor of
autophagy.
Methods: To investigate the neuroprotective effect of enhance-
ment of lysosomal biogenesis in an in vivo model, we used a genetic
model of PD based on the overexpression of human mutant A53T
synuclein (A53TSyn) by adeno-associated virus serotype 9 (AAV2/9)
S493
in the rat midbrain. Briefly, rats will be stereotactically unilaterally
injected with either one (A53T a-synuclein) or two viruses (A53T
a-synuclein and TFEB or shZKSCAN3) in the right substantia nigra
pars compacta (SNpc). Sixteen weeks after surgery, rats will be ana-
lyzed both from a behavioural stand-point and for the extent and pat-
tern of lesion as well as for the possible occurrence of inclusions and
autophagy activation.
Results: We here report that unilateral AAV2/9-mediated overex-
pression of TFEB or repression of ZKSCAN3 through silencing strat-
egy in the substantia nigra pars compacta (SNpc) reverse the toxicity
of a-synuclein in the AAV2/9-A53TSyn rat model. Behavioral inves-
tigations have shown that overexpression of TFEB and silencing of
ZKSCAN3 restored left paw use in cylinder test. Histological analy-
ses performed at the level of SNpc dopaminergic neuron cell bodies
and striatal dopaminergic terminals were used to assess extent of
dopaminergic lesion as well as occurrence of a-synuclein pathology.
Conclusions: In order to assess the translational value of such
strategies, we are currently analyzing the neuroprotective effect in a
primate model of PD.
1267
From the bedside to the bench: Stem cells from non-familial
young-onset patients with Parkinsons disease
S. Sances, W. Lv, M. Tagliatti, C. Svendsen (Los Angeles, CA, USA)
Objective: The generation of induced pluripotent stem cell lines
for the modeling of young-onset Parkinsons disease.
Background: Pathogenesis of Parkinsons disease (PD) is com-
plex, involving multiple brain regions and neural subtypes that are
not completely understood. Induced Pluripotent Stem Cell (iPSC)
technology enables the generation and study of living brain tissue
relevant to Parkinsons disease (PD) ex vivo. Utilizing cell lines
from PD patients seen in the clinic presents a powerful discovery
system that links cellular phenotypes observed in vitro with real clin-
ical data.
Methods: We have focused on non-familial cases of young-onset
PD in patients presenting with motor-symptoms at less than 50 years
of age. After informed consent, 5 patients contributed peripheral
blood samples in the clinic at Cedars-Sinai Medical Center, which
were subsequently purified for peripheral blood mononucleocytes
(PBM) and reprogrammed to pluripotency using non-integrating epi-
somal techniques.
Results: Taking a PD relevant path back down differentiation,
patient-derived iPSCs were directed towards a dopaminergic (DA)
neural fate. These cells exhibit molecular and functional properties
of DA neurons in vitro that are observed to significantly degenerate
in the substantia nigra of PD patients. Clinical symptoms that drive
the generation of other relevant cell types may also yield novel PD-
specific phenotypes in vitro that have the potential to lead to new
therapeutic avenues for patients with PD.
Conclusions: Due to their early onset and non-familial origin,
differentiated nervous tissue from these patients offer a key opportu-
nity to discover neuron subtype-specific pathological mechanisms
and importantly interrogate the contribution of their genetic back-
ground in susceptibility to PD using multi-omic cellular analyses.
1268
Optogenetic modulation of striatal dopaminergic cell transplants
in Parkinsonian rats
T. Subramanian, K. Venkiteswaran, T.P. Gilmour, B. Zhang, C.A.
Lieu, M. Dawson, Z. Liu, M.P. Subramanian, E. Handly, C.
Ramakrishnan, K. Deisseroth (Hershey, PA, USA)
Objective: To test the effectiveness of external optogenetic mod-
ulation of functionally integrated striatal dopaminergic grafts in Par-
kinsonism and to determine pathophysiological basis of its
therapeutic effects.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S494 POSTER SESSION
Background: Basal ganglia circuit functions have largely been
studied using lesioning, stimulation or pharmacological manipula-
tions. Restorative cell based therapies that can be turned off or
on using optogenetics potentially provide a novel approach to
study basal ganglia pathophysiology. To test this concept, we tested
whether Natronomonas halorhodopsin (eNpHR 3.0) mediated optoge-
netic inactivation can achieve functional neuromodulation in dopami-
nergic cell transplants.
Methods: To ensure specificity, an AAV5 recombinant virus that
contains double-floxed Cre-dependent eNpHR3.0EYFP (AAV5-
Ef1a-DIO-eNpHR3.0- EYFP) was used to transfect mouse fetal ven-
tral mesencephalic (FVM) dopaminergic grafts prior to transplanta-
tion into the striatum of 6-OHDA lesioned hemiParkinsonian rats
that was previously transfected with a transsynaptically mediated
switch (AAV2- Ef1a-mCherry-IRES-WGA-Cre) to turn on eNpHR
3.0. Thus, only mouse FVM neurons that make synaptic connections
with the host striatum expressed eNpHR 3.0. Animals were repeat-
edly tested for Parkinsonian behavior at baseline and weekly for 12
weeks post-transplantation to demonstrate reversal of
hemiParkinsonism.
Results: Optogenetic activation of eNpHR 3.0 within the FVM
grafts caused loss of graft derived behavioral benefits that was com-
pletely reversible when optogenetic activation was discontinued. All
appropriate control animals showed no effects from optogenetic laser
exposure. Histology demonstrated well developed dopaminergic
mouse FVM neurons that expressed eNpHR 3.0 and EYFP sur-
rounded by mCherry expressing medium spiny neurons in the rat
host striatum decorated with EYFP labeled graft derived synapses.
Conclusions: This is the first in vivo demonstration of a novel
experimental therapeutic approach that provides external functional
control of dopaminergic grafts in Parkinsons disease. These results
provide conclusive evidence of functional integration of dopaminer-
gic grafts and their role on restoring continuous dopaminergic stim-
ulation in experimental therapeutic approaches to Parkinsons
disease.
POSTER SESSION 8
Thursday, June 18, 2015
12:0013:30
Coronado Ballroom
Cognitive disorders
1269
The effects of the facial expression of emotions on time
perception in patients with Parkinsons disease
L. Bartolomei, G. Mioni, F. Stablum, L. Malesani, L. Meligrana
(Vicenza, Italy)
Objective: In the present study, we investigate the magnitude of
temporal distortions caused by the presentation of facial expression
of emotions in PD patients and controls.
Background: Several studies have demonstrated an interaction
between time perception and affective dimensions in healthy partici-
pants, and many of them showed that time distortions are caused at
the view of facial emotional expressions. Previous studies have dem-
onstrated temporal judgment impairment in Parkinsons disease (PD)
patients. No previous studies have investigated the distortion caused
on time perception by facial expression of emotion in PD patients.
Methods: Twenty-five older adults with PD and 17 healthy older
adults took part in the present study. PD patients were also divided
into two sub-groups, with (PD-MCI) and without mild cognitive
impairment (PD-non-MCI), according to their score at a neuropsy-
chological evaluation.
Movement Disorders, Vol. 30, Suppl. 1, 2015
Stimuli used in the time bisection task were black-and-white pic-
tures of male and female with the facial expression of anger or
shame, or a neutral expression. Two standard durations were used:
400 ms (short standard) and 1600 ms (long standard). Participants
were required to judge if the duration presented was closer to the
short standard or to the long standard.
Results: PD-MCI were less accurate than PD-non-MCI and con-
trols in the way that PD-MCI perceived temporal intervals as shorter
than the presented interval. Moreover, PD-MCI patients judged lon-
ger temporal intervals as shorter and short intervals as longer than
the presented durations. When the stimuli showed the facial expres-
sion of anger, temporal intervals were over-estimated whereas when
the stimuli showed the facial expression of shame, temporal intervals
were under-estimated. Moreover, significant differences were found
between emotional stimuli (anger and shame facial expressions) and
neutral stimuli only at 400 ms in PD-MCI patients.
Conclusions: Effect of facial emotional stimuli on time percep-
tion is evident in all participants. Also, PD-MCI patients were less
accurate than PD-non-MCI and controls: PD-MCI patients under-
estimated long and over-estimated short temporal intervals more than
PD-non-MCI patients.
1270
Parkinsons disease study with virtual week manipulated for
emotional valence
L. Bartolomei, L. Meligrana, G. Mioni, F. Stablum (Vicenza, Italy)
Objective: This study investigated the effect of Parkinsons dis-
ease (PD) on prospective memory (PM) tasks with varying the emo-
tional content of the PM actions.
Background: Prospective memory, or remembering to carry out
previously formed intentions at the appropriate moment, is a com-
plex cognitive construct that has received increasing attention in PD.
PM dysfunctions in PD patients can be very frustrating and limit
patients everyday independence. Previous studies conducted with
healthy older adults have demonstrated that presenting stimuli with
emotional content (negative and positive valence) affect PM per-
formance in the way that stimuli with emotional valences are better
remembered compared with neutral stimuli.
Methods: Twenty-one older adults with PD (M=9, F=12) without
diagnosis of dementia, and 25 healthy older adults (M=10, F=15)
took part in the present study. Virtual Week task, a computer based
memory task that simulates everyday prospective memory activities
was used. Participants performed three virtual days in which they
were required to remember to perform 8 PM actions. We manipu-
lated the emotional content of the PM actions so participants every
virtual day performed actions with positive (i.e. tell Roberta that
Maria had a baby girl when you talk to Roberta), negative (i.e.
visit your friend at the hospital when you go shopping) or neutral
(buy the bus tickets after breakfast) content. Immediately following
each virtual day, participants completed a recognition test to assess
their retrospective memory for the various prospective memory tasks.
Participants also performed a complete neuropsychological
evaluation.
Results: PD patients were less accurate than controls and there
was also a main effect of emotional valence indicating that all partic-
ipants were more accurate on positive PM tasks than both negative
and neutral. Participants did not differ on negative compared to neu-
tral PM tasks. Thus there was a positive enhancement effect but no
negative enhancement or impairment when comparing PM perform-
ance on emotionally valence tasks with neutral tasks. To clarify the
impact of emotional valence positivity and negativity enhancement/
impairment indexes were calculated, the positivity enhancement was
greater than zero for participants with Parkinsons.
Conclusions: Our study confirmed PM impairment in PD patients
and extended previous findings showing how emotional valence can
manipulate PM performance.
 POSTER SESSION S495

1271 Results: Analysis of the neuropsychological examinations showed

that delayed recall, as shown by verbal learning tests, was signifi-
Pallidal deep brain stimulation improves memory in patients with cantly improved after DBS (mean baseline score of 5.9 6 2.0 and
cervical dystonia: Is the effect on the nucleus basalis of Meynert? mean postoperative score of 7.0 6 2.1, P=0.041).
M. Chung, R. Huh, I.U. Song (Incheon, Korea)
Objective: We investigated whether the cognitive function and
memory of patients with CD were affected by GPi DBS using retro- Neuropsychologic examination data
spective data from neuropsychological examinations. Baseline Follow P-
Background: Medically refractory cervical dystonia (CD) may Items test up test value*
be treated with surgical treatment such as deep brain stimulation
(DBS). Recently, the nucleus basalis of Meynert (NBM) has been Digit span forward 6.0 (1.3) 6.4 (1.3) .336
suggested as a potential target for memory impairment. As the Digit span backward 4.0 (1.0) 4.0 (1.0) 1.00
globus pallidus internus (GPi), which is the optimal target for CD, is Korean-Boston Naming test 50.1 (4.2) 51.3 (3.8) .324
anatomically close to the NBM, electric stimulation for the therapeu- Rey complex figure test 34.2 (3.0) 33.7 (2.1) .396
tic purpose of CD potentially affects the NBM. SVLT immediate recall 19.4 (4.1) 19.1 (3.7) .587
Methods: The neuropsychological examinations, which were con- SVLT delayed recall 5.9 (2.0) 7.0 (2.1) .041
ducted pre- and postoperatively, of nine patients with CD were retro- SVLT Recognition 21.6 (2.5) 22.6 (1.2) .263
spectively analyzed. Before performing the neuropsychological tests, RCFT Immediate recall 14.8 (5.4) 17.2 (6.8) .138
the location of the active contact was plotted on the Schaltenbrand- RCFT Delayed recall 14.3 (3.7) 17.2 (7.4) .213
Wahren atlas, and the patients were separated into two groups RCFT Recognition 20.2 (2.2) 20.4 (1.5) .671
according to whether the active contact was adjacent to the NBM.
(Continued)

Fig. 1. (1271).

Movement Disorders, Vol. 30, Suppl. 1, 2015

S496 POSTER SESSION

Table (Continued) Methods: Fourteen macaque monkeys (six cynomolgus monkeys, one
rhesus monkey, and seven Japanese monkeys) ranging 10-31 years old
Controlled oral word 21.9 (5.5) 23.3 (7.0) .404 were used. We performed counts of amyloid-beta plaques in the brain.
association test Results: There were no amyloid-beta depositions in the brains less
Stroop test Word reading 111.3 (1.7) 103.3 (17.9) .285 than twenty-one years old. As the age went, the number of amyloid-
Stroop test Color reading 86.4 (22.7) 79.3 (23.1) .176 beta plaques was increased. These depositions were found in amygdala
and nucleus accumbens in monkeys more than twenty-one years old,
and spread to temporal lobes, cingulate gyrus, hippocampus. At brains
Seoul verbal learning test (SVLT), Rey Complex figure test (RCFT),
older than twenty-six years old, amyloid-beta depositions further
*Wilcoxon Signed Rank Test
appeared in the orbitofrontal cortex and striatum. The average number
of the plaques in the aged brains more than twenty-six years old was
The mean length of the intercommissural line was 25.1 mm, with 672% as many as in twenty-one to twenty-five years old cases, respec-
a range of 23.6-26.3 mm, as measured from the nine CT scans of the tively. However, no marked cognitive deficits and abnormal behaviors
enrolled patients. The active contacts were plotted on the Schalten- were observed even in the aged monkeys.
brand altas. [figure1] Five of the nine patients had active contacts Conclusions: These results indicate that the distribution and pro-
adjacent to the NBM, and this group (median 37.5%, range of 0- gression of the amyloid-beta accumulation in aged macaque monkeys
100%) presented with higher memory improvement rates than the display some similarities to those observed in the aged humans and
other group (median 0%, range of 0-20%, P=0.096). AD cases. Therefore, the aged macaque monkeys might be a pre-
symptomatic model for AD.

Comparison of the improvement rates between the groups

1273
The NBM The non-NBM P-
Clinical scales group group value Parkinsons disease and cognitive reserve
F. Mancini, S. Guzzetti, L.G. Manfredi, A. Caporali, R. Daini, A.
TWSTRS severity 37.5 (31.8-65.5) 78.8 (35-100) .140 Antonini (Milano, Italy)
K-MMSE 0 (-11.5-0) 1.9 (-7.1-6.9) .260
SVLT Immediate -4.5 (-7.7-16.7) -5.4 (-15.8-17.7) .712 Objective: The aim of this study is to evaluate the role of Cogni-
recall tive Reserve (CR) in Parkinsons disease (PD), specifically, if the
SVLT Delayed recall 37.5 (0-100) 0 (0-20) .096 presence of a high CR may be related to a better cognitive and/or
SVLT Recognition 9.1 (-4.4-27.8) 0 (-4.35-5.26) .387 motor performance.
RCFT Immedicate 30 (-20.8-67.9) 1.2 (-27.3-54.2) .327 Background: Dementia is a frequent feature of PD. The main
recall risk factors for PD dementia have been extensively explored but
RCFT Delayed recall 16.7 (-8.7-133.3) -5.9 (-45-66.7) .327 recent studies suggests that CR needs to be considered when moni-
RCFT Recognition 0 (-9.5-17.7) 3.1 (-13.6-15.8) .803 toring the evolution of cognition in PD. CR refers to the modality of
cognitive system elaboration of information and it has been used to
explain the individual differences in the ability to cope with neuro-
The nucleus basalis of Meynert (NBM) group includes patients logical damage: individuals with more efficient neural networks
whose, at least one side of, active contact was located inside or adja- could be more resilient to neurological damage.
cent of the NBM. The non-NBM group was the patients other than Methods: Eighteen consecutive PD patients (16 males, mean age:
the NBM group. TWSTRS Toronto Western Spasmodic Torticollis 69 6 7,3 years; mean disease duration: 8 6 4,8 years; mean educa-
Scale, K-MMSE Korean-Mini mental status examination, COWAT tion: 12 6 4,6 years) were enrolled in the study and underwent clini-
Controlled word association test. All statistic analyses were per- cal and neuropsychological evaluations, during ON state, with:
formed by Mann-Whitney U test. Unified Parkinsons disease Rating Scale (UPDRS), Hoehn and Yahr
scale (HY), a standard neuropsychological test battery and the Cog-
Conclusions: The patients with CD who underwent GPi DBS nitive Reserve Index questionnaire (CRIq).
showed significant improvement in verbal memory delayed recall. Results: A significant positive association between CRIq and
This positive effect on memory function likely correlated with unin- scores of MMSE and specific tests for the evaluation of frontal-
tended stimulatory effects on the NBM, thereby playing an important executive functions, verbal short-term memory and mental lexicon
role in modulating human cognitive function. size was found. In particular a higher CRI correlates with a better
semantic fluency score (< 0.05).
The analysis of the other clinical and neuropsychological test
1272 scores confirmed that disease duration is a good predictor of cogni-
Age-dependent distribution change of amyloid-beta protein in tive function. No correlation emerged between CR and the UPDRS
macaque brains III score.
Conclusions: CR may be considered a good predictor of the clin-
K. Kimura, K. Inoue, F. Tanaka, M. Takada (Yokohama, Japan)
ical manifestation of cognitive impairment in PD. Long term pro-
Objective: To survey the distribution pattern of amyloid-beta spective detailed studies on larger populations are useful to study
expressions during aging in aged macaque brains. effects of CR on cognition, cognitive decline and the time of onset
Background: Alzheimers disease (AD) is the most common of dementia in PD.
form of dementia, accounting for approximately 60% of all dementia References:
cases. AD is characterized by gradual deterioration of cognitive func- Nucci M, Mapelli D, Mondini S. The cognitive reserve question-
tions including memory, and neuropsychiatric symptoms. Extracellu- naire (CRIq): A new instrument for measuring the cognitive reserve.
lar amyloid plaques composed primarily of aggregated amyloid-beta Aging Clinical and Experimental Research 2011;24(3): 218226.
are one of the main pathological features of AD brain, and mainly Hindle JV, Martyr A, Clare L. Cognitive reserve in Parkinsons
found in the temporal cortex, amygdala, and hippocampus. It is also disease: A systematic review and meta-analysis. Parkinsonism and
found during normal aging. When the deposition starts and how the Related Disorders 2014;20: 1-7.
deposition proceeds and spreads remain unclear. In the present study, Poletti M, Emre M, Bonuccelli U. Mild cognitive impairment and
we investigated the distribution pattern of amyloid-beta expressions cognitive reserve in Parkinsons disease. Parkinsonism and Related
in aged macaque brains. Disorders 2011;17:579-586.

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
1274
Characteristic of cognitive and emotional personality disorders in
patients with essential tremor
R.J. Matmurodov, K.K. Khalimova (Tashkent, Uzbekistan)
Objective: To study the cognitive, emotional and personality
functions in patients with ET.
Background: The study of essential tremor is (ET) an actual
problem of modern neurology. ET is characterized by non-motor
manifestations that contribute to the disease. Almost all patients suf-
fer from cognitive impairment and depression.
Methods: A total of 29 patients (15 men and 14 women), mean
age 44,3 6 2,5 years with ET. The mean duration of disease was
4,64 6 2,7 years. All patients underwent clinical, neurological, neuro-
psychological and neurophysiological studies. The control group con-
sisted of 14 patients without ET.
Results: In 4 (13.7%) patients with ET was not observed cognitive
impairment. In 18 (62.15) patients met predement cognitive impair-
ment, while the MMSE was 24-27 (24,8 6 3,6). 7 (24.1%) patients
with dementia MMSE 11-23 ball (18,4 6 2,3), 5 (71.4%) patients with
dementia, mild degree, and 2 (28.6%) moderate dementia expressive-
ness. Analysis of emotional-personal sphere show that trait anxiety
common in both groups (p <0,01 (38,3 6 2,3 and 27,4 6 2,1) com-
pared. In 17 (58.6%) patients had mild anxiety, y (7 24.1%) patients
the mean anxiety and in 4(13.7%) patients met high anxiety. Depres-
sion was observed in both groups of patients, but patients with ET
met a deep depression, major depression of moderate severity
(60.3%). Mild depression was observed in 6 (20.6%) patients.
Conclusions: Patients ET longer observed predement cognitive
impairment and also, more common trait anxiety. At a late stage of
the disease begins depression. Extent of these disorders depends on
the course of the disease.
1275
Effects of early iron deficiency on catecholaminergic transporters
in rat brain
W. Mohamed (Shebin el Kom, Egypt)
Objective: In this study, we investigated the possible effects of
infantile ID on catecholaminergic membrane transporter densities in
the brain. At postnatal day-4 (PND4), all pups were out-fostered.
Animals were sacrificed at 21, 45 and 75 days of age.
Background: Iron deficiency (ID) is the most common single
nutrient disorder worldwide.
Methods: We examined individual brain regions specific for
DAT; striatum, nucleus accumbens (NA), substanitia nigra (SN), and
olfactory tubercle (OT); and others specific for NET; frontal cortex
(FC), dentate gyrus (DG), and locus coeruleus (LC). DA transporter
ligand binding was performed using [125I]-RTI-55 while NET trans-
porter ligand binding was performed using Nisoxetine HCl [N-
Methyl-3H].
Results: Results reveal a significant age effect on DAT levels in
NA, OT, and SN respectively but not in the striatum. Specifically,
21-day-old rats had greater DAT levels compared to 45-day-old rats
in the NA, OT and SN as well as in the OT compared to 75-day-old
rats. There was no main effect for diet and no diet-age interactions.
Furthermore, there was a significant age difference on NET levels in
the dentate gyrus but not in the frontal cortex or the locus coeruleus.
Specifically, NET levels were increased among 45-day-old rats com-
pared to 75-day-old rats. There was no main effect for diet and no
diet-age interaction on any of the dependent variables.
Conclusions: In summary, early ID in rats alters many
monoaminergic-mediated behaviors. Such changes might be irrevers-
ible despite the fact that there is a restoration of peripheral and/or
central iron. Future studies measuring monoamine transporter activ-
ities may highlight the effects of brain iron deficiency on various
neural pathways with further defining the functional ramifications.
S497
1276
Parkinsonism in fragile X-associated tremor/ataxia syndrome
(FXTAS) is associated with impaired implicit verbal memory and
reduced N400 word repetition effect
J.M. Olichney, X.H. Wang, J.C. Yang, R. Hagerman, L. Zhang
(Davis, CA, USA)
Objective: To test for differences in language and memory as
indexed by event-related potentials (ERPs) in fragile X-associated
tremor/ataxia syndrome (FXTAS) patients with (FXTASp1) vs.
without Parkinsonism (FXTASp-).
Background: Parkinsonism is common in patients with FXTAS,
with a prevalence of near 30%. The neurodegeneration of FXTAS
commonly manifests with progressive impairments in executive func-
tion, attention, memory, and visual-spatial processing. However, little
is known regarding whether FXTAS patients with or without Parkin-
sonism have different patterns of cognitive deficits, or different clini-
cal course. An ERP word repetition paradigm has been shown
sensitive to the impairments in semantic processing and implicit
verbal memory in FXTAS compared to normal controls. Prior studies
have also found implicit memory deficits in patients with Parkinsons
disease (PD). Therefore, in the current study, we employed an ERP
word repetition paradigm to test implicit and explicit verbal memory
processes in FXTASp1 and FXTASp-.
Methods: Two demographically-matched patient groups with
FXTAS were studied: 11 FXTASp1 (mean age 5 62.2 yrs) and 11
FXTASp- (mean age 5 63.7 yrs). 32-channel EEG data was recorded
during a semantic judgment task in which semantically congruous
(50%) and incongruous pairs repeat pseudo-randomly (between 10-
140 seconds later). The N400 and P600 repetitions effect amplitudes,
reflecting implicit and explicit verbal memory, respectively, were
analyzed with ANOVA to compare these two patient groups.
Results: The analyses revealed a significantly reduced N400 repeti-
tion effect amplitude, a well-studied marker of repetition priming and
implicit verbal memory, in FXTASp1 (-0.26 6 0.33 lV) compared to
FXTASp- (-1.43 6 0.33; p 5 0.02). No group differences in N400 con-
gruity effect (indexing semantic processing of new incongruous vs.
congruous words) or the P600 repetition effect were found.
Conclusions: FXTAS patients with Parkinsonism show more
severe impairments in repetition priming and implicit verbal mem-
ory, compared to FXTAS without Parkinsonism. This finding is in
line with prior studies which have found impaired implicit memory
in patients with PD, and suggest that Parkinsonian signs in FXTAS
may be attributable to some common underlying neuropathological
mechanisms with PD (e.g., cortical Lewy bodies).
1277
Status of working memory in patients of Parkinsons disease
A. Pal, M. Behari, R. Sharma (New Delhi, India)
Objective: To assess existence of the working memory deficits in
the patients of Parkinsons disease with or without dementia.
Background: Parkinsons disease is a progressive neurodegenera-
tive motor disorder characterized by the loss of dopaminergic neurons
in substantia nigra of midbrain leads to depletion of dopamine levels
in the basal ganglia. With the progression of disease, cognitive deficits
also occur in various domains like executive functions, attention, set
shifting and memory. Impairment in working memory has been docu-
mented in Parkinsons and it involves central executive component.
Methods: Forty-six patients with PD matched for mean age, years
of education, onset of disease and duration of the disease participated
in this study. Mini mental state examination (MMSE) and clinical
dementia rating (CDR) scale were used to classify PD patients as PD
without dementia (PDND, n 5 28) and PD with dementia (PDD,
n518). Patients with MMSE score  24 were considered as PD
demented and with MMSE score >24 as PD non-demented.
To evaluate working memory status, word memory and picture
memory test were performed for each subject. Ten neutral words and
Movement Disorders, Vol. 30, Suppl. 1, 2015
S498 POSTER SESSION
pictures were shown to the each subject thrice. Scoring of both
working memory test was taken into consideration for analysis and
correlated with the MMSE and CDR score of the patients.
Results: PDD patients scored lower than PDND on both working
memory measures (two-sample Wilcoxon rank-sum (Mann-Whitney)
test). MMSE were significantly lower in PDD as compared to PDND
(Unpaired t test P< 0.0001). CDR score showed an increase in PDD
patients as compared to PDND patients but not significantly. The scale
showed a clear trend toward lower cognition scores for PDD patients.
Conclusions: results of this study indicate that in PDD patients
cognitive impairment are more as revealed by their lower, MMSE
score and higher CDR than PDND. Working memory test score also
showed significant differences in between groups.
1278
Cerebral microbleeds in dementia with Lewy bodies and
Alzheimers disease and their influence on cognitive decline
T. Poliakova, N. Trusova, A. Arablinskiy, O. Levin (Moscow, Russia)
Objective: We hypothesize that cerebral microbleeds (CMBs)
presence and localization might be an additional criteria for diagno-
sis of dementia with Lewy bodies (DLB).
Background: There are no precise data about frequency and
localization of CMBs in patients with DLB despite histopathological
description of CAA in DLB. Pathologically, patients with DLB as
well as Parkinsons disease with dementia have a significantly higher
neuritic Braak stage, cortical amyloid load and capillary CAA than
cognitively normal Parkinsons disease patients. Cerebral micro-
bleeds may influence the speed of cognitive decline.
Methods: We studied 120 outpatients with cognitive decline
older than 65 years. MRI was performed on MR tomograph with a
magnetic field of 1.5 Tesla Signa Excite. Neuropsychological bat-
tery included Montreal Cognitive Assessment scale (MoCA), Adden-
brookes Cognitive Examination (ACE-R), Clock Drawing Test,
fluency test and the visual memory test.
Results: In pure DLB patients, CMBs were seen in 48% of the
patients. In mixed dementia (DLB and AD) their frequency was
higher (60%). Specifically, CMBs were associated with worse mem-
ory and visuospatial domains and the total ACE-R score especially
in DLB, they were also present in mixed AD and VaD patients
(p<0.05). Concerning the localization, more DLB patients had sub-
cortical CMB (83%).
Conclusions: CMBs might contribute to the cognitive decline in
mixed dementia groups. Multiple CMBs might represent an independent
factor of cognitive decline. Isolated cases of multiple subcortical CMBs
in DLB might be considered as sporadic cerebral amyloid angiopathy.
1279
Learning effect plays a significant role in performance on the
Montreal cognitive assessment in patients with Parkinsons
disease
J.P. Squires, E. Nosova, K. Co, A. Book, O. Yu, V. Silva, C.
Thompson, V. ONeill, S. Yardley, S. Burden, M. McKeown, A.J.
Stoessl, S.A. Cresswell (Vancouver, BC, Canada)
Objective: To determine clinical and demographic variables asso-
ciated with change in score on the Montreal Cognitive Assessment
(MoCA) in a cohort of subjects with PD from a tertiary Movement
Disorder clinic.
Background: Cognitive impairment is common in Parkinsons
disease (PD), affecting up to 83% of patients (1). Older age at symp-
tom onset, predominantly axial symptoms and male gender are
known predictors of cognitive impairment (2). The MoCA is widely
used in clinical and research settings yet few studies have addressed
the suitability of using the MoCA to track deterioration of cognitive
status over time; existing studies have provided mixed results,
Methods: Clinical data included the MoCA in all subjects; some
also had Becks depression inventory (BDI), Unified Parkinsons dis-
Movement Disorders, Vol. 30, Suppl. 1, 2015
ease rating scale motor part (UPDRS3), and/or Hoehn & Yahr
(H&Y) scores. Multivariate analysis was carried out to identify vari-
ables significantly associated (p <0.05) with cognitive impairment as
defined by MoCA scores: >26 5 normal cognition (NC); 21-
25 5 mild cognitive impairment (MCI), <21 5 dementia (PDD).
Results: 468 subjects had one or more MoCA score (mean 5 2)
with a mean follow up of four years. At baseline, 320 (68%) had
NC, 126 (27%) had MCI and 22 (5%) had PDD. Mean values for
BDI, H&Y and UPDRS3 were 8.8, 2, and 17.5, respectively. Depres-
sion, and older age at testing were associated with cognitive impair-
ment. There was no correlation between gender, H&Y or UPDRS3
and MoCA score. While there was no significant change in MoCA
score over follow-up for the entire cohort, 151/468 (32%) subjects
improved in their MoCA scores on repeat testing. This improvement
was found to be associated with a shorter time interval between tests,
usually when the interval was less than one year. No variable was
found to correlate with decrease in MoCA score in this population.
Conclusions: Older age at testing and at disease onset was asso-
ciated with cognitive impairment in our cohort. Shorter time intervals
between MoCAs were associated with improved scores, suggesting a
learning effect which needs to be taken into account in repeat test-
ing. Future prospective studies should systematically vary the MoCA
versions used and include neuropsychological testing and a clinical
interview as gold standard to determine the suitability of the MoCA
for longitudinal testing.
1280
A new perspective in cervical dystonia: Neurocognitive
impairment
Y. Sucullu Karadag, P. Kurt, S. Bilen, N. Subutay Oztekin, F. Ak
(Ankara, Turkey)
Objective: This study is aimed to investigate neurocognitive pro-
file of cervical dystonia patients in comparison to healthy controls
(HC) by employing a detailed set of neuropsychological tests in
addition to self-reported instruments.
Background: Primary cervical dystonia is thought to be a purely
motor disorder. But recent studies revealed that patients with dysto-
nia had additional non-motor features.
However, there are limited studies indicating cognitive impair-
ment in patients with cervical dystonia.
Methods: Totally 29 (M/F: 7/22) cervical dystonia patients and
30 HC (M/F: 10/20) were included into the study. After a careful
neurological evaluation, all subjects were given a comprehensive bat-
tery of neuropsychological tests: Self report of neuropsychological
condition (by visual analogue scale-VAS, 0-100), RAVLT, STROOP,
PASAT, TMT, SDMT, JLOT, DST, COWAT, ACTT and FST.
Patients and HC were compared regarding demographic, clinical fea-
tures and neurocognitive tests.
Results: There was no difference between patients and HC
regarding socio-demographic variables such as age, gender and years
of education (p levels were 0.36, 0.436, 0.869; respectively).
Dystonia patients had significantly impaired verbal learning and
memory (RAVLT, p<0.001), divided attention and working memory
(ACTT, p<0.001), attention speed (TMT-A and B, p50.008, 0.050),
executive functions (PASAT, p<0.001; SDMT, p5 0.001; FST,
p<0.001), verbal attention (DST, p50.001), verbal fluency
(COWAT, p<0.001), visio-spatial processing (JLOT, p<0.001) in
comparison to healthy controls.
But focused attention (STROOP-spontaneous correction) was not
different between two groups (p>0.05).
No relationship was found regarding disease duration and disabil-
ity index with any neurocognitive tests.
Conclusions: Our study showed that neurocognitive functions of
dystonia patients were worse than control group. This decline does
not have correlation with clinical features like disease duration and
disability index. This situation may be the result of possible cortical
and subcortical changes in dystonia patients. 1-2 Advanced
 POSTER SESSION
neuroimaging techniques might be helpful to explain these changes
in cervical dystonia patients.
References:
1. Romano R et al. Impaired cognitive functions in adult onset
primary cranial dystonia. Park Related Disorders 2014;20:162-65.
2. Karadag YS, Neurocognitive assessment in adult onset primary
cranial cervical dystonia. Park Related Disorders 2014;20(8):940.
Dystonia
1281
Focal hand dystonia after stroke: Sooner or later?
M. Batule Dominguez (Santa Clara, Cuba)
Objective: Determine time to develop focal hand dystonia after
stroke.
Background: The anatomical bases of dystonia are mainly in the
basal ganglia or its connections. The reported cases after a stroke
are located in these regions, whereas time to develop this feature can
vary.
Methods: Discussion of two cases with focal hand dystonia
immediately after stroke and a third of a later onset, with review of
literature.
Results: A 73 year old right handed woman with chronic hyper-
tension, developed acute numbness and dystonic movements and
posture of her left hand, homonymous hemianopia, optic ataxia and
difficulties with spatial discrimination. The second case, a 67 year
old right handed man with history of hypertension and ischemic car-
diopathy presented with acute dystonic movements and mild weak-
ness of the right arm. The third case, a 82 year old right handed
woman with hypertension developed focal hand dystonia after recov-
ering from the mild weakness of a stroke in several weeks. Stroke of
the posterior cerebral artery in the first case and branches of the
medial cerebral artery in the others were diagnosed.
Conclusions: Although the majority of cases with focal hand dys-
tonia are described after acute stroke, others develop the disorder
after weeks or months; even there are delayed onset Movement Dis-
orders that appear in years. Mechanisms underlying these phenomena
are related to the improvement of motor deficit, which contributes to
the abnormal movement with neuronal reorganization.
1282
Depression in blepharospasm A question of facial feedback?
J.R. Bedarf, S. Kebir, J.P. Michelis, B. Wabbels, S. Paus (Bonn,
Germany)
Objective: To assess the effect of botulinum neurotoxin (BoNT)
injection into the forehead region on depressive symptoms in patients
with blepharospasm.
Background: Recent controlled studies give evidence that a sin-
gle injection of BoNT into the frown lines may alleviate symptoms
of major depression disease (MDD) in psychiatric patients, with a
remarkable reduction of BDI values. In focal dystonias, depression is
the most important non-motor symptom, associated with stigmatiza-
tion, among other factors. In blepharospasm, dystonia may lead to an
overactivity of grief muscles. We wondered whether depressive
symptoms in patients with blepharospasm differ in patient subgroups
with and without forehead BoNT application.
Methods: We retrospectively analyzed treatment details and BDI
values of patients with idiopathic blepharospasm. BDI values were
compared in subgroups with and without forehead BoNT application.
Statistical analysis was corrected to exclude an effect of age on
depressive symptoms. Also, as patients with MDD were mainly
female, gender was considered.
S499
Results: 90 patients (28 male and 62 female) were included. In
45 patients, BoNT treatment included forehead BoNT application.
Total BDI values did not differ significantly between both groups
(median and 95%CI: forehead application 6 (6.1-9.5), caudal applica-
tion 7 (6.1-10.1)). In subgroup analysis according to gender, male
patients had significant lower BDI values when treatment included
the frown lines (BDI value with frown line 4.5 (2.4-6.6), with caudal
application 8 (5.4-11.4); p5 0.023; median and 95% CI). However,
the number of frown line treatment cycles was significantly higher in
women (23 (23.5-41.5)) than in men (16.5 (7.6-22.2); median and
95% CI).
Conclusions: In this pilot observation, BoNT injections into the
frown lines were associated with remarkably less depressive symp-
toms in male blepharospasm patients. Our observations might be
explained by the so called facial feedback hypothesis, which impli-
cates a mutual influence of facial muscle activity and emotions. So
far, this hypothesis was not studied in neurological disorders. The
exact mechanism behind these interactions is currently unknown.
However, interpretation of data is limited due to the small sample
size and the retrospective analysis. Hence, we are currently conduct-
ing further prospective clinical research to prove our observations.
1283
Using the oculus rift for recording head turns
I.M. Beiser, B. Quinlivan, L.J. Williams, E.M. McGovern, S.
ORiordan, J.S. Butler, R.B. Reilly, M. Hutchinson (Dublin, Ireland)
Objective: We aim to measure head turns in a controlled envi-
ronment which can then be deployed in any setting.
Background: In daily life, we perform gaze shifts to address
changes of the environment around us. This often includes not only
movement of the eye and head but trunk and foot rotations. Many
different and complex mechanisms are involved to facilitate visual
tasks. While many of the neural circuits underlying these eye move-
ments are well understood, those relating to the role of head move-
ment have been less studied. Here we explore the mechanism of
head turn in relation to the visual system. This will allow us to
investigate abnormal head movement in disorders such as cervical
dystonia in the future.
Methods: Participants will wear lightweight head mounted dis-
play, the Oculus Rift, to monitor head rotations. The Oculus Rift has
a built-in 3-axis gyroscope, accelerometer and magnetometers and
was developed as a stereo 3D virtual reality head mounted display
for application in computer gaming. Its ability to present stimulus on
a wide field (1-40 degrees) with a very high resolution (960x1080
pixels per eye) and simultaneously precisely record head rotations
along the three axis (yaw, pitch and roll) make it an ideal tool for
research purposes. The experiment entails participants making differ-
ent sized head turns to the left and right in a Posner cue target para-
digm, where the cue can be either valid (indicating the correct
direction) or invalid.
Results: Here we validate the setup on a group of healthy control
subjects. We will present data from healthy adults to illustrate the
feasibility of acquiring head movement data with the Oculus Rift,
and the extraction of head turn biomarkers. These results show the
feasibility of recording precise head movement data outside of a lab
environment.
Conclusions: In future studies, we intend to investigate the link
between head turning and the abnormal temporal discrimination of
visual stimuli of patients with dystonia. This will strengthen the role
of the mid-brain in the disorder.
1284
Anatomical basis for the application of
onabotulinumtoxinA(BoNT-A) in dystonias
M. Bendersky, N.S. Garretto, J.V. Humberto, T. Arakaki, R.Q. Sergio
(Buenos Aires, Argentina)
Movement Disorders, Vol. 30, Suppl. 1, 2015
S500 POSTER SESSION

Objective: 1. To study the anatomical landmarks for BoNT-A

infiltration in head and neck muscles.
2. To investigate the biomechanical patterns of activation of these
muscles.
Background: Dystonias challenge our knowledge of the anatomy,
biomechanics and function of the muscles involved. Improving their
knowledge would lead to better results and less complications using
botulinum toxin (BoNT-A).
Methods: 1. Facial and neck muscles were dissected in 72 cadav-
ers fixed with formalin. Anatomical landmarks for identifying differ-
ent structures in surface anatomy were drawn on that basis. Colorant
material was injected in 10 undissected cadavers in order to confirm
the accuracy of those landmarks.
2. Biomechanics and activation pattern of mimic muscles, masti-
cation and neck muscles were studied at rest and with voluntary Fig. 2. (1285).
movements in 11 healthy controls, 8 facial dystonias and 3 neck dys-
tonias, employing 4-6 simultaneous electromyography (EMG)
channels.
Results: 1. Anatomical landmarks for BTX infiltration could be
The pathophysiology of BSP remains largely obscure, but physiologi-
accurately identified in the studied structures. This was confirmed by
cal studies suggest a sensitization of the trigeminal nerve system
the dissection of the colored preparations.
along with abnormal sensorimotor network function play a role.
2. The biomechanical study in healthy volunteers showed: a)
Methods: 10 BSP patients (7F, 61.7 6 9.2) and 9 healthy controls
More than one muscle was used for a single gesture. b) One muscle
(6F, 60.4 6 5.6) underwent an 8-minute fMRI scan during which air
was activated to make more than one gesture. c) A specific and coor-
puffs were delivered to each participants left eye in a pseudo-
dinated pattern of muscles activation defined each particular gesture
randomized fashion (40 per scan). The eliciting of blinks was con-
d) Healthy controls could activate each mimic muscle independently.
firmed using both simultaneous camera visualization and EMG moni-
The dystonic muscles showed aberrant activation patterns with early
toring. Data were analyzed using an event-related design, and groups
recruitment of simultaneous muscles, which normally are not used
were compared using a two-sample t test. Pearson correlation coeffi-
for that gesture.
cients were used to test for relationships between clinical severity
Conclusions: Mimicry muscles lack of precise boundaries
and changes in brain activity as measured by BOLD signal. Signifi-
between them, have mobile cutaneous insertions and are all inner-
cance was defined as p<0.05, FWE corrected, for the group contrast
vated by a single nerve. However, normal subjects can move each
and p<0.05 for the correlations.
one independently. In patients with dystonia this property seems to
Results: Compared to healthy controls, BSP patients showed an
be lost. The EMG study of dystonias allows identifying clinically
increase brain activity within their left premotor and inferior parietal
and subclinically involved muscles. Mimicry EMG has been poorly
cortex, and decreased activity within their left insula and right supra-
studied so far because of the lack of suitable surface anatomical
marginal gyrus and superior temporal lobe. Increasing activity in the
landmarks for the individualization of each muscle. Perhaps many
left premotor cortex and right supramarginal gyrus were correlated
failures or undesired responses with BoNT-A injections are also due
with their Burke-Fahn-Marsden score (r=0.74, p50.01; r=0.70,
to this trouble. Through this work we defined easy landmarks for
p50.002) and Blepharospasm Disability Index (r=0.63, p50.05;
every head and neck muscles.
r=0.63, p50.05; Figure 1). [figure1] Decreasing activity in the left
insula was also correlated with severity on the Jankovic Blepharo-
1285 spasm Rating Scale (r=-0.66, p50.03; Figure 2) and Burke-Fahn-
Marsden (r=-0.73, p50.01). [figure2]
Neural responses during reflexive blinking are abnormal in
Conclusions: BSP is associated with abnormal brain responses
blepharospasm (BSP)
during reflexive blinking. Activity with the supramarginal gyrus is
B.D. Berman, D. Kelly, E. Shelton (Aurora, CO, USA) decreased compared to controls, but increases with symptom severity
Objective: Use fMRI to investigate the neural mechanisms under- suggesting overactivity in this region during reflexive blinking might
lying reflexive blinking responses in BSP patients compared to serve as an early marker of disease. Enhanced response of the pre-
healthy controls. motor cortex during reflexive blinking may stem from diminished
Background: BSP is a focal dystonia characterized by excessive inhibition within the sensorimotor network, and raises the possibility
orbicularis oculi muscle spasms leading to involuntary eye closure. that inhibitory transcranial magnetic stimulation of the premotor cor-
tex could potentially have therapeutic benefit in BSP.

1286
Non-parametric bootstrapping method for measuring the
temporal discrimination threshold for Movement Disorders
J.S. Butler, L. Williams, I. Beiset, E. McGovern, A. Molloy, B.
Quinlivan, S. ORiordan, M. Hutchinson, R.B. Reilly (Dublin,
Ireland)
Objective: A new analysis method of the temporal discrimination
threshold (TDT) to improve its utility as an endophenotype for
Movement Disorders.
Background: Recent studies have proposed that the TDT, the
shortest detectable time period between two stimuli, is a possible
Fig. 1. (1285). endophenotype for adult onset idiopathic isolated focal dystonia
(AOIFD). Patients with AOIFD, the third most common Movement

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
Disorder, and their first-degree relatives have been shown to have
abnormal visual and tactile temporal discrimination thresholds. For
this reason it is important to fully characterize each participants
data. To date the TDT has only been reported as a single value.
Methods: The responses, during visual TDT testing, of 78
healthy control participants (33 men) were analysed as to the relative
frequencies with which they reported a single or double image at
each inter-stimulus interval. The individual participant responses
were fitted with a cumulative Gaussian to extract the mean and
standard deviation of the distribution. The mean represents the point
of subjective equality (PSE), the inter-stimulus interval at which par-
ticipants were equally likely to respond that two stimuli were one
stimulus (synchronous) or two different stimuli (asynchronous). The
standard deviation represents the just noticeable difference (JND)
which indicates how sensitive participants were to changes in tempo-
ral asynchrony around the PSE. We extended this method by submit-
ting the data to a non-parametric bootstrapped analysis to get 95%
confidence intervals on individual participant data.
Results: Both the JND and PSE correlated with the TDT value
(r=0.53, p<0.001 and r=0.76, p<0.001) but were independent of
each other (r=-0.012). Hence this suggests that they represent differ-
ent facets of the TDT. We divided groups by age (18-35 years and
35- 65 years) and compared the TDT, PSE, and JND values. The
analysis revealed analysis revealed no statistical differences between
the groups for the TDT values (p50.056) and JND values (p50.95)
but did reveal a statistical difference for the PSE parameter
(p<0.0167).
Conclusions: The analysis revealed a statistical difference for the
PSE which was only trending for the TDT, thus illustrating subtle
differences between control and patient groups, not apparent in the
standard TDT measure. The analysis technique allows for the investi-
gation of changes in TDT within participants and across groups.
1287
Excitatory motor cortical circuitry in focal hand dystonia and its
modulation following incobotulinumtoxinA treatment
R.F.H. Cash, K. Udupa, N. Phielipp, C.A. Gunraj, R. Pellicciari, R.
Chen (Toronto, ON, Canada)
Objective: To examine excitatory motor cortical circuitry in focal
hand dystonia (FHD) and central changes following treatment with
incobotulinumtoxinA.
Background: In FHD, basal ganglia dysfunction has been
hypothesised to increase thalamic input to motor cortical areas lead-
ing to changes in cortical excitability and plasticity. Studies using
transcranial magnetic stimulation (TMS) have implicated changes in
inhibitory circuitry in motor cortex. However, little is known about
excitatory circuitry or how it is affected by treatment. Short interval
intracortical facilitation (SICF) is the motor cortical facilitation pro-
duced by a test stimulus (TS) when preceded by a conditioning stim-
ulus (CS) at three peak interstimulus intervals (ISIs) of 1.5, 3.0
and 4.5 ms (peaks 1, 2 and 3).
Methods: Six FHD patients (57 6 3 years, 2 women) and seven
healthy controls (39 6 4 years, 2 women) were recruited. SICF was
investigated at ISIs (1-4.9ms) encompassing the 3 SICF peaks, with
TS intensity set to generate a 1mV MEP and CS intensity was set at
90% of resting motor threshold (RMT). Patients were examined prior
to incobotulinumtoxinA treatment, and at 1 month and 3 months fol-
lowing injection.
Results: RMT was 48 6 3% (mean6SEM) of maximum stimula-
tor output (MSO) in HC and 54 6 3%MSO in FHD. Intensity for
generating a 1mV MEP was 59 6 4% MSO in HC and 74 6 7% in
FHD (average across all sessions). SICF at all peaks was lower in
FHD patients compared to healthy individuals. SICF was partially
normalised at 1 month and 3 months post- treatment.
Conclusions: These data suggest abnormally reduced strength of
excitatory local motor cortical circuit SICF in FHD patients.
Reduced excitability was also reflected by the higher RMT and the
S501
higher intensity required for 1mV MEP. IncobotulinumtoxinA treat-
ment was associated with partial normalisation of SICF circuitry.
The reduction in the strength of excitatory circuits could be an adap-
tation to compensate for disinhibition of cortical inhibitory circuitry
in FHD and for changes in the basal ganglia. These findings are con-
sistent with the hypothesis that central adaptations contribute to treat-
ment effects of botulinum toxin in FHD.
1288
The evolution of cervical dystonia and patient satisfaction with
repeat botulinum toxin therapy: An interim analysis from the
INTEREST IN CD2 study
D. Charles, V.P. Misra, C. Colosimo, S. Om, P. Maisonobe
(Nashville, TN, USA)
Objective: Report interim first cycle data from the INTEREST
IN CD2 study.
Background: Botulinum neurotoxin-A (BoNT-A) injections are
standard treatment for cervical dystonia (CD). Patients typically
return for reinjection when the benefits wear-off, however the natural
history of patients undergoing continued treatment is not well
characterized.
Methods: INTEREST IN CD2 is an ongoing 3-year study fol-
lowing the course of CD treated with BoNT-A. Subjects undergo a
CD assessment at baseline/1st injection Visit & at each injection
Visit, according to usual practice. A preplanned interim analysis
was conducted in subjects with complete data at Visit 1 (V1, base-
line) & Visit 2 (V2, 2nd injection). Subjects rated their highest level
of satisfaction with BoNT-A treatment (at any time since the last
injection).
Results: Recruitment completed in July 2014. As of June 2014,
239 subjects had complete data. Subjects were mainly from Europe
(87%), 72% were female; mean 6SD age was 54.5 612.0 years &
median time since diagnosis was 6.0 (range: 0-49) years. At baseline,
166 (70%) subjects were injected with abobotulinum toxin A
(median dose 500U), 48 (20%) with botulinum toxin a (163U) & 25
(10%) with incobotulinum toxin A (160U). The majority (86%) had
received previous BoNT-A treatment (median time from starting
BoNT treatment: 64.2 months; time since last injection: 3.4 months).
For all patients, the median interval between visits was 3.2 months.
Mean TWSTRS Total scores improved from 31.4 612.7 at V1 to
29.5 613.1 at V2 (mean [95%CI] decrease of 1.9 [-2.9;-1.0]); sever-
ity scores improved from 15.7 65.6 to 14.9 65.6 (decrease of 0.8 [-
1.2;-0.3]); disability scores from 9.6 66.1 to 8.9 66.3 (decrease of
0.8 [-1.2;-0.3]) & pain from 6.1 6 4.8 to 5.7 64.6 (decrease of 0.4 [-
0.8;-0.0]). Highest satisfaction with treatment remained stable over
the two visits; 85% (174/204) of previously treated subjects reported
satisfaction (completely or rather satisfied) with treatment at Visit 1
& 86% (176/205) at Visit 2. Overall 88% (30/34) of previously
untreated patients reported satisfaction at V2.
Conclusions: TWSTRS scores were observed to slightly improve
from V1 to V2, suggesting that patients may not fully return to base-
line before the next injection. Overall highest satisfaction with
BoNT-A therapy was generally good. Future analyses will provide
important information about natural history of CD treated with
BoNT.
1289
Temporal patterns of pallidal deep-brain stimulation parameters
in patients with cervical dystonia
M. Chung, R. Huh, I.U. Song (Incheon, Korea)
Objective: The purpose of this study was to identify temporal
patterns in stimulation parameter settings using a predetermined
parameter adjustment algorithm.
Background: Medically intractable cervical dystonia should be
managed with surgical modalities, including deep-brain stimulation
Movement Disorders, Vol. 30, Suppl. 1, 2015
S502 POSTER SESSION

Temporal patterns of the stimulation parameters

1 week* Between 1w-3m 3 months* Between 3m-6m 6 months* Overall

Amplitude (V) 3.1 6 0.5 .359 (<.001) 3.7 6 0.6 .118 (.054) 3.8 6 0.7 .291 (<.001)
Frequency (Hz) 132.2 6 11.7 .278 (<.001) 143.6 6 18.9 -.004 (.945) 144.5 6 18.8 .079 (.156)
Pulse Width (msec) 78.9 6 20.2 .047 (.500) 78.9 6 23.6 -.044 (.477) 82.9 6 24.6 .081 (.145)
*The columns show cross sectional data on the indicated time. The P-value calculated by the Chi-Square test between two periods or among all
the three periods. The correlation coefficient (P-value) produced by the Pearsons correlation test, in which the correlation data are not based on
the cross sectional data shown in the each column but calculated using consecutive data between two periods on both side of columns or between
periods of 1 week and 6 months.

The groups by clinical benefits analysis

Group by Clinical Benefits Time of Evaluation (month) Amplitude (V) Frequency (Hz) Pulse Width (msec)
Good (60-100%) 10.7 (5.4-16.1) 3.5 (3.2-3.8) 135.3 (127.2-143.4) 74.1 (65.9-82.4)
Intermediate (30-60%) 3.0 (1.7-4.4) 3.4 (3.3-3.6) 138.1 (134.5-141.7) 81.6 (73.2-89.9)
Poor (0-30%) 2.2 (.8-3.6) 3.4 (3.2-3.7) 140.6 (133.0-148.3) 75.0 (63.3-86.7)
P-value .003 .981 .576 .393
The data are shown in average (95% confidence interval) otherwise not indicated. The groups were classified according to the severity improve-
ment rates. The Analysis of Variance was used to verify differences among the groups. Only difference among those is the time of exam. The
times of examinations are significantly late in the group of good improvement rate, which may reflect a characteristic of deep brain stimulation
delayed benefits. The stimulation parameters are not differ significantly from each other.

Fig. 1. (1289).

(DBS) at posterior ventral portion of the globus pallidus internus
(GPi) or selective peripheral denervation. An investigation of chang-
ing patterns of the stimulation parameter based on a predetermined
parameter adjustment algorithm should yield results that help clini-
cians to identify parameters that will result in improved patient
outcomes.
Methods: Nineteen patients with medically refractory idiopathic
cervical dystonia who underwent GPi DBS were enrolled. The algo-
rithm of stimulation parameter adjustment included a test stimula-
tion, initial adjustments, and follow-up adjustments. Baseline and
follow-up parameters were analyzed according to their dependence
on time after DBS. The changing pattern in the stimulation parame-
ter with respect to time, the differences across the four active
contacts, and the relationship between the stimulation parameters and
clinical benefits were evaluated.
Results: The mean age and the duration of the disease were 50.9
years and 54.7 months, respectively. Total 543 sessions of the
parameter adjustments had been performed during the study period.
The results were summarized about temporal patterns the stimulation
parameters during first 6 months after GPi DBS.
During the first time section (1week-3months), the significant cor-
relations with the time were found in the amplitude and the fre-
quency while the pulse width did not show a correlation. [figure1]
The groups from the clinical benefits (good, partial, and poor bene-
fits) were evaluated, and there was no significant difference among
the clinical benefits group except the time of evaluation.

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
Conclusions: High intensities in the pulse width are not recom-
mended. Although, sufficiently high intensities in the amplitude and
frequency may be needed to achieve improvements in GPi DBS in
patients with cervical dystonia, increasing intensities in the amplitude
and the frequency are not determinants of clinical benefit. Rather,
clinical benefits increase over time, independent of other factors.
1290
Correlation between Tsui tremor scores and the Toronto
Western Spasmodic Torticollis Rating Scale (TWSTRS): An
analysis of data from the ongoing INTEREST IN CD2 study
C. Colosimo, D. Charles, V.P. Misra, P. Maisonobe, S. Om (Rome,
Italy)
Objective: To evaluate if there is a correlation between Tsui
tremor scores and disease severity as assessed by the Toronto West-
ern Spasmodic Torticollis Rating Scale (TWSTRS).
Background: Recent consensus guidelines for dystonia empha-
size the importance of assessing tremor, however it is unclear if
tremor is an independent symptom of cervical dystonia (CD) or if it
correlates with other symptoms.
Methods: INTEREST IN CD2 is an ongoing 3-year study follow-
ing the course of adult idiopathic CD treated with BoNT-A. Subjects
undergo a comprehensive CD assessment at baseline/first injection
Visit, at each injection Visit and end of study according to investiga-
tors usual practice. A preplanned interim analysis was conducted in
subjects with complete data at Visit 1 (baseline) and Visit 2 (time of
second injection). Associations between Tsui tremor component
scores and TWSTRS Total and subscales scores were assessed by
visit using the non parametric Kendall correlation test.
Results: As of June 2014, 239 subjects had complete data. Over-
all, 72% of patients were female and the mean 6SD age was 54.5
612.0 years. Mean TWSTRS scores and Tsui categories are shown
in Table 1.
Although improvements were seen in both rating scales from
Visit 1 to Visit 2, correlation analyses did not find any statistically
significant or clinically relevant associations between Tsui tremor
and any of the TWSTRS scores (all correlation coefficients less than
0.1 and all p>0.05).
Conclusions: No associations were found between Tsui tremor
(severity or duration) and the TWSTRS and its components, suggest-
ing that tremor is an independent symptom of CD.
1291
Patient survey in cervical dystonia (CD): Insights into burden of
illness and treatment in the United States
C.L. Comella, D. Charles (Chicago, IL, USA)
Objective: This patient survey was developed to investigate
patient perceptions of their experiences with the health care system
in the United States (US) as it relates to cervical dystonia.
Tsui tremor severity Tsui tremor duration Total TWSTRS
(N=239)
(N=239) n(%) (N=239) n(%) mean6SD
Visit 1 None:109(45.6) None:109(45.6) 31.4 6 12.7
Mild:113(47.3) Occasional:74(31.0)
Severe:17(7.1) Continuous:56(23.4)
Visit 2 None:121(50.6) None:121(50.6) 29.5 6 13.1
Mild:100(41.8) Occasional:62(25.9)
Severe:18(7.5) Continuous:56(23.4)
S503
Background: Despite effective treatment, little is known about
the real life experiences of CD patients.
Methods: This descriptive study included patients from 38 coun-
tries including US with a diagnosis of cervical dystonia who were
invited to participate in a 38 question on-line survey distributed by
the Dystonia Medical Research Foundation and Dystonia Europe.
This survey focuses on those in the United States. The survey
included questions focusing on patient experiences with symptoms,
diagnosis, and treatments.
Results: There were 1071 international respondents, 389 (36%)
were from the US (mean age of 56.3 (6 11.5years), duration of
symptoms 11.0 6 11 years, 82% female). Of these, 36% were
employed part or full time, 27% retired, and 30% disabled. The time
to diagnosis was greater than one year in 31% and over 5 years in
23%. Prior to diagnosis of CD, 66% received other diagnosis includ-
ing psychological illness/stress or cervical muscle strain. The life
areas most affected by CD symptoms included well being (70%),
work and school performance (59%), and health (57%). Treatment
options included botulinum toxin injections (85%), oral medications
(69%), and physiotherapy (27%). Of those receiving treatment, 56%
were fairly or completely satisfied with outcome. The areas of
improvement included reduced symptoms (70%), improvement in
mood (39%), improved confidence (30%), and regained independ-
ence (21%). Of those treated with botulinum toxin, 62% reported
improvement and were satisfied with outcome. Of the 126 patients
not satisfied, the most common reasons included lack of benefit
(46%), side effects (31%), and expense (19%). Additional treatments
included rest (44%), exercise (26%), physical (21%) and massage
(26%) therapy. Patient support organizations were contacted by 66%
and 80% would recommend this to others.
Conclusions: Although the US subgroup analysis of this survey
is limited by moderate sample size and results are based on patient
self-report of diagnosis, the responses highlight that there remains
important unmet needs in US patients with CD. These include delay
in diagnosis, misdiagnosis, and a substantial proportion of patients
that are not satisfied with currently available treatments.
1292
Characteristics of dystonia in multiple system atrophy
E.A. Coon, J.E. Ahlskog, M. Suarez, P.A. Low, W. Singer (Rochester,
MN, USA)
Objective: To characterize features of dystonia in a large cohort
of multiple system atrophy (MSA) patients.
Background: Dystonia is a recognized clinical feature of MSA;
orofacial dystonia, disproportionate antecollis, camptocormia and/or
pisa syndrome are used as supporting features to make a diagnosis of
MSA[1]. However, the frequency, type, and association of dystonia
with medications in MSA patients are not well described.
Methods: All cases of MSA evaluated at Mayo Clinic, Rochester
assessed with an autonomic reflex screen between January 1998 and
December 2012 were retrospectively reviewed. Dystonia was
TWSTRS Severity TWSTRS Disability TWSTRS Pain
(N=239) (N=239) (N=239)
mean6SD mean6SD mean6SD
15.7 6 5.6 9.6 6 6.1 6.1 6 4.8
14.9 6 5.6 8.9 6 6.3 5.7 6 4.6
Movement Disorders, Vol. 30, Suppl. 1, 2015
S504 POSTER SESSION
classified according to consensus criteria [2]. MSA was categorized
by subtype of Parkinsonism (MSA-P) or cerebellar ataxia (MSA-C).
Demographic data, clinical variables and electrophysiologic results
were reviewed and compared between those with and without
dystonia.
Results: Of 685 MSA patients identified, 55 (8%) had evidence
of dystonia. Fifty MSA patients with dystonia had MSA-P (91%)
and when compared to all patients with MSA, were more likely to
be women (34, 62%; p50.03). Focal dystonia was the most common
type (42, 76%) followed by multifocal (4, 7%), generalized (3, 5%)
and hemidystonia (1, 2%). Camptocormia was present in 5 patients
(9%). As far as focal dystonias, antecollis was the most common
type (37 patients) which represented 5% of all MSA and 9% of
MSA-P patients. Antecollis was the presenting complaint in 2
patients and classified as severe in 18; two patients had accompany-
ing laterocollis. Blepharospasm was noted in 2 patients while 3 had
focal limb dystonia. Dystonia was not attributable to dopaminergic
medications in the majority of patients; only 3 patients experienced
dystonia due to dopaminergic medications, while it was an off state
manifestation in one. Botulinum toxin injections were performed in
12 patients and clearly helped 5, including those with
blepharospasm.
Conclusions: Dystonia was found to be relatively infrequent in
our large retrospective cohort of MSA patients and was more fre-
quently seen in MSA-P. Antecollis was the most common form of
dystonia in MSA.
1. Gilman, S., et al., Second consensus statement on the diagnosis
of multiple system atrophy. Neurology, 2008. 71(9): p. 670-6.
2. Albanese, A., et al., Phenomenology and classification of dys-
tonia: a consensus update. Movement Disorders: official journal of
the International Parkinson and Movement Disorder Society, 2013.
28(7): p. 863-73.
1293
Athletes dystonia
J.K. Cutsforth-Gregory, J.H. Bower (Rochester, MN, USA)
Objective: Characterize a rare form of adult-onset focal dystonia
among athletes.
Background: A new form of focal task-specific dystonia was
recently described among runners, with only 20 reported cases to
date. We wished to characterize further our cases of runners dysto-
nia, determine the usefulness of electrophysiology in making the
diagnosis, determine whether non-runner athletes could suffer a simi-
lar disorder, and describe long-term outcomes in these patients.
Methods: We retrospectively reviewed the clinical and neurophy-
siologic information of adult patients with task-specific dystonia aris-
ing after a prolonged history of any repetitive lower limb exercise.
Follow-up data were gathered via telephone or mailed questionnaire.
Results: Nineteen patients (53% men) were identified, 13 runners
and six non-runner athletes. Median age at dystonia onset was 49.2
years (range 2569 years). Correct diagnosis was delayed by a
median of 2.5 years, by which time nearly 40% of patients had
undergone or been recommended unnecessary invasive procedures.
Most patients had dystonia onset in the distal lower limb (68%). A
novel observation was truncal dystonia in four patients. Strict task
specificity was seen at onset in every patient. Dystonia progressed to
affect walking in most patients (84%). Sensory tricks were reported
in six patients. In general, MRI of the brain and spine were unre-
markable, as were nerve conduction studies and needle EMG. Sur-
face EMG and gait analysis confirmed task-specific dystonia in ten
patients and allowed distinction from stiff limb syndrome in one and
orthostatic myoclonus in another. At median follow up of 4.8 years
(range 0.423 years) from dystonia onset and 2.1 years (range 018
years) from diagnosis, all patients were still symptomatic. Effective
treatment was rare, with most patients achieving only partial return
to their pre-dystonia activity level with the same (56%) or a different
(25%) exercise. Beneficial treatments included botulinum toxin injec-
Movement Disorders, Vol. 30, Suppl. 1, 2015
tions (in 3 of 5 cases tried), physical therapy (6/15), clonazepam (2/
5), carbidopa/levodopa (3/8), and trihexyphenidyl (1/3).
Conclusions: We describe the largest series of athletes dystonia,
a task-specific lower limb and truncal dystonia seen in runners and
other athletes. Electrophysiology is helpful in confirming the diagno-
sis, potentially avoiding unnecessary tests and procedures. Botulinum
toxin and physical therapy are sometimes helpful.
1294
What predicts progression of idiopathic adult-onset dystonia?
A. DAbreu, L. Piovesana, I. Lopes-Cendes, L. Marc, N. Sharma
(Campinas, Brazil)
Objective: Evaluate clinical predictors of progression in adult-
onset idiopathic dystonia.
Background: Dystonias result from involuntary muscle contrac-
tions leading to abnormal torsional movements and postures. Pro-
gression to other sites is associated with initial site of presentation,
which is in turn associated to gender and age-at-onset. Blepharo-
spasm has the highest probability of spread and the lowest time
elapsing from dsytonia onset to initial spread. Blepharospasm, cervi-
cal dystonia and laryngeal dystonia are more common in females,
and women with craniocervical dystonia have a later onset than men.
Methods: We gathered data in the University Hospital
UNICAMP-Brazil and at The Dystonia Partners Research Bank,
Massachusetts General Hospital. We used logistic regression and a
stepwise regression to model progression using age-at-onset, gender,
family history, disease duration and site of onset as covariates. We
dichotomized self-reported race into white and non-whites due to the
small number of non-white subjects. Race was included in the final
model. In each of the steps we checked the likelihood ratio test, the
goodness of fit and C-statistics.
Results: A full model with the initial sites controlling for age-at-
onset, gender, family history and duration demonstrated a significant
effect of initial site of onset in progression (orbicular: OR=
5.63,p=0.000; limb: OR=3.01, p5 0.007). This full model had
adequate calibration (Hosmer-Lemeshow (HL) chi2(8)=
6.23p=0.6215) and discrimination (AUROC=0.7174). For the model
including race, we decided on a simpler model including only initial
site, since it was not significantly different from the full model (LR
chi2(5)=3.75 p50.5860). Non-white race had 4.29 times the odds of
progressing comparing to self-reported whites (p < 0.001). This
model had adequate calibration and discrimination (HL chi2(5)=
0.35p=0.9965 AUROC=0.7534). An ad-hoc analysis comparing non-
whites to whites in the US dataset showed an OR=3.13 (p50.007)
and an OR= 6.88 (p50.011) in the Brazilian dataset.
Conclusions: Initial site and race seem to drive progression in
idiopathic dystonia. Since we used a dichotomized race classification,
future studies are warranted to confirm these findings.
1295
Neuropsychological and psychiatric outcome of GPi-deep brain
stimulation in dystonia Preliminary report
C.M. de Gusmao, L.E. Pollak, N. Sharma (Boston, MA, USA)
Objective: We report the preliminary results of an ongoing study
examining cognitive and neuropsychiatric outcomes of pallidal deep
brain stimulation (GPi-DBS) in patients with primary dystonia.
Background: Patients with dystonia may occasionally have cog-
nitive and psychiatric comorbidities. The cognitive and psychiatric
side effects of GPi-DBS in patients with primary dystonia have been
debated in the literature; some evidence suggests that no major
impact in cognition occurs but that, in some patients, declines in sus-
tained attention may occur.
Methods: Eleven patients with primary dystonia were evaluated at
baseline and post-GPi DBS placement (mean time between DBS place-
ment and follow-up testing: 13.2 months, SD 2.9). Cognitive tests
 POSTER SESSION
included the Mini-Mental Status Exam, selected subtests from the
Wechsler Adult Intelligence Scale, 3rd edition; Trail Making Test;
Controlled Oral Word Association Test; Stroop Interference Procedure;
Wisconsin Card Sorting Test; Boston Naming Test, Hooper Visual
Organization Test, the Verbal Learning subtest from the Wide Range
Assessment of Memory and Learning, 2nd edition; and the Faces subt-
est from the Wechsler Memory Scale, 3rd edition. Mood inventories
included the Beck Anxiety, Depression and Hopelessness Scales, as
well as the State-Trait Anxiety Inventory. Statistical significance was
calculated with one-tailed student t-test, defined as p value < 0.05.
Results: Of the 11 subjects, 7 were male (63%) and the mean
age at baseline assessment was 44.1 years (range 13 68; SD 17.5).
The majority had focal or segmental dystonia (8/11, 72%), 3 patients
had generalized dystonia. Two patients had positive genetic testing
(DYT 1 and DYT 3). Analysis of the subjects post-surgical exami-
nation data revealed that performance on most cognitive tests
remained stable or improved, with statistically significant improve-
ments noted on measures of working memory (letter-number
sequencing; digit span) as well as self-reported symptoms of both
anxiety and depression.
Conclusions: Our preliminary findings confirm those of other
(currently limited) studies showing that, in patients with primary dys-
tonia, GPi-DBS is safe from both a cognitive and psychiatric per-
spective. In fact, our results suggest that the procedure may have a
beneficial impact on both mood and working memory. Potential
explanations for the observed improvement in working memory will
be discussed.
1296
Rapid onset dystonia-Parkinsonism: Report of 3 cases and novel
mutation associated with ataxia and cerebellar atrophy
C.M. De Gusmao, M.E. Dy, T.J. Multhaupt-Buell, N. Sharma (Bos-
ton, MA, USA)
Objective: We report three cases with Rapid Onset Dystonia-
Parkinsonism (RDP) associated with different mutations in the
ATP1A3 gene, including a novel mutation presenting with ataxia and
dysphagia.
Background: Mutations in the ATP1A3 gene, encoding the a-3
subunit of the Na1/K1 ATPase, are associated with RDP, alternat-
ing hemiplegia of childhood (AHC) and CAPOS syndrome (Cerebel-
lar Ataxia, arreflexia, pes cavus, optic atrophy and sensorineural
hearing loss). Extensive phenotypic variation is described and
genotype-phenotype correlations continue to be refined.
Methods: We describe 3 patients evaluated in a tertiary Move-
ment Disorders clinic with distinct phenotypes. Consent for videotap-
ing the examination was obtained. Patients were investigated with
imaging and genetic testing (ATP1A3 mutation analysis) in a Clini-
cal Laboratory Improvement Amendments (CLIA)-certified lab (Neu-
rogenetics DNA diagnostic laboratory - Boston, MA).
Results: Case 1 had a history of Attention-Deficit disorder and
infantile feeding difficulties. At age 12 he developed marked dyspha-
gia, chorea and limb dystonia after a febrile illness. Testing demon-
strated a mutation in exon 17; c2267G>A (pArg756His). Case 2
presented with limb dystonia at age 26, and 3 years later developed
severe dysarthia/dysphagia after a febrile ilness. Testing demon-
strated a mutation exon 8; G829A (pGlu277Lys). Case 3 had a his-
tory of learning disability and developed imbalance, ataxia and
fluctuating dysarthria and dysphagia at age 20. Neuroimaging dem-
onstrated cerebellar atrophy and genetic testing identified a novel
mutation, predictably pathogenic in exon 8; c946G>A (pGly316Ser).
Conclusions: All cases presented with the core features of RDP
including abrupt onset of dystonia, predominant bulbar findings and
a rostrocaudal gradient. They also illustrate the variability of pheno-
types associated with ATP1A3 mutations, including a fluctuating
course newly described cognitive abnormalities, chorea and ataxia.
One case had a novel mutation, G316S, previously undescribed and
associated with prominent cerebellar atrophy. Clinicians should be
S505
attentive to the core features of this condition as new cases are likely
to be diagnosed as knowledge about the phenotypic spectrum contin-
ues to increase.
1297
Psychiatric features of GNAL and THAP1 mutation dystonia
E. Deegan, A. Glickman, H. Sarva, R.A. Ortega, D. Raymond, L.J.
Ozelius, M. Groves, S.B. Bressman, R. Saunders-Pullman (New York,
NY, USA)
Objective: To determine whether mutations in the GNAL and
THAP1 genes are associated with higher prevalence of anxiety and
depression.
Background: While depression and anxiety are known to be
increased in cervical dystonia and depression may be associated with
harboring a DYT1 GAG deletion independent of manifesting dysto-
nia, only limited reports of depression in DYT6 mutation individuals
have been reported. Psychiatric features of GNAL mutation dystonia
are not well characterized.
Methods: We evaluated depression and anxiety with the Beck
Anxiety Inventory and Beck Depression Inventory administered by
phone or in person to 12 GNAL mutation carriers manifesting symp-
toms of dystonia (MC), 10 non-manifesting GNAL mutation carriers
(NMC), 32 non-carrying family members (NC-F), 13 THAP1 MC,
16 NMC, 8 NC-F, and 28 healthy controls.
Results: GNAL MC (mean age: 57.7 6 10.9) were significantly
(p<0.05) older than NMC (46.3 6 15.2), controls (45.6 6 18.2),
THAP1 MC (37.8 6 16.2), and THAP1 NMC (36.96 13.9). Gender
did not differ between groups. Depression scores were increased in
GNAL MC compared with NC-F (median 7.0 vs. 4.0, p50.02), but
not compared to NMC (6.0) or controls (4.5). GNAL mutation car-
riers (MC1NMC, n522) scored higher than non-carriers (n560)
(6.5 vs. 4.0, p50.03). GNAL carriers also scored higher than THAP1
mutation carriers (MC1NMC, n529) (6.5 vs. 2.0, p50.02); how-
ever, in a logistic regression model adjusting for age, the difference
was no longer significant. Anxiety scores were also increased in
GNAL MC (8.5) compared with NC-F (1.5, p<0.01) and controls
(3.0, p<0.01), and in GNAL mutation carriers compared with non-
carriers (6.5 vs. 2.0, p50.01). NMC scores (2.5) were not increased
in comparison with NC-F or controls. THAP1 MC, NMC, and NC-F
depression and anxiety scores did not differ between groups nor
compared with controls, and no differences were found between
THAP1 mutation carriers and non-carriers.
Conclusions: Increased depression and anxiety in GNAL mutation
carriers suggests that there is a GNAL gene effect. However, the
absence of an association with NMC does not allow us to determine
whether the effect may be independent of manifesting dystonia, as
has been observed in DYT1 dystonia, or if it is due to the small sam-
ple size. Of note, we did not find any increase in depression or anxi-
ety in THAP1 mutation carriers.
1298
ICA shows enhanced functional connectivity between cerebellum
and thalamus in writers cramp
C. Dresel, J. Kraenbring, V. Wilzeck, V. Riedl, C. Zimmer, B.
Haslinger (Muenchen, Germany)
Objective: To assess changes in resting-state networks (RSN)
and functional connectivity (FC) between cerebellum and thalamus
in patients with writers cramp (WC).
Background: WC is a task-specific focal dystonia (FD) of the
hands which typically occurs during writing. Previous studies found
disinhibition and abnormal activation of cortical areas as well as
structural changes within cerebello-thalamic circuits.
Methods: Independent component analysis (ICA) was used to
extract five RSNs: the cerebello-thalamic network (CN), sensorimo-
tor function network (SMFN), lateral motor function network
Movement Disorders, Vol. 30, Suppl. 1, 2015
S506 POSTER SESSION
(LMFN), default mode network (DMN) and primary visual network
(PVN).
Results: Compared to healthy controls, patients with WC showed
increased FC of thalamus and cerebellum within the CN bilaterally
which correlated with disease severity, and a reduced FC of the ver-
mis. Patients also had weaker coupling of the right somatosensory
cortex within the SMFN and DMN.
Conclusions: In agreement with our hypothesis, this study found
increased FC of cerebellum and thalamus within the cerebellothala-
mic RSN (CN) emphasizing the functional relevance of the cerebel-
lum in dystonia. A reduced FC of the primary sensory cortex within
the DMN and SMFN is congruent with earlier data and a maladap-
tive reorganization of somatosensory areas in dystonia.
1299
Genotype-phenotype correlation in X-linked dystonia-
Parkinsonism (XDP/DYT3)
M.E. Dy, M.E. Talkowski, T.J. Multhaupt-Buell, L.R. Paul, D.C.
Bragg, N. Sharma (Boston, MA, USA)
Objective: To carefully characterize the severity of movement
abnormalities and disease course in those with XDP and their family
members and determine if there is correlation with the presence of
single nucleotide polymorphisms (SNPs) in the TAF1 gene.
Background: X-linked dystonia Parkinsonism (XDP/DYT3) is
associated with multiple sequence variations in a region of the X
chromosome containing several genes, the largest of which encodes
the TATA binding protein-Associated Factor-1 (TAF1). XDP, also
known as Lubag disease, occurs primarily in Filipino males. It is
characterized by neurodegenerative dystonia and Parkinsonism. The
majority of patients begin with focal dystonia that can generalize
with development of Parkinsonism later in disease course. Of the
cases described, there is phenotypic variability such as age of onset,
location of disease onset, and rate of severity/disease progression.
Unknown genetic and environmental factors may be contributing to
phenotypic variation. It is not known if the presence or absence of
various single nucleotide polymorphisms (SNPs) in the TAF1 gene
affects the clinical course.
Methods: 39 subjects within families referred for XDP agreed to
participate in our study. 26/39 subjects had genetic testing. 7/8 men
clinically suspected to have XDP were confirmed via sequencing to
bear previously reported markers of the XDP haplotype. There were
9 genetically confirmed XDP carriers and 8 genetically confirmed
controls. All subjects provided their medical history and were sys-
tematically examined, using the Burke-Fahn-Marsden and Unified
Parkinsons disease rating scales. A rater blinded to genetic status
and family relationship reviewed 39 subject videos. Another rater,
unblinded to family relationships and genetic status, systematically
examined subjects. Severity of disease in confirmed XDP subjects
made it impossible to be blinded to their genotype.
Results: In this small sample size, no clear correlation was identi-
fied between the presence of specific SNPs and a distinct XDP
phenotype.
Conclusions: A large sample of subjects with XDP, and their
family members, as well as genetic data regarding the presence of
various SNPs in a Filipino control population is needed for definitive
genotype-phenotype correlation.
1300
Ranking of dystonia severity by pairwise video comparison A
useful method to select items for automated movement analysis
T. Ellermeyer, K. Otte, F. Heinrich, S. Mansow-Model, P. Krause, B.
Kayser, K. Lauritsch, F. Paul, A.A. K uhn, A.U. Brandt, T. SSchmitz-
Hubsch (Berlin, Germany)
Objective: To show that ranking of dystonia severity by paired
video comparisons is feasible and valid.
Movement Disorders, Vol. 30, Suppl. 1, 2015
Background: Motor symptoms of dystonia are heterogeneous and
current scales miss phasic components as an important disease aspect.
We aim to develop tools for video-based movement analysis. A main
step in this process is the selection of appropriate assessment items.
Methods: 34 patients with cervical or generalized dystonia (16
with tremor) and 23 healthy controls were assessed with clinical rat-
ing scales and performed 25 scripted movement tasks that involved
simple movements of different body parts. Multiple permutations of
pairs of videos from 22 subjects were presented for comparison (bet-
ter/worse, equal) until a full rank order of all cases was achieved for
each movement item. The agreement between raters is expressed as
percent and normalized Kendall tau distance. Rankings of 2-4 raters
were merged into one order for each item using the rank centrality
algorithm. Spearman correlations of rank order with clinical scale
scores were repeated for subgroups w/o tremor.
Results: The interrater agreement for phasic components was 70-
90%. Normalized Kendall tau distances of ranking were <0.3 for 19
items, the remaining six were excluded from rank order correlations.
The rank order for quiet sitting, standing and head movement in all
planes correlated with clinical scores for the whole group (rho 0.5 to
0.9, strongest for posture sitting and head rotation) and in subgroups
without tremor, but not in the tremor subgroup except for sitting. For
arm movements, only rankings for elbow flexion correlated with clini-
cal score for the whole group but not in the tremor/phasic subgroup.
Conclusions: The agreement of video-based rankings between
raters is remarkable, as ratings were done without explicit criteria
and by raters with different levels of expertise. The lack of correla-
tion with clinical scales in the tremor resp. phasic subgroup may be
interpreted as tremor being acknowledged in video comparisons but
not in clinical rating scales. This supports video based rank ordering
as a more comprehensive clinical rating of dystonia. This approach
may be useful for research purposes, e.g. selection of items or
regions of interest for instrumental movement analysis and is cur-
rently applied to data from 3D motion capture in dystonia patients.
1301
Sensory rehabilitation in pseudoathetosis and secondary dystonia.
A report of two cases
T. Emara, H. Mohsen (Cairo, Egypt)
Objective: We hypothesized that an intense sensory rehabilitation
program may decrease involuntary movements and facilitate better
motor control in two cases of pseudoathetosis and secondary
dystonia.
Background: The presence of clinically subtle sensory deficits in
cases of Parkinsons disease, the famous sensory tricks, and the evi-
dence of abnormal sensory processing in neuroimaging studies of
different types of Movement Disorders are well documented. The
concept of using sensory rehabilitation techniques in the management
of these disorders has not been thoroughly studied.
Methods: We used a treatment protocol consisting of simultane-
ous biparietal TDCS (Anodal stim contralateral to the affected
hand)1TENS on the affected median nerve1mirror therapy, sensory
education techniques, and task specific training. No change of medi-
cation was allowed during the study period.
Results: Case 1: 78 years old lady with a MMSE 29, had severe
left proprioceptive deficit 3 years after her second stroke with intact
motor power. She had pseudoathetosis in her left upper limb. Her
left hand would get in her way when working with her right unaf-
fected hand. Bimanual activities were obviously worse. This was not
corrected with visual guidance. After 24 one hourly sessions over a
period of two months, she was much better in practicing her ADLs
and she can now enjoy knitting.
Case 2: 17 years old male who has just finished highschool pre-
sented with right (dominant) focal hand writing dystonia. The condi-
tion started 6 months after undergoing surgery to resect a
craniopharyngioma and prevented him from going to college. His
examination showed impaired joint position and movement sense in
 POSTER SESSION
distal phalanges, 1-2 point discrimination and tactile localization
along with dystonic posturing upon holding the pen and tremors
upon using it, he had no weakness. Medical treatment was not suc-
cessful. He underwent the same treatment protocol with special
attention to writing practice. Six weeks after starting therapy his
grasp was better tremors decreased and speed and clarity of writing
increased. He was encouraged to start going to college while in ther-
apy and was gradually weaned off the sessions.
Conclusions: Adjusting the sensory input may improve motor
control and decrease secondary involuntary movements associated
with sensory deficits. Sensory rehabilitation strategies should be stud-
ied in both primary and secondary cases of Movement Disorders.
1302
Primary writing tremor is a dystonic trait: Evidence from a
single family
R. Erro, M. Ciocca, A. Batla, J. Rothwell, K.P. Bhatia (London,
United Kingdom)
Objective: To bring new clinical evidence regarding Primary
Writing Tremor (PWT) pathophysiology.
Background: Primary writing tremor (PWT) is a task-specific
tremor that occurs and interferes with handwriting. Although handwrit-
ing is primarily affected, subsequent development of a postural or
kinetic tremor has been described in some cases. Given its rarity, PWT
pathophysiology is still unknown. Familial clustering of PWT with both
Essential Tremor (ET) and Writers Cramp (WC) has been reported
and this leaves the question open as to whether PWT should be classi-
fied as a discrete entity, a variant of ET, or a type of focal dystonia.
Methods: We describe here a single family with three affected
members, of whom one presenting with a pure PWT phenotype with-
out overt signs of dystonia.
Results: The index case of this family is a 73-year-old man, who
has had writing difficulties for the last 5 years. His symptoms fea-
tured a tremor of his right hand at certain angles when writing. This
was most evident when he had to perform anticlockwise movement
as part of his signature. This has not progressed over the years, but
he further referred a mild tremor when holding a glass or an object
during the last 6 months. He has had previous trials with anti-
cholinergics and propranolol without benefit. On examination, he had
a tremor of his right arm upon writing, but not on other tasks. The
remaining examination was unremarkable.
His brother, aged 76, had tremor of his hands featuring both a pos-
tural and rest component for the last 4 years. Given the presence of a
rest component and the fact that tremor was asymmetric, a suspicion of
Parkinsons disease had been raised by another neurologist, but dopa-
mine transporter imaging turned out to be normal. On examination, he
had a tremor of his hands (left>right) both at rest and on posture, with
dystonic posturing of the fingers of his right hand. There was no brayki-
nesia or rigidity, and the remaining neurological examination was clear.
His daughter, aged 43, had abnormal posturing of her right hand
since her late twenties. On examination there was a clear dystonic
posturing of her right hand with no additional signs.
Conclusions: We have reported here a family with three affected
family members, including one with pure PWT. Such a familial clus-
tering would support the notion that PWT is a dystonic trait, suggest-
ing a genetic involvement for this disorder.
1303
The role of TorsinA in developing neurons
B. Fabry, K. Bretzel, T. Ott, K. Grundmann-Hauser, O. Rie
(T
ubingen, Germany)
Objective: The aim of this study was to further analyze the role
of TorsinA during neurogenesis. To this aim we analyzed whether
overexpression of TorsinA in PC6-3 cells alters length and quantity
of neurites. In addition analyzed whether the disease-related mutation
S507
of TorsinA (DGAG) had effects on neurite outgrowth in PC6-3 cells.
These experiments were complemented by analysis of neurite out-
growth in in murine primary neuron cultures from TorsinA-knockout
and -knockin mouse models.
Background: The 3-basepair mutation of TorsinA (DGAG) leads
to the early onset autosomal dominant inherited Movement Disorder
DYT1 Dystonia, which leads to involuntary muscle contractions,
causing twisting and repetitive movements or abnormal postures,.
Due to the fact that loss of TorsinA leads to early death in the
affected mouse models and shows high expression levels in early
brain development we conclude that TorsinA plays an important role
during neurogenesis and our aim was to further investigate the role
of TorsinA in the developing central nervous system.
Methods: We used Doxycyclin-induceable PC6-3 cells expressing
TorsinA in wildtype and DGAG variants, differentiated using NGF
in orderto measure the length and amount of neurites and the size of
the growth cone. Analysis was performed by means of immunofluo-
rescence microscopy and computational analysis was done using
NeuronJ. Additionally, hetero-and homozygous TorsinA knockout-
and knockin (DGAG]) mice were sacrificed at embryonic day 19 to
obtain primary neuron cultures of the hippocampus.
Results: Our results indicate that overexpression of TorsinA leads
to a significant increase in growth cone size and elongation of neu-
rites in PC6-3 cells, even when the mutant form of TorsinA is
expressed. In contrast, loss of TorsinA leads to a significant reduc-
tion in the length of dendrites in hippocampal primary neurons.
Conclusions: As seen in our experiments, TorsinA seems to play
an important role during the neurogenesis, controlling the regulation
of dendrite length. This may be causative for DYT1-Dystonia, since
a reduction of dendrite length may lead to unexpected consequences
for the whole brain structure which have to be elucidated in further
experiments, as does the mechanism behind the ability of TorsinA to
control the growth of dendrites.
1304
Case series of platysmal dystonia
J.Y. Fang, K.E. Bradley, C.M. Tolleson, F.T. Phibbs, P. Hedera, T.L.
Davis (Nashville, TN, USA)
Objective: To determine the optimal treatment for platysmal dys-
tonia by a retrospective chart review.
Background: Dystonia affecting the platysma muscle can occa-
sionally be a disabling component of cranio-cervical and other dysto-
nia conditions. This condition and may be an underdiagnosed cause
of jaw opening dystonia, dysphagia or dysarthria. Various treatments
including anticholinergics, dopaminergic agonists, dopaminergic
antagonists, benzodiazepines, gaba-agonists, botulinum toxins, and
surgical procedures have all been employed, but the relative respon-
sive to each is unknown.
Methods: We performed a search for cases of platysmal dystonia
with the search terms platysma or platysmal in an electronic
medical record system in place since 1998. We examined age at pre-
sentation, years of disease duration, presence of family history, and
prior or current treatments. We also searched these charts for prior
or current treatment with any of these therapies: anticholinergics,
baclofen, benzodiazepines, botulinum toxin (A or B), dopaminergics,
gabapentin, primidone, propranolol, or deep brain stimulation (DBS).
Any other identified treatments were also examined. Treatment
response was assessed on a 7-point clinician based impression of
change scale (CBIC) since the initiation of treatment where 1=very
good improvement; 2=good improvement; 3=minimal improvement;
4=no change from baseline; 5=minimal worsening; 6= much wors-
ened; 7=very much worsened.
Results: A total of 13 patients with age range of 40-74 years and
disease duration of 6-31 years were identified with platysmal dysto-
nia. All patients also had another type of craniocervical dystonia.
Ten patients were trialed on botulinum toxin, with 5/13 experiencing
CBIC score 1 and another 5/13 having CBIC=2. Four patients
Movement Disorders, Vol. 30, Suppl. 1, 2015
S508 POSTER SESSION
underwent bilateral GPI DBS for their dystonia, with one experienc-
ing CGIC= 1 and one having CGIC=2. Surgery and botulinum ther-
apy demonstrated the best response to treatment when multiple
treatments had been utilized. One patient did have CGIC=2 to beta
blockers added to benzodiazepines and botulinum toxin. No other
therapy produced CBIC=2 or 1.
Conclusions: Our data from this small subset of platysmal dysto-
nia patients suggests a higher rate of response to botulinum toxin
compared to surgery and other drug therapies. More research is
needed to assess the clinical efficacy of these treatments in a larger,
controlled patient population.
1305
XCiDaBLE: Observational, prospective trial evaluating xeomin
(incobotulinumtoxinA) for cervical dystonia or blepharospasm in
the USA
H.H. Fernandez, J. Jankovic, F. Pagan, D. Greeley, K. Sethi, A.
Verma (Cleveland, OH, USA)
Objective: To report results from XCiDaBLE: a prospective,
observational study evaluating Xeomin (incobotulinumtoxinA) for
cervical dystonia (CD) or blepharospasm in a real-world clinical
practice setting (NCT01287247).
Background: There is a lack of prospective data on real-world
clinical practice experience with botulinum neurotoxins (BoNTs) to
treat CD or blepharospasm.
Methods: Subjects with CD or blepharospasm received 2 incobo-
tulinumtoxinA treatment cycles. Subject-reported outcomes included
Patient Global Impression-Severity (PGI-S), CD Impact Profile
(CDIP-58; CD only), Jankovic Rating Scale (JRS; blepharospasm
only), Work Productivity and Activity Impairment questionnaire, and
quality of life (QoL; SF-12v2). An interactive voice/web response
system was used to assess outcomes between clinic visits (4 weeks
after each treatment). The Clinical Global Impression of Severity
(CGI-S) was collected at each injection visit and the study end visit.
PGI-S and CGI-S were assessed on a 7-point descriptive scale.
Results: Most of the 688 subjects (CD, n5369; blepharospasm,
n5319) had prior treatment with BoNTs (CD, 75.3%; blepharo-
spasm, 94.4%). Mean [standard deviation] doses at the 1st and 2nd
treatment were similar (CD, 213.9 [126.1] U and 229.1 [132.9] U;
blepharospasm 70.6 [37.7] U and 71.0 [36.9] U). Incobotulinumtox-
inA treatment significantly improved PGI-S from the 1st to the 2nd
injection (CD, p50.002; blepharospasm, p50.026). CDIP-58 and
JRS scores significantly improved from each treatment to 4 weeks
post injection (p<0.001 for all). Improvements in SF-12v2 mental
health and physical QoL scores were seen in both groups and
reached significance in subjects with CD. IncobotulinumtoxinA treat-
ment led to less absenteeism for subjects with CD and improved
work productivity for subjects with blepharospasm (p<0.05 for
both). CGI-S scores showed significant improvements over the study
duration (p<0.05 for both indications). Adverse events in both indi-
cations were mild to moderate in intensity and resolved by the end
of the trial.
Conclusions: XCiDaBLE provides important real-world disease
state information for patients with CD or blepharospasm receiving
incobotulinumtoxinA, confirming the effectiveness and favorable
safety profile of incobotulinumtoxinA observed in randomized clini-
cal trials.
1306
Lack of association between cancer and THAP1 mutation
dystonia
A. Glickman, R.A. Ortega, H. Sarva, M. San Luciano, D. Raymond, L.J.
Ozelius, S.B. Bressman, R. Saunders-Pullman (New York, NY, USA)
Objective: To determine whether mutations in the THAP1 gene
are associated with higher rates of cancer.
Movement Disorders, Vol. 30, Suppl. 1, 2015
Background: THAP1 is a nuclear pro-apoptotic factor that inter-
acts and co-localizes with prostate apoptosis response factor-4 (Par-
4). Par-4 is up-regulated in cells undergoing apoptosis and has been
associated with prostate cancer. As mutations in THAP1 cause
DYT6 primary torsion dystonia, we sought to determine whether
there was a potential association between THAP1 mutations and
cancer.
Methods: 12 THAP1 mutation carriers manifesting symptoms of
dystonia (MC) (mean age: 39.58 6 16.92 years; all with the indel
founder mutation F45fs73X), 17 non-manifesting THAP1 mutation
carriers (NMC) (36.06 6 13.80 years), 8 non-carrying family mem-
bers of THAP1 MC (NC-F) (47.25 6 19.52 years), and 27 healthy
controls (45.93 6 18.44 years) were administered a health history
questionnaire assessing type of and age at cancer. Cancer rates were
compared in MC versus NMC, NC-F, and controls, and in THAP1
mutation carriers versus non-carriers.
Results: Among the 12 MC, none had a history of cancer, com-
pared to 5.88% of NMC (n51/17, age at non-melanoma skin can-
cer=37, age at melanoma=61) and 7.41% of controls (n52/27,
average age at cancer=65.5 6 2.1). This was not significant in a haz-
ards model censoring at age at first cancer or age at exam.
Conclusions: Mutations in THAP1 causing primary torsion dysto-
nia do not appear to be associated with cancer in mutation carriers,
both those with and without symptoms of dystonia. However,
because of the relatively young age of our sample, longitudinal
follow-up, or sampling an older population, would better determine
whether there is a higher lifetime risk of developing cancer associ-
ated with THAP1 mutations.
1307
Long-term clinical and radiological evolution and DBS therapy
outcome in rapid-onsed dystonia Parkinsonism: A case report
V. Gonzalez, L. Cif, A. Flaire, E. Sanrey, E. Le Bars, N. Menjot de
Champfleur, P. Coubes (Montpellier, France)
Objective: To describe long-term clinical evolution, imaging
studies and therapy outcome in one patient with rapid-onset dystonia
Parkinsonism (RDP).
Background: To date, there is limited knowledge about the
pathophysiology and long-term clinical evolution of RDP. Pallidal
DBS has been reported not to be effective in this clinical condition.
Methods: A 19-year-old patient presented with acute dysarthria,
swallowing disorder, oromandibular dystonia and right upper limb
tremor. These clinical signs were triggered by acute alcohol con-
sumption. Within some weeks he developed asymmetric (left>right)
generalized dystonia with cervical and trunk involvement. Distribu-
tion of dystonia followed a rostrocaudal gradient. Initial cerebral
MRI was normal. Molecular testing for ATP1A3 gene mutations
confirmed sporadic RDP.
Results: This patient was refractory to Levodopa. Oral baclofen
led to mild clinical improvement. Botulinum toxin injections were
proposed in order to alleviate painful dystonia in the trapezius and
the left arm. This patient was refractory to bilateral pallidal deep
stimulation (DBS) in 2001 and to bilateral subthalamic (STN) DBS
in 2004. Intrathecal baclofen therapy was also tried with poor clini-
cal response of hypertonia. DATscan showed mild reduction in the
left caudate nucleus and bilateral putamen. PETscan did not show
relevant abnormalities. Cerebral MRI performed at the age of 35
years showed mild cerebellar left hemispheric and vermis atrophy.
Functional MRI (fMRI) was performed using a motor paradigm task
consisting of rhythmic self-paced elbow flexion/extension movements
showed prominent bilateral cerebellar cortex, dentate and vermis
activity, together with right occipital cortex activity associated with
left arm movements. Left sensorimotor cortex and right occipital cor-
tex and right cerebellar cortex activity was associated with right arm
movements. Diffusion tensor imaging was also performed to study
the main white matter tracts of motor circuit.
 POSTER SESSION
Conclusions: Our data support prior knowledge regarding the
lack of response of RDP to pallidal DBS. This patient was also
refractory to STN DBS. Structural MRI showed mild unilateral cere-
bellar atrophy at last follow-up visit The implication of cerebellar
pathways in the pathogenesis of dystonia in RDP could be suggested
by fMRI results in this study, but our data are not conclusive and
should be replicated in other patients.
1308
Malignant Wilsons disease: Extensive cerebral parenchymal
involvement on MRI brain, severe neurological disability and
poor therapeutic response
S. Gupta, A. Aggarwal, M. Munshi, D. Sanghvi, M. Bhatt (Mumbai,
India)
Objective: To study the clinical implications of cerebral paren-
chymal changes (CPC) on MRI brain (T2W/FLAIR images) in
patients with Wilsons disease (WD).
Background: MRI brain in WD typically reveals symmetric
hyperintense signal on FLAIR/T2W images in the basal ganglia and
brainstem. Cerebral parenchymal changes (CPC) have been described
but their frequency and clinical implications are not well known.
Methods: We examined pretreatment MRI scans of patients with
WD-related neurological symptoms visiting our WD Clinic from
2005-2014, for CPC on T2W/FLAIR images. The pattern and extent
of CPC were analyzed and correlated with the clinical features and
course. All patients received decoppering (trientine/penicillamine).
Treatment was tracked using the Global Assessment Scale for Wil-
sons disease (GAS for WD).
Results: Of the 154 patients with WD-related neurological dis-
ability seen during 2005-2014, 73 had pretreatment MRI brain. CPC
were seen in 7/73 MRIs reviewed. The observed CPC comprised 2
groups, (1) Extensive grey and white matter CPC: involving 30% or
more of the cerebral hemisphere (n54); (2) Limited CPC: 1 or more,
small (few mm), discrete hyperintensities dispersed in the cerebral
white matter (n52), and isolated splenial hyperintensity (n51). All 7
patients with CPC had symmetrical but variable involvement of basal
ganglia and brainstem.
All 4 patients with extensive CPC (M:F::3:1; mean age 13.5 years
(range 9 -18)) had compensated liver cirrhosis and severe WD-
related disability with mixed-Movement Disorders, cognitive and
behavioural problems.Three had seizures. After decoppering for an
average of 4.3 years (range 3.5 - 6), 3 patients have shown no
improvement while 1 has shown only partial recovery. Serial MRIs
showed temporal evolution of the observed CPC . The 3 patients
with limited CPC had moderate to severe WD-related neurological
disability and in all 3, the neurological disability reversed with
treatment.
Conclusions: Cerebral parenchymal changes (CPC) on brain MRI
are rare (approximately 10%) in Wilson[apos]s disease. Our report
suggests that extensive CPC (involving substantial part of the cere-
bral parenchyma) represents a malignant phenotype of WD. Exten-
sive CPC were invariably associated with severe neurological
disability that unlike other patients (with limited/no CPC) were
refractory to decoppering.
1309
Dystonia in Arab ancestry
S. Hanif, T.M. Muhammad, S. Kalantan, J.A. Bajwa (Riyadh, Saudi
Arabia)
Objective: To describe characteristics of Dystonia patients eval-
uated at Movement Disorders center,National Neuroscience Institu-
te,King Fahad Medical City,Riyadh,Saudi Arabia.
Background: Dystonia is a neurological syndrome characterised
by sustained involuntary contractions leading to abnormal muscle
movements and posturing.It is the third most prevalent Movement
S509
Disorder.Dystonia can be focal or generalized.The underlying patho-
physiology is considered etiologically hetrogeneous.There is very
limited literature on Dystonia from the Arabian peninsula limiting
clinical understanding from etiology to pathophysiology to phenome-
nology to treatment.
Methods: A single center retrospective observational study was
conducted by reviewing patients charts being evaluated from 2012 to
2014 in the clinic.Twenty patients were identified by age,type of dys-
tonia,age of onset of Dystonia,handedness,genetic testing and neuroi-
maging findings.
Results: Out of 20 patients,14 were males (70%) and 6 (30%)
were females with mean age (6SD) of 37.10 6 13.06.There was stat-
istically mean significant(p 5 0.014)difference between age of onset
and Dystonia types.Whereas mean age of primary Dystonia was
18.1y and of secondary Dystonia was 38.1y.Primary Dystonia was
found in eleven patients (55%) while 8 (45%) patients had secondary
Dystonia.Cervical Dystonia was the most common accounting for
66% of all focal Dystonias.Among secondary Dystonias stroke,
trauma,drugs,psychogenic and infections were possible underlying
etiologies.90% of patients were right handed and 60% had clinical
manifestations predominantly affecting right side of the body.75% of
patients did not report any triggers whereas stress and anxiety aggra-
vated symptoms in 25% of the patients.For neuroimaging correla-
tion,two patients with secondary Dystonia showed basal ganglia
hyperintense lesions,4 patients had old strokes,5 patients had normal
imaging and 2 showed cerebellar atrophy.Among primary Dystonia,-
genetic testing was done for four patients with positive family histo-
ry,DYT1,DYT5,GSCE and PKAN were all negative.
Conclusions: Our data indicates primary Dystonias are slightly
more common than secondary Dystonias.Extensive genetic work up
is required to identify etiology in primary Dystonias given possibil-
ity of novel genetic mutations in this cohort.Our findings are limited
given small sample size.Further clinical and genetic studies are
required to assess Dystonia etiology,phenomenology,course,progres-
sion and treatment in Arab ancestry.
1310
Eye hand coordination abnormalities in patients with writers
cramp
K.R. Jhunjhunwala, R. Kotikalapudi, A. Lenka, J. Saini, R. Yadav,
M. Netravathi, P.K. Pal (Bangalore, India)
Objective: To study eye-hand coordination abnormalities in
patients with Writers Cramp (WC).
Background: The sensorimotor plasticity is known to be malad-
aptive in patients with WC. The role of cerebellum in sensorimotor
adaptation is well documented in dystonia. Cerebellum is known to
influence the neural pathways of saccadic eye movements and eye
hand coordination. In this study we have studied the saccadic param-
eters to get a further insight of the involvement of cerebellum in
WC.
Methods: Fifteen patients with WC (women: men= 3:12) and 15
age and gender matched controls performed oculomotor and eye
hand coordination tasks. Initially a visually guided stimuli (VGS)
task was performed with Only Eye Condition (OEC) condition and
then with Eye hand Condition (EHC). Saccade velocity, acceleration,
deceleration, latencies, accuracy rate and average acceleration index
was recorded for OEC and EHC. For EHC, hand parameters such as
peak velocity, peak acceleration, peak deceleration, the total move-
ment duration and the duration of the terminal phase were recorded.
Results: There was no significant difference between the mean
age of the patients and controls (38.6 6 11.2 years vs 35.6 6 9.2
years, p>0.05). The mean duration of symptoms was 7.9 6 5.5 years.
The mean Writers Cramp Rating Scale (WCRS) in WC patients was
14.1 6 3.4.
The average acceleration of the saccade was significantly lower in
patients in EHC task compared to controls (11541.5 6 3858.7 /sec2 vs
12321.4 6 1689.7 /sec2, p50.008). There was no significant difference
Movement Disorders, Vol. 30, Suppl. 1, 2015
S510 POSTER SESSION
between patients and controls in OEC task in saccadic parameters. The cur-
vature index of acceleration was significantly more in patients compared to
controls (patients vs controls, 2.4 6 0.4 vs 1.8 6 0.2, p50.01). The average
acceleration of the saccade was significantly lower in patients while per-
forming OEC task compared to EHC task (9016.1 6 2734.7 /sec2 vs
11541.5 6 3858.7 /sec2, p50.048). There was no significant correlation
between the WCRS and the saccadic parameters.
Conclusions: The saccadic accuracy and acceleration is essen-
tially controlled by cerebellum and its connections. Saccadic acceler-
ation abnormalities in eye hand coordination tasks in patients with
WC gives further insight of the role of cerebellum in pathogenesis of
focal dystonia.
1311
Long-term results of the treatment of craniofacial dystonia with
onabotulinumtoxinA
A. Jochim, F. Castrop, C. Huber, B. Haslinger (Munich, Germany)
Objective: To evaluate long-term efficacy and safety of focal
dystonia treatment with OnabotulinumtoxinA since the introduction
of its new formulation in 2000.
Background: Current OnabotulinumtoxinA was introduced in
Germany in 2000 and due to its lower content of complex proteins
significantly decreased the risk of antibody formation.
Methods: We conducted a retrospective analysis of the treatment
data of all patients with cervical dystonia, blepharospasm and/or
meige syndrome who had been treated at least three times with cur-
rent OnabotulinumtoxinA in our outpatient clinic for Movement Dis-
orders between August 2000 and November 2014.
Results: Analyzing 1216 facial and 2010 cervical treatment ses-
sions of 165 patients we found a moderate increase of dosage in the
first years succeeded by a stable level over the following years
(mean dose 38 and 138 mouse units respectively), while the injection
intervals were quite stable from the beginning. The most frequent
side effects were ptosis (4%) and sicca/epiphora (4%) after facial
treatment and mild dysphagia (3%), muscle weakness (2%) and pain
(2%) after cervical therapy. 56% of the patients with facial dystonia
and 47% with cervical dystonia were still treated in our outpatient
clinic in November 2014. Reasons for discontinuation of the facial/
cervical therapy were change to a another nearby hospital, age, other
diseases, spontaneous improvement of symptoms (42% in both
groups), side effects (17%/6%), primary (13%/10%) or possible sec-
ondary (4%/13%) treatment failure and unknown reasons (13%/
29%). Extensor-digitorum-brevis-(EDB)-tests conducted in three
patients did not prove a secondary treatment failure. One patient
with already pathological EDB-test during pre-treatment with other
botulinum toxin preparations showed botulinum toxin A antibodies.
Conclusions: Treatment of dystonia with current Onabotulinum-
toxinA is a safe long-term therapy with stable dosage and injections
intervals over many years.
1312
Comparative study of spread of A1 and A2 subtypes of
botulinum toxin preparations for blepharospasm: Proof-of-
concept randomized controlled trial
R. Kaji, A. Miyashiro, S. Kaji, T. Takeuchi (Tokushima, Japan)
Objective: To test the clinical efficacy and safety of low-
molecular weight (150kDal) A2 subtype botulinum toxin preparation
(A2NTX) compared to A1 preparation (onabotulinumtoxinA).
Background: Animal experiments (Torii et al 2014) demon-
strated its safety and efficacy twice higher than subtype A1 prepara-
tions. Phase 1 study in man demonstrated 6.5 mouse LD50 units of
A2 had a similar efficacy to 10 units of A1, with similar duration of
action (Mukai et al. 2014). We have conducted a proof-of-concept
randomized controlled study to compare its efficacy and spreading of
its effects in blepharospasm to A1 subtype (onabotulinum toxin).
Movement Disorders, Vol. 30, Suppl. 1, 2015
Fig. 1. (1312).
Methods: We enrolled 12 blepharospasm patients (2 men) aged
27-82 years (mean 64.75 years), and these backgrounds were similar
between A1 (n56) and A2 (n56) groups. Two patients were
excluded for efficacy evaluation because of the effect of needle
insertion pain on one side. A blinded physician injected 25 units of
A1 or A2 toxins into oribicularis oculi and corrugator muscles on
each side (total 50 units). A blinded rater measured the anhidrotic
area (length from the medical canthus to the sweating margin above)
with iodoiodo-starch reaction for sweating.
Subjective rating of the eye symptom changes on each side were
reported by the patients using Visual-Analog Scale (VAS).
Results: The spread of the toxin action as measured by sweating
inhibition was significantly smaller (p50.025) for A2NTX (A2NTX
n512, 17.9 1 3.2 (SE) vs onabotulinumtoxinA n512, 24.4 1 3.0 (SE)).
[figure1]
Subjective improvement as measured by the change in VAS was
not significantly different between A1 and A2 (A2NTX n511,
16.5 1 7.2 onabotulinumtoxinA n511, 7.8 1 5.0).
Conclusions: The fact that spread of the toxin action was less for A2
may indicate less spread to neighboring facial muscles, thus A2 being
less like to produce so-called botulinum toxin a face in cosmetic use.
1313
The Burke-Fahn-Marsden movement scale is age-dependent in
healthy children
M.J. Kuiper, L. Vrijenhoek, R. Brandsma, R.J. Lunsing, H. Eggink,
K.J. Peall, M.F. Contarino, J.D. Speelman, M.A.J. Tijssen, D.A.
Sival (Groningen, Netherlands)
Objective: To investigate the Burke-Fahn-Marsden Movement
Scale (BFMMS) for the influence of age and for the reliability of the
scores.
Background: In young children and adults, dystonia rating scales
are interpreted according to identical guidelines. However, in young
children the central nervous system is still developing, potentially
giving the false impression of disappearing dystonic features when
children grow up. For adequate longitudinal interpretation of
BFMMS scores from child- to adulthood, this implicates that age
validated normative values are needed, first.
Methods: Nine Movement Disorder specialists from different
backgrounds (3 paediatric neurologists, 3 Movement Disorder
research students and 3 adult neurologists) cross-sectionally scored
the BFMMS independently in 52 healthy children (4 - 16 years;
m:f=1). We associated outcomes with age and we additionally inves-
tigated the reliability of the scale by calculating the inter- and intra-
observer agreement and test-retest reliability.
 POSTER SESSION
Results: In healthy children, total BFMMS scores were signifi-
cantly predicted by age (b 5 -0.71; p < 0.001). The effect of age per-
sisted at least until 16 years of age. Intraclass Correlation
Coefficients (ICCs) were statistically significant (p < 0.05) and var-
ied between fair to almost perfect [inter-observer agreement: 0.33;
intra-observer agreement: 0.69; test-retest reliability: 0.94]. The
inter-observer agreement appeared statistically significant (p < 0.05),
varying from substantial to only slight [paediatric neurologists: 0.65;
research students: 0.45; neurologists: 0.20].1
Conclusions: In healthy children, BFMMS is age-dependent, at
least until 16 years of age. For reliable interpretation and longitudi-
nal surveillance of quantitative dystonia rating scales in children,
international paediatric normal values are needed, first.
1. Landis JR, Koch GG. The measurement of observer agreement
for categorical data. Biometrics 1977 Mar;33(1):159-174.
1314
The Babinski-2 sign in hemifacial spasm. A report from a
Movement Disorder clinic in El Salvador
J.R. L
opez-Castellanos, J.R. L
opez-Contreras (San Salvador, El
Salvador)
Objective: To assess the frequency of Babinski-2 sign among
patients with HFS and determine its use in differentiating HFS and
blepharospasm (BSP).
Background: The Babinski-2 sign (the other Babinski sign,
brow-lift sign), is a physical sign specifically found in patients
with hemifacial spasm (HFS), is manifested by unilateral contraction
of the frontalis muscle, causing eyebrow elevation, with simultaneous
contraction of the ipsilateral orbicularis oculi muscle, causing eyelid
closure.
Methods: We conducted a prospective study for the presence of
the Babinski-2 sign, from August 2013 to December 2014. Subjects
fulfilled the diagnostic criteria for HFS and BPS. The assessment
was performed by medical observation and video recordings.
Results: 131 patients fulfilled the inclusion criteria of HFS, 91
females with mean age of 64.8 years (range, 27-90 yrs), 40 males
with mean age of 62.3 years (range, 38-96 yrs). 58 subjects fulfilled
the inclusion criteria of BPS, 38 females with mean age of 66.0
years (range, 20-91 yrs) and 20 males with mean age of 72.0 years
(range, 55-86 yrs). The Babinski-2 sign (Fig. 1) was present in none
of the BSP patients but was evident in 85 (64.9%) of the HFS
patients (female: 52, male: 33), (Table 1).
20 patients had secondary mild HFS resulting from Bells palsy,
but only 3 of them had Babinski-2 sign. All patients with HFS and
BPS had an excellent response to treatment with botulinum neuro-
toxin type A, independent of the severity of the Movement Disorder
and the presence or absence of Babinski-2 sign.
[figure1] [figure2]
Conclusions: The Babinski-2 sign, found in 64.9% of our cases
of HFS, is an under-recognized physical sign which can be used to
Fig. 1. (1314).
S511
Fig. 2. (1314).
distinguish HFS from BSP and may improve the accuracy of differ-
ential diagnosis of other pathologies such as tics, cranial dystonia,
other facial dyskinesias, focal epilepsy or psychogenic Movement
Disorders.
1315
Bilateral hemifacial spasm: Report of 6 cases in El Salvador
J.R. Lopez-Castellanos, J.R. Lopez-Contreras (San Salvador, El
Salvador)
Objective: Describe the clinical characteristics of patients with
bilateral HFS and evaluate the therapeutic effect of botulinum neuro-
toxin type A (BoNT/A).
Background: Hemifacial spasm (HFS) is usually manifested by
unilateral irregular, clonic, or tonic contractions of muscles inner-
vated by the ipsilateral facial nerve; but bilateral hemifacial spasm is
rarely reported in the literature.
Methods: We conducted a retrospective study in a Movement
Disorders Clinic of Instituto Salvadore~ no del Seguro Social, from
2004-2014. Subjects fulfilled the diagnostic criteria for bilateral HFS.
Baseline measures were determined before and after (30, 90, 180
and 270 days) BoNT/A injections. Assessment by medical observa-
tion, video recordings.
Results: From 292 patients with HFS, only 6 subjects (2%) ful-
filled the inclusion criteria of bilateral HFS; these six patients had
unilateral onset followed by bilateral, asymmetric, and asynchronous
contractions of facial muscles. The mean age of the patients (5
female and 1 male) was 70.3 years (range, 5388 yrs), and the mean
duration of symptoms was 12.3 years (range, 118 yrs). The facial
twitching started in the right eyelid in 3 patients and in the left eye-
lid in 3 cases, and the opposite side of the face began to twitch on
the average 8 years (range, 118 yrs) later. Only two subjects
showed Babinski-2 sign positive, ipsilateral to the facial side where
the Movement Disorder began. Neuroimaging studies were normal in
all subjects (Table 1). After BoNT/A treatment, all patients had a
significant improvement of the Movement Disorder without side
Fig. 1. (1315).
Movement Disorders, Vol. 30, Suppl. 1, 2015
S512 POSTER SESSION

edge is important to avoid misdiagnosis and make an appropriate

differential diagnosis with facial tics, blepharospasm, cranial dystonia
and other facial dyskinesias.

Fig. 2. (1315).
effects. Only one patient refused treatment (Table 2). [figure1]
[figure2]
Conclusions: Bilateral HFS in our study shows a very low fre-
quency, similar to that reported by other researchers, but their knowl-
1316
Mutations in ANO3 and GNAL gene in thirty-three isolated
dystonia families
L. Ma, L. Wang, Y. Yang, T. Feng, X. Wan (Beijing, Peoples
Republic of China)
Objective: To determine the frequency and spectrum of ANO3/
GNAL mutations in familial isolated dystonia patients in China using
direct sequencing.
Background: Dystonia is an involuntary Movement Disorder.
With the use of whole-exome sequencing and linkage analyses,
mutations in ANO3 and GNAL gene have recently been found to be

Fig. 1. (1316).

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION S513

the cause of isolated dystonia with predominantly craniocervical TABLE 1. Demographics of subjects
involvement.
Methods: We ascertained thirty-three pedigrees of Chinese origin Patients No.
with isolated dystonia (affected number n5118, 53 focal, 7 segmen-
tal, 1 generalized, 57 dystonic tremor) and performed mutational Total no. 214
screening of ANO3/GNAL in the 33 probands by direct Sanger Mean age at onset(years, SD) 33.9 6 12.7 (5-66)
sequencing. All probands were negative for mutations in TOR1A, Male (n, %) 79 (36.9%)
THAP1 and CIZ1. Female (n, %) 135 (63.1%)
Results: A heterozygous missense substitution, c.2540A>G Family history (n, %) 12 (5.6%)
(p.Y847C), was identified in the probands of Family N and R. This Clinical phenotype by sites involved
substitution, resulting in a change from tyrosine to cysteine at posi- Focal (n, %) 167 (78.0%)
tion 847 of the protein [figure1](A), was not found in 100 healthy Segmental (n, %) 18 (8.4%)
controls or reported in the publicly available databases of the public Multifocal (n, %) 12 (5.6%)
single-nucleotide polymorphism (SNP) (www.ncbi.nlm.nih.gov/proj- Generalized (n, %) 17 (7.9%)
ects/SNP/), Exac (http://exac.broadinstitute.org/) or National Heart,
Lung, and Blood Institute exome sequencing project (NHLBI-ESP,
http://evs.gs.washington.edu/EVS/). It affected amino acid that was Background: Dystonia is an involuntary Movement Disorder and
highly conserved between species [figure1(B)] and was predicted to its pathogenesis is not completely understood. With the use of
be deleterious by MutationTaster, SIFT, and PolyPhen-2. This muta- whole-exome sequencing, mutations in GNAL gene have recently
tion was also found in two affected brothers (III-3 and III-5) in Fam- been found to be the cause of isolated dystonia. Previous study
ily N, while unaffected individuals (III-7,8) were homozygous for screening 59 Chinese isolated dystonia cases identified one patho-
the normal allele. The phenotypes of patients with Y847C mutation genic mutation (c.284C>T) in GNAL.
are shown in [figure1(C)]. No variants were found in GNAL gene. Methods: We recruited a large cohort of 214 patients of Chinese
Conclusions: We identified one missense mutation in the ANO3 origin (79 men, 135 women, M:F 1:1.7, mean age at onset of
gene, c.2540A>G (p.Y847C), in 2 of 33 isolated dystonia pedigrees. 33.9 6 12.7years (5-66)) with various forms of dystonia, including
The mutation frequency of ANO3 gene in familial dystonia patients 12 familial cases. Of these, 167 had focal dystonia (133 torticollis,
is 6.1% (2/33) in China. 30 cranial, 2 writers cramp, 2 spasmodic dysphonia), 18 had segmen-
tal dystonia, 12 had multifocal dystonia and 17 had general dystonia.
Mutational screening of GNAL was performed by direct
sequence. All patients were negative for TOR1A and THAP1. Con-
1317 trol DNA samples were obtained from 100 Chinese unrelated healthy
Mutations in GNAL gene in 214 cases with isolated dystonia individuals.
Results: We identified 11 variants in the 12 exons and 5UTR
L. Ma, L. Wang, Y. Yang, T. Feng, X. Wan (Beijing, Peoples
region of GNAL: c.-37A>G, c.-41T>C, c.-111C>T, c.-116A>G, c.-
Republic of China)
142G>C, c.-485T>C, c.15C>T (p.G5=), c.30G>T (p.T10=),
Objective: To determine the frequency and spectrum of GNAL c.44G>A (p.G15D), c.1059C>T (p.A353=) and c.360C>T (p.S120=)
mutations in familial and sporadic isolated dystonia patients of Chi- (see [figure1]for details of variants and clinical presentation). Among
nese origin. these, c.-111C>T (rs61495657), c.-41T>]C (rs9303742), c.-37A>G

Fig. 1. (1317).

Movement Disorders, Vol. 30, Suppl. 1, 2015

S514 POSTER SESSION
(rs200432196), c.360C>T (p.S120=, rs76888098), c.30G>T (p.T10=,
rs78167172) and c.44G>A (p.G15D, rs199761315) were found in
dbSNP database. In silico analyses (Mutation Taster) revealed that
c.44G>A most likely affects the protein feature and splice site whereas
SIFT and Polyfhen-2 define it as benign, thus a potential pathogenic
impact of this variant cannot be excluded. c.15C>T (p.G5=), c.30G>T
(p.T10=), c.1059C>T (p.A353=) and c.360C>T (p.S120=) were syn-
onymous mutations and protein were not changed. These variants were
not detected in healthy controls. Counting 214 cases with previous Chi-
nese study (59 cases) together, the prevalence of GNAL mutations in
Chinese dystonia patients is 0.37% (1/273).
Conclusions: We did not identify clearly pathogenic mutations in
GNAL gene in 214 Chinese patients. Mutations in the GNAL gene
may not be a common cause of isolated dystonia, at least in Chinese
population.
1318
FMRI during standardized sensory stimulation reveals
overactivity and topographic changes in the somatosensory
system in patients with embouchure dystonia
T.A. Mantel, C. Dresel, E. Altenm
uller, C. Zimmer, B. Haslinger
(Munchen, Germany)
Objective: To investigate activity changes in pimary and particu-
larly also nonprimary centers of somatosensory processing in embou-
chure dystonia (ED) and to directly relate these to changes in
topographic representations.
Background: The focal task-specific ED presents with a loss of
fine motor control in orofacial muscles of professional brass musi-
cians during play. Sensory system dysfunction seems to be of partic-
ular importance in task-specific musicians dystonias, and previous
studies in ED have suggested impairment of sensorimotor integration
and primary somatosensory organization.
Methods: We used functional MRI with automized
monofilament-mediated tactile stimulation of dystonic (upper lip) and
nondystonic body regions (forehead, dorsal hand) on either side in
both 15 brass players with and without ED. Central activity changes
were investigated in a whole-brain quantitative analysis, topographic
changes in a region of interest based analysis of local peak max-
ima and extent of activation in the primary and secondary somato-
sensory cortex, thalamus and cerebellum.
Results: Musicians with ED showed significantly increased activ-
ity during stimulation of dystonic body regions (right primary, bilat-
eral secondary somatosensory cortex, left cerebellum) as well as
when stimulating nondystonic body parts (left primary, bilateral sec-
ondary somatosensory cortex). Topographic analysis revealed
changes of somatotopic organization in the right primary, bilateral
secondary somatosensory cortex and the left cerebellum. These mani-
fested in altered intracortical distances, as well as in shifts of central
representations, the latter interestingly in nondystonic body regions.
Especially for facial stimulation there was a reduced positional vari-
ability of representations of dystonic and nondystonic body regions
in patients with ED.
Conclusions: Our results show aberrant processing of somatosen-
sory input in ED. This could be based on dysfunctional central inhi-
bition with primary and/or adaptive plastic changes. The
involvement of representations of both dystonic and nondystonic
areas suggests an existing subclinical predisposition. Changes in cer-
ebellar activation point to an important cerebellar role in impaired
sensory processing.
1319
A functional magnetic imaging study of the response in the
superior colliculus to looming stimuli in cervical dystonia
patients and their relatives
E.M. Mc Govern, J.S. Butler, S. Narasimham, L.J. Williams, I.
Beiser, R.B. Reilly, S. ORiordan, M. Hutchinson (Dublin, Ireland)
Movement Disorders, Vol. 30, Suppl. 1, 2015
Objective: To demonstrate the functional magnetic resonance
imaging response to looming stimuli in the superior colliculus of cer-
vical dystonia patients and their relatives with and without abnormal
temporal discrimination thresholds.
Background: Adult onset idiopathic focal dystonia (AOIFD) is
the third most common Movement Disorder and cervical dystonia
(CD) is the most common phenotype of AOIFD. Temporal discrimi-
nation threshold (TDT) detects the point at which an individual
determines two stimuli to be asynchronous (normal 5 30 - 50 ms). A
majority of patients with CD (97%) and a proportion of their unaf-
fected relatives have abnormal TDT results. We hypothesize that an
abnormal TDT and CD are due to a disorder of the mid-brain net-
work for covert attentional orientating caused by reduced GABA
inhibition. This inhibition manifests sub clinically as an abnormal
TDT due to prolonged firing of the visual sensory neurons in the
superficial layer of the superior colliculus and clinically as CD due
to excess cephalomotor neuronal activity in the deep layer of the
superior colliculus. Looming visual stimuli (as opposed to receding
stimuli) activate both superior colliculi. We predict patients with CD
and their unaffected relatives with abnormal TDTs will demonstrate
reduced activation within the SC during looming stimuli.
Methods: We aim to examine by 3 tesla fMRI the responses
within the SC to looming, receding and random stimuli in partici-
pants (16 CD patients, 16 unaffected first degree relatives with
abnormal TDTs, 16 healthy first degree relatives with normal TDTs
and 16 healthy controls with normal TDTs). All participants will be
age and sex matched.
Results: We will present provisional fMRI data from a subset of
participants in order to illustrate activation of the superior colliculus
during looming stimuli with failure of activation during receding and
random stimuli.
Conclusions: In this study we aim to demonstrate that an abnor-
mal TDT indicates disordered processing within the SC and thus fur-
ther our understanding into the pathogenesis of CD.References.
1320
Hikers cramp: A rare adult-onset isolated focal dystonia due to
overuse
E.M. Mc Govern, L.J. Williams, I. Beiser, M. Hutchinson, S. O
Riordan (Dublin, Ireland)
Objective: To report a case of adult-onset, focal, lower extremity
dystonia associated with a long history of persistent, excessive
hiking.
Background: Adult-onset focal dystonia of the lower limb is rare
(0.7% of all adult-onset dystonia). Adult-onset focal lower extremity
dystonia associated with repetitive & excessive exercise is an uncom-
mon subset of this clinical phenotype.
Methods: A 70-year-old, right-handed woman presented with a
three-year history of walking difficulties. Her left foot assumed an
abnormal posture (inversion, plantar flexion and toe flexion) on gait
initiation. Symptoms began two months after climbing to Mount
Everest Base Camp for the third time. Symptoms were action-
induced, confined to the left foot and triggered only by walking for-
ward. They were relieved by rest and were not provoked by walking
backwards, dancing or cycling. Orthopedic assessment was sought
prior to neurology review; surgery was performed on the left toes.
She had been a keen hiker and climber for more than 20 years (esti-
mated cumulative hiking distance 7,800 miles). Examination revealed
left foot inversion and toe flexion on initiation of gait. Abnormal left
foot posturing increased with each successive step (see video).
Symptoms diminished on walking backwards. The remainder of the
neurological examination was normal.
Results: Magnetic resonance imaging of the brain & spine and
nerve conduction studies of the left lower limb were normal. Trials
of botulinum toxin & L-dopa were not helpful. Further botulinum
toxin injections are planned.
 POSTER SESSION
Conclusions: We report the rare clinical phenomenon of adult-
onset, focal, lower extremity dystonia associated in this case with a
history of persistent and excessive hiking. The exact etiology is
incompletely understood but it probably results from a combination
of environmental (excessive use) and genetic factors.
1321
Ultrasound in the treatment of levator scapulae muscle in
cervical dystonia with botulinum neurotoxin A: A randomized
trial
J.P. Michelis, J.R. Bedarf, S. Paus (Bonn, Germany)
Objective: To investigate if ultrasound-guided injections (UGI)
of botulinum neurotoxin A (BoNT) of the levator scapulae muscle
(LSM) improve treatment outcome compared to conventional injec-
tions using anatomical landmarks in cervical dystonia (CD). Interin-
dividual comparability of treatment effects in CD is limited due to
complex movement patterns and involvement of several head and
neck muscles. As such, common rating scales for CD depict global
effects only, which might miss minor interventional benefits. To
avoid these limitations, we aim to examine the effects of UGI in CD
for each muscle individually, beginning with LSM.
Background: UGI of BoNT improves symptoms in patients with
spasticity compared to manual needle placement. The value of UGI
in treating CD is not clarified and there is a lack of systematic stud-
ies (1). In the sternocleidomastoideus muscle, UGI reduced dyspha-
gia compared to EMG guiding injection. Another study was
discontinued due to a lesser reduction of dystonic muscle activity in
patients treated with UGI.
Methods: Patients with idiopathic CD, pre-treatment with BoNT,
stable effect of therapy, and involvement of LSM were included.
Patients were randomized to be treated with UGI (n520) or with
sham ultrasonography and use of anatomical landmarks (n520).
BoNT doses were unchanged compared to previous injections. At
baseline, four and twelve weeks after treatment, patients were eval-
uated by an independent examiner, who was blinded to the injection
method. To monitor treatment effects, the TWSTRS (including sub-
scales) was used.
Results: Preliminary data show a tendency of benefit of UGI
treatment of LSM in CD, which was not statistically significant.
Conclusions: The use of UGI tends to improve BoNT treatment
of LSM in CD. In contrast to a previous study on UGI in CD, no
disadvantageous effects became apparent. The lack of statistical sig-
nificance could be due to the small sample size. Also, subgroup anal-
ysis might reveal factors which predict a benefit of UGI. Although
further investigations with larger sample size are required, our study
supports the recommendations for implementing UGI in CD, also
suggested in a recent publication (1). The investigation of UGI in
other muscles in CD are in preparation.
1) Schramm A et al. Relevance of sonography for botulinum
toxin treatment of cervical dystonia: an expert statement. 2014, J
Neural Transm. 2014 Dec 30
1322
Clinical characteristics of cervical dystonia patients presenting
for treatment with abobotulinum toxin A: A meta-analysis
comparing data from the US and Europe
V.P. Misra, R. Trosch, S. Om, P. Maisonobe (London, United
Kingdom)
Objective: To characterize the clinical characteristics (baseline
TWSTRS scores) of patients with cervical dystonia (CD) in the US
and Europe.
Background: The diagnosis of CD is derived based on clinical
findings alone; adjunctive imaging and laboratory measures may be
utilized to define an etiology, but cannot establish a diagnosis. The
Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) has
S515
been employed to quantify the severity and functional impact of CD
in randomized clinical trials and as a tool in clinical practice in the
US and Europe.
Methods: A meta-analysis was conducted on the baseline data
from 2 observational international studies (INTEREST IN CD1 & 2)
and 1 US registry (ANCHOR-CD). INTEREST IN CD2 is an
ongoing study; data from a pre-planned interim analysis were used.
Presented here are baseline data from patients who were treated with
Abobotulinum toxin A prior to study entry and returned for next
injection.
Results: Data are reported for the overall population (n5365),
the US population (n596) and the Europe population (n5249); 20
patients were treated in the rest of world (not shown). In general, US
patients being treated with ABO had slightly less severe disease, but
slightly more pain than those in Europe. Mean 6SD TWSTRS
scores are shown in Table 1.
Baseline TWSTRS scores in previously treated CD patients pre-
senting for routine treatment with ABO
Overall US (n596) Europe
(n5365) (n5249)
mean 6 SD mean 6 SD mean 6 SD
Total TWSTRS 34.5 6 10.9 32.8 6 11.5 34.6 6 10.5
TWSTRS severity 18.2 6 4.6 16.5 6 4.5 18.6 6 4.5
TWSTRS disability 9.8 6 5.6 8.9 6 6.1 9.9 6 5.3
TWSTRS pain 6.5 6 4.8 7.5 6 4.8 6.1 6 4.6
Conclusions: There appears to be subtle variations in patient pre-
sentation between the US and Europe.
1323
Which are the most frequently injected muscles in cervical
dystonia? An interim analysis of data from the INTEREST IN
CD2 observational study
V.P. Misra, C. Colosimo, D. Charles, P. Maisonobe, S. Om (London,
United Kingdom)
Objective: To characterize the evolution of botulinum neurotoxin
type A (BoNT-A) injection patterns used in the treatment of cervical
dystonia (CD).
Background: Appropriate muscle selection is key to the effec-
tiveness of BoNT-A injections for CD. Observational studies can
provide insights into how injectors use BoNT-A in routine practice
and if it becomes necessary to change injection patterns over
repeated treatments.
Methods: INTEREST IN CD2 is an ongoing 3-year study follow-
ing the course of adult idiopathic CD treated with BoNT-A. Subjects
undergo a comprehensive CD assessment at baseline/first injection
visit, at each injection visit and study end according to investigators
usual practice. A preplanned interim analysis was conducted in sub-
jects with complete data at Visit 1 (baseline) & Visit 2 (time of sec-
ond injection).
Results: As of June 2014, 239 subjects had complete data for
Visits 1 and 2. The median time since diagnosis was 6.0 (range: 0-
49) years, and between Visits 1 and Visit 2 was 3.7 months. Twenty-
one muscles were selected for injection at Visit 1; of these the 5
most commonly injected were splenius capitis (93% of patients),
sternocleidomastoid (SCM) (91%), trapezius (63%), levator scapulae
(42%), and the semispinalis capitis (27%). Other muscles were
injected with a frequency between 0.46%. The mean total injected
volumes were 1.05 61.16 mL for splenius capitis, 0.68 60.78 mL
for SCM, 0.67 60.58 mL for trapezius, 0.42 60.26 mL for levator
scapulae and 0.56 60.33 mL for semispinalis capitis. Mean number
of injection points were: splenius capitis (2.7 61.5), SCM (2.2
61.2), trapezius (2.7 61.6), levator scapulae (1.5 60.7), and
Movement Disorders, Vol. 30, Suppl. 1, 2015
S516 POSTER SESSION
semispinalis capitis (2.0 61.3). At Visit 2 the frequency of muscle
injected, the injected volume, and injection points were very similar
to Visit 1. Injection guidance techniques were used in 37% (SCM) to
57% of baseline injections (levator scapulae), and this did not change
at Visit 2. Analyses by study center revealed that when an injector
uses guidance for one muscle, they generally use it for all muscles.
Conclusions: In these interim analyses, 5 muscles were identified
as being most frequently injected for CD, with other muscles being
injected at much lower rates. The muscles and injection method (vol-
ume and number of injection points) are in line with recommenda-
tions in the literature and did not change between visits.
1324
Cervical dystonia and work productivity: Results from the
cervical dystonia patient registry for the observation of
onabotulinumtoxinA efficacy
E.S. Molho, M. Stacy, P. Gillard, D. Charles, C.H. Adler, J.
Jankovic, M. Schwartz, M.F. Brin (Albany, NY, USA)
Objective: This analysis examines the impact of CD on work
productivity and employment as well as the influence of onabotuli-
numtoxinA treatment on these parameters.
Background: Data on the disease burden of cervical dystonia
(CD) are limited. The CD Patient Registry for the Observation of
OnabotulinumtoxinA Efficacy (CD PROBE) is the largest registry to
examine the characteristics of CD in a real-world setting.
Methods: CD PROBE is an observational, multicenter, prospec-
tive, standard-of-care, clinical registry of subjects with CD who
received up to 3 treatments of onabotulinumtoxinA (ClinicalTrials.-
gov NCT00836017; Jankovic, et al. BMC Neurol 2011;11:140). Sub-
jects were botulinum toxin (BoNT)-nave, new to physicians
practice, or had a previous BoNT treatment of 16 weeks in another
clinical trial. Work productivity and employment status were
assessed at baseline and final visit via subject questionnaire. Baseline
presence of pain, disease severity and subtype, previous exposure to
BoNT, and/or utility of a sensory trick were used to assess the
impact on employment. Results of work productivity assessments
were compared at baseline and final visit in BoNT-nave subjects
who received 3 onabotulinumtoxinA treatments.
Results: The analysis population included 1038 subjects; 42.8%
were employed, 6.1% unemployed, 32.7% retired, and 11.8% dis-
abled. Of the employed subjects, CD affected the work status of
26.0%, resulted in 29.8% missing work in the past month (mean
5.16 6.4 days), and decreased work productivity in 57.8%. At symp-
tom onset, 49.9% of unemployed subjects had been employed, and
38.5% of those patients attributed lost employment to CD. Work sta-
tus/productivity was most affected by pain, anterocollis/retrocollis,
and increasing disease severity. Absenteeism (work missed due to
health problems) and presenteeism (impairment while working due
to health problems) were significantly decreased following onabotuli-
numtoxinA treatment in subjects BoNT-nave at baseline.
Conclusions: These analyses suggest that employment is nega-
tively impacted by CD, with CD-associated pain, disease severity,
and CD subtype as important drivers. OnabotulinumtoxinA treatment
is associated with improved work productivity in CD.
1325
Sun exposure is an environmental factor for the development of
blepharospasm
A. Molloy, L. Williams, O. Kimmich, J. Butler, I. Beiser, E.
McGovern, S. ORiordan, R.B. Reilly, C. Walsh, M. Hutchinson
(Dublin, Ireland)
Objective: To investigate sunlight as a possible factor in dystonia
phenotype expression.
Background: Adult-onset isolated focal dystonia may present
with various phenotypes including blepharospasm and cervical dysto-
Movement Disorders, Vol. 30, Suppl. 1, 2015
nia. Although inherited in an autosomal dominant manner with a
markedly reduced penetrance, environmental factors are considered
important in both disease penetrance and expression. We observed
marked variation by latitude in the reports of the frequency of
patients with blepharospasm relative to those with cervical dystonia;
we hypothesised that sun exposure is an environmental risk factor
for the development of blepharospasm in genetically susceptible
individuals.
Methods: From published clinic cohorts and epidemiological
reports, the ratio of the number of cases of blepharospasm tocervical
dystonia (phenotype case ratio) at each study site was analysed with
regard to latitude and measures of annual insolation. Meta-regression
analyses of the phenotype case ratio to these environmental factors
were performed.
Results: The phenotype case ratio in 15 eligible study sites over
41 degrees of latitude demonstrated a statistically significant inverse
association with latitude (p50.0004, R2 5 53.5%). There were signif-
icant positive associations between the phenotype case ratio and
quarter-one (January- March) insolation (p5 0.0005, R2 5 53%) and
average annual insolation (p5 0.003, R2 5 40%).
Conclusions: The increase in the blepharospasm: cervical dysto-
nia case ratio with decreasing latitude and increasing insolation sug-
gests that sunlight exposure is an environmental risk factor for the
development of blepharospasm (rather than cervical dystonia) in
individuals genetically susceptible to adult-onset dystonia.
1326
Relationships among reproductive health variables and cervical
dystonia
C.C. Nazor, M.M. Thompson, M.S. LeDoux (Memphis, TN, USA)
Objective: To evaluate the relationships among reproductive
health factors and cervical dystonia (CD) using an online
questionnaire.
Background: CD, or spasmodic torticollis, most commonly
affects middle-aged Caucasian females. Genetic studies suggest that
cervical and other forms of adult-onset cranio-cervical dystonia may
be due to dysfunction at the G1/S checkpoint of the cell cycle which
is regulated, in part, by hormonal factors. Our study aims to expand
upon previous work which has suggested that hormonal status and
reproductive factors may contribute to the risk of developing CD.
Methods: Data was gathered via an anonymous 33-item web-
based survey which included questions regarding personal history of
CD and reproductive health history. Subjects were recruited via web-
site postings, email communications, and periodicals published by
foundations dedicated to the support of individuals with dystonia.
Results: As of December 2014, a total of 390 individuals
responded to the survey. Of this total, 102 were females diagnosed
with isolated CD. This sample of females with isolated CD was 93%
Caucasian and 67.4% were post-menopausal (60.9% natural and
30.4% surgical) with mean age at the time of survey completion of
55.0 6 12.0 yrs and mean age-of-onset of 39.8 6 14.8 yrs. Mean age
at menopause, regardless of cause, was 46.8 6 7.8 yrs. Two-thirds
(66.7%) of women admitted to having used some form of hormonal
therapy during their lives, with 27.9% reporting greater than 10
years duration of usage prior to age 40. The majority of women
(54.5%) observed no clear effect of hormonal therapy on the severity
of their CD, whereas 10.3% felt that hormonal therapy improved
their signs and symptoms. Most (56.8%) women could not draw an
association between their menstrual cycles and dystonia symptoms.
Conclusions: Our data suggests that long-term use of hormonal
therapy may be relatively common amongst women who ultimately
develop CD. In addition, females with isolated CD may have higher
rates of hysterectomy than population norms. Larger studies which
delve into the specific types of hormonal therapies used, the reasons
behind their use, and the specific indications for hysterectomy may
help to establish whether or not gynecological disorders and
 POSTER SESSION
hormonal dysfunction are truly more common amongst those affected
by CD, and if hormonal status contributes to risk of developing CD.
1327
Clinical profile of writers cramp patients
S. Pandey, N. Sarma, G. Soni (New Delhi, India)
Objective: We present our experience of 19 patients with writers
cramp patients, their clinical profile and their response to electromy-
ography (EMG) guided Botulinum toxin injection. There is no report
of EMG guided botulinum toxin injection in writers cramp patients
from India to the best of our knowledge.
Background: Writers cramp is a type of task specific focal hand
dystonia. It usually presents as sporadic or as an initial manifestation
of segmental or generalized dystonia. Uses of Botulinum toxin has
significantly improved the treatment of focal dystonia patients
including Writers cramp. Out of 23 hand muscles individual patients
have specific muscle involvement making the disease challenging to
diagnose and treat.
Methods: We reviewed 19 patients of writers cramp that pre-
sented to the Neurology OPD of a tertiary care teaching institute
over a period of 12 months. Patients were assessed and the diagnosis
was made on clinical grounds. Electromyography guided Botulinum
toxin injection was given to patients after getting their consent, while
others were placed on oral medications.
Results: Our study group had 17 males and 2 females with a
mean age of 40.10 years. All patients were right handed except one.
The duration of symptoms varied from 5 months to 4 years. Two
patient had concomitant cervical dystonia and three had dystonic
tremor. Eleven patients had flexor type, 3 had extensor type and 5
had mixed type of writers cramp. Mirror dystonia was present in 12
patients. Ten out of nineteen patients were injected with type A bot-
ulinum toxin with mean dosage of 49.6 U. The flexor digitorum
superficialis was the most common muscle injected followed by
extensor carpi ulnaris. Beneficial effects appeared in most patients
within 2 weeks of injection. Two of those patients developed hand
weakness after injection.
Conclusions: Writers cramp is a commoner variant of focal
hand dystonia causing significant disability in patients, however it
portrays a good response to injection botulinum toxin. Mirror dysto-
nia is helpful in muscle localization. Electromyography guided injec-
tion leads to better muscle localization and less incidence of post
injection weakness.
References:
1. Karp BI. Botulinum toxin treatment of occupational and focal
hand dystonia.Mov Disord. 2004 Mar;19 Suppl 8:S116-9.
2. Zeuner KE, Peller M, Knutzen A, Holler I, M unchau A, Hallett
M, Deuschl G, Siebner HR. How to assess motor impairment in writ-
ers cramp. Mov Disord. 2007 Jun 15;22(8):1102-9.
1328
First report of two brothers with Panay ancestry with Mohr-
Traenbjaerg syndrome
J.M.G. Penamora-Destriza, R.L. Rosales, A. Domingo, C. Klein
(Quezon City, Philippines)
Objective: To present a case of two Filipino brothers with Panay
ancestry with Mohr-Traenbjaerg Syndrome.
Background: Dystonia syndromes have a remarkable degree of
phenotypic variability with frequent overlap among different syn-
dromes. Among the inherited dystonia syndromes, two X-linked
recessive syndromes are are of notable interest: the Sex-linked Dys-
tonia Parkinsonism (XDP, DYT3, Lubag) and the Mohr-Traenbjaerg
Syndrome (MTS, or Deafness-dystonia-optic neuronopathy, DDON).
XDP is endemic in the Panay Islands, Philippines, while MTS is a
rarer condition, and has not been documented among Filipinos
before. Both conditions present with dystonia, but additional neuro-
S517
logic manifestations such as deafness, optic atrophy, and cognitive
decline are seen in MTS patients.
Methods: We report for the first time 2 Filipino brothers with
ancestors from Capiz who presented with dystonia, along with deaf-
ness and other neurologic features of MTS. Diagnosis was supported
by genetic testing.
Conclusions: Identification of these patients would give way to
early and regular surveillance, and to opportunities in research.
1329
A literature review of possible environmental factors in the
pathogenesis of dystonia
D.A. Peterson, T.J. Sejnowski (La Jolla, CA, USA)
Objective: The objective of this study was to summarize evi-
dence for environmental factors in the pathogenesis of dystonia.
Background: There is evidence for genetic factors in the etiology
of an increasing proportion of the dystonias. However with rare
exceptions the genetically-identified forms exhibit reduced pene-
trance. Although multi-genic interactions not yet discovered cannot
be ruled out, environmental factors are also likely to play a role.
Methods: We have previously hypothesized that a category of
environmental factors under the umbrella of behavioral use pat-
terns play a synergistic role with subtle abnormalities in striatal syn-
aptic plasticity to induce abnormal functional basal ganglia circuitry
in dystonia (Peterson et al. 2010 Neurobiol Dis). In this study we
conducted a PubMed literature review of environmental factors in
dystonia.
Results: We found over 30 journal publications describing envi-
ronmental factors in dystonia. As expected, most fall under the cate-
gory of use-dependence, including the traditionally labeled task-
specific dystonias, dystonias secondary to peripheral injury, and
childhood onset dystonias in which developmental periods of motor
learning may also play a role.
Conclusions: Broadly defined, motor use patterns may be a
prominent pathogenic factor that unifies many of the disparate forms
of dystonia. Although prospective studies to investigate this factor
should be conducted, more practically viable retrospective studies
may begin to offer clues about how and when use factors trigger
dystonia onset.
1330
Baseline characteristics and health-related quality of life in
patients treated with onabotulinumtoxinA for cervical dystonia
in a multicentre, prospective, observational study: POSTURe
M. Petitclerc, S. Dhani, M. Bhogal, L. Belle Blagrove (Saint-
Romuald, QC, Canada)
Objective: To describe baseline patient demographics, clinical
characteristics, and health-related quality of life (HRQoL) in cervical
dystonia (CD) patients treated with onabotulinumtoxinA (onabotA)
in Canada.
Background: Although onabotA has been approved for CD in
Canada since 1995, limited data is available describing the benefit of
treatment on patients HRQoL.
Methods: This is a multicenter, prospective, observational study
in CD patients initiating treatment with onabotA (NCT01655862).
Treatments will be administered at the physicians discretion (up to
9 treatments). HRQoL data (ie, pain numeric rating scale [PNRS]
and cervical dystonia impact profile questionnaire [CDIP-58]) is the
primary outcome measure, collected at baseline, at 4 or 8 weeks
post-treatment, and prior to final treatment. Secondary measures
include work productivity. Demographics and clinical characteristics
were collected at baseline.
Results: A total of 54 patients with a mean age of 57 years
(SD=12) are enrolled; majority are female (74%) and primarily
employed full-time (44%) or retired (28%). Overall, 98% of the
Movement Disorders, Vol. 30, Suppl. 1, 2015
S518 POSTER SESSION
patients had been employed at some time. Of those currently
employed, 21% found that CD affected their employment status,
45% experienced a decrease in their work productivity, and 13% had
to stop working. On average, patients were 47 years old (SD=12) at
symptom onset and diagnosed with CD an average 8 years (SD=9)
later. Treatment with onabotA occurred an average 11 years (SD=9)
after symptom onset. The majority of patients presented with CD
that was rated mild (43%) or moderate (50%) in severity and classi-
fied as torticollis (70%) and/or laterocollis (39%). At baseline, the
average PNRS score was 4.6 (SD=3.2) and mean CDIP-58 score for
the pain and discomfort subscale was 58.0 (SE=27.0). Mean baseline
CDIP-58 conceptual domain scores were 59.0 (SD=20.3) for symp-
toms, 40.5 (SD=22) for daily activities, and 53.1 (SD=18.6) for psy-
chosocial sequelae.
Conclusions: Patient demographics, disease characteristics, and
baseline HRQoL data are consistent with previously published data
on typical CD patient populations. Results from this study further
emphasize the impact of CD on patients lives and will bring added
awareness on the effect proper treatment can have on HRQoL.
1331
A case of severe dystonia secondary to pediatric hemolytic
uremic syndrome
T. Pham (Portland, OR, USA)
Objective: Describe a case of severe dystonia in a pediatric case
of hemolytic uremic syndrome.
Background: Hemolytic Uremic Syndrome (HUS) is a clinical
syndrome that includes microangiopathic hemolytic anemia, throm-
bocytopenia and acute kidney injury. The incidence of HUS is 2-3
per 100,000 in children less than five years of age. Neurologic seque-
lae have been described in 7-25% of cases of HUS including seiz-
ures, coma, hypertonia, hemiparesis, cortical blindness, and dystonia
(Remuzzi, Giuseppe, and Piero Ruggenenti. The Hemolytic Uremic
Syndrome. Kidney International 48.1 (1995): 2-19).
Methods: A single case report.
Results: VW was a previously healthy, developmentally nor-
mal, 20-month-old girl who initially presented with bloody stools.
She was later found to have E. Coli 0157 positive hemolytic uremic
syndrome. Her clinical course was complicated by renal failure
requiring hemodialysis, profound thrombocytopenia and hemolytic
Fig. 1. (1331).
Movement Disorders, Vol. 30, Suppl. 1, 2015
normocytic anemia requiring blood product transfusions, as well as
bilateral basal ganglia and deep white matter ischemic infarcts. [fig-
ure1]Her cerebral infarcts resulted in severe generalized dystonic
posturing primarily in her left arm and leg, but also present on her
right side. Other symptoms included bruxism, dysautonomia, as well
as concern for cortical blindness. She was initially treated with
baclofen with minimal symptomatic benefit and then transitioned to
triphexyphenidyl, which greatly improved her dystonia, hypertonicity
and overall comfort. Once started on trihexyphenidyl, the patient was
able to start working with physical and occupational therapy and
eventually transition to inpatient rehabilitation.
Conclusions: HUS is an uncommon syndrome that can result in
significant neurologic injury including severe dystonia, epilepsy,
coma, ischemic infarcts, and visual deficits. The mechanism of neu-
rologic injury is hypothesized to be due to a combination of hyper-
tension, hyponatremia, local microangiopathy, and
neuroinflammation through massive cytokine release. (Nathanson, S.,
T. Kwon, et al. Acute Neurological Involvement in Diarrhea-
Associated Hemolytic Uremic Syndrome. Clinical Journal of the
American Society of Nephrology 5.7 (2010): 1218-228.) Our case
demonstrates a patient with a rare case of severe generalized dysto-
nia from HUS that responded to trihexyphenidyl.
1332
Whole exome sequencing in a case of rapidly progressive
generalized dystonia with Parkinsonian features
T.T. Pham (Portland, OR, USA)
Objective: Describe a case of rapidly progressive generalized
dystonia with Parkinsonian features and results of whole exome
sequencing.
Background: SY is a 30-year-old woman with history of devel-
opmental delay, mood disorder and traumatic brain injury who
presents with 2 years of progressive dystonia with Parkinsonian
symptoms. Her symptoms began with a bilateral upper extremity
action tremor, chin and tongue tremor. Over the next year, the
patient continued to decline and then developed increased tone and
dystonic posturing of all four extremities. She had an extensive eval-
uation as outlined below. She was trialed on carbidopa-levodopa 25/
100 3 tablets 3 times daily and high dose IV steroids without signifi-
cant response. She also underwent upper limb botulinum toxin a
injections and was given scheduled trihexyphenidyl and diazepam
for her dystonia. Eventually the patients family transitioned her to
hospice care.
Methods: Case report.
Patient Video.
Results: Evaluation included (all with unremarkable results):
MRI brain; serum for copper, TPO antibody, thyroid stimulating
immunoglobulin, anti GAD, ammonia, ceruloplasmin, CK, SSA,
SSB, centromere antibody, Jo antibody, and SCL-70 antibody. CSF
for cell count, gram stain, oligoclonal bands, flow cytometry, cytol-
ogy, HSV 1/2 PCR, bacterial culture, and CJD 14-3-3 protein nor-
mal. Abnormal testing: slightly elevated calcium channel binding
antibody P/Q type on serum paraneoplastic panel and whole exome
sequencing with deleterious heterozygous SHANK3 gene mutation
and heterozygous GCH1 variant.
Conclusions: Deleterious SHANK3 mutations are responsible for
an autosomal dominant condition called Phelan-McDermid syn-
drome, which can present with global developmental delay, neonatal
hypotonia, and autistic behavior. Defects in the GCH1 gene cause an
autosomal dominant GTP cyclohydrolase 1 deficient dopa responsive
dystonia, typically with childhood onset (average age of 6). Initial
symptoms usually include foot dystonia causing gait difficulties,
diurnal fluctuation of symptoms and Parkinsonism, with the dystonia
dramatically responsive to dopamine. Although the SHANK3 muta-
tion may explain some of the patients developmental delay, neither
of the discovered mutation clearly explains the patients clinical
 POSTER SESSION
decline. One of the major limitations of whole exome sequencing
remains our ability to clinically interpret the results.
1333
Molecular investigation in dystonia: A new THAP1 mutation and
the questionable role of a polymorphism in the TOR1A gene
L.G. Piovesana, F.R. Torres, P.C. Azevedo, T.P. Amaral, M.M.V.
Rosa, M.C. Franca, Jr., I. Lopes-Cendes, A. DAbreu (Campinas,
Brazil)
Objective: Our goal was to characterize patients with inherited
and isolated dystonia in the Brazilian population and search for the
presence of the mutations responsible for DYT1 and DYT6.
Background: Dystonia is a hyperkinetic disorder characterized
by sustained or intermittent muscle contractions that cause repetitive
movements and/or abnormal postures. There are a few reports of the
DYT1/TOR1A and the THAP1gene mutations in the Brazilian popu-
lation and there seems to be a different prevalence of dystonia
caused by those mutations in Brazil.
Methods: We recruited 78 subjects at the Movement Disorders
and Dystonia Outpatient Clinics. Patients were assessed by a standar-
dized questionnaire, followed by molecular testing for DYT1 and
DYT6.
Results: Our cohort showed similar results with the literature,
where young, generalized and positive family history commonly
group together, as well as focal and segmental cases tend to appear
in adulthood with progression to contiguous sites. All subjects were
negative for the GAG-del mutation. We found a missense mutation
(rs1801968 C> G/D216H) described in SNPs databases (ensemble
genome browser). It was present in 14 of our patients. There was no
significant difference in gender, family history, age of onset, loca-
tion, distribution and progression in those with the mutation com-
pared to those without. Of note, one of those 14 subjects had a
sister, with a very similar dystonia syndrome, that did not present
the mutation. Sequencing of the DYT6 gene showed a novel 10bp
deletion at the end of exon 1, causing alternate splicing and a prema-
ture stop codon in preliminary analysis.
Conclusions: These results suggest that the classical mutation for
DYT1 dystonia is below the international average in Brazil. The mis-
sense mutation is thought to contribute to low penetrance in subjects
with the typical DYT1 mutation or to be a risk factor when found in
isolation. Our findings do not necessarily corroborate thar. Further
studies should concentrate in uncovering the most common forms of
dystonia in our population and possibly in other regions of the world.
This will improve guidelines for genetic testing and assist on genetic
counseling.
1334
Abnormal cerebellar plasticity in primary cervical dystonia: A
preliminary report
P. Porcacchia, F.J. Palomar, J.F. Martin-Rodriguez, I. Huertas-
Fernandez, M.A. Ruiz-Rodriguez, M. Gomez-Crespo, F. Carrillo,
M.T. Caceres-Redondo, G. Koch, P. Mir (Seville, Spain)
Objective: We used cerebellar cTBS and iTBS to test the hypoth-
esis that cervical dystonic patients had an abnormal modulation of
the excitability of the contralateral M1.
Background: In normal subjects cerebellar cTBS and iTBS are
able to induce a change of Motor Evoked Potentials (MEPs), Short
Intracortical Inhibition (SICI) and Intra-Cortical Facilitation (ICF) on
contralateral primary motor area (M1).
Methods: We enrolled 10 patients (4 men, 6 women, age 45 6 9
years) with cervical primary dystonia and 8 controls (5 men, 3
women, age 40 6 8 years). Transcranial magnetic stimulation (TMS)
was performed with a figure of eight flat coils. 20 MEPs and SICI
were tested, in different blocks, over the left M1 before and after
TBS applied over the right contralateral cerebellum. 20 MEP and
S519
SICI protocols was repeated three times: before, immediately after
(t0) and after 20 minutes (t20) of TBS . MEPs were also tested 40
minutes (t40) after TBS. TBS over cerebellum was delivered at 80%
of the active motor threshold intensity on the right cerebral hemi-
sphere. Amplitudes of motor evoked potential (MEP) were analysed.
Each subjects carried out two sessions, at least a week apart: in a
random order, TBS delivered in one session was intermittent and it
was continuous in the other one.
Results: MEP amplitudes were reduced significantly after cTBS in
controls subjects but showed only a slight and no significant reduction
in dystonic patients. cTBS induced a reduction of SICI in control sub-
ject but not in dystonic patients. In control subjects, 2 and 3 ms were
the ISIs where changes were evident. Difference at 2 and 3 ms between
controls and patients were evident before cTBS, at baseline conditions,
with the patients showing a minor SICI inhibition at these intervals.
Cerebellar iTBS produced different effects in control and dystonic
patients. In controls but not in dystonic patients MEP amplitude after
cerebellar iTBS was increased and ICF was decreased. In particular
ICF reduction was evident in control subjects at 7, 10 and 15 ms ISI.
Conclusions: Dystonic patients had an abnormal cerebellar plas-
ticity both in terms of reduced effect of TBS and in terms of loss of
specificity (inhibition or increase depending on repetitive stimulation
protocol). Differences we found in SICI-ICF protocols probably
account for intracortical excitability changes in dystona but we can-
not exclude an effect of abnormal plasticity in addition.
1335
Electrophysiological and behavioural measures of the dynamics
of motor learning: implications for probing learning in
neurological conditions
B. Quinlivan, J.S. Butler, A.R. Ridwan, L. Williams, I. Beiser, E.
McGovern, S. ORiordan, M. Hutchinson, R.B. Reilly (Dublin,
Ireland)
Objective: Motor learning describes the ability to learn novel
movements and adapt those that have been learned previously. It is
an important process that can be impaired in Movement Disorders
such as dystonia or Parkinsons disease. An objective measure of
motor learning would be a useful tool to determine severity of this
impairment and allow its development to be tracked over the course
of such disorders.
Background: Although behavioural measures are useful in the
study of motor learning, it can be difficult to determine robust met-
rics that isolate the motor learning process from other non-motor
learning processes.
Methods: Electroencephalography (EEG) and behavioural data
were acquired from 12 healthy participants. Participants were
instructed to explore an area, represented on a computer screen,
using a track ball with the aim of finding a target location on 30 con-
secutive occasions, each trial starting at a different location. Partici-
pants performed two experimental conditions, motor learning (ML)
where the target location was hidden and continuous cue (CC),
where the target location was visible. Reaction times (RT) and the
amplitude of the P3 and N2 components and mu rhythm power over
the consecutive trials were used as behavioural and EEG measures
of motor learning.
Results: Results demonstrate that RT is correlated with P3
(R=0.86,p<.001), N2 (R=-0.4,p<.05) and mu rhythm (R=-0.5,p<.005)
in the ML experimental condition at a trial by trial level. An increase
in mu rhythm power was observed over trials in both experimental
conditions. As increased mu rhythm has been associated with
decreased motor task difficulty, it is plausible that mu rhythm may be
useful as a measure of motor learning. N2 amplitude, which has been
associated with attentional demand, increased with trial and correlated
with mu power in the ML condition (R 5 0.71,p<.001) suggesting
that N2 may also reflect motor learning.
Conclusions: The results presented here suggest that a combination
of mu rhythm and N2 amplitude in conjunction with RT and P3
Movement Disorders, Vol. 30, Suppl. 1, 2015
S520 POSTER SESSION
amplitude may hold more promise as objective metrics of motor learn-
ing in target location tasks. This task it is repeatable without a learning
effect, it provides an objective measure of performance, it is intuitive
and engaging for participants and scalable in difficulty, making it suita-
ble for investigating motor learning in Movement Disorders.
1336
Multifocal task specific dystonia in a 61-year-old-female: A case
report with sensory trick physiology
V.F.M.L. Ramos, A.L. Holmes, B.I. Karp, C.I. Lungu, K. Alter, H.
Mark (Bethesda, MD, USA)
Objective: To describe a case of multi-focal task specific dysto-
nia, with a demonstration using electromyography of walking back-
wards as a sensory trick.
Background: Although task-specific dystonias are common, it is
uncommon to find multifocal task specific dystonias within the same
patient. Sensory tricks aid dystonia diagnosis, and walking back-
wards is a common sensory trick, for foot or runners dystonia.
Methods: A 61-year old woman developed typing-associated
curling of digits 2,3, and 4, in her left hand at the age of 30. She
then had curling of digits 3, 4, and 5 of the right hand with writing
at the age of 51. After long being an avid jogger, she had curling of
her right toes and right foot inversions when running at high speed
at age 56. At age 60, she noted head- turning to the right. She had
sensory tricks of resting chin on right knuckle for cervical dystonia
and walking backwards for her runners dystonia. She has one son
with texting dystonia and one daughter with cervical dystonia and
runners dystonia. Temporal discrimination threshold testing showed
slightly prolonged values, compatible with known abnormalities in
dystonia. To better isolate ideal muscles for botulinum toxin injec-
tions, we performed gait testing with fine wire electromyography to
the right tibialis posterior, and surface electrodes on the right flexor
digitorum longus, bilateral rectus femoris, medial hamstrings, gastro-
cnemii and tibialis anterior. Trials of barefoot walking were collected
at slow pace, fast pace and during backward walking.
Results: We found significant decrease in muscle activity on
electromyography with backward walking, quantifying her known
sensory trick. We diagnosed her with multi-focal task specific dysto-
nia with left hand typing dystonia, right hand writing dystonia, right
foot runners dystonia and also cervical dystonia.
Conclusions: Gait testing with electromyography is useful in
delineating muscles for botulinum toxin injections and demonstrating
sensory tricks for diagnosis.
1337
Comparison of the safety and efficacy of botulinum toxin type-A
and anticholinergics in the treatment of cervical dystonia
patients
M. Relja, J. Bozikov (Zagreb, Croatia)
Objective: To compare the safety and efficacy of botulinum toxin
type-A (BTX-A) vs anticholinergic therapy as biperiden HCl in the
treatment of cervical dystonia patients.
Background: After first report from Fahn in 1979 that high doses
of anticholinergic therapy is beneficial in patients with dystonia these
drugs have been used for treatment of generalized dystonia while
BTX-A today is the first line treatment for patients with focal dysto-
nia. However, studies performed to compare the effects of BTX-A
and oral anticholinergic therapy are missing.
Methods: This was a single-blind, randomised, comparative, par-
allel and two-way crossover study to compare the safety and efficacy
of BTX-A (as incobotulinum toxin A and/or botulinum toxin A) ver-
sus anticholinergic drug biperiden HCl in the treatment of 14 nave
idiopathic cervical dystonia patients using the Toronto Western Spas-
modic Rating Scale (TWSTRS). Secondary efficacy comprised pain
frequency and severity, physician and patient global assessment, and
Movement Disorders, Vol. 30, Suppl. 1, 2015
quality of life (QoL). In phase I, Group A received botulinum BTX-
A (as botulinum toxin a and/or Incobotulinum toxin A, dose range
from 100 to 200 U) and Group B received biperiden as Biperiden
(dose range from 4 mg to 6 mg) for 6 weeks. In phase II Group A
was not treated again but Group B swiched to BTX-A injections.
Results: BTX-A group showed a greater decrease in TWSTRS
score (p<0.0001 at Week 6). Greater decreases in pain frequency
and severity were also noted in Group A at Week 6 (decreased fre-
quency, p50.005; decreased severity, p50.008). Similar reductions
were seen in Phase II when biperiden patients were swiched to BTX-
A . Physician global assessment, patient global assessment and QoL
all improved more following BTX-A treatment compared to biperi-
den treatment, with statistically significant differences being seen for
all analyses at Weeks 2 and 6. Patients also experienced more
adverse events following anticholinergic treatment with biperiden
(80%) compared to BTX-A treatment (phase I: 30%, phase II: 25%).
The three most common side effects of anticholinergic therapy were
dry mouth, blurred vision, constipation.
Conclusions: BTX-A treatment (both as botulinum toxin a and/or
incobotulinum toxin A) provided a significant benefit compared to
anticholinergic (biperiden) oral medication.
1338
A study of motor and non-motor gains following placement of a
deep brain stimulator in a pediatric non-ambulatory patient with
dystonia
N. Remec, K. Wing, R. Bhardwaj, S. Flecky, J. Semanta (Phoenix,
AZ, USA)
Objective: The purpose of this case report is to describe motor
and non-motor changes occurring following surgical intervention in a
12 year-old female following DBS placement.
Background & Case description: Children with dystonia present a
unique set of challenges for clinicians, as currently there are no medica-
tions to prevent or slow dystonia. Therefore, therapy services have been
typically adjunct to other pharmacological approaches, with interven-
tions targeted at compensatory strategies and prevention of secondary
impairments. Surgical Deep Brain Stimulation (DBS), has returned the
role of therapies to recovery movement, mobility and communcation.
Methods: Outcomes: After 7.5 weeks of inpatient rehabilitation,
the patient was able to perform bed mobility, transitions and trans-
fers without physical assistance, safely sit for indefinite periods, and
walk with a walker and orthotics at a speed of .25meters/sec
(GMFCS level III). Improvements in upper extremity coordination
and grip strength (0.0 to 7.0lbs) allowed for self-feeding, and a cor-
responding 12% increase in body weight. Additionally, increases in
participation and decreases in pain/bother domains in the Cerebral
Palsy Quality of Life Questionnaire (CPQOL) were also noted.
Results: After 6 months of outpatient therapy services, the patient
was noted to have an increase in grip strength to 12.0 lbs, improved
times on the 9-hole-peg test resulting in increased dextermity to allow
for texting as primary means of communication (1-2 letters/sec) and a
corresponding 14% increase in body weight (remaining wtihin normal
BMI). Walking speed increased to 0.48meters/sec, (GMFCS level
III) and was limited by hip subluxation. Additional increases in com-
munciation and participation CPQOL measures were also noted.
Conclusions: Early and intensive therapy following DBS surgery
may improve gross functional mobility and decrease pain/bother,
while on-going therapy services may increase communcation and
participation, allowing for return to more age expected activities.
Positive changes in weight/BMI and health were also noted.
1339
Neurochemical and behavioral dysfunction in a new mouse
model of dopa-responsive dystonia
S.J. Rose, X.Y. Yu, H.A. Jinnah, E.J. Hess (Decatur, GA, USA)
 POSTER SESSION
Objective: We sought to better understand the role of dopamine
in dystonia using a new knockin mouse carrying a dopa-responsive
dystonia (DRD)-causing tyrosine hydroxylase (TH) mutation
(c.1160C>A; p.381Q>K).
Background: Although the pathogenesis of dystonia is not under-
stood, reduced dopamine neurotransmission is observed across many
different forms of dystonia, including DRD. DRD is cause by muta-
tions in genes integral to dopamine synthesis, including TH, the rate-
limiting enzyme in dopamine synthesis.
Methods: Here, we present the generation and characterization of
DRD knockin mice.
Results: TH activity is reduced by 90% in vivo in these mice,
causing a dramatic reduction in dopamine concentration. Behavior-
ally, DRD knockin mice exhibit abnormal movements reminiscent of
human dystonia. These mice exhibit diurnal fluctuations in dystonic
symptoms, with dystonia worsening through the active period. These
movements are ameliorated by L-DOPA and exacerbated by dopa-
mine receptor antagonists, illustrating the role for reduced dopamine
tone in the expression of dystonia.
Conclusions: These studies establish DRD knockin mice as a useful
model for examining dopaminergic mechanisms underlying dystonia.
1340
Kinematic biomechanical characterization guides
incobotulinumtoxinA treatment in cervical dystonia patients
O. Samotus, H. Vafadar, F. Rahimi, M. Jog (London, ON, Canada)
Objective: To quantify irregular head movements in order to
identify dystonic neck muscles to be treated by onabotulinumtoxinA
injections.
Background: Visual assessment of cervical dystonia (CD) is a
challenging task many clinicians face today. As the complexity of
CD involves variations in rhythm, velocity, amplitude, and direction,
tailoring focal therapy commonly results in a randomized or fixed
dosing regimen associated with mediocre relief of symptoms.
Sensor-based kinematic technology is an affordable, objective
method to measure neck biomechanics.
Methods: 24 drug-nave CD participants were injected with onabo-
tulinumtoxinA at baseline, and completed clinical rating scales
(TWSTRS and UDRS) and kinematic assessments during follow-up
visits at weeks 6 and 16. Kinematic recordings involved an inclinome-
ter positioned above the right ear and a goniometer at C2 and T2 spi-
nal segments to capture severity of natural head and neck twisting in
three degrees of freedom (DOF): rotational, lateral, and vertical tilts.
Static posturing, measured as angular deviation from calibrated neutral
head position, and dynamic movements, measured by angular RMS
amplitude, were collected in three 10-second trials. Dosing and muscle
selection were based on kinematic data and with clinicians experience.
Results: Mean TWSTRStotal score significantly improved from
study baseline to weeks 6 and 16 by 17.1% and 10.1%, respectively.
Kinematics objectively isolated static head posturing (angular
deviation > 5.5 degrees) from dystonic movements (angular RMS
amplitude > 0.35 degrees). Participants who presented with static
posturing at baseline displayed a mean reduction in severity by
42.0%, 12.3% and 18.4% in lateral, vertical, and rotational DOFs,
respectively, at week 6. Participants with dystonic movements
showed a mean decrease in severity by 28.8%, 35.2%, and 23.1% in
lateral, vertical, and rotational planes of motion at week 6.
Conclusions: Kinematics provides an objective understanding of
neck biomechanics and can easily identify hyperkinetic muscles for
focal therapy.
1341
Adult-onset axial dystonia responds to globus pallidus deep brain
stimulation
A.G. Shaikh, K. Mewes, H.A. Jinnah, M.R. DeLong, R.E. Gross, S.
Triche, A. Freeman, S.A. Factor (Cleveland, OH, USA)
S521
Objective: Assessment of efficacy of deep brain stimulation for
treatment of adult-onset axial dystonia.
Background: Primary and secondary forms of generalizd dysto-
nia, tardive dystonia, and idiopathic cervical dystonia are responsive
to globus pallidus interna (GPi) DBS. There is a paucity of investiga-
tions showing efficacy of DBS on adult-onset axial dystonia. We
report that rare adult-onset axial dystonia responds to GPi DBS.
Methods: We assessed response of GPi DBS on adult-onset axial
dystonia. Primary outcome measure was improvement in the motor
component of the Burke-Fahn-Marsden (BFM) rating scale. Second-
ary outcome measures were quality of life as determined by the SF-
36 questionnaire, time to achieve best possible benefit and DBS
parameters that accounted for the best response. We also used the
Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) in
patients with prominent concomitant cervical dystonia.
Results: GPi DBS improved BFM scores by 87.63 6 11.46%,
while improvement in total severity scale of TWSTRS was
71.5 6 12.7%. Quality of life also remarkably improved.
Psychometrically-based physical component summary (PCS), and a
mental component summary (MCS) score improved by
109.38 6 82.97 and 7.05 6 21.48% respectively.
Conclusions: GPi DBS is an effective treatment for adult-onset
axial dystonia.
1342
Ocular palatal tremor plus dystonia A novel syndromic entity
A.G. Shaikh, F.F. Ghasia, M.R. DeLong, H.A. Jinnah, A. Freeman,
S.A. Factor (Cleveland, OH, USA)
Objective: Describing dystonia in a novel variant of ocular pala-
tal tremor.
Background: The syndrome of ocular palatal tremor typically
develops after a breach in the Guillian-Mollaret triangle. We herein
describe a variant of this syndrome in which dystonia is also present,
hence called, here, ocular palatal tremor plus dystonia.
Methods: We used eye and head position trackers to quantita-
tively assess movements and Burke Fahn Marsden dystonia rating
scale to quantitatively determine the burden of dystonia.
Results:: Among six patients with ocular palatal tremor two had
focal dystonia, three had multifocal dystonia, and one had generalized
dystonia. The dystonia affected the upper extremities and neck in four
patients, the lower extremities in three and the face in two. Three out
of four cervical dystonia patients had head tremor. Two patients also
had speech involvement. The motor score from the Burke Fahn Mars-
den rating scale ranged between 6 and 90. We also measured eye and
head movements in three of the patients. As expected from the syn-
drome of OPT, the eye oscillations were irregular, coarse, and dyscon-
jugate. The frequencies of horizontal, vertical, and torsional eye
oscillations were 3.4 6 1.6 Hz, 3.5 6 2.3 Hz, and 3.8 6 1.7 Hz respec-
tively. The head oscillations were irregular and coarse with frequencies
of 4.0 6 2.3 Hz and 3.6 6 2.4 Hz in horizontal and vertical directions.
Conclusions: We describe a novel variant of ocular palatal
tremor with dystonia where the dystonia is not an epiphenomenon
but can be explained by abnormal and increased cerebellar outflow
in patients with a breach in Guillain-Mollaret triangle.
1343
Neural correlates of GNAL mutation in laryngeal dystonia
K. Simonyan, G. Putzel, T. Fuchs, E. Rubien-Thomas, A. Blitzer, S.J.
Frucht, L. Ozelius (New York, NY, USA)
Objective: To examine imaging abnormalities of GNAL mutation
carriers.
Background: Mutation in GNAL has been recently identified as
a cause of primary torsion dystonia. However, its neural correlates
and the exact mechanisms contributing to the dystonic cascade
remain poorly understood.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S522 POSTER SESSION
Methods: We screened a cohort of 275 patients with different
forms of focal dystonia for GNAL mutation and examined brain acti-
vation in GNAL mutation carriers compared to healthy controls as
well as to sporadic and familial cases using functional MRI during
symptomatic task production.
Results: Out of 275 patients, two patients had a mutation in
GNAL. Both patients presented clinically as classical laryngeal dys-
tonia (LD) phenotypes, one with adductor type and one with abduc-
tor type. Compared to 10 controls, all LD patients, including 10
sporadic, 10 familial forms and 2 GNAL mutation carriers, showed
reduced brain activity during symptom production in the cerebellum
and parietal cortex as well as increased activity in the basal ganglia
and sensorimotor cortex (corrected p  0.05). When compared with
either sporadic or familial LD, GNAL patients showed additional
alterations of brain activity in the basal ganglia and prefrontal cortex
(corrected p  0.05).
Conclusions: Our data show that mutation in GNAL represents one
of the causative genetic factors in LD. Evidence of distinct neural
abnormalities in LD GNAL mutation carriers may suggest the presence
of divergent pathophysiological cascades underlying this disorder.
1344
Effectiveness of onabotulinumtoxinA in patients with cervical
dystonia naive to botulinum toxin treatment
C. Singer, R. Barbano, M. Schwartz, M.F. Brin, C.H. Adler (Miami,
FL, USA)
Objective: To assess effectiveness and safety following onabotu-
linumtoxinA treatment for cervical dystonia (CD) in a large botuli-
num toxin (BoNT)-naive population within a real-world clinical
setting.
Background: A prospective, observational, multicenter registry
(Cervical Dystonia Patient Registry for Observation of Onabotuli-
numtoxinA Efficacy) evaluated the safety, effectiveness, and treat-
ment utilization of onabotulinumtoxinA for CD in clinical practice
(ClinicalTrials.gov NCT00836017).
Methods: Assessments included Toronto Western Spasmodic
Torticollis Rating Scale (TWSTRS), Clinician Global Impression of
Change (CGIC), Patient Global Impression of Change (PGIC), Cervi-
cal Dystonia Impact Profile-58 (CDIP-58), and adverse events (AEs).
Only subjects who were naive to BoNT at baseline are included in
this report. Subjects could receive up to 3 treatments. Assessments
were at baseline, at treatment visits, and 4-6 weeks post-treatment.
OnabotulinumtoxinA dosing and treatment intervals varied due to the
real-world nature of the design.
Results: Of the 1046 enrolled subjects, 661 (63.2%) were naive
to BoNT at baseline (73.7% female; mean age, 58.0 6 15.3 years;
mean time from onset to diagnosis, 5.4 6 8.7 years; mean time from
diagnosis to first treatment, 0.9 6 3.2 years). Mean onabotulinumtox-
inA dose was 165.2 6 75.1U, with a mean of 14.6 and 15.2 weeks
between treatments. Mean TWSTRS total score in subjects complet-
ing all TWSTRS assessments (n5298) improved from 39.2 at base-
line to 27.1 at final visit (P<0.0001). From first to last post-
treatment assessment, a significantly higher percentage of physicians
reported improvement as measured by CGIC (n5297, 90.6% vs
94.6%; P<0.0001), and significantly higher percentages of subjects
reported improvement as measured by PGIC (n5293; 82.6% vs
94.2%; P<0.0001). All 8 mean CDIP-58 subscale scores decreased
significantly from baseline after the first treatment, as well as at each
subsequent assessment (each P<0.0001). The most common AEs
were muscular weakness (7.0%), dysphagia (6.4%), and neck pain
(3.8%). One hundred and twenty subjects (18.2%) reported 1
treatment-related AE and 3.2% (n521) reported a serious AE.
Conclusions: OnabotulinumtoxinA significantly decreased CD
symptoms, disability, and severity and improved quality of life, with
no new safety signals, in a real-world treatment setting in subjects
naive to BoNT at baseline.
Movement Disorders, Vol. 30, Suppl. 1, 2015
1345
DBS in dystonic camptocormia: A case report and review
P. Surathi, A. Zafar, R. Yadav, D. Srinivas, P.K. Pal (Bangalore,
India)
Objective: (i) To report management challenges in a patient with
dystonic camptocormia and review the current literature,(ii)to
describe the role of deep brain stimulation (DBS) in its management.
Background: Camptocormia is seen with Parkinsons disease
(PD), segmental or generalised dystonia, extensor myopathies, ante-
rior horn cell disorders and muscle disorders. In severe selected cases
of PD with camptocormia and dystonic camptocormia DBS has been
tried with variable success.
Methods: A 42-year-old male, presented with dystonia of 5-year
duration, initially with cervical dystonia. It progressed to severe dis-
turbance of posture causing involuntary truncal flexion induced by
standing or sitting and completely relieved when sitting on chair or
lying down on bed. All relevant investigations for secondary dystonia
including Magnetic resonance imaging (MRI) of the brain and MRIs
of thoracic and lumbar spine were normal. The electromyogram of
lumbar and thoracic paraspinal muscles was also normal.
Results: Patient was treated with various combinations of trihexy-
phenidyl (24mg/day), clonazepam (1.5mg/day), baclofen (30 mg/day),
levodopa (600 mg/day), and tetrabenazine (75 mg/day), with no signif-
icant benefit. He also received multiple injections of Botulinum toxin
A in with which he had partial transient improvement. Subsequently
he underwent bilateral Globus pallidus interna (Gpi) DBS surgery.
The improvement noted at 2 weeks post surgery was approximately
30% and further improvement up to 50% was observed in long term
follow up, as assessed by subitem (trunk) of the Burke-Fahn-Marsden
(BFM) dystonia score (reduction from 16 to 8). Cervical dystonia
improved by 90% in subitem (neck) of BFM scale (reduction from 8
to 0.5). Total BFM score reduced from 20 to 10.5.
Conclusions: Similar to our case in another series of 3 patients
of dystonic camptocormia by Reese et al (2014) there was a signifi-
cant response to bilateral GPi- DBS within weeks in postoperative
period that was sustained till about 3 years of follow up. Thus GPi
DBS may be an effective option of treatment in drug refractory dys-
tonia associated camptocormia. Although only reported in PD associ-
ated camptocormia, evaluation for truncal extensor myopathy is
mandatory in these cases to have a good outcome.
1346
Zolpidem in Movement Disorder after cardiac arrest
H.A.G. Teive, M.S. Silva, D.B. Bertholdo, W.O. Arruda (Curitiba,
Brazil)
Objective: To present a case of Movement Disorder after cardiac
arrest with therapeutic response to zolpidem, a drug used to
insomnia.
Background: Cerebral hypoxic lesions can be cause of neurologi-
cal dysfunctions, including coma, seizures, cognitive impairments
and Movement Disorders (MD). The presentation of MD is variable
and the treatment is a challenge sometimes.
Methods: Case report.
Results: A 42 years old woman with intense epigastric pain and
tachypnea arrives at the Emergency Department of the Hospital of
Federal University of Parana. Diagnosed as acute pancreatitis, after
three days, she has a clinical worsening and a cardiac arrest. Resus-
citation maneuvers are applied during 25 minutes, followed by rever-
sal of cardiac function. The patient is submitted to orotracheal
intubation and stays in induced coma. After 30 days she wakes up
with a Movement Disorder characterized by generalized dystonia.
Therefore she cant communicate with others. The Movement Disor-
der ceased during sleep. She tried baclofen, buspirone, levodopa and
clonazepam with no satisfactory outcomes. With 10 mg of zolpidem,
the patient had a good response at sleep induction. On an equivocal
of the relative responsible to offer the medication, the patient
 POSTER SESSION
received half of the daily dose of zolpidem. After that, the family
noted that patient ceased the dystonic movements. Although she got
bradykinetic and had some difficulty to speak, she could walk with
help and take foods to the mouth. With this outcome, the family
started offering 5 mg of zolpidem before meals. The drug effects
appeared 30 minutes after the administration and had a duration of 2
hours. Brain Magnetic Resonance showed diffuse volumetric reduc-
tion and a bilateral T2 hyposignal at globus pallidus, indicating iron
deposition.
Conclusions: Although zolpidem is currently indicated as a hyp-
notic drug, some case reports had observed their beneficial effects with
rigidity and bradykinesia of Parkinso ns disease and progressive supra-
nuclear palsy, restless legs syndrome, spinocerebellar ataxia type 2, and
dystonia. A new indication of zolpidem must be considered because
their effects observed at cases of Movement Disorders. Additional stud-
ies are necessary to better understanding this interesting effect.
1347
Depression is an under-recognized feature in X-linked dystonia
Parkinsonism
P. Termsarasab, A. Patel, S.J. Frucht, W. Tse (New York, NY, USA)
Objective: To describe a patient with X-linked dystonia Parkin-
sonism (XDP) diagnosed after admission for attempted suicide.
Background: The main clinical features of XDP are cranio-
cervical dystonia and Parkinsonism. Neuropsychiatric features are
sparsely reported in the literature and may be under-recognized. One
case-control study reported depression in 92.9% of XDP patients,
and major depression in 14.3%.
Methods: A case report.
Results: A 51-year-old Filipino man was hospitalized after a sui-
cide attempt. One week prior, a neurologist diagnosed him with
Parkinsons disease (PD) and recommended levodopa therapy. One
day after starting levodopa, he took 76 tablets of 500-mg acetamino-
phen in a suicide attempt. He developed acute hepatic failure (SGOT
and SGPT were 10,878 and 5,530 U/L, respectively) which improved
with supportive treatment over the next two weeks. He was trans-
ferred to psychiatry and his depression treated with mirtazapine
30 mg/day, with improvement in his mood.
A Movement Disorders consult was requested for management of
his PD. His history was notable for four months of blepharospasm,
and involuntary left hand and jaw opening. He was from the Iloilo
province on the island of Panay and had multiple maternal family
members (see pedigree) diagnosed with PD, with no male-to-male
transmission (compatible with X-linked recessive inheritance).
On exam (see video), he had neck dystonia with frequent com-
plex side-to-side head twisting, severe blepharospasm, and jaw-
opening dystonia. There was intermittent slow repetitive left hand
flapping. He had mild Parkinsonian features including bilateral hand
bradykinesia, decreased stride length, and reduced bilateral arm
swing. There was limited improvement of dystonia on trihexyphe-
nidyl 2mg/day. Blepharospasm was treated with botulinum toxin.
Conclusions: We report an XDP patient with major depression
and attempted suicide. Limited studies suggest a high prevalence of
depression in XDP; however, it remains under-recognized among
clinicians and further studies focusing on the neurobehavioral fea-
tures of XDP are required.
1348
Embouchure dystonia: Phenomenology, natural history and
mimicks
P. Termsarasab, S.J. Frucht (New York, NY, USA)
Objective: To define the phenomenology, natural history and dif-
ferential diagnosis of embouchure dystonia (ED).
Background: ED refers to a form of focal task-specific dystonia
affecting complex movements of lower cranial muscles in brass and
S523
woodwind musicians during playing. We expand our previous series
of 89 patients by adding 19 new patients with ED, and 30 musicians
with non-dystonic embouchure problems.
Methods: Retrospective review of medical records and patient
videos.
Results: 109 ED patients were classified into 6 main phenotypes:
39 tremor variant (T), 22 jaw dystonia (J), 21 lip-pulling (LP), 15
lip-locking (LL), 4 tongue dystonia (Tg), 4 Meige syndrome (M),
and 4 unspecified. Of 20 newly added patients, T remained the most
common (10/20), followed by LP and LL (3/20 each). Male-to-
female ratio was 2.4 (77/32). Mean age at onset was 37.6 years. The
most common instrument in each phenotype was French horn (FH)
in T and LP; trombone in LL; flute in J and Tg; and trumpet in M.
The most common phenotype in each instrument was: T in FH, tuba
and trumpet; LL in trombone; J in flute, clarinet, and saxophone.
Of 30 patients in the non-ED group (22 men, 8 women), the most
common diagnosis was anterior superior alveolar neuropathy
(36.7%), followed by overuse (23.3%), orbicularis oris tear (13.3%),
essential tremor (ET), and miscellaneous (Bells palsy, temporoman-
dibular joint irritation, and glossopharyngeal neuralgia). Time from
age at onset to age at evaluation was shorter in the non-ED group,
compared to the ED group (median 1 vs 3 years).
Conclusions: This is the largest series of ED reported and the
largest report of patients with embouchure related difficulty. It is
critical to distinguish conditions that mimick ED, as these disorders
have distinctly different prognosis and management strategies.
1349
Do positive family history influence on the characteristics of the
adult onset dystonia?
S. Tomic, T. Gilman Kuric, M. Petek, T. Pucic, S. Juric, S. Butkovic
Soldo (Osijek, Croatia)
Objective: To evaluate frequency of positive family history for
Movement Disorders in dystonia patients and its influence on clini-
cal characteristics of the dystonia.
Background: Primary cervical dystonia is typically an adult onset
condition and patients usualy have positive family history about
some other Movement Disorders.
Methods: In this retrospective study we have analyzed patients
with idiopathic focal, multifocal or segmental dystonia in regard to
age of symptom onset, sex, type of dystonia, clinical characteristics
of cervical dystonia (subtypes of cervical dystonia, side of deviation,
presence of pain and tremor) and family history for Movement Dis-
orders. Data were analyzed using student t-test with statistical signifi-
cance of p<0,05.
Results: There were 54 patients, 37 (68,6%) female and 17
(31,4%) male, mean age of 51 years. We have found statistical sig-
nificant differences between sex in regard to age of dystonia onset
(45,18 years in male and 53,68 years in female) (p<0,022). Most of
the patients had cervical dystonia (53,7%) and blepharospasm
(27,80%). Positive family history (PFH) had 24% of the patients and
negative (NFH) 76%. There was no statistical significant differences
in between NFH and PFH group according to age of dystonia onset
(51,61 in regard to 49,08 years) (p<0,539). In both groups, most of
the patients were female (85% in PFH and 63% in NFH), but this
difference was not significant (p<0,905). In the patients with cervical
dystonia we have found no difference in clinical presenstation
(tremor, pain and head deviation) in between groups. Most of the
patients had torticolis in the both groups, while combinated cervical
dystonia appear only in the NFH group.
Conclusions: Idiopathic focal dystonia appear most often in
female, while male patients had earlier dystonia onset. Most pre-
sented types were cervical dystonia and blepharospasm. Positive
family history do not influence on the age of dystonia onset nor on
dystonia characteristics (tremor, pain, side of deviation and subtype
of cervical dystonia).
Movement Disorders, Vol. 30, Suppl. 1, 2015
S524 POSTER SESSION
1350
Botulinum toxin for neurogenic thoracic outlet syndrome
A.T. Tran, R. Koopot, G. Moguel-Cobos, A. Lieberman, A.T. Tran
(Phoenix, AZ, USA)
Objective: To report a case-series of four patients who have sig-
nificant relief of their neurogenic thoracic outlet syndrom (NTOS)
symptoms with Botulinum toxin and describe our muscle selection
and injection technique.
Background: There are three types of TOS: neurogenic, venous,
and arterial. NTOS is the most common of the three, accounting for
about 95% of all TOS patients, for unknown reason. The reason to
inject Botulinum toxin in NTOS is to weaken the muscles that likely
impinge upon the brachial plexus. The thoracic outlet syndrome has
three potential spaces where muscles compression upon the brachial
plexus can contribute to pain: the interscalene space where the ante-
rior and medial scalene lie, the costoclavicular space with the subcla-
vius muscle, and the pectoralis minor space containing the pectoralis
minor muscle. The typical presentation is a patient with vague com-
plain of pain and numbness in the neck, shoulders, arms, hands or
fingers with a history of trauma or repetitive movements. The injury
subsequently results in intrascalene muscle inflammation and/or hem-
orrhage and later scarring within the muscles and nerves. The predis-
posing factors for TOS are congenital anatomic features that narrow
the thoracic outlet such as cervical ribs, anomalous first ribs, and
variation in the placement of the scalene muscles. The causative fac-
tor is commonly hyperextension neck injury.
Methods: All four patients diagnoses were confirmed by our
Movement Disorder specialist and a thoracic surgeon experienced in
treating thoracic outlet syndrome. All other diagnosis that can
explain TOS were excluded based on imaging. All four patients had
positive Roos maneuver and Tinnels sign over the brachial plexus
and complained of significant pain. All four patients have their ante-
rior scalene, middle scalene, subclavius, and pectoralis minor
muscles injected.
Results: All patients have more than 50% subjective report of
decrease in pain symptom.
Conclusions: Botulinum toxin injection is an effective treatment
for neurogenic thoracic syndrome, an otherwise debilitating and diffi-
culty condition to treat. Botulinum toxin is an effective conservative
treatment with minimal risk compare to surgical decompression. Bot-
ulinum toxin works synergistically with physical therapy. We find
that by targeting all muscles that can potentially compressed the
three potential spaces of the thoracic outlet, patients get significant
relief of their pain symptom.
1351
Patterns of cervical dystonia: A meta-analysis of three large
observational studies
R. Trosch, P. Misra, S. Om, P. Maisonobe (Farmington Hills, MI,
USA)
Objective: To characterize the dystonic pattern of cervical dysto-
nia (CD) patients treated in clinical practice with botulinum neuro-
toxin type A (BoNT-A).
Background: Dystonic posturing in CD is routinely described by
its predominant movement (rotation, tilt, anteroversion, retroversion)
or combination of movements (e.g. rotation with tilt) and by other
movement characteristic (skew, tremor). Understanding the pattern of
dystonic posturing can provide insights into the causes of dystonia
and the management of these patients.
Methods: A meta-analysis was conducted on the baseline data
from 2 observational international studies (INTEREST IN CD1 & 2)
and 1 US registry (ANCHOR-CD). INTEREST IN CD2 is an
ongoing study; data from a pre-planned interim analysis were used.
Results: This meta-analysis included 752 patients with idiopathic
CD. Most patients (92%) had a focal dystonia, but 5% had segmental
dystonia, 2% had multifocal dystonia and 1% had generalized dysto-
Movement Disorders, Vol. 30, Suppl. 1, 2015
nia. The predominant dystonic posture in the majority of patients
had a pattern of rotational torticollis (71.4%), 20.4% patients had lat-
erocollis, 4.4% had retrocollis, 2.5% had anterocollis. Only 23.6% of
patients had a simple pattern of CD, while 76.4% had a complex pat-
tern (2 patterns and associated components); 22% of patients had
at least 4 documented patterns. Overall, 27.8% of patients had rota-
tional torticollis as a secondary pattern, 39.4% had laterocollis,
16.6% had retrocollis, 11.7% had anterocollis, 14.1% had a lateral
shift of the column and 6.1% had a sagittal shift. Shoulder elevation
was also a relatively common secondary pattern (31.6%). Half of
patients (49%) had a head tremor, which was mostly mild. Of those
patients with tremor, 52% had occasional tremor and 48% had con-
tinuous tremor.
Conclusions: Most patients presenting for routine injections of
BoNT-A for CD have a predominant pattern of rotational torticollis/
laterocollis. The majority had a complex pattern of CD, and almost
half of all patients were experiencing tremor. These data highlight
the need to tailor treatments to each individual patient.
1352
TWSTRS scores in cervical dystonia patients previously treated
with botulinum neurotoxin A (BoNT-A) versus those nave to
treatment
R. Trosch, P. Misra, P. Maisonobe, S. Om (Farmington Hills, MI,
USA)
Objective: To compare the clinical characteristics (as assessed by
TWSTRS) and treatment of botulinum neurotoxin type A (BoNT-A)
nave patients with cervical dystonia (CD) presenting for treatment
to those previously treated with BoNT-A who are at the end of the
injection cycle and requiring reinjection.
Background: Chemodenervation with BoNT-A is established as
a first-line treatment for patients with CD. After receiving their first
injection, patients typically return for re-injection every 3-4 months
or when the patient reports that their prior injection has worn off.
The natural history of CD following BoNT-A treatments has not
been well characterized; in particular it is not known if at the end of
each treatment cycle there is a difference in clinical presentation
from BoNT-A nave patients.
Methods: A meta-analysis was conducted on the baseline data
from 2 observational international studies (INTEREST IN CD1 & 2)
and 1 US registry (ANCHOR-CD). INTEREST IN CD2 is an
ongoing study; data from a pre-planned interim analysis were used.
Results: There were no significant differences between sub-
groups in patient demographics, but small differences in the pre-
dominant pattern of CD (previously treated vs. BoNT-A nave)
were noted: (rotational torticollis: 73% vs. 64%; laterocollis 19%
vs. 26%; retrocollis 4% vs. 6%; other patterns <3% of patients).
Previously treated patients had received a median of 8 (range 1-99)
injection cycles; the median time since their first BoNT-A injection
was 44.7 months (range 2-280 months). Overall, 60% patients had
previously been treated with AbobotulinumtoxinA (median dose
500 U), 37% with OnabotulinumtoxinA-botulinum toxin a (190 U)
and 3% with IncobotulinumtoxinA (150 U). BoNT-A naive patients
tended to have a higher TWSTRS total, disability and pain scores
at baseline.
Previously BoNT-A
Overall treated nave
(n5752) (n5616) (n5136)
mean 6SD mean 6SD mean 6SD
Total TWSTRS 35.2 6 11.9 34.5 6 11.7 38.4 6 12.4
TWSTRS severity 18.0 6 4.7 18.0 6 4.7 17.9 6 5.0
TWSTRS disability 10.1 6 6.2 9.8 6 6.0 11.7 6 6.6
TWSTRS pain 7.0 6 5.1 6.6 6 5.0 8.9 6 5.1
 POSTER SESSION S525

Conclusions: When compared to previously treated CD patients,
new patients presenting for treatment with BoNT-A tend to have
higher levels of pain and disability. This suggests that continued
treatment reduces the severity of CD pain or that the therapeutic
effects of their prior injection series has not yet worn off and the
benefits of BoNT-A may last longer than patients perceive.
1353
Botulinum toxin modulates motor cortical potentiation and
depotentiation in focal hand dystonia
K. Udupa, N. Phielipp, R.F.H. Cash, C. Gunraj, R. Pellicciari, T.
Hoque, R. Chen (Toronto, ON, Canada)
Objective: To study depotentiation in focal hand dystonia
patients and the effects of Botulinum toxin treatment on
depotentiation.
Background: Botulinum toxin (BoNT) is an accepted treatment
for focal hand dystonia (FHD). Central mechanisms of action of
BoNT are not fully understood. Previous studies demonstrated exag-
gerated plasticity in the human primary motor cortex in FHD. Ani-
mal models have shown deficient depotentiation in slice preparations
of corticostriatal networks. However, potentiation/depotentiation-like
plasticity induced by theta burst stimulation (TBS) has not been
explored in FHD patients. We hypothesized that there is exaggerated
potentiation and impaired depotentiation in dystonia. Therapeutic
effects of BoNT may be partially mediated by restoration of these
abnormalities.
Methods: We studied six FHD (4 writers cramp and 2 musi-
cians dystonia) patients (age: 57 6 3 years, 2 women) with estab-
lished response to BoNT. They were studied at baseline (four
months after last BoNT injection), one and three months after treat-
ment with incobotulinumtoxinA. Eight age and gender-matched
healthy volunteers were studied as controls. Intermittent (i)TBS at
80% of motor threshold and 600 pulses (3 stimuli at 50Hz, repeated
at 5Hz, 2 sec train duration, 8 sec inter-train interval) was used to
induce long-term potentiation like plasticity. This was followed by a
depotentiation protocol consisting of continuous (c)TBS with 150
pulses (3 stimuli at 50Hz, repeated 50 times at 5Hz for 10 sec).
Motor-evoked potential (MEP) amplitude was measured at baseline
before and after iTBS, and at five different time intervals (T1, T5,
T10, T20 and T30), up to 30 min after cTBS.
Results: MEP amplitudes significantly increased after iTBS
(>170% of baseline) in controls. Potentiation was decreased in patients
at baseline and inhibition was observed at one month after BoNT injec-
tion, when peak effect is expected. cTBS led to depotentiation in con-
trols and in patients at baseline and at 3 months post incobotulinumA
injection, but led to potentiation at 1 month after injection.
Conclusions: Our preliminary findings suggest that BoNT treatment
modulates cortical plasticity in FHD and may be related to its thera-
peutic effect. This is ongoing study with more patients being recruited.
PPC and PMd in mediating WC pathophysiology and abnormal sen-
sorimotor control remain unclear.
Methods: Ten patients with writers cramp and ten aged-matched
controls will be studied. Transcranial magnetic stimulation (TMS) in
a paired-pulse paradigm was used to test interactions between PPC-
M1 and PMd-M1. Cortico-cortical interactions were measured by
paired-TMS with a conditioning stimulus to either PPC or PMd fol-
lowed by a suprathreshold test stimulus to ipsilateral M1 at intersti-
mulus intervals (ISIs) of 4, 6, 8, and 10 ms. PPC stimulation
intensities were 90% and 110% of resting motor threshold (RMT).
PMd stimulation intensities were 70% and 90% of RMT. Measure-
ments were performed at rest or before movement execution and dur-
ing the action-planning phase (100 ms after a LED light cued the
subject to trace a circle) with both the affected and unaffected hand.
Results: Preliminary results in three patients with WC indicate
PPC-M1 and PMd-M1 connections at rest were similar for the
affected and unaffected hemispheres. However, there were increased
excitatory parietal and dorsal premotor connections with the ipsilat-
eral primary motor cortex in the affected but not in the unaffected
hemisphere during the planning of writing movements.
Conclusions: These initial results suggest abnormal parietal to
motor and premotor to motor cortical interactions during motor pro-
gramming of goal-directed actions in WC.
1355
Task specific oromandibular dystonia secondary to chewing khat
(cantha edulis)
P.M. Wadia, J.N. Khanna (Mumbai, India)
Objective: A retrospective study of patients with task specific
oromandibular dystonia (OMD) from Yemen.
Background: Khat (Catha edulis), colloquially called Kat or
Gatis a flowering plant native to the Horn of Africa and the Ara-
bian Pennisula. Chewing the leaves of the plant is a common habit
amongst men in this region. We described a unique task specific
OMD in men from Yemen who have been chewing Khat prior to the
onset of dystonia.

1354
Increased excitatory parietal and dorsal premotor connections to
the primary motor cortex during action planning in focal hand
dystonia
M. Vesia, G. Jegatheeswaran, R. Isayama, R. Pellicciari, R. Chen
(Toronto, ON, Canada)
Objective: To examine the excitability of the cortical projections
from the posterior parietal (PPC) and dorsal premotor (PMd) cortices
to the ipsilateral primary motor cortex (M1) at rest and during the
planning of goal-directed actions in focal hand dystonia.
Background: Parietal-frontal circuits are actively involved in
movement planning. The pathophysiology of focal hand dystonia
such as writers cramp (WC) has been related to abnormal sensory
processing, deficient inhibitory circuits, faulty sensorimotor integra-
tion, and impaired motor planning. However, the causal roles of the Fig. 1. (1355).

Movement Disorders, Vol. 30, Suppl. 1, 2015

S526 POSTER SESSION
Methods: Clinical records of patients from Yemen presenting
with oromandibular dystonia from 2009 to Dec 2014 were retrospec-
tively analyzed based on their clinical features, consumption of Khat
and response to therapy.
Results: Seventeen men from Yemen with an average age were
45 years presented with task specific OMD involving chewing,
speech or both in this study period. Eight had a jaw opening dystonia
and 9 had jaw closure dystonia. The average age of onset of symp-
toms was 40 yrs and average duration of symptoms was 5 yrs. Dys-
arthria was seen in 15 and chewing difficulty in 16 patients each (14
patients had both), 5 also had teeth grinding. Patients had a negative
family history, normal MRI and no evidence of a secondary cause of
dystonia. All the patients had a history of chewing khat for a pro-
longed period of time prior to the onset of dystonia [figure1] . Seven
patients had stopped chewing khat after diagnosis the remaining con-
tinued to chew khat.
Conclusions: Chewing of khat is a repetitive task involving the
jaw musculature which may be one of the pathophysiological factors
in the etiology of this unique dystonia. We propose a new task spe-
cific oromandibular dystonia due to prolonged chewing of khat. The
exact causative mechanism needs further evaluation. Recognition of
this entity could have widespread ramifications in preventing disabil-
ity in young men in countries where this habit is common.
1356
Thalamic volume is reduced in multiple types of dystonia
J.L. Waugh, J.K. Kuster, J.M. Levenstein, N. Makris, T.J. Multhaupt-
Buell, L. Sudarsky, H.C. Breiter, N. Sharma, A.J. Blood (Boston,
MA, USA)
Objective: To identify structural abnormalities in primary
dystonia.
Background: Dystonia, a debilitating Movement Disorder charac-
terized by abnormal fixed positions and/or twisting postures, is
thought to result from dysfunction in motor control networks. While
gross brain lesions can produce secondary dystonias, advanced neu-
roimaging techniques have been required to identify abnormalities in
primary dystonias. These abnormalities have included functional acti-
vation, structural connectivity, and morphometric differences. Prior
neuroimaging studies have provided valuable insights into the patho-
physiology of primary dystonia, but few have examined the gross
volume of motor control regions and none have assessed volume
across multiple primary dystonias.
Methods: We used multiple morphometry techniques to compare
regional volume and gray matter density (GMd) between matched
healthy controls and patients with idiopathic primary dystonia (cervi-
cal, n517, laryngeal, n57) and one individual with generalized
degenerative dystonia (DYT3). We used (1) automated volume meas-
ures of eight motor control regions using the FreeSurfer analysis
package; (2) blinded, anatomist supervised manual segmentation of
the thalamus; and (3) voxel based morphometry of both whole-brain
and thalamic GMd.
Results: Using both automated and manual volumetry, we dem-
onstrated a thalamus-specific volume reduction in two focal dystonias
and in one subject with DYT3. Smaller thalami in patients were
independent of clinical variables (age, laterality of symptoms, dura-
tion or severity of disease) and independent of large-scale volume
measures (total grey matter, subcortical grey matter, supratentorial,
and total intracranial volume). GMd was unchanged for all motor
control regions, including the thalamus.
Conclusions: Reduced thalamic volume, detected in two inde-
pendent analyses, suggests a common anatomical abnormality in
diverse types of dystonia. The absence of parallel GMd changes for
the thalamus serves as a reminder that gross volume and grey matter
morphometry are complementary, rather than synonymous, techni-
ques. Defining the structural underpinnings of dystonia may require
such complementary approaches.
Movement Disorders, Vol. 30, Suppl. 1, 2015
1357
Capturing what is important to patients with dystonia: A
systematic review and assessment of health-related quality of life
(hrqol) measures
N. Wickert, S. Walleser Autiero (Tolochenaz, Switzerland)
Objective: To identify the health-related quality of life tools used
in studies of patients with dystonia, and to assess their usefulness in
this population.
Background: Health-related quality of life (hrqol) outcomes are
important to capture the impact of diseases and health conditions
from the patient perspective, however in dystonia, hrqol research has
been scarce.
Methods: A systematic literature review was performed to select
relevant dystonia studies. Comprehensive database search was under-
taken, and identified studies were included in the review if they
included at least 10 primary or secondary dystonia patients, and used
a hrqol tool. Key hrqol tools were assessed for methodological qual-
ity using the COSMIN (COnsensus-based Standards for the selection
of health Measurement Instruments) checklist.
Results: The systematic search identified 1048 studies, of which
61 studies were in dystonia patients and included in the review; they
covered a total of nine generic, and five disease-specific health-
related quality of life tools. The SF-36 was the mostly commonly
used generic tool, used in 34 studies. The Craniocervical Dystonia
Questionnaire (CDQ-24) and the Cervical Dystonia Impact Scale
(CDIP-58) were the most frequent disease-specific tools, accounting
for five and four identified studies in adult dystonia patients respec-
tively. Across almost all studies, significant health-related quality of
life gains were achieved through Deep Brain Stimulation therapy. An
assessment of instrument methodological quality demonstrated both
the CDQ-24 and CDIP-58 have good/excellent reliability and excel-
lent validity.
Conclusions: This systematic review found relatively little use of
quality of life tools in dystonia studies, and no use in a pediatric
population. In particular, validated disease-specific tools were not
widely used, and only exist for the cervical and craniocervical dysto-
nia population. Further research to identify the most appropriate
hrqol tools for use in the dystonia population is indicated.
1358
A SPECT study of type 2 dopamine receptors in patients with
adult onset primary torsion dystonia and their unaffected first
degree relatives
L. Williams, O. Kimmich, A. Molloy, I. Beiser, E. McGovern, R.
Killeen, S. Skehan, C. Collins, J. Butler, R. Reilly, S. ORiordan, M.
Hutchinson (Dublin, Ireland)
Objective: To examine type 2 dopamine receptor (D2R) avail-
ability in the striatum of patients with adult onset isolated focal dys-
tonia (AOIFD) and their unaffected first degree relatives. A
secondary aim is to determine if a correlation exists between partici-
pant temporal discrimination threshold(TDT) scores and availability
of D2R.
Background: Altered striatal dopamine neurotransmission has
been demonstrated in primary dystonia phenotypes through imaging
techniques,post mortem studies and mouse models. It is proposed
that reduced availability of striatal post-synaptic D2Rs, gives rise to
reduced inhibitory effect of dopamine on the indirect pathway to the
globus pallidus externa. This results in disinhibited thalamocortical
output and therefore contributes to excessive dystonic movements.
To date there have been no studies of dopamine receptor availability
in unaffected relatives of idiopathic cervical dystonia patients. The
TDT has been proposed as a meditational endophenotype in AOPTD.
We postulate the TDT is a function of the midbrain-basal ganglia
network for covert attentional orienting.
Methods: 16 patients with cervical AOPTD, along with 32 age
and sex matched unaffected first-degree relatives, will be recruited.
 POSTER SESSION
32 relatives are divided into two groups 16 with abnormal and 16
with normal TDT scores. Participants undergo [123I] IBZM SPECT
scanning. Specific striatal uptake is examined using the ratio of stria-
tal to occipital [123I] IBZM binding (SOR).
Results: Recruitment is ongoing and todate 15 patients, 11 rela-
tives with abnormal TDTs and 7 relatives with normal TDTs have
participated. No asymmetry between left and right SORs was
detected in any group thus far (p5>0.05; Wilcoxon signed ranks
test). Results will be presented on all 48 participants using Mann
Whitney analysis to assess differences in striatal binding between the
three subgroups.
Conclusions: This study of D2R availability in AOPTD patients
and their unaffected first-degree relatives will add to our understand-
ing of the pathogenesis of dystonia. An in-vivo finding of reduced
striatal D2R availability in patients and relatives with abnormal TDT
scores versus relatives with normal TDT scores, would further shed
light on the mechanisms involved in temporal discrimination and fur-
ther establish the TDT as a mediational endophenotype of this
disorder.
1359
Characterisation of adult onset isolated focal dystonia in an Irish
population
L. Williams, A. Molloy, O. Kimmich, E. McGovern, I. Beiser, R.
Walsh, D. Healy, H. Moore, F. Molloy, J. Butler, L. Cassidy, P.
Moriarty, S. ORiordan, M. Hutchinson (Dublin, Ireland)
Objective: To examine the clinical characteristics of adult onset
isolated focal dystonia (AOIFD) in an Irish population for the first
time, which might aid future genetic studies.
Background: AOIFD has multiple phenotypes including cervical
dystonia(CD), blepharospasm (BSP), focal hand dystonia (FHD),
spasmodic dysphonia (SD) and oromandibular dystonia (OMD).The
pathogenesis of AOIFD is incompletely understood. It is thought to
have aheterogenous genetic basis with reduced penetrance. Autoso-
mal dominant (AD), recessive and sporadic patterns of disease have
been described. Factors including age at onset (AaO), gender and
environmental exposures appear to influencephenotype and
penetrance.
Methods: Patients with AOIFD were recruited from outpatient
clinics in five Irish centres. Clinical notes were examined for gender,
AaO, symptom spread, gesteantagoniste, family history and co-
morbid psychiatric illness.
Results: Our cohort consists of 465 AOIFD patients (CD:330,
BSP:57, FHD: 43, SD:19OMD:9and 7 with Meige syndrome). Data
collection is ongoing and currently available on 235 patients. Mean
ages of onset of were: FHD:32, CD: 45, BSP:54 and SD: 68 years.
The female: male ratio was 2.0 for all phenotypes except for FHD,
which had an equal sex ratio. 56 (24%) patients had a family history
of dystonia. Of these 44 (79%) had a first degree relative affected
with dystonia. Thus far we have identified 22 multiplex pedigrees (3
or more family members affected) and 22 doubleton pedigrees (two
family members affected).
Conclusions: We confirm previous observations of sporadic and
AD inheritance with reduced penetrance. Our results to date show a
larger number of multiplex pedigrees however and suggest a higher
rate of AD inheritance. We believe further characterization of the
dystonic populationand their families from a relatively undiluted
genetic pool, such as Ireland,offers unique insight in order to guide
future genetic studies.
1360
Women do it better: Sexual dimorphism in temporal
discrimination: Biological implications
L. Williams, A. Molloy, O. Kimmich, D. Bradley, I. Beiser, E.
McGovern, R. Reilly, S. ORiordan, J.S. Butler, M. Hutchinson
(Dublin, Ireland)
S527
Objective: We sought to examine the effect of gender on tempo-
ral discrimination thresholds (TDTs) in healthy control participants.
Background: The TDT is the shortest time interval at which two
separate sensory stimuli can be detected as asynchronous and is a
measure of the detection of environmental change. TDT testing has
been investigated as a mediational endophenotype in adult onset pri-
mary torsion dystonia (AOPTD), a disorder which shows higher pen-
etrance in women. We have proposed the TDT as a function of the
evolutionarily preserved midbrain-basal ganglia network for covert
attentional orienting a mechanism that at a basic level is essential
for predator detection and survival. There are established gender dif-
ferences in cognitive function, including those related to attention.
Demonstration of sexual dimorphism of TDTs would add strenght to
our hypothesis of the TDT as measure of covert attention and the
detection of rapid environmental change.
Methods: 220 control participants (106 women), 20 to 65 years
were examined. TDT testing was carried out for two modalities, vis-
ual and tactile. The task involves commenting on the timing of two
flashing LED light stimuli and electrical impulses to the fingertips.
The combined TDT was analysed in relation to gender and age.
Results: Mean combined TDTs were significantly faster in
women than men for the age group 20-65 years with a uniform effect
of age on the TDT in both sexes (p5 0.0137). The mean TDT was
approximately 4-5 ms faster in women than men at all ages; {age
20-35 years: mean TDT: women: 27.5 ms (SD:10.9), men 31.6 ms
(8.7), p =0.043}{age 35-65 years: mean TDT women 35.1ms (13.4),
men 39.8 ms (12.5), p 5 0.066}. When the TDT data was further
analysed by fitting individual participant data to extract mean and
variance terms, the mean values were consistent with the traditional
TDT analysis. However female participant response variability
increased at 0.24 ms/per year versus 0.14 ms/per year in age
matched males.
Conclusions: Temporal discrimination is considered to be impor-
tant for the detection of environmental change and is an index of
covert (bottom-up) attentional orienting. Faster temporal discrimina-
tion in women may have survival and evolutionary significance,
given their lower body mass and the role of women in protecting
off-spring . Gender influences in sensory processing may relate
tosexual dimorphism in GABAergic circuitry observed in animal
models.
1361
A novel THAP1 sequence variant does not co-segregate with
blepharospasm in a large African-American pedigree
J. Xiao, M.M. Thompson, S.R. Vemula, M.S. LeDoux (Memphis, TN,
USA)
Objective: To characterize a large African-American pedigree
with familial blepharospasm and the potential pathogenic role of a
novel THAP1 sequence variant (SV) identified in the proband.
Background: Over 80 THAP1 SVs have been reported in patients
with various anatomical distributions of dystonia, including blepharo-
spasm. In the absence of family history and strong in silico or in
vitro evidence of deleteriousness, the pathogenicity of novel SVs in
THAP1 or other dystonia-associated genes can be indeterminate.
Given the reduced penetrance characteristic of isolated dystonia,
large pedigrees suitable for co-segregation analysis are rare and none
have previously been reported in African-Americans. Moreover, the
genomic contributions of race/ethnicity can affect the pathogenicity
of individual SVs.
Methods: Phenotypic characterization and Sanger sequencing of
a large African-American pedigree with blepharospasm. A total of 6
family members exhibited possible or definite blepharospasm among
14 subjects spanning two generations. The proband was screened for
SVs in dystonia-associated genes including TOR1A, THAP1 and
GNAL.
Results: A total of 6 family members exhibited increased blink-
ing and/or stereotyped bilateral and synchronous orbicularis oculi
Movement Disorders, Vol. 30, Suppl. 1, 2015
S528 POSTER SESSION
spasms with age of onset ranging from early childhood to late adult
life (7 to 56 yrs). The proband has severe blepharospasm responsive
to injections of botulinum toxin and was found to harbor a novel
THAP1 SV (c.314T>C, p.L105S). The p.L105S SV did not co-
segregate with blepharospasm given that it was found in only 2 of
the other 5 definitely or possibly affected subjects and 1 unaffected
family member. In addition, in silico analyses with PolyPhen-2,
MutationTaster, SIFT, LRT, and CADD predict that p.L105S is non-
pathogenic or not significantly deleterious. In particular, the CADD
C-score for this SV is only 0.48.
Conclusions: Blepharospasm can be familial and may be heredi-
tary in African-Americans. All SVs in dystonia-associated genes
should be examined with in silico tools, particularly CADD. Further-
more, pedigrees should be expanded and subjected to co-segregation
analysis if novel SVs are identified in probands.
1362
The Addenbrookes cognitive examination-revised detects
cognitive deficits in primary blepharospasm
J. Yang, N. Shao, W. Song, Q. Wei, X. Guo, R. Ou, B. Cao, H.
Shang (Chengdu, Peoples Republic of China)
Objective: To evaluate the cognition and effects of cognition on
quality of life in primary blepharospasm (BSP) patients.
Background: Growing evidence indicates an important non-
motor component to primary dystonia. Evidence supporting cognitive
impairment is limited and conflicting.
Methods: The Chinese version of Addenbrookes Cognitive
Examination-Revised (ACE-R) and Mini-mental state examination
(MMSE) were applied to detect cognitive impairment in BSP
patients and investigated the relationship between performance on
ACE-R and quality of life measured by the Medical Outcomes Study
36-item Short-Form (SF36).
Results: Seventy-nine BSP patients were compared with 40
healthy controls matched by age, gender, and education level. The
prevalence of cognitive deficits was 19.0% and 32.9% based on the
MMSE and ACE-R, respectively. BSP patents had a broad range of
cognitive deficits with the most frequent cognitive deficit orientation/
attention (31.6%), followed by language (30.3%), visuospatial func-
tion (25.3%), memory (25.3%) and verbal fluency (17.7%). The
logistic regression indicated that lower education level (OR: 0.642,
95%CI: 0.503-0.819) and older onset age (OR: 1.161, 95%CI: 1.051-
1.283) were potential independent determinants of cognitive impair-
ment. Patients with cognitive deficit had lower scores of SF36 and
its domains including physical functioning and social functioning
than those without. The ACE-R score exhibits a significant associa-
tion with scores of SF36 (r=0.252, p50.034) and its domain of phys-
ical functioning (r=0.301, p50.011) after adjustment for age, disease
duration, education level, depression, anxiety and motor disability.
Conclusions: Cognitive deficit is common in BSP patients with
different prevalence in various domains. Age of onset and education
level were potential independent determinants for cognitive impair-
ment. ACE-R is a simple and reliable screening instrument for BSP,
and poor performance is related to quality of life.
1363
Dystonic head tremor in a musician playing daegeum, Korean
traditional bamboo woodwind
H.J. Yang, B.J. Gwon, W.J. Kim, J.H. Kwon, H.J. Kim, B.S. Jeon
(Ulsan, Korea)
Objective: To describe a rare clinical presentation of musicians
dystonia.
Background: Dystonic tremors in musicians have been mainly
described on upper limb tremor including hand, wrist, elbow, or
shoulder in string instrumentalists. Although dystonic head tremor is
one of the most prevalent tremor disorders due to dystonia, little
Movement Disorders, Vol. 30, Suppl. 1, 2015
attention has been paid to dystonic head tremor on woodwind
players.
Methods: We report the clinical presentation of a 48 year-old
male woodwind player with features that suggest the diagnosis of
task-specific cervical dystonia with tremor.
Results: The daegeum (hangul: ; hanja: or ) is
a large bamboo transverse woodwind used in Korean traditional
music. A 48-year-old daegeum player presented with abnormal
tremorous movements of his head and neck, electively triggered
when playing daegeum. On examination, he showed no-no head
tremor while blowing Korean bamboo flute daegeum and affect-
ing his performance. This patient was diagnosed with a musi-
cians dystonic head tremor. His treatment consisted of the
botulinum toxin local injections at neck muscles with physiother-
apy, and his tremorous symptoms were significantly improved on
follow-up.
Conclusions: Musicians dystonia is a relatively rare clinical con-
dition that occurs due to repetitive excessive motor activity, such as
playing instruments or singing. This is the first dystonic head tremor
case associated with playing woodwind so far, and our description
enlarges the spectrum of musicians dystonia.
1364
Pregnancy in a series of dystonia patients treated with deep
brain stimulation (DBS): Outcomes and management
recommendations
N. Ziman, R.R. Coleman, P.A. Starr, H. Walker, M. Volz, S. Guthrie,
J.L. Ostrem (San Francisco, CA, USA)
Objective: To describe a series of dystonia patients who had suc-
cessful pregnancies after DBS and to provide guidelines for women
considering pregnancy with DBS.
Background: DBS is a highly effective treatment for isolated idi-
opathic dystonia when oral medications and botulinum toxin fail to
provide sufficient symptomatic relief. Dystonia often affects children
and young adults and DBS therapy can allow patients to regain func-
tional independence. Some of these individuals eventually start fami-
lies and become pregnant; however, there is limited literature to
guide physicians and to help patients navigate this scenario. Addi-
tionally, with expanding indications for DBS and earlier use in well-
established indications, pregnancy with DBS may become more
prevalent.
Methods: We reviewed all DBS cases implanted at UCSF and
UAB from 1998 to 2014 and identified patients who became preg-
nant. Patient records were reviewed and a structured interview was
conducted.
Results: We identified 5 dystonia patients implanted at 2 centers
that became pregnant and had successful pregnancies (6 pregnancies,
7 live births; 1 twin pair). Patients presented with generalized dysto-
nia (n52;one DYT11), cervical dystonia (n51), juvenile onset pri-
mary hemidystonia (n51), and hemidystonia secondary to a striatal
infarct (n51). All patients received GPi implants (n53 bilateral,
n52 unilateral). The average time from 1st DBS implant to 1st preg-
nancy was 5.7 years. Pulse generators present at birth included
Activa RC (n52), Activa PC (n52), Activa SC (n51), and Soletra
(n51). All pregnancies were uncomplicated and each patient
received appropriate prenatal care. Mode of delivery was not influ-
enced by the presence of DBS. Four children were born by spontane-
ous vaginal delivery and 3 by planned c-section. Stimulation
remained ON during 3 of the births (all vaginal deliveries) and was
turned OFF for 4 (1 vaginal and 3 c-section deliveries). All deliv-
eries were uncomplicated and all children were born full term and
healthy as defined by APGAR scores. Pulse generators did not hinder
breast-feeding.
Conclusions: In this small sample, pregnancy, delivery, and
breastfeeding were well tolerated by women with various forms of
dystonia who were receiving DBS therapy. Treatment with DBS
therapy should not be considered a contraindication to pregnancy.
 POSTER SESSION
Huntingtons disease
1365
Investigating disinhibited behaviour in Huntingtons disease
(HD): Subjective ratings and motor and cognitive correlates
S.C. Andrews, D. Craufurd, R. Reilmann, S.J. Tabrizi, J.C. Stout,
Track HD Investigators (Melbourne, Australia)
Objective: To examine self- and companion-ratings of disinhib-
ited behaviour in pre-symptomatic and symptomatic HD, and
whether motor or cognitive symptoms relate to these behaviours.
Background: Disinhibited behaviour is common in HD but its
progression and the way it relates to other clinical features of the
disease is not well understood.
Methods: 123 early diagnosed HD participants, 120 pre-
symptomatic HD participants and 123 healthy controls took part in
this research as part of a broader study (TRACK-HD). A subset of
pre-HD participants (n562) and HD participants (n580) also had
companions who provided additional ratings. Participants and com-
panions completed the Frontal Systems Behavior scale (FrSBe), as
well as a battery of cognitive and motor tasks. Groups did not differ
significantly for gender. The HD group was significantly older than
pre-HD group.
Results: After controlling for age, HD participants rated them-
selves significantly more disinhibited than controls, with pre-HD
having an intermediate level of disinhibition. Companions rated HD
participants as significantly more disinhibited than pre-HD partici-
pants. Patient and companion ratings of disinhibition showed good
agreement, with moderate correlations. In HD, higher self-ratings
(but not companion-ratings) were weakly correlated with poorer self-
paced tapping and but better working memory performance. For pre-
HD no motor or cognitive measures were associated with either self-
or companion-ratings of disinhibited behaviour.
Conclusions: These findings indicate that disinhibited behaviour
becomes more common as HD progresses, and that self-ratings and
companion-ratings show moderate agreement, indicating patients
have reasonable insight into this behaviour. In symptomatic HD,
self-ratings were weakly correlated with one motor and cognitive
measure, however, in general disinhibited behaviour in HD seems to
develop independently of motor and cognitive features. These find-
ings underline the need to consider the presence, functional impact,
and management of disinhibited traits separately from the cognitive
and motor features of HD.
1366
Multisensory cues could be effective to improve balance and gait
in Huntingtons disease?
T.T.C. Capato, M.S. Haddad, M.E.P. Piemonte, E.R. Barbosa (S~ ao
Paulo, Brazil)
Objective: To evaluate the effectiveness of a Multisensory Cues
(MC) physiotherapy program to improve balance, gait and functional
mobility in Huntingtons Disease (HD).
Background: In HD the chorea is not the only important mani-
festation of the neurodegenerative disease. Many cognitive and
non-motor symptoms may be more disabling than the motor symp-
toms. A loss of balance and gait could lead to functional decline
and increase the risk for falls in individuals with HD. However,
there are few evidences that a physiotherapy treatment with MC
improve functional disturbances of the basal ganglia motor circuit.
The mechanisms by which improvement occur in HD remains
inexplicable.
Methods: 30 HD were assessed by a single blind examiner before
and after 10 training sessions (1x week during 45 min) and after 60
days of the end of the training. Balance was assessed by Berg Bal-
ance Scale (BBS) and Mini BESTest. Gait by TUG and 6 min walk
test. Mobility was evaluated by Functional Capacity (FC), Functional
S529
Independence Measurement Scale (FIM) and Barthel Scale. Through
interviews independence to AVDS; motor performance and cognition
through UHDRS. The subjects should have HD diagnosis genetically
confirmed and they were expected to understand tests and exercises
sequences according to inclusion criteria. During the study period
there wasnt medication changing. The patients were divided on 3
groups according criterial rules; aged 45.91. Group (I) done treat-
ment programme comprised generalized exercises with MC and was
divided in 3 parts: 1. Warming (10 min stretching, trunk mobility
and motor control); 2. Main Part (30 min/gait and balance training
with MC and functional activities/attention strategies; 3. Relaxation
(5 min/breathing exercises and trunk control). The Group II did the
same exercises without MC. Group III receives only orientations.
Results: There was an improvement according to media score for
the Group I e II of BBS (p50,01) Mini BESTest (p50,00) TUG
(p50,01) FMI (p5 0,01). After 60 days the scores are maintained
only on Group I.
Conclusions: The physiotherapy programme with MC proposed
in this study is effective and connected to medicine seems to be
effectiveness to minimize balance and gait disorders in HD and pro-
vides improvement in functional independence.
1367
Withdrawn by Author
1368
Clinical characteristics and motivations of individuals
undergoing predictive testing for Huntingtons disease (HD)
J. Corey-Bloom, S.K. Nam, A. Herndon, L. Korty (La Jolla, CA,
USA)
Objective: To examine the clinical characteristics and motiva-
tions of individuals choosing to undergo predictive testing for Hun-
tingtons disease (HD) at one academic site.
Background: Predictive testing programs for HD have been
available in the US for over 20 years now; yet little has been pub-
lished regarding the <10% of individuals at risk for HD who
actually pursue presymptomatic testing.
Methods: Participants were asked to fill out a questionnaire prior
to testing that explored items such as family history, social supports,
reason(s) for testing, likelihood that the individual possessed a posi-
tive gene, and expected outcomes after the result. Over a 16-year
period (1998-2014), a total of 164 individuals at risk for HD
requested predictive testing.
Results: The mean age was 39.7 (range 19-75); 58.5% were
female. Most were white (83.3%), married (56.8%), and already
had children prior to testing (57.7%). More males (60.9%) had an
affected mother; more females (55.7%) had an affected father.
Most participants (67.6%) did not have siblings who had already
gone through predictive testing. Reasons for testing were evenly
distributed among family planning (23.6%), know how to
spend next 20 years(20.7%), clarify childrens status(22.9%),
reduce uncertainty(21.4%); however, more males wanted to
know how to spend next 20 years(29.8%), whereas, more
females wanted to reduce uncertainty(27.7%). Of the subjects
who eventually tested positive, over 40% felt they were likely,
very likely, or certain to carry the mutation. Interestingly, of the
subjects who eventually tested negative, 24% felt that they would
likely feel uncomfortable with their siblings. Almost half of all
subjects felt that depression, either temporary or longlasting,
might be a potential outcome.
Conclusions: We conclude that, although predictive testing obvi-
ously helps some individuals with reproductive and life planning, the
possible social and psychologic consequences of pursuing presympto-
matic testing should also be considered.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S530 POSTER SESSION
1369
The Huntingtons disease-behavioral questionnaire (HD-BQ): A
new screening tool for behavioral disturbances in HD
J. Corey-Bloom, A. Herndon, A. Lam, P. Gilbert (La Jolla, CA,
USA)
Objective: To examine the usefulness of a new behavioral ques-
tionnaire for patients with, and at risk for, Huntingtons disease
(HD).
Background: Behavioral changes, including apathy, depression,
irritability, anxiety, and difficulty prioritizing and initiating activities,
are characteristic features of HD. For families and caregivers, they
are often the most distressing aspect of the disease. There is evidence
that behavioral manifestations may predate motor signs by a decade
in HD. The assessment of these behavioral disturbances is therefore
important.
Methods: The UCSD HD-BQ was administered to 55 HD, 28 at-
risk gene positive (AR1), and 13 normal control (NC) subjects at
our Center. The UCSD HD-BQ was also administered to 32 HD
caregivers. We used Cronbachs alpha analysis to examine the inter-
nal consistency of the HD-BQ components; One-Way ANOVA/
Tukey Posthoc to compare groups on dependent variables; Pearson
product-moment correlations to compare HD-BQ scores with other
variables.
Results: The HD-BQ showed substantial internal consistency
(Cronbach a 5 0.94). It showed construct validity with high-very
high correlations with other behavioral measures (PBA r=0.55-0.70;
HADS r=0.73-0.90), and poor correlations with measures of cogni-
tive functioning and motor impairment (r=-0.04-0.16 and 0.00,
respectively). The HD-BQ discriminated between HD (mean 30.5),
preHD (mean 25.3), and control subjects (mean 4.9) (p50.000).
When questionnaires were completed independently by 32 HD sub-
ject/caregiver pairs, there was a discrepancy in the perception of
impairment between patients and their caregivers, with caregivers
identifying more behavioral changes (mean difference=16.17 points).
Items with the largest discrepancies included more indecision, diffi-
culty shifting thoughts or activities, increased sensitivity, and less
insight with regard to symptoms.
Conclusions: The HD-BQ is a quick, reliable instrument for
screening behavioral changes in patients with, and at risk for, HD.
When possible, information regarding behavior should be corrobo-
rated by an informant since HD patients tend to underestimate their
impairment.
1370
Assessing psychiatric symptoms in individuals with, and at risk
for, Huntingtons disease
J. Corey-Bloom, S.J. Howell, A. Herndon (La Jolla, CA, USA)
Objective: To examine the usefulness of the Symptom Checklist-
90-Revised (SCL-90R), a 90-item self-report psychiatric symptom
inventory, for assessing psychiatric symptoms in patients with, and
at risk for, HD.
Background: HD is an autosomal dominant, neurodegenerative
disease, characterized by motor, cognitive, and various psychiatric
symptoms, including depression, irritability, anxiety, and obsessive-
compulsive features. Evidence suggests that psychiatric manifesta-
tions may predate motor signs by a decade in HD but studies of psy-
chiatric functioning in pre-manifest HD have been equivocal.
Methods: We administered the SCL-90-R to 36 normal controls
(NC) and 88 gene carriers, stratified on the basis of the UHDRS
Total Functional Capacity (TFC) and Penny Burden of Pathology
(BOP) score as early pre-manifest, transitional (patients transitioning
from pre-manifest to symptomatic), or later HD. Participants also
completed additional assessments commonly used in HD, including
the UHDRS Total Motor Score (UHDRS-TMS), and brief cognitive
measures including the MMSE, MoCA, and Symbol Digit Modalities
(SDM) Test. One-way ANOVA with Tukey post-hoc comparisons
Movement Disorders, Vol. 30, Suppl. 1, 2015
were used to compare psychiatric symptom dimensions for each
group.
Results: Not surprisingly, there were significant differences
between NC and later HD subjects with regard to anxiety and
depression (p<0.05) and especially, obsessive-compulsive symptoms,
psychosis, and paranoia (all p<0.01). Motor (UHDRS-TMS, p<0.01)
and cognitive differences (MMSE, MoCA, SDM, all p<0.01) were
only observed between later HD subjects and NC. In contrast, transi-
tional subjects showed significant differences with regard to
obsessive-compulsive symptoms and psychosis (p<0.01) compared
to NC. It was the early pre-manifest subjects who showed the strong-
est difference with regard to anxiety (p<0.01).
Conclusions: The SCL-90R can be useful for assessing psychiat-
ric functioning in individuals with, and at risk for, HD, and suggests
that significant psychiatric symptoms may be present early in the
course of the disease in individuals with little to no cognitive or
motor decline.
1371
Relationship of body mass index with Huntingto ns disease
severity: A Spanish multicenter study
E. Cubo, J. Rivadeneyra, D. Armesto, R. Camara, N. Mariscal-P
erez
(Burgos, Spain)
Objective: To analyze the association of body mass index (BMI)
with Huntingto ns disease (HD) severity.
Background: Patients with HD are at risk for an unintended
body weight loss and subsequent increased risk for institutionaliza-
tion, morbidity and mortality.
Methods: National, observational, cross-sectional study of the
European Huntingto ns Disease Network (EHDN). The frequency of
food consuming, caloric and nutrients intake in patients with HD
were assessed using validated questionnaires for the Spanish popula-
tion, and calculated using Alimentaci on and Salud, version 2.0.
Nutritional state was estimated by the body mass index (BMI), and
disease severity using the Unified Huntingto ns Disease Rating Scale
and Total Functional Capacity (TFC). Lineal regression models were
performed using the BMI as the dependent variable, and energy bal-
ance, TFC, presence of caregiver, dysphagia, CAG repeats, comor-
bidities, intake of supplements and pharmacological treatments, age,
gender, education, and physical activity as the independent variables.
Results: Two hundred and twenty four patients with HD were
included (59% women) with a mean age of 47.41 614.26 years,
median TFC 9 (3-13), and median UHDRS motor score of 33.5
(3.75-56). In our sample, 53% had moderate-high adherence to the
Mediterranean diet, 75.8% had normal-high caloric intake, 124
(55.4%) normal BMI, and 13 (6.7%) low BMI. Patients on antidopa-
minergic and antiepileptic drugs had lower BMI compared to those
not taking those (p50.006; p50.01, respectively). In the lineal
regression model (corrected R2=0,27) BMI was associated with age
(b=0.003, p50.01), gender (males) (b=0.13, p50.003) and energy
balance (b=-0.0001, p<0.0001).
Conclusions: Younger, female patients are at risk for weight loss
in HD. However an adequate calorie intake might help to prevent it.
1372
Outcomes of bilateral GPi DBS in three patients with
Huntingtons disease
C. Delorme, A. Durr, C. Karachi, J. Yelnik, M.L. Welter, D. Grabli
(Paris, France)
Objective: To evaluate efficacy and safety of bilateral Globus
pallidus internus (GPi) deep brain stimulation (DBS) in three patients
with genetically confirmed Huntingtons disease (HD).
Background: Medication for chorea in HD offer limited benefits
and may worsen some symptoms like bradykinesia. GPi DBS has
been suggested to be an interesting alternative in alleviating
 POSTER SESSION
abnormal movements in HD, mostly based on the experience of DBS
in other hyperkinetic Movement Disorders like levodopa induced
dyskinesias and dystonia. Previous reports of GPi stimulation in HD
patients have highlighted a significant improvement in motor symp-
toms, particularly chorea. However, very little is known about the
long term benefits and tolerability of this treatment.
Methods: Three patients (aged from 24 to 56 years) who had
prominent pharmacoresistant chorea without severe cognitive or psy-
chiatric impairment were considered for DBS. They underwent bilat-
eral GPi implantation between 2012 and 2013 and were
prospectively followed up for up to 30 months. The main outcome
measure was the change in the total motor score and the chorea sub-
score of the Unified Huntingtons Disease Rating Scale (UHDRS)
between preoperative and tardive postoperative assessments (30, 24
and 12 months respectively). Tolerability was also evaluated; with
particular attention to any worsening in bradykinesia, dysarthria or
cognitive impairment.
Results: A significant reduction of chorea was observed in all
patients (13%, 67% and 18% respectively) between preoperative and
late postoperative assessments. Total UHDRS was reduced at tardive
postoperative assessment for two patients (27% and 3% respec-
tively). We found severe and quick worsening of total UHDRS score
and chorea subscore for all patients after turning OFF the stimula-
tion. The main side effect of DBS was an increase in dysarthria.
There were no complications related to the surgery or significant
worsening of bradykinesia, psychiatric or cognitive impairment.
Conclusions: GPi DBS may be a valuable option for alleviating
chorea in HD patients, and is well tolerated. The significant worsen-
ing of motor symptoms after turning OFF the stimulation supports
the efficiency of this method. GPi DBS. Further studies are war-
ranted to evaluate the long-term benefit of DBS and to define the
most appropriate inclusion criteria.
1373
PPAR- a activation attenuates 3-nitropropionic acid induced
behavioral and biochemical alterations in rats: Possible
neuroprotective mechanisms
D.K. Dhull, D. Bhateja, A. Sidhu, B.V.K. Reddy, S.S.V. Padi, A.
Kumar (Chandigarh, India)
Objective: To explore whether peroxisome proliferator-activated
receptor (PPAR)- a agonist may attenuate various behavioral and
biochemical alterations induced by systemic administration of 3-
nitropropionic acid (3-NP).
Background: PPAR is regarded as potential therapeutic targets to
control various neurodegenerative disorders. However, none of the
study has elucidated its effect in the treatment of Huntingtons
disease.
Methods: 3-NP (20mg/kg, i.p., an irreversible inhibitor of succi-
nate dehydrogenase, was administered for 4 consecutive days. Feno-
fibrate (100mg/kg, and 200mg/kg; p.o.) was administered once daily
for a period of 4 days, 30 min before 3-NP administration. MK886
(1mg/kg, i.p.), was administered 30 min before fenofibrate only at
high dose (200 mg/kg, p.o.) once daily for a period of 4 days 30 min
before 3-NP administration. Effects of such drugs were assessed on
behavioral and biochemical parameters.
Results: Intraperitoneal administration of 3-NP (20 mg/kg., i.p.)
for 4 days in rats produced hypolocomotion, muscle incoordination,
and cognitive dysfunction. Daily treatment with fenofibrate (100 or
200 mg/kg., p.o.), 30 min prior to 3-NP administration for a total of
4 days, significantly improved the 3-NP induced motor and cognitive
impairment. Biochemical analysis revealed that systemic 3-NP
administration significantly increased oxidative and nitrosative stress
(increase lipid peroxidation, protein carbonyls and nitrite level), lac-
tate dehydrogenase activity whereas, decreased the activities of cata-
lase, superoxide dismutase, reduced glutathione, and succinate
dehydrogenase. Fenofibrate treatment significantly attenuated oxida-
tive damage, cytokines and improved mitochondrial complexes
S531
enzyme activity in brain. In the present study, MK886, a selective
inhibitor of peroxisome proliferators activated receptor-a was
employed to elucidate the beneficial effect through either receptor
dependent or receptor independent neuroprotective mechanisms.
Administration ofMK886 (1 mg/kg, i.p.) prior to fenofibrate
(200 mg/kg, p.o.) abolished the effect of fenofibrate.
Conclusions: The results showed that receptor dependent neuro-
protective effects of fenofibrate in 3-NP administered rats provide a
new evidence for a role of PPAR-a activation in neuroprotection
that is attributed by modulating oxidative stress and inflammation.
1374
Alternative for reducing chorea in Huntingtons disease (ARC-
HD): Results from the Switch cohort
S. Frank, Huntington Study Group/ARC-HD Switch Investigators
(Boston, MA, USA)
Objective: To evaluate the safety and efficacy of switching
patients from stable doses of tetrabenazine (TBZ) directly to SD-809
in Huntingtons disease (HD).
Background: SD-809 is a deuterated form of TBZ, a centrally
acting VMAT-2 inhibitor. Worldwide, TBZ has been used for deca-
des to treat hyperkinetic Movement Disorders such as chorea, tics
and tardive dyskinesia. Deuterium is a non-toxic, naturally occurring
form of hydrogen that when substituted at key positions on a mole-
cule, can alter drug metabolism and pharmacokinetics. In SD-809,
the intrinsic pharmacological activity of TBZ is retained but with a
comparable AUC and lower Cmax from lower doses. The properties
of SD-809 allow for less frequent dosing and reduced interpatient
variability with potential to improve the overall safety profile while
maintaining or improving chorea control in HD.
Methods: 36 patients (60% male, mean age 52.4, mean
CAGn=44.5) with HD and adequately controlled chorea on stable
doses of TBZ for at least eight weeks were enrolled at 14 sites. After
an overnight switch from TBZ to an AUC-matched dose of SD-809
(about half the dose of TBZ), patients returned for evaluation at
Weeks 1, 4 and 8. Dose adjustment was permitted after Week 1.
Chorea was measured using the Total Maximal Chorea (TMC) sub-
score of the Unified Huntingtons disease Rating Scale.
Results: The mean (SE) change in TMC was -0.8 (0.4) at Week
1 and -0.8 (0.5) at Week 4, compared to baseline. The most com-
monly reported adverse events were somnolence, fall, and nasophar-
yngitis. In addition, the mean (SE) change in TMC in 21 patients
who had reached Week 8 was -1.9 (0.8) points; no subject discontin-
ued before Week 8. The mean TBZ dose at baseline was 41 mg and
the mean SD-809 dose at Weeks 1 and 4 was 20 mg and 29 mg,
respectively. At Week 8, the mean SD-809 dose was 33 mg.
Conclusions: Patients with chorea associated with HD can safely
and rapidly convert from TBZ to open-label SD-809. There was con-
tinued control of chorea with the possibility of improving chorea
control based on minimal adverse effects. Switching from a stable
medication directly to an AUC-matched dose of a deuterated com-
pound may be accomplished overnight, without an extended titration
period or loss of symptom control.
1375
First time use of SD-809 in Huntingtons disease (first-HD)
S. Frank, Huntington Study Group/First-HD Investigators (Boston,
MA, USA)
Objective: Evaluate the efficacy, safety and tolerability of SD-
809 in treating chorea associated with Huntingtons disease (HD).
Background: SD-809 is a deuterated form of tetrabenazine
(TBZ), a centrally acting VMAT-2 inhibitor. TBZ is used to treat
hyperkinetic Movement Disorders. Deuterium can alter drug metabo-
lism and pharmacokinetics in small molecule drugs. SD-809 retains
Movement Disorders, Vol. 30, Suppl. 1, 2015
S532 POSTER SESSION
the intrinsic pharmacological activity of TBZ. Half the mg dose
delivers a comparable AUC to a full dose of TBZ and lower Cmax.
Methods: This randomized, double blind, placebo-controlled, trial
evaluated SD-809 in ambulatory subjects with chorea associated with
HD. Study drug was titrated to adequate chorea control over 8
weeks, maintained for 4 weeks, followed by a 1 week washout. The
total daily dose ranged from 6 to 48 mg. Entry criteria included a
Total Maximal Chorea (TMC) score 8, Total Functional Capacity
score 5 and no untreated or undertreated psychiatric illness.
Results: 90 subjects (45:45) were enrolled (44% female, mean
age=53.7, mean CAGn=43.9). The TMC score on SD-809 improved
by 2.5 points (21 percentage points) over placebo from baseline to
maintenance therapy (p<0.0001). Total Motor Score (TMS)
improved 4.0 points over placebo (p50.002). Secondary endpoints
which improved significantly for SD-809 vs. placebo included the
patient global impression of change (p50.002), clinical global
impression of change (p50.002) and SF-36 Physical functioning
scale (p50.03). The mean SD-809 daily dose at end treatment was
approximately 40 mg. One SD-809 subject terminated early. Overall,
adverse event (AE) rates were similar for SD-809 and placebo. The
most common AEs reported by all subjects were irritability (SD-809:
6.7% vs. placebo: 13.3%), somnolence (11.1% vs. 4.4%), dry mouth
(8.9% vs. 6.7%) and dizziness (4.4% vs. 8.9%). Depression, anxiety,
akathisia and Parkinsonism were reported at the same or lower fre-
quency for SD-809 than for placebo.
Conclusions: SD-809 effectively reduced chorea in HD with an
impressive safety and tolerability profile. Treatment with SD-809
improved TMS beyond chorea, and improved quality of life meas-
ures, suggesting that an effective symptomatic treatment with good
tolerability and twice-daily dosing provides significant overall benefit
to HD patients.
1376
Determining Huntingtins endogenous functions using drosophila
and mammalian systems
E. Furr Stimming, Y.N. Rui, Z. Xu, Z. Chen, D. Chen, Y. Sun, A.
Tito, S. Zhang (Houston, TX, USA)
Objective: Although the Huntingtin gene has been extensively
studied since its identification in 1993, its normal function remains
elusive. Characterizing a Huntingtin homolog in Drosophila will
complement the established mammalian models for Huntingtin
studies.
Background: We established a null-mutant (dhtt-ko) for Dro-
sophila Huntingtin (dhtt) and performed preliminary characterization
of its phenotypes. We found expression of human Huntingtin could
rescue the dhtt-ko mutant phenotypes, suggesting its evolutionally
conserved functions.
Methods: Using this dhtt-ko mutant, we conducted genetic modi-
fier screens to identify cellular pathways that require the presence of
normal dhtt activity. We developed tools that allow convenient
detection and isolation of endogenous dHtt proteins. Using Pacman
and MiMIC approaches, we have generated and confirmed a set of
genome dhtt transgenic lines with different fluorescence and epitope
tags that allow tracking and isolation of endogenous dHtt protein.
Because the tagged dhtt gene in these established lines is still in its
endogenous genomic DNA context, the expression of the tagged dhtt
remains under the control of its native regulatory elements, thus
ensuring the normal patterns and expression levels of the tagged
dHtt protein. Using these genome-tagging lines, we carried out
affinity-purification followed by mass spectrometry from Drosophila
tissues and identified a large number of unique dHtt-interacting
proteins.
Results: The majority (96%) of the isolated dHtt-interactors are
conserved in humans, some of them have previously been reported
as Huntingtin-interacting partners from mammalian-based studies.
Functionally, these Huntingtin-interactors can be grouped into multi-
ple categories. Examination of the available dataset supports that
Movement Disorders, Vol. 30, Suppl. 1, 2015
Huntingtin functions as a scaffold to integrate multiple signaling
pathways and cellular processes.
Conclusions: Based on the results from the dhtt-ko mutant-based
genetic screens and the proteomic data from Drosophila studies, we
are conducting further analyses in mammalian cells to validate the
relevance of the findings to humans. By combining genetic and
genomic approaches in Drosophila and mammalian systems, the
knowledge gained will help elucidate the normal functions of the
human Huntingtin gene and how its dysfunction due to polyglut-
amine expansion can contribute to HD pathogenesis.
1377
Progressive degeneration of nigrostriatal pathway in
Huntingtons disease. A 123I-FP-CIT SPECT three-year follow-up
study
J. Gamez, O. De Fabregues, C. Lorenzo-Bosquet, G. Cuberas-
Borros, M. Salvado, F. Carmona, J. Alvarez-Sabin, J. Castell-
Conesa (Barcelona, Spain)
Objective: To study the potential of [123I]-FP-CIT SPECT
DaTSCANV R in investigating the progression of presynaptic dopami-
nergic degeneration in Huntingtons disease (HD).
Background: HD is a progressive polyglutamine disease that
leads to a severe selective striatal neuronal loss. Degeneration of
brainstem nuclei (substantia nigra, pontine, reticulotegmental, raphe
and vestibular nuclei, and superior and inferior olives) has been
observed in HD patients. [123I]-FP-CIT SPECT is useful in investi-
gating presynaptic dopaminergic degeneration.
Methods: Open and prospective study in HD patients that under-
went SPECT scans with 123I-FP-CIT at baseline, first, second and
third year of follow-up, evaluating the SPECT imaging based on
qualitative and semiquantitative analysis.
Results: Five patients were included. The mean annual decline in
[123I]-FP-CIT uptake in caudate and putamen after 3 years of follow-
up was 5.8% and 9.6%, respectively.
Conclusions: Our findings confirm that the degeneration of nigro-
striatal pathway may occur in HD patients. We suggest that [123I]-
FP-CIT SPECT is useful in investigating the progression of presyn-
aptic dopaminergic degeneration in HD, and may be useful as a dis-
ease biomarker, providing an objective method for measuring the
effectiveness of future neuroprotective therapies.
1378
Time perception in Huntingtons disease
E.M. Gatto, P. Agostino, M. Cesarini, A. Sanguinetti, J.L.
Etcheverry, D. Golombek (Buenos Aires, Argentina)
Objective: to assess temporal cognition in two different experi-
ments: a peak-interval time production and a reaction time task in
patients with Huntingto ns disease (HD).
Background: Interval timing-(IT) is the ability to perceive,
remember, and organize behavior in the seconds-to-minutes-range,
that contributes to spatiotemporal performance and structures our
action and cognition.
Timing disruptions have been reported in neurodegenerative dis-
orders with dopaminergic and fronto-striatal impairment, including
relatively small populations of HD patients. Moreover, fMRI
reported abnormal striatal, prefrontal, frontal and parietal cortices
activation in these patients.
Methods: 11 HD patients and 11healthy controls matched by
age, sex and years of education were analyzed. The study was
approved by Institutional Committee. Timing assessment: a visual
time production task at 3, 6 and 12 seconds target intervals was
assessed in separate blocks. The reaction time task was adapted and
validated from Thorne et al., 2005, Behav. Res Methods 37:111.
Briefly, Participants were asked to respond as quickly as possible to
black circles appearing on a white screen. Statistical analysis:
 POSTER SESSION
MATLAB was used for data analysis and ANOVA or t tests were
administered when appropriated.
Results: 11 HD patients, mean age: 48.09 6 13.69, mean
expanded allele 42.9 6 1.59 and mean disease duration 7.57 years
(range 1-12 years) showed significant differences in peak location,
width and amplitude at 6s target intervals compared to controls. S1
rate index (period prior target time) was statistically different at 3, 6
and 12s, while S2 rate index (period after target time) was significant
only at 3s. The mean reaction time was higher in HD patients
(p<0.001, two-tailed t-test).
Conclusions: According with our results subjective timing is sig-
nificantly impaired in HD and its assessment might represent a useful
measurement of the progression of disease.
1379
Circadian rhythm and chronotype in Huntingtons disease
C.O. Godeiro, Jr., J.E. Rosado, Jr., L.A. Freire, R.A. Lucena, T.L.
Silva, J.A. Fontenele (Natal, Brazil)
Objective: We aimed to (1) assess the association between circa-
dian rhythm disorders in patients diagnosed with HD and symptoms
of the disease, (2) identify the existence and describe the characteris-
tics of the sleep disorder between the study group and (3) test
whether an association exists between sleep disorders, motor symp-
toms, chronotype and olfaction in the selected sample.
Background: Huntingto ns Disease (HD) is a disorder that causes
motor and emotional control changes, impaired cognitive ability,
involuntary movements and the clinical manifestations can be pre-
dicted by some motor, behavioral anf psychological changes. The
restoration of this cycle can retard the cognitive decline characteristic
of the disease and improve the quality of life of patients with this
genetic condition.
Methods: Actigraphy was used for objective assessment of sleep
and rest - activity rhythm. The cognitive state of patients with HD
was measured through experimental Brazilian version of Montreal
Cognitive Assessment. For the analysis of motor symptoms was
applied to motor part Unified Huntingtons Disease Rating Scale
Motor, These symptoms were also investigated by the International
Scale Degrees of Restless Legs Syndrome (EPI). In the subjective
assessment of sleep was used Quality Index Pittsburgh Sleep and
Sleepiness Scale Epworth, the chronotype was characterized accord-
ing to the Questionnaire for Identifying Individuals Morning and
Evening. The olfaction was assessed according to the Sniffin Sticks.
Results: We found that as lower is the ability of olfactory dis-
crimination, greater is the severity of EPI (p 5 0.04). The objective
evaluation of sleep and rest - activity rhythm, actigraphy data
showed that as greater is the fragmentation of the rest - activity
rhythm (IV60), greater is the activity during the 5 hours of lower
activity (L5) (p 5 0.002). Correlating the tests applied to the actigra-
phy data, we found no statistical significance.
Conclusions: There are sleep disorders in patients with HD, but
we need more studies to detail them. They did not correlate to motor
symptoms and neither to olfaction. There is a correlation between
resteless legs syndrome motor symptoms and olfaction.
1380
Using a brief balance assessment to estimate disease onset in
Huntingtons disease
A. Herndon, J. Corey-Bloom, A. Lam, C. Heil, S.K. Nam, P. Gilbert,
D. Goble (La Jolla, CA, USA)
Objective: To enhance estimates of Huntingtons disease (HD)
onset using a simple and practical body sway assessment device (i.e.
Wii Balance Board).
Background: HD is a progressive neurodegenerative disorder
with motor, cognitive, and psychiatric symptoms that typically
emerge in the fourth or fifth decades. Balance difficulties have been
S533
demonstrated in individuals who are near to disease onset using state
of the art balance equipment, but more practical balance assessments
are required for clinical implementation. Balance assessments may
be useful for predicting disease onset and progression, but studies
are limited. Predicting when HD onset will occur is a critical factor
for disease management.
Methods: We assessed total body sway (TBS) on 59 HD gene
carriers and 29 normal controls (NC) employing a Wii balance board
and laptop software. Gene carriers were stratified on the basis of dis-
ease severity using the Penny Burden of Pathology score and/or
UHDRS total Functional Capacity (TFC) as 1) early pre-manifest
(n514); 2) transitional (i.e. individuals close to disease onset or with
very mild HD, n517); or 3) later HD (n528). Subjects were admin-
istered a balance test consisting of 12, 10-second static balance trials
that included combinations of eyes open or closed while standing on
a stable versus unstable (i.e. foam) surface. A one-way ANCOVA
adjusting for age was used in each condition to compare total body
sway (TBS). Correlations were assessed in gene carriers using Pear-
sons r.
Results: Participants were well matched with regard to age and
education. The later HD subjects showed statistically significant TBS
in all conditions (p<0.001) compared to NC. Importantly, even the
transitional subjects showed significantly more TBS in the eyes open
(p<0.01) and eyes closed/stable (p<0.05) and eyes closed/unstable
(p<0.001) conditions. TBS correlated most strongly with measures
of motor ability (r=.485 to .702) and TFC (r=-.418 to -.658), as
opposed to cognition (r=-.289 to -.484).
Conclusions: Increased body sway, easily evaluated using a brief
balance assessment, may serve as an important functional marker in
patients with, and during the transition to, HD. Further studies will
be needed to confirm and extend these findings.
1381
Examining cognitive processing speed in Huntingtons disease
(HD)
A. Herndon, A.S. Nathan, J. Corey-Bloom (La Jolla, CA, USA)
Objective: To enhance estimates of Huntingtons disease (HD)
onset using the Computerized Test of Information Processing (CTiP).
Background: Reaction time may be a useful marker for predict-
ing disease onset and progression in HD. The CTiP, administered on
a laptop, is a relatively simple and useful tool for evaluating the
extent to which neurological conditions affect cognitive processing
speed. It consists of three reaction time subtests that successively
increase in task complexity.
Methods: Gene carriers (n546) were categorized, using the
UHDRS Total Functional Capacity (TFC) and Penny Burden of
Pathology score (BOP), as early pre-manifest, transitional (i.e. indi-
viduals close to disease onset or with very mild HD), or later HD.
Subjects were administered the three computerized reaction time
(RT) subtestsSimple RT (SRT); Choice RT (CRT), with an added
decisional component; and Semantic Search RT (SSRT) with a con-
ceptual component. Each subtest included 10 practice trials followed
by 30 test trials. Subjects were also administered traditional cognitive
assessments commonly used in HD, including the MMSE, MoCA,
Symbol Digit Modalities Test (SDMT), Trail Making Test and
Verbal Fluency FAS. A one-way ANCOVA adjusting for age was
used to compare group performance on the RT subtests.
Results: Patient groups were well matched with regard to age
and education. The later HD subjects showed significantly slower
reaction times in all conditions (p<0.001 - p<0.01) as compared to
NC. There were no statistically significant differences between tran-
sitional subjects and NC on the traditional cognitive measures; how-
ever, importantly, transitional subjects did show significantly slower
reaction times on the SRT (p<0.01), CRT (p<0.01), and SSRT
(p<0.05) subtests.
Conclusions: Our results suggest that the CTiP can detect deficits
in the speed at which information is processed in individuals with,
Movement Disorders, Vol. 30, Suppl. 1, 2015
S534 POSTER SESSION
and during the transition to, HD. Further studies will be needed to
confirm and extend these findings.
1382
Objective measurement of gait abnormalities in Huntingtons
disease using a shoe-worn inertial sensor
P. Hogarth, A. Lenahan, A. Portillo, R.K. Ramachandran, K.A.
Stenson, A.T.R. Legedza, M.C. Botfield, F.B. Horak, J. McNames, M.
El-Gohary (Portland, OR, USA)
Objective: To evaluate the feasibility and utility of a shoe-worn
inertial sensor to measure gait abnormalities in Huntingtons disease
(HD) in the home setting.
Background: Clinical rating scales provide only point assess-
ments of disease-related impairments in HD, lack sensitivity, and
require that a clinician experienced in the scales use evaluate the
patient. A tool that would allow longitudinal, objective, quantitative
measurement of impairments may offer advantages over standard
clinical rating scales.
Methods: This was a pilot, single-blind, controlled observational
study. Five ambulatory HD subjects and 5 age and gender-matched
healthy controls wore inertial sensors manufactured by APDM, Inc.
attached to each shoe during waking hours for 7 days. Gait parame-
ters calculated from the sensors included stride length (% height);
stride velocity (% height/sec); step duration (sec); double support
time (%); pitch at toe off (degrees) and heel strike (degrees); cadence
(steps/min); and variability in each of these measures. Following
blinded descriptive data analysis by APDM, independent samples t-
tests were used to compare means for selected gait metrics between
HD and control subjects, and Pearson correlation coefficients were
used to interrogate the relationships between gait metrics, chorea
score, and Total Functional Capacity (TFC, a measure of disease
severity).
Results: Subjects were able to successfully apply, wear and
charge the sensors. Blinded gait analysis correctly identified the
HD and control subjects for 4 out of 5 of the HD/control pairs. Sig-
nificant differences were found between HD and control groups in
mean (SD) stride length [53.96 (9.25), 67.68 (7.25), p50.03]; mean
(SD) variability per week (as measured by coefficient of variation)
in stride length [28.57 (5.54), 20.27 (3.78), p50.02] and pitch at
toe off [25.57 (4.00), 17.56 (4.07), p50.01]. Lower TFC scores cor-
related with greater variability in stride length [R= -0.82]; pitch at
toe off [R= -0.80]; and increased double support time[R= -0.75].
Higher chorea scores correlated with shorter stride length [R= -
0.76].
Conclusions: Inertial sensors may offer a feasible mechanism to
objectively measure clinically-relevant gait abnormalities in Hunting-
tons disease.
1383
Effects of motor rehabilitation on walking economy in patients
with Huntingtons disease
J.L. Kubica, J. Szymura, E. Mirek, M. Filip, M. Rudzi nska, K.
Banaszkiewicz, M. Maciejczyk, M. Wie R cek, U. Pustuka-Piwnik, J.
_ S. Pasiut (Krakow, Poland)
Stozek,
Objective: The aim of the study was evaluation of effectiveness
of motor rehabilitation on walking economy in a patients with Hun-
tingtons Disease.
Background: Movement Disorders in Huntingtons Disease are
the cause of functional disability, leading to impaired balance and
gait.
Methods: The study was carried on 14 patients with a geneti-
cally confirmed HD diagnosis (HD group: 6 women and 8 men)
and 14 healthy participants (C group: 6 women and 8 men). The
participants from both groups were similar in age, body height and
body mass. The physiological response and walking economy were
Movement Disorders, Vol. 30, Suppl. 1, 2015
evaluated in walking on mechanical treadmill with two velocities:
3,6 kmh-1 and 4,8 kmh-1. During the test the oxygen intake
(VO2), pulmonary ventilation (VE), tidal volume (TV), breathing
frequency (FR), and heart rate (HR) were measured. The therapeu-
tic intervention involved balance and gait rehabilitation. Rehabilita-
tion was provided five days for week, for 1.5 h/day and lasted 3
weeks.
Results: Before and after rehabilitation VE, BF, VO2 (absolute
and relative to body mass and lean body mass) and HR during walk-
ing were significantly higher in HD group compared to controls, but
there was no significant difference between groups in tidal volume.
The physiological response to walking significantly decreased in HD
group after motor rehabilitation. The walking economy (VO2 relative
to body mass) was significantly improved after motor rehabilitation.
The VE, FR and HR was higher before rehabilitation in HD group
(p<0.005). Both before and after rehabilitation no significant differ-
ences in TV were noted in HD group.
Conclusions: The physiological response during walking in HD
group was significantly higher than in control group. Due to this, the
walking-induce fatigue can occur earlier in HD patients than in
healthy people. After rehabilitation walking economy in HD group
have significantly improved.
1384
Safety of pridopidine when taken with antidepressants or
antipsychotics: Pooled analysis from two Huntingtons disease
clinical trials
G.B. Landwehrmeyer, S. Zhao, V. Abler (Ulm, Germany)
Objective: Key safety outcomes among subjects with Hunting-
tons disease (HD) treated concomitantly with pridopidine (PRD),
antidepressants (ADs) and/or antipsychotics (APs) in PRD clinical
trials were evaluated.
Background: Safety of concomitant medications is an important
concern in treatment of patients with HD, who often receive multiple
medications.
Methods: Subjects with HD in the MermaiHD trial (clinical-
trials.gov: NCT00665223) received placebo (PBO), PRD 45 mg once
daily or PRD 90 mg/day (45 mg twice daily [BID]) for 26 weeks.
Subjects in HART (NCT00724048) received placebo, PRD 20 mg/
day (10 mg BID), PRD 45 mg/day (22.5 mg BID) or PRD 90 mg/
day (45 mg BID) for 12 weeks. Concomitant treatment with ADs
(both studies) and APs (MermaiHD only) was permitted. Treatment-
emergent adverse events (TEAEs) were assessed. White blood cell
(WBC) counts were recorded at baseline and week 12. Electrocardio-
gram (ECG) readings at baseline and weeks 1, 4, 5, and 12 were
classified as normal, abnormal/not clinically significant (CS) or
abnormal/CS.
Results: Among n5664 subjects in the Safety Population
(n5437, MermaiHD; n5227, HART), n5141 subjects received both
AP & AD; n566, AP only; n5235, AD only; n5222, neither AP
nor AD (no AP/AD). Rates of TEAEs by treatment group are
shown in Table 1.
Mean (SD) WBC counts by treatment group are shown in
Table 2.
Six subjects displayed abnormal/CS ECG readings during the
studies: 3 on PBO, 1 on PRD and no AP/AD, and 2 on PRD and
AD only; no participant developed treatment-emergent abnormal/CS
ECG findings while exposed to PRD in combination with APs.
Conclusions: The frequency of TEAEs did not differ systemati-
cally or in a dose-dependent fashion between HD patients receiving
PBO or PRD in the 2 studies evaluated. Mean WBC count was not
lowered in patients on PRD and concomitant AP or AD and leukope-
nia did not emerge. In addition, there was no meaningful shift to
clinically significant abnormal ECG while on PRD in combination
with AP or AD compared with the PBO group. These initial findings
suggest a potentially favorable safety profile for PRD alone and
 POSTER SESSION S535

TABLE 1. Occurrence of treatment-emergent adverse events by pridopidine dosage and concomitant medication status
Placebo PRD 20 mg/day PRD 45 mg/day PRD 90 mg/day PRD (any dose)
Both AP & AD 27/40 (67.5%) n/a 32/48 (66.7%) 36/53 (67.9%) 68/101 (67.3%)
AP only 15/26 (57.7%) n/a 14/25 (56.0%) 8/15 (53.3%) 22/40 (55.0%)
AD only 42/69 (60.9%) 23/42 (54.8%) 26/53 (49.1%) 52/71 (73.2%) 101/166 (60.8%)
No AP/AD 41/67 (61.2%) 7/14 (50.0%) 44/77 (57.1%) 43/64 (67.2%) 94/155 (60.6%)
AD, antidepressant; AP, antipsychotic; PRD, pridopidine.

TABLE 2. Mean (SD) white blood cell count (x10^9/L) at week 12 by pridopidine dosage and concomitant medication status
Placebo PRD 20 mg/day PRD 45 mg/day PRD 90 mg/day PRD (any dose)
Both AP & AD 7.515 (1.992) n/a 7.640 (1.675) 7.117 (1.855) 7.375 (1.778)
AP only 6.576 (1.500) n/a 7.718 (2.015) 7.165 (1.674) 7.529 (1.900)
AD only 7.026 (1.976) 6.359 (1.375) 6.944 (2.272) 6.718 (1.522) 6.699 (1.777)
No AP/AD 6.840 (1.990) 7.133 (1.699) 6.799 (1.964) 6.766 (1.909) 6.813 (1.911)
AD, antidepressant; AP, antipsychotic; PRD, pridopidine.

when combined with AD or AP, frequently prescribed co-
medications in HD.
1385
Microglial dysfunction plays a critical role in Huntingtons
disease pathogenesis
B.R. Leavitt, C. Connolly, A. Hill, L. Hayardeny, M.R. Hayden
(Vancouver, BC, Canada)
Objective: To investigate the pathogenic role of microglial dys-
function caused by mutant huntingtin in a transgenic mouse model
of Huntingtons disease.
Background: Microgliosis and neuroinflammation have been
implicated in Huntingtons disease (HD) pathogenesis. Bacterial arti-
ficial chromosome transgenic mice (BAC-HD mice) express mutant
huntingtin with an expanded polyglutamine tract, replicate key fea-
tures of HD, and have a floxed human mutant huntingtin transgene
(two LoxP sites flanking the transgene). We use these mice to assess
the potential role of mutant huntingtin expression in microglia on the
motor and neuropathologic HD phenotype of BAC-HD mice. Laqui-
nimod is an experimental immunomodulatory drug which modifies
astrocytic and microglial activation of cytokine secretion in neurode-
generative disease models and is currently in clinical trials in HD.
Our hypothesis is that mutant huntingtin expression in microglia
influences the pathogenesis of HD, and that treatment with agents
like laquinimod will reverse the pathogenic effects of microglial dys-
function in HD.
Methods: We assessed the effects of microglia-specific deletion
of mutant huntingtin in BAC-HD mice by crossing them with mice
carrying the Cre recombinase enzyme under control of the endoge-
nous lysozyme promoter. This promoter will cause Cre to be
expressed in all cells of the myeloid lineage (including microglia)
and will result in cell-specific deletion of the mutant huntingtin trans-
gene in these cells. We then compared the motor and neuropatho-
logic phenotype of BAC-HD mice with and without Cre expression.
Results: Behavioral studies up to 12 months of age demonstrate
that selective Cre-mediated deletion of the BAC transgene expressing
mutant huntingtin in brain microglia caused a significant improve-
ment of the motor phenotype of this HD model. Neuropathologic
analysis found that mutant huntingtin expression in microglia plays a
role in the HD neuropathology seen in BAC-HD mice with benefit
observed on brain weight and microglial activation.
Conclusions: These studies demonstrate the pathogenic role
mutant huntingtin expression in microglia plays on the motor and
neuropathologic phenotype of the BAC-HD model. This study pro-
vides important proof-of-principle data supporting microglial dys-
function as a therapeutic target in HD in general, and support the
clinical testing of agents such as laquinimod in this devastating neu-
rodegenerative Movement Disorder.
1386
What determines the behavioral onset in Huntingtons disease?
Insight from 90 genetically confirmed patients
A. Lenka, N.L. Kamble, S. Venugopal, K.R. Jhunjhunwala, R. Yadav,
M. Netravathi, M. Kandasamy, N. Moily, M. Purushottam, S. Jain,
P.K. Pal (Bangalore, India)
Objective: To identify the factors associated with behavioural
onset (BO) of Huntingtons disease (HD) by comparing the demo-
graphic and genetic characteristics of HD patients with BO of the
disease with those having motor onset (MO).
Background: HD is a neurodegenerative disorder caused by
abnormal expansion of CAG triplets in the Huntingtin gene. Involun-
tary movements, behavioral problems and cognitive dysfunctions are
commonly found in HD. Though few patients may have behavioral
symptoms at onset of the disease, studies on the factors associated
with BO of HD are few.
Methods: A chart review of 90 HD patients who had attended
the neurology outpatient clinics of National Institute of Mental
Health and Neurosciences, India was done. Data of patients eval-
uated by a single Movement Disorder specialist and a psychiatrist
were analysed.
Results: The mean age of the patients was 42.2 6 10.9 years,
mean age at disease onset (AAO) was 37.5 6 10.7 years and mean
duration of disease was 4.5 6 3.6 years. Men (n554) outnumbered
women (n536) in a ratio of 3:2. BO of disease was present in 24
patients while the rest had MO. Irritability with anger outbursts
(n59) was the commonest behavioral symptom among those with
BO of disease. Other behavioral symptoms were depressive episodes
(n55), delusion of infidelity (n54), delusion of persecution (n53),
delusion of control (n51), apathy (n51) and subclinical obsessive-
compulsive symptom (n51). Though there was no significant differ-
ence in the mean age and mean number of CAG repeats, patients
with BO had earlier AAO (33.7 6 10.8 years vs 38.9 6 10.5 years,
p5 0.03) and longer duration of disease (6.3 6 5.3 years vs 3.8 6 2.5
years, p50.004) compared to those with MO of disease. In both the
groups, AAO had a significant negative correlation with CAG repeat
length (BO: r= -0.525, p50.008; MO: r= -0.746, p5 <0.001). Posi-
tive family history of HD was documented in significantly higher
numbers in patients with BO compared those with MO (95.8% vs.

Movement Disorders, Vol. 30, Suppl. 1, 2015

S536 POSTER SESSION
72.7%; p50.01). Ratio of patients inheriting the disease from mater-
nal side to those inheriting from paternal side was significantly
higher in the group with BO compared to those who had motor
symptoms at the onset (2.3:1 vs. 1:2; p50.005).
Conclusions: Early age at onset of HD, presence of positive fam-
ily history of HD and inheritance of HD from maternal side are asso-
ciated more with BO of HD than those with MO.
1387
Metabolic brain correlates of apathetic symptoms in pre-
manifested Huntingtons disease: An 18-FDG PET study
S. Martinez-Horta, J. Perez-Perez, F. Sampedro-Santalo, R.
Fernandez-Bobadilla, M. Carceller, J. Pagonabarraga, A. Campo-
longo, B. Gomez-Anson, B. Pascual-Sedano, V. Camacho-Marti, D.
Lopez-Mora, J. Kulisevsky (Barcelona, Spain)
Objective: To elucidate the metabolic correlates sub-serving the
clinical expression of apathetic symptoms in far-to-onset premani-
fested Huntingtons disease (HD).
Background: Apathy is an extremely common symptom of HD
identifiable more than fifteen years before motor-based clinical diag-
nosis. Despite a poorly responsive linear involution and potential
utility as biomarker, little is known about its underlying mechanisms.
Methods: 18-FDG PET scans were done in fifteen premanifested
individuals (CAG  36; Unified Huntingtons Disease Rating Scale
Total Motor Score (UHDRS)  4; Total Functional Capacity
(TFC) > 11) with minimum estimated time-to-onset above 10 years.
The Problems Behavior Assessment Scale (PBA-S) was administered
to assess the severity of apathetic symptoms. Individuals scoring  2
on other PBA-S domains and/or Depression score  11 on the Hospi-
tal Anxiety and Depression Scale (HADS) were not included. Cogni-
tion was assessed through the UHDRS Cognitive component.
Regressions analysis controlling for age was conducted between 18-
FDG metabolism and apathy scores (significance level set at
p<0.005; extent voxel threshold 5 20).
Results: Socio-demographic and clinical data showed mean
age 5 36.3 6 8; education 5 14.6 6 6; CAG 5 42.3 6 2; disease burden
score 5 240 6 54; years-to-onset 5 16.4 6 7; UHDRS Motor 5 1.7 6
1.4; TFC 5 13; UHDRS Cognition 5 294 6 58, PBA-S apathy score-
5 4.8 6 5.1; HADS-D 5 3.6 6 3.3. Higher apathy scores appeared
related to a pattern of hypomethabolism involving the orbital and
fronto-polar PFC (BA10), caudate nucleus, thalamus, GPe/Putamen,
precuneus and posterior cingulate. A pattern of increased metabolism
was seen at a level of motor (SMA) and premotor areas.
Conclusions: In far-to-onset premanifested individuals, apathetic
symptoms are related to diminished brain metabolism in regions
linked to the proper guidance of motivated behavior, emotional proc-
essing and social interaction along regions critically related to dis-
ease progression. Increased metabolism at a level of motor/premotor
areas points for early compensatory mechanisms. Apathetic symp-
toms seem to results from early malfunctioning in key cortical and
subcortical structures when compensatory mechanisms stills prevent-
ing for the clinical expression of other symptoms. Taking together,
apathetic symptoms and related 18-FDG metabolic correlates appears
as a potential early biomarker of HD.
1388
PET/CT findings along premanifested and early symptomatic
Huntingtons disease
J. Perez-Perez, S. Martnez-Horta, F. Sanpedro-Santalo, M.
Carceller-Sindreu, J. Pagonabarraga, B. Pascual-Sedano, A. Campo-
longo, V. Camacho, D. Alonso, B. Gomez-Anson, J. Kulisevsky (Bar-
celona, Spain)
Objective: To assess metabolic changes in cerebral PET/CT
between premanifested (preHD) and early symptomatic Huntingtons
Movement Disorders, Vol. 30, Suppl. 1, 2015
disease (earlyHD) patients and determine the correlation between 18-
FDG-uptake and clinical progression.
Background: Previously PET-18FDG studies have shown meta-
bolic changes in symptomatic and premanifested HD patients, how-
ever they did not have evaluate the course of the changes across
premanifested individuals far and near to the disease onset and along
symptomatic stages.
Methods: 33 individuals (8 male; mean age=46 (26-68) positive
gene carriers (mean CAG=43) were included. Patients were assessed
and classified based on the UHDRS motor score and TFC, cognition
was also evaluated. 18 were earlyHD (UHDRS>4 TFC 7-13) while
15 were preHD (UHDRS  4 TFC 11-13). We classified preHD as
near <10-years from disease expected onset (preHDA; n58) and far
>10-years (preHDB; n57) to onset based on Langbehn formula and
disease burden score (DBS). Analysis was performed using SPM8.
Significance was set at p<0.005; extent voxel threshold k=20. We
evaluated the correlation of motor and cognitive status with metabo-
lism in regions of interest.
Results: We observed an inverse correlation between DBS and
caudate metabolism in all the groups spreading to putamen and pre-
frontal cortex (PFC) along disease stages. In preHDB we found
hypermetabolism in PFC relative to preHDA. Conversely, preHDA
showed hypermetabolism in postrolandic areas relative to preHDB,
extending to frontal-motor areas in earlyHD when compared to pre-
HDA. EarlyHD also presented hypometabolism in caudate and puta-
men when we compared to preHDA.
We found an inverse correlation between motor score and metab-
olism in caudate (r=-0.8 p<0.001) and putamen (r=-0.78 p<0.001).
We also observed a direct correlation between cognitive score and
metabolism in caudate (r=0.82 p<0.001), putamen (r=0.79 p<0.001)
and dorsolateral prefrontal cortex (r=0.58 p50.006).
Conclusions: Caudate hypometabolism correlated with disease
burden score and can be observed up to 15-years before the expected
motor-based disease onset. It decreases along disease progression
and spreads to caudate and PFC areas. Hypermetabolism in somato-
sensorial areas is present since preHDA, extending to motor and pre-
motor areas in earlyHD and could reflect metabolic compensatory
mechanisms. Motor and cognitive scores have a strong correlation
with the metabolic changes seen at a caudate nucleus and putamen.
1389
Functional limitations of the upper limb in prodromal and early
manifest Huntingtons disease
A.K. Rao, J. Uddin, C.C. Chen, K.S. Marder (New York, NY, USA)
Objective: To examine (1) earliest functional limitations of the
upper limb and (2) the association between functional limitations and
motor and cognitive function in Huntingtons disease (HD).
Background: Impairments of hand movements are well studied,
and include bradykinesia, increased temporal delay, excessive grasp-
ing forces, and increased temporal and force variability. However,
early functional limitations that arise from these motor impairments
are not well understood.
Methods: We conducted a cross-sectional observational study with
twenty healthy controls, 23 prodromal (pHD) and 20 manifest HD
(mHD) subjects. Prodromal subjects were classified as near onset
and far from onet based on the CAP score. Hand function was
assessed with the Manual Ability Measure (MAM), a task oriented,
self-report questionnaire that contains 20 one-handed and two-handed
upper limb functional tasks. Participants rated their functional ability
on a 5-point scale, with higher scores indicating better function. Gen-
eral function was evaluated with the HD-Activities of Daily Living
(HD-ADL), a 17-item self-report questionnaire. Items are rated on a
4-point scale (0-3) with higher scores indicating greater functional lim-
itations. Motor function was assessed with the UHDRS total motor
score and cognitive function was assessed with the Stroop task.
Results: Hand function (MAM score) was significantly worse for
pHD far from predicted onset (p<0.01), pHD near predicted onset
 POSTER SESSION
(p<0.003) and mHD (p<0.0001) compared with controls. General
functioning (HD-ADL) was worse for pHD near predicted onset
(p<0.03) and mHD (p<0.001) compared with controls. Item analysis
revealed that the earliest functional limitations were seen in complex
tasks such as handwriting, opening medicine bottle, wringing a
towel, handling money and cooking. MAM was significantly corre-
lated with motor (r= -0.29, p<0.05) and cognitive function (r=0.63,
p<0.003).
Conclusions: Our data suggest that MAM is a sensitive instru-
ment to assess early functional limitations of the upper limb in HD.
Earliest functional limitations were noted in tasks that either required
bimanual control or integration of cognitive and motor skills.
1390
Gait speed modulation in prodromal and early manifest
Huntingtons disease: Role of internal and external cues
A.K. Rao, F. Porciuncula, J. Uddin, K.S. Marder (New York, NY,
USA)
Objective: To examine (1) modulation of gait speed in prodromal
(pHD) and manifest (mHD) Huntingtons disease (HD); and (2) to
characterize the stride length-cadence relationship.
Background: Slow speed, in addition to increased variability, is
evident during gait in prodromal (pHD) and early manifest (mHD)
HD. While mHD subjects can modify gait speed, stride length is
lower than controls at different speeds. It is unclear if this impair-
ment is seen in pHD. Moreover, mechanisms underlying stride
length-cadence relationship are not known in prodromal HD.
Methods: Our sample included 20 pHD (mean age 5 41.75 y), 19
mHD (mean age 5 44 y, and 20 controls (mean age 5 42.45 y).
Experiment I (internally generated speed modulation) subjects were
asked to walk at self-selected normal speed (baseline); fast and slow
speed. In a second experiment (externally cued speed modulation), we
asked subjects to walk in time with a metronome at baseline cadence;
and 110% of baseline cadence. Outcomes were speed, stride length,
and cadence. To assess speed modulation, we used group by condition
repeated measures analysis of variance (ANOVA). To examine stride
length-cadence relationship, we used linear regression analysis. Inter-
cept, slope, and R2 were assessed using one-way ANOVA.
Results: pHD and mHD subjects were able to modify gait speed
similar to controls. However the intercept of stride length - cadence
was significantly lower in both pHD and mHD than controls
(p < 0.05). Thus, stride length in pHD and mHD was dampened at
different cadences. With external cues, both pHD and mHD success-
fully adjusted cadence to match metronome frequency similar to con-
trols. However, the intercept of stride length - cadence was
significantly lower in mHD (p < 0.05) but not pHD (p > 0.05) rela-
tive to controls. Slope and R2 was comparable across groups under
all conditions.
Conclusions: pHD and mHD subjects were capable of modifying
gait speed by adjusting stride length and cadence under internally
generated and externally cued conditions. For mHD subjects, stride
length modulation was impaired under both internally generated and
externally cued conditions. For pHD subjects stride length modula-
tion was impaired only during internally generated conditions. Our
results suggest that impairment in stride length regulation begins
before clinical onset of HD, and may be partly compensated by the
use of external cues in prodromal HD.
1391
Design of the LEGATO-HD study: A multinational, randomized,
double-blind, placebo-controlled, parallel-group study to evaluate
the efficacy and safety of laquinimod (0.5, 1.0 and 1.5 mg/day) as
treatment in patients with Huntingtons disease
R. Reilmann, S. Tabrizi, B. Leavitt, J.C. Stout, P. Piccini, K.E.
Anderson, A. Feigin, M. Hayden, M. Grozinski-Wolff, E. Eyal, A.
Wickenberg (Tuebingen, Germany)
S537
Objective: The primary objective of this study is to assess the
efficacy and safety of laquinimod 0.5, 1.0, and 1.5mg versus placebo
in a 12-month study in patients with HD.
Background: Introduction: Huntingtons disease (HD) is a neu-
rodegenerative disorder with an autosomal dominant mode of inheri-
tance, associated with a triad of motor, behavioral, and cognitive
symptoms. Laquinimod, is an orally active, CNS penetrant, immuno-
modulator believed to downregulate the inflammatory monocytic,
microglial and astrocytic activation, that may contribute to neuronal
loss in patients with HD. Laquinimod up-regulates BDNF secretion
which is reduced in HD and thought to contribute to degeneration of
the striatum. Laquinimod treatment reduces brain atrophy and dis-
ability progression in patients with multiple sclerosis, an immune-
mediated neurodegenerative disease. Laquinimod is in clinical devel-
opment as a possible candidate for modulation of disease course and
reduction of neurodegeneration in patients with HD.
Methods: A total enrollment of 400 patients (100 patients per
dose arm, 1:1:1:1) is planned. Primary endpoint is change from base-
line in the Unified Huntingtons Disease Rating Scale Total Motor
Score (UHDRS-TMS) at month 12. Secondary endpoints include
assessing safety of laquinimod, its effect on brain atrophy (in partic-
ular caudate volume) and cognitive capacity using Huntingtons dis-
ease cognitive assessment battery (HD-CAB), clinical global
impression using the Clinicians Interview-Based Impression of
Change plus Caregiver Input (CIBIC-Plus), and change from baseline
in functional capacity using the UHDRS TFC (Total Functional
Capacity). Ancillary studies will investigate laquinimods effect on
microglial activation using PET imaging, peripheral inflammatory
markers, and neuronal integrity using MRS analysis.
Conclusions: There is a significant unmet medical need to ameli-
orate the progressive neurodegeneration that occurs in HD. This
study will provide essential data towards possible effective and safe
use of laquinimod to reduce neuronal loss and subsequent disease
progression. Enrollment for this study is underway.
Study is sponsored by Teva Branded Pharmaceuticals in collabo-
ration with the European Huntingtons Disease Network and the
Huntington Study Group.
1392
Longitudinal assessment of PDE10 in Huntingtons disease (HD)
using [18F]MNI-659 PET imaging
D.S. Russell, D.L. Jennings, O. Barret, G.D. Tamagnan, V.M.
Carroll, D. Alagille, T.J. Morley, C. Papin, J.P. Seibyl, K.L. Marek
(New Haven, CT, USA)
Objective: To further evaluate the feasibility of [18F]MNI-659
PET, a striatal PDE10A imaging tracer, as a biomarker for progres-
sion of HD.
Background: [18F]MNI-659 is a selective PET tracer for phos-
phodiesterase PDE10A, an enzyme specifically and highly expressed
in striatal neurons. Prior studies demonstrated a strong correlation
between extent of loss of [18F]MNI-659 striatal uptake and clinical
and molecular indices of HD severity. Development of a progression
marker for PDE10 in HD has the potential to improve our under-
standing of neurodegeneration in both manifest (mHD) and premani-
fest (preHD) HD subjects and serve as a tool for therapeutic
development.
Methods: All subjects completed baseline clinical assessments,
including UHDRS rating, and brain MRI. PET imaging was acquired
over 90 minutes following injection of 5 mCi [18F]MNI-659.
Standard uptake values were determined for the basal ganglia and
component subnuclei. Binding potentials (BPnd) were estimated with
SRTM (cerebellum as reference). Subjects underwent clinical assess-
ments and [18F]MNI-659 PET imaging at 1 and 2 years following
baseline.
Results: Eight HD subjects (6 mHD [Stage 1 (n52), Stage 2
(n54)]; and 2 preHD) participated, including 7 with known CAG
repeat lengths. At baseline, HD subjects demonstrated reduced
Movement Disorders, Vol. 30, Suppl. 1, 2015
S538 POSTER SESSION
striatal [18F]MNI-659 uptake of 50% compared to existing an
healthy control cohort (n57). At 1 year, [18F]MNI-659 uptake
declined in the basal ganglia in all eight subjects with mean annual-
ized rates of signal reduction in caudate, putamen, and globus pal-
lidus of 16.6%, 6.9% and 5.8%, respectively. A typical rate and
range of decline in clinical status assessed by UHDRS was also
observed in this cohort. To date, 3 subjects have completed year 2
imaging with continued mean annualized reduction in [18F]MNI-659
uptake at a rate comparable to year 1 (caudate 15.5%, putamen
7.2%, and globus pallidus 9.4%).
Conclusions: [18F]MNI-659 appears to be an excellent striatal
imaging biomarker for early HD. Furthermore, [18F]MNI-659 PET
can detect annual decrements in striatal PDE10A binding in longitu-
dinal studies of early mHD and preHD over 2 years. Additional stud-
ies are currently underway.
1393
The effect of olanzapine on cognition in Huntingtons disease
L. Schwab, S. Mason, R. Barker (Cambridge, United Kingdom)
Objective: This study aims to investigate the effect of Olanza-
pine, a drug commonly used in Huntingtons disease, on the Move-
ment Disorder and the cognition of HD patients.
Background: Huntingtons disease (HD) is an autosomal domi-
nant condition which leads to progressive neurodegeneration and
presents with a combination of motor, cognitive, affective and meta-
bolic problems. The gene for the disease is known and one of the
challenges is trying to ascertain when the patient transitions from a
pre-manifest gene carrier into the disease state. Diagnosis of manifest
HD currently relies solely on the motor features but in recent years
increasing evidence has shown that the cognitive features begin
before the motor features.
In the brain, this pathology affects the dopaminergic system with
a early decrease in dopamine receptor 2 expression in the striatum
but also other regions including the hippocampus. Interestingly, the
most commonly used treatment for the symptoms of HD blocks
dopamine receptors.
Methods: 11 early manifest HD patients experiencing involuntary
movements were prescribed Olanzapine. Patient motor changes were
assessed using the Unified Huntingtons disease Rating Scale
(UHDRS) prior to treatment administration and will be followed up
at 3 and 6 months after the beginning of treatment. Participants were
also evaluated on a number of cognitive tasks from the computerised
Cambridge Neuropsychological Test Automated Battery (CANTAB)
as well as a novel hippocampal-dependent test. This study is a pro-
spective study with a within-subjects design.
Results: The study is ongoing at the moment, but we are aiming
to have results ready to be presented at the conference.
Conclusions: Previous studies have found improvement in motor
deficits of HD patients following chronic treatment with Olanzapine
and in healthy volunteers, subacute Olanzapine treatment lead to
acute impairments in performance on attention and memory tasks.
However, no study to date has investigated the effect of Olanzapine
on the cognitive performance of HD patients.
The study will enable a better understanding of dopaminergic
modulation and its effect on cognitive processes in Huntingtons dis-
ease. Ultimately, this study will have important implications for the
use of dopaminergic therapies, including antipsychotics in neurode-
generative and neuropsychiatric diseases of the CNS and may pro-
vide novel targets of treatment in these disorders.
1394
A genetically-proven case of Huntingtons disease in the
Philippines
M.L.D. Supnet, A.F. Diaz (Manila, Philippines)
Movement Disorders, Vol. 30, Suppl. 1, 2015
Objective: To discuss a genetically-proven case of Huntingtons
disease in the Philippines.
Background: Huntingtons disease (HD) is a rare, neurodegener-
ative disorder characterized by chorea, behavioral manifestations,
and dementia. Studies revealed an incidence of 0.38 per 100,000 per
year with a lower incidence in the Asian studies. The worldwide
service-based prevalence of HD was 2.71 per 100,000 and overall
prevalence conducted in Asia showed 0.40 per 100,000. A literature
review revealed no previous reports of genetically-proven case of
Huntingtons disease in the Philippines.
Methods: A case report of a 30-year old Filipino male from Jolo,
Sulu, who consulted to the hospital with the complaint of involuntary,
brief, irregular, jerky movements of extremities. There was gradual pro-
gression of symptoms which initially started as jerky, repetitive, pur-
poseless movements of the head and shoulders until there was
involvement of trunk and all extremities. He developed behavioral
changes in the form of frequent outbursts of anger, loss of temper and
irritability, and manifested with cognitive problems that he had to stop
schooling. His father had the same manifestations when he was still
alive. He has 2 paternal uncles and an aunt who also presented to the
hospital with the same symptoms. On physical examination, he has ran-
dom facial grimaces with intermittent protrusion of the tongue and
irregular shoulder jerks with athethoid movement of the distal extrem-
ities. He has generalized random movement of the different parts of the
body including truncal musculatures and has involuntary, brief, irregu-
lar, jerky movements that flow from proximal to distal extremities.
Results: Cranial CT scan was done which showed atrophy of
bilateral caudate nucleus. Genetic testing was done to our patient.
Blood specimen was sent to Mayo Clinic and PCR based assay was
utilized to detect CAG repeat expansions in exon 1 of the HTT gene.
The CAG repeat of the patient was 53 revealing full penetrance.
Conclusions: HD is rare among Asians and this is the first
genetically-proven case in the Philippines. Since relatively uncom-
mon, Huntingtons disease can be devastating for patients and their
families. This case illustrates the potential benefit of utilizing genetic
testing and counseling to the other family members, and conducting
further study on the ancestral place of the patient.
1395
Abnormal electrophysiological motor responses in Huntingtons
disease: Evidence of premanifest compensation
L.M. Turner, R. Croft, A. Churchyard, J.C.L. Looi, D. Apthorp, N.
Georgiou-Karistianis (Canberra, Australia)
Objective: To evaluate the integrity of EEG motor potentials in
Huntingtons disease during preparatory and execution phases of
movement elicited across a simple tapping task.
Background: Huntingtons disease (HD) causes progressive
motor dysfunction through characteristic atrophy. Changes to neural
structure begin in premanifest stages yet individuals are able to
maintain a high degree of function, suggesting involvement of sup-
portive processing during motor performance. Electroencephalogra-
phy (EEG) enables the investigation of subtle impairments at the
neuronal level, and possible compensatory strategies, by examining
differential activation patterns. We aimed to use EEG to investigate
neural motor processing (via the Readiness Potential; RP), premotor
processing and sensorimotor integration (Contingent Negative Varia-
tion; CNV) during simple motor performance in HD.
Methods: We assessed neural activity associated with motor
preparation and processing in 20 premanifest (pre-HD), 14 sympto-
matic HD (symp-HD), and 17 healthy controls. Participants per-
formed sequential tapping within two experimental paradigms
(simple tapping; Go/No-Go). RP and CNV potentials were calculated
separately for each group.
Results: Motor components and behavioural measures did not
distinguish pre-HD from controls. Compared to controls and pre-HD,
symp-HD demonstrated significantly reduced relative amplitude and
latency of the RP, whereas controls and pre-HD did not differ.
 POSTER SESSION
However, early CNV was found to significantly differ between con-
trol and pre-HD groups, due to enhanced early CNV in pre-HD.
Conclusions: For the first time, we provide evidence of atypical
activation during preparatory processing in pre-HD. The increased
activation during this early stage of the disease may reflect ancillary
processing in the form of recruitment of additional neural resources
for adequate motor preparation, despite atrophic disruption to struc-
ture and circuitry. We propose an early adaptive compensation mech-
anism in pre-HD during motor preparation.
1396
Dopamine D2 receptor and phosphodiesterase 10A loss in
Huntingto ns disease measured with high-resolution PET and
partial volume effect correction
C. Fitzer-Attas, A. Varrone, P. Fazio, M. Schain, L. Mrzljak, J.
Bronzova, B. Landwehrmeyer, N. Al-Tawil, S. Martinsson, C. Hall-
din, C. Sampaio, EHDN Recruiting sites (Stockholm, Sweden)
Objective: To examine the change of dopamine D2 receptors
(D2R) and phosphodiesterase 10A enzyme (PDE10A) in Huntingto ns
disease (HD) gene expansion carriers (HDGECs) using high-
resolution positron emission tomography (PET) and correction for
partial volume effect (PVE).
Background: D2Rs and PDE10A are known to be altered in HD.
In the basal ganglia, a reduction of D2Rs and PDE10A occurs in
combination with atrophic changes progressing from pre-manifest to
symptomatic stages. Therefore, brain atrophy may enhance PVEs
due to limited resolution of PET thus resulting in an underestimation
of D2R and PDE10A availabilities.
Methods: Fifteen HDGECs (5 stage I, 4 M/1F, age:53 6 9y, dis-
ease burden score (DBS):388 6 50; 10 pre-manifest, 6M/4F,
age:42 6 7y, DBS:325 6 64) and 15 age- and gender-matched control
subjects (10M/5F, age:46 6 11y) were examined with the D2R radio-
ligand [11C]raclopride and the PDE10A radioligand [18F]MNI-659,
using the high-resolution research tomograph. PVE correction
(PVEc) was applied to the PET data using 3T MR images and the
method described by Rousset et al. (JNM, 1998). The outcome mea-
sure was the binding potential (BPND), using the simplified refer-
ence tissue model (D2R) and the Logan graphical analysis
(PDE10A) with the cerebellum as reference region. The regions
examined were caudate (CAU), putamen (PUT), and globus pallidus
(GP). Differences between groups were assessed with un-paired t-test
(p<0.05). Correlations with DBS were performed with regression
analysis.
Results: [11C]raclopride and [18F]MNI-659 BPND were signifi-
cantly lower in HDGECs compared with control subjects. In stage I
HDEGCs, the mean BPND reduction vs. controls for D2R and
PDE10A availability was 63% and 91% in CAU, 43% and 69% in
PUT and 25% and 65% in GP. In pre-manifest HDGECs, the corre-
sponding BPND reduction was 32% and 53% in CAU, 31% and
43% in PUT, 16% and 41% in GP. A statistically significant negative
correlation was observed between DBS and striato-pallidal BPND of
[11C]raclopride (r=-0.63, p50.012) and [18F]MNI-659 (r=-0.678,
p50.005).
Conclusions: Our findings obtained with PVEc confirm that stria-
tal PDE10A is more severely reduced than striatal D2R in HD,
already at the earliest stages of HD examined. The reduction of
apparent D2R and PDE10A availabilities reflect a genuine loss of
binding targets in the remaining striatal tissues and is not a reflection
of PVE.
1397
Callosal thickness progressively changes in Huntingtons disease:
30 month IMAGE-HD data
F.A. Wilkes, M. Walterfang, C. Adamson, J.C.L. Looi, M.L. Seal, D.
Velakoulis, J. Stout, A. Churchyard, P. Chua, G.F. Egan, N.
Georgiou-Karistianis (Canberra, Australia)
S539
Objective: To investigate longitudinal changes in corpus cal-
losum thickness profiles in Huntingtons disease (HD) and to corre-
late these with clinical and neurocognitive outcomes.
Background: Neurodegeneration in HD affects cortical regions
and white matter tracts as well as the neostriatum. As the major
interhemispheric commissure, the corpus callosum provides a unique
opportunity to investigate more widespread neurodegeneration in
HD. State-of-the-art structural neuroimaging methods give the poten-
tial for development of simple biomarkers of disease while minimis-
ing processing time and complexity. In this study, we investigated
callosal thickness across different stages of HD using a novel method
of estimating mid-sagittal thickness profiles.
Methods: Thirty-six pre-symptomatic HD participants (pre-HD),
37 symptomatic HD participants (symp-HD), and 36 healthy controls
were included in this investigation, all recruited as part of the
Australian-based IMAGE-HD study. Structural MRIs were taken of
all participants at baseline and at two follow-up time points of 18
and 30 months. Clinical data, neurocognitive and motor test results
were also collected. A fully automated pipeline was used to generate
a thickness profile for each mid-sagittal corpus callosum. Thickness
profiles were compared at 100 nodes along the length of the cal-
losum utilising two-sample Welchs T-test, with age and intracranial
volume accounted for via regression. Cross-sectional and longitudinal
changes were investigated and correlations were performed with clin-
ical and neurocognitive outcomes.
Results: Participants with symp-HD showed significant reductions
in callosal thickness compared to controls and to pre-HD, and also
showed significant decreases in callosal thickness over time. After
controlling for multiple comparisons there were no significant corre-
lations between regional callosal thickness and clinical or neurocog-
nitive outcomes.
Conclusions: Findings from this study suggest that the corpus
callosum is more sensitive to atrophy during symp-HD.
Quality of life/caregiver burden in Movement
Disorders
1398
Impact of cognitive dysfunction on dysphagia and dysarthria in
Parkinsons disease: A study in Uruguay
B. Aguiar, J. Higgie, R. Aljanti, M. Martinovic, R. Buzo, V. Raggio,
A. Ojeda, G. Montado, V. Pomar, G. Nogueira, L. Aguerre, E.
Cortinas, F. Martinez (Montevideo, Uruguay)
Objective: In this retrospective study, we investigated the preva-
lence of dysphagia and dysarthria in 99 PD patients and furhter the
diferences of drooling in patients with dementia and without
dementia.
Background: A significant number of patients with Parkinsons
disease (PD) experience dysphagia, dysarthria and drooling. Swal-
lowing disturbances are associated with afective responses such anxi-
ety and depression. We will know the relationships between these
afective symptoms and dysphagia in two gruops of PD patiensts with
an d without demmentia.
Methods: Assessments included Unified PD Ratings Scale
(UPDRS), Montreal Cognitive Assessment (MOCA), PD Question-
aire -39 (PDQ-39), Hamilton Depresion and Anxiety Scale (HADS)
and Questionaire of dysphagia (DISFAPARK).
Sixty -six PD patients, non demented by MOCA, and forty -three
PD demented answered if experience any symptom (dysphagia, dys-
arthria, etc.),completed all rating and questionarie.
Dysarthria, drooling and dysphagia were defined as UPDRS items
5,6 or 7 >1.
Dementia were defined with MOCA minor 26 points.
Results: Dysarthria, and dysphagia were present in both groups,
demented(MOCA <26): 51%, non demented (MOCA >26) 37%.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S540 POSTER SESSION
Dysphagia correlated with male gender and disease severity.
Drooling had higher scores fot he UPDRS and higher scores for
the domains of PDQ-39.
Conclusions: Patients with swallowing disorders and dysarthria
exhibit more depresion and anxiety in both groups. Quality of life
decresae with drooling in patients without dementia. Drooling is not
correlated with disease duration and motor severity of PD.
1399
Socioeconomical analysis in a population of Parkinsons disease
patients in a public hospital of Argentina
M.L. Assante, S.A. Rodrguez-Quiroga, M.J. Casen, C. Christie, M.
Mancuso, V. Daz Aragunde, T. Arakaki, N.S. Garretto (Buenos
Aires, Argentina)
Objective: To assess the socioeconomic status and the access to
the medication in a group of PD patients.
Background: Parkinsons disease (PD) results in high health
costs that increase with the progression of the disease.
Methods: Observational, descriptive and cross-sectional study
conducted from April to November 2014. A structured questionnaire
was performed which included: health coverage, employment status,
transportation to hospital, need for caregiver, among others.
Results: One hundred PD patients were evaluated. Male: 56%,
average age: 65,3 years [39-83], and average disease time: 7,1 years
[0,5-22]. Most of the patients (98%) belong to Buenos Aires city and
suburbs. An 80% of the population had health coverage: 86,2%
health care system, 12,5% state health program and 1,3% prepaid
medicine plan.
Over 56% of the patients were retired (33% due to PD) and 37%
had a disability certificate issued by a state agency.
In order to arrive to the Hospital, 64% of patient used public
transportation; 22% used private transport (taxi, cars); ambulance
service needed by 3% and 11% arrived walking because they lived
near to the hospital.
In 25% some family member had to reduce their working hours
in order to take care of the patient. A caregiver was required in 15%
of the patients and in more than 60% they were a family member.
All received specific treatment for the disease. Patients achieved
their medication through health coverage in 59%, direct purchase in
12%, free medical samples in 7%, and in 22% a combination of the
above. Regardless a medical indication, only 39% received non phar-
macological treatment (physiotherapy, speech therapy, etc.).
Conclusions: All patients had access to treatment and regardless
a medical recommendation, a high percentage of patients did not per-
form any non - pharmacological treatment. Frequently, some family
members had to take an active participation in caregiving tasks. The
progression of the disease forced the patients to reduce their working
hours and in certain cases to retired at an early age than the usual.
1400
Quality of lifes evaluations in Parkinsons disease: Self and
caregiver agreement
Y. Balash, A.D. Korczyn, J. Knaani, T. Gurevich (Tel Aviv, Israel)
Objective: To examine proxy-patient agreements on the domains
of the PD Questionnaire (PDQ-39), the Scale of Quality of Life of
Care-Givers (SQLC) and the Multidimensional Caregiver Strain
Index (MCSI).
Background: Self-reports about quality of life (QoL) of patients
with Parkinsons disease (PD) themselves and of their spouses/care-
givers are subjective and not always reliable.
Methods: Patients and their spouses (proxies) were separately
interviewed and completed the questionnaires. Comparisons of
patient-proxy mean scores were calculated.
Results: 12 proxy-patient pairs were assessed. Proxies were
slightly younger (age: 70.6 6 5.3vs. 75.8 6 6.7years, P=0.06), both
Movement Disorders, Vol. 30, Suppl. 1, 2015
groups had a similar education level (14.7 6 5.9 and 14.3 6 3.4
years). Agreements for QoL items were strong and comparable:
PDQ-39, SQLC and MCSI (75.4% 614%; 78.1% 614.1% and
78.2% 614.3, respectively) for patients-proxies. Patients - proxies
reports better correlated in terms of physical condition (PDQ items-
3,8,12-15, ICC 95% CI 0.637-0.713) and depression (PDQ items-
17, 23, 24, ICC 95% CI 0.6-0.874). Divergences in assessments in
the items of SQLC and MCSI were considerable (averaged ICCs
0.1 both for PDQ and SQLS). Interrelationships between each of the
couples were modest for QoL items both in patients and caregivers
(averaged ICCs 0.41 for PDQ, and 0.429 for SQLS). They were
especially low for caregivers strain (averaged ICCs 0.27).
Conclusions: PD patients and their spouses/caregivers had
acceptable approximate agreements for most of QoL domains among
a majority of couples whereas the patient-caregiver interrelationships
were complex, diverging and should be taken with caution.
1401
Parkinsons and parenting: The impact on children, teens and
young adults
E.S. Book (Vancouver, BC, Canada)
Objective: To raise awareness and better understand the issues
and challenges commonly faced by children and parents living with
Parkinsons disease in the family.
Background: According to the World Health Organization, the
management of chronic diseases should incorporate the well being of
the patients whole family. For a number of reasons, more children
are growing up today affected by various parental chronic medical
conditions. With respect to Parkinsons disease more specifically,
approximately 10% of patients are diagnosed with PD before the age
of 50. Early onset diagnosis, postponement of childbearing and sec-
ond marriages with younger families increase the likelihood of chil-
dren/teens being impacted by Parkinsons disease. It is critical that
health care professionals are educated about how illness can impact
families and the importance of adopting a family centered approach.
Methods: The poster content is the result of clinical experience,
informal qualitative interviews with children/teens and a review of
previous research on the impact of Parkinsons disease on the
family.
Results: Key issues and practical suggestions for patients/families
and health care professionals will be presented as well as detailing
current resources.
Conclusions: Parkinsons disease in the family does not necessar-
ily mean that children/teens will have adjustment issues. Health care
professionals play a vital role in acknowledging and addressing the
needs of children and parents with Parkinsons disease. With appro-
priately timed support and resources, children and parents may expe-
rience a more positive family environment helping them to live well
with Parkinsons disease.
1402
Quality of life, motor symptoms and subthalamic deep brain
stimulation in Parkinsons disease. How do they interact with
each other?
J.F. Daneault, C. Duval, A.F. Sadikot (Montreal, QC, Canada)
Objective: Understand the interactions between different aspects
of quality of life and motor symptoms in Parkinsons disease (PD)
before and after subthalamic deep brain stimulation (STN DBS).
Background: Therapeutic interventions in PD is geared towards
improving quality of life (QoL). Little is known about the relation-
ship between different aspects to QoL in PD. Furthermore, while
current treatment options such as STN DBS predominantly target
motor symptoms they aim to improve QoL.
Methods: Patients diagnosed with PD and scheduled for STN
DBS were evaluated in the weeks prior to surgery while ON
 POSTER SESSION
medication using the Unified Parkinsons disease rating scale
(UPDRS) motor section. They were also asked to fill-out the PDQ-
39. These evaluations were repeated 6 to 9 months post-surgery
while patients were ON medication with stimulation.
Results: STN DBS improved motor function as assessed by the
UPDRS in all patients. Significant improvements in QoL were
observed after surgery for mobility, activities of daily living (ADL),
emotional well-being, and bodily discomfort. Significant interactions
between sub-sections of the PDQ-39 were observed prior to surgery.
Interestingly, those interactions were altered after STN DBS surgery.
In addition, the current study also shows that there was no significant
interaction between the UPDRS motor score and aspects of QoL
prior to surgery. However, after surgery, significant interactions
emerged between the UPDRS motor score and aspects of QoL.
When examining the association between the change in score of the
UPDRS and the change in score for different aspects of QoL, no sig-
nificant interactions were observed.
Conclusions: The current study shows that in patients with
advanced PD that are candidates for STN DBS, motor function is
only weakly related to QoL. Furthermore, the improvements in motor
functions following STN DBS are not linearly associated with differ-
ent aspects of QoL. Finally, STN DBS modifies the interaction
between the different aspects of QoL; indicating that interventions
focusing on improving specific aspects of QoL may need to be
altered after STN DBS in order to optimize the outcome.
1403
Rehospitalization in Parkinsons disease patients
S. De Jesus, L. Shahgholi, S.S. Wu, Q. Pei, A. Hassan, P. Schmidt,
M. Okun (Gainesville, FL, USA)
Objective: To investigate the associated risks factors for PD
patients with repeated hospital encounters and compare them to PD
patients with only a single encounter.
Background: The rate of hospital encounters for patients with
Parkinsons disease (PD) has been approximated to be 30%, and this
rate increases following the first hospitalization. The factors associ-
ated with repeat hospital encounters have not been explored. The
aim of this study was to investigate the associated risks factors for
PD patients with repeated hospital encounters and compare them to
PD patients with only a single encounter.
Methods: The National Parkinsons Foundation Parkinsons
Quality Improvement Initiative (NPF-QII) is an international, multi-
center prospective longitudinal clinical study that includes over
7,500 PD patients followed for up to 5 years. The current study ana-
lyzes a subset of that population who reported a hospital encounter
at baseline. Regression analysis and a survival model with backward
selection were performed to identify indicators for repeat hospital
encounters within PD patients, and to evaluate the average time to
the next hospital visit.
Results: There were 1919 PD patients who reported a hospital
encounter in their baseline visit and these were analyzed for rehospi-
talization effects in subsequent years. Of these, 641 PD participants
had a subsequent repeat hospital encounter, 416 patients did not have
a repeat encounter, and 862 patients were lost to follow up. Compar-
ing the two active groups, a significant positive effect for repeat hos-
pital encounters included older age (p 0.032), longer disease duration
(p 0.0004), higher Hoehn and Yahr Stage (p <0.0001), number of
medications (p<0.001), PDQ39 quality of life total score (p <0.001),
use of anti-depressant(s) (p <0.0001), TUG (p 0.0001) and the
multi-dimensional caregiver strain index (MCSI) index score (p
0.003). The average time from the first to the second hospital
encounter was 19.1 6 9.8 months (median 15 months).
Conclusions: PD patients with advanced disease, older age, mul-
tiple medications, and worse quality of life had a higher risk for
rehospitalization. Also, strain on the care partner impacted
rehospitalization.
S541
1404
Measuring community mobility of people with Parkinsons
disease and their spouse using WIMuGPS
C. Duval, L. Zhu, P. Boissy, C. Lavigne-Pelletier, M. Jog, R.
Edwards, M. Speechley (Montreal, QC, Canada)
Objective: Measure and compare mobility of people with Parkin-
sons disease (PwPs) and their spouse.
Background: Mobility declines in PwPs compared to aged-
matched controls are well documented. However, existing literature
has not considered if such declines are found in PwPs when com-
pared against their spouse.
Methods: Over 14 days, 23 PwPs (Hoehn and Yahr stages I - III;
mean age: 67.6 67.2 years; mean disease duration: 6.1 6 4.5 years;
18 men) and their cohabiting spouses (mean age: 67.6 68.0 years; 5
men) wore a GPS embedded with wireless inertial motion units
(WIMuGPS) during awake hours. Participants also completed daily
mobility diaries. Outcomes of interest were: displacement from
home, spatial life space area, number of hotspots in which people
spent at least 5 minutes. Only days with  8 hours of dyad data
recorded during the same time frame were included. Spearmans rs
was performed to estimate the correlation between PwP and spouse
mobility outcomes. Results were compared with r2 from simple lin-
ear regressions to assess effects of demographic covariates. Wilcoxon
rank-sum and Kruskal-Wallis tests of difference were performed.
Results: PwPs and their spouse spent similar amounts of time at
home/day (PwPs: 8.4 6 2.2 hours; spouses: 8.7 6 1.9 hours;
p 5 0.08). This was not affected by years since diagnosis, age or sex
(all p > 0.05). Spousal pairs average displacement outside of home
was correlated (rs 5 0.76, p<0.01). PwPs and spouses also occupied
similar number of hotspots/day (4.6 6 0.5 vs 5.4 6 0.4; p 5 0.13).
Average area occupied/day by PwPs (17.8 6 3.2 km2) and spouses
(17.1 6 1.2 km2) were similar (p =0.1). However, the sizes of life
space of suburban PwPs were significant larger than urban and rural
PwPs (both p 5 0.03). As well, spousal pairs self-reported to take
more trips separately than together/week (7.8 6 4.9 vs 6.1 6 1.2;
p 5 0.04 respectively).
Conclusions: This study suggests that PwPs maintain similar
mobility patterns and life spaces as their spouse. Although effects of
disease progression on the mobility of PwPs and spouses cannot be
inferred, this study showed independence in community mobility in
early to mid-stage PwPs. Finally, results indicated residence setting
should be taken into account when using life spaces as a mobility
indicator. We are now in a position to better appreciate the impact
of the disease on both the patient and their spouse.
1405
Improvement of individual quality of life in caregivers and
patients under L-dopa/carbidopa duodenal infusion therapy
C. Ehlers, H. Honig, P. Odin (Bremen, Germany)
Objective: A detailed analysis of the effect of continuous dopa-
minergic stimulation, CDS, with L-dopa/Carbidopa intestinal gel
(LCIG) infusion on the individual quality of life in patients with
advanced Parkinsons disease and their respective caregivers.
Background: The value of CDS, as achieved with continuous
infusion of Apomorphine or LCIG, regarding motor and non-motor
symptomatology, NMS, has increasingly come into focus and several
studies indicate that NMS might be even more relevant for patients
health-related quality of life, HrQoL, compared to motor symptoma-
tology. Recent studies indicate that moving to CDS-based therapies
might also lead to improvement concerning several NMS. The ques-
tion remains, however, if the improvements in motor and non-motor
symptoms and their effect on the Health related quality of life neces-
sarily correlate with patients individual quality of life.
Methods: Thirteen patients with advanced idiopathic Parkinsons
disease were included in a prospective non-controlled study on the
effect of L-dopa/Carbidopa duodenal infusion on the patients
Movement Disorders, Vol. 30, Suppl. 1, 2015
S542 POSTER SESSION
individual quality of life. The patients were followed for a minimum
of 6 months, with evaluations before start of therapy and after 6
months. The following instruments were used: SEIQoL-Q, QuaQoLs,
PWI, PDQ-39, EQ5D-3L and VAS, Non-Motor-Scale, UPDRS II-IV,
Transition Question, HADS, MMSE and Zarits Caregiver Burden
Scale.
Results: The instruments showed an improvement in individual
quality of life, as measured with SEIQoL-Q, in patients and caregiv-
ers. Furthermore, caregivers improved on the Zarits and HADS.
Moreover, there was an improvement in several non-motor symptom
categories, as reflected by the non-motor scale. Sleep and micturition
improved in all patients. Regarding psychiatric/neuropsychological
symptoms, improvements were registered for depression, anxiety and
hallucinations/psychotic symptomatology (HADS, NMS). The effects
seen on non-motor symptoms were accompanied by an improvement
of the motor symptomatology in most patients.
Conclusions: These observations indicate that continuous dopa-
minergic stimulation might not only have advantages for motor and
non-motor symptomatology when treating advanced Parkinsons dis-
ease, but more importantly could have an impact on the individual
quality of life for patients as well as caregivers.
1406
Anxiety and depressive symptoms are independent predictors of
physical health related quality of life in a Brazilian sample of
Parkinsons disease patients evaluated for deep brain stimulation
F.C. Freitas, A.P. Diaz, M.E.R.O. Thais, F.Z.S. Areas, P.E.L. Vieira,
R. Guarnieri, R.D.S. Prediger, M.N. Linhares, R. Walz
(Florian
opolis, Brazil)
Objective: To evaluate predictors of HRQOL domains which are
linked to physical symptoms in a Brazilian sample of Parkinsons
disease patients presenting for deep brain stimulation.
Background: Depression is highly prevalent in PD patients and
has been associated with a faster progression of the disease, care-
giver burden and a worse health-related quality of life (HRQOL).
Methods: Participants (n559) presenting for DBS were evaluated
in the outpatient Unit for Movement Disorders of the Hospital Gov-
ernador Celso Ramos in Florian opolis, state of Santa Catarina, Bra-
zil, from May 2009 to March 2013. The SCID I was applied for
psychiatric diagnosis classification. Anxiety and depressive symp-
toms were quantified with the Hospital Anxiety and Depression Scale
(HADS). UPDRS MDS III, HADS scores, duration of the disease,
age and presence of general diseases were the predictors variables.
Mobility, Activities of daily living and Bodily discomfort domains
scores of the 39 item Parkinsons disease questionnaire (PDQ-39)
were the outcomes. After a series of simple linear regression, multi-
ple linear regression analysis was performed to determine independ-
ent predictors of the outcomes.
Results: The sample was predominantly male, married, with few
years of education and a mean age of 58 (68 SD). The mean on
state UPDRS MDS III score was 26.9 (616.8 SD) and the median
HY stage 2 (IQ 2/3). The mean HADS scores was 11.9 (6 8 SD)
and the prevalence of Major Depression was 18.6%. PDQ-39
domains Mobility, Activities of daily living and Bodily discomfort
mean scores were 60.8 (626.3 SD), 64.1 (628.7 SD) and 56.4
(629.3 SD), respectively. After multiple linear regression, HADS
scores (B coef. 1.36, 95% CI 5 0.55 2.16) and UPDRS MDS III
scores (B coef. 0.42, 95% CI 5 0.03 0.81) were independently
associated with Mobility domain scores (r2 5 0.25). HADS scores (B
coef. 1.57, 95% CI 5 0.67 2.48) was independently associated with
Bodily discomfort domain scores (r2 5 0.24).
Conclusions: Poor physical quality of life in PD patients present-
ing at the best on state for DBS treatment possibly is associated both
to motor function and anxiety and depressive symptoms. The poten-
tial impact of appropriate psychiatric treatment in physical quality of
life independently of motor function deserves further investigation.
Movement Disorders, Vol. 30, Suppl. 1, 2015
1407
Burden in caregivers of patients with Parkinsons disease
D. Gr
un, V. Pieri, M. Vaillant, N.J. Diederich (Luxembourg,
Luxembourg)
Objective: Our research explored various factors potentially con-
tributing to caregiver burden (CB) of people carrying for people with
Parkinsons disease.
Background: Parkinsons disease is a neurodegenerative illness
in which patients often require burdensome assistance. In many cases
this is delivered by informal caregivers e.g. spouse.
Methods: We recruited 59 patient-caregiver pairs from different
neurological consultations in Luxembourg.
We explored the caregiver by the following tools: Zarit Burden
Interview, Health Related Quality of Life (HRQoL: EuroQol EQ-
5D), Generalized Anxiety Disorder Assessment-7, Patient Health
Questionnaire-9 (Depression) and the Montreal Cognitive Assessment
(MoCA). We evaluated the following symptoms in the patient: motor
symptoms (MDS-UPDRS III-IV, Hoehn & Yahr staging), sleep qual-
ity (Parkinsons disease Sleep Scale), autonomic dysfunction
(SCOPA-AUT), apathy (Starkstein Apathy Scale), cognitive status
(MoCA) and HRQoL (EuroQol EQ-5D).
Results: Higher CB was seen with worsening motor symptoms in
the patient (p < .05). Sleep problems and autonomic dysfunction neg-
atively influenced CB (r 5 -.414 to .335, p < .01) as well as caregiv-
ers HRQoL (r 5 -.335 to .314, p < .05). Nocturnal care and greater
total amount of time invested resulted in higher CB (p 5 .000). The
cognitive status of the caregiver did not contribute to CB (p >.05).
However, the mood of the caregiver was linked both to CB and
to caregivers HRQoL (p < .01).
Conclusions: In a holistic approach of Parkinsons disease, physi-
cians should be attentive to the often substantial burden of informal
caregivers. Preservation of the physical and mental health of these
persons may have a reciprocal effect on the patients well-being.
1408
Factors influencing the poor quality of life in patients with
Parkinsons disease
M.I. Khalil, M.R. Rahman, M. Hakim, N.C. Kundu, P.C. Das, M.M.
Islam (Dhaka, Bangladesh)
Objective: To investigate the factors associated with a poor Qual-
ity of life (QoL) in Parkinsons disease (PD) in a Bangladeshi
sample.
Background: Quality of life is increasingly recognized as a criti-
cal measure in health care and is an important treatment outcome
indicator in Parkinsons disease.
Methods: A cross-sectional study was conducted in the Depart-
ment of Neurology, Shaheed Suhrawardy Medical College and Hos-
pital in Dhaka, Bangladesh. One hundred fifty five, clinically
diagnosed PD cases were enrolled. Brain MRI was done in all cases
and patients with aphasia, significant cognitive deficits, secondary
Parkinsonism, abusive use of alcohol or illicit drugs, past history of
psychiatric disorders were excluded. A translated (Bangla) and pre-
tested, Parkinsons disease Questionnaire (PDQ-39) was used to
assess the quality of life. A face to face interview and a complete
neurological examination, including Hoehn and Yahr stage, parts of
the unified Parkinsons disease rating scale, DSM-IV for depression
and modified Rankin Scale (mRS) for disability (0-1 mild, 2-3 mod-
erate, and 4-5 severe) were performed. Statistical analysis was done
using SPSS v 21(p<0.05 for statistical significance). Stepwise linear
regression model was used to determine the factors that best
accounted for variance in QoL scores.
Results: The Mean (SD) age was 66.65 (10.79) years, disease
duration 5.13 (3.26) years, PDQ-39 summary index score 43.64
(11.51) respectively and male: female ratio was 1.67:1 in our partici-
pants.There was no significant difference in frequency of age, sex,
education, socioeconomic condition, smoking, marital status,
 POSTER SESSION
diabetes, hypertension and coronary heart disease. Higher PDQ-39
score correlated significantly (p<0.0001) and positively with disease
duration, severe disease stage, having depression, sleep disturbance,
postural instability, motor fluctuation and disability. Whereas in step-
wise linear regression analysis, severe disease stage (p<0.0001),
presence of depression (p<0.0001), having disability (p50.023) and
prolong disease duration (p50.044) have the greatest influence on
higher PDQ-39 score and hence the worse quality of life.
Conclusions: In this case series, the poor quality of life in PD
was significantly associated with severe disease stage, depression,
disability and prolonged disease duration. The translated PDQ-39
was applicable to Bangladeshi patients.
1409
Translation into Polish and validation of two quality of life
assessment modules for patients with Parkinsons disease-QLSM-
MD and QLSM-DBS
A.T. Krygowska-Wajs, K.A. Tomaszewski, A. Gorecka-Mazur, W. Pie-
traszko, K. Potasz (Kracow, Poland)
Objective: The aim of the present study was to translate into Pol-
ish and validate two quality-of-life (QoL) questionnaires: Questions
on Life Satisfaction Module (QLSM) Movement Disorders
(QLSM-MD) and deep brain stimulation (QLSM-DBS).
Background: Deep brain stimulation (DBS) is increasingly used
as a therapeutic option in MD. QoL starts to be recognized as an
important endpoint in clinical trials. This shows the need to have
valid instruments for Qol assessment in culturally differing groups.
Methods: Patients with the diagnosis of Parkinsons disease (PD)
according to UK Parkinsons disease Society Brain Bank Criteria
were included in the study. The QLSM-MD and the QLSM-DBS
modules were translated into Polish following a standardized
forward-backward procedure. All patients filled out the Polish ver-
sion of the QLSM-MD, PDQ-39, and a demographic questionnaire.
A subset of patients treated with DBS (n530) filled out the QLSM-
DBS. The severity of PD symptoms was assessed using the Hoehn &
Yahr scale. Standard validity and reliability analyses were per-
formed. The re-test took place 2 weeks after the initial assessment.
Results: One-hundred-and-nineteen patients (47 women and 72
men) were enrolled into the study group (mean age6SD 63.0 6 10.5
years). The mean disease duration of the enrolled patients was
9.0 6 5.4 years. The mean summary index score of the QLSM-MD
was 0.06 6 4.2; 4.7 6 3.6 for the QLSM-DBS, and 2.6 6 0.73 for the
Hoehn & Yahr scale. Cronbachs alpha coefficient for the QLSM-
MD summary index was 0.92, and for the QLSM-DBS 0.69, demon-
strating respectively excellent and bordering on acceptability internal
consistency. Re-test was undertaken with 78 patients (65.6%). The
interclass correlation for the QLSM-MD was 0.87 (95%CI 0.77-
0.89), and for the QLSM-DBS 0.97 (95%CI 0.95-0.98) proving
appropriate test-retest reliability. Satisfactory convergent and dis-
criminant validity in multi-trait scaling analyses was seen.
Conclusions: The Polish translation of the QLSM-MD and QLSM-
DBS evaluate the QoL of patients with PD similarly to the original lan-
guage versions. Psychometric analysis proved that they are reliable and
valid tools. PD patients acknowledge that these modules are an accepta-
ble way to measure their QoL. Thus the QLSM-MD and QLSM-DBS
can be recommended for use in Polish clinical and research settings.
1410
Quality of life predictors in Parkinsons disease at the Lagos
University Teaching Hospital
T.A. Lawal, N.U. Okubadejo, O.O. Ojo, M.A. Danesi (Lagos, Nigeria)
Objective: To determine quality of life predictors in Parkinsons
disease.
Background: Quality of life is deemed to be affected in chronic
progressive degenerative conditions such as Parkinsons disease.
S543
Among a wide spectrum of disease variables, the factors that portend
health related quality of life in our Parkinsons disease cohort are
however yet to be fully determined.
Methods: This study was carried out between November 2011
and December 2012. Demographic and clinical data were obtained.
Clinical evaluation included the use of the following instruments:
Hoehn and Yahr (H&Y) staging, Movement Disorders Society spon-
sored version of the United Parkinsons disease Rating Scale (MDS-
UPDRS), Parkinsons disease Questionnaire-39 (PDQ-39) and Zung
Self Rating Depression Scale (ZSDS). The direction and magnitude
of association between disease variables and quality of life (using
the PDQ-39 summary index-SI) were compared and independent pre-
dictors of quality of life were analyzed.
Results: Fifty (50) PD patients were studied including 35 (70%)
males and 15 (30%) females. The mean age (6SD) of PD patients
was 62.26 9.3 years (range 41-80). The PDQ 39-SI correlated sig-
nificantly and positively with disease duration, MDS-UPDRS score
(and subscales), H&Y stage and ZSDS scores (Spearman rank coeffi-
cient 0.4-0.8, P< 0.001-0.005) while the age at onset and years of
education had a weak inverse correlation (spearman rank coefficient
-0.1, P=0.6 and -0.2, P=0.2 respectively).
Using multiple linear regression analysis, the significant inde-
pendent predictors of PDQ 39-SI were observed to be ZSDS scores
(b 0.32, 95% CI 1.08-10.40) and the motor experience of daily liv-
ing (mEDL) subscale scores of the MDS-UPDRS (b 0.71, 95% CI
4.95-16.11).
Conclusions: Depression and motor experience of daily living
were significant predictive factors influencing the quality of life in
Parkinsons disease.
Reference: Slawek J, Derejko M, Lass P. Factors affecting the
quality of life of patients with idiopathic Parkinsons disease-a cross
sectional study in an out patient clinic attendees. Parkinsonism Relat
Disord. 2005; 11:465-8.
1411
Mood disorders and health-related quality of life in Parkinsons
disease
T. Maeda, T. Shinoda, D. Takano, T. Yamazaki, Y. Fujimaki, Y.
Satoh, K. Nagata (Akita, Japan)
Objective: Parkinsons disease (PD) frequently comorbids mood
disorders and sleep problems. Both can deteriorate the health-related
quality of life (HRQOL) as well as motor problems. However, the
relationship between the HRQOL and these problems remain to be
clarified. In this study, we investigated the relationship using with
some questionnaires and statistically analyzed.
Background: The HRQOL is increasingly noticed as an impor-
tant factor in a clinical practice in PD as well as motor management.
PD patients can retain variable nonmotor symptoms and the nonmo-
tor symptoms can deteriorate their HRQOLs more intensively than
the motor problems.
Methods: We consecutively recruited PD patients who visited
our outpatient division from October 2010 to September 2011. The
Ethical Committee of the Research Institute for Brain and Blood
Vessels-Akita, approved this study. Written informed consent to par-
ticipate in this study was obtained from all the patients. The 39-item
PD questionnaire (PDQ39) were performed in all patients and the
summery index (iPDQ39) were calculated. Mood disorders were
examined using with the Becks depression inventory version 2
(BDI2) as a depression scale, the Snaith-Hamilton pleasure scale
(SHAPS) as an anhedonia scale and the apathy scale (AS). Sleep
problems were examined using with the PD sleep scale (PDSS) and
the rapid eye movement sleep behavior disorder screening question-
naire (RBDSQ). We also examined clinical severity using with
Hoehn-Yahr stage (H&Y) and unified PD rating scale (UPDRS). The
HRQOL were statistically analyzed.
Results: We could recruit 109 PD patients (62 females and 47
males). Their mean age, duration of illness, H&Y and UPDRS were
Movement Disorders, Vol. 30, Suppl. 1, 2015
S544 POSTER SESSION
70.7 years, 82.6 months, 2.4 and 30.9, respectively. The mean value
of scales were 37.4 in the iPDQ39, 13.2 in the BDI2, 0.2 in the
SHAPS, 2.5 in the AS, 6.5 in the PDSS and 3.9 in the RBDSQ,
respectively. There was a statistically significant relationship between
the iPDQ39 and the BDI2 (p<0.01), the PDSS (p<0.01), the
RBDSQ (p50.04) and UPDRS part 2 and part 4 (p<0.01) in the
Spearmans rank correlation coefficient. In the multiple logistic
regression analysis, the BDI2 (r=0.24,95%CI 0.11-0.85,p=0.01) was
detected as a correlating factor of the iPDQ39.
Conclusions: It was suggested that mood disorders could be a
deteriorating factor of the HRQOL in PD patients. The comprehen-
sion and treatment of mood disorders were important to improve the
HRQOL in PD patient.
1412
Collaboration and consultation, improving quality of care and
life for people with Parkinsons
V. McConvey, B. Wotherspoon, T. Osborn, N. Graham (Cheltenham,
Australia)
Objective: 1) Identify the challenges of delivering expert care to
people living with Parkinsons and other Movement Disorders in
Victoria Australia. 2) Illustrate the multidisciplinary response devel-
oped by Parkinsons Victoria to address clinical needs and grow
capacity. 3) Identify the importance of interagency collaborations to
improve care. 4) Demonstrate value of synergies created by
collaborations.
Background: Victoria is the smallest mainland state of Australia
with an estimated population of 27,000 people living with Parkin-
sons. The state has well organised socialised health services how-
ever the care of people living with Parkinsons and other Movement
Disorders is often poor with very few specific services available. In
response Parkinsons Victoria has developed a unique clinical con-
sultancy model to improve the care along the continuum of illness.
Methods: The Health information service at Parkinsons Victoria
is a specialised multi-disciplined service which operates web and
tele-health information services, having contact with over 120,000
individuals annually. Central to this service is a Health Professional
education program and a comprehensive network of support groups.
The hub and spoke model of care connects generalist health pro-
fessionals and patient groups with specialist multi-disciplinary health
professionals and clinical researchers to increase knowledge, build
capacity, improve patient outcomes and support better self-
management. Connections are supported by technology and can be
by phone, internet or face to face.
Results: Qualitative and market research data indicates both pro-
fessionals and consumers identify improvements in clinical manage-
ment and quality of life when accessing the service. It has been
difficult to demonstrate a health economic benefit in the absence of
robust health informatics.
Conclusions: The Parkinsons Victoria model of multi-
disciplinary care improves care and promotes better self-care in peo-
ple living with Movement Disorders. The absence of formalised
funding and sound data demonstrating an economic benefit are limit-
ing and require further investigation.
1413
Evaluating mortality in hospitalised patients with Parkinsons
disease
M. Modi, K. Dean, A. Chatterjee (Reading, United Kingdom)
Objective: We aimed to 1) characterise the major causes of death
(CoD) in patients with known Parkinsons disease (PD) at a large dis-
trict general hospital 2) evaluate whether PD was identified on death
certificates 3) identify a relationship between CoD and duration of PD.
Background: Patients with PD have 2-5 times higher mortality
than age matched controls. While PD itself is not fatal, progression of
Movement Disorders, Vol. 30, Suppl. 1, 2015
the disease is associated with significant physical and functional
impairment including dysphagia causing aspiration, gait instability lead-
ing to falls and neuropsychiatric symptoms impacting quality of life.
Methods: Clinical notes of patients with PD who died at Royal
Berkshire Hospital between 1st January 2010 and 31st December
2012 were retrospectively analysed.
Results: 98 patients were identified using the Hospital Death
Registry. 88 clinical notes were available for analysis (55 male, 33
female patients, mean age at death of 83 years). 5 patients did not
have a cause of death available.
Infection was identified as the primary CoD in 61% of patients
(n551), 80% of these deaths (n541) were due to respiratory tract
infections, including aspiration pneumonia. Respiratory disease
accounted for 51% of deaths (n543) (NB: in majority of cases respi-
ratory disease and infection co-existed). Other CoD included cardiac
disease (n57), gastrointestinal pathology (n59) and neurological
pathology (n58). PD itself was identified as the primary cause of
death for 3 patients. 54% of patients (n548) had the diagnosis of PD
documented on their death certificates.
Data for duration between diagnosis of PD and death was avail-
able for 70 patients: range 1 year to 26 years, mean 6.3 years.
Conclusions: Respiratory disease and infection are the major
CoD in PD. During 2011, 15% of all deaths in patients older than 65
in England and Wales were attributed to respiratory disease, com-
pared to 51% in the study population. Infections, especially pneumo-
nia, were a particularly common cause of death in this cohort.
Prompt identification and treatment of infection needs to be instituted
in such patients.
Over a third of patients did not have their diagnosis of PD docu-
mented on death certification. This has implications on research and
understanding of disease processes co-existing with PD, and there-
fore needs to be addressed.
1414
End-of-life treatment preferences in Parkinsons disease
H.L. Ng, W. Li, A.N. Piano, S. Abdul Karim, W. Li, K.Y. Tay, W.L.
Au, L.C.S. Tan (Singapore, Singapore)
Objective: To evaluate the factors affecting treatment preference
in patients with Parkinsons disease.
Background: Understanding the factors affecting treatment pref-
erences in patients with Parkinsons disease (PD) is essential to ena-
ble optimal care planning.
Methods: Patients with PD were recruited from the Movement
Disorder Centre by convenience sampling. A questionnaire modified
from the Willingness to Accept Life-Sustaining Treatment (WALT)1
instrument was administered to assess the treatment preference. Four
different scenarios were presented to the patients to obtain their views
on their treatment preference. In each scenario, patients had to choose
between receiving the treatment (low or high-burden) and accepting
the resultant outcome (poor or good outcome). Logistic regression was
used to evaluate the predictors of treatment preference in PD.
Results: 136 PD patients (84 males and 52 females) were recruited
(Table 1). The significant predictors of treatment preference in PD are
shown in Table 2. The predictors varied for each scenario. For the
low burden-poor outcome scenario, patients with higher UPDRS motor
scores (>17) were significantly more likely to opt for treatment as
compared to those with low UPDRS motor score (17). Those with
religious faith were significantly more likely to opt for treatment with
either resultant low burden-poor outcome or high burden-good out-
come as compared to free-thinkers. Married patients were significantly
more likely to opt for treatment with resultant high burden-good out-
come. For the high burden-poor outcome scenario, Chinese were less
likely to opt for treatment that would result in high burden-poor out-
come as compared to other ethnicities. Patients with higher UPDRS
motor scores (>17) were more likely to opt for treatment. Patients
with more knowledge of PD were less likely to opt for treatment with
resultant high burden treatment-poor outcome.
 POSTER SESSION S545

Characteristics of PD Patients

Characteristics Mean (Standard Deviation)

Age 63.53 (9.83)
Duration of PD (years) 5.80 (4.33)
UPDRS 18.77 (9.22)
Hoehn & Yahr 2.10 (0.64)
Schwab & England 86.80 (11.91)
MMSE 26.57 (3.14)
PDQ8 14.48 (16.52)

Significant predictors of treatment preference in PD

Predictors Odds Ratio 95% Confidence Interval p value

Low burden-poor outcome: Religion 7.430 1.967-28.069 0.0031
Low burden-poor outcome: UPDRS (>17) 2.507 1.143-5.499 0.0219
High burden-good outcome: Religion 6.930 2.234-21.493 0.0008
High burden-good outcome: Marital status (Married) 6.930 2.234-21.493 0.0008
High burden-poor outcome: Race (Chinese) 0.286 0.103-0.791 0.0159
High burden-poor outcome: Knowledge 0.365 0.160-0.802 0.0121
High burden-poor outcome: UPDRS (>17) 3.047 1.345-6.900 0.0076

Conclusions: Patients with better knowledge about PD were less
likely to opt for treatment that required a higher burden of care with
poor outcome. This may be related to the reluctance to impose stress
and burden on the caregivers. In addition, the motor ability of
patients, race, marital status and religion are other factors affecting
treatment preference. A better understanding of patients wishes
relating to end-of-life care will aid advance care planning.
1415
Evaluating a new multidisciplinary Movement Disorders clinic
J.S. Riley, A.K. Chatterjee, S.E. Williams, A. Plowman, J. Caffrey
(Reading, United Kingdom)
Objective: To establish the users of and evaluate our Movement
Disorder Clinic.
Background: Dedicated to older patients with Movement Disor-
ders, the principal aim of the clinic is to work with patients to
improve their quality of life. The team includes a specialist consul-
tant, occupational therapist (OT) and physiotherapist (PT). The serv-
ice is funded by PD UK and a legacy left by a patient.
Methods: We analysed clinic letters and notes to establish the
demographics, stage of disease and therapies given. We conducted a
survey from August 2013 to July 2014 evaluated by Meridian, a
scoring system comparable to the National Survey scoring system.
Results: 181 patients attended clinic. 3 records were unavailable.
107 were male, 71 female, average age was 81. 77.53% of patients
were from their own home. 92.13% of patients had Parkinsonism,
(57.8% had Idiopathic Parkinsons disease, 6.74% vascular Parkin-
sonism, 3.93% drug-induced Parkinsonism). 23.17% had dementia
and 5.06% had complex stage. Between December and August, 107
of audited notes showed 92.5% of patients saw a PT. Advice on
exercise was given in 62.6%, on mobility in 66.7% and safety in
20.2%. Cueing techniques were shown in 36.4%. In the same time of
the 120 notes audited, 93.33% of patients saw an OT, 60.7% of these
underwent cognitive testing, 50% had equipment ordered or recom-
mended. The following interventions were undertaken: carer burden
management (47.3%), ADL management (33.9%), transfer techni-
ques (31.2%), physical activity improvement (30.4%), falls preven-
tion (26.8%), leisure (21.4%), hand therapy (12.5%), feeding
management (12.5%), fatigue management (10.71%) and sleep man-
agement (8.9%). 135 surveys were completed before the clinic
attendance and 31.11% described their knowledge of Parkinsons dis-
ease as poor or non-existent. 48 patients completed the post clinic
survey. The overall scores were recorded as follows: clinic attend-
ance beneficial 81.25%, enough time with therapists 80.73%, time
with therapists useful 77.60%, information provided useful 74.48%,
clinic helped confidence levels 67.18%.
Conclusions: Our data suggests the clinic serves our target popula-
tion of elderly patients (with a variety of residences, diagnoses and stage
of disease) with helpful information, a broad spectrum of useful inter-
ventions, improves patients confidence levels and is overall beneficial.
1416
Economic burden of Parkinsons disease (PD) on caregivers
K. Sail, J. Signorovitch, R. Sorg, F. Mu, T. Marshall (North
Chicago, IL, USA)
Objective: To compare the direct and indirect costs of PD
patients caregivers with demographically matched non-PD caregiver
controls in the US.
Background: PD is a progressive, disabling neurodegenerative
disorder that imposes a significant economic burden on patients and
their caregivers.
Methods: Primary policyholders ages 18-64 linked to a PD patient
(2 PD ICD-9-CM codes; 332.0) from 1/1/98-3/31/14 were selected
from a de-identified, privately insured claims database (PD care-
givers). The index date was the patients first observed PD diagnosis.
PD caregivers with continuous eligibility 6 months before (baseline)
and 1 year after (study period) the index date were matched 1:5 on sex,
age, region, and index year to primary policyholders without a depend-
ent with PD (controls). Baseline characteristics included the Charlson
comorbidity index (CCI) and caregiving-related comorbidities. Direct
costs included all-cause medical (inpatient, emergency department
[ED], outpatient, other), prescription drug, and comorbidity-related
medical costs. Indirect costs included disability and medically-related
absenteeism costs. Baseline characteristics and 12-month study-period
costs (2014 USD) were compared using generalized estimating equa-
tion regression models to account for matching. Multivariable regres-
sions of costs were conducted to adjust for baseline characteristics.
Results: A total of 1,211 PD caregivers (mean age 56 years) met
the inclusion criteria and were matched to 6,055 controls. PD care-
givers had significantly higher rates of caregiving-related comorbid-
ities, including backache (16.5% vs 12.5%), hypertension (24.5% vs
20.3%), GERD/heartburn (4.5% vs 3.4%), and irritable bowel

Movement Disorders, Vol. 30, Suppl. 1, 2015

S546 POSTER SESSION
syndrome (1.5% vs 0.6%) compared with matched controls. Results
from the adjusted regression analysis indicated that PD caregivers
incurred higher mean direct medical costs, with significantly higher
ED ($269 vs $180), outpatient ($2,038 vs $1,664), comorbidity-
related medical ($1,503 vs $1,136), and prescription drug ($1,612 vs
$1,336) costs. Among the 418 PD caregivers and 2,090 matched con-
trols with workloss data, PD caregivers had significantly higher
adjusted medically-related absenteeism costs ($1,493 vs $1,140).
Conclusions: PD caregivers exhibited higher rates of comorbid-
ities and direct and indirect costs compared with matched controls.
These results provide evidence on the comprehensive burden of PD.
1417
Health care disease burden severity among caregivers of
Parkinsons disease patients in an Arab cohort
Y.A. Seddeq, N.H. Al-Shammari, T.M. Mohammad, M.S. Bashir, J.A.
Bajwa (Riyadh, Saudi Arabia)
Objective: To study the impact of potential factors on health care
disease burden severity in caregivers of patients with Parkinsons dis-
ease at Movement Disorders/Neurorestoration program, National Neu-
roscience Institute, King Fahad Medical City, Riyadh, Saudi Arabia.
Background: Parkinsons disease (PD) is a neurodegenerative
disorder that results in progressive disability. This can increase
health care disease burden among caregivers thus effecting quality of
life of the patient and the caregiver.
Methods: A total of 40 Saudi PD patients and their caregivers
agreed to participate in this study. Caregivers were assessed by Hos-
pital Anxiety and Depression Scale (HAD) and Zarit caregiver bur-
den Interview (ZCBI) as a measure of Health related quality of life
(HRQoL). Patients were assessed by Hoehn & Yahr staging (HY),
Schwab and England Activity of Daily Living Scale (SEADL), mini
mental status exam (MMSE) and modified Unified Parkinsons dis-
ease Rating Motor Scale (UPDRS). Sociodemographic data of care-
givers and PD patients was collected through a questionnaire.
Results: There is statistically significant (p 5 0.025) relationship
or association between PD patients and caregiver according to gender
distribution. Educational differences observed between PD patients
and caregiver was significant (p 5 0.007). The mean age difference
results between PD patients and caregiver were significant
(p < 0.001). Caregivers on Ziert Burden Score had a mean of
41.8 6 23.1, . patients had a mean score on UPDRS of 39.5 6 15.9
and a mean MMSE of 22.5 6 6.3. Caregivers HAD-A and HAD-D
mean score was 7.3 6 5.1 and 7.5 6 23.5 respectively. There is statis-
tically significant (p < 0.001) association between UPDRS score and
H&Y scoreshowing strong positive magnitude correlation (r 5 0.731)
. We have found statistical significant mean differences among
HAD-D and ZCBI with respect to H & Y Score as well.
Conclusions: Majority of caregivers (32%) showed little or no bur-
den and this could be explained by their perspective that caregiving is
a part of religious believe. This may reveal two types of burden: objec-
tive versus subjective as the actual burden might be the same but if it
is perceived differently by caregivers, it may have a different effect on
quality of life. Further research into factors associated with health care
disease burden severity is required in this unique Arab cohort.
1418
Gender differences in health care disease burden severity among
caregivers of Parkinsons disease patients in an Arab cohort
Y.A. Seddeq, N.H. Al-Shammari, T.M. Mohammad, M.S. Bashir, J.A.
Bajwa (Riyadh, Saudi Arabia)
Objective: To study the impact of caregiver burden among gen-
ders taking care of Parkinsons disease patients at Movement Disor-
ders/Neurorestoration program, National Neuroscience Institute, King
Fahad Medical City, Riyadh, Saudi Arabia.
Movement Disorders, Vol. 30, Suppl. 1, 2015
Background: Parkinsons disease (PD) is a neurodegenerative
disorder which not only burdens PD patients themselves but also
affects their caregivers. Most caregivers describe their role as stress-
ful and challenging while the burden increases with progressive long-
standing disability from the disease.
Methods: A total of 40 Saudi PD patients and their caregivers
agreed to participate in this study. Caregivers quality of life were
assessed (HRQL) by different measures as Hospital Anxiety and
Depression Scale (HAD) and Zarit caregiver burden Interview (ZCBI)
. Patients disease severity were assessed by Hoehn & Yahr staging
(HY), Schwab and England Activity of Daily Living Scale (SEADL),
mini mental status exam (MMSE) and modified Unified Parkinsons
disease Rating Motor Scale (UPDRS). Sociodemographic data of care-
givers and PD patients was collected through a questionnaire.
Results: There is significant (P 5 0.008) association or difference
between caregiver gender and their income,56% female caregivers
have low income that would be considered an impact on caregiver
burden. Mean significant (P 5 0.001) difference were observed
between duration of caregiving and gender.although females were
providing care over longer duration as compared to male caregiver,
2.2 years of difference between gender and caregiving would be con-
sidered as statistical difference.
Conclusions: Our study indicates that females are spending more
time in caregiving with low income while both of these factors can
significantly increase the burden in presence of cultural differences
and absence of support in many aspects for this cohort. Further stud-
ies are required to identify gender differences and health care disease
burden severity in this unique cohort.
1419
Parkinsons disease impact on quality of life of individuals in
mild and moderate stages
R.C.P. Silva e Moreira, M.B. Zonta, H.A.G. Teive (Curitiba, Brazil)
Objective: To compare the QoL of individuals with PD in mild
(MID) and moderate (MOD) stages and investigate which factors are
associated to its decline.
Background: Parkinsons disease (PD) is a chronic degenerative
disorder that significantly affect these individuals quality of life
(QoL).
Methods: There were considered neurological clinical data col-
lected from medical records and those obtained in the UPDRS, Daily
Living Activities (DLA) and Motor Examination Domains (MED),
and in the PDQ-39.
Results: There were compared two groups of 50 PD individuals,
classified as MID and MOD according to the Hoehn-Yahr Scale.
Groups were homogeneous as to gender, age (6080 years), race, mari-
tal status and education level. Average time of disease progression
(TDP) was 3.4 years (62.2) for MID and 8.1 years (64.7) for MOD.
The MOD presented greater impairment in DLAs-UPDRS (p50.05),
and worsening was observed especially as to salivation (p<0.004),
need for assistance with hygiene (p50.02) and freezing frequency
(p50.042). MOD scores indicated greater impairment in thirteen of the
14 MED-UPDRS, especially considering the presence of resting tremor
(p50.035), pill rolling (p50.001) and bradykinesia (p50.031). QoL
in MOD was more impaired considering mobility (p50.013), stigma
(p50.043), cognition (p50.002), DLAs (p50.05) and body discomfort
(p50.04). Among married individuals the lake of support from friends
and family was related to worse QoL in both groups (p<0.001) and
Stigma (p50.02) in the MOD. No relationship was found between age
and clinical/functional data and QoL in MID, whereas in MOD higher
age ranges were related to higher dependence in DLAs (p50.02) and
greater cognition impairment (focus and memory) (p50.01). The lon-
ger TDP was associated to worse QoL in the domains of DLAs (MID)
(p50.03) and Emotional Wellbeing (MOD) (p50.01).
Conclusions: Increased salivation, the need for help for Hygiene,
the highest frequency of freezing, bradykinesia, greater intensity of
the resting tremor and pill rolling were clinical and functional
 POSTER SESSION S547

worsening markers to the moderate stage of PD. The impact in QoL
was related to Stigma, cognition and impairment in mobility and
DLAs. In this sample older, male and married individuals and those
with longer TDP had greater impairment in QoL.
1420
The quality of life in Korean hemifacial spasm patients
S.K. Song, J.H. Kang (Jeju, Korea)
Objective: To assess factors affecting the quality of life in
patients with HFS in respect of influence of the severity of motor
and non-motor symptoms of HFS.
Background: Hemifacial spasm (HFS) is a Movement Disorder
manifested by unilateral spasms of the muscles innervated by the
facial nerve. Botulinum toxin provides an effective medical treat-
ment. Since HFS is a chronic disease, it frequently interferes with
social life, causing social isolation and depression and having a sig-
nificant impact on the quality of life. The aim of the study was to
assess factors affecting the quality of life in patients with HFS in
respect of influence of the severity of depression symptoms.
Methods: Fifty-two patients included from the Outpatient Clinic,
Department of Neurology, Jeju National University Hospital, who
fulfilled the inclusion criteria and had no exclusion criteria (suffering
from concomitant Movement Disorders, other severe chronic diseases
or cognitive impairment).Demographic and clinical data were col-
lected. Severity of HFS was assessed by the five-point clinical scale.
Quality of life was assessed with the 36-Item Short-Form Health Sur-
vey (SF-36) questionnaire and severity of depressive symptoms was
evaluated with the Beck Depression Inventory. Accompanying HFS
non-motor and motor-related symptoms were asked by a question-
naire without quantifying their severity.
Results: The mean global score of SF-36 was 58 6 20, and BDI
was 16 6 5. Over 75% of patients reported HFS non-motor and
motor-related symptoms. Decreased score of SF-36 was affected by
increased severity of HFS and the number of accompanying non-
motor and motor-related symptoms.
Conclusions: Our data suggest that the severity of HFS and the accom-
panying non-motor symptoms affect the quality of life in HFS patients.
1421
Advance care planning: Perspectives of people living with
Parkinsons disease (PD)
M.P. Sritharan (Bristol, United Kingdom)

Perspectives of people with Parkinsons disease regarding advance care planning

Theme Sub-theme Patient Quote

Attitude to future Importance of it means you have got control over that stage in your life [.] you know you have still
planning planning ahead got [.] that final say [.] I think it might be a relief to know that I was on that down-
ward stage and wasnt going to linger around for too much longer hopefully [.] I
think there is a certain dignity in it then. I think however well meaning those, you
know that love you and care for you think they are doing the best for you, I think it
has got to come from you really [.]but I think it is very important
Fear of looking ahead I cant visualise it happening at the moment, so I dont really want to I dont think
I would want to know [. . .], it frightens me to death [. . .]because if these horrible
things are going to happen, there isnt much you can do to stop them is there?
Role of advance Maintaining control I just thought it was really empowering for you, you are still a human being no matter
care planning whats wrong with you, I just thought it was really good. I liked that control
Immaterial as unaware I wouldnt feel the need to stamp my requirements over my own life, because its not
when incapacitous that I hold it lightly but what happens to it is what happens to it, Im not actually,
not that bothered, if that makes sense
Impact of ACP [ACP discussion] could be [useful] provided it didnt upset my feeling of well being,
on present mood little that I have, I dont want to lose any sense of well being, any sense of future!
Impact of ACP on family I wouldnt want to almost force them down a new avenue, if they could see some-
thing else was more beneficial and that maybe I was suffering from dementia and
really was out of it [. . .] I wouldnt want to constrain them
Right timing for Not at diagnosis I dont think thats a good idea because you want to get to know the disease, you
ACP discussion want to get to know how you feel with it [.] get happy with the situation you are in
or accept the situation you are in, because I think if you start to approach it on diag-
nosis, people are going to suddenly think Im dying [.] it will upset people even
more than they are already
After coming to terms with I would be quite happy now [.] Ive settled, because to start with its sort of confusing,
the diagnosis [.] you need to understand where you are before you start considering these things
As part of growing older its 17 years [since diagnosis], we are getting older now so perhaps we should be
thinking about it
When starting to I think at the point where serious independent living starts to be jeopardised
deteriorate physically
ACP documentation Importance of a You have got to record it in some way [. . .]I dont think its much good me saying to
written document [my wife] I want this, this and this if when the times comes to it, someone says
how do you know he wanted that?
Fear of misinterpretation I worry about how it could be interpreted [. . .]so long as its realistically interpreted
and compassionately interpreted
Leaving decision Expectation of the family I am quite happy for them to decide for me because I know they would do it for my
making to the to know what the best [. . .] I would trust my family implicitly to deal with it [. . .] because theyve got
family individual would want my interests at heart
Not wanting to burden I want to make that decision first [. . .] because I dont want them to have to decide. I
the family would take their views into consideration, but its me thats going to make the decisions

Movement Disorders, Vol. 30, Suppl. 1, 2015

S548 POSTER SESSION

Views of spouses/partners of people with Parkinsons disease regarding advance care planning

Theme Sub-theme Patient Quote

Perception of ACP
The role of the spouse
in ACP discussions
Making decisions on behalf
of the affected spouse in
the absence of an ACP
A useful clinical tool
Not suitable for the
individual and effect
of fluctuations in PD
Ensures affected partners
wishes are upheld
Broaching the subject
Inability to initiate discussion
Quite a good idea really to save a lot of unnecessary suffering and pain
and discomfort [. . .]theres no point in enduring months of suffering
unnecessarily prolonging life to achieve nothing, nothing to be gained
[. . .] once you know what the outcome is going to be, really its to do
it peacefully and dignified
I was all for the idea of it, but I have just heard [my husband] talk, and
I have just realised that its really not going to be [.] something for
him, because the answers he would give at 12 oclock wont be the
same answers he will give at 3 oclock [.] a week later could be dif-
ferent again [.] Its all down to how he is feeling at the time. Its not
so much physically, its mentally [.] there will be a very brief window
in time when [he] will go from feeling absolutely compos mentis [.]
and suddenly one day will find that the disease has gone so far that
maybe he is no longer giving rational answers and the answers he is
giving will no longer be of any relevance anyway
I wouldnt want to make decisions for [my wife] that werent what she
wanted, so yes, I think it is a very good thing
If you care for the person, then surely you should do it, shouldnt
you?
I dont think I would be able to broach it with him [.] purely because I
feel that if we havent been able to talk about it up until then, now
may be not [.] the correct time
I would do it [. . .] I could do it [. . .] I would sit down and really work
out what he had talked about over the years [. . .] that wouldnt cause
me problems

Objective: To understand perceptions & preferences of people
with Parkinsons disease (PwPD) & their spouses about advance care
planning (ACP).
Background: In advanced PD palliative care supersedes active
disease management. Ascertaining patients wishes at this point is
limited by communication difficulty, dementia or severe illness. ACP
enables patients to consider & record their healthcares choices for
the end of life. Used in oncology, where prognosis is more defined,
its use in PD is unclear, particularly the timing of discussions. Retro-
spective studies of carers experiences found such communications
lacking1 & whilst a recent study2 found PwPD would like ACP,
there was little insight into their beliefs.
Refs:
1. Hasson F, Kernohan WG, et al. An exploration into the pallia-
tive & end-of-life experiences of carers of people with PD. Pall
Med. 2010; 24(7): 731-736
2. Tuck KK, Brod L et al. Preference of patients with PD for
communication about advance care planning. Am J Hosp Palliat
Care. epub 19/9/13
Methods: PwPD at different stages of PD without clinically diag-
nosed dementia & their spouses who chose to participate were given
an example ACP document & interviewed in person.
Results: 17 PwPD, 8 male, mean age 65 years (SD8.9), mean
disease duration 8.9years (SD5.5) and mean Hoehn-Yahr (HY) 2.3
(SD1.1), and 10 spouses were interviewed.
Of 5 PwPD aware of ACP prior to participation, none considered
it personally relevant. All felt future planning was important, but
those with longer disease duration & greater HY felt ACP less bene-
ficial as they struggled to consider future deterioration and feared
detriment of mood. Less disabled people with shorter disease dura-
tion felt ACP removed the burden of decision from their family.
PwPD & spouses agreed ACP at diagnosis was too early. Most
felt timing of ACP discussion was person-specific, rather than stage
of disease or age. Spouses felt ACP would reduce anxiety and sup-
port future care but in its absence, most spouses felt confident to
make decisions if the affected spouse lacked capacity, even without
prior discussions.
Conclusions: PwPD are open to ACP and should have the oppor-
tunity to discuss end of life care. Timing is person-specific but this
study suggests that people in the earlier stages of PD are more able
to consider future planning than those in later stage PD. This may
reflect subtle cognitive change and should prompt clinicians to initi-
ate ACP discussions early.
1422
Interdisciplinary home visits to improve outcomes for advanced
Parkinsons disease patients
B. Stone, A.C. Lemen, M.M. Sweeney, J. Fleisher, G. Dacpano, M.
Harris, R.M. Gilbert, M.J. Nirenberg, A. Di Rocco (New York, NY,
USA)
Objective: To show that an interdisciplinary home visit care
model can extend medical treatment, psychosocial support and health
education into the home; demonstrate patient satisfaction as reflected
by program retention; and improve outcomes in patients with
advanced Parkinsons disease (PD), including reduced caregiver
strain and emergent healthcare utilization, and improved quality of
life.
Background: PD is the second most common neurodegenerative
disease. As PD advances, motor fluctuations, falls and non-motor
symptoms become more prominent, quality of life deteriorates and
caregiver burden rises. Quality measures detail the importance of
interdisciplinary care, yet advanced PD can render travel to clinics
difficult or impossible. Reduced access to care can lead to poor treat-
ment adherence, unresolved clinical concerns and increased hospital
visits. Novel approaches to preserving care are critically needed.
Methods: Homebound patients with advanced PD are eligible to
participate in the Home Visit Program (HVP) at the New York Uni-
versity Parkinsons and Movement Disorders Center. All non-

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
demented, English-speaking HVP patients are asked to participate in
this study. Targeted enrollment is 30 patients with 4 home visits
over 1 year. Visits entail an evaluation by a Movement Disorders
specialist, social worker and nurse, and include a detailed history,
physical examination, Unified Parkinsons disease Rating Scale,
Modified Mini-Mental State Examination, Neuro-QOL and Multidi-
mensional Caregiver Strain Index. Interventions and referrals are pro-
vided as needed.
Results: This interim analysis includes the first 16 subjects, all of
whom have completed visit 1; 8 have completed visit 2. Our reten-
tion rate is 100%. Referrals have been made to physical therapy
(n512), occupational therapy (11), speech and language pathology
(14), mental health services (19) and community support services
(18). Participants and caregivers have reported high satisfaction with
the HVP.
Conclusions: We are demonstrating that an interdisciplinary
home visit program is a feasible model for improving patient access
to care. Participation in the HVP has been well-received by patients
and caregivers. Data regarding improvements in quality of life and
healthcare utilization are forthcoming. Given the prevalence and
growing burden of PD, it is critical to develop sustainable, scalable,
effective programs to broaden access to care.
1423
Translation of the 39-item Parkinsons disease questionnaire to
Filipino
C.T.R. Suratos, G.M. Saranza, R.D.G. Jamora, D.G. Sumalapao
(Manila, Philippines)
Objective: The objective of this study is to translate and validate
the 39-item Parkinsons disease Quality of Life Questionnaire (PDQ-
39) into Filipino (P-PDQ-39) and use it to assess the quality of life
of Filipino patients with PD.
Background: Health-related qual:ity of life (HrQoL) is consid-
ered critical in chronically ill pa:tients. A disease-specific measure
of subjective health status, the Parkinsons disease Questionnaire
(PDQ-39) has been shown to have good reliability, validity, respon-
siveness and reproducibility. In Parkinsons disease, the PDQ-39, is
the most widely used patient reported rating scale endpoint in clini-
cal trials to assess effectiveness of treatment.
Methods: The original PDQ-39 was translated into Filipino using
forward and backward translation by independent bilingual transla-
tors. A convenience sample of 21 patients with PD from a tertiary
hospital clinic in the Philippines, completed the P-PDQ-39.
Results: The mean total summary index of the P-PDQ-39 was
26.71%, and ranged from 0% to 67.5%. A higher score in each P-
PDQ-39 domain means greater discomfort felt by the patient: mobil-
ity (39.40%) was the major complaint, while cognitive impairment
(2.38%) and bodily discomfort (5.48%) were the least of the patients
problems.
Conclusions: The P-PDQ-39 has been used in the Filipino-
speaking PD popula:tion. The questionnaire is a reliable assessment
tool for assessing the HrQoL of Filipino PD patients.
1424
The effects of Movement Disorders affecting cervico-facial region
on quality of life
F. Tokucoglu, B. Selbes, M.M. Ozcelik, N. Tuncay (Izmir, Turkey)
Objective: Aim of our study to search if there is a difference of
depressive symptoms, anxiety, and quality of life (QoLF) properties
between hemifacial spasm (HFS), blepharospasm, (BP) and cervical
dystonia (CD) patients. The effects of severity and frequency of
motor symptoms on psychiatric symptoms and QoLF also
investigated.
Conclusions: All group of patients had some QoLF issues and
BEP patients seemed more affected than other groups probably.
S549
Larger pateint groups would be benficial to evalute patient charcter-
istics. Inclusion of naive patients before toxin injection might pro-
vide better insights when compared to their status after botulinum
toxin treatment.
Background: Movement Disorders like CD, BP, HFS cause dis-
ability via physical resctrictions as well as psychiatric symptomatol-
ogy that together cause impairment of quality of life (QoLF).
Depressive disorders, anxiety disorders, obsessive compulsive disor-
ders were reported in these patients. Severity of motor symptoms
may be related to presence of these disorders.
Methods: BP, HFS, CD patients were included. Most of them
previously treated with botulinum toxin injections. They were eval-
uated prior to injection in the outpatient clinic. Beck depression test,
Hamilton anxiety test, SF-36 tests were used. Groups compared to
each other for demographics, duration of illnesses and all above
mentioned parameters.
Results: 28 female,15 female patients were included. There were
29 HFS, 8 BP, 6 CP cases. HFS group was significantly older even
there was no significant difference between disease duration. BP
patients vitality and social functioning was worse than other groups.
Physical, social,emotional role functioning impairment were nega-
tively affected by as severity and frequency. Dystonia patients had
more bodily pain as the duration of the illness increased. Higher fre-
quency negatively correlated with mental health and vitality.
Conclusions: Our study showed that degree of visual functional
impairment is closely related to psychiatric morbidity and QoLF
therefore psychiatric treatment and psychological support should not
be negelected.One of the limitations of our study is the limited
patient number which will be overcomed since this is an ongoing
study. Inclusion of naive patients before toxin injection might pro-
vide better insights when compared to their status after botulinum
toxin treatment.
1425
Life sustaining treatment orders, location of death, and co-
morbid conditions for Oregon decedents with Parkinsons disease
K.K. Tuck, D.M. Zive, T.A. Schmidt, J. Nutt, J. Carter, E.K. Fromme
(Portland, OR, USA)
Objective: Determine end-of-life care preferences, location of
death and co-morbid conditions in people with Parkinsons disease
(PD).
Background: Most people would prefer to die at home (Dunlop
1989). However in Oregon, 38% of people die at home while the
national average is 23% (Facts on Dying 2004). There is little litera-
ture on where people with PD die or would like to die. Knowing this
would provide an opportunity to improve the dying process and pro-
vide patient centered care.
Physician Orders for Life Sustaining Treatment (POLST) forms
are portable orders that address resuscitation status and preferences
for artificial nutrition and medical care. In Oregon, they are collected
in an easily accessed electronic registry.
Methods: Death certificates in Oregon from years 2010-2011
were analyzed for all natural deaths and any additional deaths with
PD listed as an underlying cause. Descriptive analyses were con-
ducted and univariate tests (chi-square) were used to assess differen-
ces between demographic groups, location of death and POLST
orders in those with and without PD as a cause of death.
Results: Of 58,034 death certificates in 2011-2012, 1073 had PD
as a cause of death. In the PD group there were more males (62% vs
48% p50.00) and more urban deaths (58% vs 54% p50.008). Peo-
ple with PD were less likely to die in hospital (13% vs 24%
p50.000) or at home (32% vs 40% p50.000), however more likely
to die in a long term care setting (52% vs 29% p50.000). 17,534
decedents without PD (31%) and 373 decedents with PD (35%) had
a matched POLST form in the Registry. POLST forms showed no
significant differences in DNR orders (94% vs 93% p50.176),
request for comfort measures only (69% vs 66% p50.354) or
Movement Disorders, Vol. 30, Suppl. 1, 2015
S550 POSTER SESSION

declination of artificial nutrition (80% vs 80% p50.453). Dementia

(16%), other (16%), cardiovascular disease (13%) and pulmonary
disease excluding pneumonia (9%) were the leading co-morbid
causes of death in people with PD.
Conclusions: Using DNR orders, comfort measures and request
for artificial nutrition as surrogate markers for preferring to die out-
side hospital, patients with and without PD who had POLST forms
in the Registry had similar rates of preferring not to die in hospital.
People with PD were less likely to die in hospital than those without
because more of them were in long term care settings. Dementia was
the leading co-morbid condition listed on death certificates.

1426
Withdrawn by Author

1427
A systematic review of self-management of Parkinsons disease,
as a chronic disease
S.A. Wherry, C. Das, P. Dugdale, C. Lueck (ACT, Australia)
Objective: This poster reports on a systematic review of the
existing literature relating to self-management in PlwP.
Background: The burden of chronic, neurodegenerative diseases,
including Parkinsons, is a growing problem worldwide, and the
understanding of how to optimise self-management for these condi- Fig. 2. (1426).
tions is central to contemporary care and quality of life. This paper

presents results from a systematic review of ways to support People

Living with Parkinsons (PlwP) and their carers world-wide.
Methods: The Cochrane Database of Systematic Reviews, Psy-
cINFO, CINAHL and Embase were used to identify evidence such
as randomised controlled trials and original literature, as well as
evidence-based guidelines, evidence-based review articles and meta-
analysis relevant to the topics reviewed. Ten studies were judged as
meeting the inclusion criteria and included in this review. Data was
extracted and summarised.
Results: Five of the papers provided evidence of the effectiveness
of self-Management. Self-management improves Quality of Life, as
measured by self-efficacy scales in PlwP. This is related to the pro-
gressive, fluctuating nature of Parkinsons.
Conclusions: There is some evidence that self-management is a
valuable tool in the overall management of Parkinsons for people
living with the condition. Healthcare staff who provide support for
self-management can enable patients to learn about things they can
do to manage their own symptoms and re-engage with them when
circumstances change or their disease progresses. Parkinsons disease
Nurse Specialists are well placed to encourage and support self-
management by healthcare staff working with Parkinsons patients as
a central element of health care for these people.

1428
Evaluation of sarcopenia in Parkinsons disease
O. Yilmaz Kusbeci, B. Donmez Colakoglu, I. Inci, E. Duran, R.
Cakmur (Izmir, Turkey)
Objective: To evaluate sarcopenia in PD patients with portable
bioelectrical impedance body composition analyzer and caliper.
Background: Sarcopenia has been defined as the loss of skeletal
muscle mass and strength that occurs with advancing age. Central
and peripheral nervous system alterations, hormonal, nutritional,
immunological and physical activity changes are etiological factors
of sarcopenia. Bioelectrical impedance analysis and skinfold caliper
are simple and noninvasive methods of assessing sarcopenia.
Methods: The study evaluated the sarcopenia by applying Tanita
Fig. 1. (1426). Body Composition Analyzer (Tanita, Tokyo, Japan) and skinfold

Movement Disorders, Vol. 30, Suppl. 1, 2015

 POSTER SESSION
caliper. It included age and gender matched study and control groups
of which were composed of seventy three patients with PD and sev-
enty one healthy subjects respectively. Weight, fat mass, muscle
mass, bone mass, basal metabolism rate, body mass index (BMI) and
caliper measurements of patient and control groups were done.
Results: The mean age of PD and control groups were
67,46 6 8,45 and 65,73 6 8,67, (p50,227), respectively. Fat mass
(18,80 6 9,84 vs 23,04 6 8,84, p50,007), BMI (26,77 6 3,76 vs
28,30 6 4,25, p50,24) and skinfold caliper measurements
(14,85 6 5,35 vs 24,36 6 8,91, p50,00) were significantly higher in
control group. Also body weight was higher in control group but it
was not statistically significant.
Conclusion: Our study indicated that sarcopenia could be seen
more common in PD patients. Sarcopenia, is known to affect elderly
individuals by decreasing mobile function and increasing frailty and
imbalance that lead to falls and fragile fractures. Therefore evalua-
tion of sarcopenia should be a part of PD management.
Conclusions: Our study indicated that sarcopenia could be seen
more common in PD patients. Sarcopenia, is known to affect elderly
individuals by decreasing mobile function and increasing frailty and
imbalance that lead to falls and fragile fractures. Therefore evalua-
tion of sarcopenia should be a part of PD management.
Spasticity
1429
Usefulness of communication calendar for botulinum toxin
therapy of spasticity in an outpatient setting
F. Adib Saberi, H. Pickenbrock, D. Dressler (Hamburg, Germany)
Objective: To introduce and to evaluate the usefulness of Com-
munication Calendar for Botulinum Toxin Therapy of Spasticity
(CC) to facilitate the communication between physicians (P) and
physiotherapists (PT) in botulinum toxin (BT) therapy of post-stroke
spasticity in our outpatient clinics.
Background: BT therapy of spasticity is best applied together in
combination with additional therapies including physiotherapy and
occupational therapy. To improve this collaboration we introduced
and evaluated the usefulness of CC and used it in our outpatient
clinics.
Methods: CC consists of two parts: Part 1 is a muscle table on
which P documents the target muscles used for BT therapy. The PT
is requested to evaluate the muscle relaxing effect of BT was
adequate, too weak, too strong, whether this target muscle should be
abandoned on re-injections or whether new target muscles should be
introduced. Part 2 is a goal table providing activities from which P
and PT may select a treatment goal which is later evaluated using
the Goal Attainment Scale (GAS). The design of the study is based
upon a written questionnaire distributed to all P and all PT involved
in CC-based BT therapy of 100 subsequent outpatients suffering
from post-stroke spasticity.
Results: 100 patients were included in this study. BT therapy
involved 7 P and 42 PT. Time used for completing each CC session
was 9.5min (P) and 8.8min (PT). All CC features together were
judged as excellent or good by 60.3 6 15.9% of P and by 76.9 6 15.2
of PT. Values for practicality were 67.3% (P) and 93.4% (PT), for
clarity 42.1% (P) and 73.9% (PT) and for comprehensibility 71.4%
(P) and 63.4% (PT). CC was judged as effective by 74.3 6 21.2% of
P and 52.3 6 19.9% of PT. Values for generally helpful were 100%
(P) and 86.4% (PT), for improving motivation 85.7% (P) and 64.4%
(PT), for improving physiotherapy 71.4% (P) and 40.4% (PT), for
improving BT therapy 71.4% (P) and 51.9% (PT) and for improving
quality of feedback 42.9% (P) and 36.5% (PT).
Conclusions: CC is a quick, easy and effective instrument to
facilitate communication between P and PT in an outpatient setting
receiving BT therapy for spasticity.
S551
1430
Systematic literature review of abobotulinumtoxinA in clinical
trials for lower limb spasticity
J.J. Chen, K. Dashtipour, H. Walker, M.Y. Lee (Fullerton, CA, USA)
Objective: To systematically assess the clinical trial efficacy,
safety and dosing methodology of abobotulinumtoxinA (ABO) in the
treatment of adults with lower limb spasticity (LLS).
Background: Adult lower limb spasticity (LLS) due to stroke,
spinal cord injury, or other neurological disorders can significantly
impair stride, gait and balance.
Methods: A Cochrane-quality, systematic, PRISMA-guided, pro-
tocol-defined, literature review was designed and implemented to
identify randomized controlled trials of ABO in the treatment of
adult lower limb spasticity.
Results: Of the 295 records identified, 6 unique publications met
inclusion criteria. The etiology of LLS was stroke (4 studies, total
n5288 patients) and multiple sclerosis (MS; 2 studies, total n5180
patients). Three of the post-stroke LLS studies were small (<25
patients each). Total ABO doses ranged between 500 to 2000U
depending on the muscles injected. All studies utilized EMG-guided
injections and adjunctive electrical stimulation was studied in 2
stroke-LLS studies. Concomitant standard of care physiotherapy and
adjunctive oral medications were allowed. At 8 to 12 weeks post-
injection, ABO was associated with statistically significant reductions
in muscle tone (Ashworth or Modified Ashworth Score) in the
stroke-LLS studies. In MS-LLS studies, ABO did not improve func-
tional outcomes or MAS scores, compared to placebo, but improved
distance between the knees in one study of hip adductor spasticity.
Across all 6 studies, improvements in walking distance and func-
tional endpoints were inconsistent. ABO was well tolerated with a
few reports of weakness and dysphagia.
Conclusions: ABO improves muscle hypertonicity associated
with post-stroke LLS. Clinical trials pre-specify muscles for injection
in an attempt to standardize findings, but it is likely that this
restricted approach may have affected the outcome of some studies.
Patients with post-stroke LLS may gradually improve gait and func-
tion with rehabilitation; however, patients with spasticity secondary
to central neurodegenerative disorders will usually worsen and in
MS, the degree of deficit is subject to remission and exacerbation.
Our results illustrate that the effect of ABO in post-stroke LLS is not
generalizable to LLS due to other neurologic conditions. We also
identified the need for conducting larger clinical trials.
1431
Botolinum toxin injection to the upper limb indirectly improves
gait in patients with post-stroke spasticity
O.S. Cohen, E. Shprits, S. Hassin-Baer, Y. Dotan-Marom, G. Yaha-
lom, O. Marzeliak, L. Ephraty, H. Strauss, E. Stein, H. Baransi, R.
Inzelberg, M. Plotnik (Ramat-Gan, Israel)
Objective: To evaluate whether isolated injections of Botulinum
toxin (BonTA) to the upper linb (UL) can improve gait in patients
with post-stoke upper limb spasticity (PSULS).
Background: Injection of BonTA is an effective treatment for
patients with PSULS. Since arm swing during gait has some physio-
logical functions the reduced motility and swing of a spastic arm
may further compromise the already impaired gait in patients with
post stroke spastic hemiparesis.
Methods: Consecutive patients with PSULS newly or routinely
treated by BonTA were recruited. Evaluation was performed twice:
A few hours prior to injections and a 4-6 weeks following the treat-
ment including: 1) Ashworth Spasticity Scale (ASS) for the injected
muscles 2.Timed Up and Go (TUG) 3. Functional Ambulation Clas-
sification (FAC) 4) Functional Independence measure (FIM). Gait
analysis included over ground gait speed (GS) and spatio-temporal
parameters (Zebris FDM-T Treadmill).
Movement Disorders, Vol. 30, Suppl. 1, 2015
S552 POSTER SESSION
Results: Eight patients [7 males, mean age: 62.3 6 14.8 years]
were recruited. The mean dose 6 SD of BonTA was 1148 6 382 IU .
A significant clinical improvement was evident as the ASS score
diminished from 19.9 6 3.5 pre-injection to 11.76 4.8 post-injection
(p<0.001). Following the injection gait speed increased from
0.40 6 0.24 m/s to 0.57 6 0.24 m/s ( 140%; p50.05). Feet rotation
(outward inclination) decreased from 11.5 6 5.7 to 9.6 6 4.3
(p50.046). Gait line length in the paretic leg trended to increase in
response to injections (from 197 6 66 to 224 6 73 mm; p50.075),
indicating more dynamic control during stance. The scores of other
neurological scales, the TUG and other gait parameters (e.g., step
length) did not change significantly.
Conclusions: Isolated BonTA injection to the UL improves gait
in patients with spastic hemiparesis, presumably due to partial resto-
ration of arm swinging during walking. Future studies in larger
cohorts are mandatory to consolidate our findings.
1432
Prevalence and treatment of spasticity among veterans living in a
long-term care facility
A.D. Currie, M. Turchan, T.S. Hudson, J.D. Roach, L.E.
Heusinkveld, F.T. Phibbs, C.M. Tolleson, A.L. Molinari, C.E. Gill,
D. Charles (Nashville, TN, USA)
Objective: To determine the prevalence of spasticity among vet-
erans living in a long-term care facility (LTCF) and to identify the
barriers to spasticity treatment in this population.
Background: Prior population studies of adults in a nursing
home(1) and adults with intellectual and developmental disabilities
in a LTCF(2) have suggested that approximately 21% and 35% of
these residents have spasticity, respectively. The prevalence of spas-
ticity among veterans in these settings has not been reported.
Methods: All residents of a LTCF for veterans and their spouses
were invited to participate in this IRB-approved prospective popula-
tion study. Participants who provided informed consent were exam-
ined by a Movement Disorders neurologist for the presence of
spasticity. The most recent comprehensive Minimum Data Set was
collected, and participants with spasticity were interviewed using a
standardized survey to determine the barriers to treatment.
Results: Informed consent was obtained for 43 veterans in this
140-bed facility. Spasticity was present in 33% of participants. Of
these, 57% did not previously have spasticity documented in the
medical record. Only three (21%) were receiving physical or occupa-
tional therapy (PT/OT), and none were receiving oral antispasticity
medication, intrathecal baclofen (ITB), or neurotoxin injection. Bar-
riers to treatment included a perceived difficulty in access to special-
ists (27%), transportation to appointments (27%), and lack of
awareness of available treatments for spasticity. Most patients (91%)
were aware of PT/OT, 45% were aware of neurotoxin injections,
36% were aware of tendon release surgery and oral antispasticity
medications, and only 18% were aware of ITB.
Conclusions: We found that the prevalence of spasticity among
veterans at this LTCF was 33%. This prevalence rate is consistent
with rates of spasticity in other LTCFs and demonstrates that more
education is needed for physicians and patients concerning the diag-
nosis and treatment of spasticity in LTCFs.
References:
(1) Gill CE, et al. Spasticity prevalence, treatment and functional
impact in the nursing home. Ann Neurol, 2008;64(Suppl. 12):S52.
(2) Pfister AA, et al. Spasticity in adults living in a developmen-
tal center. Arch Phys Med Rehabil, 2003;84:1808-12.
1433
Safety profile of repeat onabotulinumtoxinA doses of 400U for
the treatment of upper limb spasticity
L. James, R. Dimitrova, G. Pan, C. Asare, C. Thompson (Irvine, CA,
USA)
Movement Disorders, Vol. 30, Suppl. 1, 2015
Objective: To assess the safety profile of onabotulinumtoxinA for
treatment of upper limb spasticity (ULS) across a range of doses,
including doses 400U.
Background: OnabotulinumtoxinA is approved in the U.S. for
the treatment of ULS to decrease the severity of increased muscle
tone in elbow, wrist, and finger flexors in adult patients. Onabotuli-
numtoxinA treatment of ULS is individualized based on patient pre-
sentation, so a range of doses may be used. Extensive ULS clinical
study data allows for exploration of the safety profile across a range
of doses over multiple treatments.
Methods: Safety data from 18 studies of onabotulinumtoxinA for
ULS were integrated for analysis and were divided into 4 dose
groups (<150U, 150-250U, 251-399U, 400U). Treatment exposure
and the incidences of adverse events (AEs), serious AEs, and AEs
indicating possible distant spread of toxin (PDSOT) were assessed in
patients who received 1 onabotulinumtoxinA treatment; the safety
profile of patients who received 4 consecutive onabotulinumtoxinA
400U treatments was also assessed.
Results: Overall 1342 patients received 1 onabotulinumtoxinA
treatment; 183 received 400U, with 6.6% (88/1330), 12.3% (115/
936), 23.3% (113/486), and 31.2% (96/308) of patients receiving
doses of 400U at treatment cycles 1, 2, 3, and 4, respectively. AE
rates were similar across dose groups, with no consistent increase in
incidence of any individual AE/serious AE or PDSOT AEs at doses
400U across treatments. The overall AE rate among the subset of
patients with 4 consecutive 400U treatments (n551) was similar
(43.1%, 43.1%, 43.1%, 41.2%), with no overall change in profile for
AEs/serious AEs with increasing treatments.
Conclusions: OnabotulinumtoxinA across a range of doses,
including 400U, was well tolerated in ULS patients, with no con-
sistent pattern of increase in AEs, reported systemic AEs, or change
in safety profile over consecutive treatments.
1434
Comparative clinical study of A1 and A2 subtypes of botulinum
toxin preparations for post-stroke spasticity: Proof-of-concept
randomized controlled phase 2/3 trial
R. Kaji, A. Miyashiro, T. Furumoto, N. Sato, W. Sako, S. Kaji
(Tokushima, Japan)
Objective: To test the clinical efficacy and safety of low-
molecular weight (150kDal) A2 subtype botulinum toxin preparation
(A2NTX) compared to A1 preparation (onabotulinumtoxinA).
Background: Animal experiments (Torii et al 2014) demon-
strated its safety and efficacy twice higher than subtype A1 prepara-
tions. Phase 1 study in man demonstrated 6.5 mouse LD50 units of
A2 had a similar efficacy to 10 units of A1, with similar duration of
action (Mukai et al. 2014). We have conducted a proof-of-concept
randomized controlled phase 2/3 study to compare its efficacy and
safety in post-stroke spasticity to A1 subtype (onabotulinum toxin)
(NCT01910363, ClinicalTrials.gov).
Methods: We enrolled 31 post-stroke hemiplegic patients (6
women) aged 43-78 years. Disease duration was from 22 to 241.5
months, and these backgrounds were similar between A1 (n516) and
A2 (n515) groups. A blinded physician injected 300 units of A1 or
A2 toxins into tibialis posterior (150 units) and medial gastrocnemius
(150 units) muscles with EMG guide. Patients were randomly
assigned to either group by the controller. Inclusion criteria were
Modified Ashworth Scale (MAS) of ankle joint, being either flexor
or extensor being equal to or more than 2, and both flexor and exten-
sor being more than 0. All the evaluation including MAS was done
by a blinded rater, who excluded 3 from A1 and 4 from A2 because
of MAS criteria. For functional analysis, Japanese version of Func-
tional Independence Measure (FIM; Dodds, et al. 1993) was used, 35
points being fully independent, and 5 being totally dependent. For
safety analysis, we measure the hand grip of the unaffected hand.
 POSTER SESSION
Fig. 1. (1434).
Results: MAS changes at day 30 were significantly higher
(p50.022) for A2 (-10.2 6 4.8; mean6SE) than A1 (-3.5 6 2.5),
whereas no significant difference was noted for day 60 (p50.123).
FIM was significantly increased for A2 (0 day, 26 6 1.5; 60 days,
27.7 6 1.2; p50.031, paired t), whereas no significant increase was
observed for A1 (p50.191). For safety, grip power was significantly
Fig. 2. (1434).
S553
decreased for A1 (p50.036, paired t), but not for A2 (p50.669),
indicating less spreading for A2 than A1
Conclusions: In this proof-of-concept study, A2 toxin had earlier
onset of action and better functional outcome as measured by FIM
with less spreading of its action than A1. A larger study confirming
these aspects are warranted.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S554 POSTER SESSION
1435
Long-term treatment of spasticity with onabotulinumtoxinA in
intellectually and developmentally disabled adults
A.L. Molinari, M. Turchan, A.D. Currie, C.E. Gill, H.M. Taylor, D.
Charles (Nashville, TN, USA)
Objective: To report long-term data on the treatment of spasticity
with onabotulinumtoxinA (BoNTA) in patients with intellectual and
developmental disabilities (IDD).
Background: BoNTA is an effective treatment for adult spastic-
ity that reduces pain and increases functional independence. Long-
term treatment data is limited in the literature, particularly in the
IDD patient population.
Methods: During a 9 year period, patients residing at a develop-
mental center were evaluated for spasticity by a single neurologist as
part of a bimonthly spasticity clinic. Patients who were diagnosed
with spasticity and treated with BoNTA were included in the study
(Vanderbilt IRB #110168). Treatment data was deidentified and ana-
lyzed as part of a retrospective chart review.
Results: Thirty patients (13 males, 17 females, average age 44.4
years, average duration of follow-up 56.1 months) were included in
the study. Fourteen patients were treated for upper limb spasticity,
13 were treated for lower limb spasticity, and 3 were treated for both
upper and lower limb spasticity. The adductor magnus (n512),
biceps brachii (n59), and brachioradialis (n59) were the most com-
monly treated muscles. Average doses in these muscles were 193.1,
159.5, and 60.3 Units (U), respectively. The average total starting
dose of BoNTA was 283.3 U, and the average total dose for all visits
was 376.59 U. The average interval between injections was 4.6 and
5.5 months for upper and lower limbs, respectively. Twelve patients
discontinued treatment during the course of the study, but only two
did so due to treatment inefficacy.
Conclusions: This study suggests that patients with IDD who are
treated with BoNTA for spasticity experience nominal dose increases
over time in affected muscles and benefit for several months from
treatment, even after long-term BoNTA use. Additionally, this study
suggests that treatment non-response is not common in patients with
IDD who are treated long-term with BoNTA for spasticity. A large
prospective trial is necessary to provide definitive evidence regarding
long-term dosing trends and other treatment data.
1436
Phenotypical variability in a family with PLA2G6 p.R747W
mutation
J.K. Park, T.O. Son, Y.E. Huh, H.T. Kim, J.W. Cho (Seoul, Korea)
Objective: To describe homozygous PLA2G6 p.R747W mutation
showing the pure form of spastic paraplegia & L-dopa responsive
Parkinsonism in a family.
Background: Mutations of PLA2G6 gene can cause autosomal
recessive neurodegenerative diseases classified as infantile neuroaxo-
nal dystrophy (INAD), neurodegeneration with brain iron accumula-
tion (NBIA), and dystonia-Parkinsonism. Here we report on a family
with two affected siblings showing different phenotypes.
Methods: These siblings were born to healthy, consanguineous
parents of Arabian ancestry. Sibling 1 showed slowly progressive
difficulty in walking with urinary incontinence, onset age at 11. His
examination at age 28 revealed spastic gait disturbance, spasticity on
lower limbs, hyperactive deep tendon reflexes and positive Babinski
more prominent on Rt. side. Rigidity and resting tremor were absent,
and he showed normal cognition. Sibling 2 presented with severe
bradykinesia, rigidity and difficulty in walking, at age of 22. He was
diagnosed as PD and showed excellent response to L-dopa treatment.
Examination at age 24 revealed bilateral rigidity and bradykinesia of
the limbs more prominent on Lt. side, resting tremor on Rt. hand in
partial-off state. Spastic gait disturbance, diminished volume of
lower legs, and hyperactive deep tendon reflexes with positive
Movement Disorders, Vol. 30, Suppl. 1, 2015
Babinskis sign were observed. He developed wearing off and levo-
dopa induced dyskinesia within 1 year of levodopa treatment.
Results: Brain MRI demonstrated no significant abnormality on
both siblings. FP-CIT PET imaging on sibling 2 demonstrated signif-
icant reduced FP-CIT uptake on bilateral putamen, more prominent
on left side. A homozygous c.2239C>T (p.R747W) pathogenic vari-
ant in the PLA2G6 gene was detected in this sibling. Both of the
parents were heterozygous for this variant.
Conclusions: The affected siblings of PLA2G6 mutation showed
clinical heterogeneity. PLA2G6 mutation can present as a pure form
of spastic paraplegia mimicking hereditary spastic paraplegia or L-
dopa responsive Parkinsonism with motor fluctuation.
1437
Is onabotulinum toxin effective in long-term spasticity?
I. Reuter, S. Mehnert (Giessen, Germany)
Objective: Assessment of the efficacy of onabotulinum toxin in
patients with long-term spasticity.
Background: Botulinum toxin A is recommended as first line
treatment for spasticity. Since long-term spasticity might be associ-
ated with structural muscle alterations, one might doubt whether
treatment with BoNT A is effective.
Methods: 100 patients with either one sided upper limb (Group
A), unilateral upper and lower limb (Group B) or one sided lower
limb spasticity (Group C) (Age >18 <80 yrs), duration of
spasticity > 5 years, an MAS of  2, stable spasmolytic medication,
able to give informed consent were recruited. Exclusion criteria:
Baclofen pump, phenol or alcohol injections, peripheral nerve
lesions, fixed contractures. All subjects underwent the following test
battery: MAS, Pain VAS-scale, Pittsburg sleep quality index, HAD-
scale, Time up and go Test, 2-min walking distance 2 min, Motor
activity Log 5 items, lung function test (safety). The study period
included 5 treatment cycles. Assessments were conducted every 6
weeks.
Results: Group A (n535, age: 58.6 6 4.7yrs), Group B
(n532, age: 59.56/6.2yrs) and Group C (n530, age:
57.4 6 3.8yrs) did not differ significantly in duration of spasticity:
12.56 6.5yrs vs. 12.3 6 6.4yrs vs. 13.4 65.1 yrs and baseline
scores (MAS baseline scores of corresponding muscles, intensity of
pain). MAS-score decreased in all groups significantly by 1.8
points. Group B and Group C improved significantly in the 2-min
Walking distance (Group B:baseline: 18.5/5.6m; T4m: 34.6m
69.8m; Group C: baseline: 23 611.9m; T4m: 37.2 611.9m) (p
=0.01) and in the Time up and go test (Group B: 10.2 63.5s;
Group C: 8.9 62.7s). Hand function improved in group A and
group B significantly (p 5 0.01). Pain decreased significantly in all
groups from 7.2 to 3.4 points on the VAS-scale. No effect was
observed on depression and anxiety. Mean dosages of BoNT A used
in upper limb spasticity ranged from 350 to 370 Units, in lower limb
from 370 to 380 Units, subjects of group B received the highest total
doses with 500 to 750 Units. Lung function did not deteriorate in the
subjects.
Conclusions: Treatment of patients with long-term spasticity is
safe and effective with significant reduction of muscle tone, pain,
handfunction and walking. The results may encourage physicians to
treat patients with long-term spasticity with botulinum toxin A.
1438
Rationale and design of a randomised, double-blind, placebo-
controlled study to assess the impact of early use of
abobotulinum toxin A on spasticity progression in adults with
post-stroke upper limb spasticity in Asia (ONTIME study)
R.L. Rosales, J. Balcaitiene, P. Maisonobe, K.H. Kong, K.J. Goh, W.
Kumthornthip (Manila, Philippines)
 POSTER SESSION
Fig. 1. (1438).
Objective: To assess the efficacy and safety of early treatment
(<12 weeks from stroke) with botulinum toxin type A (abobotulinum
toxin A) in adults with post-stroke upper limb spasticity (ULS).
Background: ULS is common in stroke survivors, causing pain,
impairment of active and passive limb functioning and significant
impairment of quality of life. The current standard clinical practice
for treatment of post-stroke ULS is for botulinum toxin type A to be
administered only after clinical signs of increased muscle tone are
established; evidence shows that between 612 weeks secondary
complications such as post-stroke contractures are completely estab-
lished, despite patients receiving routine treatment.1 Early interven-
tion may alter disease progression and prevent development of
severe spasticity.2
Methods: ONTIME is a multicentre, prospective, double-blind,
randomised, placebo-controlled, pilot study. Subjects will be
recruited in the Philippines, Singapore, Malaysia and Thailand.
Adults (n542) with moderate to severe ULS (Modified Ashworth
Scale [MAS] score 2 in at least one of the following, elbow flexors
or pronators, wrist flexors, or finger flexors, will be randomised 2:1
to receive abobotulinum toxin A 500 U or placebo in a single IM
dose 212 weeks after first-ever stroke. [figure1] It is planned that
4060% of subjects will have asymptomatic ULS (score 0 on Likert
scales for active function, passive function and involuntary move-
ment, pain <4 on a numeric pain rating scale [NPRS]), and 4060%
of subjects will have symptomatic ULS (1 of the following: pas-
sive and active function symptoms, involuntary movements, pain 4
on an NPRS). Primary efficacy endpoint will be time from initial
injection to the appearance of reinjection criteria (MAS score 2 in
the primary targeted muscle group and signs of symptomatic ULS).
Follow-up visits will be 4-weekly to a maximum of 28 weeks.
Results: Study results will be reported in peer-reviewed journals
and by conference presentations.
Conclusions: The ONTIME pilot study should provide useful
insights into the use of botulinum toxin type A in patients with ULS
<12 weeks from stroke.
1. Malhotra et al. Clin Rehabil 2011;25:184191.
2. Rosales et al. Neurorehabil Neural Repair 2012;26:81221.
1439
Brachial plexus botulinum toxin a injection - Case report
Z. Sycz (Wroclaw, Poland)
S555
Objective: To evaluate possible mechanism of action of Onabotu-
linumtoxin A on nerve bundles and considering different approach to
spasticity treatment.
Background: The main mechanism of action of Onabotulinum-
toxin A is associated with neuromuscular junction blockade, by
suppressing acetylcholine relies. There are other mechanisms of
action like analgesic in chronic migraine. There are still assump-
tion of this mechanism of action like suppressing central and
peripheral sensitization. There is still lack of knowledge about
action mechanism of Onabotulinumtoxin A on living body and cor-
responding spasticity treatment. Late years, approaches to spastic-
ity treatment using Onabotulinumtoxin A, focussing on precise
finding a spastic muscle or even finding a neuromuscular junction
in spastic muscle.
Methods: 19 years old male with cerebral palsy and severe spas-
ticity of all extremities and trunk. According to Ashworth scale, the
spasticity in majority of muscles 3 pts. This specific patient was cho-
sen because he is mechanical ventilated and a risk of respiratory
insufficiency and death, was minimized after botulinum toxin a
injection.
After obtaining consent from the mother, and to clarify all the
doubts related to procedure, performed brachial plexus injection first
on the right side, and after 3 month the second one on the left side.
Every time 100 units of botulinum toxin a were injected. The proce-
dure were performed without complications.
Results: Every time approx. 2 weeks, there were decrease in
spasticity. The significant effect was noticed after 3 weeks. There
were significant muscle relaxation in shoulder girdle on injected site.
Increase of shoulder movability. Decrease of Ashworth scale to 1.
Easiest extension in elbow and wrist. Because of differences in spas-
ticity in both limbs, the results are slightly different on both sites.
Before injections forearm orthosis time was 1 hour. After 3 weeks
the time increase to 3 hours. The respiratory insufficiency didnt
change. Before and after injection the time without ventilation sup-
port was 1 hour.
Conclusions: Brachial plexus botulinum toxin a injection, demon-
strated different mechanism of action of Onabotulinumtoxin A on
the living organism. The drug act also on nerve bundles. This gives
opportunity to change approach to the spastic patients. This method
can lead to minimize injections in severe spastic patients and give
them chance to improve quality of live.
The procedure is safe but must be done by physician familiar to
ultrasound nerve blockades.
Movement Disorders, Vol. 30, Suppl. 1, 2015
S556 POSTER SESSION
1440
Hereditary spastic paraplegia: Characterization of an Albertan
cohort
A. Venkitachalam, E. McKenzie, S. Ashtiani, C. Huculak, L.
McLaren, O. Suchowersky (Edmonton, AB, Canada)
Objective: To identify families with Hereditary Spastic Paraple-
gias, create a clinical registry and genomic DNA bank to screen for
known and novel mutations.
Background: Hereditary spastic paraplegias (HSP) are rare neu-
rological disorders with onset from early childhood to late adulthood,
inherited as autosomal dominant (AD), autosomal recessive (AR) or
X-linked (XR) traits with over 50 identified genes. HSP is classified
as uncomplicated or complicated. Prevalence is estimated at 5 per
100,000, but epidemiological data is scarce and misdiagnosis
common.
Methods: Participants were recruited through Neurogenetic and
Neuromuscular clinics in Alberta, and assessed yearly by Spastic
Paraplegia Rating Scale and SPATAX-EUROSPA disability score.
DNA will be sent for exome sequencing to McGill University (Dr.
G.Rouleau), as part of a Canadian consortium.
Results: 49 families with 64 patients (36 men and 28 women)
have been identified. Thirty one patients (48%) have a positive fam-
ily history, with AD inheritance in 18 families (37%), AR (9 fami-
lies) and XR (4 families). Eighteen families (37%) had sporadic
HSP. Mean age of onset for AD was 36 years, sporadic 32 years,
AR 11 years and XR 1.5 years. Complicated HSP was seen in 27
patients (46%). Abnormalities among complicated patients include
dysarthria (n519), sensory deficits (n517), occulomotor abnormal-
ities (n514), ataxia (n517), amyotrophy (n512), dysphagia (n59),
cognitive deficits (n511) and peripheral neuropathy (n58). Neuroi-
maging was abnormal in 9 patients. Thirty four patients (53%) had
SPATAX-EUROSPA disability stage of 3 or more (moderate to
severe functional handicap). Results of genetic testing are pending.
Conclusions: This is the first comprehensive population based
study looking at all forms of HSP. Prevalence is 2 per 100000. This
lower than expected rate could be due to either incomplete ascertain-
ment or lower prevalence in this population. The most common mode
of inheritance was AD with almost 50% having the complicated form.
1441
OnabotulinumtoxinA improves pain in post-stroke spasticity
patients: Findings from a randomized controlled trial
J. Wissel, V. Ganapathy, J. Ma, A.B. Ward, J. Borg, P. Ertzgaard,
A. Fulford-Smith, P. Gillard (Berlin, Germany)
Objective: This study examined the effect of onabotulinumtox-
inA (botulinum toxin a) on pain among post-stroke spasticity
patients.
Background: Patients with post-stroke spasticity often experience
pain in the spastic limbs.
Methods: 273 post-stroke patients with upper and/or lower limb
spasticity were randomized to onabotulinumtoxinA 1 standard of
care (SC) or saline 1 SC in the botulinum toxin a Economic Spastic-
ity Trials double blind phase. Muscle tone using the Resistance to
Passive Movement Scale (REPAS) and pain using an 11-point pain
numeric rating scale (0 to 10) were assessed at week 12. Mean
change from baseline pain and proportion of patients with 30%
improvement were compared between treatment groups using analy-
sis of covariance and chi-square or Fishers exact tests. The correla-
tion between change in muscle tone and pain scores from baseline
was measured using Pearsons r.
Results: Patients mean age was 61 years (SD:11.4); 41% were
female. Of 273 patients who received treatment, 202 (74%) experi-
enced baseline pain with the majority of those patients (129/202,
64%) having pain intensity 4. The mean change in pain at week 12
among onabotulinumtoxinA 1 SC and saline 1 SC groups were -0.77
(95% CI:-1.14, -0.40) and -0.13 (-0.51, 0.24), respectively (p<0.05).
Movement Disorders, Vol. 30, Suppl. 1, 2015
The proportion of patients with baseline pain intensity 4 achieving
30% improvement was 54% (29/54) for onabotulinumtoxinA 1 SC
versus 29% (17/59) for saline 1 SC (p<0.05). Change in pain score
was weakly associated with change in muscle tone at week 12
among patients with moderate to severe spasticity at baseline
(r=0.146).
Conclusions: This is the first large targeted RCT showing statisti-
cally significant and clinically meaningful improvement in pain with
onabotulinumtoxinA treatment for post-stroke spasticity.
Tremor
1442
Fahn-Tolosa-Marin scale, digitizing tablet and accelerometry
have comparable minimum detectable change
E. Akano, T. Zesiewicz, R. Elble (Springfield, IL, USA)
Objective: To compute the minimum detectable change (MDC)
for an accelerometer, digitizing tablet, and the Fahn-Tolosa-Marin
tremor rating scale (FTM) in the assessment of patients with essen-
tial tremor (ET).
Background: Tremor rating scales provide crude, nonlinear and
subjective assessments of tremor severity. By contrast, motion trans-
ducers are capable of providing precise, linear and objective meas-
ures of tremor. However, the advantages of transducers over rating
scales are diminished when random variability in tremor is large.
Transducers will measure random variability precisely, but changes
in tremor must exceed random variability to be recognizable as true
change due to treatment or disease progression.
Methods: Two baseline FTM ratings were obtained 13 weeks
apart in a double-blind, crossover trial of pregabalin for ET (22
patients, 4 raters) (Zesiewicz et al. Mov Disord 2013;28:249-250).
Data from the two baseline assessments were used to compute the
MDC for parts A, B and C. In a separate study, the MDC of acceler-
ometry was obtained from two measurements of postural hand
tremor, 3 min apart, with forearm supported (158 ET patients with
FTM upper limb ratings of 0 to 3), and the MDC of the digitizing
tablet (Wacom Intuos 2) was computed from two trials, 3 minutes
apart, of cursive es, cursive ls and Archimedes spirals. Mean
tremor amplitude was obtained from accelerometry and tablet data
using spectral analysis (Elble et al. Mov Disord 1996;11:70-78).
Results: The mean (SD) FTM part A, B and C baseline scores
were 9.2 (3.7), 15.6 (5.4) and 9.0 (4.3). The MDC (percentage of
baseline mean) for part A, B and C were 58%, 52% and 56%. The
MDC estimates (percentage of baseline geometric mean) for the digi-
tizing tablet were 50%, 56% and 59% for cursive es, cursive ls and
spirals, and the MDC for accelerometry was 73%.
Conclusions: Digitizing tablets and accelerometers provide very
precise linear measures of tremor amplitude. However, this advantage
over rating scales is reduced by the considerable natural variability in
tremor amplitude over time. This variability probably would be greater
for longer time intervals between measurements. Regardless, the natu-
ral variability in tremor amplitude is so great that the MDCs of the
transducers (i.e., the smallest change exceeding random variability) are
comparable to the MDCs of the FTM tremor rating scale.
1443
A simultaneous case of Parkinsons disease (PD) and essential
tremor (ET)
H. Amirjanyan, K. Harutyunyan, I. Gabrielyan, H. Manvelyan (Nor
Hachen, Armenia)
Objective: PD and ET are the most common neurodegenerative
disorders in clinical practice. There is now growing evidence that ET
and PD are related.
 POSTER SESSION
Background: A 55 year old male presented to our clinic with 4
years history of tremor in right limbs, bradykinesia and hypomimia.
PD diagnosis was established and L-DOPA was started.
Methods: Neurological examination revealed cogwheel rigidity in
right limbs, mixed tremor with rest and kinetic components in right
limbs, mildly reducing after alcohol intake. Brain MRI was per-
formed showing no abnormalities. Laboratory tests were within nor-
mal ranges. Family history was positive for ET.
Results: Based on family history and clinical findings the diagnosis
of PD simultaneous with ET was established and treatment with Pro-
pranolol was initiated. On follow-up reduction of tremor was notable.
Conclusions: Even though it is difficult to differentiate PD from
ET, in some cases simultaneous occurrence of both diseases could be
suspicious.
1444
Rate-controlled syllable repetitions improve comparability of
DBS-induced dysarthria between on- and off-state in patients
with essential tremor
J. Becker, D. M ucke, A. Hermes, T.A. Dembek, A.F. Josten, I.
Meister, V. Visser-Vandewalle, M. Grice, L. Timmermann, M.T.
Barbe (Cologne, Germany)
Objective: In this study, we investigate the effect of bilateral
VIM-DBS on speech production in patients with essential tremor
(ET). We use rate-controlled syllable repetitions to employ acoustic
parameters related to stimulation induced dysarthria (SID), both with
and without stimulation.
Background: VIM-DBS is an effective treatment to suppress
medically resistant ET. However, SID is a common side effect,
reportedly affecting between 10% and 75% of the patients. In recent
studies, we used temporal- and intensity-related acoustic parameters
to show deterioration in speech of ET patients under stimulation.
However, we found that some patients seem to compensate for lack
of articulatory precision by slowing down their speech rate, while
others do not.
Methods: 10 German ET patients were recorded acoustically
with DBS-on and -off. Speech materials consisted of oral diadocho-
kinesis (DDK) tasks; patients were instructed to produce the CV
sequence/kakaka/at different predefined speech rates (between 3 and
7 repetitions of/ka/per second) which were paced with a metronome
via headphones. In order to capture the degree of articulatory preci-
sion, we calculated the ratio between minimum intensity in the con-
sonant and maximum intensity in the vowel as a measure for voicing
and/or spirantization during stop consonant production. Controlling
for speech rate allows for a comparison across conditions that is not
mediated by a reduction in rate as a compensation strategy. We thus
matched speech rates (slowest and fastest common speech rate) in
both DBS states to ensure comparability between DBS-on and -off.
Results: Preliminary results suggest that articulatory precision is
affected by stimulation to a different degree across speech rates. In
slow condition, intensity ratio increased by 36% (from 0.22 in DBS-
off to 0.30 in DBS-on), representing a deterioration in precision in
terms of more voicing and/or spirantization during the production of/
k/under stimulation. In fast condition, we found a much greater
increase of 55% (from 0.33 in DBS-off to 0.51 in DBS-on).
Conclusions: Our results might explain why some patients with
SID reduce their speech rate while DBS is on in order to compensate
for lack of articulatory precision. Therefore, rate-controlled DDK is
a useful method for investigating DBS induced speech changes
allowing for direct comparison between DBS-on and -off.
1445
Smartphone apps provide a simple, accurate bedside screening
tool for orthostatic tremor
D. Bhatti, R. Thompson, A. Hellman, C. Penke, J.M. Bertoni, D.
Torres-Russotto (Omaha, NE, USA)
S557
Objective: To evaluate the diagnostic properties of smartphone
applications (Apps) as screening tools for Orthostatic Tremor (OT).
Background: OT is characterized by the presence of sensation of
instability while standing, associated with high frequency tremor in
legs. Diagnosis is confirmed with surface EMG, but most patients go
undiagnosed for many years. A simple bedside screening tool would
be useful. Discrimination ability and accuracy studies of the use of
accelerometers in OT diagnosis are needed.
Methods: We obtained recordings (60 secs or less) using iPhones
(Model 5, 5s and 6) free Apps (LiftPulse by LiftLabs, California,
USA [App1] and iSeismometer by ObjectGraph LLC, New York,
USA [App2]) at default settings. (Anupam Pathak, LiftLab, Google,
Apple and ObjectGraph LLC were not involved in the research and
are not responsible for any claims made by our research team).
iPhone was secured vertically, just above the patella using a phlebot-
omy tourniquet. A positive test meant: For App1, the presence of
any tremor frequency peak between 12-19 Hz; and for App2, the
presence of a tremor frequency in any axis between 12-19Hz.
Results: 24 EMG-confirmed OT patients and 15 age-matched
spousal controls were evaluated. Two control subjects did not have
App2 data collected. OT patients were mostly female (22/24) and
controls mostly males (11/15), average age in years for OT patients
was 70 (54-87) and for controls 72.7 (56-86).
App2 provides frequencies in all three axes individually. OT
range tremor was seen in all three axes in only 2/24 patients while
majority had it in 2 axes.
App1 detected OT range tremor (12-19Hz) in 22/24 patients and
none of the controls. (Sensitivity 5 92%, Specificity =100%, Nega-
tive Predictive Value (NPV) =88%, Negative Likelihood Ratio
(NLR) <0.1). App2 detected OT range tremor in 21/24 patients and
in 1/13 controls (Sensitivity=88%, Specificity=92%, NPV=80%,
NLR=0.14). When combined, 24/24 patients and 1/13 controls had
OT range tremor on at least one of the two Apps (Sensitivity
=100%, Specificity 5 92%, NPV=100%, NLR 5 0).
Conclusions: Smartphone Apps that use the built-in accelerome-
ter provide a simple, accurate and inexpensive bedside screening
diagnostic tool for patients with Orthostatic Tremor.
1446
EEG analysis in 30 patients with orthostatic tremor
D. Bhatti, N. Murr, A. Hellman, R. Iske, J.M. Bertoni, D. Torres-
Russotto (Omaha, NE, USA)
Objective: To assess abnormalities on EEG recordings in patients
with Orthostatic Tremor (OT).
Background: OT is characterized by a sensation of instability
while standing, associated with high frequency tremor in legs (13-18
Hz). The role of EEG in OT has not been fully investigated. In a
previous report, 19 patients underwent EEG recordings with extra
midline electrodes. Five patients had a fast 14-24 Hz midline dis-
charge greatest at Cz, with worsening upon standing in two (McMa-
nis & Sharbrough, Muscle Nerve, 1993). Few other case reports
noted normal EEG. Presence of EEG abnormalities in OT can
expand our understanding of the pathophysiology of the disease and
open up new research avenues.
Methods: We prospectively enrolled 30 OT patients (28 females),
average age of 68.3 years (range 54-87). The average duration of OT
was 16.3 years (range 4-44). A modified-protocol EEG was devel-
oped using additional midline electrodes, and surface EMG electrode
on limbs. Recording was performed at rest, during sleep (when avail-
able) and while standing unassisted. Hyperventilation and photic
stimulation were also performed. Recordings were visually analyzed
by a fellowship-trained epileptologist.
Results: In all subjects, EEG showed normal background, normal
drowsiness and/or stage 2 sleep, and normal responses to hyperventi-
lation and photic stimulation. These normal results persisted during
stance. EEG abnormalities were found in 4/30 subjects, and seemed
unlikely to be related to OT. Three patients had medium voltage,
Movement Disorders, Vol. 30, Suppl. 1, 2015
S558 POSTER SESSION
intermittent, irregular slow activity in anterior mid-temporal region,
and one subject showed generalized beta activity likely related to
medications. These EEG changes were not position-dependent.
Tremor artifact while standing was noted in EEG and EKG leads
in 67% and 13% of the subjects respectively.
Conclusions: Visual EEG analysis in OT patients did not reveal
electrographic abnormalities even upon standing unassisted. Clini-
cians interpreting Video-EEGs should be aware of the OT artifact
that can be seen in EEG and EKG leads while standing.
1447
Frequency of tremor in postural orthostatic tachycardia
syndrome
A. Deb, A. Hohler (Boston, MA, USA)
Objective: To evaluate the frequency of tremor in patients with
postural orthostatic tachycardia syndrome.
Background: Postural orthostatic tachycardia syndrome, or PoTS,
is a type of dysautonomia seen commonly in young adults. It is
defined as a heart rate increase of 30 points in adults and 40 points
in children upon standing without a corresponding drop in blood
pressure. Tremor is a frequently seen feature on examination of our
patients. We sought to survey our population to determine how fre-
quently this was reported.
Methods: A prospective, qualitative survey was distributed to
PoTS patients, diagnosed by tilt table testing. The survey consisted
of questions regarding the presence of tremor. Questions were also
geared to determine the body regions involved with tremor and
whether tremors worsened at rest or with action. Patients answered
questions on a Likert scale. Positive responses of strongly agree
and agree were summated and similarly negative responses of
disagree and strongly disagree were summated. Neutral role in the generation of ET and palatal tremor. The olivary hypothe-
responses were not included. A total of 22 responses were collected.
Results: Fifty percent of PoTS patients reported tremor. Close to
one third (27%) reported the tremors were worse at rest and involved
parts of the body other than the hands. A smaller percentage, 18%,
of respondents reported the tremor worsened with action.
Conclusions: Postural orthostatic tachycardia syndrome may be associ-
ated with a variety of symptoms. Interestingly, about half of PoTS patients
report tremor as a symptom. Although more patients report tremor at rest
than with action, our questions did not differentiate between postural and
rest tremor. Further studies are needed to determine the underlying patho-
physiology for this autonomic associated phenomenon.
1448
Fahn-Tolosa-Marin tremor scale and digitizing tablet have
comparable minimum detectable change
R. Elble, T. Zesiewicz (Springfield, IL, USA)
Objective: To determine if a digitizing tablet is better than the
Fahn-Tolosa-Marin part B tremor rating scale (FTM-B) in detecting
changes in tremor that exceed random variability in tremor
amplitude.
Background: Tremor rating scales provide crude, nonlinear and
subjective assessments of tremor severity. By contrast, digitizing tab-
lets are capable of providing precise, linear and objective measures
of tremor in writing and drawings. However, the advantages of tab-
lets over rating scales are diminished when random variability in
tremor is large. Tablets will measure random variability precisely,
but changes in tremor must exceed random variability to be recog-
nizable as true change due to treatment or disease progression.
Methods: Baseline FTM-B ratings and digitizing tablet (Wacom
Intuos 3) assessments of patients with essential tremor were derived
from a published double-blind, placebo-controlled crossover trial of
pregabalin (22 patients; 4 raters) (Zesiewicz et al. Mov Disord
2013;28:249-250). Two baseline assessments, performed 13 weeks
apart, were used to compute the minimum detectable change (MDC)
Movement Disorders, Vol. 30, Suppl. 1, 2015
for the FTM-B and digitizing tablet measurements, which were per-
formed simultaneously. The two spirals and three lines of FTM-B
were recorded with the tablet, and tremor amplitude in each drawing
was computed using spectral analysis (Elble et al. Mov Disord
1996;11:70-78). The grand average of root-mean-square tremor in
the two spirals and 3 lines was used as the tablet measure of tremor
for each trial, and these measures were compared with the FTM-B.
Results: The mean (SD) FTM-B score was 15.6 (5.4) (maximum
score 5 36). The MDC for the digitizing tablet was 81% of the base-
line geometric mean tremor amplitude. The MDC for FTM-B was
52% of mean baseline score. Using the Weber-Fechner equation
(slope 5 0.5), the FTM-B score was converted to actual tremor
amplitude (Deuschl et al. Lancet Neurol 2011;10:148-161), and the
MDC for this estimate was 64%.
Conclusions: Digitizing tablets provide precise linear measures
of tremor amplitude in writing and drawing. However, this advantage
over rating scales is reduced by the considerable natural variability
in tremor amplitude over time. This variability in tremor amplitude
is so great that MDC of the digitizing tablet (i.e., the smallest change
exceeding random variability) is comparable to the MDC of the
FTM-B tremor rating scale.
1449
Hypertrophic olivary degeneration does not reduce essential
tremor
A. Elkouzi, J.C. Kattah, R.J. Elble (Springfield, IL, USA)
Objective: To describe a case of longstanding essential tremor
(ET) that was not diminished by the development of bilateral hyper-
trophic olivary degeneration, progressive ataxia and palatal tremor.
Background: The inferior olive is postulated to play a critical
sis of ET stems mainly from the harmaline animal model, in which
action tremor resembling ET is caused by harmaline-induced olivary
oscillation. However, human postmortem and neuroimaging studies
have produced little support for the olivary hypothesis of ET (Louis
ED. Cerebellum 2014;13:501-512). By contrast, there is considerable
support for the olivary hypothesis of palatal tremor, which occurs in
the context of hypertrophic olivary degeneration, producing a pro-
found loss of olivary neurons (Shaikh et al. Brain 2010;133:923-40).
Lesions in the cerebellothalamocortical pathway reduce ET, but the
effect of olivary lesions on ET has not been reported.
Methods: We examined a 77-year-old man with a 30-year history
of ET and a 3-year history of progressive gait ataxia and falls. He
denied recent change in his hand tremor. Physical examination revealed
a 2-Hz palatal tremor and mild gait ataxia. His MRI revealed bilateral
inferior olivary hypertrophy. His hand tremor was assessed clinically
with the Essential Tremor Rating Assessment Scale (TETRAS) and
electrophysiologically with accelerometry and forearm EMG.
Results: The patient exhibited grade 2 postural and kinetic tremor
in both hands and grade 2 tremor in his spiral drawings and hand-
writing. Electrophysiologic studies revealed a 5.2-Hz postural tremor
in the wrist, and the tremor frequency did not change when a 454-
gm load was attached to his horizontally extended hand, with fore-
arm supported. These electrophysiologic results are characteristic of
ET.
Conclusions: This patient exhibited typical 5.2-Hz ET despite
hypertrophic degeneration of both inferior olives and the develop-
ment of 2-Hz palatal tremor. Given the marked neuronal loss and
dysfunction that occurs in hypertrophic olivary degeneration, the per-
sistence of ET in this patient seems incompatible with the hypothesis
that olivary oscillation is the origin of ET.
1450
The long-term outcome of orthostatic tremor
C. Ganos, L. Maugest, E. Apartis, C. Gasca-Salas, M.T. C aceres-
Redondo, R. Erro, I. Navalpotro, A. Batla, E. Antelmi, B. Degos, E.
 POSTER SESSION
Roze, M.L. Welter, T. Mestre, F.J. Palomar, C. Cordivari, P. Mir,
A.E. Lang, S.H. Fox, K.P. Bhatia, M. Vidailhet (London, United
Kingdom)
Objective: To determine the long-term outcome of patients with
orthostatic tremor.
Background: Orthostatic tremor is a rare condition characterised
by high frequency tremor that appears on standing. Although the
essential clinical features of orthostatic tremor are well established,
little is known about the natural progression of the disorder. Here,
we report the long-term outcome based on the largest multi-centre
cohort of patients with orthostatic tremor.
Methods: Clinical information of 68 patients with clinical and
electrophysiological diagnosis of orthostatic tremor and a minimum
follow-up of 5 years is presented.
Results: There was a clear female preponderance (76.5%) with a
mean age of onset at 54 years. Median follow-up was 6 years (range
5 25). On diagnosis, 86.8% of patients presented with isolated
orthostatic tremor and 13.2% had additional neurological features. At
follow-up 7 patients who initially had isolated orthostatic tremor
then developed further neurological signs. 79.4% of patients reported
worsening of orthostatic tremor symptoms. These patients had signif-
icantly longer symptom duration than those without reported worsen-
ing (median 15.5 vs 10.7 years respectively; p 5 .005). There was no
change in orthostatic tremor frequency over time. Structural imaging
was largely unremarkable and dopaminergic neuroimaging (DaTS-
CAN) was normal in 18/19 cases. Pharmacological treatments were
disappointing. Two patients were treated surgically and showed
improvement.
Conclusions: Orthostatic tremor is a progressive disorder with
increased disability although tremor frequency is unchanged over
time. In most cases orthostatic tremor represents an isolated syn-
drome. Drug treatments are unsatisfactory but surgery may hold
promise.
1451
Hereditary geniospasm in a Central American family
E. Haberfeld, L. Timothy (Philadelphia, PA, USA)
Objective: Description of a rare inherited hyperkinetic disorder
in a previously unreported geographic region.
Background: Hereditary geniospasm is a rarely reported inherited
hyperkinetic Movement Disorder with autosomal dominant transmis-
sion. It is believed to have genetic heterogenity with a locus on the
long arm of chromosome 9q13-q21 reported in one large British
family. Since it was first reported by Massaro in 1894 roughly thirty
families with this disorder have been reported in the literature.
Nearly all reports of this disorder have emanated from from Europe
or the United States with one large family with European roots
reported in Argentina. This is the first report of a case from Central
America.
Methods: The index patient and her five year old daughter were
interviewed, examined and videotaped. The literature on hereditary
geniospasm was reviewed.
Results: Interview and examination of the index patient disclosed
a 38 year old woman with lifelong tremor of the chin. The tremor
was of the entire chin not unilateral. It was present intermittently,
exacerbated by situations of stress or high emotion. It disappeared in
sleep. There was no associated jaw or palatal tremor, or signs typical
of essential tremor. It was not induced by cutaneous stimuli. She had
no other neurological problems apart from an incidental cavernous
malformation and headaches that had been previously treated with
topiramate. She had no psychiatric history and had never been
treated with psychiatric or neuroleptic medication. Her family history
was notable for an identical tremor in her five year old daughter.
The daughter was also examined. She had had the identical tremor
since her first year of life. The tremor was non-disabling in both
cases and neither patient had received treatment for it.
S559
The index patients mother had not had geniospasm. The index
patient was raised by her step-father in El Salvador, and was
estranged from her biological father. No other family members were
known to have geniospasm, including the index patients two other
daughters with the same paternity. Both of the index patients
parents were originally from El Salvador. Thus, this report is of two
generations of geniospasm in a Central American family.
Conclusions: Herediatry geniospasm is an uncommon hyperki-
netic Movement Disorder that has been rarely reported in the past
century. This report adds to the literature on this subject and is the
first description of a family of Central American origin.
1452
A case of misdiagnosed essential tremor (ET)
K. Harutyunyan, I. Gabrielyan, H. Amirjanyan, S. Khachaturyan, A.
Voskanyan, G. Avagyan, H. Manvelyan (Yerevan, Armenia)
Objective: Tremor is one of the most common involuntary move-
ments, frequently seen in clinical practice as manifestation of Parkin-
sons disease (PD) and ET. ET is characterized by slowly
progressive postural and/or kinetic tremor.
Background: A 63 year old female presented to our clinic with
one year history of bradykinesia and unilateral tremor, which lately
was interfering with her daily activities. A year ago she was diag-
nosed with PD and L-DOPA was started.
Methods: Neurological examination revealed mild bradykinesia
with normal muscle tone, tremor in her both arms, more severe on
right side, which was present at rest, but worsened during voluntary
movement. Laboratory tests were within normal range. Brain MRI
scan was without abnormalities. ENMG revealed high frequency
tremor in both arms. Patients family history for PD or ET was
negative.
Results: Based on these findings the diagnosis of ET was sus-
pected. Treatment was modified by gradual discontinuation of L-
DOPA and prescription of Propranolol. 3 months follow-up revealed
obvious reduction in tremor amplitude. There was no change in bra-
dykinesia severity and no other Parkinsonian features were evident
despite L-DOPA discontinuation.
Conclusions: This case once more demonstrates the actuality of
ET misdiagnosis and the necessity of carefully reviewing PD diagno-
sis in order to prevent patients from receiving long-term unnecessary
medication.
1453
Electromyographic assessment of essential and Parkinsonian
hand tremor
E. Ivanova, P. Fedin, A. Broutian, I. Ivanova-Smolenskaya, S. Illar-
ioshkin (Moscow, Russia)
Objective: To analyze spectral and cross-spectral parameters of
essential and Parkinsonian tremor using surface electromyography.
Background: Differential diagnosis of Parkinsons disease (PD)
and essential tremor (ET) may be challenging, so there is a need for
futher investigation of electrophysiological specifics of these two
kinds of tremor.
Methods: Forty six patients with tremulous PD and 38 patients
with ET were enrolled into the study. Seven patients within ET
group had rest tremor of one or both hands. Surface electromyogra-
phies were recorded from wrist flexors and extensors of the arm with
higher tremor amplitude.
Results: There was a slight, but statistically proven, difference in
frequency of muscle tremulous activity between ET and PD groups
with lower frequency in PD group. In test with cognitive task (count-
ing backwards) EMG spectral power in 1-30 Hz frequency range
increased to a higher extent in PD group compared with ET group
with some overlap between groups. EMG-EMG coherence in antago-
nist muscles at tremor frequency didnt differ between groups while
Movement Disorders, Vol. 30, Suppl. 1, 2015
S560 POSTER SESSION
EMG-EMG coherence at double tremor frequency was significantly
higher in PD group compared with ET group. In resting tremor
assessment all ET patients demonstrated synchronous pattern of
EMG activity in the antagonist muscles while in PD group a wide
spectrum of EMG patterns was observed - from synchronous to inter-
mediate and alternating. Postural tremor pattern showed more over-
lap between groups varying from synchronous to alternating in both
conditions, whereas in ET group synchronous pattern was presented
significantly more often than in PD patients. None of the explored
measures showed high diagnostic accuracy in separating ET from
tremulous PD.
Conclusions: Most measures explored in the present study
showed a considerable overlap between groups (the partial exclusion
is muscle bursting pattern of resting tremor as long as alternate or
intermediate pattern was observed only in PD group). To our knowl-
edge this is the first report of difference of EMG-EMG coherence at
double tremor frequency between ET and PD. High intermuscular
coherence at double tremor frequency in PD patients supports the
hypothesis that in Parkinsonian tremor spinal motor neuron pool is
driven by motor cortex primarily at double tremor frequency.
1454
Different features of iron deposition in subcortical nuclei
between essential tremor and tremor-dominant Parkinsons
disease
L. Jin, J. Wang, G. Fei, C. Zhong (Shanghai, Peoples Republic of
China)
Objective: To investigate the difference in the pattern of iron
deposition in subcortical nuclei between essential tremor (ET) and
tremor-dominant Parkinsons disease (PD).
Background: Essential tremor (ET) is the most common Move-
ment Disorder in older adults and has been well documented in clini-
cal features. Recent post-mortem studies have found the clearly
identifiable structural changes in the brains of ET patients, indicating
that ET is a neurodegenerative disorder . However, the underlying
pathophysiology of neurodegeneration in ET patients is little to
know.The imbalance of brain iron homeostasis has been demon-
strated to contribute to neurodegeneration in patients with Parkin-
sons disease (PD) and Alzheimers disease.To date, there is no
Fig. 1. (1455).
Movement Disorders, Vol. 30, Suppl. 1, 2015
study to compare the difference in brain iron deposition between ET
and PD.
Methods: The iron levels of substantia nigra (SN), globus pal-
lidus (GP), putamen, the head of caudate (CA), and red nucleus
(RU) were estimated using bilateral average phase values in 53 ET
patients, 29 tremor-dominant PD patients, and 60 healthy control
subjects by susceptibility-weighted phase imaging of 3.0 Tesla mag-
netic resonance system. Serum ceruloplasmin level of all subjects
was determined.
Results: ET patients showed significantly increased iron level
represented by lowered bilateral average phase values in the bilateral
SN and GP as compared with control subjects (p<0.01). ET patients
manifested the different pattern of brain iron deposition from tremor-
dominant PD patients who exhibited significantly enhanced iron con-
tent only in bilateral SN (p<0.01). There was significant difference
of brain iron level in GP between ET patients and tremor-dominant
subgroup PD patients(p<0.05). Furthermore, the bilateral average
phase values in SN and GP of ET patients did not correlate with
serum ceruloplasmin level, while nigral bilateral average phase val-
ues in patients with Parkinsons disease correlated highly with the
level of serum ceruloplasmin.
Conclusions: These findings may provide evidence that ET is a
neurodegenerative disorder associated with brain iron accumulation
with different underlying mechanism as compared with tremor-
dominant PD.
1455
The efficacy of electrical muscle stimulation in various tremor
syndromes: An open-label, pilot study including 68 patients
O. Jitkritsadakul, C. Thanawattano, C. Anan, R. Bhidayasiri
(Bangkok, Thailand)
Objective: This study is to determine the efficacy of electrical
muscle stimulation (EMS) as a therapeutic option for intractable
hand tremor in patients with Parkinsons disease (PD), essential
tremor (ET), and dystonic tremor (DT).
Background: Hand tremor can be an obviously, debilitating
symptom and may not be adequately response to pharmacologic
interventions that probably documented in term of the intractable
tremor. We postulate that modulation of peripheral reflex mechanism
 POSTER SESSION
Fig. 2. (1455).
by strong stimuli, such as electrical muscle stimulation (EMS), may
reset the central oscillators in the basal ganglia resulting in the tran-
sient reduction of tremor.
Methods: This is an opened-labeled, non-randomized, compara-
tive study to determine the efficacy of EMS in the reduction of hand
tremor among 3 groups of patients as following; PD, ET, and DT
groups. The assessment of tremor was performed before and during
EMS by a tremor monitoring device. Stimulation of the affected
hand muscle was performed with the EMS stimulator.
Results: From total 68 patients with various tremors (including
34 PD, 22 ET, and 12 DT patients), there were no statistically signif-
icant differences in age, gender, disease duration, the side of tremor
predominance, and TMSE scores between the 3 groups of patients.
During stimulation [figure2], PD group had highest in peak magni-
tude and RMS than ET and DT groups (p<0.001, each) [figure1].
The percentage in tremor reduction, calculated from differences of
peak magnitude and RMS, was highest in the PD group compared to
ET and DT groups (p50.001, p50.006, respectively). Compared to
ET and DT groups, PD group had up to 70.6% of tested patients (24
from 34) and 61.8% (21 from 34) improvement calculation for dif-
ference in peak magnitude and RMS, respectively, and PD group
had well responsiveness above the 30% improvement that may be
observed with placebo intervention compared to those in ET and DT
groups (p50.001, p<0.001, respectively).
Conclusions: We demonstrated the effectiveness of EMS in the
suppression of intractable hand tremor in PD patients, but not with
ET and DT patients. The significant tremor reduction was observed
in the amplitude domain (peak magnitude and RMS), but not with
frequency. These findings support the possibility that modulation of
peripheral reflex mechanism can probably modulate central oscillator
resulting in a transient reduction of tremor.
1456
Evaluation of retinal nerve fiber layer in essential tremor and
Parkinsons disease with optical coherence tomography
H. Kaleagasi, H. Fidanci, U. Adiguzel, O. Dogu (Mersin, Turkey)
S561
Objective: To determine potential retinal nerve fiber involvement
in essential tremor (ET) patients.
Background: ET is a common chronic progressive disease, char-
acterized with postural and action tremor. The relationship between
ET and Parkinsons disease (PD) has been reported in recent studies.
In postmortem studies lower retinal dopamine contents have been
reported in PD patients. And studies evaluating the retinal morphol-
ogy in PD with optical coherence tomography (OCT) have shown
the reduced peripapillary retinal nerve fiber layer thickness (RNFL).
Methods: Thirty ET patients diagnosed according to WHIGET
criteria, 30 PD patients diagnosed according to UK Brain Bank crite-
ria and 30 age-matched healthy control cases are included to study.
Neurological and ophthalmic examinations, and OCT are performed
in all cases.
Results: Twelve of ET patients (40%), 8 of PD patients (38.2%)
and 19 of control cases (42.3%) were female. No statistically signifi-
cant difference was determined between ET, PD and control cases in
terms of average age (respectively, 61.1 611.3 years, 62.0 610.4
years, 60.5 6 11.9 years, p50.874). Average values of RNFL in ET
(85,6 6 11,4lm) and PD (86,2 6 10,5lm) groups were significantly
lower than the values in control group (92,5 6 8,0lm) (p<0.05).
Also average nasal RNFL value in ET group was significantly lower
than the control group (respectively, 66,5 6 12,0lm, 73,3 6 9,9lm,
p<0.05). The mean RNLF did not differ significantly between the
ET and PD groups (p>0.05).
Conclusions: Our data show that reduced RNFL may be seen in
ET which is a complex and heterogenic disease in addition to the
other known non-motor findings, and also may support that ET may
be a neurodegenerative disease like PD.
1457
Case report: Replacement therapy of head shaking syndrome by
transcranial magnetic stimulation
B.B. Khodaie, M.M. Ahmadi, M.M. Lotfinia, A.A.A.A. Lotfinia
(Tehran, Iran)
Movement Disorders, Vol. 30, Suppl. 1, 2015
S562 POSTER SESSION
Objective: Essential tremor (ET) has been reported as the most
common Movement Disorder worldwide. ET is supposed to be trig-
ger by electrical fluctuations in the brain which send abnormal sig-
nals out to the muscles. Poly synaptic brain-stem reflex abnormalities
are believed to play major role in initiation of ET. Cortical excitabil-
ity reported in ET patients. Various medications have been proposed
for ET including primidone, propranolol and benzodiazepines, which
may reduce brain-stem poly synaptic reflexes and change neuronal
excitability. However, new therapeutic strategy could introduce.
Background: ET also referred to as orthostatic tremor, is an
unusual Movement Disorder initiated by signals travel through a
variety of brain regions before they make it out to muscles. Correla-
tion of brain electrical activity with ET needs to be defined. Electri-
cal stimulation of the brain was first reported by Barker et al. in
1985. Bunch of clinical and basic investigation indicated its effec-
tiveness on many neurological disorders. Current study reported a
case of ET who replaces Propranolol treatment with transcranial
magnetic stimulation (TMS).
Methods: A 42-year-old man presented with a shaking of his
right side head. The tremor began immediately after looking at left
side. His medical history was irrelevant to this problem. He starts
using Propranolol (10 mg). However, due to fasten heart rate after
drug usage we suggested replacing medicine with TMS. TMS by 2
Hz with in 10 minute administrated on brain-stem region surface on
the back of head.
Results: At this approach after TMS induction neurologic exami-
nation showed significant reduction in frequency of tremor
(P < 0.05). Furthermore, heart rate reverse to normal.
Conclusions: The idea of ET treatment with changes in neuronal
activity in our patient might have been a coincidence. However, the
fact that the tremor reduced after TMS supports this relation. There
is also more data in this regard. Finding revealed that TMS may trig-
ger some neurotransmitter enhancement in central nerve system.
Including dopamine and some other inhibitory neurotransmitter
which was not studies in present study but previously reported. Fur-
thermore, depression in neuronal activity have been reported by low-
frequency of TMS.
1458
The involvement of dopamine receptors in the regulation of
harmaline-induced tremor measured by force plate actimeters
B. Kosmowska, U. Gowacka, J. Wardas, K. Ossowska (Krak ow,
Poland)
Objective: The aim of the study was to investigate the involve-
ment of dopamine (DA) receptors in regulation of harmaline-induced
tremor in rats. For this purpose, we used three different DA agonists:
apomorphine (non-selective), pramipexole (D3 preferential) and 7-
OH-DPAT (D3 selective). Propranolol (a first-line drug in essential
tremor, ET) was used as a reference compound.
Background: The postural/kinetic tremor induced by harmaline
is characterized by frequency of 10-12 Hz in rats and is generally
accepted as a model of ET. The main cause of harmaline-induced
tremor is abnormal activation of olivo-cerebellar glutamatergic
climbing fibers, and in consequence excessive glutamate release and
induction of complex spike activity of Purkinje cells (PCs). How-
ever, mechanisms underlying this behaviour seem to involve also
other neurotransmitter systems. The whole cerebellum is innervated
by dopaminergic mesencephalic neurons. Furthermore, cerebellar
PCs express tyrosine hydroxylase, VMAT2 and DAT, and also
release DA, which then excites them by D3 autoreceptors.
Methods: The tremor and locomotor activity were measured
objectively by the Force Plate Actimeters. To quantify the intensity
of the tremor, the following parameters were measured: power in the
0-8 Hz band (AP1) and 9-15 Hz band (AP2) and tremor index (dif-
ference in power between the AP2 and AP1). In order to examine
the locomotor activity and to evaluate a relationship between tremor
Movement Disorders, Vol. 30, Suppl. 1, 2015
and locomotion, the total distance travelled by an animal and AP2/
distance ratio were measured respectively.
Results: Harmaline (15 mg/kg ip) induced tremor, which was man-
ifested by an increase in the AP2 and tremor index, and propranolol
(20 mg/kg ip) reversed both of these effects. Apomorphine (0.5, 1 mg/
kg sc) enhanced the AP2 and AP2/distance ratio, and at the lower
dose also the tremor index, in harmaline-treated animals. In turn, pra-
mipexole (0.1, 0.3, 1 mg/kg sc) had no effect on tremor index, but at
the lowest dose reduced AP2, while 7-OH-DPAT (0.1 mg/kg sc)
decreased both the tremor index and AP2 elevated by harmaline.
Conclusions: The present results indicate that apomorphine
enhances the tremor induced by harmaline independently of hyperac-
tivity induced by this DA agonist. In addition, the effects of prami-
pexole and 7-OH-DPAT administration revealed the contribution of
D3 receptors in inhibition of harmaline-induced tremor.
1459
Climbing fiber-Purkinje cell synaptic changes correlate with
clinical features in essential tremor
S.H. Kuo, R.J. Louis, C.Y. Lin, A.H. Koeppen, P.L. Faust, E.D. Louis
(New York, NY, USA)
Objective: To investigate the clinicopathological correlations of
abnormal climbing fiber (CF)- Purkinje cell (PC) synaptic connec-
tions and tremor severity in essential tremor (ET).
Background: Changes of CFs innervations on PCs have been
postulated to be involved in ET. We previously reported that in ET
cases, more CF-PC synapses on the thin, distal PC dendritic branch-
lets, which are parallel fiber innervation territories. However, the cor-
relations of these abnormal CF-PC connections to clinical tremor
remain poorly understood.
Methods: Thirty-seven ET brains from the New York Brain
Bank were studied. During life, severity of action tremor in the
hands was rated (total tremor scores [TTS] and the presence of rest
tremor, head and voice tremors were noted. Dual immunofluores-
cence of VGlut2 and calbindin was used to visualize CF-PC synapses
in the cerebellar sections. We calculated the percentage of CF-PC
synapses on PC dendrites < 1lm thickness (%CFPC1) (i.e., VGlut2
puncta on PC dendrites < 1lm thickness divided by the total VGlut2
puncta in a given PC dendritic arbor).
Results: There was a robust, inverse correlation between TTS
and %CFPC1 (r 5 -0.45, p 5 0.005). The %CFPC1 was not related to
the age of tremor onset (r 5 -0.04, p 5 0.79) or age of death
(r 5 0.02, p 5 0.90). The %CFPC1 was lower in ET cases with vs.
without voice tremor (31.8 6 10.0% vs. 38.3 6 8.7%, p 5 0.045).
%CFPC1 was lower in women than men (33.4 6 9.9% vs.
41.4 6 6.2%, p 5 0.02). When taking voice tremor into account, men
without voice tremor significantly differed from woman with voice
tremor (43.2 6 5.1% in men without voice tremor vs. 30.6 6 10.5%
in women with voice tremor, one way ANOVA with Tukeys multi-
ple comparison, p < 0.05). %CFPC1 was not associated with pres-
ence of head tremor or rest tremor (p 5 0.34 and 0.13, respectively).
Conclusions: We showed a robust association between the CF-
PC synaptic pathology and tremor severity in ET, and uncovered
additional sources of clinical-pathological heterogeneity. Our present
study highlighted that CF-PC synaptic pathology could be an impor-
tant neuropathological substrate for tremor in ET.
1460
Essential tremor in patients with Parkinsons disease
K. Kurako, S. McMahan, N. Galvez-Jimenez (Weston, FL, USA)
Objective: To present two nonrelated Ashkenazi Jewish patients
who had essential tremor features with Parkinsons disease.
Background: Parkinsons disease is a neurodegenerative disorder
is diagnosed based on clinical criteria including rest tremor, bradyki-
nesia, rigidity, and loss of postural reflexes. It is presumed that most
 POSTER SESSION
patients develop Parkinsons disease from a complex interaction of
environmental, genetic factors, and other unknown factors.15%
patients have a family history. In some patients with Parkinsons dis-
ease, there is an increased frequency of mutations of the glucocere-
brosidase gene, which is responsible for Gaucher disease.
Furthermore, mutations in the leucine-rich repeat kinase 2 (LRRK2)
gene may cause autosomal dominant Parkinsons disease.
Methods: Case reports.
Results: Patient 1: A 72-year-old Ashkenazi women presented
with a 5-year history of progressive bilateral hand tremors. Exam
showed moderate amplitude bilateral hand tremors when walking.
Writing tremor but no micrographia. There was decreased arm swing
bilaterally but no other Parkinsonian features. There had been despite
treatment with amantadine and pramipexole, and primidone. A radio-
pharmaceutical (iodine I 123 ioflupane) scan (DaTSCAN) was abnor-
mal, consistent with a Parkinsonian disease. Testing for mutations of
the LRRK2 was done.
Patient 2 A 50-year-old Ashkenazi man presented with a 37-year
history of bilateral essential tremor. Physical examination showed
right foot dystonia. There was decreased right arm swing with mini-
mal bradykinesia. There had been no improvement despite previous
treatment with ropinirole and propranolol, and primidone. An iodine
I 123 ioflupane scan consistent with dopamine deficiency. Genetic
testing showed that the patient was a carrier for Gaucher disease but
negative for mutations of the LRRK2 gene.
Conclusions: Both patients were of Ashkenazi Jewish ancestry
and had an essential tremor phenotype that had not responded to
therapy. Essential tremor previously has been associated with Parkin-
sons disease. The patients also had abnormal iodine I 123 ioflupane
scans, consistent with Parkinsons disease.
1461
Upper limb kinematics guides longitudinal, incobotulinumtoxinA
therapy of Parkinsons disease tremor
J. Lee, O. Samotus, F. Rahimi, M. Jog (London, ON, Canada)
Objective: To objectively measure the longitudinal efficacy and
safety of incobotulinumtoxinA injections for treatment of Parkinsons
disease tremor using multi-sensor kinematic technology.
Background: Focal treatment of upper extremity (UE) tremor has
not been widely adopted as an alternative non-pharmacological
option for tremor due to significant adverse effects, such as muscle
weakness. As tremor is complex to assess visually, an objective
method can accurately capture tremor biomechanics and can be used
to determine injection patterns.
Methods: This open-label study recruited 28 PD participants who
were injected in the UE every 16 weeks, a total of six injection
cycles, and attended follow-up visits six weeks following treatment,
for a total of 13 study visits. Clinical rating scales (UPDRS and
FTM) were taken at each visit. Kinematic recordings were taken as
seated participants performed two rest and two postural tasks. Goni-
ometers were placed on the wrist, elbow, and shoulder joints and to
measure tremor severity, angular RMS amplitude, in multiple
degrees of freedom: flexion-extension (F/E), pronation-supination,
radial-ulnar at wrist, F/E at elbow, and F/E and abduction-adduction
deviations at shoulder. Dosing and muscle site of injection were
determined based on kinematic data and clinicians experience.
Results: A statistical significant reduction in tremor severity was
observed using both clinical and objective measures. Rest and action
tremor, represented by UPDRS items 20 and 21, was significantly
reduced by 50.1% and by 53.3%, respectively, at week 96. In paral-
lel, kinematics measured rest and postural tremor severity at each
arm joint and displayed a significant mean reduction of 79.6%,
81.6%, and 79.3% at the wrist, elbow, and shoulder, respectively.
Seven participants (25%) experienced functional benefit, reported by
FTM part C. Two participants (14.2%) experienced mild weakness
in injected wrist muscles following six injection cycles.
S563
Conclusions: IncobotulinumtoxinA injection parameters deter-
mined using kinematics provides efficacious outcomes with minimal
to no effect on arm function.
1462
Gait variability changes after unilateral VIM DBS in essential
tremor patients are correlated with changes in midline and
upper extremity tremor
H. Morita, M. Higuchi, L.A. Zukowski, R. Roemmich, K.D. Foote,
C.J. Hass, M.S. Okun (Gainesville, FL, USA)
Objective: To investigate the relationship between changes in
tremor and gait function following unilateral deep brain stimulation
(DBS) in persons with essential tremor.
Background: Essential tremor (ET) characteristically presents
with an upper extremity postural and kinetic tremor, but a mild
abnormality of gait and balance has been observed. DBS targeting of
the ventral intermediate nucleus (VIM) has been the traditional neu-
rosurgical treatment for tremor in ET. Though it has been suspected
that DBS may contribute to worsening gait performance, the conse-
quences of DBS on gait performance in ET are not yet clear.
Methods: Seventeen consecutive ET patients receiving unilateral
VIM-DBS were recruited. The patients walked on a treadmill for five
minutes at preferred walking speeds and completed the Fahn-Tolosa-
Marin Tremor Rating scale (TRS). Gait performance and gait variabil-
ity magnitude (coefficient of variation) were evaluated for the follow-
ing spatiotemporal variables: stride length, stride time, step length,
step time, step width, single support time, double support time, and
swing/stance time ratio. Gait variability structure was determined
using a detrended fluctuation analysis technique. Differences in gait
performance and variability were investigated in one condition before
surgery and in two conditions after surgery (on/off stimulation).
Results: From baseline to On DBS, changes in step time coefficient
of variation (CV) and changes in single support CV and swing/stance
ratio CV from baseline to On DBS were all significantly related to
changes in postural trunk tremor severity. From baseline to On DBS, the
change in postural tremor severity of the more affected upper extremity
was a significant predictor of changes in step length CV (p < 0.01).
Conclusions: Our study suggest that changes in tremor severity
may be associated with changes in gait performance after unilateral
VIM-DBS.
1463
Non-motor symptoms of essential tremor are independent of
tremor severity and have an impact on quality of life
T. Musacchio, V. Purrer, A. Papagianni, A. Fleischer, D.
Mackenrodt, C. Malsch, G. Gelbrich, F. Steigerwald, J. Volkmann,
S. Klebe (W
urzburg, Germany)
Objective: We present the results of a variety of neuropsychiatric
tests and their impact on quality of life in a community based cohort
of ET patients.
Background: In the last years several publications focused on
accompanying non-motor symptoms (NMS) in ET patients. Until
now it remains unclear if the NMS are an intrinsic part of the disease
itself or if they are a secondary phenomenon.
Methods: Participants were recruited by a newspaper article
about ET published in the local media and the Internet. Tremor was
clinically classified regarding the TRIG criteria. All participants had
to fill out the self-questionnaires SF36, AES, STAI-T and ESS and
underwent neuropsychiatric testing with FAB, PANDA-cognition and
BDI. To compare differences between cases and controls the Stu-
dents t-test with Bonferroni-Holm post hoc test was used. Spear-
mans correlation coefficient for correlations was used.
Results: 110 patients with definite or probable ET were enrolled.
Our patients showed no significant changes in the physical compo-
nent score (PCS) of SF36 with 2.3 [Confidence interval (CI) 0.4;
Movement Disorders, Vol. 30, Suppl. 1, 2015
S564 POSTER SESSION
4.2] but a highly significant reduction of -6.4 [CI -8.5; -4.3]
(p<0.001) points in the mental component score (MCS) compared
with age matched German healthy controls (HC). Overall MCS did
not significantly correlate to any attribute of study population. Com-
pared to normal controls the mean total score in AES was increased
by 9.5 [CI 6.6; 12.5] points to 33.0 (p<0.001). STAI-T was 39.8 and
significantly increased by 3.7 [CI 1.6; 5.9] points (p50.001) com-
pared to HC. Results of FAB testing showed a highly significant
change of -1.0 [CI -1.5;-0.7] (p<0.001) points to a mean score of
16.2 points. In PANDA-cognition compared to HC we obtained a
highly significant (p<0.001) decrease of -4.3 [CI -5.8; -2.9] points to
a mean score of 19.3. Only PANDA-cognition correlated to FTRS,
for all other significant changes we could not obtain this correlation.
Conclusions: In our view the significant changes in the neuro-
psychiatric test battery and QoL expresses itself a degree of illness.
Our observation that this is above all caused by mental suffering can
be explained with the presence of the reported neuropsychiatric deficits
(apathy, anxiety, frontal executive dysfunction) as a subclinical non-
motor phenotype. In the future NMS should carefully be explored in
ET patients because they might have an impact on QoL and treatment.
1464
Possibility of differential diagnosis between functional and
organic tremor
N.M. Pavlyshyna, O.M. Stoyanov (Odessa, Ukraine)
Objective: Making differential diagnosis between functional and
organic Movement Disorders. Definition of autonomic nervous sys-
tem functional status in patients with functional and organic tremor.
Background: Tremor is the most common and most affordable
for objectification shaking hyperkinesis. It occurs in healthy people,
or as a symptom in most cases of neurological disorders.
Methods: Two patients groups were examined: 1st group - 25
patients with functional tremor (somatoform autonomic dysfunction
(SAD)), 2nd group - 21 patients (chronic brain ischemia CBI)).
Patients age was between 30 - 55 years. Tremor was studied by
Tremor detector A.C. USSR @1695885. Were investigated the num-
ber of touches, total time of all touches. And tremor index (TI) was
calculated.
Results: Visually defined and subjectively perceived trembling of
hands and fingers was registered in 18 (32.2%) patients. In cases of
CBI - 8 (38%) patients had kinetic tremor with elements of intention,
in cases of SAD - 8 (32%) patients had unstable, mainly postural
tremor. In time of emotional stress tremor had always aroused.
In cases of SAD average value of TI 5 1, 43 60, 05, in the case
of sympathicotonia these rates were highest - 1, 7 6 0, 033, eutonia -
1, 3 6 0, 045, vagotonia - 1, 0 6 0, 04. In cases of CBI average value
of TI 5 2, 2 6 0, 045, when expressed sympathicotonia - 2, 5 6 0,
05, eutonia - 2, 2 60, 05, vagotonia - 2, 0 60, 033.
Conclusions: Study of tremor by Tremor Detector really allows
to make differential diagnosis between functional and organic Move-
ment Disorders, being that were obtained reliably different data in
both groups. Autonomic nervous system really influence on the pres-
ence and characteristics of tremor. The lowest data of TI were
obtained in patients with somatoform autonomic dysfunction in case
of vagotonia, middle rates of TI were in patients with amphotonia in
both groups, the highest data were in patients with CBI in case of
sympathicotonia.Increasing of TI provides a basis to think about
growth of disadaptative motor components as a consequence of their
transition from functional disorders of nervous system (1st group) in
organic (2nd group).
1465
Functional connectivity in the sensorimotor cortex in Parkinsons
patients with and without tremor
S.E. Qasim, C. de Hemptinne, N. Swann, P.A. Starr (San Francisco,
CA, USA)
Movement Disorders, Vol. 30, Suppl. 1, 2015
Objective: To characterize the changes in cortical functional con-
nectivity during spontaneous epochs of Parkinsonian resting tremor.
Background: Resting tremor of 4-8 Hz is one of the cardinal
motor signs of Parkinsons disease (PD). Tremor is mysterious in
that it fluctuates spontaneously, does not increase in severity with
increased dopamine denervation (though some denervation is neces-
sary for tremor to occur), and never occurs in 1/3 of PD patients. PD
is characterized by increased neuronal synchronization in the motor
network, but it is unclear whether tremor represents a compensatory
mechanism for this or a primary manifestation. Here we utilize intra-
operative electrocorticography (ECoG) during spontaneous epochs of
tremor and rest, to understand tremor-related alterations in cortical
synchronization.
Methods: We studied 8 PD patients who had experienced inter-
mittent resting tremor during awake implantation of a deep brain
stimulator. Patients were temporarily implanted with either a 6 con-
tact (n 5 4) or 28 contact (n 5 4) ECoG strip over sensorimotor cor-
tex for the duration of the surgery. We calculated average coherence
between contacts spanning the premotor and sensorimotor cortices,
in the theta, alpha, beta, and broadband gamma frequency ranges,
during spontaneous epochs of rest and tremor and compared these
values within subjects.
Results: We compared coherence across three areas: premotor,
hand area of primary motor (M1), and hand area of somatosensory
cortex (S1). We found increased coherence during epochs of tremor,
limited to the beta frequency range, between M1 and PMC. There
were no significant coherence differences in any frequency range
between M1-S1 and PMC-S1 when comparing rest and tremor
epochs.
Conclusions: Excessive beta synchronization is thought to play a
role in PD, and our results indicate that tremor is associated with
increased synchronization at the cortical level and is thus unlikely to
represent a compensatory phenomenon. The involvement of premotor
cortex is unexpected given the unintentional nature of resting tremor,
and supports the notion that a diffuse motor circuit contributes to
tremor genesis. Furthermore, the absence of change in functional
connectivity between sensory cortex and motor cortical areas during
tremor onset adds to existing evidence that sensory feedback is not
necessary for tremor genesis.
1466
Head tremor in essential tremor: Yes-yes, no-no, or round
and round?
D. Robakis, L.D. Elan (New York, NY, USA)
Objective: To determine the primary direction of head tremor in
essential tremor.
Background: Essential Tremor (ET) is one of the most common
Movement Disorders but it is also misdiagnosed approximately 30-
50% of the time. One contributing factor may be the lack of well-
described phenomenology. A clinical feature that has received little
attention is head tremor, which affects over one-third of patients
with ET, predominantly women. There are few descriptions in the
literature and no consensus regarding the predominant direction of
head tremor in ET. The existing reports suffer from small sample
sizes, are case reports, or were conducted prior to modern descrip-
tions of ET and other disorders causing head tremor such as
dystonia.
Methods: We identified 51 ET patients with head tremor who
were participating in a clinical-epidemiological study at Columbia
University. Each had their neurological examinations video recorded.
The patients head was observed while sitting quietly, reading, vocal-
izing, and performing hand maneuvers. Videos were viewed by a
Movement Disorders specialist and coded for clinical features. Head
tremor was categorized as either horizontal (no-no), vertical (yes-
yes), or mixed, which included multidirectional tremor and tremor
alternating between yes-yes and no-no. Tremor was categorized
as continuously, intermittently, or rarely present.
 POSTER SESSION
Results: Twenty-seven percent (n514) of cases fell into the
no-no category, 18% (n59) fell into the yes-yes category, and
55% (n528) were in the mixed category. Women comprised 23
(82%) of the 28 mixed cases, compared to 12 (52%) of 23 with uni-
directional tremor (chi-square 5 5.27, p50.02). Six of the mixed
tremor cases were predominantly no-no, 3 were predominantly
yes-yes, 9 were multidirectional, and the remainder alternated
between yes-yes and no-no. Tremor was continuously present tulinumtoxinA injection parameters in order to reduce functional
in 18/28 (64%) with mixed tremor, 1/9 (11%) with yes-yes
tremor and 1/14 (7%) with no-no tremor (chi-square=16.41,
p<0.001).
Conclusions: 1) There was no yes or no answer to the extremities (UE). In the past, focal therapy has reduced postural
question of head tremor: a mixed directionality is more common
than either a purely vertical or horizontal tremor. 2) Mixed
tremor was associated with female gender. 3) Mixed tremor was
more likely to be continuously present therefore, unidirectional
tremor may represent a precursor phenotype to mixed tremor. 4)
These findings may aide in the differential diagnosis of head
tremor.
1467
Unilateral palatal tremor in a patient with brainstem vasculitis
F.A.S. Sallem, S.C.B. Casagrande (S~
ao Paulo, Brazil)
Objective: To report on a 35-year-old female patient with unilat-
eral palatal tremor and discuss its relationship with a vasculitic
disorder.
Background: Palatal tremor may be a primary disorder or a sign
of lesions to the Guillain-Mollaret triangle in the brainstem. Unilat-
eral palatal tremor has rarely been described. We report on a young
female patient with unilateral palatal tremor due to a vasculitic
disorder.
Methods: A 35-year-old patient was seen at the neurology outpa-
tient office of our institution with dysphagia, hypogeusia, dysarthria
and dysphonia. She presented later on with diminished right face
sensibility and diplopia. She was further found to have a right palatal
tremor and left vocal cord palsy. [figure1]
Results: An MRI revealed a T2-hyperintense lesion in the right
cerebellar peduncle suggesting ischemic lesion. There was no inferior
ollivary hypertrophy. Digital subtraction angiography revealed a
beading aspect of the distal intracranial arterial segments, compatible
with cerebral vasculitis. The patient was treated with high-dose
methylprednisolone pulsotherapy with partial resolution of the
symptoms.
Conclusions: Unilateral palatal tremor is a rare disorder that
must be thoroughly addressed as it may carries an ominous diagnosis
which needs quick evaluation and treatment.
Fig. 1. (1467).
S565
1468
Longitudinal kinematic characterization of upper limb essential
tremor to effectively guide incobotulinumtoxinA treatment
O. Samotus, J. Lee, F. Rahimi, M. Jog (London, ON, Canada)
Objective: To demonstrate the use of kinematic
characterization of upper limb tremor for determination of incobo-
disability.
Background: Essential tremor (ET) is one of the most common
Movement Disorders which causes debilitating tremor in the upper
tremor severity but has not provided functional benefit. Multi-sensor
technology objectively distinguishes complex movements of upper
limb tremor which can be utilized for individualizing injection
patterns.
Methods: 24 ET participants attended a total of 13 visits and
were injected in UE every 16 weeks, totalling six injection cycles,
and attended a follow-up visit six weeks following treatment.
Clinical rating scales (item 20, 21 UPDRS, FTM, and QUEST)
and kinematic assessments were completed at each visit. Partici-
pants in a seated position performed two postural and two weight-
bearing functional tasks. Goniometers were placed over each UE
joint to quantify tremor severity, as RMS angular amplitude, into
directional components: flexion-extension (F/E), pronation-
supination, and radial-ulnar in wrist, F/E in elbow, and abduction-
adduction and F/E deviations in shoulder. Dosing and muscle
selection were determined using kinematic data and clinicians
experience.
Results: Action tremor score (UPDRS item 21) showed a statisti-
cally significant mean decrease of 68.0% at week 96. FTM tremor
severity displayed a similar significant reduction of rest, postural,
and action tremor by 41.7%, 80.6%, and 57.6%, respectively, at
week 96. Likewise, wrist postural and action tremor total RMS
amplitude significantly decreased by 86.4%. Handwriting and func-
tional performance (FTM parts B and C) significantly improved by
38.3% and 41.7%, respectively, at week 96. During this time, quality
of life (QUEST) significantly improved by 43.3%. Mild weakness
was experienced by less than 10% of participants and did not affect
arm function.
Conclusions: Kinematic assessment of tremor allows clinicians to
characterize multi-joint tremor for optimal selection of injection
parameters.
1469
Improvement of repeated Archimedes spirals in essential tremor:
Evidence for a learning effect?
N. Schuhmayer, C. Weber, M. Kieler, W. Pirker, E. Auff, D.
Haubenberger (Vienna, Austria)
Objective: To assess changes of spiral tremor amplitudes during
repeated spiral drawings.
Background: Essential Tremor (ET) is one of the most common
Movement Disorders among adults. Physiologic parameters charac-
terizing tremor objectively are amplitude and frequency. It has been
shown that scores derived from spiral drawings correlate well with
disability. To objectively assess spiral tremor, digitizing tablets have
been used to assess frequency and amplitude. However, manual tasks
can be subject to a learning effect and therefore confound changes
observed after treatment interventions. This effect needs to be quanti-
fied before a task can be applied to measure effects of treatment
interventions.
Methods: 40 subjects (24m), aged between 26 and 88 (mean
age 64.65), and diagnosed with ET participated in an electrophysi-
ological study characterizing features of ET. They were asked to
draw 10 Archimedes spirals per hand on a digitizing tablet. After
calculation of the velocity spectrum in the 1-20 Hz range, a peak
frequency was defined for each spiral and the average spectral
Movement Disorders, Vol. 30, Suppl. 1, 2015
S566 POSTER SESSION
amplitude of the 1/- 1Hz range computed. Changes of spiral
amplitudes over time were analyzed using repeated measures
ANOVA. For post-hoc comparisons between time-points, the Wil-
coxon Rank Test was applied.
Results: A significant change of amplitude over time in the domi-
nant (p50.01) and non-dominant hand (p50.01) could be demon-
strated. The median amplitude of the tenth spiral of the dominant
hand was 36.4% below that of the first one. Post-hoc analysis with
Wilcoxon Rank Test shows a significant difference in amplitude
between the first and the last spiral (p<0.001). These findings sug-
gest a learning effect after repeated Archimedes Spirals. Pairwise
comparisons suggest a stabilization of the amplitude in the dominant
hand after the fourth repetition.
Conclusions: Tremor amplitude was found to decline signifi-
cantly across the ten spirals using a digitizing tablet setup. We postu-
late that this improvement without any treatment intervention could
be explained by a learning effect. Post-hoc comparisons between
time-points suggest that spirals of the dominant hand tend to stabilize
after the fourth Archimedes spiral. This effect has to be accounted
for when measuring effects of treatment interventions on Archimedes
spirals in ET.
1470
Elderly onset essential tremor and cognitive impairment
H.A. Shill, J.G. Hentz, J.N. Caviness, E. Driver-Dunckley, S. Jacob-
son, C. Belden, M.N. Sabbagh, T.G. Beach, C.H. Adler (Sun City,
AZ, USA)
Objective: To examine the neuropsychological profile of elderly
onset essential tremor (ET) subjects and compare to a control popu-
lation without tremor.
Background: Previous population studies have shown that elderly
onset ET is associated with a greater risk of cognitive decline and
some small cross sectional studies of advanced, longstanding ET
show greater cognitive impairment than controls while others show
no increased cognitive impairment in ET.
Methods: Subjects with ET in the Arizona Study of Aging and
Neurodegenerative Disorders were compared with controls across a
variety of neuropsychological measures. Subjects with neurodegener-
ative disorders were excluded from both groups.
Results: There were 119 subjects with ET and 534 controls. ET
subjects were older than controls (80.4 6 7.0 vs 77 6 8.6, p<0.001)
with a mean tremor duration of 14 years. There was no difference in
MMSE, Judgment in Line Orientation (JLO), Clock Drawing, Stroop
Interference, Controlled Oral Word Association (COWA) and Audi-
tory Verbal Learning Tests (AVLT). Animal Fluency and Trail Mak-
ing A and B were significantly worse in ET subjects but these
differences disappeared after controlling for age and AVLT
improved significantly over controls. Separating out the elderly onset
ET (ET onset after age 65), there were 86 ET subjects with an aver-
Fig. 1. (1471).
Movement Disorders, Vol. 30, Suppl. 1, 2015
age age 82.0 6 5.9. Nearly identical findings were seen in this group
with age corrected scores being non-significantly different than con-
trols except for AVLT total learning which was better in ET
(p50.03).
Conclusions: This large cross sectional study does not support
that elderly onset ET is associated with greater cognitive
impairment.
1471
A patient with bilateral cerebellar tremors secondary to a
unilateral brainstem lesion
A.T. Tran, G. Moguel-Cobos, N. Salins, A. Deep, A. Lieberman
(Phoenix, AZ, USA)
Objective: To describe a patient with bilateral cerebellar tremors
secondary to a unilateral midbrain lesion.
Background: Mollarets triangle (MT), a classically described
anatomic model for palatal myoclonus, is also useful in the localiza-
tion of cerebellar tremors. The triangle consists of the dentate
nucleus of the cerebellum of one side connecting to the red nucleus
and the inferior olivary nucleus of the opposite side via the superior
cerebellar peduncle, the central tegmental tract and the inferior cere-
bellar peduncle, respectively.
Methods: A case study.
Results: A 42 year-old man developed a left sided cerebellar
tremor after a right midbrain bleed from a cavernous malformation.
Thirteen years later, he developed a right-sided cerebellar tremor
after another bleed in the same region from the malformation. He
now has bilateral cerebellar tremors. MRI of the brain, at the time of
the second bleed, [figure 1], revealed a right midbrain tegmental
lesion affecting the right cerebellar peduncle, the right substantia
nigra, and the right red nucleus.
The first bleed into the right red nucleus caused a contra-lateral
left-sided rubral tremor, illustrating the involvement of the contralat-
eral MT (the green triangle) [figure 2]). The second bleed into the
right superior cerebellar peduncle resulted in a right cerebellar
tremor, illustrating the involvement of a second MT on the ipsilateral
side (the red triangle in Figure 2). The involvement of two MT is
evident on MRI brain showing bilateral hypertrophic olivary
degeneration.
The involvement of the right substantia nigra in the second bleed
prompted a dopamine transporter (DAT) scan, which revealed a
complete loss of dopamine uptake in the right striatum. A trial of
levodopa resulted in no improvement in the tremor. Interestingly, the
patient had no clinical signs of Parkinsons disease. [figure1]
[figure2]
Conclusions: The MT model explains accurately how a unilateral
midbrain lesion can cause bilateral tremors.
 POSTER SESSION
Fig. 2. (1471).
1472
Induced jaw and hand tremor and their relationship with motor
asymmetry in Parkinsons disease
E. Wang, C. Considine, L. Verhagen (Chicago, IL, USA)
Objective: To examine (1) how the amplitude and frequency of
the induced jaw tremor via clenched jaw compare to those of the
induced hand tremor via holding a pen on each side of the body and
(2) To examine whether the intensity of the induced jaw tremor
would, like the induced hand tremor, correlate with the unilateral
pattern of onset and symptom severity over the course of PD (H&Y
1-3).
Background: The onset and symptom severity over the course
of PD follow a unilateral pattern including hand tremor (Djaldetti
et al, 2006; Jankovic, 2008). Clinically, we were able to make the
unilateral jaw tremor clearly detectable when the patients were
asked to clench their jaw, although it was subtler than the hand
tremor when the patients were asked to hold a pen. Two hypothe-
ses were tested in this pilot study: (1) the induced hand and jaw
tremor would exhibit similar tremor frequency (4-6 Hz); and (2)
the induced jaw tremor, like the induced hand tremor, would
exhibit greater intensity on the side of body that was with more
severe symptoms.
Methods: First, the hand and jaw agility was tested by alter-
nating motion rates. Next, the subjects were asked to clench
their jaw or hold a pen pretending to write and the induced
tremor was measured using Liftpulse, an IPhone application
(Lemoyne et al, 2010) and the dominant frequency and highest
amplitude of the tremor were recorded both real time and to a
website.
Results: The initial testing of 6 subjects (4 f, 2 m) with a mean
age of 65.6 (SD 9.33) years, a mean disease duration of 12.6 (SD
9.69) years and a mean H&Y stage of 2.5 (SD 1.22) showed encour-
aging results. Although no statistical tests were run due to the small
sample size, the data did show that the intensity measures of the
induced hand tremor and the induced jaw tremor coincide with the
side of the body presenting more severe motor symptoms. More sub-
jects are currently being tested.
Conclusions: The initial testing results seem to be in the direc-
tion as predicted although more subjects are needed to test the statis-
tical significance of the findings.
S567
1473
Saccade-related modulation of beta oscillation in the human
thalamus
A. Yugeta, W.D. Hutchison, R. Chen (Tokyo, Japan)
Objective: To investigate whether oscillations in the ventral
intermediate (Vim) nucleus of the thalamus in essential tremor
patients are modulated by saccades, and to compare the responses to
prosaccades and antisaccades. We hypothesize that antisaccades
would produce more prominent saccade-related beta-band desynchro-
nization (beta-SRD) than prosaccade.
Background: We reported beta-SRDs in the subthalamic nucleus
(STN) of Parkinsons disease (PD) patients and internal globus pal-
lidus (GPi) in primary dystonia patients during both prosaccades and
antisaccades. Since the STN, GPi and Vim thalamus are parts of the
basal ganglia thalamocortical loops, we expect that beta-SRDs also
occur in the Vim thalamus. Although saccade abnormalities caused by
thalamic lesions have been reported, saccade-related modulation of
oscillatory activities in the thalamus has not been studied in human.
Methods: We recorded the local field potentials from deep brain
stimulation electrodes implanted in the Vim thalamus in 4 essential
tremor patients 1 to 5 days after electrodes implantation when the leads
were externalized. One patient was implanted in the right and three
were in the left Vim thalamus. The patients performed visually guided
prosaccade and antisaccade tasks. We analyzed the Molet wavelet
power spectrum averaged on saccade onsets using bipolar derivations.
Results: The beta-SRDs were observed in the Vim thalamus just
prior to and during saccades during prosaccade tasks in all patients
and antisaccade tasks in two patients. Beta-SRDs during prosaccades
were observed in the contralateral or the ipsilateral Vim thalamus,
and in two patients bilaterally. Beta-SRDs during antisaccades were
observed in the ipsilateral Vim thalamus in one patient and bilater-
ally in another patient. The average onset of beta-SRDs was
181 6 247 [mean 6 SD] and 280 6 119 ms before the saccade onset
during prosaccades and antisaccades respectively. The average dura-
tion of beta-SRDs was 496 6 236 and 712 6 191 ms. The average
peak-gain of beta-SRDs was -4.5 6 0.84 and -5.5 6 0.94 dB.
Conclusions: Beta-SRDs were observed in the Vim thalamus of
essential tremor patients, similar to the STN in PD and the GPi in dys-
tonia patients. The onsets, duration, and peak-gain of beta-SRDs tended
to be earlier, longer, and deeper during antisaccades than prosaccades.
Movement Disorders, Vol. 30, Suppl. 1, 2015