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Movement Disorders

Vol. 30, Suppl 1, 2015, pp. S1S567

2015 International Parkinson and Movement Disorder Society S1

POSTER SESSION 1 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
Monday, June 15, 2015 3.66 1.1). The results revealed a significant widespread increase in
12:3014:00 baseline AAT in both the IPD phenotypes (TD and PIGD) and the
Grand Hall 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
Parkinsons disease: Neuroimaging and CVD groups when compared to controls.
neurophysiology Conclusions: Despite significantly fewer CV risk factors, IPD
subjects of both the TD and PIGD phenotypes had similar patterns
1 of diffuse, prolonged AAT to that of known CVD. Prolonged AAT
has been attributed to increased collateral circulation, chronic vasodi-
Neurovascular status in idiopathic Parkinsons disease; an MRI latation and/or increased tortuosity of vessels in other studies. Col-
study lectively these results provide evidence in a clinical setting of an
S. Al-Bachari, H.C.A. Emsley, R. Vidyasagar, L.M. Parkes (Man- alteration in NVS in IPD warranting further investigation.
chester, United Kingdom)
Objective: To determine whether novel magnetic resonance 2
imaging (MRI) techniques can reveal altered neurovascular status Apathy in Parkinsons disease (PD) as a disconnection
(NVS) in idiopathic Parkinsons disease (IPD) phenotypes, compar- syndrome A resting state fMRI study
ing findings to established cerebrovascular disease (CVD). S. Appel-Cresswell, A. Liu, S.J. Lin, N. Baradaran, T. Kang, J.Z.
Background: Vascular mechanisms are rapidly emerging as key Wang, M.J. McKeown (Vancouver, BC, Canada)
players in the neurodegenerative process in IPD in preclinical stud-
ies, yet results of clinical studies are equivocal. MRI arterial spin Objective: to improve the understanding of network pathology in
labelling (ASL) is rapidly emerging as a suitable, non-invasive tool PD apathy.
for quantifying cerebral haemodynamics including measurements of Background: Apathy is one of the most debilitating non-motor
cerebral blood flow (CBF) and arterial arrival time (AAT) and may features in PD yet underlying mechanisms are not entirely eluci-
help to overcome the discrepancies in clinical data. dated, preventing the development of much needed specific treat-
Methods: Participants were recruited into 4 study groups; the ments. Changes in limbic and variable other brain regions have been
tremor dominant [TD] IPD, postural instability and gait dominant identified to be associated with apathy. Although apathy implies a
(PIGD) IPD, CVD and control (C) groups. All participants under- network malfunction, studies so far have focused on individual brain
went a 3T MRI scan protocol including structural and physiological regions; connectivity and network characteristics of apathy are
measures of NVS including ASL. largely unknown.
Results: 12 subjects with CVD (manifesting as minor stroke or Methods: 13 subjects diagnosed with idiopathic PD but without
TIA within the previous 2 years), 19 TD IPD subjects (mean age depression (BDI <14) or cognitive impairment (MoCA<=26) were
67.2 6 0.6), 17 PIGD IPD subjects (mean age 70.7 6 6.6) and 23 C assessed with the Apathy Scale. Other clinical indices collected
subjects (mean age 65.1 6 5.7) completed the scanning protocol. included the UPDRS motor and H&Y scores, and dopaminergic
The number of cerebrovascular risk factors for the control (mean medication. Resting state fMRI (3T) in the OFF state was performed

Fig. 1. (1).

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


and connectivity inferred with Bayesian network analysis. Apathy scores Objective: To evaluate the volume of the corpus callosum on
were correlated with connection strength between two brain regions and structural magnetic resonance imaging (MRI) in Parkinsons disease
relevant connections were identified to predict apathy scores. (PD) subjects with varying degrees of cognitive impairment.
Results: Severity of apathy was positively correlated with the fol- Background: Approximately 80% of PD patients develop demen-
lowing connections: left (L) sup. frontal cortex (FC) to L middle FC tia (PDD), which is often preceded by a prodromal phase of mild
(p50.01), L sup. parietal cortex (PC) to L inf PC (p<0.05), L middle to cognitive impairment (PD-MCI). Neuroimaging studies in other
L inf. temporal cortex (TC) (p<0.05), L hippocampus to right (R) amyg- forms of cognitive impairment (e.g., Alzheimers Disease, amnestic
dala (p<0.05), L amygdala to L entorhinal (p<0.05). Negative correla- MCI) show volume loss of the corpus callosum, but little is known
tions were found for L to R inf. TC (p<0.01), L caudate to L accumbens about this structure in PD cognitive impairment. The corpus cal-
(p<0.01), R sup FC to R middle FC (p<0.01), L to R insula (p50.01), L losum is of particular interest given its critical role in interhemi-
lat. orbitofrontal cortex (OFC) to L insula (p<0.05), R supramarginal PC spheric communication and cognitive function.
to R post cingulate (p<0.05), L to R post central cortex (p<0.05), R ant Methods: 101 PD subjects and 25 healthy controls (HC) under-
cingulate cortex (ACC) to R inf FC (p<0.05), and R to L middle FC went clinical/neuropsychological evaluations and MRI brain scans.
(p<0.05). Predicted apathy scores based on the connectivity analysis cor- PD subjects underwent cognitive classification by The International
related to true apathy scores with 0.91. Apathy correlated with motor Parkinson and Movement Disorder Society criteria (cognitively nor-
severity and bradykinesia subscores but not with disease stage. mal (PD-NC), n529; mild cognitive impairment, n547; demented,
Conclusions: Apathy is a network disorder, mainly affecting con- n525). Z-scores for cognitive domains (attention/working memory,
nections between limbic and cognitive areas, despite the clinical corre- executive function, memory, language, visuospatial function) were
lation to motor severity and bradykinesia. In apathy, interhemispheric calculated. T1-weighted sequences were processed by FreeSurfer,
connections appear to be weakened whereas mostly local connections and volumes for total and corpus callosum subsections (anterior,
are strengthened, possibly acting as compensation. 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,
Cortical metabolic alterations underlying cognitive decline in correcting for multiple comparisons as appropriate. Stepwise regres-
Parkinsons disease sion analyses were performed on cognitive domain scores and cal-
T. Baba, Y. Hosokai, Y. Nishio, A. Kikuchi, T. Hasegawa, K. losal segment volumes.
Hirayama, K. Suzuki, M. Aoki, Y. Itoyama, S. Takahashi, H. Fukuda, Results: Total corpus callosal volume was smaller in PD subjects
A. Takeda, E. Mori (Sendai, Japan) than in HCs (p5.008), particularly in central (p5.003) and mid-
anterior (p5.008) segments. PDD showed smaller volumes than PD-
Objective: To clarify cortical metabolic pattern underlying longi- NC in mid-posterior (p5.025), central (p5.009), mid-anterior
tudinal cognitive decline in Parkinsons disease. (p5.014), and anterior (p5.002) segments. In the regression models,
Background: Cognitive impairment is common in patients with anterior callosal segment volumes showed the highest relationship
Parkinsons disease (PD). Mild cognitive impairment (PD-MCI) is with the cognitive domains.
thought as an intermediate stage before PD dementia (PDD). The Conclusions: The corpus callosum demonstrates atrophy in PD
International Parkinson and Movement Disorders Society (MDS) subjects compared to HCs. Among PD cognitive subgroups, smaller
recently published the criteria for PD-MCI. However, neuroimaging callosal volumes were found in more anterior regions and especially
evidence of progressive neuronal dysfunction associated with the those PD with greatest cognitive deficits. Greater anterior callosal
proposed neurocognitive stages is still lacking. atrophy in PD cognitive impairment may suggest abnormalities in
Methods: We analyzed the data from a 3-year longitudinal study connectivity, particularly to frontal cortical regions.
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 5
as PD-MCI and PDD based on the MDS criterias. We analyzed cort-
The role of the supplementary motor area in freezing of gait - A
ical metabolic alterations associated with longitudinal change in
theta-burst stimulation study in Parkinsons disease
these cognitive status by using SPM8 software (Wellcome Depart-
ment of Cognitive Neurology). F. Brugger, R. Wegener, S. Bohlhalter, E. Abela, S. H
agele-Link, J.
Results: At baseline, 29 patients were classified as cognitively Walch, G. Kagi (St. Gallen, Switzerland)
normal PD, and 17 patients fulfilled PD-MCI level I criteria. At Objective: To assess the role of the supplementary motor area
follow-up, 28 patients were classified as cognitively normal group, (SMA) in Parkinsons disease related freezing of gait (FOG) by
12 patients were classified as PD-MCI, and 6 patients were classified using a multimodal approach including i) a morphological, ii) an
as PDD. Dementia converting rate was much higher in the PD-MCI electrophysiological and iii) an interventional part.
group compared with that in the cognitively normal PD group Background: The SMA is crucial for the planning and control of
(17.6% vs 10.3%). All dementia converters showed metabolic abnor- complex motor sequences. Previous studies showed that structural
malities in bilateral parietal lobe at baseline independently of initial and functional abnormalities in this brain region are related to FOG
cognitive stage. in PD.
Conclusions: Current PD-MCI criteria is useful in predicting Methods: PD patients were categorized into freezers and non-
dementia in PD, but which yet offers a satisfactory predictive accuracy freezers according to the FOG questionnaire and the patients his-
for PDD. In this study, we demonstrated that cortical metabolic abnor- tory. Gait, FOG and FOG-associated parameters were assessed in the
malities in bilateral parietal lobe are associated with dementia conver- joint gait lab of the Kantonsspital and Childrens Hospital St.Gallen.
sion within 3 years. A combination of PD-MCI criteria and imaging FOG-provoking tasks included starting, passing tight quarter, turning
biomarker can improve predictive accuracy for dementia in PD. and reaching destinations. i) For morphological assessment grey mat-
ter changes (GM) were calculated using voxel-based morphometry
4 by the means of standardized 3T MRI scans. ii) For the electrophysi-
ological assessment of the SMA we recorded the Bereitschaftspoten-
Corpus callosal atrophy in Parkinsons disease tial in the off and on state. iii) For the interventional part we applied
I.O. Bledsoe, G.T. Stebbins, B.A. Bernard, J.G. Goldman (Chicago, bilateral intermittent theta burst stimulation (iTBS), a facilitating
IL, USA) rTMS protocol, over the SMA in the off state. Gait was analyzed

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


before and immediately after iTBS. The interventional part was Objective: The purpose of this study was to examine longitudinal
designed as a sham-controlled cross-over study. changes in resting state networks in Parkinsons disease (PD).
Results: 12 PD patients with FOG, 13 without FOG and 13 Background: Previous research on resting-state functional con-
healthy controls were analyzed. i) PD- and FOG-related gait character- nectivity in Parkinsons disease (PD) has consistently demonstrated
istics correlated with GM changes in the SMA with additional clusters disruption of cortico-striatal motor networks. Yet most studies have
in the frontal and parietal brain regions as well as the pedunculopon- focused on cross sectional evaluation and not determined whether
tine nucleus. ii) the late component of the BP showed smaller ampli- such alterations change over time.
tudes in PD patients with FOG. The administration of dopaminergics Methods: Resting-state BOLD scans (Seimens 3T Trio) were
led to group specific changes of early premotor and postmotor compo- obtained from non-demented PD participants (N 5 21) while off
nents of the BP. iii). Intermittent TBS resulted in significant changes medication and from controls (N 5 10), matched for age and head
of few gait parameters, particularly on turning tasks. movement. Follow-up resting-state BOLD scans were obtained
Conclusions: We conclude that cortical alterations not only in within 1-3 years after the initial scans. For each of the primary rest-
the SMA, but in a widespread network including frontal and parietal ing state networks (default mode, dorsal attention, control, salience,
brain regions are involved in the pathophysiology of PD-related gait somatomotor), composite scores were computed based on the corre-
impairment and FOG, respectively. However, specific BP patterns lations among network nodes and compared across groups and across
and alteration of FOG-associated gait parameters after iTBS over the time points.
SMA supports the notion that this brain region is essentially involved Results: PD participants demonstrated significantly lower func-
in locomotion. 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
A sensory geste-like movement to stop tremor in Parkinsons in functional connectivity within the default mode network (p 5 .03)
disease A clinical and electrophysiological case report and the dorsal attention network (p 5 .01). Interestingly, functional
F. Brugger, B. Balint, R. Erro, F. G
overt, E. Antelmi, J.C. Rothwell, connectivity of the somatomotor network in the PD participants did
K.P. Bhatia (London, United Kingdom) not change significantly (p 5 .76), whereas functional connectivity
increased in controls (p 5 .04). Controls had no other significant
Objective: To describe the clinical and electrophysiological fea- changes in network connectivity (all ps > .34).
tures in a patient with Parkinsons disease (PD) who uses a sensory Conclusions: These data demonstrate reduced cortical motor net-
geste-like movement to stop his tremor. work functional connectivity in PD. Within network functional con-
Background:: Resting tremor at a frequency of 4-6 Hz is a com- nectivity longitudinally decreased in the default mode network and
mon clinical sign in PD. Tremor intensity can be modulated by dif- the dorsal attention network in PD participants without further loss
ferent factors including stress, expectation, distraction as well as by in the cortical motor network. We speculate that such changes in
superimposed voluntary muscle activation (also known as re- cortical resting state networks may be sensitive to the non-motor fea-
emergent tremor). Sensory gestes as they are observed in dystonic tures associated with disease progression in PD.
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- 8
ing tremor. Surface EMG of the biceps and triceps was used to
Visual motor control in patients with Parkinsons disease
record tremor activity. NeuroSpec 2.0 software was used to analyse
time-dependent spectra and coherence. J. Chen, S.L. Ho, M.C. Lee, S.K. Chang, Y.Y. Pang, L. Li (Hong
Results: We report a 58-year old patient who came to medical Kong, Hong Kong)
attention due to a right-sided resting tremor of about 6 Hz. Tremor Objective: To understand how Parkinsons disease(PD) and anti-
activity was most prominent in the right biceps and triceps. Interest- Parkinsonian medication affect the perceptual and motor abilities in
ingly, he was able to stop his tremor by a slight touch of the right visual motor control using a control-theoretic approach.
hand with the contralateral hand, similar to a sensory geste in dys- Background: Although previous studies have suggested deterio-
tonic conditions. Auto- and crossspectra revealed maxima in the 6 rated visual motor control in PD is likely due to deficits in both the
Hz band at the time when the patient was showing the tremor. perceptual and motor systems, none of them has directly separated
Coherence analysis revealed a high synchronisation of muscle activ- the effects of deficits in the perceptual and neuromuscular systems
ity in the pair of antagonists within one second before he touched on visual motor control. In addition, no study has directly measured
the right hand and thus stopped the tremor. The frequency of the the effects of antiParkinsonian medication on the perceptual and neu-
muscle activity then shifted from the 6 Hz more towards a 15-25Hz romuscular systems for visual motor control.
band. Methods: We tested 20 PD patients ON and OFF mediation and
Conclusions: This PD patient shows an intriguing strategy to 20 healthy controls with a typical closed-loop compensatory manual
stop his resting tremor which rather resembles a sensory geste as it control task in which participants used a joystick to keep a red target
is observed in dystonic conditions. As the electrophysiological fea- centered on a CRT display (37 Hx21 V) as its horizontal position
tures change even before the patient touches the shaking hand, was perturbed by the sum of seven harmonically-unrelated sinusoids
expectation can be assumed to play an important role in the control (0.1-2.19Hz). The time series of target position and joystick displace-
of tremor here. The occurrence of muscle activity in the 15-25 Hz ment were Fourier analyzed and averaged across six trials. The per-
frequency band relates to voluntary muscle activation and is thought formance data were fit by an extensively validated Crossover Model
to originate from the contralateral motor cortex. These results from (McRuer et al., 1965) to evaluate how PD and antiParkinsonian med-
the coherence analysis are of interest as they allow insights into the ication affect the perceptual system that processes visual information
modulation of tremor in PD. to generate the control command and the neuromuscular system that
executes the control command.
7 Results: Although antiParkinsonian medication improved visual
motor control in PD patients, they still showed significantly less con-
Disruption of resting state functional connectivity with trol precision (measured by RMS error) and response amplitude
Parkinsons disease progression (gain) as well as more response delay (phase) compared with the
M.C. Campbell, J.M. Koller, A.Z. Snyder, J.S. Perlmutter (St. Louis, healthy controls. The Crossover-Model-based analysis showed that
MO, USA) PD patients impaired visual motor control was due to (1)

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


deteriorated perceptual sensitivity to input visual error signal for showed more severe cognitive impairment, as they are frequent
online motor control, (2) impaired perceptual ability to anticipate the comorbidities.
input error to generate control response ahead of the error signal, Methods: 27 FOG1 patients (age 71.67 6 8.05), 21 FOG- (age
and (3) decreased stability of the neuromuscular system. AntiParkin- 70 6 5.81) and 21 healthy controls (age 66.24 6 7.16) were eval-
sonian medication improved the former two but not the latter. uated. FOG1 was defined as a score 1in the item 3 of the FOG
Conclusions: PD affects patients perceptual ability to process questionnaire (Giladi et al. 2000). A MRI study (3-T Magnetom Trio
visual information for online motor control and the stability of the Tim scanner, Siemens AG, Erlangen, Germany) was obtained in
neuromuscular system to execute the online motor control. The effect each participant. T1-MRI and DW-MRI images were obtained.
of antiParkinsonian medication on visual motor control appears to be Results were considered statistically significant at a conservative
primarily through improving perceptual processing. 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-
9 sion scale (p50.26). The neuropsychological variables were not dif-
The impact of amyloid deposition on brain network functional ferent between them, i.e., mean composite z scores for attention and
connectivity in Parkinsons disease working memory (p50.551), executive function (p50.808), memory
(p50.165), visuospatial function (p50.323) and (language p50.607).
L. Christopher, M. Criaud, A. Kucyi, Y. Koshimori, P. Rusjan, N.
Lobaugh, A.E. Lang, S. Houle, A.P. Strafella (Toronto, ON, Canada) Respect to controls, FOG1 and FOG- separately had a similar pat-
tern of impaired neuropsychological tests. The FOG1 group had lon-
Objective: The objective was to measure amyloid-b deposition in ger disease duration (9.93 vs 6.81 years; p50.02) and higher score
the brain with [11C] Pittsburgh compound B (PIB) PET in Parkin- in the UPDRS-II (20.93 6 7.75 vs 12.57 6 6.39; p50.000), and
sons disease (PD) and whether this is associated with functional UPDRS-III (28.67 6 11.27 vs 18.43 69.60; p50.02). Compared with
connectivity (FC) changes in core neurocognitive brain networks. controls, FOG1 group had a reduction of GM volume in the in right
Background: The presence of amyloid in the brain has been inferior temporal, fusiform, Heschls, inferior frontal and superior
linked to cognitive decline in PD. There is growing evidence that parietal gyri, in the right temporal pole, superior temporal sulcus and
amyloid deposition contributes to alterations in the FC of brain net- right/left amygdala. No difference between FOG1 and FOG- and
works in healthy aging and neurodegenerative diseases. Cognitive between FOG- and controls were observed. TBSS did not reveal any
decline in PD could be associated with amyloid deposition and the significant difference in WM among groups.
resulting effects on brain network function. Conclusions: To our knowledge, this is the first study comparing
Methods: PD patients (n58) were recruited and each underwent groups of FOG1 and FOG- patients with a similar cognitive profile,
a [11C] PIB PET scan to measure amyloid retention and resting state showing that there are no differences in GM or WM between them.
MRI scan to measure FC in comparison to a group of healthy con- In contrast, the presence of FOG is associated with GM atrophy
trols. [11C] PIB non-displaceable binding potential (BPND) was mainly in the right hemisphere, in areas involved in cognitive proc-
measured in the cortex and striatum. Regions demonstrating essing such as the temporal areas as well as in amygdala bilaterally.
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. 11
Results: [11C] PIB BPND was highest in the striatum and the Cerebral mechanisms underlying initiation and propagation of
cingulate cortex in PD. [11C] PIB binding in the striatum was asso- Parkinsons tremor A dynamic causal modeling study
ciated with reduced FC between the ACC and frontal pole/superior
M.F. Dirkx, H.E. Den Ouden, E. Aarts, M. Timmer, R. Cools, R.A.
frontal gyrus. [11C] PIB in the striatum was also associated with
Esselink, B.R. Bloem, I. Toni, R.C. Helmich (Nijmegen, Netherlands)
reduced FC between the right DLPFC and the bilateral lateral occipi-
tal cortex/angular gyrus as well as the bilateral precuneus. [11C] PIB Objective: To determine the cerebral mechanisms underlying
in the cingulate cortex was associated with reduced FC between the causation and propagation of Parkinsons resting tremor.
right DLPFC and the frontal pole, angular gyrus and right ACC. Background: Resting tremor in Parkinsons disease is linked to
Conclusions: Our findings demonstrate an association between pathophysiological changes both in the basal ganglia and in the
level of [11C] PIB binding in the striatum and cingulate cortex, and cerebello-thalamo-cortical circuit. We previously showed transient
reduced FC between networks, primarily between the executive and brain activity at the onset of tremor episodes in the internal globus
salience networks, and between the executive and default mode net- pallidus (GPi), and tremor amplitude-related activity in the cerebello-
works. Striatal [11C] PIB was also associated with reduced FC thalamo-cortical circuit. This led to the hypothesis that pathological
within the central executive network. [11C] PIB was not associated activity in the basal ganglia drives the cerebello-thalamo-cortical cir-
with any increases in FC. These findings suggest that amyloid depo- cuit into producing tremor. This hypothesis remains to be tested,
sition contributes to reductions in FC within and between cognitive because the presence of tremor-related activity may be the cause or
brain networks in PD. 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.
10 Methods: Using concurrent functional MRI and electromyogra-
Gray matter changes in Parkinsons disease with freezing of gate phy (EMG), we tested two independent cohorts of tremor-dominant
M. Delgado-Alvarado, L. Garca-Penton, H. Jim enez-Urbieta, B. Parkinsons patients (n519 and n522). We compared four different
model families where transient activity at the onset of tremor epi-
Gago, C. Caballero, M. Carreiras, M.C. Rodriguez-Oroz (San
sodes (assessed using the EMG regressor) influences the tremor cir-
an, Spain)
cuit either through the GPi, motor cortex, thalamus, or cerebellum.
Objective: To investigate differences in white (WM) and gray Furthermore, we tested whether the GPi influences the cerebello-
matter (GM) integrity between patients with Parkinsons disease thalamo-cortical network through the motor cortex or the cerebellum.
(PD) with freezing of gate (FOG1) and without FOG (FOG-) with a Results: We found that in both cohorts, activity at the onset of
similar cognitive profile. tremor episodes causally influenced the tremor circuit through the
Background: FOG is one of the most disabling features of PD GPi. The magnitude of the influence was larger in patients with a
whose pathophysiology remains unclear. MRI studies have shown more dopamine-responsive tremor. Finally, the GPi causally influ-
that FOG1 patients have more cerebral GM and WM abnormalities enced the cerebello-thalamo-cortical circuit through the motor cortex,
than FOG- patients. However, in these studies FOG1 patients not the cerebellum.

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


Conclusions: Our findings indicate that the basal ganglia initiate stimulus conditions were randomized in 3 blocks of 100 trials with
tremor in the cerebello-thalamo-cortical circuit through the motor random interstimulus interval. Participants were asked to press a but-
cortex. This suggests that tremor may be treated by uncoupling the ton in response to all stimuli. Reaction times were computed for
basal ganglia from the cerebello-thalamo-cortical circuit. The differ- each stimulus condition and the Miller Race model was tested to
ence between patients with relatively dopamine-resistant and evaluate the multisensory integration contribution to the audiovisual
dopamine-responsive tremor suggests that regions outside the basal condition. A regression analysis was performed to assess for correla-
ganglia may trigger dopamine-resistant tremor. 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
12 Miller Race model revealed that audiovisual responses were facili-
Derivation of a levodopa-related pattern with metabolic imaging tated by enhanced multisensory integration. To account for variabili-
in idiopathic Parkinsons disease ty in motor response times, the auditory and visual reaction times
C. Dresel, C. Tang, D. Eidelberg (Manhasset, NY, USA) were normalized by subtracting the audiovisual reaction time. A
regression analysis showed that the normalized visual reaction time
Objective: To derive a Levodopa-related pattern (LDRP) from correlated with disease duration (r=0.62, p<0.05), whereas the nor-
metabolic brain images in patients with idiopathic Parkinsons dis- malized auditory reaction time correlated with multisensory integra-
ease (PD). tion measures (r=0.69, p<0.05).
Background: Principle component analysis (PCA) allows extract- Conclusions: Sensory processing is altered in PD with slower visual
ing disease-related spatial covariance patterns by comparing [F-18]flu- reaction times and patients becoming more reliant on the auditory modal-
oro-deoxy glucose positron emission tomography (FDG PET) images ity for multisensory processing. The changes in visual processing speed
between patients and healthy subjects. These patterns may serve as bio- correlate with disease duration and contrast with healthy older adults
markers for better differential diagnosis or prognosis of PD or other who tend to have faster visual reaction times and visual dominance for
neurodegenerative disorders, as well as for objective evaluation of ther- multisensory integration. These findings support progressive adaptive
apeutic interventions. For example, levodopa (LD) modulates the sensory processes in PD, which differ from that of normal aging.
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- 14
terns of monotonic changes within subjects across conditions or over Transcranial static magnetic field stimulation (tSMS) decreases
time. The goal of the present study is utilizing the OrT/CVA method to cortical excitability in Parkinsons disease
derive an LD-related pattern that is less dependent on the underlying G. Foffani, M.C. Carrasco-L opez, J.C. Segundo-Rodriguez, N.
PD pathology and more specific for the therapeutic intervention itself.
opez-Ariztegui, F. Alonso-Frech, M.J. Catalan-Alonso, A. Oliviero
Methods: We applied OrT/CVA to FDG PET scans of a heteroge-
(Mostoles, Spain)
neous group of 15 PD patients with moderately advanced disease
acquired before and after LD treatment. An LDRP was derived to cap- Objective: To test the hypothesis that transcranial static magnetic
ture levodopa-specific metabolic changes in the brain of PD patients. field stimulation (tSMS) reduces motor cortex excitability in patients
Results: OrT/CVA on this preliminary PD sample revealed a sig- with Parkinsons disease.
nificant LDRP (p<0.005, non-parametric permutation test) character- Background: We recently introduced tSMS as a novel non-
ized by LD-induced metabolic decreases in the bilateral pons, pharmacological, non-invasive, DBS-compatible, low-cost neuromodu-
midbrain and posterior putamen, and concurrent metabolic increases lation technique to decrease cortical excitability in humans (Oliviero
in the inferior parts of the primary sensorimotor cortex. Bootstrap re- et al., J Physiol 2011). The present study is the first step of a larger project
sampling of the data demonstrated a significant stability of this pat- that aims to test the therapeutic potential of tSMS to manage levodopa-
tern (inverse coefficient of variation ICV=[-2.50, 12.39], p<0.008). induced dyskinesias, supported by the Michael J. Fox Foundation.
Conclusions: The LDRP contains regions known to be involved in Methods: A randomized double-blind sham-controlled cross-over
or linked to nigrostriatal dopaminergic neurotransmission and LD study was performed to assess cortical excitability before and imme-
pathology. In the long run, this pattern may allow for direct and puta- diately after 10-min of tSMS or sham applied to the motor cortex in
tively more accurate assessment of treatment-associated changes in PD. patients with Parkinsons disease. Patients were studied off medica-
It may be used as an imaging biomarker for monitoring LD effects or tion after overnight withdrawal of dopaminergic drugs. Cortical
for developing customized treatment plans for individual patients. 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
13 interosseus (FDI), which was the hot spot, and the abductor pollicis
Differential audiovisual processing in Parkinsons disease brevis (APB). The EMG background was used to exclude trials with
C. Fearon, J. Butler, C. McDonnell, I. Killane, R. Reilly, T. Lynch muscle pre-activation, often present in tremulous patients.
(Dublin, Ireland) 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
Objective: To investigate auditory and visual processing in Par- in the first 4 min after tSMS compared to sham (FDI, 6.9 6 16.9%,
kinsons disease using an audiovisual task. paired t-test p50.0415; APB, 0.6 6 31.1%, p50.0102).
Background: Altered visual processing occurs in PD, as evi- Conclusions: These preliminary results suggest that tSMS is able
denced by both clinical and electrophysiological data, often correlat- to decrease cortical excitability in Parkinsons disease.
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 15
multisensory gain attributed to the visual modality. This is likely a Comparative study of anatomical connectivity of prelemniscal
strategy to compensate for loss of peripheral sensory processing but radiations in healthy subjects and Parkinsos disease patients
may be maladaptive. We hypothesize that a similar adaptive process M.G. Garca-Gomar, F. Velasco, L. Concha (Queretaro, Mexico)
occurs in PD to compensate for loss of automaticity of movement.
Methods: We studied PD patients under three stimulus condi- Objective: Characterize the anatomic connectivity of prelemnis-
tions: auditory, visual and audiovisual. Participants were presented cal radiations (Raprl) and identify differences in the fiber populations
with a tone or a red disc or both simultaneously on a laptop. The that conform the Raprl using probabilistic tractography.

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


Background: The Raprl have been proposed as a neurosurgical responses in the cohort of freezers in key regions that have previ-
target for deep brain stimulation (DBS) for the treatment of PD since ously been associated with turning and freezing of gait, such as fron-
1970s. Despite its clinical usefulness the anatomic connectivity of tal regions, even when behavioral freezing episodes were removed
the Raprl remains unknown. (p < 0.001; k > 10). Peak ROI analyses also revealed highly signifi-
Methods: Images from 12 healthy subjects and 6 PD patients cant functional connectivity between the bilateral mesenchephalic
were acquired using a 3T Philips Achieva scanner. Diffusion- locomotor regions during periods of turning in the group of freezers.
weighted images were acquired using 120 unique diffusion-gradient Conclusions: Combining fMRI with a virtual reality task allowed
directions with b=2000s/mm2 (voxel size of 2x2x2mm3). Con- for the investigation of neural correlates underlying turning deficits
strained spherical deconvolution was performed, followed by the cre- in patients with Parkinsons disease and freezing of gait.
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- 17
lamic structures. We seeded 50000 streamlines at the level of the
Raprl, differences of streamlines interconnecting the Raprl between White matter abnormalities as a marker of Parkinsons disease
groups were assessed by Students t-test. cognitive impairment: A diffusion tensor imaging study
Results: All subjects showed Raprl connectivity with cortical and J.G. Goldman, D. Merkitch, B. Bernard, G.T. Stebbins (Chicago, IL,
subcortical structures, when these fiber bundles enter the posterior USA)
limb of internal capsule they show a clear spatial organization
Objective: To investigate markers of white matter (WM) micro-
according to their targets, from anterior to posterior as follows: 1)
structural integrity across the Parkinsons disease (PD) cognitive
orbitofrontal cortex, 2) globus pallidus (GP) 3) supplementary motor
spectrum using diffusion tensor imaging (DTI) measures of fractional
area and 4) primary motor cortex and cerebellum. In 87.5% of
anisotropy (FA) and mean diffusivity (MD).
healthy subjects GP showed connectivity with the contralateral dorsal
Background: Dementia develops in about 80% of PD patients in
brainstem in a region that corresponds to the location of the contra-
longitudinal studies. Abnormalities in WM may contribute to PD
lateral pedunculopontine nucleus (PPN), the same connectivity pat-
cognitive impairment and can be identified with neuroimaging tech-
tern is present in 83.3% of PD patients. The number of reconstructed
niques. Thus, DTI holds promise as a biomarker for advancing our
streamlines obtained showed differences between groups in the con-
understanding of the neural substrates of PD cognitive impairment
nectivity to pallidum (left p50.017, right p50.045) and in thalamus
and for identifying those at risk for PD cognitive decline.
(left p50.02, right p50.006).
Methods: Sixty-three PD patients underwent clinical/neuropsy-
Conclusions: PD patients that have undergone Raprl-DBS show
chological evaluations, T1- and diffusion-weighted magnetic reso-
an improvement on gait that also occurs after unilateral GP-DBS,
nance imaging brain scans, and cognitive classification by the
which could be explained because of the bilateral connections from
International Parkinson and Movement Disorder Society criteria
Raprl to PPN through fibers crossing the midline at lower midbrain.
(cognitively normal (PD-NC), n520; mild cognitive impaired (PD-
Our findings provide new insights into subthalamic connectivity that
MCI), n528; demented (PDD), n515). DTI data were processed
allow explaining clinical benefits obtained after Raprl-DBS.
with mrDiffusion, and wholebrain comparisons of the resulting
smoothed FA and MD maps, controlling for PD duration, were ana-
16 lyzed in SPM8 (p<0.001, uncorrected, k=10).
Results: The groups differed in PD duration (mean [SD]: PD-NC
Neural correlates underlying turning during a virtual reality task 8.8 [3.6], PD-MCI 9.4 [4.2], PDD 13.4 [5.5] years, p50.007), but
in patients with Parkinsons disease and freezing of gait not in gender, age (73.4 [6.2] years) or education (15.3 [3.1] years).
M. Gilat, J.M. Shine, J.M. Hall, C.C. Walton, S.J.G. Lewis (Sydney, The PD-MCI group showed decreased FA in frontal, temporal, parie-
Australia) tal, and occipital lobes, including the anterior corona radiata, anterior
thalamic radiation, inferior fronto-occipital fasciculus, and uncinate
Objective: To investigate the pathophysiology underlying turning
fasciculus, and increased MD in frontal, parietal, and temporal lobes,
as a trigger for freezing of gait in Parkinsons disease.
including the superior longitudinal fasciculus, compared to PD-NCs.
Background: Difficulty with turning often causes injuring falls in
The PDD group had decreased FA in similar regions but also the
Parkinsons disease patients. More specifically, turning is recognized
posterior corona radiata, and increased MD in frontal, temporal/pari-
to be the most provocative trigger for freezing of gait, a debilitating
etal, and limbic lobes, including corpus callosum splenium and supe-
symptom that affects around half of patients with Parkinsons dis-
rior longitudinal fasciculus, compared to PD-NCs. Comparisons of
ease. Previous studies have used fMRI in combination with saccade
PD-MCI and PDD groups revealed no significant FA/MD
tasks or gait imagery to better understand turning in Parkinsons dis-
ease, yet no consensus has been reached regarding its underlying
Conclusions: WM microstructural abnormalities occur in cogni-
tively impaired PD patients, particularly in those brain regions under-
Methods: This study therefore utilized a validated virtual reality
lying attention/working memory, executive function, memory, and
task in combination with fMRI to explore the neural correlates
visuospatial processing. Furthermore, greater disruption of WM path-
underlying turning in 17 Parkinsons disease patients with clinically
ways in posterior regions may signify greater PD cognitive impair-
confirmed freezing of gait and 10 non-freezers, both off their dopa-
ment and thus, provide a biomarker for impending cognitive decline.
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 18
right foot pedals. This allowed for BOLD responses and behavioral Attentional modulation of activity in the nucleus basalis of
footstep latencies to be compared between groups during periods of Meynert in patients undergoing deep brain stimulation for
straight walking and periods of turning. BOLD data was analyzed Parkinsons disease dementia and Lewy body dementia
using a mixed-effects analysis in SPM8.
J. Gratwicke, A. Oswal, S. Little, M. Beudel, V. Litvak, L. Zrinzo, M.
Results: Patients with freezing of gait were more variable and Hariz, P. Brown, M. Jahanshahi, T. Foltynie (London, United
experienced longer delays in their footstep latencies during the turn- Kingdom)
ing task compared to the non-freezers group (p < 0.05). In addition,
a significant group x task interaction effect revealed that compared Objective: To investigate the role of the human nucleus basalis
to straight walking, turning was associated with altered BOLD of Meynert (NBM) in mediating different modes of attention by

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


examining in vivo local field potential (LFP) recordings during the depending on the mode of attention employed and this modulation
resting-state and during two types of attention task. was distinct from that seen in GPi, which corresponded more with
Background: The NBM is the major source of cholinergic inner- motor components of the task.
vation to neocortex, and lies just below the globus pallidus internus Conclusions: Our data indicate that while activity in the human
(GPi) bilaterally. Lesions to the NBM in animals lead to impaired GPi reflects movement, activity in the human NBM is more closely
performance on attention tasks, implicating a key role for the NBM related to the mode of attention employed. Deficits in orienting and sus-
in this cognitive domain. However, how activity in the NBM relates tained attention are characteristic symptoms of both PDD and DLB,
to performance on attention tasks is unknown. and the NBM is known to degenerate severely in both conditions.
Methods: We recorded bilateral LFPs simultaneously from the Therefore, our data support the hypothesis that damage to the NBM is
human NBM and from the GPi in patients enrolled in two ongoing a mechanism underlying attentional impairments in PDD and DLB.
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 19
in the GPi directly above. Recordings were obtained during the rest- Structural and functional neuroimaging analysis of Parkinsons
ing state, and also while the patients performed two tasks; one test- disease
ing orienting of attention (Posners covert attention task), and the
other testing sustained attention (Sustained attention to response R.P. Guimar~aes, K. Larcher, L. Campos, L. Piovasana, P.C. Azevedo, Y.
task). Spectral analysis of the data was subsequently performed using Zeighami, A.C.F. DAbreu, F. Cendes, A. Dagher (Campinas, Brazil)
MATLAB software and open-source academic toolboxes. Objective: Our main purpose was to explore structural and func-
Results: Resting state recordings in all hemispheres demonstrated tional abnormalities in Parkinsons disease (PD) patients through
peaks in delta (0.1-3Hz) and theta (4-7Hz) activity in the NBM, resting state fMRI and cortical thickness analysis.
which progressively diminished as contacts moved up into the GPi. Background: Parkinsons disease (PD) is the second most neuro-
During task performance NBM activity was differentially modulated degenerative disease worldwide. Cortical Thickness (CT) and resting

Fig. 1. (19).

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


Fig. 2. (19).

state functional MRI (rs-fMRI) are well defined MRI techniques that gyrus, left gyrus rectus, right temporal pole, right fusiform gyrus,
assess the brains structure and functionality. Most studies use a right middle temporal gyrus, and right occipital gyrus (P<0.05).
Regions of Interest (ROI) based analysis, however ROI identification There were no areas of increased CT. Results are shown in [figure2].
is based on a priori hypothesis, and this approach is, to some degree, Conclusions: The structural and functional abnormalities found
prone to user-introduced bias. We employed a data driven approach in corresponding areas demonstrate that PD involves a great number
focusing on structural and functional abnormalities. of neuronal circuits, including areas responsible for visual process-
Methods: 58 patients with PD (60.31, SD 8.99) according to the ing. A better understanding of the involved areas may further refine
UK Parkinsons disease Society Brain Bank criteria were compared our comprehension of the disease and its clinical subtypes.
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 20
Kit) release 0.7 (Bellec et al. 2010, NIAK website), and CT data was Population analysis of beta band local field potential (LFP)
processed with the CIVET pipeline (version 1.1.10; Montreal Neuro- oscillations as a physiomarker in Parkinsons disease (PD)
logical Institute at McGill University, Montreal, Quebec, Canada). R. Gupta, S. Stanslaski, T. Denison, P. Stypulkowski (Minneapolis,
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 Objective: To investigate in a multi-center population of PD
[figure1]. For the CT analysis we stratified patients into 3 subgroups, patients the characteristics of the LFP oscillations in the beta band
early PD (EPD), moderate PD (MPD) and severe PD (SPD). (13-35 Hz) and their relevance as a physiomarker of PD.
The comparison between EPD and HC revealed decreased CT in Background: Abnormal synchronization in the beta band of
left superior temporal gyrus, left gyrus rectus and left olfactory cor- LFPs within the basal ganglia has been proposed as a pathophysio-
tex (p<0.05); MPD group, the areas with lower CT were right post- logical hallmark of PD. A population level analysis of this physio-
central gyrus, right SMA and right inferior frontal gyrus (P<0.05). marker across multiple centers with different surgical workflows is
SPD patients had significant lower CT in left inferior frontal gyrus, necessary to understand its generalizability and potentially learn
left precentral and postcentral gyrus, left SMA, left inferior frontal best-practices. Through our Activa PC1SV R brain sensing program,

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


we have the opportunity to look at a population database of LFP sig- gender, symptom duration, and striatal dopaminergic activity in the
nals from PD patients collected via a number of investigator- posterior putamen (p 5 0.010).
sponsored studies. Conclusions: These results suggest that dominant-side PD
Methods: We analyzed LFP data recorded from the STN of 17 patients have a greater neural reserve to cope with PD-related patho-
PD patients (4 centers) while the patients were asked to be awake logical changes (i.e., less motor deficits despite of similar dopamine
and at rest. Data were collected using a fully implanted chronic DBS reduction) compared to non-dominant-side patients.
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- 22
ing artifacts and then analyzed via power spectral analysis techniques
to investigate the frequency content. The changes of the visual evoked magnetic field using the
Results: A distinct peak in the beta band was detected in 12/17 magnetoencephalography and its connectivity using MRI in
patients (70.6%). Average amplitude of the peaks was 2.471/- 1.66 aging and Parkinsons disease
uV RMS (calculated as average over 1/-1 Hz around the detected M. Hirayama, Y. Fujisawa, S. Goto, J. Uemura, M. Hoshiyama, S.
peak). Considerable inter-center variability was observed in the Yamada (Nagoya, Japan)
amplitude of the peaks, possibly reflecting different surgical targeting
Objective: To clarify a pathophysiology of visual processes in
approaches and target placements. Furthermore, the peaks were
Parkinsons disease (PD), visual evoked magnetic cortical fields
often, but not always, consistent across different follow-up visits. A
(VEFs) and diffusion weighted MRI were recorded in patients with
subgroup analysis revealed that the contact pair with the highest beta
PD, age-matched healthy control and young subjects.
power matched the contact selected as the stimulation cathode to
Background: Patients with PD often complain hallucination,
deliver therapy. This is consistent with findings from prior studies.
which is one of the non-motor symptoms in PD. Histological degen-
The analysis also revealed that patients with higher beta power were
erative changes in retina and visual tract have been reported in
programmed to higher stimulation voltages, contrary to prevailing
patients with PD. Functional abnormality of the visual processes in
PD remains unclear.
Conclusions: Our data suggest the prevalence of a peak in the
Methods: Twenty nine healthy subjects (13 younger and 16
beta band to be 70.6% across a multi-center population of PD
elderly) and 10 PD patients participated in this study. We measured
patients. Both inter-patient and intra-patient variability were observed
visual evoked magnetic field (VEF) using the magnetoencephalogra-
in the characteristics of the beta band power. Such variability needs
phy (MEG). Checker pattern reversal (CPR) and monotonous grating
to be taken into consideration when designing algorithms that use
pattern (MGP) stimulation were used. MRI was performed to mea-
this physiomarker as a feedback signal.
sure the current source position estimation of VEF component and
analyzed brain size and tractogram. Cognitive function test, the smell
21 test and UPDRS were evaluated in the PD.
Results: Four VEF components (1M, 2M, 3M, 4M) were seen
Does side onset influence neural reserve in patients with until the stimulus after 250ms. In CPR stimulus, the latency of 2M
Parkinsons disease? and 3M had significantly delayed in the elderly, which compared to
J.H. Ham, Y. Lee, J.J. Lee, P.H. Lee, Y.H. Sohn (Seoul, Korea) the younger. The current of 1M, 2M and 3M were significantly
greater and the latency of 1M was delayed markedly in the PD,
Objective: Handedness is the most prominent human behavioral
which compared to the elderly. In MGP stimulus, no significant dif-
asymmetry.9 The dominant motor cortex (M1) has a greater disper-
ference between elderly and the younger was observed. The current
sion of elementary movement representations with more profuse hor-
of 1M was significantly greater than elderly. In the PD, 1M latency
izontal connections than does the non-dominant M1.10-12 Therefore,
correlated with UPDRS-1, 3 in both stimuli, and it also correlated
it is conceivable that the dominant hemisphere could have more effi-
with the smell test in CPR stimulus. Brain volume using MRI, no
cient motor networks with greater neural reserve to cope with patho-
difference was not observed, while diffusion tensor imaging was sig-
logical changes in PD. We performed this study to investigate
nificantly different between younger and elderly, but no difference
whether dominant-side onset PD has a greater neural reserve, and
was found between PD and elderly.
shows less motor deficits despite of similar pathological changes
Conclusions: It was suggested that conduction delay correspond-
than non-dominant-side onset PD.
ing to the checker stimulus occurred in peripheral than the primary
Background: Parkinsons disease (PD) symptoms do not develop
visual cortex. Degeneration of Midget cells might be involved in the
until 50-60% of dopaminergic neurons in the substantia nigra are
retina. It is suggested that degeneration of the retina with aging
lost, suggesting the presence of a significant neural reserve in the
occurred more in PD.
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 23
motor deficits despite similar degree of dopamine reduction than the Manifestation of Parkinsonian rest tremor is associated with
non-dominant hemisphere. changes in high frequency oscillation power in the subthalamic
Methods: We included the data of 157 consecutive, de novoPD nucleus
patients with documented right-handedness(mean age, 64.7 6 7.7 J. Hirschmann, M. Butz, C.J. Hartmann, N. Hoogenboom, J. Vesper,
years; range, 46 84 years; 47 men) who underwent dopamine trans-
L. Wojtecki, A. Schnitzler (D
usseldorf, Germany)
porter PETscans for an initial diagnostic work-up. Among them, 118
patients who showed significant asymmetry of motor deficits were Objective: To investigate the potential relationship between Par-
selected for the analyses. kinsonian rest tremor and high frequency oscillations (HFOs; 200 to
Results: Dominant-side patients (i.e., greater motor deficits on 500Hz) in the subthalamic nucleus (STN).
the right-side) showed significantly less motor deficits than non- Background: Neuronal oscillations in the STN are related to
dominant-side patients (18.0 6 8.1 and 22.9 6 10.1, respectively; motor control and undergo drastic changes in patients with Parkin-
p 5 0.005). Other variables including symptom duration and striatal sons disease. While alterations of oscillatory activity in lower fre-
dopaminergic activities were comparable between the two groups. A quency bands are well characterized, the role of HFOs is less clear.
general linear model showed this difference in motor deficits Recent findings suggest that HFO power is modulated by voluntary
remained statistically significantafter controllingthe patients age, movement and administration of levodopa.

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


Methods: Local field potentials were recorded from 17 STNs in 25

12 patients with tremor-dominant Parkinsons disease. Simultane-
ously acquired forearm EMG allowed for the identification of Impact of datscan on clinical decision making: Diagnosis and
tremor-containing and tremor-free epochs. Spectral power in the management of clinically uncertain Parkinsonian syndromes
HFO band was computed using a multi-taper approach and normal- J.R. Isaacson, S.H. Isaacson (Boca Raton, FL, USA)
ized by mean band power. For each STN, the channel with the high- Objective: To assess changes in clinical diagnosis and/or treat-
est HFO peak was selected for further analysis, and power and ment of 100 consecutive patients with clinically uncertain Parkinso-
phase-amplitude coupling were compared between tremor-containing nian syndromes who underwent DaTscan imaging with ioflupane for
and tremor-free epochs. striatal dopamine transporter degeneration.
Results: The average power spectra revealed a slow HFO rhythm Background: Clinically, the differentiation of Parkinsonism can
(sHFO) of around 260Hz and fast HFO rhythm of around 340Hz be challenging due to numerous factors, including symptom overlap
(fHFO). sHFO power was stronger in tremor-containing epochs than and variable response to treatment. It is not uncommon for patients
in tremor-free epochs, while the opposite was true for fHFO power. to be initially treated, but later to have diagnosis revised and treat-
Eight of eight peaks above 300Hz decreased during tremor, and ment changed. Striatal dopamine transporter is a marker of presynap-
seven of nine peaks below 300Hz increased during tremor. Notably, tic dopaminergic neuroterminals. Datscan imaging can identify loss
peak frequency was stable in all cases, i.e. the change in relative of striatal dopamine transporters, indicative of dopaminergic degen-
power was not due to peak shift. In addition, some STNs showed a eration. Striatal dopamine transporter imaging can help distinguish
clear change in beta-HFO PAC. However, this change was not sig- between Parkinsonian disorders with (PD, SND, PSP, etc) and with-
nificant on the group level. out (drug-induced, ET, vascular, etc) dopaminergic degeneration.
Conclusions: These results demonstrate an association between Methods: Retrospective ongoing analysis of 100 consecutive
STN HFO power and tremor manifestation. The data further support patients whose clinical diagnosis was unclear and in whom a Move-
the existence of two distinct HFO rhythms, which seem to be inver- ment Disorder specialist ordered DATscan imaging to clarify diagno-
sely related. The relationship reported here is strikingly reminiscent sis by determining whether dopaminergic degeneration was present.

of the association between HFO power and medication state (Ozkurt All patients had assessment of % likely abnormal scan prior to imag-
et al., Experimental Neurology 2011). Thus, it seems plausible that ing based on clinical examination and prior treatment response. After
changes in the sHFO/sHFO power ratio reflect dynamic changes of DaTscan imaging, changes to clinical diagnosis and treatment were
the endogenous dopamine level, which might influence the likelihood assessed.
of tremor emergence. 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
24 patients had a provional diagnosis changed. We identified several
clinical scenarios where Datscan imaging seem most useful: drug-
GBA variations accelerate degeneration of the nigrostriatal induced; prominent action tremor; lower extremity predominant;
pathway in Parkinsons disease: An [123I]FP-CIT study early subtle signs with nonmotor symptoms; and clinically stable
I. Huertas-Fernandez, S. Jesus, P. Gomez-Garre, F.J. Garcia-Gomez, and/or without fluctuations after 5 years. Changes in treatment fol-
I. Bernal-Bernal, M. Bonilla-Toribio, M.T. Caceres-Redondo, F. Car- lowed clarification of clinical diagnosis and whether dopaminergic
rillo, D. Garcia-Solis, P. Mir (Seville, Spain) degeneration was identified on Datscan.
Conclusions: In several clinical scenarios in which diagnosis of
Objective: To compare the [123I]FP-CIT SPECT between Par- Parkinsonian syndromes is unclear, visualization of striatal dopamine
kinsons disease (PD) patients with variations in glucocerebrosidase transporters using DaTscan can differentiate between disorders with
gene (GBA) and other sporadic PD cases. and without nigrostriatal dopaminergic degeneration, clarifying diag-
Background: PD patients with mutations in GBA show an ealier nosis and impacting treatment.
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 26
more affected in PD patients with variations in GBA. Cortical excitability changes induced by L-dopa mirror the
Methods: We included a total of 45 GBA variation carriers PD unbalanced nigro-striatal denervation in Parkinsons disease
patients and a control group of 60 non-carriers PD patients. We
I.U. Isaias, F. Turco, M. Rosanova, G. Marotta, G. Frazzitta, C.
stratified patients based upon disease durarion when underwent Landi, A. Perretti, L. Giusti del Giardino, M. Canesi, M. Massimini,
[123I]FP-CIT SPECT and compared age-matched groups in early G. Pezzoli, S. Casarotto (Wurzburg, Germany)
stages (27 GBA variation carriers and 30 non-carriers, mean 2 years)
and mid stages (18 GBA variation carriers and 30 non-carriers, mean Objective: To evaluate the effects of acute administration of L-
8 years). Images were processed and normalised to the MNI atlas dopa on cortical excitability in frontal and parietal cortices and to
with Statistical Parametric Mapping (SPM) and we calculated mean assess the asymmetry of this effect in relation to nigro-striatal dopa-
[123I]FP-CIT BPND in bilateral putamen, caudate, and nucleus minergic denervation.
accumbens. The inter-group statistics were done with T-test. Background: L-dopa is an effective and established treatment for
Results: We found in the subgroup of PD patients at mid stages Parkinsons disease (PD). However, its indirect effects on cortical
a decreased [123I]FP-CIT BPND in GBA variation carriers com- functions have not been fully uncovered, but could be very important
pared to non-carriers in bilateral putamen, caudate, and nucleus to understand the pathophysiology of some L-dopa-related adverse
accumbens. Differences were more pronounced in the regions ipsilat- effects (e.g. dyskinesia).
eral to the most-affected side (p<0.001) than those contralateral Methods: Thirteen PD patients were investigated by Single Pho-
(p<0.01). Conversely, no significant differences were found in the ton Computed Tomography (SPECT) and [123I]FP-CIT. The brain
early-stage subgroup comparisons. side (hemisphere H) with lower/higher striatal-specific binding ratio
Conclusions: This study shows that GBA variation carriers PD was labeled as H-/H1. Cortical potentials evoked (TEPs) by trans-
patients have a more severely affected nigrostriatal pathway in the cranial magnetic stimulation (TMS) were recorded by means of
mid stages. However, a similar affection is found in the early stages. high-density EEG (hdEEG) from each patient 12 hours after with-
Our results suggest that GBA variation carriers PD patients do not drawal of all dopaminergic drugs (meds-off) and at 90 minutes after
have a more aggressive onset than other sporadic PD but in few oral intake of 200 mg of fast-released soluble L-dopa (meds-on).
years they experience higher rates of degeneration. TMS was delivered to the supplementary motor area (SMA) and

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


superior parietal lobule (SPL) bilaterally. Cortical excitability was 28

measured by the immediate response slope (IRS) and immediate
response area (IRA) computed from TEPs averaged across region-of- Levodopa-induced changes in neurovascular reactivity in
interest neighboring channels. The effects of acute L-dopa intake Parkinsons disease
were measured as the percentage change of IRS and IRA (D%) V.A. Jourdain, F. Holtbernd, C.C. Tang, V. Dhawan, D. Eidelberg
between meds-off and meds-on conditions. D%IRS and D%IRA (Manhasset, NY, USA)
were compared between H- and H1 at the group level. Objective: To determine whether the difference in levodopa-
Results: The morphology of TMS-evoked potentials was similar induced increase in striatal levels of dopamine between dyskinetic
across patients and characterized by an early positive wave between and non-dyskinetic patients depends, at least in part, on functional
12-35 ms followed by a negative peak at about 45 ms. D%IRS and and structural alterations of the brain microvasculature.
D%IRA on the same side of the stimulation target was significantly Background: In our original study of 8 subjects without
higher in H- as compared to H1 only when SMA was targeted levodopa-induced dyskinesia (LID) and 3 with LID (Hirano et al., J
(p<0.05 for IRS; p<0.02 for IRA). The same analysis performed on Neurosci 2008;28:4201-9), we demonstrated that blood flow/metabo-
the opposite side of the stimulation target did not reveal any signifi- lism dissociation was created by levodopa in dopa-decarboxylase-
cant difference between H- and H1 for stimulation of either SMA or rich brain regions in putamen and internal globus pallidus (GPi), and
SPL. in the dorsal pons.
Conclusions: Acute administration of L-dopa specifically Methods: Eleven LID and 5 non-LID PD subjects, as well as 14
increases neuronal excitability of premotor cortex on the brain side healthy volunteers underwent dual tracer [15O]-H2O and [18F]-FDG
with greater nigro-striatal dopaminergic denervation. This study also PET to measure cerebral blood flow (CBF) and cerebral metabolic
demonstrates the feasibility of measuring cortical excitability in PD rate for glucose (CMR) at baseline (OFF) and during an intravenous
patients by means of TMS together with hdEEG. 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-
27 rent PD cohort to measure whether LID is associated with abnormal
hypercapnic response (an index of underlying capillary density) in
Differential diagnosis of Parkinsonism using two PD-related areas of levodopa-mediated flow metabolism dissociation.
metabolic patterns Results: The regions identified in the original voxel-based analy-
V.A. Jourdain, C.C. Tang, D. Eidelberg (Manhasset, NY, USA) sis were highly concordant with those identified in the new PD
cohort. As in the original study, significant levodopa-mediated flow
Objective: To determine whether individual subjects with idio- metabolism dissociation was also seen at the network level for the
pathic Parkinsons disease (PD) can be distinguished from atypical PD motor-related pattern (PDRP). When combining both cohorts (14
Parkinsonian syndromes (APS) based on differences in expression LID, 13 non-LID, 8 test-retest PD and 14 healthy controls),
values for established PD metabolic covariance patterns relating to levodopa-mediated flow metabolism dissociation was greater in LID
motor and cognitive disease manifestations. relative to non-LID subjects in the putamen/GPi, as well as the net-
Background: Accurate discrimination of patients with PD vs. work level. These results were mainly driven by an increase in CBF
APS (represented mainly by progressive supranuclear palsy (PSP) in the ON-state. Under normocapnic conditions, no difference was
and multiple system atrophy (MSA)) can be clinically challenging. observed between controls and PD or between LID and non-LID
We have found that PD is characterized by increases in PDRP and subjects. Normal and PD subjects both exhibited increased CBF dur-
PDCP expression, with greater expression of the former relative to ing hypercapnia with a significantly greater increase in LID patients.
the latter in individual subjects. However, these network changes are Conclusions: The findings suggest that LID subjects have greater
uncommon in APS. flow metabolism dissociation in response to levodopa treatment than
Methods: 167 Parkinsonian patients (96 PD, 41 MSA and 30 their non-LID counterparts. Moreover, the increase in capillary
PSP) with uncertain clinical diagnosis, in which 55 (30 PD, 11 MSA reserve seen with LID suggests that this side effect is associated with
and 14 PSP) had disease duration of 2 years, underwent FDG PET. underlying microvascular changes in key brain regions.
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 29
PDRP-PDCP, the difference in the two scores. Logistic regression Alternations of human brain connectome in Parkinsons disease
was followed by ROC analysis. Area under the curve (AUC) was using network based statistics (NBS)
used to determine the accuracy of delta PDRP-PDCP as a predictive A. Kamalian, M.H. Aarabi (Tehran, Iran)
classifier for PD, MSA, and PSP.
Results: Delta PDRP-PDCP was a significant classifier Objective: To determine impaired interconnecting fibers of
(AUC=0.82, p<0.0001) that distinguished PD from APS patients. A patients with Parkinsons disease using Diffusion Tensor Imaging
similar result was obtained (AUC=0.78, p50.002) in the short dura- (DTI) and a statistical approach Network Based Statistics (NBS)
tion patients. This measure, however, did not differentiate MSA from to analyze brain connectivity matrices.
PSP (AUC=0.52, p>0.57) in either the whole sample or the short Background: Neuroimaging is an accurate method to examine the
duration subgroup. Classification was overall less accurate with this areas engaged in PD neurodegeneration. Previous DTI studies had
logistic algorithm than with one based on individual subject scores used topological features e.g. degree and clustering coefficient to
for previously validated metabolic patterns for PD, MSA, and PSP investigate PD-correlated brain network alterations. However, we com-
(Tang et al., 2010). puted average tract length and fiber volumes as measures of white
Conclusions: Delta PDRP-PDCP is a potentially useful network matter integrity. In addition, we adopted a novel statistical approach to
classifier for the differential diagnosis of Parkinsonism. This measure conduct group connectivity analyses between PD patients and healthy
is consistently positive (delta>1) in classical PD, reflecting Braaks controls.
pathological timeline. In PD, relatively greater PDRP expression Methods: Data Acquisition:
may represent earlier subcortical involvement (analogous to Braak Data used in the preparation of this abstract were obtained from
Stage V), while consistently smaller PDCP levels reflect the later the Parkinsons Progression Markers Initiative (PPMI) database
development of neocortical pathology (analogous to Braak Stage VI). ( with permission. For up-to-date informa-
This network timeline, represented by delta PDRP-PDCP, is specific tion on the study, visit
for classical PD, thereby providing accurate differential diagnosis. Methods:

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


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


Fig. 2. (29).

performed using a stopping criterion of 0.2 FA and 30 curvature adjusting the window setting of the PET image, we could appreciate
threshold. The whole-brain fiber tract reconstructions of the previous the decreased uptake in the bilateral basal ganglia. Thus he was
step were parcellated using the automated anatomical labeling (AAL) finally diagnosed as juvenile Parkinsonism. Gene test confirmed that
atlas. By applying the ROI masks to the reconstructed fiber tracts his Parkinsonism was due to Park2 gene mutation.
using the ExploreDTI, the volume and average tract length that origi- Conclusions: Proper window setting is important during visual
nated in one ROI (i) and terminated in another one (j) was deter- assessment of dopamine transporter imaging.
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 31
(p-values < 0.05) were reported. Putaminal dopamine turnover in de novo Parkinsons disease
[Figure 1] predicts levodopa-induced motor complications
Results: The regions exhibiting significantly diminished intercon-
M. L
ohle, J. Mende, M. Wolz, B. Beuthien-Baumann, L. Oehme, J.
nections including: cingulum, hippocampus, parahippocampus,
van den Hoff, J. Kotzerke, H. Reichmann, A. Storch (Dresden,
olfactory lobe, occipital lobe, cuneus, and basal ganglia are pre-
sented extensively in Tables I,II, and Figure 2.
[Figure 2] Objective: To investigate the predictive value of baseline striatal
Conclusions: Our results confirm prior studies reporting fibers dopamine metabolism in de novo Parkinsos disease for the onset of
interconnecting olfactory lobe, occipital lobe, cingulum, hippocampus, later motor complications.
parahippocampus, and basal ganglia as major sites of damage in PD. 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-
30 logical and neuroimaging studies have not completely unravelled the
Importance of proper window setting on visual assessment of underlying pathogenesis of these complications, which hinders reli-
dopamine transporter image able prediction and potential prevention.
Methods: We performed a retrospective, observer-blind, long-
A. Kim, H.J. Kim, B.S. Jeon (Seoul, Korea)
term follow-up study in 31 patients with early, drug-nave Parkin-
Objective: To describe a young male patient with Park2 mutation sons disease, who had originally received quantitative 18F-dopa PET
whose FP-CIT PET was misinterpreted as normal initially. imaging to estimate striatal 18F-dopa uptake (Kocc) and effective
Background: Diagnosis of neurological conditions associated with dopamine distribution volume ratio (EDVR) as the inverse of dopa-
disturbances of dopaminergic functioning can be challenging, especially mine turnover prior to treatment allocation. The onset of wearing-off
in the early stages or atypical manifestation. In those cases, dopamine and LID was estimated based on blinded clinical assessments and
transporter imaging can assist the early diagnosis. Although there are patient records. The predictive value of baseline PET results of stria-
quantitation methods for dopamine transporter image assessment, they tal subregions for the development of motor complications (wearing-
are laborious and generally are not used for routine clinical practice. off, LID and any motor complication) was evaluated using Cox pro-
Therefore, visual assessment is used in routine clinical practice. portional hazard models.
Methods: Case report. Results: Over a mean observation period of 6.8 years, 18
Results: A 17 year-old man presented with progressive gait dis- (58.1%) patients developed wearing-off, 11 (35.5%) LID and 20
turbance, cervical dystonia and head tremor. His neurologic examina- (64.5%) any motor complication. Patients with LID and any motor
tion showed mild rigidity and resting tremor of bilateral legs which complication showed lower EDVR (higher dopamine turnover) in the
was slightly dominant on the left side. 18F-FP-CIT positron emission putamen than those without LID and any motor complication, with
tomography (PET) was done and interpreted as normal at other hos- differences most markedly present in the posterior putamen. EDVR
pital, and his diagnosis remained elusive. He visited our hospital sev- in the whole and the posterior putamen predicted development of
eral months later, and the FP-CIT PET image was reviewed by the motor complications with an increasing risk with lower EDVR
radiologist in our hospital, who also interpreted it as normal. How- (higher dopamine turnover), whereas EDVR in other regions and
ever, we reviewed his FP CIT-PET image because his clinical pic- Kocc did not correlate with motor complications. Kaplan-Meier
ture was strongly suggestive of juvenile Parkinsonism. After curves showed reduced survival from motor complications in patients

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


with lower baseline EDVR (higher dopamine turnover) in the poste- motor and non-motor symptoms, response to deep brain stimulation
rior putamen with ongoing levodopa treatment and disease duration. and even those in plasma a-synuclein concentrations. The neuropro-
Conclusions: Elevated putaminal dopamine turnover in de novo tective influence of estrogen to dopaminergic neurons, and male-
Parkinsons disease is associated with an increased risk for later female difference of brain morphology and functions are suggested
motor complications. This increase in putaminal dopamine turnover as possible mechanisms of those distinction.
might constitute an early compensatory mechanism and could play Methods: This study included 307 drug-nave patients (152 men
an important role in the development of levodopa-related motor com- and 155 women) with de novo PD who completed an 18F-FP-CIT
plications as a disease-intrinsic predisposing factor. 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-
32 gions of which comprised with 2 caudate subregions (anterior and
Understanding the effects of subthalamic nucleus (STN) deep posterior), ventral striatum, and 3 putaminal subregions (anterior,
brain stimulation (DBS) with preoperative diffusion tensor posterior, and ventral). Gender difference of DAT activities in each
imaging (DTI) striatal subregion as increase of age at onset was assessed using lin-
ear regression analyses.
P.M. Lauro, N. Vanegas, Z. Kareem, L.I. Codrin, S.S. Ziad, H.G.
Results: We found no significant male-female differences in age
Silvina (Bethesda, MD, USA)
at onset, disease duration and Unified PD rating scale (UPDRS) part
Objective: We aimed to characterize the specific stimulator- III. In scatter plot of age at onset versus DAT activities, the DAT
neuronal connectivity associated with favorable clinical outcomes activities were reduced with increase of the age at onset and those in
using preoperative DTI and stereotactic electrode locations. female were higher than those in male in all striatal subregions. In
Background: DBS is an effective therapy for treating Parkinsons linear regression analysis adjusting for age at onset, disease duration
disease (PD). Symptom relief is achieved by targeting specific areas and UPDRS III, the degree of gap of DAT activities between male-
of the STN. Studies have suggested that stimulation of white matter to-female was reduced as increase of age at onset in all striatal sub-
structures adjacent to the main target have similar beneficial effects. regions, and these gaps were in significance in anterior putamen
Methods: Twenty patients (9 male, average age: 57.9 6 9.49, (Estimated slope [ES], -0.005 vs -0.018; p50.001), anterior (ES, -
average disease duration: 13.25 6 6.69) with idiopathic PD who 0.021 vs -0.039; p<0.001) and posterior (ES, -0.013 vs -0.025;
received STN DBS surgery at the NIH were studied. All patients p<0.001) caudate but not in ventral striatum, posterior and ventral
underwent preoperative MRI including diffusion-weighted imaging putamen.
(b=1000 s/mm2, 32 directions). Postoperative CT images were co- Conclusions: We found that nigrostriatal dopamine neurons are
registered to preoperative T1, T2, and DTI for DBS lead localization. significantly more preserved in anterior part of the basal ganglia in
Diffusion images were processed with TORTOISE and tensors were female with exception of posterior part which is well known suscep-
estimated non-linearly with AFNI. Grey-matter ROIs were created tible region for Lewy body degeneration. These findings suggest that
from preoperative T1 images with Freesurfer and aligned to DTI neuroprotective effect in female may not be associated with PD
volumes. pathogenesis per se.
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- 34
ing contact. The volume of tissue activated (VTA) was estimated as Evaluation of saccadic eye movements in patients with
a sphere whose radius was calculated using contact impedance and Parkinsons disease: Effect of levodopa
voltage. Probabilistic tractography was used to determine the number
A. Lenka, K.R. Jhunjhunwala, R. Kotikalapudi, P.K. Pal (Bangalore,
of streamlines from each VTA to selected gray-matter ROIs using India)
FATCAT. To adjust for differences in conduction volume, the num-
ber of streamlines was scaled by VTA size. Objective: To assess the saccadic eye movements in patients
Results: Tractography networks were determined for all chronic with Parkinsons disease (PD) and to investigate the effect of levo-
stimulation contacts and for contacts with side effects and no clinical dopa on saccadic eye movements.
benefit. The total percentage of connections with three gray matter Background: Cortical and subcortical brain regions which control
structures (ventral diencephalon, caudate and thalamus) ipsilateral to saccadic eye movements, are known to be involved in PD. Though
the stimulating contacts (left 81.46 6 14.83%; right 79.03 6 15.09%) abnormalities of saccadic eye movement have been reported in PD,
was higher compared with the one obtained for contacts without clin- the effect of levodopa on saccadic eye movements is not clear.
ical benefit (left 63.45 6 17.48%; right 66.45 6 18.48%). Methods: Eye movements of 15 patients (10 men) with PD
Conclusions: By co-registering preoperative DTI and postopera- patients and 15 age and gender matched controls were recorded by
tive CT, we were able to determine specific connectivity patterns an IVIEW X HI-SPEED eye tracker (SensoMotoric Instruments
that characterize clinically effective DBS electrodes. This type of GmbH, Germany) using a Visually Guided Stimulus (VGS) task.
network analysis provides a potential targeting and prospective pro- Various saccadic parameters such as latency, average velocity, peak
gramming approach for DBS therapy. 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-
33 ters between three groups a) OFF state b) ON state c) Controls.
Gender difference in depletion of presynaptic nigrostriatal Paired t test was used to compare between ON and OFF state in PD
dopamine in de novo Parkinsons disease patients. Since saccadic latency does not have a normal distribution,
J.J. Lee, J.S. Oh, J.H. Ham, D.H. Lee, I. Lee, P.H. Lee, J.S. Kim, median of reciprocals of latencies were taken which showed a Gaus-
Y.H. Sohn (Seoul, Korea) sian distribution.
Results: The mean age of the patients was 52.9 6 11.6 years and
Objective: To explore whether a gender difference in presynaptic that of controls was 51.7 6 7.4 years. The mean age at disease onset
nigrostriatal dopaminergic density in patients with de novo Parkin- was 48.2 6 12.1 years and mean duration of illness was 4.1 6 2.5
sons disease (PD) using a quantitative analysis of 18F-FP-CIT posi- years. The mean UPDRS- OFF and ON scores of PD patients were
tron emission tomography(PET) scans. 35.4 6 8.4 and 20.1 6 10.4 respectively. On comparison between the
Background: Several antecedent studies have been reported of three groups (a, b and c) there was no significant difference in all
gender difference in PD including different clinical characteristics of the saccadic parameters except average acceleration, which was

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


significantly lower in OFF state compared to controls and ET tremor by single- and paired-pulse transcranial magnetic
(8344.5 6 2944.2 /sec2, vs 10327.3 6 2971.1 /sec2, p50.039). On stimulation (TMS).
comparison, though the saccadic parameters improved from OFF to Methods: Ten PD patients with resting tremor, six of them also
ON state, the differences were not statistically significant: reciprocal with postural tremor, and 10 ET patients with postural tremor were
latencies (2.9 6 0.9 sec-1 vs 3.1 6 0.8sec-1), average velocity studied. Randomized single- and paired-pulse TMS with an intersti-
(200.8 6 56.1 /sec vs 207.8 6 63.8 /sec), peak velocity mulus interval of 100 ms were delivered over M1, SMA and cerebel-
(389.6 6 135.1 /sec vs 397.2 6 157.3 /sec), average acceleration lum. TMS effects were evaluated by calculating a tremor-resetting
(8344.5 6 2944.2 /sec2 vs 9546.3 6 3286.5 /sec2) and peak accelera- index (RI).
tion (16501.6 6 5818.1 /sec2 vs 17885.1 6 6318.6 /sec2). Results: Single- vs. paired-pulse TMS showed no difference. M1-
Conclusions: PD patients during OFF state had reduced average TMS and SMA-TMS but not by cerebellar TMS induced a signifi-
acceleration of the saccades compared to controls. Levodopa did not cant RI in PD and ET. M1-TMS resulted in a significantly higher RI
significantly improve any of the saccadic parameters, though larger in PD than ET. Furthermore, M1-TMS in PD but not in ET resulted
cohort need to be studied. 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-
35 vides a useful marker to explore the differential functional role of
M1, SMA and cerebellum in PD versus ET tremor.
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. 36
Tsai (Taichung, Taiwan)
White matter microstructure damage in tremor-dominant
Objective: To investigate whether tremor in Parkinsons disease Parkinsons disease patients
(PD) and essential tremor (ET) is differentially modulated by pertur-
C. Luo, X. Guo, W. Song, H. Shang, Q. Gong (ChengDu, Peoples
bation of the motor-related cortices.
Republic of China)
Background: The pathogenesis of tremor in PD and ET is not
fully understood. This study tested the role of primary motor cortex Objective: The current study aims to investigate the differences
(M1), supplementary motor area (SMA) and cerebellar cortex on PD in white matter integrity in Parkinsons disease (PD) patients with

Fig. 1. (36).

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


and without tremor and to identify possible structural correlates of correlated with tremor scores in tremor-dominant PD patients. There
rest tremor. was no significant difference between nontremor-dominant PD
Background: Rest tremor is a hallmark of PD, yet its pathogene- patients and controls. [figure1]
sis is incompletely understood. Several lines of evidence suggest Conclusions: Our results support the notion that tremor in PD as
tremor may have different underlying pathophysiology processes a distinct condition in which significant microstructural white-matter
from those of bradykinesia and rigidity. It is unclear whether PD changes exist and provide evidence for the involvement of CTC in
patients with and without tremor are also different concerning white tremor genesis of PD. These findings suggest that objective measures
matter integrity. of white matter integrity may be useful in future genotype-phenotype
Methods: We recruited two carefully matched groups of PD analyses and in targeted therapeutic trials focused on PD subtypes.
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 37
assessment and diffusion tensor MRI. We used tract-based spatial
statistics to investigate white matter integrity across the entire white The trajectory of disturbed resting-state cerebral function in
matter tract skeleton. Parkinsons disease at different Hoehn & Yahr stages
Results: Compared with both healthy controls and nontremor- C. Luo, W. Song, X. Guo, H. Shang, Q. Gong (Chengdu, Peoples
dominant PD patients, tremor-dominant PD patients were character- Republic of China)
ized by increased MD and AD along multiple white matter tracts Objective: We aim to investigate the disturbance of neural net-
within cortico-cerebello-thalamo-cortical (CTC) pathway and some work associated with the different clinical stages of Parkinsons dis-
regions of association fibers. Mean MD value in white matter tracts ease (PD).

Fig. 1. (37).

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


Fig. 2. (37).

Background: Studies using advanced methods of time series circuits is negatively correlated with UPDRS III score. In addition,
analysis of oscillatory brain activity have demonstrated that synchro- PD patients, especially those at stage II, exhibit increased regional
nization of neuronal activity within and between distributed neuronal activity in the posterior regions of default mode network (DMN),
populations is an important mechanism in a variety of cognitive and increased anti-correlation between posterior cingulate cortex (PCC)
motor functions, including movement preparation, sensorimotor inte- and cortical regions outside DMN, and higher temporal coherence
gration and attention. It has been suggested that PD is characterized within DMN. Those indicate more highly functioned DMN in PD
by changing patterns of disturbed neural synchrony that appear to be patients at stage II. [figure1] [figure2]
dependent on the stage of disease. Resting-state fMRI (rfMRI) allows Conclusions: Our study demonstrated the trajectories of resting-
the interrogation in vivo of the neural synchrony disturbance. How- state cerebral function disturbance in PD patients at different H&Y
ever, few experiments have utilized rfMRI to depict the changing stages. Impairment in functional integration of occipital-temporal
course of abnormal functional integration in PD. cortex might be a promising measurement to evaluate and potentially
Methods: We recruited 80 patients at different H&Y stage of PD track functional substrates of disease evolution 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- 38
tion (ALFF) of blood oxygen level-dependent signals was used to Difference between brain activations for self- and cue-initiated
characterize regional cerebral function. Functional integration across movements in people with Parkinsons disease
the brain regions was evaluated by a seed voxel correlation
M.K. Mak, V. Cheung, D. Wang, C. Wong, Z.L. Lu, L. Shi, W. Lou,
approach. V. Mok, W.C.W. Chu (Hong Kong, Peoples Republic of China)
Results: PD patients had deceased regional activities in left occi-
pital and lingual regions; these regions show decreased functional Objective: To compare the brain activation patterns during self-
connection pattern with temporal regions, which is deteriorating as and cue-initiated movements in healthy subjects and people with Par-
H&Y stage ascending . Functional integrity in occipital-temporal kinsons disease (PD).

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


Background: It has been reported that people with PD had diffi- cal distribution in control group, while in PD group each lobe of the
culties in performing self-initiated movements and the application of brain hemispheres, caudate nucleus, putamen, thalamus were asym-
external cues improved the speed and/or amplitude of the move- metry reduction.
ments. It is hypothesized that, due to dysfunctions of the basal gan- (2)The uptake of 18F-FDG PET/CT in nigrostriatal system of PD
glia, PD patients use the dorsal visual pathway, including the parietal patients gradually reduced with increases on the severity of the dis-
cortex, pre-motor cortex and cerebellum, to replace the supplementary ease, a negative correlation (r 5 -0.709, P < 0.05) with UPDRS-
motor area-basal ganglia cortical pathways. Previous studies reported IIIscores; the longer the duration, the lower uptake ratios of caudate
that PD patients could perform well-learnt sequential finger move- nucleus/cerebellum, putamen/cerebellum, thalamus/cerebellum, the
ments by activating more brain areas than healthy subjects (Wu et al. substantia nigra red nucleus/cerebellum in PD;
2005). However, no study has compared the brain activation patterns (3) The UPDRS-IIIscores in ART, MT, TDT patients had no sig-
between self- and cue-initiated movements in patients with PD. nificant correlation with 18F-FDG uptake ratio.
Methods: Twelve PD patients and seventeen healthy subjects were Conclusions: 18F-FDG PET/CT imaging can be used for early
instructed to perform finger tapping with their left index finger in 2 diagnosis and disease stage in PD.
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 40
a tap when they saw a 1 on the computer screen. Data were acquired F-DOPA PET reveals a rostro-ventral striatal dopaminergic
in self-initiated, cue-initiated, and rest conditions using a block design. depletion in Parkinsons disease with impulse control disorders
There were 5 self- and 5 cue-initiated blocks and 10 rest blocks.
A. Mari, M.C. Rodriguez Oroz, C. Juri, R. Gonzalez-Redondo, J.
Results: During self-initiated movements, PD patients activated
Arbizu, E. Prieto, J.A. Obeso (Pamplona, Spain)
the dorsolateral prefrontal cortex, anterior cingulate cortex and the
declive of the cerebellum whilst healthy controls activated the sup- Objective: To ascertain the striatal pattern of dopaminergic
plementary motor area and the declive of the cerebellum (corrected, depletion by L-3,4-Dihydroxy-6-[18F] fluorophenylalanine
p<0.05). During cue-initiated movements, PD patients activated the ([ F]FDOPA) Positron Emission Tomography (PET) in Parkinsons
inferior parietal lobe and mid-cingulate cortex and healthy controls disease patients with and without impulse control disorders(ICD).
activated the supplementary motor area and the culmen and declive Background: ICD occur in a significant number of PD partients.
of the cerebellum (corrected, p<0.05). While these abnormal behaviours are associated with dopaminergic
Conclusions: PD patients had hypoactivation of the supplemen- treatments, a differential pattern of nigro-striatal dopaminergic dener-
tary motor areas during self-initiated movement. In both self- and vation has been suggested by findings in DAT-scan. However, most
cue-initiated movements, PD subjects activated the cingulate cortex, studies are confounded by the effect of dopaminergic drugs on the
suggesting that they used more attention than healthy subjects to per- activity and uptake of the dopamine transporter protien.
form both types of movements. The findings suggest that PD patients Methods: Thirty PD-ICD patients with ICD and 30 PD patients
may activate the attention network to compensate for their disrupted without a life history for ICD were matched for age and disease
basal ganglia-cortical pathways in generating body movements. 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
39 ventral striatum Volume of Interest were applied to measure 18F-
18F-FDG PET/CT imaging in the diagnosis of Parkinsons FDOPA uptake (Ki) in all patients.
disease Results: All PD patients showed a typical striatal denervation
pattern with predominance reduction in 18F-FDOPA uptake in the
Z. Mao, S. Ji, Q. Yang, H. Ye, Z. Xue (Wuhan, Peoples Republic of
China) caudal putamen. 18F-FDOPA uptake was significantly reduced in the
anterior and ventral striatum in ICD-PD patients compared to those
Objective: To investigate imaging characteristics of 18F-FDG without ICD. (p<0,01). Total Levodopa equivalent dose was higher
PET/CT in patients with Parkinsons disease (PD), exploring its value. (p50,006) in ICD-PD patients (mean 957,2) compared to the non-
Background: 11C-CFT dopamine transporer (DAT) positron ICD group (mean 501,27). No significant difference was found in the
emission tomography (PET) has important value on the diagnosis of mean dose of dopaminegic agonist LEDs.
Parkinsons disease, but the imaging agent is expensive and scarce, Conclusions: This study confirms previous findings with DAT-
18F-FDG is the most common imaging agent,and its role in Parkin- scan showing a significant reduction in ventral striatal dopaminergic
sons disease is to be developed. activity in ICD-PD patients by F-dopa PET which is less influnced
Methods: (1) Using UPDRS-III score, Hoehn-Yahr (HY) score to by drug treatments. However, the ICD-PD group received higher
evaluate disease duration, severity of 30 PD patients, 10 age- and dose of dopaminergic agents. The interaction between denervation
sex-matched without central nervous system disorders patients as and treatment probably defines in the origin of ICD in PD.
(2) 30 PD patients and 10 controls underwent brain tomography
imaging by intravenous injected 18F-FDG to get the respective ratio 41
of radioactive count per unit area of caudate nucleus, putamen, thala- Multimodal MRI changes in Parkinsons disease over one year
mus, frontal lobe, temporal lobe, parietal lobe, occipital lobe and cer- T.R. Melzer, D.J. Myall, M.R. MacAskill, L. Livinston, T.L. Pitcher,
ebellum (Rcl/cb). According to H-Y score 30 PD patients were R. Watts, R.J. Keenan, J.C. Dalrymple-Alford, T.J. Anderson (Christ-
divided as the early, middle and late stage, compare if there were
church, New Zealand)
difference in ratio of radioactive count between different stages of
the caudate nucleus/cerebellum, putamen/cerebellum, thalamus/cere- Objective: To investigate brain changes associated with Parkin-
bellum, substantia nigra red nucleus/cerebellum by ANOVA; sons disease (PD) over one year with structural, diffusion tensor
According to UPDRS-III score 30 PD patients were divided into imaging (DTI) and perfusion magnetic resonance imaging (MRI).
tremor-predominant (TDT), rigidity and bradykinesia predominant Background: Previous studies demonstrate that MRI can effec-
(ART), mixed type (MT), the correlation between UPDRS-III score tively stage PD in terms of both motor severity and cognitive status.
and radioactivity ratio of substantia nigra and red nucleus in PD However, the contribution of MRI parameters to monitor disease pro-
patients with different clinical symptoms were analyzed. gression over short time periods is uncertain.
Results: (1) Metabolic imaging of each brain lobe, caudate Methods: Twenty-three non-demented PD (19 with normal cogni-
nucleus, putamen, thalamus, cerebellum, cerebral were of symmetri- tion and 4 with MCI) and 23 age-matched control participants

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


completed extensive neuropsychological and disease assessment in 43

addition to multimodal 3T MRI scanning at baseline and one year
later. Global cognition was expressed as an aggregate z score derived Neural correlates of the effect of cueing on writing skills in
from the entire neuropsychological battery. SPM was used to prepro- Parkinsons disease
cess structural (grey matter) and perfusion scans, while FSL and E. Nackaerts, E. Heremans, R.C. Pineda, B.C.M. Smits-Engelsman,
TBSS were used to assess DTI metrics along major skeletal white S.P. Swinnen, W. Vandenberghe, A. Nieuwboer (Leuven, Belgium)
matter tracts. A voxel-based approach assessed change over time and Objective: This study investigated for the first time the neural
any group by time interactions for each modality. correlates of visual cueing on writing performance in Parkinsons
Results: Compared to controls, PD participants showed greater disease (PD).
grey matter atrophy over one year in bilateral inferior and right mid- Background: Patients with PD often experience handwriting dif-
dle temporal, and left orbito-frontal cortices. There was no significant ficulties. As the basal ganglia (BG) are important for internally-
perfusion change over time. While PD and control participants generated movements, it was hypothesized that patients may benefit
exhibited similar change in DTI metrics and global cognition over from external cueing to enhance motor output via the use of compen-
time, grey matter atrophy and change in DTI metrics were associated satory brain networks.
with change in global cognition in the PD group over time. Methods: Seventeen PD patients and 14 healthy controls (CTRL)
Conclusions: Our results suggest that disease-specific progression performed cued (reference lines) and uncued writing tasks on a
in non-demented PD patients across one year is associated with touch-sensitive tablet in the MRI scanner. At the behavioral level a 2
regional grey matter changes, but not changes in diffusion or perfu- (GROUP) x 2 (CUE) ANOVA was used to compare writing size and
sion MRI. Larger studies following patients for longer durations, and speed. BOLD responses were analyzed using two-sample t-tests to
those with patients showing more severe cognitive decline, may compare groups while writing either with or without cues and to
show the utility of multimodal MRI to track progression in PD. compare cued and uncued writing in each group separately (p<.001,
Results: Behaviorally, no differences were found between groups.
Both groups wrote smaller and slower with cues compared to with-
42 out. Comparing brain activity during cued and uncued writing,
increased activity in bilateral medial and inferior occipital cortex,
Neuroanatomical correlates of cognitive functioning across the left superior parietal cortex, including precuneus, and left cerebellum
Parkinsons disease cognitive spectrum lobule VI in CTRLs was found. Uncued writing by CTRLs led to
D.V. Merkitch, G.T. Stebbins, B. Bernard, J.G. Goldman (Chicago, increased activity in bilateral orbitofrontal (OFC), ventrolateral pre-
IL, USA) frontal (VLPFC) and anterior cingulate cortex and left postcentral
gyrus. A similar pattern of brain activity was present in PD, with
Objective: To investigate relationships of gray matter atrophy on additionally increased activation of the right hippocampus during
structural magnetic resonance imaging (MRI) to cognitive domains cued writing. When comparing both groups during cued writing,
in Parkinsons disease (PD). CTRLs showed increased activation of the left OFC and putamen,
Background: Cognitive dysfunction is a frequent and debilitating while in PD there was increased activity in left precuneus compared
consequence of PD. Detecting neuroanatomical correlates of different to CTRLs. During uncued writing, CTRLs presented increased activ-
aspects of cognitive functioning on brain MRI may provide bio- ity in bilateral VLPFC and right precentral gyrus compared to
markers that can predict cognitive decline in PD. patients, whereas patients showed increased activity in left
Methods: 101 PD subjects underwent clinical/neuropsychological precuneus.
evaluations, T1-weighted MRI brain sequences, and cognitive classifi- Conclusions: Contrary to our hypothesis, adding cues imposed
cation by The International Parkinson and Movement Disorder Society extra task difficulty in both groups. Overall, these results suggest
criteria (cognitively normal, n529; mild cognitive impairment, n547; that the BG and prefrontal cortex showed less activity during cued
demented, n525). Z-scores for the cognitive domains (attention/work- writing in PD, consistent with the affected frontostriatal system. Fur-
ing memory, executive function, memory, language, visuospatial func- ther analysis will reveal whether the strikingly increased BOLD
tion) were calculated. Whole-brain voxel-based morphometry analyses response in the precuneus operates as part of a dorsomedial compen-
were conducted using SPM8, covarying for age, PD duration, and scan satory network, and not a dorsolateral one as suggested in previous
type. Gray matter volume differences between subject groups were studies.
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- 44
based, and cerebellar. Stepwise multiple regressions were performed Chronic recordings of subthalamic oscillatory activity using an
adjusting for age and PD duration with the regional gray matter vol- implanted pulse generator in patients with Parkinsons disease
umes as criterion variables and cognitive domain z-scores as predictor W.J. Neumann, F. Staub, J. Schanda, A. Horn, G.H. Schneider, P.
variables. Brown, A.A. K
uhn (Berlin, Germany)
Results: Multiple regression analyses demonstrated significant brain-
behavior correlates: executive function domain scores best predicted atrophy Objective: To investigate the stability of beta oscillatory activity
in the frontostriatal cognitive-control (R2=.28, p<0.005) and ventral object- in the subthalamic nucleus (STN) and its modulation by deep brain
based systems (R2=.37, p<0.005), memory domain scores best predicted stimulation (DBS) in patients with Parkinsons disease (PD) over
atrophy in the medial temporal memory system (R2=.38, p<0.005), lan- time.
guage domain scores best predicted atrophy in the dorsal spatial-based sys- Background: Oscillatory synchronisation recorded from the sub-
tem (R2=.06, p50.02), and attention and working memory domain scores thalamic nucleus in the b-band (13-30 Hz) has previously been
best predicted gray matter atrophy in the cerebellum (R2=.08, p5.01). shown to be a biomarker for PD symptoms. DBS suppresses this
Conclusions: These atrophy patterns follow brain-behavior corre- activity in parallel with alleviation of motor symptoms. However,
lates of cognitive dysfunction and thus, may be useful biomarkers most previous studies have only investigated b-band activity directly
for measuring progression of PD cognitive decline and treatment after the implantation of DBS electrodes before the implantation of
effects. Furthermore, they provide insights on neuroanatomical and the impulse generator (IPG). Hence, little is known about the long
neuropathological differences responsible for clinical heterogeneity term fluctuations of b-band activity and its modulation by DBS.
with some patients having greater attention/executive dysfunction Methods: Subthalamic recordings from 7 PD patients (age 65.6
and others, greater memory deficits. years 6 1.8 SEM; disease duration 9.4 6 1.3 years) after withdrawal

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


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.

A new manual ROI improves diagnostic accuracy for cardiac Fig. 1. (46).
sympathetic neuronal dysfunction in Parkinsons disease
H. Odagiri, T. Baba, Y. Nishio, O. Iizuka, M. Matsuda, K. Inoue, M. Background: DBS is an effective treatment for PD, yet its
Iwasaki, Y. Taki, E. Mori (Sendai, Japan) mechanisms of action and influences on cortico-STN networks are
Objective: The purpose of this study was to determine the diag- unknown. It has previously been shown that two spectrally and spa-
nostic impact of 123I-MIBG cardiac SPECT/CT imaging compared tially distinct resting STN-cortical networks exist in PD: 1) An STN-
with conventional scintigraphic evaluation in the diagnosis of PD. temporo-parietal alpha band (7-12Hz) network and 2) An STN-pre-
Background: 123I-metaiodobenzylguanidine (123I-MIBG) car- motor/motor beta (13-30 Hz) band network. We sought to examine
diac scintigraphy is now widely used to assess cardiac sympathetic the effect of DBS on these networks.
neuronal dysfunction in Parkinsons disease (PD) and dementia with Methods: We performed simultaneous magnetoencephalography
Lewy bodies(DLB). Manually defined regions of interest (ROIs) on (MEG) and bilateral STN local field potential recordings (LFPs) in
planar images are conventionally used to assess myocardial uptake 15 post-operative PD patients, whose DBS electrodes had been tem-
of 123I-MIBG (the heart-to-mediastinum ratio; H/M ratio). However, porarily externalised for recording. Using a purpose built amplifier
arbitrary placing of ROIs on planar image leads to decrease the we were able to simultaneously stimulate the STN and record its
accuracy. electrical activity during concurrent MEG recording. Source recon-
Methods: We studied 28 patients with PD and 19 patients with struction of cortical signals was performed using beamforming to
idiopathic normal pressure hydrocephalus (iNPH), which is a non- allow the computation of coherence between cortical regions and the
neurodegenerative Parkinsonian disorder as controls. We calculated STN signal.
the H/M ratio both from planar images and fused SPECT/CT images Results: Unilateral monopolar DBS at 130 Hz suppressed low
obtained with a hybrid SPECT/CT system, then we compared diag- beta power (12-20Hz) locally within the STN and also suppressed
nostic accuracy of these two methods. low beta (12-15 Hz) coupling between both STNs. Furthermore, low
Results: Difference in the H/M ratio between PD group and beta coupling (13-22 Hz) between the STN and the premotor peak of
iNPH group was significantly higher in the SPECT/CT method(Early resting beta activity was suppressed by 130 Hz DBS, despite cou-
p<0.0001, Delayed p<0.0001) compared with conventional planar pling in the high beta range (22-35 Hz) remaining unchanged. Figure
method(Early p50.082, Delayed p50.041). The sensitivity and spec- 1 shows STN power and STN-premotor coherence results averaged
ificity between PD group and iNPH group was significantly higher in across all subjects and hemispheres [figure1]. We are currently corre-
the SPECT/CT method (sensitivity 92.9%, specificity 57.9%) com- lating the observed spectral changes with clinical parameters on and
pared with conventional planar method (sensitivity 67.9%, specificity off DBS.
47.4%). Conclusions: Our results highlight that DBS preferentially sup-
Conclusions: The SPECT/CT method is useful in differentiation presses low rather than high beta activity in cortico-STN motor cir-
of the neurodegenerative disease. cuits in PD. This finding suggests that low beta may be an important
pathological process in PD, suppressed by both levodopa and DBS.

46 47
The effect of deep brain stimulation (DBS) on cortico- Multimodal MRI markers discriminate Parkinsons disease from
subthalamic nucleus coupling in Parkinsons disease (PD) multiple system atrophy patients
A. Oswal, A. Jha, S. Neal, A. Reid, P. Limousin, T. Foltynie, L. P. Peran, M. Sierra, A. Pavy-Le Traon, O. Rascol (Toulouse,
Zrinzo, M. Hariz, V. Litvak, P. Brown (London, United Kingdom) France)
Objective: To evaluate the effect of DBS on functional connec- Objective: Using multimodal MRI, the aims of the study were (i)
tivity within a network comprising the subthalamic nucleus (STN) to compare changes in patients with idiopathic Parkinsons disease
and cortical regions in PD. (iPD) compared to multiple system atrophy (MSA) patients with

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


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
Fig. 1. (47). 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
Parkinsonian syndrome (MSA-P) and with cerebellar syndrome between the PAC comodulogram results and the clinical evaluation
(MSA-C) (ii) to discriminate iPD patients from MSA patients. scores using the modified Unified Parkinsons disease Rating Scale
Background: Multimodal MRI approach is based on combination (UPDRS) were performed.
of MRI parameters sensitive to different tissue characteristics (e.g. Results: Significant PAC was found in 2/8 PD patients in the off
volume atrophy, iron deposition, microstructural damage). Previous medication state, and in both cases, Levodopa-Carbidopa reduced the
findings revealed that multimodal MRI is able to discriminate iPD PAC values in conjunction with improvement in Parkinsonian motor
patients from healthy control subjects with high accuracy (Peran signs. Another patient had significant PAC values only after the
et al., Brain, 2010). The combination of different MR biomarkers could administration of Levodopa-Carbidopa, but the patient also had wors-
help to discriminate different pathologies with Parkinsonian syndrome. ened tremor after medication. No significant PAC was found in any of
Methods: 26 iPD patients with and 29 MSA patients (16 MSA-P, the control subjects. Across the cohort, inter-subject regression analy-
13 MSA-C) underwent 3-T MRI comprising: T2*-weighted, T1- sis showed no correlation between PAC and motor signs (R2 < 0.2).
weighted and diffusion tensor imaging scans. We used the same Conclusions: Significant PAC, while present in some PD patients,
method as in the previous work (Peran et al., Brain, 2010) to extract was not found to be consistent in the sensorimotor cortex for all PD
MRI markers (volume, R2* value, mean diffusity and fractional ani- patients in this study.
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 49
computed using results from the previous voxel-based analysis.
Aberrant cerebral network topology and mild cognitive
Results: Concerning region-based analysis, the main results
impairment in early Parkinsons disease
showed significant changes in brainstem and in putamen in MSA
patients compared to PD patients. The sub-group of MSA-P showed J.B. Pereira, D. Aarsland, C. Ginestet, A. Lebedev, L.O. Wahlund, A.
a loss of microstructural integrity (higher mean diffusity) in putamen Simmons, G. Volpe, E. Westman (Stockholm, Sweden)
compared to iPD or compared to MSA-C. The sub-group of MSA-C Objective: The aim of the current study was to assess whether
showed a loss of microstructural integrity (higher mean diffusivity) mild cognitive impairment (MCI) is associated with disruption in
in brainstem compared to iPD or compared to MSA-P. Voxel-based large-scale structural networks in newly diagnosed, drug-nave
analysis confirmed the previous localizations and identified differen- patients with Parkinsons disease (PD).
ces for all markers in the cerebellum. Predictive analysis showed Background: Mild cognitive impairment has a strong impact on
that markers for discriminating iPD from MSA-P were mainly the quality of life and frequently progresses to dementia in patients with Par-
grey density of putamen, the mean diffusivity in the cerebellum and kinsons disease. Although the study of network disruption could provide
the fractional anisotropy in the superior corona radiata. [figure1]Fig- an important insight into the cortical and subcortical patterns underlying
ure: MSA-P vs iPD (voxel-based). red: " R2* green: " MD blue: # cognitive decline in Parkinsons disease, the organization of the brains
FA yellow: # grey density. structural architecture has not been assessed in these patients to date.
Conclusions: This study demonstrates that multimodal MRI is Methods: Graph theoretical analyses were applied to 3T MRI data
able to discriminate patients with iPD from MSA with a high accu- from 123 PD patients and 56 controls from the Parkinsons Progression
racy. The combination of different MR biomarkers could be a great Markers Initiative (PPMI). Thirty-three patients were classified as hav-
tool to follow disease progression. 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-
48 cient, characteristic path length, global efficiency, small-worldness) and
Phase-amplitude coupling heterogeneity in the Parkinsonian regional measures (local clustering coefficient, local efficiency, hubs)
sensorimotor cortex were assessed in the structural networks that were constructed based on
E. Pe~na, L. Rosedahl, T.M. Mohammed, F. Al-Mohammed, L. cortical thickness and subcortical volume data in each group.
Results: Patients with MCI showed a marked reduction in the
Soualmi, M.D. Johnson, J.A. Bajwa (St. Paul, MN, USA)
average correlation strength between cortical and subcortical regions
Objective: To investigate magnetoencephalographic (MEG) compared to controls. These patients had larger characteristic path
measures of phase amplitude coupling in sensorimotor cortex on and length and reduced global efficiency in addition to a lower local effi-
off medication in Parkinsons disease (PD) patients. ciency in frontal and parietal regions compared to cognitively normal
Background: The phase amplitude coupling (PAC) measure patients and controls. A reorganization of the highly connected
describes the degree to which oscillatory activity in one frequency regions in the network was observed in patients with and without
band phase-locks to oscillatory activity in a lower frequency band. cognitive deficits.
Such coupling is thought to be indicative of information transfer Conclusions: This study shows the earliest stages of cognitive
between neuronal populations at different spatiotemporal scales, and decline in PD are associated with a disruption of the large-scale
has been shown to play a critical role in cognitive processes such as coordination of the brain network and with a decrease of the effi-
learning. In some cases, this type of coupling may be pathological, ciency of parallel information processing. These changes are likely
and recent intraoperative studies in PD patients have noted strong to herald further cognitive decline and provide support to the view
coupling between the amplitude of gamma/high-frequency oscillatory of PD as a disconnection syndrome capable of spreading along the
activity and the phase of beta-band oscillations in primary motor cor- connections of the cerebral network.

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


50 Objective: We acquired rs-fMRI data in PD patients in the ON

and OFF medication conditions and age-matched HC and used the
Progressive cerebellar atrophy in patients with tremor- seed Partial Least Squares Correlation (PLSC) analysis to assess
predominant Parkinsons disease impact of the disease and medication on connectivity strength from
C.C. Piccinin, L.G. Piovesana, R.P. Guimaraes, M.C.A. Santos, B.M. our seeds of interest.
Campos, T.J.R. Rezende, L.S. Campos, P.C. Azevedo, F. Torres, Background: Resting state functional connectivity within the
M.C. Franca, A.C. Amato-Filho, I. Lopes-Cendes, F. Cendes, A. large-scale brain networks between healthy subjects (HC) and PD
DAbreu (Campinas, Brazil) patients in the ON (PD_ON) and OFF (PD_OFF) medication condi-
Objective: Our aim was to identify whether the cerebellar grey tions has not been systematically studied.
matter (GM) atrophy presented in tremor-predominant Parkinsons Methods: We inluded 19 non-demented and non-depressed males
disease (PD) patients is associated to disease severity using a specific with PD (age 64.6 6 7.5 years, disease duration 29 6 6 months,
cerebellar tool for voxel-based morphometry (VBM) analysis. levodopa-equivalent dose 1092.7 6 353.8 mg) and 15 matched HC
Background: Recent neuroimaging studies comparing tremor- males (age 62.9 6 8.2 years). PD subjects were scanned before and
predominant-PD versus bradykinesia-predominant-PD demonstrated after administration of their first morning dose of DA medication.
decreased GM in the cerebellum of tremor-predominant-PD patients fMRI data were preprocessed using SPM8. Based on literature and
only, underlying a potential cerebellar role in the physiopathology of our previous work we chose 2 coordinates for motor seeds (left pri-
PDs tremor. mary motor cortex for hand [L hand SM1] and right primary orofa-
Methods: We divided our tremor-predominant-PD patients group cial cortex [R orofacial SM1], and 6 coordinates for non-motor seeds
into three groups in according to the progression of symptoms and (precuneus, anterior cingulate cortex [ACC], right middle temporal
level of disability (trough Hoehn and Yahr rating scale H&Y) and gyrus/middle occipital gyrus [MTG/MOG], right insula [RI], right
compared each group with an age-gender-matched healthy control inferior frontal gyrus [IFG], R caudate). We extracted the BOLD sig-
(HC) group. Group 1 included 9 early PD patients (mean age nal as the first eigenvariate from a sphere with radius of 6 mm.
61.89 6 10.6) with H&Y scores between 1 and 1.5 and 9 HC (mean These seed signals were used to compute seed correlation matrices.
age 61.33 6 9.85); group 2 was comprised of 21 patients Results: The PLSC analysis revealed significant impact of the
(58.52 6 12.46) with H&Y scores between 2 and 2.5 - and 21 HC disease (but not medication) on the connectivity strength of spatial
(58.81 6 12.24); and group 3 presented 15 patients (58.87 6 9.16) correlation maps seeded by R caudate (p 5 0.047), ACC (p 5 0.006),
with H&Y score  3 and 15 HC (58.80 6 9.18). We acquired T1 MTG/MOG (p 5 0.045), and R orofacial SM1 (p 5 0.025). The RI
weighted scans at a 3T scanner and compared the paired groups and L hand SM1 almost reached statistical significance (p 5 0.058
using VBM in SPM8. We used the SUIT tool (Spatial Unbiased and 0.076, respectively). In PD patients the connectivity within all
Infratentorial Template) for a specific and detailed evaluation of the studied networks decreased in most of the brain regions as compared
cerebellar GM. Statistics were done applying p5.001, uncorrected to HC. In motor networks the connectivity differences were most
and extent-threshold  20 voxels. prominent between PD_OFF and HC while in all studied non-motor
Results: We detected no changes in the cerebellar GM in patients networks the major connectivity differences were found between
classified as early and moderate tremor-predominant-PD. The severe PD_ON and HC.
group however, demonstrated large GM decreased in the right ante- Conclusions: We observed impact of the disease (PD vs. HC sta-
rior lobe, in the left crus I and bilaterally in the lobules V, VI tus) while the impact of medication (PD_ON vs. PD_OF states) did
(including the vermis) and VIIIa. 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
Decreased GM areas in the cerebellum demonstrated in the default mode networks.
severe group of patients (H&Y score  3)
The neural correlates underlying dual tasking in Parkinsons
Right Hemisphere I - IV 61
Left Hemisphere V 98
Right Hemisphere V 536 K. Rosenberg-Katz, I. Maidan, Y. Jacob, S. Shema, N. Giladi, T.
Left Hemisphere VI 294 Hendler, H.M. Jeffrey, A. Mirelman (Tel Aviv, Israel)
Vermis VI 57 Objective: The aim of this study was to use functional MRI
Right Hemisphere VI 193 (fMRI) to study the neural mechanisms underlying dual tasking (DT)
Left Hemisphere Crus I 316 in PD.
Left Hemisphere VIIIa 51 Background: The ability to divide attention plays an important
Right Hemisphere VIIIa 82 role in DT and in the so called DT decrement. In the context of
gait, this decrement has major negative consequences as it impacts
*in voxels 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-
Conclusions: We concluded that the decreased cerebellar GM ing brain mechanisms are still lacking.
observed in tremor-predominant-PD patients using a special tool for Methods: Twenty-two patients with PD (mean age: 72.69 6 4.17
cerebellar analysis parallels the progression of the clinical symptom- yrs) and 14 healthy controls (mean age: 71.18 6 5.97 yrs) were stud-
atology and it is possibly only detectable in patients with bilateral ied using an fMRI paradigm that included three conditions that were
disease and some level of postural instability (H&Y3). presented in a block design: 1) alternating feet movements against
foot pedals (single task), 2) subtracting 3s from a predefined number
51 (single task), and 3) performing both tasks simultaneously (DT). DT
related brain activations were examined by comparing the DT condi-
Impact of the disease and medication on resting state functional tion with both of the single tasks conditions. DT related brain activa-
connectivity in Parkinsons disease tions were further correlated with measures related to attention and
I. Rektorova, N. Elfmarkova, M. Gajdos, M. Mrackova (Brno, Czech task switching, the Trail Making Test (TMT), and with DT gait
Republic) speed decrement (i.e., usual walking gait speed minus DT speed).

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


Results: Both groups showed significant increase in DT related Background: The neuropathology of PD is hypothesized to have
activations in the middle frontal gyrus, precentral gyrus, inferior early changes in the brainstem, particularly the medulla oblongata,
frontal gyrus (Brocas areas), thalamus, and superior parietal lobe followed by changes in the midbrain and eventually the neocortex.
(SPL) (p FWEcorr <0.05). Compared to the healthy elderly, patients Structural MRI provides an opportunity to examine differences in
with PD had significantly lower DT related activations in the occipi- brainstem volumes between PD patients and healthy controls. Brain-
tal cuneus and lingual gyrus (p FWEcorr <0.05), SPL, middle frontal stem atrophy detected on MRI scans could potentially be used as a
gyrus, medial frontal gyrus/anterior cingulate and right caudate biomarker of PD progression.
nucleus (p<0.0005, uncorrected). The SPL fMRI beta values of DT Methods: Twenty-nine clinically diagnosed, cognitively normal
related activations were negatively correlated with the time to com- PD patients and 24 age-matched, healthy controls underwent clinical
plete the TMT part b (r=-0.412, p<0.01, corrected for age) but not evaluations and MRI brain scans (1.5T GE Signa, T1-weighted
with TMT part a duration (r=-0.247, p50.159, corrected for age). In sequences [MPRAGE, IR-FSPGR]). Whole brain voxel-based mor-
addition, higher SPL beta values were correlated with lower DT gait phometry analyses were conducted using SPM8. Images were
speed decrement (r= -0.345, p<0.05). smoothed with a 6mm kernel. Regions of interest for midbrain, pons,
Conclusions: These findings suggest that part of the difficulties and medulla gray matter volumes were extracted from modulated
that patients with PD have during DT are related to a decreased abil- non-linear scans using the Wake Forest University Pickatlas. Gray
ity to recruit brain regions including occipital, parietal, frontal and matter differences between the PD and control groups were exam-
motor regions. Our results support the involvement of the SPL as a ined using a MANCOVA, covarying for scan sequence and gender
principal factor in DT. 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.
53 Results: The PD and healthy control subjects did not differ sig-
Evaluation of striatal PDE10 expression in Parkinsons disease nificantly in age (mean [SD] PD 70.66 [4.65] years, Controls 71.75
(PD) using [18F]MNI-659 PET imaging [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
D.S. Russell, D.L. Jennings, O. Barret, G.D. Tamagnan, D. Alagille,
J.P. Seibyl, K.L. Marek (New Haven, CT, USA) 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).
Objective: To evaluate the feasibility of [18F]MNI-659 PET, a There were no significant differences found in the other brainstem
striatal PDE10A imaging tracer, as a biomarker in early PD and PD regions. Logistic regression with midbrain volume significantly pre-
with motor fluctuations. dicted PD/control classification (v2=34.29, p<0.0005). ROC analyses
Background: PDE10 is highly and specifically expressed in brain revealed an area under the curve of 0.84, and a midbrain relative
in striatal neurons, primarily medium spiny neurons. This enzyme volume threshold of 0.188 optimally differentiated PD from controls
plays a critical role in striatal dopaminergic function via regulation with a sensitivity of 79% and specificity of 83%.
of cyclic nucleotides. [18F]MNI-659 PET is a well-validated, highly Conclusions: Patterns of brainstem atrophy on MRI, particularly
specific PET radioligand targeting PDE10A. in the midbrain, can distinguish cognitively normal PD patients from
Methods: Eight PD subjects participated, de novo (n52) and healthy controls. This finding may reflect underlying PD-related neu-
treated with dopaminergics (n56). All subjects were imaged with rodegeneration and thereby, has potential as a biomarker for diagnos-
[18F]MNI-659 for 90 minutes. Standard uptake values were deter- ing PD and monitoring disease progression.
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 55
with the PET images for anatomical localization. Early diagnosis of multiple system atrophy in patients with
Results: Participants (7M, 1F) had a mean age of 65.7 y (range Parkinsons disease and orthostatic hypotension by 123I-IBZM
61.6-69.0 y) and mean duration of diagnosis of 8.0 (range 1.5-12.7). SPECT
Treated subjects all manifest dyskinesia and on-off phenomena.
D.E. Shan, S.J. Wang, K.K. Liao, H.H. Hu (Taipei, Taiwan)
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 Objective: To evaluate the probability of 123I-IBZM, a ligand
was 2.29 (S.D. 0.30) compared to mean 2.45 (S.D. 0.21, P=0.34) for D2-receptor binding, SPECT in make the differential diagnosis
among older HS (n55, >40 yrs). No correlation was noted between between patients with multiple system atrophy (MSA) and patients
striatal BPnd and diagnosis duration (R2 5 0.04), total UPDRS score with Parkinsons disease with orthostatic hypotension (PD1OH).
(R2 5 0.02), or motor subscale score (R2 5 0.02). Mean striatal BPnd Background: Some patients with Parkinsons disease have auto-
for untreated did not differ from treated (2.27, S.D. 0.034 vs. 2.30, nomic dysfunction, including orthostatic hypotension. Differential
S.D. 0.32, P=0.91). Comparison between more affected putamen diagnosis between these PD1OH patients and those with MSA is a
(2.93; S.D. 0.36) and less affected putamen (2.98; S.D. 0.45) did not difficult but important issue.
detect a difference (P=0.66). Methods: Twelve PD1OH patients were recruited into an 123I-
Conclusions: In this limited cohort of de novo and treated PD IBZM SPECT study and compared with the data from 9 patients
subjects, there is good brain penetration and binding of [18F]MNI- with MSA, 6 patients with idiopathic PD (IPD), and 3 normal con-
659 in the striatal regions. While this study is limited by its small trols. To make the diagnosis of MSA, the lowest data from normal
sample size, no significant difference in [18F]MNI-659 binding was controls were used as the cut-off values, i.e. the striatum/occipital
detected when compared to a similarly aged HS. (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
54 data from two patients with PD1OH were excluded from analysis
Decreased gray matter volume in the brainstem: A potential because they had taken pramipexole or antipsychotic within 5 days
biomarker of Parkinsons disease? before SPECT examination.
C.D. Schroeder, G.T. Stebbins, J.G. Goldman (Chicago, IL, USA) 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
Objective: To investigate regional brainstem atrophy on struc- four patients with PD1OH (40%) were below the cut-off value.
tural magnetic resonance imaging (MRI) in Parkinsons disease According to the P/O ratio from the worst side of lesion, none with
(PD). IPD (0%), six patients with MSA (66.7%) and two patients with

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


PD1OH (20%) were below the cut-off value. Although the initial step was performed, and acceptable images (68 controls, 105 PD)
autonomic dysfunction in one of the two PD1OH patients below the were analyzed using the analysis of functional neuro-imaging (afni)
cut-off value of the P/O ratio was not severe enough to meet the imaging suite. The afni package 3dQwarp is being iteratively
diagnostic criteria of MSA, her follow-up studies showed poorly recoded to to allow more fine grain registration of images, and we
levodopa-responsiveness, progressive worsening of orthostatic hypo- analyze the transformation matrix for evidence of difference in fiber
tension and the development of hot cross-bun sign on MR imaging, caliber between groups. Fractional anisotropy in the registered
which made her diagnosis to be revised to MSA. images was also analyzed.
Conclusions: The P/O ratio of 123I-IBZM SPECT is more sensi- Results: At the time of this abstract, adequate registration is
tive and more specific than the S/O ratio in making the diagnosis of available in 37 controls and 77 subjects with PD. Among these sub-
MSA. The diagnosis of PD1OH should be made cautiously, particu- jects, fiber tract caliber differs in PD subjects compared to controls
larly in those patients with a short duration of illness. Our study in the fornix, basal forebrain (including the anterior commissure),
reveals that one-tenth of them may be an early manifestation of and adjacent to deep cerebellar nuclei. Fractional anisotropy differed
MSA. 123I-IBZM SPECT may help in making the correct diagnosis in the midbrain, including in the peri-nigral regions, as well as in the
early in the course. This work was supported by grants (#NSC- 98- pons and medulla.
2314- B- 075- 034) from the National Science Council, ROC, grants Conclusions: Our data suggest that individuals with PD have
(#INIBA071213) from the Institute of Nuclear Energy Research, measurable morphological changes in caliber of white matter struc-
ROC, and grants (#140-V-B-030) from the Taipei Veterans General tures. Nonlinear image registration protocols, which accurately regis-
Hospital - National Yang-Ming University Excellent Physician Sci- ter structures, can obscure important disease related information in
entists Cultivation Program. 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
56 that in addition to previously described FA changes in peri-nigral
regions, individuals with PD show changes in fiber tract caliber in
Fiber tract atrophy in idiopathic Parkinsons disease multiple structures, including limbic structures.
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- 57
ing (DTI). Increased dopamine turnover: A possible contributor to the
Background: During image registration, fiber tracts are morphed increased risk of Parkinsons disease in LRRK2 mutation
and matched across subjects. This is a necessary process to localize carriers
structures in, but information may be lost. We analyzed changes in
V. Sossi, R. Nandhagopal, D. Wile, M. Schulzer, J. McKenzie, K.
fiber tract caliber (radial to the primary fiber direction) in idiopathic Dinelle, M. Farrer, Z.K. Wszolek, J. Aasly, A.J. Stoessl (Vancouver,
Parkinsons disease compared to healthy controls, by evaluating mor-
BC, Canada)
phological changes during image registration to a common template.
DTI data was collected from the Parkinsons Progressive Markers Objective: To investigate the role of the impaired dopamine
Initiative (PPMI) dataset. (DA) storage capacity or its inverse, DA turnover in the asymptom-
Methods: DTI images from the PPMI dataset were downloaded atic stage of subjects with LRRK2 mutations, which increase the risk
and processed using the NIH Tortoise suite. A visual quality control of Parkinsons disease (PD).

Fig. 1. (57).

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


Background: An increase in dopamine turnover has been previ- binding. Apathetic patients had reduced bilateral DAT and SERT
ously demonstrated in asymptomatic LRRK2 mutation carriers [1]. binding in anterior caudate nuclei, anterior putamen, ventral striatum,
Whether such increase would represent an initial compensatory reac- substantia nigra, as well as a specific decreased DAT binding in pos-
tion to incipient disease or be pathogenic by itself is still a matter of terior caudate nuclei, posterior putamen and globus pallidus. The
speculation. comparison between apathetic and non-apathetic patients revealed a
Methods: 17 asymptomatic subjects with LRRK2 mutations greater 5-HT and DA denervation in caudate nuclei. Our data also
(Y1699C, R1441C, G2019S, N1437H, G2019S and I2020T, age suggest a link between the severity of rigidity and the 5-HT denerva-
49 6 12 yrs) and 4 mutation negative subjects (age 61 6 8) yrs tion in putamen and anterior caudate nuclei in all patients. The
underwent a positron emission tomography (PET) scan with the severity of apathy and depression seem to be mainly associated with
dopamine transporter (DAT) marker 11C-methylphenidate (MP), DA and 5-HT disruption in ventral striatum.
quantified with the tissue input binding potential BPND and a pro- Conclusions: Altogether, these preliminary findings highlight
longed 18F-fluorodopa (FD) scan to evaluate the effective dopamine both DA and 5-HT dysfunction in de novo drug-naive PD patients
distribution volume (EDV), the inverse of DA turnover. The decrease suffering from neuropsychiatric signs with a specific contribution of
in EDV and DAT binding relative to age matched normal controls the caudate nucleus.
were compared.
Results: Unlike previous studies performed in early PD subjects,
which showed a very strong positive correlation between DAT bind- 59
ing and EDV[2], no correlation was found for the mutation carriers. Transcranial sonography in LRRK2 G2019S mutation carriers
EDV was significantly (p< 0.001) more decreased compared to DAT 
D. Vilas, L. Ispierto, R. Alvarez, C. Pont-Sunyer, M.J. Mart, F. Vall-
binding (40% vs 19%). The mutation negative subjects had normal
deoriola, Y. Compta, O. De F abregues, J. Hern andez-Vara, V.
values for both tracers (figure 1). Puente, M. Calopa, S. Jaum a, J. Campdelacreu, M. Aguilar, P.
Conclusions: Given the established correlation between DAT Qulez, P. Casquero, F. Lome~ na, E. Tolosa (Barcelona, Spain)
density and dopaminergic terminal deficit, these data support the
hypotheses that impaired DA storage, which could lead to excess Objective: To assess the echogenicity of the substantia nigra
levels of DA in the cytosol, might be an independent mechanism (SN) in LRRK2 G2019S mutation carriers.
leading to an increased risk of PD, consistent with recent findings in Background: Hyperechogenicity of the SN has been proposed as
animal models [3]. Further work is required to establish if very a risk marker of Parkinsons disease (PD). Asymptomatic LRRK2
recently observed alterations of the serotonergic innervation may mutation carriers (aLRRK21) are subjects at high risk for develop-
influence the measurement of dopamine turnover. ing PD.
References: Methods: Transcranial sonography was performed in twenty-six
1. Sossi, V. et al., Mov Disord, 2010. 25(16): p. 2717-23. LRRK2 G2019S PD patients and 50 of their first-degree relatives.
2. Sossi, V. et al., Ann Neurol, 2007. 62(5): p. 468-74. Twenty-four of them were aLRRK21. Thirty-one idiopathic PD
3. Shen, J. et al., Neurodegenerative Diseases, 2010. 7(1-3): p. (IPD) patients and 26 unrelated control subjects age and sex matched
80-83. 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
58 examinations.
Motor and nonmotor symptoms in drug-naive de novo Results: 75% of the LRRK2-PD patients and 95.5% of the IPD
Parkinsonian patients and their relationship to dopaminergic and patients showed SN1 (p50.087). The age of the aLRRK21, first-
serotonergic lesions degree relatives non mutation carriers and controls was similar (45
S. Thobois, A. Maillet, E. M et
ereau, H. Klinger, E. Lhomm ee, E. [38; 50], 45 [38; 51 and 45 [40; 60], respectively]. aLRRK21 sub-
Schmidt, A. Bichon, P. Pelissier, C. Caire, V. Fraix, D. Le Bars, E. 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%;
Broussolle, P. Krack (Bron, France)
p5 0.002). aLRRK21 had a larger area of SN echogenicity than the
Objective: To investigate the respective involvement of DA and first-degree relatives non mutation carriers (0.22 cm2 [0.16; 0.25] vs
5-HT neurotransmission dysfunction in the pathophysiology of both 0.16 cm2 [0.1; 0.2]; p5 0.030) and controls (0.11 cm2 [0.09; 0.15];
motor and nonmotor features in drug-naive de novo PD patients, p< 0.001).
using Positron Emission Tomography (PET) imaging. Conclusions: Hyperechogenicity of the SN is present in most
Background: Beyond the well-known dopaminergic (DA) deple- LRRK2-PD patients and in approximately sixty percent of the
tion, several lines of evidence indicate that serotonergic (5-HT) neu- asymptomatic LRRK2 G2019S mutation carriers. Properly designed
rons also degenerate in Parkinsons disease (PD). Previous works prospective studies should clarify whether hyperechogenicity of the
have suggested a link between the alteration of the 5-HT system and SN is a risk marker for development of Parkinsonism in asymptom-
the occurrence of motor (tremor, dyskinesia) and nonmotor (depres- atic LRRK2 mutation carriers.
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 60
the confounding effect of antiParkinsonian treatment. Cerebral blood oxygenation changes in the frontal lobe caused
Methods: Twenty-nine untreated and recently diagnosed (< 2 by deep brain stimulation in Parkinsons disease: A functional
years disease duration) PD patients, and fifteen age-matched healthy near infrared spectroscopy study
controls, were enrolled. Fourteen de novo PD patients presented apa-
K. Vyas, E. Sanchez, D. Smith, F. Vale, T. Malapira, T. Zesiewicz,
thy (LARS score  -21) with/without depression or anxiety. All sub- R. Murtagh, G.A. de Erausquin (Tampa, FL, USA)
jects underwent two PET-scans using DAT and SERT transporters
ligands ([11C]-PE2I and [11C]-DASB, respectively). We used Objective: We study the patterns of cerebral blood oxygenation
regions-of-interest (focused on caudate, putamen, ventral striatum) changes in the frontal lobe caused by electrical stimulation of subtha-
approach to explore the causal role of these two systems in PD lamic nucleus (STN) in patients with Parkinsons disease (PD) using
symptomatology. a new imaging method called functional near infrared spectroscopy
Results: Compared to controls, non-apathetic patients exhibited (fNIRS).
reduced bilateral DAT binding in anterior and posterior parts of puta- Background: Deep Brain Stimulation (DBS) surgery for idio-
men, globus pallidus and substantia nigra, but no alteration of SERT pathic PD is a well established treatment. Studies with PET scan

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


have shown that electrical stimulation of STN causes changes in cer- vated PD striatum (Politis et al. 2014); binding of the 5HT transporter
ebral blood flow in various cortical areas. NIRS opticallly measures (5HTT) reduces after onset (Politis et al. 2010). Patients at high genetic
oxyhemoglobin and deoxyhemoglobin concentration changes in cere- risk for PD including those with leucine-rich repeat kinase 2 (LRRK2)
bral vessels by means of characteristic absorption spectra of hemo- mutations provide a unique opportunity to compare the presymptomatic
globin in near infrared range. Previously, NIRS activation studies and symptomatic state of 5HT function in vivo. We hypothesized that
have shown that neuronal activation causes increases in oxyhemoglo- in LRRK2 mutation carriers, changes in 5HTT would precede both
bin, decrease in deoxyhemoglobin at the activated cortical area. We phenoconversion to PD and striatal DA denervation.
attempt to understand the hemodynamic changes in the frontal cortex Methods: 10 subjects with LRRK2 mutations (5 asymptomatic, 5
during STN-DBS using fNIRS. with manifest PD) and 7 with sporadic PD were compared to 7
Methods: Seven patients with Parkinsons disease were evaluated healthy controls. 5HTT binding was assessed using PET with [11C]
with electrodes implanted in the subthalamic nucleus. We measured (N,N-dimethyl-2-(2-amino-4-cyanophenylthio) benzylamine (DASB),
changes in oxyhemoglobin and deoxyhemoglobin in the bilateral fron- and DA innervation in striatum with (1)[11C]dihydrotetrabenazine
tal and prefrontal lobes during 2 stimulation conditions, stimulation- (DTBZ). DASB binding potentials were calculated for regions of
on and stimulation-off. We recorded time locked near infrared optical interest in cortex, striatum, diencephalon and brainstem. Regional
signals using 24 photoiodide channels arranged bilaterally over frontal binding was compared between presymptomatic mutation carriers,
and prefrontal lobes for optical detection (NIRx Medical Technolo- symptomatic carriers and sporadic PD using ANOVA.
gies, Los Angeles) with a sensitivity of <1 pW NEP and a dynamic Results: Unaffected mutation carriers had widespread increases
range of 90 dBopt, using 760nm and 850 nm wavelengths. in DASB binding, significant in anterior cingulate cortex (ACC)
Results: High frequency electrical stimulation of STN consis- compared to affected carriers (p50.02) and sporadic PD (p50.04),
tently increased deoxyhemoglobin with decreases in oxyhemoglobin in amygdala (p50.003, p50.008), and putamen (p50.05, p50.003).
in the frontal lobe in a time dependent manner when the patients No significant group differences were seen in other cortical, striatal,
were in the optimal electrode setting. There was an immediate diencephalic or brainstem sites or between the two affected groups.
increase in deoxyhemoglobin with the onset of stimulation. By con- All affected patients showed reduced striatal DTBZ binding. DASB
trast, when the stimulation was turned off, there was an increase in binding correlated significantly with DTBZ binding in the more
oxyhemoglobin. denervated putamen (R2 5 0.28, p50.03).
Conclusions: Our study showed various frontal lobe hemody- Conclusions: Compared with patients with LRRK2 PD and spo-
namic changes associated with electrical stimulation of subthalamic radic PD, unaffected LRRK2 mutation carriers have elevated 5HTT
nucleus. This might be due complex neuronal connections between binding in the putamen, amygdala and ACC. 5HT neurons may pro-
the frontal lobe and basal ganglia. Thus fNIRS offers a new way to vide an alternate means of DA biosynthesis as an early compensatory
investigate superficial brain activation and neural connectivity. mechanism before the motor onset of PD.

61 62
Striatal and cortical elevations in serotonin transporter binding Co-ordinate based meta-analysis of motor activation deficits in
precede motor onset in asymptomatic patients with LRRK2 gene people with Parkinsons and its relation to medication and
mutations attentive demand
D.J. Wile, K. Dinelle, J. McKenzie, N. Heffernan, M. Adam, Q. Y. Xing, M. Wongwandee, C.R. Tench, N. Bajaj, D.P. Auer
Miao, C. Zabetian, Z. Wszolek, J. Aasly, M. Farrer, V. Sossi, A.J. (Nottingham, United Kingdom)
Stoessl (Vancouver, BC, Canada)
Objective: To investigate (1)changes in motor brain activation pat-
Objective: To compare serotonin (5HT) function using PET tern(BAP) in people with Parkinsons disease(PwP) relative to elderly
imaging in asymptomatic and symptomatic patients with dominantly healthy controls(HC); (2)the influence of attention and dopaminergic
inherited pathogenic gene mutations for Parkinsons disease (PD) medication on BAP using co-ordinate based meta-analysis(CBMA).
and apparently sporadic PD. Background: Dopaminergic deficiency in the nigrostriatal path-
Background: The earliest (premotor) neurochemical changes in way is established as the major driver of motor dysfunction in PwP.
subjects who will develop PD are incompletely understood but may Previous motor task(MT) studies have identified some consistent
involve nondopaminergic systems including the 5HT system. 5HT neu- areas related to this defect. However, they also yielded numerous
rons share monoamine biosynthetic components with dopamine (DA) divergent results, which might be associated with study-wise
neurons and are known to contribute to DA processing in the dener- differences.

Fig. 1. (62).

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


Fig. 2. (62).

Methods: We undertook a systematic review searching all year 63

Medline, ScienceDirect and Neurosynth databases for functional neu-
roimaging studies involving PwP and age-matched HC. The search Withdrawn by Author
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). 64
Results: We identified differences between the common BAP Diagnostic flowchart using FP-CIT and MIBG scintigraphy in
during right upper extremity MT in elderly HC(1st row in Fig1) differentiating Parkinsonian syndromes in Japan
compared with PwP, which was most prominent for PwPoff(2nd row
M. Yogo, S. Omoto, K. Kawasaki, M. Ariizumi, M. Suzuki (Tokyo,
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 Objective: The aim of this study was to propose a diagnostic
medication effect as PwPon showed higher BAP in putamen, frontal flow chart for differentiating Parkinsonian syndromes (PS) in routine
gyrus and thalamus versus PwPoff, more consistent with a elderly clinical practice.
HCs BAP. Furthermore, we found a significant effect of attention in Background: [123I]FP-CIT SPECT (FP-CIT) was approved in Japan
PwP but not HC: significantly hyperactivation in medial frontal gyrus for clinical use for suspected PS in 2014. Thus, in vivo nuclear imaging of
and amygdala when attention was demanded for MT. presynaptic nigrostriatal neuronal degeneration and sympathetic cardiac
[figure1] innervation with SPECT is now available to distinguish idiopathic Parkin-
Motor-related BAP in HC(1st row) and PwPoff(2nd row). sons disease (PD) from other atypical Parkinsonian disorder (APD). How-
CBMA results for HC>PwPoff. ever, the use of these nuclear methods as stand-alone diagnostic means is
[figure2] not adequate for differentiating different types of PS.
Conclusions: CBMA demonstrated a consistent BAP of known Methods: A consecutive series of 49 patients with PS attending
motor networks in HC, and the expected cortico-striato-thalamic hypo- our clinic was prospectively recruited between May and November
activation in PwP. We also found supporting evidence for the consistent in 2014. First,we performed brain MRI to exclude advanced morpho-
role of limbic system and frontal lobes in compensatory mechanism logical changes due to APD, and then divided into 4 groups, Group1:
related to motor planning and attention. The less disparate BAP cases presenting gross morphological changes on MRI, Group2:
between PwPoff and HC provides proof for the symptomatic effect of cases showing normal findings on MRI and FP-CIT, Group3: cases
dopaminergic drugs at the neural network level, and a caveat for report- presenting abnormal findings on FP-CIT and low MIBG uptake,
ing functional BAP for both on- and off-medication in future studies. Group4: cases showing abnormal findings on FP-CIT and preserved

Fig. 1. (64).

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


uptake of MIBG. We proposed PS diagnostic flow chart based on Objective: To investigate L-Dopa effects on resting tremor (RT)
these conditions. (Figure 1). parameters, influenced by behavioral settings.
Results: Among the 49 Parkinsonism patients in whom a final Background: Parkinsons disease (PD) RT responds variably to
diagnosis could be made, there were 5 patients with advanced APD dopaminergic treatment.However,the influencing factors on the L-Dopa
such as multiple system atrophy, progressive supranuclear palsy, and effect are unclear. In contrast to many other PD symptoms,RT varies
cortico basal degeneration in group 1, 19 with drug induced Parkin- depending on behavioral context like cognitively demanding tasks.
sonism, essential tremor, vascular PD, scan without evidence of Methods: In 42 tremordominant PD patients(RT score>2UPDRS
dopaminergic deficits in group 2, 17 with Lewy body disease such as pts.)clinical scores(UPDRS,tremor rating scale) and accelerometry in
PD, dementia with Lewy bodies, and incidental Lewy body disease the 2 contexts:rest(3x60s) and cognitive coactivation(COCO;counting
in group 3, 8 with very early stage of degenerative PS in group 4. backwards in steps of three;3x60s)were collected in ON and OFF
Conclusions: This provisional flow chart including FP-CIT and state. RT power at individual RT frequency was estimated in Field-
MIBG SPECT might assist clinicians in making an accurate clinical trip by calculating time frequency representations between1-
diagnosis and minimizing costs and radiation exposure. Because the 20Hz.For the RT variability we calculated the coefficient of variation
present data are based on a small sample size from 1 center, confir- of the resulting RT amplitude regressor.Using repeated measures
mation of this flow chart in a large population is warranted using a ANOVA,we analyzed the effect of factors TREATMENT(OFF vs.
multicenter design. 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
The relative preservation of the nigral dopaminergic neuroal loss increased it(p<0.001). The L-Dopa effect was sign.smaller during
of the patients with Parkinsons disease having dopamine- COCO than during rest(TREATMENTxCONTEXT interaction,-
unresponsive resting tremor p=0.036).In fact, RT power during COCO ON L-Dopa was similar
S. You, H.W. Kim (Daegu, Korea) 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-
Objective: To evaluate the influenc of dopaminergic neuronal ficient>0.5;Spearmans q<0.001). RT variability increased after L-
loss to dopa-responsiveness of resting tremor in Parkinsons disease Dopa(p<0.001) and was smaller during COCO than rest(p<0.001);
patients. there were no sign. interactions. RT variability was inverse related to
Background: It has not been reported yet that whether there is a dif- clinical tremor constancy(correlation coefficient<-0.6;Spearmans
ference of dopaminergic neuronal loss between Parkinsons disease (PD) q<0.001).
patients with dopamine-unresponsive and -responsive resting tremor. Conclusions: A cognitively demanding task reduces the L-Dopa
Methods: Between September 1st 2012 and April 30th 2014, effect on RT(inconsistent with a previous study(Sturman
seven tremor dominant PD cases were obtained from neurology et al.,2007)).This emphasizes the importance of a simple counting
clinic stipulating: no other abnormal neurological signs or exposure task in clinical practice,as measurements at rest will overestimate the
to tremor reducing drugs. We defined the dopamine-responsiveness treatment effect.L-Dopa increased RT variability, indicating that
of resting tremor as a reduction of at least two points for more than patients experience more alternations between rest and tremor epi-
3 months in the UPDRS tremor score of the limb with prominent sodes. Both factors may contribute to the subjective experience of
resting tremor. All patients had underwent [18F] FP-CIT PET on many patients that L-Dopa is ineffective for RT.Future research is
OFF state within 1 year after PD diagnosis. We also executed the aimed to identify clinical, electrophysiological and cerebral factors
quantitative analyses of FP-CIT PET in all patients cases. FP-CIT influencing the L-Dopa effect on RT.
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 Parkinsons disease: Pathophysiology
index were compared between patients with dopamine-unresponsive
resting tremor and -responsive resting tremor.
Results: There were 3 men and 4 women (Average 67
age=60.9 6 10.9). The mean age of onset was 59.7 6 10.2 years. The
Auto-antibodies to a-synuclein are present in Parkinsons disease
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- R.S. Akhtar, K.C. Luk, J.Q. Trojanowski, V.M.Y. Lee (Philadelphia,
tive analysis of FP-CIT PET, BR for the substantia niagra of the PA, USA)
more affected side in patients with dopamine-unresponsive resting Objective: To develop an assay for auto-antibodies to a-
tremor was significantly higher than that in patients with dopamine- synuclein (a-syn) in biological fluid samples, and to measure auto-
responsive resting tremor (0.7163 6 0.08 vs. 0.43 6 0.02, P < 0.005). antibody titers in CSF and serum from Parkinsons disease (PD)
The BR for all striatal subregions in patients with dopamine- patients and healthy participants as a potential disease biomarker.
unresponsive resting tremor were higher than those in patients with Background: Biomarkers hold great promise in allowing early
dopamine-responsive resting tremor, but those were not significant. detection of PD and in identifying sub-populations within an otherwise
Conclusions: This study suggests that nigral dopaminergic neuro- clinically similar cohort of patients. Endogenous auto-antibodies to
nal loss in PD patients having dopamine-unresponsive resting tremor amyloidogenic proteins like a-syn have been proposed as biomarkers
can be less severe. This is a preliminary study, and the further in several neurodegenerative conditions, including PD. We hypothe-
research is needed for sure. 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-
66 syn as a capture substrate. We optimized this ELISA by systemati-
cally testing incubation parameters and blocking reagents to maxi-
L-Dopa effect on power and variability of Parkinsons tremor is mize the signal-to-noise ratio. We then assessed serum and CSF
influenced by the behavioral setting samples from PD patients and age-matched healthy controls (HC) for
H. Zach, M.F. Dirkx, J.W. Pasman, B.R. Bloem, R.C. Helmich a-syn auto-antibodies. Each sample was analyzed at least three times
(Vienna, Austria) in independent experiments.

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


Results: CSF samples from 54 HC and 93 PD patients and serum 69

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 Dopaminergic fibers from the substantia nigra to the olfactory
as compared to HC samples. Auto-antibody titers did not correlate bulb in the rat
with participant sex or age. In 15 serum-CSF sample pairs, there was D. Alvarez-Fischer, O. Arias-Carrion, C. Klein, W.H. Oertel, G.U.
a significant correlation in auto-antibody titer. Serum auto-antibody Hoeglinger (Luebeck, Germany)
titers were significantly higher in participants with at least one Objective: To elucidate the neuroanatomical basis of hyposmia
APOE e4 allele as compared to those without this allele. In contrast, in the pre-motor stage of Parkinsons disease (PD) and to investigate
CSF titers were not affected by presence of the APOE e4 allele. In the impact of the dopaminergic system on olfaction using a rat
the PD patients, there was no association between CSF auto-antibody model.
titers and cognitive impairment at the time of sample collection. Background: PD is a neurodegenerative disorder characterized
There was also no association between titer and cognitive and motor by a marked loss of midbrain dopaminergic neurons. Whereas onset
performance, as measured by the Dementia Rating Scale-2 and Uni- of motor impairments reflects a rather advanced stage of the disor-
fied Parkinsons disease Rating Scale, respectively. der, hyposmia is considered as a very early non-motor symptom of
Conclusions: Auto-antibodies to a-syn are enriched in both the disease. Little is known about the role of nigral dopaminergic
serum and CSF of PD patients as compared to age-matched healthy projection system in olfaction under physiological conditions and
participants. Further studies are necessary to determine if auto- about the anatomical basis of hyposmia in PD. Yet, the early occur-
antibodies that bind pathological forms of a-syn can also be detected rence of olfactory dysfunction implies that pathogens such as envi-
in PD patient biofluid samples. Furthermore, studies of longitudinally ronmental toxins could incite the disease via the olfactory system.
collected samples will determine whether auto-antibodies change Methods: We performed axonal tracing studies, retrograde intoxi-
with respect to disease progression. 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-
68 tion led to impaired olfactory perception, as evidenced in two
independent test paradigms (using unconditioned appetitive and con-
Admixing of two mice strains with differential susceptibility to ditioned aversive stimuli). Hyposmia following dopaminergic deaf-
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) positively ferentiation was reversed by means of pharmacological activation of
modulates the nigral dopaminergic phenotype dopamine receptors.
P.A. Alladi, D.J. Vidyadhara, H. Yarriephang, T.R. Raju (Bangalore, Conclusions: We demonstrate here the existence of a direct dopa-
India) minergic projection into the olfactory bulb and identify its origin in
the substantia nigra pars compacta of rats. These observations may
Objective: Systematic neuroanatomical evaluation of dopaminer- provide a neural basis for toxin or pathogen invasion into the basal
gic (DA) neurons of Substantia Nigra pars compacta (SNpc) in ganglia and for hyposmia as an early and frequent symptom in Par-
C57BL/6 mice (MPTP susceptible), CD-1 mice (MPTP resistant) and kinsons disease.
their crossbreds to delineate the phenomenon of differential suscepti-
bility to MPTP induced neurotoxicity.
Background: An interesting aspect of Parkinsons disease (PD) is 70
that it has differential prevalence among different ethnic groups. For Gait patterns associated with freezing of gait in patients with
example, PD is less prevalent in Asian-Indians compared to Caucasians. Parkinsons disease
Further, Anglo-Indians the admixed population of European and Asian M. Amboni, L. Iuppariello, I. Lista, R. Rucco, P. Varriale, M.
Indian origin are 5 times lesser vulnerable than Indians. We aim to under- Picillo, A. Iavarone, G. Sorrentino, P. Barone (Baronissi (Salerno),
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, Objective: To investigate gait patterns associated with freezing
CD-1 mice and the first filial generation of the reciprocal crosses of gait (FOG) in Parkinsons disease (PD).
(F1X1 & F1X2) were studied (n56/group). Unbiased stereology of Background: FOG is a common and debilitating symptom in
tyrosine hydroxylase (TH) immunostained serial midbrain sections patients with PD. FOG refers to paroxysmal events in which a sub-
provided the absolute neuronal numbers; densitometry based image ject is unable either to initiate locomotion and to turn or to walk
analysis and immunoblotting revealed protein expression levels; and through a doorway. Beyond freezing episodes, inconsistent walking
morphometry revealed their cellular character. abnormalities have been reported.
Results: Stereological quantification showed significantly higher Methods: Thirty PD patients were enrolled. All patients were nei-
number of nigral DA neurons in CD-1 and the crossbred mice com- ther demented nor depressed. The clinical assessment included H&Y
pared to C57BL/6. Further, there were insignificant differences in the stage, MDS-UPDRS I, II and IV at on state, MDS-UPDRS III both
neuronal densities except for the F1X2 crossbreds. Both, densitomet- at on and off state, Mini Mental State Examination (MMSE) and
ric analysis and immunoblots revealed significantly higher TH Frontal Assessment Battery (FAB). Quantitative gait analysis was
expression in the crossbreds compared to C57BL/6. The neuronal performed by means of a motion capture system (Qualisys, Sweden).
nuclear and soma area of F1X1 and C57BL/6 matched well; while The following conditions were investigated during off state: 1) nor-
those of FIX2 and CD-1 were similar. mal gait (Gait-off); 2) cognitive dual task (Cog-off); 3)motor dual
Conclusions: The presence of higher number of nigral neurons in task (Mot-off). Any freezing episode was excluded by the analysis.
CD-1 mice provides anatomical basis for its resistance to MPTP Statistical analysis was carried out by means of the Mann-Whitney
induced toxicity. The comparability of numbers in crossbreds and CD- test followed by a logistic regression analysis.
1 mice, complemented by higher TH expression, argue for similar neu- Results: Based on the objective assessment of FOG during gait
roprotection in the crossbreds. The morphological differences in dopa- analysis, fourteen subjects were classified as patients with FOG
minergic neurons of susceptible and resistant strains indicate that (FOG1) and sixteen subjects were classified as patients without
neuronal size may be a decisive factor of vulnerability. Thus, our study FOG (FOG-). There were no significant differences on age, gender,
provides neuroanatomical basis for differential MPTP susceptibility in disease duration, H&Y stage during on, MDS-UPDRS I, II, III (dur-
mice and the admixing provides an interesting experimental paradigm ing on), MMSE and FAB scores between the two groups. The two
to study the human phenomenon of differential prevalence of PD. groups differed on MDS-UPDRS III during off and MDS-UPDRS

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


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.

Staining for unphosphorylated alpha-synuclein in the colon Fig. 2. (71).
mucosa. No difference between patients with Parkinsons disease
and healthy controls
L. Antunes, S. Frasquilho, M. Ostaszewski, J. Weber, L. Longhino, sities was not significant. However, stronger and more frequent
P. Antony, A. Baumuratov, P. Derkinderen, R. Balling, N.J. immunostaining was present in the right than in the left colon
Diederich (Luxembourg City, Luxembourg) (p50.04).
Conclusions: Our data support the results of two other recent
Objective: To search for alpha-Synuclein in the colon mucosa in studies: unphosphorylated alpha-Synuclein is present in the colon
patients with idiopathic Parkinsons disease (IPD) and in healthy mucosa of both IPD patients and HC. However, the staining is more
controls (HC). abundant in the proximal part of the gut, suggesting that the risk for
Background: The gut has been proposed as the starting point of disease generation may be segment-dependent. Importantly, these
IPD. Due to barrier leakage, a toxin could pass the mucosa and trig- data need confirmation by screening for phosphorylated alpha-
ger the disease process by misfolding alpha-Synuclein. However, Synuclein as well.
there are only scarce and so far controversial data on the presence of Immunostaining with alpha-Synuclein (Syn204) Mouse mAb;
alpha-Synuclein in the mucosa of the gut. x200 in a healthy control subject; Figure 1: medium presence of
Methods: Twenty IPD patients (age: 66.9 6 8.4 yrs.; mean disease unphosporylated alpha-Synuclein in the right colon; Figure 2: weak
duration: 6.95 6 6.8yrs., 50% male) and 8 HC (age: 65.6 6 3.9yrs., presence of unphosporylated alpha-Synuclein in the left colon.
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 72
alpha-Synuclein was performed with alpha-Synuclein (Syn204) Mouse
mAb. Presence of alpha-Synuclein was evaluated in a semi-quantitative Endemic vitamin D deficiency, impact on incidence and
manner (no presence, weak, medium, strong presence). The examiners prevalence of Parkinsons disease
were blinded for the status of the subject (IPD versus HC). J.A. Bajwa, S. Nahrir, T.M. Muhammad, M.S. Bashir, A. Mujtaba,
Results: Sufficient biopsy samples (left and right colon part) and S.R. Siddiqui (Riyadh, Saudi Arabia)
adequate immunostaining were present in 27 subjects: 19 IPD
patients and 8 HC. Unphosporylated alpha-Synuclein was present in Objective: To evaluate vitamin D (Vit. D) deficiency in Parkin-
18 of 19 IPD patients and in all controls. The difference in inten- 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
Fig. 1. (71). was no statistically significant association of Vit. D deficiency with

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


symptoms of PD. There was higher trend for Vit. D deficiency in PD sia, and rigidity. Exaggerated oscillations are observed in PD patients
patients with age of onset being less than 50 y. in local field potentials in a 13-30Hz band termed the beta band
Conclusions: Vit. D deficiency could be a potential modifiable and are correlated with emergence of bradykinesia. However, the
risk factor in PD. Endemic Vit. D deficiency may have implications relationship between beta band oscillations and symptom progression
on PD incidence and prevalence, progression and treatment. Further in PD remains unclear.
controlled studies are required in larger sample size to assess the Methods: We recorded cortical EEG in fifteen PD patients of
role of Vit. D in PD pathophysiology and treatment. 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
73 unilateral and bilateral isometric grip and rapid movement tasks. We
Gait impairment and cholinergic dysfunction in early PD: Does quantified total percent of spectral power (TPSP) in the beta fre-
vascular risk play a moderating role? quency band for each cortical channel with respect to motor state,
S.F. Bartlett, B. Galna, R.A. Lawson, S.E. Lord, R.E. Morris, A.J. disease duration, and off-medication Unified PD Rating Scale
Yarnall, D.J. Burn, L. Rochester (Newcastle upon Tyne, United (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-
Objective: To compare the relationship between short latency come measures.
afferent inhibition (SAI) and quantitative gait characteristics in Par- Results: Across all subjects and channels, TPSP in the beta band
kinsons (PD) subjects with high and low vascular risk. decreased significantly with eye closure at rest and varied little
Background: Cholinergic dysfunction contributes to gait impair- across motor tasks. Across disease duration cohorts, TPSP in the
ment in PD. Recently, cardiovascular risk factors have been impli- beta band averaged across tasks and channels was significantly
cated in higher level gait disorders in PD. We hypothesised that the increased in the 5-10yr and >10yr cohorts (p<0.0001) as compared
relationship between gait and SAI would be moderated by cerebro- to the < 3yr cohort. No significant difference was found between the
vascular damage to cholinergic pathways. 5-10yr and >10yr groups (p50.365). Across UPDRS 3 categories,
Methods: Forty one incident PD subjects and 44 age-matched TPSP in the beta band averaged across tasks and channels was sig-
controls were assessed as part of the ongoing ICICLE-GAIT study, a nificantly lower in the moderate group as compared to the mild
collaborative study with ICICLE-PD. Mean age 69.3 6 10.1 years in group (p<0.0001) and lower in the severe group as compared to
PD, 68.5 6 8.4 years in controls (p50.695). Subjects past medical the moderate group (p<0.0001). Regression analysis of average
history was obtained and relative cardiovascular risk quantified as 10 beta band TPSP as a function of UPDRS 3 score revealed a small,
year risk compared to expected risk for age and sex, using the significant negative slope (p<0.0001) and an R^2 of 0.054.
QRISK2 calculator. This was used as a proxy for risk of cerebrovas- Conclusions: Our data suggest that increasing beta band power
cular damage. Low risk was defined as a relative risk ratio 1 and may be a marker for disease duration but does not appear to be
high risk as a ratio >1, or existing cardiovascular disease. Choliner- related to degree of motor impairment.
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 75
correlations and linear regression models. Cerebellar theta-burst stimulation for the evaluation of the
Results: SAI was higher (more impaired) in PD than controls pathophysiology and the therapeutic potential for rest tremor in
(75.53 6 23.72 vs. 58.67 6 22.17, p50.001). Gait was impaired in Parkinsons disease
PD subjects, who showed reduced velocity (p50.005), step length D. Benninger, J. McNames, F. Herrmann, F. Medlin, F. Vingerhoets,
(p50.005), increased step length variability (p50.017) and stance M. Stephan (Lausanne, Switzerland)
time asymmetry (p50.027). There was no difference in SAI or gait
characteristics between high (n517) and low risk (n524) PD groups Objective: To investigate whether functional activation or inhibi-
(p50.611) . Despite this, SAI explained 45.7% of variance in step tion of the cerebellum by transcranial magnetic stimulation modu-
length in high risk PD compared to only 2.6% in low risk PD and lates rest tremor in Parkinsons disease.
0.2% in high risk controls. Background: Rest tremor in Parkinsons disease (PD) is dis-
Conclusions: Our findings suggest that vascular burden may abling and responds often incompletely to conventional therapy. The
underpin gait impairment associated with cholinergic dysfunction in pathogenesis remains largely unknown and therapeutic alternatives
PD. This relationship was only observed in those with PD and high are needed. Functional imaging, neurophysiology and structural stud-
vascular risk and was not observed in high risk control participants ies, and stereotactic surgery point to an involvement of the cerebel-
so is unlikely to be related to fitness or cerebrovascular burden alone. lum and the cerebello-thalamo-cortical pathway in generation of
Rather, it may represent a cumulative burden of cerebrovascular Parkinsonian tremor, but the precise nature of the functional disturb-
parenchymal damage, dopaminergic loss, and cholinergic dysfunc- ance remains unknown.
tion, with implications for early gait impairment. 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,
74 excitatory) and sham stimulation of both cerebellar hemispheres.
Quantification of beta activity with disease progression in EEG Assessment of rest tremor, motor function and neurophysiology were
recordings in Parkinsons disease patients performed before and after each intervention including a 14-day
C.E. Behrend, B.E. Mace, L. Gauger, B.J. Kolls, W.M. Grill monitoring of tremor and motor activity.
(Durham, NC, USA) Results: Continuous TBS, intermittent TBS and sham stimulation
of the cerebellum had no effects on tremor and motor performance
Objective: To determine how beta frequency oscillatory activity and failed to restore cerebello-cortical inhibition in Parkinsons
varies with disease progression and severity in human Parkinsons disease.
disease (PD) patients using cortical electroencephalogram (EEG). Conclusions: The contribution of cerebellar dysfunction in the
Background: PD is a progressive disease in which loss of dopa- pathophysiology of Parkinsons disease remains undetermined, but
minergic neurons results in increased burst and oscillatory firing in cerebellar stimulation may not offer a therapeutic alternative for
the cortical-basal ganglia loop and symptoms of tremor, bradykine- tremor.

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


76 Methods: To test this hypothesis, we injected intracerebroventric-

ularly (i.c.v.) high-titer bolus of AAV2/9 carrying either mutant
Progressive nigrostriatal neurodegeneration associated with a- human a-synuclein (A53T) or enhanced green fluorescent protein
synuclein pathology induced by AAV-mediated overexpression of (EGFP) under the synapsin or CMV immediate enhancer/b-actin
mutant a-synuclein in mice, rats and marmosets (CAG) promoter respectively, at embryonic day 16.5 for rat and
M. Bourdenx, S. Dovero, M. Engeln, S. Bido, C. Piron, M. Bastide, around 100 days fetal age for monkeys under ultrasound imaging
I. Vollenweider, L. Baud, Q. Li, V. Baekelandt, D. Scheller, A. guidance. Animals after birth have then be behaviourally followed-
Michel, T. Boraud, P.O. Fernagut, F. Georges, G. Courtine, E. up and were terminated at regular interval to access the brain
Bezard, B. Dehay (Bordeaux, France) pathology.
Objective: Animal models are an essential asset for basic patho- Results: We characterized the regional distribution of GFP
physiological research as well as validation of therapeutic strategies immuno-positivity in brain structures and peripheral organs. We
of human diseases. observed transduction of neurons in most regions of the brain i.e.
Background: The absence of adequate in vivo experimental mod- within hippocampus, thalamus, spinal cord, striatum, globus pallidus,
els has severe repercussions for therapeutic intervention success. To substantia nigra, choroid plexus, cerebellum, and cortex- 25 days
date, no mammalian model recapitulates the required age-dependent after injection in rats. Moreover, the efficacy of transduction seems
phenotypes associated with Parkinsons disease (PD). Both the spe- dependent on the brain structure. Transduction of mutated a-
cies and age-related differential susceptibility of dopaminergic neu- synuclein was then characterized as was defined the specific brain
rons was assessed by comparing the extent and pattern of neuronal lesions in both rats and monkeys.
loss, as well as occurrence of age-dependent intracellular inclusions Conclusions: Overall, these results indicate that an engineered
a-synuclein formation, in mice, rats and monkeys. AAV serotype 9 variant (scAAV9) injected in utero in rats or rhesus
Methods: We selected a series of models of ascending complex- macaques results in efficient, neuronal and widespread transduction
ity with three different strains of mice (i.e. C57Bl/6, senescence- of the brain. Altogether, this proof of concept study could facilitate
accelerated prone mouse (SAMP8), as a model of aging and their lit- and offer unique opportunities for modelling brain diseases in rats
termate controls, senescence-accelerated resistant mouse (SAMR1)), and rhesus macaques by targeting mutant genes with tissue-specific
adult rats and young versus aged marmoset monkeys. Each model gene expression, not mentioning future clinical applications for in
received a stereotatic injection in the substantia nigra pars compacta vivo correction of monogenic diseases or abnormalities in humans.
(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 78
WPRE enhancer element. Sixteen weeks after injection, we systemi-
cally investigated both species specifics and age-dependent differen- Does the side of onset in Parkinsons disease correlate with
tial susceptibility of dopamine neurons regarding the extent and interleukins levels?
pattern of neuronal loss and kinematic analysis for rats. We also L.S. Campos, F. Pradella, A.S. Farias, G.A.D. Moraes, R.F.O. de
assessed a-synuclein expression levels, pathological state (i.e. S129 Paula, F. Von Glehn, L.G. Piovesana, P.C. Azevedo, A.S. Moraes,
phosphorylation) and occurrence of intracellular inclusion formation. M.D. Andrade, A. DAbreu, L.M.B. Santos (Campinas, Brazil)
Results: We successfully induced dopaminergic degeneration in
all species. Mice were less susceptible to a-syn-mediated toxicity Objective: Evaluate interleukins levels- anti- and proinflamma-
compared to rats and monkeys. Both SAMP8 and SAMR1 present a tory- in subjects with Parkinsons disease (PD) and correlate those
strong a-syn staining which was not correlated with the occurence of with clinical manifestations.
degeneration. High-resolution kinematic analyses revealed that rats Background: Several studies showed altered cytokine levels in
exhibited the hallmarks of Parkinsonian syndromes during gait, Parkinsons disease (PD). However, the role of those cytokines in
including periods of freezing, postural instability, and reduced speed the pathophysiology of PD has not yet been established.
of motion. In marmosets, old animals were more susceptible to Methods: We evaluated 21 subjects who fulfilled the Brain Bank
degeneration at both fibers and cell body levels. Criteria for PD diagnosis . All patients answered a structured stand-
Conclusions: According to the species used, we observed differ- ardized clinical questionnaire and the following scale: UPDRS, The
ences in the PD-related neurodegeneration progression over time modified Hoehn and Yahr staging, Schwab and England Scale,
associated with a-synucleinopathy. 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
77 rigid-akinetic (RA) . We measured the following serum citokines
In utero delivery of scAAV9 mediates widespread brain levels: IL-6, TNF-a, TGF-b, IL-10.
transduction in rats and monkeys: Towards new models of PD Results: Lelves of IL-6 (0.0053411 6 0.0059566 versus
M. Bourdenx, L. Chansel-Debordeaux, S. Dovero, V. Grouthier, J. 0.0012878 6 0.0017099; p50.0362) and TNF-a (0.0298595 6
Uranga, N. Dutheil, S. Brun, A. Espagna, L. Groc, Q. Li, C. Jimenez, 0.0174282 versus 0.0140438 6 .009449; p50.0102) were signifi-
cantly higher in subjects with a left-sided onset compared to those
E. Bezard, B. Dehay (Bordeaux, France)
with a right-sided onset. There was no significant difference in age,
Objective: Transgenic mammals allow to study brain function sex distribution, age of onset, prevalence of dementia, depression,
and diseases. and other clinical scale scores between subjects with left-sided onset
Background: The adeno-associated virus serotype 9 (AAV2/9) compared to those with a right-side one. We also observed higher
crosses the blood brain barrier, is capable of transducing developing levels of IL-6 in subjects with dementia when compared to those
cells and neurons after intravenous injection in many species, and with normal cognition (0.0019666 6 0.0032651 versus .0064117 6
mediates a long-term stable transduction. Ability to transduce brain .0064288, p50.0496).
decreases over time, being maximum at P1 and decreasing dramati- Conclusions: We found higher levels of proinflamamtory cyto-
cally by P10 already suggesting a developmental period in which kines in subjects with a left-side onset compared to those with a
AAV2/9 transduction has maximal efficacy. While P1 is an attractive right-side onset and in those with dementia compared to those with
(and easily accessible) time point, in utero gene delivery has clearly normal cognition. Those cytokines likely mediate neuronal degenera-
demonstrated that a wide transduction of neurons is possible at tion, and their levels probably correlate with the differential clinical
embryonic stages compatible with the development of the targeted presentation previously observed in clinical studies considering side-
area. of-onset.

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


79 alpha (TNF-a), glutathione reductase, malondialdehyde, nitric oxide

and catalepsy score were measured.
Dyskinesias are associated with a narrowband 70 Hz activity as Results: MPTP induced Parkinsonism in all rats proved by the
revealed by chronic cortical and subcortical recordings in significant increase in catalepsy score and the significant decrease in
Parkinsons disease patients striatal dopamine level. Pre-existing of diabetes before Parkinsonism
C. de Hemptinne, N. Swann, S. Miocinovic, S. Qasim, S. Wang, N. induction worse the condition and increase the severity of Parkinson-
Ziman, J. Ostrem, M. San Luciano, N. Galifianakis, P. Starr (San ism. Exenatide administration to diabetic MPTP rats induced signifi-
Francisco, CA, USA) cant increase in the striatal dopamine, glutathione reductase with a
Objective: To investigate the electrophysiological characteristics significant decrease in striatal TNF-a level, nitric oxide and malon-
of cortical and subcortical activity associated with dyskinesias in Par- dialdehyde level with significant improvement in the catalepsy score
kinsons disease (PD). better than the non-treated diabetic MPTP group, and the MPTP
Background: Levodopa-induced dyskinesias (LID) are one of the group.
most frequent and disabling motor complications of long-term dopa- Conclusions: Diabetes mellitus increases the severity of impair-
mine replacement in patients with PD. Deep brain stimulation (DBS) ment in Parkinsonism disease. The benefits of incretin extend beyond
can also exacerbate or induce dyskinesia, especially shortly after their hypoglycemic effects since it success as a neuroprotective agent
implantation, limiting the therapeutic efficacy of PD treatments. In in rats with Parkinsonism through multiple mechanisms of action
order to improve these therapies it is crucial to investigate the patho- including the anti-inflammatory, antioxidant and anti-apoptotic effect
physiology underlying these periods of involuntary movements that largely independent of its hypoglycemic effects.
is still largely unknown.
Methods: Two PD patients with severe motor fluctuations, mini- 81
mal tremor and experiencing periods of dyskinesias have been
implanted with an investigational, totally implanted neural interface UPDRS asymmetry is higher for the upper extremities compared
capable of both recording and stimulation. This device was con- to the lower extremities in Parkinsons disease
nected to a standard quadripolar DBS electrode placed in the subtha- G. Foffani, J.A. Obeso (Mostoles, Spain)
lamic nucleus (STN) and one subdural quadripolar strip electrode
Objective: To test whether left-right clinical asymmetry is differ-
placed over the primary motor cortex (M1). Cortical and subcortical
ent for the upper extremities compared to the lower extremities in
signals were recorded simultaneously in the outpatient clinic over
Parkinsons disease.
multiple visits, in the on and off medication state and on and of
Background: The clinical onset of Parkinsons disease typically
stimulation, during both dyskinetic and non dyskinetic states. Signals
affects one body side with progression towards the other side taking
were sampled at 800 Hz, stored internally, downloaded noninvasively
place some few years later. Whether this clinical asymmetry differs
by radiotelemetry then analyzed.
between upper and lower extremities remains unknown.
Results: Periods of dyskinesias were associated with the emer-
Methods: Data were obtained from the Parkinsons Progression
gence of a narrow-band peak in spectral power at about 70 Hz in
Markers Initiative (PPMI) database ( We
both M1 and STN signals, although most prominent in M1. An
analyzed the UPDRS III scores of the full cohort of patients with
increase in coherence between both structures was also observed at
Parkinsons disease included in the PPMI database at their baseline
the same frequency. This pattern has been reliably observed during
screening. Left and right UPDRS scores were separately obtained for
periods of levodopa induced dyskinesias over multiple visits. Prelim-
the lower and upper extremities by summing the corresponding later-
inary results also suggest that stimulation induced dyskinesias is
alized UPDRS items for rigidity, bradykinesia and tremor (3.3b-e,
characterized by a similar pattern of activity.
3.4a-b, 3.5a-b, 3.7a-b, 3.8a-b, 3.17a-d). To minimize floor effects,
Conclusions: Dyskinesias are characterized by a narrowband 70
we considered only patients in which the sum of these UDPRS items
Hz rhythm at the cortical and subcortical level. This signal, could be
was 10 (n5252). Clinical asymmetry was measured as the absolute
used in a closed loop DBS paradigm that would automatically adjust
value of left-right UPDRS scores, expressed as a percentage of the
the DBS settings, based on this biomarker, to reduce stimulation
corresponding left1right scores.
amplitude or active configuration so as to optimize dyskinesia
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
80 decreased from 54.5% to 29.7% as left1right UPDRS scores
increased from 6 to 10 (2-way independent-measures ANOVA, factor
Neuroprotective effect of incretin in rat model of Parkinsonism
UPDRS: F(4,286)=6.6, p<0.0001). More importantly, clinical asym-
with pre-existing diabetes
metry was significantly higher for the upper extremities (54.61/-
E.A. Elbassuoni (Minia, Egypt) 30.1%) compared to the lower extremities (42.81/-31.1%; factor
Objective: The goal of this work is to study the effect of pre- EXTREMITIES: F(1,286)=33.8, p<0.0001). In the small subset of
existing streptozotocin-induced diabetes on the severity of 1-methyl- patients whose left1right UPDRS scores were identical for the lower
4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) -induced Parkinsonism and upper extremities (n517), clinical asymmetry was higher for the
in male albino rats, and to find out if GLP-1 could improve symp- upper extremities (47.61/-35.3%) compared to the lower extremities
toms of Parkinsonism in the diabetic animals, and work out how it (37.31/-28.5%; paired t-test: p50.0134).
might do this. Conclusions: Parkinsons disease seems clinically more asymmet-
Background: Previous studies have suggested associations rical in the upper extremities compared to the lower extremities.
between midlife diabetes mellitus (DM) and neurodegenerative dis- This clinical observation could reflect a different UPDRS sensitivity
eases, DM contributes to cognitive impairment in the elderly, but its between upper and lower limbs, or could suggest that motor progres-
effect in Parkinsonism is not well studied. Glucagon-like peptide-1 sion advances somatotopically in a caudal-to-rostral direction.
(GLP-1), as a member of the incretin family, has roles in glycemic
control and satiety. In addition, it appears to exert several additional 82
effects on many tissues via the widespread expression of its receptor.
Methods: 40 adult male albino rats were divided into 4 equal Fixin to die: A common death pathway in catecholamine
groups: control untreated group, MPTP group, diabetic MPTP group, neurons
and diabetic MPTP group1 exenatide (a synthetic GLP-1 mimetic). D.S. Goldstein, C. Holmes, P. Sullivan, Y. Sharabi, I.J. Kopin
At the end of the experiment striatal dopamine, tumor necrosis factor (Bethesda, MD, USA)

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-
Fig. 1. (82). 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-
Objective: We tested whether across a variety of diseases,
cific interneuron markers. The activity of each interneuron type was
including familial and sporadic Parkinsons disease (PD) and multi-
assessed by colocalization of each interneuron marker with c-fos.
ple system atrophy (MSA), neuroimaging and neurochemical evi-
Results: Changes in c-fos and interneuron markers were observed
dence for a vesicular storage defect and decreased aldehyde
both after dopaminergic depletion and LID development. 6-OHDA
dehydrogenase (ALDH) activity accompany catecholaminergic dener-
lesion led to reduced number of parvalbumin positive interneurons
vation, independently of the initial disease process.
and this change was not reversed by L-DOPA administration. On the
Background: Several neurodegenerative diseases such as PD
other hand, no significant changes were observed in the number of
involve prominent loss of catecholamine neurons. Determinants of
cholinergic interneurons within the different experimental groups.
vulnerability of catecholamine neurons have been obscure. We
Conclusions: Our findings suggest that changes in striatal inter-
hypothesized that decreased vesicular storage and decreased ALDH
neurons contribute to the maladaptive state that occur after dopamine
activity constitute a common final pathway in catecholamine neuro-
depletion. In addition, chronic treatment with L-DOPA fails to rees-
nal death. The combination would be expected to build up levels of
tablish the initial physiological scenario. Further functional studies
3,4-dihydroxyphenylacetaldehyde (DOPAL), the autotoxic metabolite
are required to elucidate if these changes are just an epiphenomenon
of dopamine. DOPAL and alpha-synuclein may be nodes in a com-
or if they actually contribute to LID development.
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- 84
ing and neurochemistry and post-mortem tissue neurochemistry in
patient groups with catecholaminergic denervation in the brain or L-DOPA induced motor changes in alpha-synculein model of
periphery (e.g., PARK1, PARK4, Gaucher/PD, sporadic PD, MSA, Parkinsons disease in C. elegans
pure autonomic failure, progressive supranuclear palsy) and in D.K. Gupta, X. Hang, Z. Feng (Cleveland, OH, USA)
groups without catecholaminergic denervation.
Objective: To establish a C. elegans model for L-DOPA-induced
Results: Accelerated loss of 18F-dopamine-derived radioactivity
dyskinesia in Parkinsons disease.
was found specifically in groups with cardiac sympathetic denerva-
Background: L-DOPA induced dyskinesia (LID) is a disabling
tion, and accelerated loss of putamen 18F-DOPA-derived radioactiv-
complication of dopaminergic therapy in Parkinsons disease (PD).
ity was found specifically in groups with Parkinsonism. Myocardial
There is a lack of simple animal models of LID that can capture this
norepinephrine depletion was associated with decreased vesicular
clinical phenomenon and enable mechanistic study and high-
storage in cardiac sympathetic nerves and putamen dopamine deple-
throughput drug screening. C. elegans, which has a short lifecycle
tion with decreased vesicular storage in nigrostriatal terminals.
( 3 weeks) and rich genetic resource, is a robust animal model to
Decreased putamen ALDH activity and low CSF 3,4-dihydroxyphe-
study pathophysiology of PD.
nylacetic acid levels were found in Parkinsonian but not in non-
Methods: We used alpha-synuclein expressing C. elegans model of
Parkinsonian groups.
PD, which exhibits progressive degeneration of dopaminergic neurons
Conclusions: Diseases involving catecholaminergic denervation
and loss of motor activity. Day 1 worms from this model and wild type
entail a pattern of decreased vesicular storage and decreased ALDH
N2 controls were divided into three groups based on their exposure to
activity, regardless of the disease etiology or initial disease process,
L-DOPA (1mM): no exposure, continuous exposure (day 2-10) and
consistent with a common death pathway in catecholaminergic
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.
83 [figure1]
Results: Compared to controls, a progressive, age-related reduc-
Contribution of striatal interneurons to L-DOPA induced tion in LS was observed in PD worms, which was alleviated by both
dyskinesia development in an animal model of Parkinsons continuous and alternating L-DOPA exposure (figure 1a). In contrast,
disease BR was not altered in PD worms. However, BR of PD worms was
G. Gomez, I.R. Taravini, M.G. Murer, O.S. Gershanik (Ciudad significantly increased by L-DOPA exposure, with more dramatic
onoma de Buenos Aires, Argentina) effect on alternating exposure (figure 1b). PD worms also exhibited

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


Fig. 1. (84).

an age-related reduction in PDBD compared to controls. PDBD of Conclusions: Like published data, our cohort also shows strong
PD worms was not changed by continuous L-DOPA exposure but association between handedness and side of initial symptom (P-value
was further reduced by alternating L-DOPA exposure (figure 1c). 0.009) even though the sample size was small. Further research is
Conclusions: PD worms exhibit progressive, age-related loss of required to determine PD side of onset, symptom at onset and corre-
motor activity, which is alleviated by L-DOPA treatment. However lation with hand dominance.
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 86
pathophysiology and may potentially represent motor phenotype of
Identification of novel biomarkers for Parkinsons disease by
LID in C. elegans. These findings need be further validated as such
metabolomics technologies
simple animal model of LID in C. elegans may have important
implications for discovering molecular mechanisms and performing T. Hatano, S. Saiki, A. Okuzumi, N. Hattori (Tokyo, Japan)
high-throughput drug screenings for LID. 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
85 study, we attempted to elucidate the candidate metabolic pathway(s)
Is handedness correlated to Parkinsons disease side of onset? associated with PD.
S. Hanif, M.S. Hassan, R.A.l. Sharif, Z.G. Aljohani, J.A. Bajwa Background: Although the pathomechanisms underlying neuronal
degeneration in PD remain unknown, various PD-related genetic-
(Riyadh, Saudi Arabia)
environmental interactions may contribute to the pathogenesis of this
Objective: To describe correlation between handedness and onset disease. Previous studies revealed the diagnostic value of measuring
of motor symptoms in Parkinsons disease patients at Movement a-synuclein and DJ-1 levels in cerebrospinal fluid; however, useful
Disorders center, National Neuroscience Institute, King Fahad Medi- biomarkers related to genetic and environmental factors have not yet
cal City, Riyadh, Saudi Arabia. been elucidated. Serum/plasma metabolomics is a useful tool for
Background: Parkinsons disease (PD) characteristically presents understanding metabolic pathways and networks in neurodegenera-
with asymmetrical motor symptoms. One hypothesis is that motor tive diseases.
asymmetry can be an epiphenomenon of underlying anatomical Methods: Serum samples were collected from 35 individuals
asymmetry. Multiple factors could be involved in asymmetric presen- with idiopathic PD without dementia; 18 males, mean age
tation of disease like age, sex, disease duration and handedness. Pub- 69.1 6 10.8 years; mean Hoehn & Yahr (H-Y) 2.9 6 1.1 and 15
lished data postulates that PD motor symptoms emerge more often healthy age-matched and sex-matched control subjects without PD: 7
on the dominant hand side. Asymmetric motor symptoms onset cor- males, age 70.7 6 9.7 years. This analysis was based on a combina-
related to dominant hand side has not been yet investigated in Arab tion of three independent platforms: ultrahigh-performance liquid
cohort. chromatography/tandem mass spectrometry (UHPLC/MS/MS) opti-
Methods: Seventy four PD patients and their charts were mized for basic species, UHPLC/MS/MS optimized for acidic spe-
reviewed to get demographic details like age, sex, disease related cies, and gas chromatography/mass spectrometry.
parameters i.e duration of PD, subtype of PD, initial motor symptom Results: The metabolomic profiles of PD were clearly different
of tremor, rigidity, bradykinesia and family history. Patients were from normal controls. PD profiles had significantly lower levels of
also interviewed over the phone to specifically ask about first motor tryptophan, caffeine and its metabolites, bilirubin, ergothioneine, and
symptom, sidedness and handedness. significantly higher levels of levodopa metabolites and biliverdin
Results: The majority (87.8%) of our patients were right handed than those of normal controls. Alterations in bilirubin/biliverdin ratio
among who 55 (74.5%) were male and 19 (25.7%) were females. and ergothioneine can indicate oxidative stress intensity and may
97% of all patients were above the age of 45 y at the time of diagno- suggest elevated oxidative stress and/or insufficient ability for scav-
sis. Tremor was the first motor symptom in 65%, bradykinesia in enging free radicals which could contribute to PD pathogenesis.
23% and rigidity in 13.5%. There was a significant association Decreased serum tryptophan level is associated with psychiatric
between handedness and site of initial symptom. 63.1% of right problems in PD. A decrease in serum caffeine levels is consistent
handed patients experienced their first symptom on the right side and with an inverse association of caffeine consumption with develop-
36% on their left side. Similarly 87.5% of the left handed patients ment of PD based on past epidemiological studies.
reported their initial symptom on the left side and remaining 12.5% Conclusions: Metabolomics analysis detected biomarkers associ-
on their right side (P-value 0.009). ated with PD pathogenesis and disease progression.

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


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


Fig. 2. (87).

NSDA neurons in a neurotoxicant model of DA neuronal degenera- Methods: Five subjects with idiopathic PD with FoG (FoG1,
tion similar to that which occurs in PD. 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
88 wireless EMG sensors on bilateral tibialis anterior (TA), gastrocne-
Insights into freezing of gait from wearable sensors mius medialis (GM) and at the hip on the tensor fasciae latae (TFL).
F.B. Horak, J.G. Nutt, M. Mancini (Portland, OR, USA) Heel-strike (Hs) and toe-off (To) events for right and left steps were
extracted from the shank angular velocities. The FoG ratio (power
Objective: To characterize the muscle activation patterns and leg spectral density ratio between high and low frequencies of shank
movements prior and during freezing episodes to better understand acceleration) and gait speed were calculated. Onset of activity from
the neural mechanisms responsible for Freezing of Gait (FoG). Hs for the TA, GM, and contralateral TFL, offset of activity for the
Background: We hypothesize that FoG is due to lack of release ipsilateral TFL; as well as duration of EMG activity were calculated
of hip abductor muscle activity for lateral anticipatory postural for the 5 steps preceding the turn.
adjustments (APAs) in preparation for stepping during gait and Results: All FoG1 subjects showed FoG. The FoG ratio was sig-
turning. nificantly larger in FoG1 compared to FoG- (1.25 6 0.3 vs

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


0.5 6 0.3, p50.007) although gait speed, excluding turns, was similar Objective: We investigated the effect of anterior or posterior cho-
(0.67m/s60.23 vs 0.88m/s60.13, p50.11). In the steps before a turn:, linergic lesions of the pedunculopontine nucleus (PPN) in rats with
i) the ipsilateral TFL offset and the contralateral TFL onset were simi- 6-hydroxydopamine (6-OHDA) lesions on gait-related motor behav-
lar between groups, whereas the subsequent, ipsilateral TFL onset was ior, and on neuronal network activity of the cuneiform nucleus
later in the FoG1 for the step prior to a freezing episode; ii) the ipsilat- (CNF) and the basal ganglia (BG) output region, the entopeduncular
eral TFL activity was reduced during stance but increased during swing nucleus (EPN).
in FoG1; iii) the contralateral TFL activity was larger during stance Background: Loss of cholinergic neurons in the mesencephalic
and reduced during swing in FoG1. The medio-lateral acceleration locomotor region, comprising the PPN and the CNF, are related to
traces were similar in amplitude, but less variable in FoG1. gait disturbances in late stage Parkinsons disease (PD).
Conclusions: We observed increased ipsilateral TFL activity and Methods: Bilateral anterior and posterior PPN lesions were
reduced contralateral TFL activity in FoG1 compared to FoG-, con- induced by stereotaxic microinjection of the cholinergic toxin
sistent with a lack of release of APA inhibition and inadequate pos- AF64A in male Sprague Dawley rats with or without 6-OHDA-
tural preparation for a step. These observations suggest that abnormal induced bilateral retrograde nigrostriatal degeneration of dopamine
temporal muscle activation patterns during FoG episodes may be due neurons, a model of PD. Movement impairments were assessed using
to abnormal coupling of anticipatory postural adjustments with step- rotarod and open field test. Thereafter, in vivo electrophysiology
ping rather than a disruption of central pattern generators. 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-
AAV1/2 overexpression of A53T a-synuclein in the substantia rated by anterior PPN lesions (P<0.05). In the activity box 6-OHDA
nigra results in behavioural deficits and degeneration of the lesions had no effect on spontaneous locomotion, but additional pos-
nigrostriatal system: A new mouse model of Parkinsons disease terior PPN lesions reduced this measure (P<0.05). In the EPN nigro-
C.W. Ip, L.C. Klaus, V. Maltese, J. Volkmann, J.M. Brotchie, J.B. striatal dopamine lesions led to significantly higher coefficient of
Koprich (Wuerzburg, Germany) variation of the inter-spike interval (P<0.001) coupled with more
bursting firing pattern (P<0.05), which were reversed after anterior
Objective: To generate and characterize a mouse model of Par- and posterior PPN lesions. In the CNF the neuronal discharge rate
kinsons disease (PD) based on AAV1/2 driven expression of human was increased after anterior PPN lesions (P<0.001) with no effect of
A53T a-synuclein (aSyn) in the substantia nigra (SN). nigrostriatal dopamine lesions. The CNF bursting pattern was
Background: a-synuclein is a protein implicated in the patho- reduced after 6-OHDA lesions, additional PPN lesions further
physiology of PD. To mimic this aspect of the disease it has been reduced this measure (P<0.05).
shown in rat and monkey models that AAV1/2 mediated overexpres- Conclusions: Combined nigrostriatal and anterior or posterior
sion of human A53T aSyn leads to degeneration of SN dopaminergic PPN lesions had different impact on motor behaviour. The complex
neurons, decline of striatal dopamine (DA) and tyrosine hydroxylase effects on neuronal activity of the CNF and the BG network may
(TH), elevation of DA turnover and behavioural abnormalities. contribute to elucidate the pathophysiology of PD gait disturbances.
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 91
a concentration of 5.1 x 10exp12 gp/ml were unilaterally injected
Development and evaluation of closed-loop deep brain
into the right SN of male adult C57BL/6 mice. Clinical examination
stimulation (DBS) in a primate model of Parkinsons disease
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 L.A. Johnson, S.D. Nebeck, C.M. Hendrix, M.D. Johnson, K.B.
after injection. Post-mortem analysis was performed by immunohis- Baker, J.L. Vitek (Minneapolis, MN, USA)
tochemistry to analyze aSyn and TH expression in the SN, striatal Objective: To develop a recording and stimulation system that
dopamine transporter (DAT) levels by autoradiography and dopa- enables closed-loop control of DBS in an animal model of Parkin-
mine metabolism by high performance liquid chromatography. sons disease (PD) and to evaluate the behavioral and physiological
Results: Significant paw use asymmetry was observed in the A53T effects of closed-loop DBS (CL-DBS) relative to traditional DBS
aSyn injected group with preference of the right front paw when com- (tDBS) and off-DBS conditions.
pared to EV controls at both 5 and 9 weeks post injection (both Background: tDBS systems are always on, continuously deliver-
p<0.05). Neurochemically, a significant reduction in striatal DAT bind- ing pulsed stimulation at a high rate (i.e., >100 Hz) regardless of the
ing (by 23%), DA (by 36%) and DOPAC (by 36%) levels in A53T clinical state. A promising approach to improve DBS therapy for PD
aSyn mice was shown as well as an increase in DA turnover (HVA/ is to incorporate feedback control of DBS based on real-time meas-
DA; by 60%) compared to controls (all p<0.05). Immunohistochemical ures of brain activity. In particular, local field potential (LFP) activ-
double staining for TH and aSyn showed that the A53T injected mice ity in the beta range (13-35Hz) has been implicated as a potential
had widespread nigral expression of aSyn and a reduction in SN DA biomarker to use for closed-loop control of DBS.
neurons. No significant effects were detected on the open field analysis Methods: The rhesus macaque 1-methyl-4-phenyl-1,2,3,6-
(velocity or distance moved) or on rotarod performance. tetrahydropyridine (MPTP) model of PD was used. A scaled version
Conclusions: These data show that unilateral injection of AAV1/ of the human DBS lead was implanted in the subthalamic nucleus
2 A53T aSyn into the mouse SN leads to persistent behavioral defi- (STN), and LFPs from the STN were recorded differentially from
cits and neurodegeneration of the nigrostriatal DA system similar to two DBS contacts, processed in real-time, and used to control the
that observed in the rat. This aSyn based model of PD is now in a timing of stimulation at an adjacent contact. High frequency stimula-
position to conduct investigations using transgenic mice. tion (135 Hz) was delivered whenever the amplitude of beta-band
LFP envelope was above a predetermined threshold level. The rela-
90 tive efficacy of CL-DBS, tDBS and off-DBS conditions were com-
pared using blinded rating scales and objective measures of motor
Motor behaviour and neuronal network activity after lesions of performance during a cued reaching task.
the anterior or posterior pedunculopontine nucleus in a rat Results: CL-DBS was as effective as tDBS at reducing rigidity in
model of Parkinsons disease the contralateral limbs. However, CL-DBS was not as effective as
X. Jin, J.K. Krauss, M. Alam, K. Schwabe (Hannover, Germany) tDBS in improving performance on the reaching task, as measured

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


by total movement time. Physiology recordings revealed that the cyte of patients with sporadic and genetic Parkinsons disease is
beta-band envelope sharply decreased during the cued reach, such altered compared with healthy subjects.
that in the CL-DBS condition stimulation was least likely to be Background: Mutations in GBA is one of the most common
delivered during the reach and beginning of the return epoch. genetic risk factor for Parkinsons disease (PD). The proposed patho-
Conclusions: Our results illustrate the importance of using multi- mechanisms by which GBA mutation leads to the development of
ple objective measures when comparing new and traditional DBS PD is impaired degradation of pathologic a-synuclein and subsequent
methods, and also motivate exploration of more robust biomarker accumulation of toxic a-synuclein species and formation of Lewy
sites and signals for closed-loop DBS, such as oscillations in other body. In this regard, it is tempting to hypothesize that b-
frequency bands (e.g. gamma) or relationship between frequency glucocerebrosidase activity is decreased even in patients with spo-
bands. The model we developed will be extremely useful to investi- radic PD without GBA mutation.
gate the optimal parameters for feedback control of DBS and to Methods: Fifty-one patient with PD or Parkinsonism (36 patients
understand the neural mechanisms underlying the therapeutic benefit with sporadic PD, 5 patients with PARK2 mutation, and 10 patients
of DBS. 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
92 standard protocol used in the screening test for Gauchers disease.
The sex-specific role of biometals in the risk of Parkinsons Results: There was no difference in the age between patients and
disease controls. Neither activity of b-glucocerebrosidase nor b-
hexosaminidase in peripheral blood leukocyte was different between
M.J. Kim, J.Y. Lee, J. Kim, K. Kim, H.S. Ryu, A.I. Bush, S.J. Chung
patients and control. Subgroup analysis also showed that the activity
(Seongnam, Korea)
of both enzymes in patients with sporadic PD, PARK2 mutation, and
Objective: To investigate the association between biometals and SCA17 with Parkinsonism was not different from that in controls.
the risk of Parkinsons disease (PD) and clinical characteristics of This was also true when only the patients with sporadic PD with
PD. abnormal FP-CIT-PET (n527) were counted.
Background: There has been growing evidence of the participa- Conclusions: The activity of b-glucocerebrosidase and b-
tion of biometals in neurobiological processes, such as the regulation hexosaminidase in peripheral blood leukocyte does not differentiate
of synaptic transmission and abnormal protein aggregation. However, the patients with PD from healthy controls.
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 94
women) and age- and sex-matched 304 controls (141 men and 163 3D-EM characterisation of axonal swellings in the engrailed-1
women). We collected clinical data of PD patients, including age at heterozygous mouse model of Parkinsons disease
onset of PD, disease duration, Hoehn and Yahr stage (H-Y stage), Z. Kurowska, G.J. Kidd, E. Benson, P. Brundin, S. Medicetty, B.D.
motor fluctuation, dyskinesia, freezing, hallucination, and mini- Trapp (Cleveland, OH, USA)
mental status examination (MMSE) score. The levels of biometals
(iron, copper, zinc, cobalt, and strontium) in serum were assayed by Objective: Our goal was to better characterize swellings of mid-
inductively coupled plasma-mass spectrometry. brain dopaminergic axons in the Engrailed-1 heterozygous mouse
Results: The age at onset of PD was 58.26 6 9.20 years model of Parkinsons disease.
(mean 6 SD) and the duration of PD was 6.95 6 4.63 years. The Background: Engrailed-1 (En1) is a transcription factor impor-
mean H-Y stage was 2.3. The serum level of copper was significantly tant for development and maintenance of dopaminergic neurons.
lower in PD patients compared with controls (13.40 6 2.43 lmol/L vs Polymorphisms in this gene are associated with sporadic PD. En11/-
13.88 6 2.62 lmol/L, respectively; P 5 0.016), but this difference was mouse model presents slow progressive degeneration of nigro-striatal
not significant in sex-specific analyses (men-only and women-only pathway. Between 2 and 8 weeks of age, before most of other path-
analyses). The serum levels of cobalt and strontium were not different ologies can be detected, progressive dopaminergic terminal defects
between PD patients and controls in overall analysis. In women-only (axonal swellings) in En11/- mice accumulate.
analysis, the serum level of cobalt was significantly higher in PD Methods: 3-dimentional electron microscopy (3D-EM) and
patients compared with controls. In men-only analysis, the serum level immunohistochemistry of dopaminergic axons in dorso-medial stria-
of strontium was lower in PD patients compared with controls. The tum at 2, 4, and 8 weeks in En11/- mice.
higher serum level of copper (OR 5 1.26, 95% CI 5 1.04 - 1.53, Results: Several weeks before the cell bodies of nigral dopamine
P 5 0.019) and the lower serum level of iron (OR 5 0.88, 95% neurons degenerate, their terminals become dystrophic, swollen and
CI 5 0.82 - 0.95, P 5 0.001) increased the risk of dyskinesia in filled with electron dense bodies consistent with abnormal autophagic
women-only analysis, with adjustment for age, disease duration and vacuoles. We have measured the size of the swellings and identified
H-Y stage. The serum level of copper was negatively correlated with three different types of swellings: early, immediate and mature,
MMSE score in PD patients (b=-0.151, P 5 0.006). The serum level based on their size and morphology.
of cobalt was positively correlated with disease duration in women- Conclusions: Our findings support a progressive retrograde degener-
only analysis and H-Y stage in men-only analysis. ation of En11/- nigrostriatal neurons, akin to what is suggested to occur
Conclusions: This study showed a sex-specific association in PD. We conclude that using axonal swelling quantification in En11/-
between biometals and PD risk and clinical characteristics of PD. mouse is highly relevant for testing PD-related therapies, as indicated by
Further experimental studies are needed to confirm these findings. a pathological progression that closely mimics that in patients.

93 95
Leukocyte b-glucocerebrosidase and b-hexosaminidase activity is Metabolomic biospecimen analysis for measuring PD progression
not altered in sporadic and genetic Parkinsons disease P.A. LeWitt, J. Li, M. Lu, L. Guo, P. Auinger (West Bloomfield, MI,
H.J. Kim, B.S. Jeon, J.Y. Kim, H. Park, W.W. Lee, C.W. Shin (Seoul, USA)
Objective: To determine if untargeted profiling of small-molecule
Objective: To examine whether the activity of b- (<1.5 kDa) constituents of CSF and plasma can yield useful state
glucocerebrosidase and b-hexosaminidase in peripheral blood leuko- biomarkers of PD.

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


Background: Since PD is associated with mitochondrial and basal ganglia. In three patients with PPFG, whose FOG did not
other metabolic alterations, metabolomic analysis (measuring hun- respond to levodopa, DaTscans revealed an absence of presynaptic
dreds of biochemicals present in minute concentrations) has the dopamine in the basal ganglia.
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 97
DATATOP study PD subjects. CSF and plasma was sampled twice Neuroprotective effects of sodium butyrate against rotenone
using a standardized protocol (at up to 24 months apart) and at times neurotoxicity in both wild-type and VMAT2 heterozygote
when UPDRS ratings were conducted. Assays used ultrahigh- knockout mice
performance liquid chromatography combined with tandem mass L. Liu, N. Xiong, J. Huang, G. Zhang, X. Xu, C. Han, J. Li, H.
spectrometry. A spectral reference library provided chemical identifi-
Jiang, J. Yang, Y. Shen, T. Wang (Wuhan, Peoples Republic of
cations. Data underwent extensive curation and quality-control meas-
ures before application of several bioinformatics statistical
approaches. Objective: To examine whether administration of sodium butyr-
Results: From 1st to 2nd specimen collections, the data provided ate can exert significant neuroprotective effects in animal model of
indications for decreased efficiency in glucose and fatty acid metabo- Parkinsons disease (PD) induced by chronic rotenone administration
lism, elevated oxidative stress, and variation in gut microflora metab- in both wild-type and VMAT2 heterozygote knockout mice.
olism. To find a panel of biospecimen constituents that predicted Background: Previous studies indicate that VMAT2-deficient
changes over time and in UPDRS Parts 2 1 3 scores, marker selec- mice display motor deficits and progressive neurodegeneration in the
tion in CSF and plasma samples was conducted using Least Absolute substantia nigra, as observed in PD. Histone deacetylase (HDAC)
Shrinkage and Selection Operator (LASSO). Compounds chosen by inhibitors have recently become a promising therapeutic candidate in
LASSO were fitted into a multiple linear regression. A composite PD and other neurodegenerative diseases because there is growing
index was created, based on each markers coefficient (and which evidence that HDAC inhibitors can exert neuroprotective effects by
was a linear combination of concentrations for each of the markers). various mechanisms. Sodium butyrate, a HDAC inhibitor, has shown
We found that, for plasma constituents, the correlation coefficient efficacy for neuroprotection in animal models of stroke and Hunting-
was highly positively correlated with measured change in UPDRS tons disease.
Parts 2 1 3 scores (0.87 for 15 compounds, p52.2e-16), while for Methods: Wild-type and VMAT2 heterozygote knockout male
CSF, the correlation coefficient was only moderately positively cor- C57BL/6 mice aged 12-months were divided into the following
related (0.58 for 3 compounds, p51.3e-5). There was no biomarker groups: rotenone-administrated (30 mg/kg/d, p.o.) and rotenone-
differentiation of two PD clinical sub-types (postural instability-gait administrated (30 mg/kg/d, p.o.) with sodium butyrate (0.3 g/kg/d,
disorder as compared with tremor-dominant Parkinsonism). A metab- i.p.) for eight weeks. Then, animals were subjected to behavioral
olomic pathway analysis of the data was not informative. (Rotarod and pole test), neurochemical (striatal content of DA,
Conclusions: Metabolomic profiling of PD plasma specimens DOPAC and HVA) and immunohistochemical (tyrosine hydroxylase,
provided findings that were highly predictive of PD severity. Our a-synuclein and ubiquitin) evaluations.
data detected a panel of biomarkers that could be useful for gauging Results: Administration of sodium butyrate significantly attenu-
PD progression in easily-sampled biospecimens. 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.
96 Moreover, administration of sodium butyrate significantly reduced
Freezing of gait early in Parkinsons: Atypical versus typical accumulation of a-synuclein and ubiquitin in dopaminergic neurons,
Parkinsons disorders which was elevated in rotenone-treated mice.
A. Lieberman, A. Deep, R. Dhall (Phoenix, AZ, USA) Conclusions: Our study indicates that sodium butyrate, a well-
known HDAC inhibitor, exerts neuroprotective effects through mod-
Objective: Freezing of Gait Early in Parkinson: Atypical versus ulation of a-synuclein expression in both wild-type and VMAT2 het-
Typical Parkinsons Disorders. erozygote knockout mice treated by rotenone. These findings provide
Background: Freezing of gait (FOG) is an episodic, often dra- further evidence that administration of sodium butyrate may be a
matic, gait pattern characterized by an abrupt inability to walk, in promising approach for the treatment of PD.
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 98
decrease in step length, a decrease in range of movement of the hips, Risk of Parkinsons disease onset in patients with diabetes,
knees, and ankles, and an increase in fall risk. hypertension, dyslipidemia and obesity in Mexican population
Methods: 850 patients were examined at Muhammad Ali Parkin- R. Llorens-Arenas, M. Rodriguez-Violante, A. Cervantes-Arriaga, H.
sons Center (MAPC) with a diagnosis of Parkinsons disease (PD) Calderon-Fajardo, G. Neri-Nani, R. Millan-Cepeda, I.E. Estrada-
over a period of 18 months.
Bellmann, D. Pi~na-Fuentes, G. Pagano, M. Tagliati (Mexico City,
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 Objective: To describe the prevalence of metabolic comorbidities
Parkinsonism. Among these 40 patients, all of whom had had symp- (hypertension [HT], diabetes [DM], dyslipidemia [DL], and obesity)
toms for  5 years, 12 had FOG. in Mexican PD patients. To establish associations between these
FOG improved with levodopa treatment in 21/27 patients with comorbidities and the occurrence of PD and its clinical course.
typical PD, but FOG did not improve with levodopa in the 12 Background: Previous studies have suggested an association
patients with atypical PD. Although FOG appears to be a problem in between PD and metabolic comorbidities. However, the evidence is
locomotion, our results suggest that impaired postural stability rather inconclusive and contradictory, with both risk and protective effects
than impaired locomotion is the main problem, and balance training reported. The prevalence of these comorbidities in Mexican general
rather than gait training is more likely to be helpful in patients with population is 9.2% for DM, 13% for DL and 32% for HT.
FOG. Methods: Patients from the Mexican PD Registry (ReMePARK)
Conclusions: Primary progressive freezing of gait (PPFG) is were enrolled from February through October 2014. Demographic
viewed as arising from a disconnection between the frontal lobes and data and history of comorbidities were recorded. Blood analysis was

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


performed screening for DM, DL and end organ damage. Results stress, is intriguing and will be examined in additional CSF samples.
from the National Health and Nutrition Survey 2012 were used as Longitudinal CSF measurements of these proteins are planned to
controls. T test and OR were calculated to compare prevalence of evaluate possible PD progression-related changes.
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 100
determine the effect of these comorbidities and the blood results on Gait outcomes characterize people with Parkinsons disease who
the clinical course, correlating with LEDD, MDS-UPDRS, Hoehn- transition to falling within the first year
Yahr scale, NMSS and SEND-PD. S. Lord, D. Burn, L. Rochester (Newcastle upon Tyne, United
Results: 452 patients were recruited. Prevalence of comorbidities Kingdom)
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 Objective: To compare the clinical features of people with Par-
significantly earlier than the onset of PD, at least 1 year prior to its kinsons disease (PD) who transition to falling within 12 months
onset. Patients had significantly higher prevalence of HT (OR 2.11, from diagnosis with those of non-fallers.
p < 0.0001, CI 95% 0.11-0.53), DM (OR 1.54, p < 0.001, CI 95% Background: Falls are common in PD and associated with loss
1.33-2.12), DL (OR 1.50, p < 0.001, CI 95% 1.39-2.06), and over- of independence and mortality. Understanding the evolution of falls
weight (OR 1.45, p < 0.0001, CI 95% 1.65-2.12) compared to gen- from diagnosis will assist in accurate prediction and effective early
eral population. Covariate analysis did not establish associations management.
between comorbidities or blood test results and clinical course. Methods: One hundred and twenty-one consecutive incident PD
Conclusions: DM, HT, DL and overweight are significantly higher subjects were assessed in Newcastle-upon-Tyne as part of the
in PD patients than in general population. These comorbidities are ongoing ICICLE-GAIT study, a collaborative study with ICICLE-
diagnosed prior to the onset of PD, suggesting altered metabolic path- PD. Falls data were collected in newly diagnosed PD prospectively
ways as possible risk factors. Nevertheless, the presence and severity over 12 months via a falls diary and telephone follow-up. A compre-
of these comorbidities does not seem to influence the clinical presenta- hensive battery of motor, cognitive, self-efficacy and gait measures
tion of PD. Further studies are warranted to clarify these associations. 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.
99 Results: At 12 months, 70 subjects were non-fallers and 27 were
Measurement of CSF proteins suggested by gene expression new fallers. Respective age was 67.4 6 9.3 v 69.4 6 10.9 years;
studies as potential Parkinsons disease biomarkers 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
D. Loeffler, P. LeWitt, J. Aasly, L. Smith, M. Coffey (Royal Oak, MI,
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
Objective: To determine if cerebrospinal fluid (CSF) concentra- stance time (P 5 0.047) and (P 5 0.033) respectively.
tions of 5 proteins previously identified by gene expression studies Conclusions: These (preliminary) results suggest that gait out-
as PD biomarker candidates, and/or the concentration of nrf2, a key comes discern new fallers from non-fallers one year after diagnosis
activator of anti-oxidant mechanisms, might offer potential PD of PD. Cognitive outcomes were not significantly different between
biomarkers. groups. This may change as disease advances and non-motor symp-
Background: No reliable biomarkers have been found for early toms emerge. Additional analysis will report prospective falls data
diagnosis of PD or its neuropathological progression. A previous over 30 months and identify predictors of first fall.
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 101
kinase-associated protein 1A (SKP1A), huntingtin interacting Effect of visual cue timing on gait initiation in Parkinsons with
protein-2 (HIP-2), and 19S proteasomal protein PSMC4. A sixth pro- freezing of gait
tein, nuclear factor (erythroid-derived 2)-like 2 (nrf2), was included C. Lu, S. Amundsen, P. Tuite, J. Vachon, C.D. MacKinnon
in this study because it is a major antioxidant response regulator.
(Minneapolis, MN, USA)
Methods: ELISAs were used to measure SKP1A, ALDH1A1,
HSPA8, PSMC4, HIP2, and nrf2 in CSF samples from subjects with Objective: The purpose of this study was to examine the effect
idiopathic PD (n 5 20), Parkinsonian LRRK2 gene mutation carriers of different visual cue timings on anticipatory postural adjustments
(n 5 9), healthy non-Parkinsonian LRRK2 carriers (n 5 20), aged (APAs) preceding and accompanying gait initiation in Parkinsons
subjects with other neurological disorders (n 5 16), and healthy aged disease (PD) patients with and without freezing of gait (FOG).
control subjects (n 5 19). Background: External cueing can markedly facilitate movement
Results: Only HSPA8 and nrf2 were detected; no statistically sig- initiation or unfreeze the patients with FOG, even when they are
nificant differences between groups were found for concentrations of off medication. These observations provide compelling evidence that
either protein. HSPA8 and nrf2 levels were weakly associated PD patients retain the capacity to initiate movement via non-
(rho 5 -.30) for all subjects. When associations between the two pro- dopaminergic pathways. However, the utility of using cues is com-
teins were examined for subgroups formed by diagnostic group or promised by inconsistency of effects and habituation. Currently there
gender, moderate negative associations were detected for women are no guidelines or standardized protocols for how cues should be
(rho 5 -.51; p 5 .001) and for PD of either type (rho 5 -.42; presented to patients with FOG.
p 5 .023). Methods: We studied twenty patients with PD, 11 freezers and 8
Conclusions: Our inability to detect SKP1A, ALDH1A1, non-freezers, in the off medication state. Step initiation was visually
PSMC4, and HIP2 in CSF underscores obstacles in PD CSF cued using three different instructed-delay (warning go) timing
hypothesis-driven biomarker studies: proteins identified as potential protocols: fixed delay period (3 s), random delay period (4-12 s) and
biomarkers based on brain or blood studies may not be detectable in countdown (3-2-1-go, 1 s between cues). Subjects also performed
CSF, and if they are detectable, their measurements may not reflect self-initiated stepping trials. The primary dependent APA timing var-
their alterations in PD brain. The negative association in PD patients iables were: time to peak amplitude of the stepping foot loading
between HSPA8, which binds to newly formed proteins to facilitate force, and initial excursions of the net center of pressure in both the
correct folding, and nrf2, a regulator of the response to oxidative mediolateral (COPml) and anteroposterior (COPap) directions. Data

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


were analyzed using a 2 x 4 repeated measures analysis of variance Objective: To determine peripheral levels of iron, ferritin and
with factors of group and cue timing (fixed delay, random delay, transferrin in Parkinsons disease (PD) patients and to evaluate
countdown and self-initiated). whether iron accumulation in the substantial nigra (SN) could be
Results: There was a significant main effect (p<0.005) of cue related to serum levels. To determine reliable peripheral biomarkers
timing for all APA timing variables. Post-hoc tests showed that the of oxidative/nitrative stress.
time to peak loading of the stepping leg and peak excursions of the Background: Parkinsons disease pathophysiology is associated
CoP in the lateral and posterior directions were significantly reduced with oxidative/nitrosative stress. Iron accumulates in the SN of PD
in the countdown and fixed-delay compared with the self-initiated patients and is related to this damage along with oxygen and nitro-
condition (p < 0.009). Loading force and COPap timing were also gen reactive species (ROS, RNS) through Fenton reaction. ROS and
significantly improved for the countdown compared with the random RNS are normally produced in cell and inflammatory processes and
delay condition (p < 0.024). are controlled by antioxidant systems.
Conclusions: The data demonstrate that visual cueing protocols Methods: Forty PD patients and 46 controls were selected to
that incorporate predictive timing (countdown and fixed delay) compare serum levels of iron, ferritin, transferrin and oxidative/nitra-
improve the timing of APAs compared to self-initiated steps in both tive stress biomarkers: superoxide dismutase (SOD), catalase, nitric
freezers and non-freezers. 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,
Reduction of alpha-synuclein in the substantia nigra of the non- ischemic-modified albumin (IMA) and vitamin C.
human primate results in neurodegeneration Results: Iron levels were decreased in patients with PD, while
F.P. Manfredsson, D.E. Redmond, Jr., J.W. Lipton, R.M. Malpass, ferritin and transferrin were not different. Oxidative stress bio-
T.J. Collier (Grand Rapids, MI, USA) markers such as TBARS, AOPP, NTPDases, IMA and myeloperoxi-
dase were significantly higher in PD patients, while FRAP, vitamin
Objective: To determine whether loss of functional alpha- C and non-protein thiols were significantly lower. SOD, catalase,
synuclein (a-syn) is a causative event in dopaminergic ecto-5-nucleotidase were not different between the groups and bio-
neurodegeneration. markers NOx and ADA were significantly increased in controls. No
Background: a-syn aggregation and pathology is integral to both correlation was found between biomarkers and sociodemographic
idiopathic and familial Parkinsons disease (PD). The correlation and disease characteristic data.
between a-syn and PD has led many to describe aggregates as Conclusions: Plasmatic levels of iron are decreased in patients
directly toxic, resulting in efforts to eliminate a-syn as a therapy for with PD compared to healthy controls. Biomarkers TBARS, AOPP,
PD. However, removal of a-syn from rodent nigral neurons via NTPDases, IMA and myeloperoxidase presented as reliable to mea-
recombinant adeno associated virus (rAAV)-mediated delivery of a- sure oxidative/nitrative damage, while non-protein thiols, FRAP and
syn shRNA results in neurodegeneration. Thus, we formulated the vitamin C show a significant decrease in the antioxidant capacity in
hypothesis that a-syn aggregates are not directly toxic; rather a-syn PD.
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. 104
Methods: African Green monkeys (n51) were injected unilater-
Hypochlorite converts dopamine into redox cycling cytotoxic
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 N.J. Mehta, K.A. Beningo, D. Njus (Detroit, MI, USA)
vectors also contained GFP as a transduction marker. Animals were Objective: To study the redox cycling of dopamine oxidized
monitored for behavioral deficits indicative of nigrostriatal denerva- metabolites and investigate the mechanism by which they cause oxi-
tion for three months until sacrifice. Brains were analyzed for striatal dative stress and kill nerve cells.
catecholamine content and neuropathology of the SN. Background: Parkinsons disease is caused by the death of dopa-
Results: The animal treated with high-dose a-syn shRNA exhib- minergic neurons in the substantia nigra, but the reason those neu-
ited a progressive deficit in a summary score of healthy behaviors, rons die is unknown. Contributing factors are thought to include
but no increase in overt Parkinsonian signs. Analysis of tissue indi- oxidative stress, mitochondrial dysfunction, dopamine oxidation and
cated that all a-syn shRNA treated animals exhibited reduced striatal microglial inflammation. Specific mechanisms relating these dispar-
dopamine levels. Reductions in TH1 neurons were observed prefer- ate factors have been elusive. The missing piece may be hypochlo-
entially in the ventral tier of the a-syn shRNA treated SN. No such rite, which we suggest plays a central role linking dopamine
decrements were observed in animals treated with equivalent doses oxidation, oxidative stress and microglial activation.
of a SCR-shRNA. GFP1 neurons were observed throughout the SN Methods: Redox Cycling Assay Redox cycling activity was
of SCR-shRNA treated subjects. In contrast, GFP was only seen in assayed as ascorbate-dependent oxygen consumption, monitored
dorsomedial neurons of a-syn shRNA treated animals, ostensibly due using a Clark-type oxygen electrode.
to the loss of ventral tier TH1 neurons. Additionally, a loss of TH Superoxide Assay Superoxide generation in cells was observed
phenotype as measured by several TH-/neuromelanin1 neurons was using MitoSOX Red, a fluorogenic dye highly selective for detection
observed with a-syn shRNA treatment. of superoxide in the mitochondria of live cells.
Conclusions: Our findings indicate that non-human primate nigral Trypan Blue Exclusion Assay Cell viability was determined
dopamine (particularly ventral tier) neurons are sensitive to the loss of using 0.4% trypan blue 24 hours after the cells were exposed to the
a-syn. This sensitivity is not due to non-specific shRNA toxicity. Our desired concentration of redox cycler.
results suggest that (functional) a-syn is crucial to neuronal survival. Results: Hypochlorite reacts with the dopamine oxidation prod-
ucts cysteinyl-dopamine and cysteinyl-DOPAC and converts them
103 into compounds that redox cycle and produce oxidative stress. In
fact hypochlorite is unique in its ability to form redox cycling com-
Iron and oxidative stress in Parkinsons disease: In search of pounds; other oxidants such as hydrogen peroxide and Fe31 are not
injury biomarkers effective. These redox cycling compounds are also formed in the
M.S. Medeiros, M.R. Fighera, A.S. Schuh, C.M. Rieder (Porto presence of myeloperoxidase and its substrates, H2O2 and Cl-, which
Alegre, Brazil) produces hypochlorite. The product made by hypochlorite treatment

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


of cysteinyl-dopamine is nearly as effective in the mitochondrial (2) oxidative stress (superoxide dismutase=SOD, glutathione peroxi-
redox cycling assay as the synthetic compounds 3-methyl-5-anilino dase=GPx, glutathione reductase=GR, lipid peroxidation=LP, protein
quinone and 9,10-phenanthrenequinone. These compounds all gener- oxidation=PO and total thiol content=TT), in different regions of rat
ate superoxide in cells as indicated by Mitosox Red fluorescence. brain, in 6-OHDA rat model of Parkinsons disease.
These compounds are also all cytotoxic at micromolar concentra- Background: 6-hydroxydopamine (6-OHDA) has been widely
tions, and the LD50 correlates with mitochondrial redox cycling used to produce lesions in the rat brain, specially substantia niagra
activity. Moreover, evidence suggests that cells undergo apoptosis pars compacta, and generate animal models of Parkinsons disease
when treated with these dopamine metabolites. for drug development and understanding the pathophysiology of the
Conclusions: This raises the possibility that hypochlorite, pro- disease. There have however, not been any exhaustive studies on the
duced by microglial myeloperoxidase, creates redox cycling com- effects of 6-OHDA on motor and non-motor behaviors associated
pounds that lead to oxidative stress and the consequent death of with the disorder as well as the oxidative stress generated in different
dopaminergic neurons in Parkinsons disease. 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.
105 Methods: 4ll of 6-OHDA (5lg/ml) or saline was stereotaxically
Association between locus coeruleus pathology and gait administered to six male Wistar rats (6-8months) in the substantia
dysfunction in Parkinsons disease: A clinical-pathological nigra. After two weeks of recovery, righting reflex, open field test,
preliminary analysis Morris water maze test, light and dark chambered test and three
chambered social behavior test were performed. Thereafter, animals
K.A. Mills, Z. Mari, C. Bakker, G.M. Pontone, J.C. Troncoso, L.S.
were sacrificed; their brains micro-dissected into hippocampus,
Rosenthal (Baltimore, MD, USA)
amygdala, cortex, midbrain, cerebellum and medulla. SOD, GR,
Objective: To correlate the degree of Lewy body pathology and GPx, LP, PO and TT were estimated. Data were expressed as mean
neuronal loss in the locus coeruleus (LC) and degree of gait dysfunc- standard deviation (S.D.) Statistical comparison was performed by
tion seen in patients with Parkinsons disease (PD). Students t- test followed by Holm-Sidak pairwise analysis.
Background: Gait disorders such as freezing of gait (FOG), Results: There was 2fold decline in motor function, 20fold
hypokinetic stride, imbalance, and postural instability all increase the greater mean latency time, 5fold more fear, anxiety and emotional
risk for falls in PD. Impaired mobility is the largest factor determin- anomaly in the test rats as compared to the controls. All rats were
ing a decline in quality of life and increased health care expendi- social but the test rats had preference for social novelty as apposed
tures. Animal studies suggest that norepinephrine secreted from the to controls that showed greater inclination towards the familiar rat.
locus coeruleus has a significant role in postural tone and Greater oxidative stress was generated in all parts of the rat brain as
locomotion. compared with the controls (SOD=1.5fold, GPx=1.5fold, GR=2fold,
Methods: Clinical rating scales and brain pathology have been LP=2fold, PO=2fold, TT=1.5fold; average of all brain regions).
collected prospectively as part of the Clinical Core of the Morris K. Conclusions: Our data suggests sustained effects of 6-OHDA in
Udall Center of Excellence for Parkinsons disease Research at Johns the rat brain and on the behavior of the animal, and this model can
Hopkins University. PD patients with at least one UPDRS score and be extrapolated to the human Parkinsons disease state.
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 107
the TUG time were analyzed for association with Lewy body scores Turning the head red: Intracranial application of near-infrared
in the LC and frontal lobe, LC neuronal loss or gliosis, LC pigment light improves behaviour and is neuroprotective in a non-human
loss, LC neurofibrillary tangles (NFT), and LC pallor using either primate model of Parkinsons disease
ordinal logistic regression, Chi-square, or ANOVA models. J. Mitrofanis, C. Moro, F. Darlot, N. El Massri, D.M. Johnstone, C.
Results: Of participants with a LC LB score and frontal LB
Chabrol, C.L. Peoples, H.D.T. Anastacio, F. Reinhart, D. Agay, N.
score, 15 subjects had at least one UPDRS Part III score and 14 sub-
Torres, T. Costecalde, V.E. Shaw, J. Stone, A.L. Benabid (Sydney,
jects had at least one TUG time. 46 participants had neuronal loss or Australia)
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 Objective: To examine whether intracranially delivered near-
X2 5 7.17, p 5 0.03) and a trend for an association with LC LB score infrared light (NIr) treatment improves the behaviour and neuropro-
(LR X2 5 7.13, p 5 0.07) was found. The presence of any Lewy tects midbrain dopaminergic cells in the MPTP (1-methyl-4-phenyl-
bodies in the LC was associated with more severe gait impairment 1,2,3,6-tetrahydropyridine) monkey model of Parkinsons disease.
on the UPDRS Part III gait item (p 5 0.03). Surprisingly, an inverse Background: NIr has been shown to be an effective neuroprotec-
association between LC Lewy LB load and TUG time was found tive agent in various rodent models of Parkinsons disease (Johnstone
(F 5 4.68, p 5 0.03). Neither frontal Lewy body load nor LC NFT et al; ChronoPhysiology & Therapy, 2014:4 1-14). In this study, we
score was associated with any of the UPDRS gait measures or TUG show - for the first time - that NIr has positive therapeutic effects in
time. the much larger primate brain. We used an intracranial optical fibre
Conclusions: Exploratory analysis of a longitudinal clinical- device, one that delivered sufficient NIr signal to the diseased dopa-
patholological autopsy series indicates that LC Lewy body load and minergic cells located deep in the brain of macaque monkeys.
neuronal loss may be associated with freezing of gait. The relation- Methods: A NIr laser (670nm) optical fibre device was implanted
ship between LC pathology and gait speed is less clear and may war- surgically into the midline midbrain of macaque monkeys, close to
rant further investigation. 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
106 of 25-35J). This was followed by a three week survival period. Mon-
Differential effect of 6-OHDA on different regions of rat brain: keys were evaluated clinically for motor activity and their brains
Oxidative stress and behavioral parameters were processed subsequently for immunohistochemistry and stereo-
N. Mishra, D. Sharma, N. Mishra (New Delhi, India) logical analysis.
Results: The MPTP-NIr-treated monkeys (n59), although not
Objective: To evaluate (1) behavioral anomalies (motor behavior, quite to control levels, achieved substantially better clinical scores
spatial cognition, fear, anxiety, emotional state and sociability) and (80%) than the MPTP-treated monkeys (n511). The NIr was not

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


toxic to the surrounding brain tissue and neuroprotected many dopa- ers with severe FOG were recorded during their everyday activities
minergic cells (30-40%) and their striatal terminations (40%) against and in the outpatient clinic. A newly developed freezing index (cross
MPTP insult. The neuroprotective effect was stronger in the lower correlation calculation based on pattern matching) was also calculated
MPTP dose regime (1.5mg/kg) than the higher one (2.1mg/kg). and compared with the previous index (ratio of power spectrum).
Conclusions: NIr improved behaviour dramatically and was neu- Results: Characteristic patterns of acceleration signals were
roprotective after MPTP insult, particularly at milder doses. Our find- recorded for simulated falls. Falls were associated with abrupt
ings indicate NIr as an effective therapeutic agent in a primate model changes in trunk angle. Knee trembling was recorded as a rapid
of the disease and lay the template for translation into clinical trial. 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
108 recorded when patients reported FOG-induced falls. The freezing
The effects of dual task on finger tapping in Parkinsons disease index increased during the start and turning hesitations, similarly to
A. Miyake, T. Yamamoto, T. Furuya, K. Ikeda, K. Takahashi, N. the index calculated using methods proposed by Moore et al.
Tamura, N. Araki (Iruma-gun, Japan) Conclusions: Motion recording using our wearable sensor is use-
ful for detecting FOG and falls in everyday life in PD fallers, and cal-
Objective: To evaluate quantitatively repetitive finger tapping culating the freezing index may improve the quantification of FOG.
(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. 110
Background: Decreased performance of FT during dual task has Humoral response against small heat shock proteins in
been well known in patients with Parkinsons disease. However, it is Parkinsons disease
not clear what components of FT motion are impaired. E. Papuc, E. Kurys-Denis, W. Krupski, K. Rejdak (Lublin, Poland)
Methods: The subjects consisted of 23 patients with PD and age-
matched 13 healthy controls. The motion of finger- to-thumb tapping Objective: The aim of the study was to check whether Parkinsons
with the rigid dominant side hand for 10 sec was recorded with disease (PD) has the ability to elicit immune response against small
high-speed video camera, with and without simultaneous pronation- heat shock proteins (sHSP), subsequent to their increased expression.
supination of the opposite side forearm. Key parameters for a cycle Antibodies titers against HSP60 and alpha B-crystallin were assessed.
of FT were finger separation amplitude, velocity, and duration, as Background: HSPs are functionally and immunologically highly
well as the coefficient of variation [CV; (standard deviation)/(mean conserved molecules present in almost all living organisms. Their
value) 3100)] of these parameters. To find the relationship between expression in the cell increases under the circumstances that are
each parameter of the FT motion and severity of Parkinsonian symp- potentially harmful to cells, for example, high temperature. This
toms, PD patients were divided into two groups based on disease increased HSP expression is present in cells exposed to mild stress
duration ( 6Y, 6Y >) and UPDRS part III scores ( 25, 25 >), and this protects them against subsequent stress. Anti-HSP antibodies
and those parameters were compared between the two groups. are present in different disorders with involvement of inflammatory
Results: I. PD patients:1. Amplitude was decreased and its CV process. In the light of evidence for the increased heat shock proteins
was increased by dual tusk (p<0.05, p<0.05, respectively). 2. Veloc- expression in neurodegenerative disorders, the presence of the adapt-
ity and its CV did not change. 3. Duration showed no change, but its ive humoral response of the immune system can be expected.
CV was increased (p<0.05). II Controls: 1.Amplitude did not Methods: IgG and IgM autoantibodies against alpha B-crystallin
change, but its CV was increased by dual tusk (p<0.05); the change were assessed in 26 PD patients 26 healthy subjects. Serum samples
was smaller as compared to that in PD patients. 2. Velocity slowed from PD patients were collected twice, at baseline and after mean of
and its CV was increased (p<0.05, p<0.05). 3.Duraition was 13 months follow up. For the assessment of anti-HSP IgG autoanti-
increased (p<0.05) and its CV did not change. III There was no rela- bodies serum samples from 31 Parkinsonian patients and 31 healthy
tionship between the changes of FT motion by dual task and disease control subjects were collected.
duration or UPDRS part III scores in all parameters. Results: Both IgM and IgG autoantibodies against alpha B-
Conclusions: 1. The differences in the changes of FT perform- crystallin in PD patients were significantly higher compared to
ance by dual tusk between PD patients and controls may be caused healthy controls (p<0.05). We also found statistically significant
by dysfunction of the basal ganglia. increase in antibodies titers against alpha B-crystallin over the time
2. The Impaired FT performance may have already existed in the of 13 months, both for IgG (p50.021) and for IgM (p<0.0001).
earlier stage of PD. 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
109 natural auto-antibodies, as they are present in healthy people, neverthe-
Detection and quantification of freezing of gait and falls in less chronic neurodegenerative process may have additional inducing
Parkinsons disease patients using a wearable motion sensor effect on humoral response involving anti-HSP autoantibodies, which is
reflected by significantly higher levels of anti-HSP 60 autoantibodies in
Y. Okuma, H. Mitoma, M. Yoneyama (Izunokuni, Japan)
PD patients compared to healthy controls. Increase in IgG and IgM
Objective: The aim of the present study is to objectively detect antibodies titers against alpha B-crystallin over the investigated period
and quantify freezing of gait (FOG) and falls in Parkinsons disease of time reflects activation of the immune response, probably secondary
(PD) patients during everyday activities. to widespreading neurodegenerative process and may suggest the
Background: FOG and recurrent falls are disabling features of involvement of the immune system in the disease progression.
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 111
for detecting FOG and falls outside of the clinic. Zinc dyshomeostasis underlies impairment of cellular energy
Methods: Patients were selected from among 36 patients who par- metabolism in ATP13A2 (PARK9)-associated Parkinsons disease
ticipated in our previous prospective study on falls. We developed a J.S. Park, B. Koentjoro, C.M. Sue (St. Leonards, Australia)
motion recorder (body-fixed 3D accelerometer) with a long-lasting
battery. First, healthy volunteers simulated FOG and falls, and accel- Objective: To investigate the pathophysiological effect of human
eration signals were analyzed. Then movements of recurrent PD fall- ATP13A2 deficiency, we assessed the change in Zn21 levels and its

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


effect on both mitochondrial and glycolytic function in ATP13A2- approved by the local ethics committee. Medtronic provided all
deficient Kufor-Rakeb syndrome (KRS) patient-derived cell models. materials and software under a research agreement.
Background: Mutations in ATP13A2 (PARK9) have been associ- Results: There was no significant modulation of STN beta band
ated with KRS, an autosomal recessive early-onset, levodopa-respon- power, neither by the motor task nor by Levodopa. STN-EMG coher-
sive Parkinsons disease (PD). Although ATP13A2 has been shown ence in the lower beta band (10-20Hz) was suppressed by alternating
to regulate Mn21 metabolism in yeast, its substrates in humans still movements irrespective of the dopaminergic state (tonic vs. alternate:
remain uncharacterised. Recently, we reported mitochondrial dys- motor OFF: p<0.0001, motor ON: p50.0001; Mann-Whitney-Test).
function in KRS patient cells harbouring compound heterozygous In medicated patients there was significantly stronger coupling com-
ATP13A2 mutations (c.3176T>G/c.3253delC). However, the molec- pared to motor OFF (tonic, motor OFF vs. motor ON: p50.0123).
ular mechanism by which loss of ATP13A2 cause mitochondrial dys- Conclusions: Long-range beta band synchronisation between
function is unknown. STN and spinal motoneurons may subserve the control of sustained
Methods: We tested toxicity of several biometals in KRS patient- postures and is facilitated by dopamine. This challenges the hypothe-
derived human olfactory neurosphere cells and examined changes in sis of beta band activity to be a state or disease marker in PD.
intracellular Zn21 levels ([Zn21]i). Then, we assessed the effect of
altered Zn21 levels on mitochondrial and glycolytic function in
these cells. 113
Results: Among the biometals tested, KRS patient cells showed Mid-life milk consumption and substantia nigra neuron density
an increased sensitivity to Zn21. Subsequently, we identified low at death
[Zn21]i, altered expression of Zn21 transporters and impaired
G.W. Ross, R.D. Abbott, H. Petrovitch, K.H. Masaki, L.J. Launer,
sequestration of Zn21 into LC3-positive vesicles, indicating zinc
L.R. White, J. Nelson, C.M. Tanner (Honolulu, HI, USA)
dyshomeostasis. Pharmacological treatments that increased [Zn21]i
induced the elevated production of H2O2 and aggravation of both Objective: The purpose of this report is to examine the associa-
functional deficits and morphological changes in mitochondria that tion between mid-life milk intake and substantia nigra (SN) neuron
resulted in ATP depletion and cell death. In addition, KRS patient density in brains from an unselected series of deceased Honolulu-
cells showed evidence of glycolytic dysfunction as demonstrated by Asia Aging Study participants.
reduced glycolytic capacity and reserve in extracellular flux analysis, Background: The bioaccumulation of organochlorine pesticides
reduced pyruvate/lactate production and NAD1/NADH ratio, which in milk may partially explain findings of an association between the
were exacerbated by increased [Zn21]i. The toxic effect of Zn21 intake of dairy products and the incidence of Parkinsons disease
on mitochondrial and glycolytic function was efficiently blocked by (PD). Whether this association exists with early nigral degeneration,
ATP13A2 overexpression, Zn21 chelation, promotion of mitochon- a pathological hallmark of PD, is unknown.
drial fusion and treatment of an antioxidant and pyruvate. Methods: Data on milk intake were collected in the Honolulu
Conclusions: Our data indicate that human ATP13A2 deficiency Heart Program from 1965 to 1968 in 449 men aged 45 to 68 years
results in zinc dyshomeostasis and impaired cellular energy metabo- with later postmortem examinations. Autopsies were performed from
lism. These findings provide valuable insights into the molecular 1992 to 2004. Neuron density (count/mm2) was measured in quad-
mechanisms underlying zinc dyshomeostasis and its contribution to rants from a transverse section of the SN. Measures also included
impaired bioenergetic function in PD with ATP13A2 as a molecular brain residues of heptachlor epoxide, an organochlorine pesticide
link between these two distinctive aetiological factors. reported to be found at excessive levels in the milk supply in
Results: Neuron density in all quadrants was lowest in nonsmok-
112 ing decedents who consumed the most amounts of milk (>16 oz/d).
Impact of Levodopa and motor task on beta band coupling of After removing cases of PD and dementia with Lewy bodies,
subthalamic nucleus and spinal motoneuron pool in Parkinsos adjusted neuron density in all but the dorsomedial quadrant was
disease 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
R. Reese, F. Steigerwald, M.M. Reich, C. Matthies, I.U. Isaias, J.
Volkmann (Wuerzburg, Germany) 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
Objective: To describe the impact of movement task and dopami- consumed no milk (p50.017). For past and current smokers, an asso-
nergic medication on the oscillatory coupling between subthalamic ciation between milk intake and neuron density was absent.
nucleus (STN) and spinal motor neurons in the beta frequency range Conclusions: Milk intake is associated with neuronal loss in the
in Parkinsos disease (PD). SN even among brains from participants unaffected by PD. While
Background: Coupling of neuronal activity in the beta band (10- these results support the idea that contamination of milk with orga-
30Hz) is common but its relevance in health and disease is contro- nochlorine pesticides may cause SN degeneration, more study is
versial. The degree and magnitude of beta band activity have been needed.
positively correlated with the severity of the akinetic rigid (AR)
motor symptoms in PD.
Methods: We recorded local field potentials (LFP) from the STN 114
in six AR-PD patients via telemetry through a fully implanted system Exploring Fyn as a novel molecule in levodopa induced
for deep brain stimulation (DBS) 14 weeks after implantation. We dyskinesias
furthermore assessed the coherence between STN-LFP and contralat-
S. Sanz-Blasco, E. Avale, S. Campana, A. Damianich, M.D. Sabo-
eral spinal motor neuron activity (EMG of the forearm extensors) in
rido, G. Gomez, I.R. Taravini, O.S. Gershanik, J.E. Ferrario (Buenos
two simple motor tasks: submaximal tonic wrist extension (tonic) Aires Capital Federal, Argentina)
and self paced alternating wrist flexion and extension (alternate) in
motor OFF and motor ON (after a levodopa challenge; DBS OFF in Objective: To determine the role of the kinase Fyn in levodopa
all conditions). The brain hemisphere exhibiting most prominent induced dyskinesias.
STN beta band activity in the motor OFF resting state was chosen Background: The administration of L-DOPA is the most effec-
for recordings (right n53, left n53). PD patients were selected for tive symptomatic pharmacological therapy for Parkinsons disease
STN-DBS by established clinical criteria and gave their written (PD). Despite its benefits, most patients develop side effects known
informed consent. They were then asked to additionally participate as L-DOPA induced dyskinesias (LID). One of the current great
in the studies related to chronic LFP recordings. The study was challenges in PD therapy is to control LID. To reach this goal it is

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


necessary to better understand the multiple cellular and molecular of UA in RBD but not PS subjects. The negative correlation between
mechanisms that take place during LID. Although some protein and disease duration and UA levels found in RBD, PS and PD, suggests
gene changes have been described within the dyskinetic striatum, the a risk for RBD subjects to convert to PD based on declining UA lev-
functions and/or mechanism in which they are involved are not fully els over time. Our results support targeting UA levels in RBD sub-
understood. In our laboratory we have shown that Pleiotrophin and jects as a disease risk modifier to develop PD.
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- 116
lates the protein kinase Fyn, a key molecule in postsynaptic signaling Beta band oscillatory activity in the subthalamic nucleus is not
and reorganization. Several evidences suggest Fyn as a potential can- correlated with levodopa motor improvement in patients with
didate involved in LID. Parkinsons disease
Methods: We have determined the amount of Pleiotrophin immu-
E. Sellaiah, A. Buot, S. Fernandez Vidal, M.L. Welter, C. Karachi,
nopositive neurons and analyzed the amount of Fyn protein and its B. Lau (Paris, France)
phosphorylation state by western blot in striata of dyskinetic rats.
Also, we have developed the model of LID in both Fyn knock-out Objective: To identify correlations between changes in subthala-
(KO) and WT mice, in which we have performed behavioral tests, mic nucleus (STN) local field potential (LFP) power in the 8-35 Hz
determined abnormal involuntary movements (AIMs) and performed frequency band and motor improvement in Parkinsons disease (PD)
histological determinations such as tyrosine hydroxylase and FosB/ patients highly responsive to levodopa.
DFosB. Background: Recordings in the STN of PD patients during deep
Results: We found that the number of PTN positive neurons is brain stimulation (DBS) procedures have revealed excessive oscilla-
increased and that Fyn is highly phosphorylated in the striatum of tory beta band activity (8-35Hz), which is reduced by levodopa treat-
dyskinetic rats, while Fyn KO mice show a significant reduction in ment (Brown et al., 2001). One hypothesis is that the degree of
the development of AIMs in comparison to WT controls. reduction in oscillatory beta activity on levodopa is causally related
Conclusions: Our data suggest that Fyn might be involved in the to the degree of improvement in Parkinsonian bradykinesia and rigid-
development of LID, yet further work is still necessary to determine ity (Eusebio & Brown, 2009). However, the significance of these
the mechanism in which it may be involved and if it could be tar- changes in beta activity remains controversial.
geted to control LID. 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
115 improvement ON levodopa of 75.8% (all patients >45%). We
Uric acid levels and disease duration in REM sleep behavior recorded STN LFPs OFF and ON levodopa 4 days after DBS sur-
disorder and Parkinsonian syndromes gery. We tested for correlations between clinical change and beta
M. Schiess, J. Suescun, B. Copeland, T. Ellmore, E. Furr-Stimming, power change by selecting for each side the contact pair with the
R. Castriotta (Houston, TX, USA) maximum power between 8-35Hz OFF levodopa and calculating a
percentage change using the same frequency ON levodopa. We
Objective: Compare uric acid (UA) levels between presympto- measured clinical change using hemibody scores for bradykinesia
matic REM sleep behavior disorder (RBD) subjects with idiopathic and rigidity contralateral to each selected contact.
Parkinsons disease (iPD), Parkinsons Syndrome (PS) and age- Results: We did not find significant correlations between
matched control subjects. Determine the role of UA in disease pro- levodopa-induced beta power suppression and clinical change
gression by comparing measures over time between groups. (p>0.05), nor did we find significant correlations when using average
Background: UA is a recognized risk factor for the development power between 8-35Hz to define beta power change. Finally, a direct
of iPD with clinical evidence supporting its actions as a CNS antiox- search for correlations at each frequency in the 8-35Hz range
idant with neuroprotective potential in preventing the progression of revealed a significant reduction in beta power ON levodopa (10-
motor symptoms. There is little information on how UA behaves in 25Hz, p<0.001), but did not yield any significant correlations
the high risk prodromal idiopathic RBD patient and whether UA lev- between clinical scores and LFP power at any frequency in this band
els could be manipulated in order to confer neuroprotective potential ON or OFF levodopa (p>0.1).
in preventing the development of PD. Conclusions: Our results do not support the hypothesis that
Methods: Prospective, longitudinal case-control study with intent reductions in STN oscillatory activity in the 8-35 Hz range are cau-
to follow at 6-month intervals 37-85 year old men and women; 28 sally linked to levodopa motor improvement in PD patients who are
early to moderate iPD, 21 RBD, 19 PS and 18 age-matched Control highly responsive to levodopa treatment. This highlights the diffi-
subjects. A single-night video polysomnogram was performed at culty in understanding the link between STN beta oscillatory activity
baseline and all visits included neurological and cognitive exams, and levodopa responsiveness, as well as the role of beta oscillations
Unified Parkinsons Rating Scale, Hoehn & Yahr, PDQ-39 survey in the pathophysiology of PD.
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- 117
ison between groups and correlations between disease duration, Beneficial effects of histone deacetylase inhibition in 6-OHDA
rating scales, disease disability and quality of life. induced behavioral and biochemical abnormalities in rats
Results: Significantly lower UA levels were observed in male PD
S. Sharma, R. Taliyan (Pilani, India)
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 Objective: To evaluate the therapeutic potential of HDAC inhibi-
quartiles (higher level of UA) (OR: 0.20, 95%CI: 0.047- 0.837; OR: tor, Trichostatin A in 6-OHDA induce Parkinsons disease (PD) in
0.028, 95% CI: 0.029-0.277, p<0.01). There was a significant nega- rats.
tive correlation between UA levels and disease duration in the RBD Background: Recent studies have investigated the involvement
subjects, PD and PS subjects (p < 0.01), r-values= -0.50, -0.28, -0.3. of epigenetic modifications in PD. Histone acetylation regulates the
There were no significant differences between groups for female expression of various neuroprotective genes. Reduced histone acety-
subjects. lation has been reported in PD. Therefore, we hypothesized that ele-
Conclusions: Our study results confirm previous findings of a vating histone acetylation by HDAC inhibition could prove to be
relationship between low UA and PD in men, and indicate low levels beneficial in PD.

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


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.

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

Fig. 1. (118).

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


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

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-
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
in the enteric nervous system 10-20 years prior to debut of motor
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,
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
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.

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


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

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


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

HV 1.9 22.2 26.8 - - -

(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


Severity Scale, UPDRS: Unified Parkinsons disease Rating Results: We detected 761 genes as 24 PD-risk genes and its PPI-
Scale genes. Among those, using drug databases, we found 77 genes which
are targeted by 54 approved-drugs for other diseases.
PDs showed a stronger negative slope in the on/VF- condition for Neuroprotective effects in vitro or in vivo had been already
both hands (left > right) compared with HV. [figure1] Higher starting reported in 16 of those 54 approved-drugs (30%), including raloxi-
F50 correlated with steeper negative slope in both groups. VF fene, an approved-drug for osteoporosis. In order to examine whether
improved the slope in both groups. Medication had no effect on the these drugs have neuroprotective effects, we performed LDH assay
slope in PDs. Left-hand slopes correlated positively with STAI-T and and cell viability assay using SH-SY5Y cells with exposure of rote-
FSS in the off/VF- and with STAI-T in the on/VF- conditions in PDs. none. We confirmed a neuroprotective effect of raloxifene in LDH
Conclusions: SE is observed within 30 s in a repetitive isometric assay. Furthermore, we found that 2 drugs significantly improved
task in PD. Medication increases initial motor energy, but does not LDH release (p50.01) and cell viability (p50.01) under the condi-
improve SE. Only VF improves SE. Elevated perception of anxiety tion of rotenone exposure, which suggests that these 2 drugs have a
and fatigue may lead to overcompensation. neuroprotective effect.
Conclusions: In silico drug discovery using GWAS-data is an effi-
cient manner to extract candidates of neuroprotective drugs for PD.
Connectivity of pedunculopontine and sub-thalamic nuclei in 128
patients with Parkinsons disease
C.H. Tsai, Y.T. Hsu, H.Y. Lai, S.M. Chiou, M.K. Lu, Y.C. Lin, Y.Y. Postural instability and gait disorder subtype in early to mid-
Chen (Taichung, Taiwan) stage Parkinsons disease: Beyond axial motor control
Objective: To investigate: 1. through which frequency band(s) G. Vervoort, A. Bengevoord, E. Nackaerts, E. Heremans, W.
are the two nuclei bridged? 2. Which nucleus leads the other one if Vandenberghe, A. Nieuwboer (Leuven, Belgium)
there is functional connectivity between them?
Background: There is anatomical connectivity between sub-thalamic Objective: To clarify the validity of PD subtypes by investigating
nucleus (STN) and pedunculopontine nucleus (PPN) in humans. However, behavioral outcomes at multiple levels.
the functional linkage between the two has not been fully explored. Background: Clinical subtypes in Parkinsons disease (PD) are
Methods: Three patients with Parkinsons disease (PD) underwent founded on the heterogeneity of symptoms and are based on the
bilateral STN and left PPN deep brain stimulation (DBS) were recruited presence of clustered motor symptoms. The postural instability and
for the investigation on the 2nd day after operation. The local field poten- gait disorder (PIGD) subtype is associated with rapid disease pro-
tials (LFPs) were recorded from the externalized electrodes in resting gression, predominantly axial motor involvement and increased cog-
states during patients off and on states . The coherence and cross- nitive impairment while the tremor dominant (TD) subtype is
power spectral density estimates were conducted for signal analysis. characterized by slow disease progression and the presence of signifi-
Results: There is a strong coherence at alpha frequency between cant tremor. It is, however, unclear if subtypes represent distinct
STN and PPN LFP. The analysis of phase spectra over the alpha fre- underlying pathologies or rather are a reflection of disease
quency showed significant coherence between STN and PPN and progression.
PPN led STN at this frequency by 5.9, 7.3 and 5.1 ms, respectively, Methods: 73 patients and 20 age-matched controls were recruited
in three subjects were detected. After levodopa treatment, the leading for this study. Patients were classified as PIGD (n543), TD (n522)
time increased in subject 2 and 3 (13.7 and 9.5 ms). or indeterminate (n58) based on MDS-Unified Parkinsons disease
Conclusions: There is functional connection between PPN and rating scale (UPDRS) III scores. Patients in the indeterminate group
STN with PPN in leading position through alpha frequency band in were excluded Spatiotemporal kinematics of gait, upper and lower
PD. Levodopa administration lengthened the leading time of PPN. It limb repetitive movements in combination with a balance and cogni-
seems that the increase of dopamine levels may open another route, tive assessment were recorded while off medication.
probable via basal ganglia, for the connection of the two nuclei and Results: Surprisingly, PIGD patients only had gait impairment in
this lead to a longer duration for the cross talk to occur. 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
127 mini-BESTest and the Frontal Assessment Battery (FAB) and trail
making test (TMT) B in PIGD patients compared to controls. Motor
In silico drug discovery for Parkinsons disease by using genome- scaling and coordination of distal movements were impaired in
wide association study (GWAS) data PIGD compared to TD patients during foot and finger tapping. TD
T. Uenaka, W. Satake, C.P. Chieng, Y. Okada, T. Toda (Kobe, Japan) patients were not significantly different from controls, except for a
greater asymmetry of repetitive movements.
Objective: To discover neuroprotective drugs for sporadic Parkin-
Conclusions: These results indicate a widespread motor impair-
sons disease (PD).
ment within the PIGD group that is not restricted to axial motor con-
Background: Sporadic Parkinsons disease (PD) is a complex
trol, but also involves distal motor control. These findings suggest
disorder caused by multiple genetic risk factors. Twenty four risk
refining the PIGD subtype to a more complex motor profile.
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 129
from GWAS into the clinic remains limited. A new method of drug Salivary alpha-synuclein: A new biomarker for Parkinsons
discovery utilizing risk genes and computational database was pro- disease?
posed in rheumatoid arthritis (Okada Y et al, Nature 2014). We
G. Vivacqua, A. Latorre, M. Nardi, A. Suppa, G. Fabbrini, C.
applied this method to discovery of drugs for sporadic PD. Colosimo, A. Berardelli (Rome, Italy)
Methods: We obtained 871 drug target genes from drug data-
bases (DrugBank and Therapeutic Target Database). Using a protein- Objective: To investigate whether salivary monomeric and oligo-
protein interaction (PPI) database, we extracted genes which show meric alpha-synuclein (a-syn) concentration can differentiate Parkin-
PPI with PD-risk genes reported by GWAS. sons disease (PD) patients from healthy controls.

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


Background: Increasing evidence support the hypothesis that a- p50.02), and higher TD/PIGD ratio (3.3 vs. 2.6, p50.05), but PIGD
syn, a 140 aminoacids protein closely related to the pathogenesis of scores were not predictive (0.11 vs. 0.14, p50.47). Between baseline
PD, might be considered a biomarker for the diagnosis and follow- and FU, the TD score increased in non-converters, while decreasing
up of PD. In addition to cerebrospinal fluid (CSF), a-syn can be eas- in converters (10.18 vs. -0.21, p50.0003). Increase in PIGD score
ily detected in several extra-neuronal tissues and biological fluids (non-converters vs. converters: 0.18 vs. 0.86, p<0.001) and decrease
including saliva. in TD/PIGD ratio (-0.3 vs. -2.1, p50.003) predicted conversion over
Methods: We collected salivary samples from 26 PD patients and time. Gender, disease duration, H&Y, MMSE, depression, anxiety
26 age- and sex-matched healthy subjects. Patients were recruited (BSI-18), SF-12 health scores, and ADL/IADL disability (OARS)
from the Movement Disorder clinic of Sapienza University of were not significant predictors of subtype fidelity.
Rome. PD patients were clinically evaluated before starting each Conclusions: Our data suggest that the TD subtype of PD is not
experimental session. Motor signs were scored using the motor sec- stable over time. Older age and less severe tremor at baseline pre-
tion of the Unified Parkinsons disease Rating Scale (UPDRS) and dicted conversion from TD to PIGD over 5 years. Conversely,
the Hoehn & Yahr (H&Y) scale. Non-motor symptoms were eval- increase of tremor over time, coupled with minimal progression pos-
uated by Non Motor Symptoms Assessment Scale (NMSS) and Ham- tural and gait problems, predicted TD subtype fidelity. These results
ilton Depression Rating Scale (HDRS). Cognitive functions were suggest two distinct subgroups of TD patients which might be rele-
tested by Montreal Cognitive Assessment (MOCA) and Frontal vant for biomarker-phenotype correlation studies.
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 131
was pre-treated with a buffer inhibiting protease activity (Sigma Characterization of PINK1 knockin mouse model for
Aldrich, St.Luis, MO, USA, Cat # P2714, concentration: 100 lL for Parkinsons disease
1 ml salive). Samples were subsequently analyzed by specific anti- T.H. Yeh, C.C. Chiu, H.L. Wang, S.C. Lai, H.C. Chang, C.S. Lu
monomeric and anti-oligomeric a-syn ELISA kits (SensoLyte Anti-
(Taipei, Taiwan)
alpha-Synuclein Quantitative ELISA and Rabbit a-syn oligomer
ELISA kit). Objective: To generate PINK1 knockin mouse model to investi-
Results: Compared with healthy subjects, PD patients have a sig- gate the molecular mechanism of Parkinsons disease.
nificantly reduced concentration of salivary monomeric a-syn Background: Parkinsons disease (PD) is the most common neu-
(p<0.01). By contrast, oligomeric a-syn concentrations in PD rodegenerative motor disorder. PINK1 is the second most frequent
patients resulted similar to those observed in healthy subjects. For causative gene in early-onset PD, which is believed to regulate mito-
each patient correlation between biochemical and clinical evaluation chondrial functions of dopaminergic neurons in substantia nigra pars
have been performed. compacta (SNpc). Clinical features exhibited by PINK1-mutation
Conclusions: The observation that monomeric a-syn is signifi- carriers are indistinguishable from those observed in sporadic PD
cantly reduced in salivary samples of patients with PD might be patients. Thus investigating PARK6 mutant PINK1-induced Parkin-
interpreted as a result of a-syn aggregation in PD. Finally, salivary sonism is important to unveil the common pathogenic mechanism of
oligomeric a-syn concentration is comparable in PD and healthy sub- PARK6 and sporadic PD.
jects probably because in PD, a-syn aggregation is not only due to Methods: In this study, we generate PINK1-knockin mice
free a-syn oligomers but also to intracellular aggregation of the expressing common PARK6 mutant (G309D). Homologous recombi-
protein. 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.
130 Then, chimeric mice were mated with wild-type albino C57BL/6-
Can we predict motor subtype fidelity in patients with C2J mice and bred to obtain F1 heterozygous mutant mice express-
tremor-dominant Parkinsons disease? ing PARK6 mutant (G308D). The LoxP-flanked neomycin selection
cassette was removed by crossing the F1 mice with Pink1 knockin
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) (G308D) allele with Cre deleter (EllA-Cre) transgenic mice to gener-
ate Pink1G308D/G308D homozygous mice. The behavior test and
Objective: To identify predictors of whether Parkinsons disease histopathology were performed.
(PD) patients initially classified as tremor-dominant (TD) later con- Results: We have generated Pink1G308D/G308D homozygous
vert to the postural instability/gait difficulty (PIGD) or indeterminate knock-in mice. Similarly to motor signs displayed by PD patients,
(ID) motor subtype of PD. 12-month-old Pink1G308D/G308D knockin mouse exhibited an
Background: TD, PIGD, and ID are commonly-used PD motor sub- impaired motor performance and the phenomenon of bradykinesia.
types. Stability of these subtypes over time and predictors of subtype The homozygous Pink1G308D/G308D knockin mouse also exhibited
fidelity have not been studied systemically. Identifying valid and stable progressive degeneration of SNpc dopaminergic neurons.
subtypes is important for future biomarker-phenotype correlation studies. Conclusions: This humanized knockin mice expressing PARK6
Methods: We performed a longitudinal analysis of 183 PD mutant could be used for investigating the molecular pathogenesis of
patients, applying an established PD motor subtype algorithm (Jan- neurodegeneration caused by PINK1 mutations.
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 132
in TD subtype at FU. We also compared the change in TD and Vitamin D deficiency and endothelial dysfunction in Parkinsons
PIGD scores from baseline to FU between the two groups. Logistic disease
regression models evaluated predictors of subtype fidelity after con- J.H. Yoon, S.W. Yong, J.M. Hong, J.S. Lee, I.S. Joo (Suwon, Korea)
trolling for time between study visits.
Results: At baseline, 103 out of 183 patients were classified as Objective: To evaluate the relationship between serum 25-
TD. At FU, 49% of those 103 TD patients were re-classified as hydroxyvitamin D (25(OH) D) levels and flow mediated dilatation
PIGD, and 15% as ID (total of 64% converters). Only 36% of (FMD) in patients with a Parkinsons disease.
patients remained in the TD subtype (non-converters). Significant Background: In recent years, increasing evidence has shown that
baseline predictors of TD subtype fidelity included younger age individuals with Parkinsons disease (PD) have lower levels of
(57.5 vs. 60.9 yrs., p50.04), higher TD score (0.75 vs. 0.57, 25(OH) D relative to healthy controls. Vitamin D insufficiency is

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


associated with endothelial dysfunction in human, irrespective of tra- life. Recently, there are growing evidences about the role of seroto-
ditional risk burden. Flow mediated dilatation (FMD) is widely used nergic system in development of LID. However, the specific molecu-
as a clinical marker of endothelial function. lar mechanisms about the pathogenesis of LID are not clearly
Methods: We enrolled 82 patients with PD patients and 45 elucidated.
healthy controls. Clinical information and disease duration were col- Methods: In present study, chronic levodopa treatment (12mg/Kg)
lected. PD severity was assessed using the motor Unified Parkinsons was done for 3 weeks after making unilateral mid-forebrain bundle
Disease Rating Stage (UPDRS). lesion with 6-hydroxydopamine in male F344 SD rats. Levodopa-
Results: The results indicated that the mean serum 25(OH) D lev- treated rats were divided into two groups based on the LID develop-
els were significantly lower in PD patients as compared to controls ment using abnormal involuntary movement scale (AIMS). We com-
(21.3 6 3.2 ng/ml VS 24.36 5.6 ng/ml) (p<0.05). FMD was signifi- pared dopaminergic cell and serotonergic fibers between two groups
cantly lower in PD patients (6.2% 6 2.2%) than in controls using immunohistochemistry and western blotting.
(8.6 6 2.7%, p < 0.05). FMD was significantly associated with serum Results: There was no difference in dopaminergic cell wipe-out
25(OH) D independently of BMI, CVD risk factor, motor UPDRS, in striatum between hemi-Parkinsonian rat models with and without
disease duration and homocysteine (r=0.232, p50.03). LID. When we compared the number of 5-HT positive cells in dorsal
Conclusions: These findings provide evidence that vitamin D raphe nucleus, there was no significant difference between two
play a role in endothelial dysfunction in patients with PD and iden- groups. However, rats without LID showed 21.7% reduction of 5-HT
tify specific outcome measure for detecting effect of vitamin D. transporter (SERT) in striatum compared with those with LID. There
were no correlations between AIMS score, and 5-HT positive cell
count or SERT.
133 Conclusions: These findings suggest relative sparing from the
Parkinsons disease-linked mutation in DNAJC13 causes specific death of serotonergic fibers in ipsilateral striatum could be related
trafficking defect in endosomal pathway with development of LID in PD.
S. Yoshida, T. Hasegawa, E. Miura, R. Oshima, N. Sugeno, A.
Kikuchi, A. Takeda, M. Aoki (Sendai, Japan) 135
Objective: The aim of this study is to investigate the effect of Withdrawn by Author
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- 136
nant, rare familial forms of Parkinsons disease (PD). DNAJC13 is a
Dnaj-domain-containing protein that is tightly associated with endo- Neuronal oscillatory activity in the ventrolateral thalamus in
somal membrane. patients with Parkinsonian tremor and essential tremor
Methods: Human wild-type (wt) and Mutant DNAJC13 cDNAs P. Zhuang, M. Hallett, T. Liu, Y. Zhang, J. Li, Y. Li (Beijing,
were subcloned into the pEGFP-C1 eukaryotic expression vector. Peoples Republic of China)
Human Rab5A, Rab7 and Rab11A cDNAs were introduced into Objective: To characterize oscillatory activity in the ventrolateral
pmStrawberry vector. COS7 were transiently transfected with GFP- thalamus (VL) in patients with Parkinsonian tremor and essential
tagged DNAJC13 as well as mStrawberry-tagged Rab GTPase con- tremor (ET).
structs using the NEPA gene square-wave electroporator. The expres- Background: The pathophysiology of Parkinsons disease (PD)
sion and subcellular localization of DNAJC13 were examined using and ET is unclear.
laser scanning microscopy (LSM) and Western blot analyses in com- Methods: 26 patients with PD and 14 patients with ET who
bination with density-gradient centrifugation. To determine how the underwent thalamic surgery were studied. Microelectrode recordings
DNAJC13 mutant affect on the different endosomal pathway, cells in the VL and EMG of contralateral limbs were performed. Single
overexpressing wt or mutant DNAJC13 were incubated in the culture unit analysis and interspike interval was used to assess neuronal
media containing Alexa555-labeled reference molecules including mean firing rate (MSFR) and pattern. Spectral characteristics were
transferrin, EGF and Shiga Toxin 1B subunit.Time-lapse images of evaluated. Coherence analysis was used to explore the relationship
internalized reference molecules were acquired using LSM at 15 sec between oscillatory activity and EMG.
intervals. Results: Of total neurons (n5224) obtained from 26 tracts of PD
Results: While wt DNAJC13 was exclusively co-localized with patients, 66.4% neurons were oscillatory. Of these neurons, 71.1%
rab5A-positive early endosome, part of DNAJC13 p.N855S was mis- neurons (n5109) with bursting activity at mean tremor frequency of
localized from Rab5A to Rab11A-positive recycling endosome. 4.5 6 0.9 Hz were correlated with tremor and defined as TFB oscilla-
Transport assay using reference molecules showed abnormal endoso- tory neurons; 28.8% neurons (n544) with frequency oscillation at
mal trafficking in cells overexpressing DNAJC13 p.N855S. 16.6 6 8.9Hz were defined as FB oscillatory neurons. Of total neu-
Conclusions: PD-linked DNAJC13 mutation impairs specific rons (n572) obtained from 14 tracts in ET, 63.9% neurons were
endosomal trafficking and would thereby contribute to the pathogene- oscillatory. Of these, 89.1% (n541) TFB neurons had burst activity
sis of disease. 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
134 18.4 67.9 Hz. The proportion of FB oscillatory neurons in PD
were significant higher than that of FB oscillatory neurons in ET
Relative sparing from the death of serotonergic fibers in (p<0.05). Moreover, MSFR of oscillatory neurons in PD were signif-
ipsilateral striatum is related with development of levodopa- icantly lower than that of oscillatory neurons in ET (26.7 66.8 Hz
induced dyskinesia in hemi-Parkinsonian rats vs. 42.3 615.6 Hz, p<0.05).
J. Youn, M.Y. Jeon, T.O. Son, J.W. Cho (Seoul, Korea) Conclusions: The proportion of thalamic FB oscillatory neu-
rons is higher in PD supporting that FB oscillatory neurons are
Objective: To investigate the relationship between serotonergic associated with dopaminergic deficits in the basal ganglia circuit.
cell death and development of levodopa-induced dyskinesia (LID). Compared with normal MSFR (estimated to be 30 Hz from record-
Background: Although, dopaminergic medication is the most ings in normal monkeys), the MSFR of oscillatory neurons in the VL
effective therapy in Parkinsons disease (PD), LID presents com- are likely high in ET suggesting an etiologic role of the thalamus
monly with chronic treatment, and has great impacts on quality of in ET.

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


Parkinsons disease: Psychiatric had dementia. During a fMRI session, all participants performed a
task of visual detection. A detection threshold was determined,
manifestations defined as the duration of presentation for which 50% of the stimuli
were seen and 50% not seen. The contrast of the seen and
137 not seen conditions for a same stimulus presented at threshold
Prevalence study of impulse control disorders and compulsive allowed the evaluation of BOLD signal variations at time of access
behaviours in Parkinsons disease in a single centre: to consciousness of visual inputs.
Association with premotor signs and clinical characteristics Results: The visual detection threshold was significantly lower
for healthy subject in comparison with PD patients with and without
A. Acarer, Z. Colakoglu (Izmir, Turkey)
VH (57 vs 159 and 173 ms respectively, p<0.05). This threshold did
Objective: We aim to determine prevalence of impulse con- not differ in both groups of PD patients. Compared with PD patients
trol disorders (ICDs) and compulsive behaviours (CBs) in Par- without VH, access to consciousness of visual inputs in PD patients
kinsons disease (PD) patient seen in our Movement Disorders with minor VH was characterized by a higher involvement of the
outpatient clinic (Department of Neurology, Ege University left anterior cingulate gyrus and the left prefrontal dorso-lateral cor-
Medical Faculty, Izmir, Turkey) between years 2005 2013 and tex, as well as a lower involvement of the left fusiform gyrus and
their associations with premotor signs and clinical characteristics the left inferior temporal gyrus.
of PD. Conclusions: In PD patients with minor VH, access to conscious-
Background: Impulse-control disorders and compulsive behav- ness of visual inputs is characterized by a hyperactivation of brain
iours occur in patients with Parkinsons disease, especially in areas involved in high level cognitive processes, and by a hypoacti-
younger patients on dopamine therapies. Studies indicate a preva- vation of regions involved in low level visual processes.
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- 139
gulation syndrome (DDS) and walkabout. Impact of depression on the rate of progression of impairment,
Methods: In this study, we investigated prevalence of ICDs and disability and quality of life in early Parkinsons disease: NET-
CBs among 477 PD patients seen our Movement Disorders outpa- PD LS1 cohort
tient clinic between years 2005 2013. 477 patients were questioned D. Bega, S. Luo, H. Fernandez, K. Chou, M. Aminoff, S. Parashos,
using a semi-structured questionnaire directed to patients and their H. Walker, D.S. Russell, C. Christine, R. Dhall, C. Singer, I. Bodis-
caregivers based on the DSM IV criteria. We directed questions to Wollner, A. Nicholas, R. Hamill, D. Truong, Z. Mari, S. Glazman, E.
our patients with PD and their caregivers about premotor signs Houston, T. Simuni, On Behalf of the NET-PD LS1 Investigators
(REM sleep behaviour disorder, constipation and smell problems). (Chicago, IL, USA)
We also investigated 477 patients records. There were 40 PD
patients with ICDs and CBs. These 40 patients records were again Objective: To characterize the relationship between depressive
examined to determine premotor signs and clinical characteristics symptoms as measured by the baseline Beck Depression Inventory
of PD. (BDI) and multiple measures of symptom progression in PD using
Results: Impulse control disorders and compulsive behaviours data from the NINDS Exploratory Trials in PD Long-Term Study
were identified in 40 patients (prevalence, 8,3%). Some patient have 1 (NET-PD LS1) cohort, which involved early, treated PD
multiple behaviour symptoms of ICDs and CBs. Pathological gam- patients.
bling was observed in 7 patients with PD, hypersexuality in 11, com- Background: Depression is one of the most common non-motor
pulsive buying in 14, punding in 11, dopamine dysregulation symptoms associated with Parkinsons disease (PD) and the major
syndrome in 15, hobbyism in 4, compulsive internet use in 2, walk- factor contributing to impairment of disease related quality of life
about in 2, compulsive eating in 2. We determined risk factors (QOL). Yet limited data exist on the impact of depression on pro-
regarding ICDs and CBs. These were male sex, younger age, gression of PD disability.
younger age at PD onset, a pre-PD history of ICDs and gambling Methods: Using baseline and longitudinal data from LS1, BDI
problems. There were not any associations between ICDs and premo- scores from participants were correlated with change in multiple
tor signs. measures of disability, impairment, and QOL over a 5-year period.
Conclusions: ICDs and CBs are common among Parkinsons In order to assess which variables have the greatest contribution to
patients. These behaviours can possibly lead to serious psychosocial the BDI in a multivariate model the analysis was reversed using
consequences. Therefore, it is extremely important to detect and change in BDI as the outcome measure.
manage these behaviours. 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
138 (SD 1.16). Mean baseline BDI score was 6.24 (SD 5.02) and
Susceptibility to visual hallucinations in Parkinsons disease: A increased to 8.57 (SD 6.60) at 5 year follow-up. At baseline 11.8%
fMRI study (n5206) of subjects had a BDI  14, and 22.0% of subjects were
using antidepressants. Baseline BDI score was strongly associated
G. Baille, S. Lefebvre, D. Pins, L. Defebvre, K. Dujardin (Lille,
France) with the rate of change in all examined measures of disease sever-
ity, disability, and QOL. In a multivariate analysis using change in
Objective: To assess the propensity to hallucinate in Parkinsons BDI as the outcome measure, baseline BDI was associated with 5-
disease (PD) by comparing the access to consciousness of visual year UPDRS Part I (with depression item removed) (p<0.01) but
inputs between PD patients with and without visual hallucinations not UPDRS ADL (p50.28) or UPDRS motor scores (p50.19). It
(VH) and healthy subjects. was also associated with QOL measures, PDQ-33 (p<0.01) and
Background: Despite their frequency and their impact, patho- EQ-5D (p50.02), but not cognitive measures (p50.17 for SCOPA-
physiology of VH in PD remains unknown. Several studies have COG). This was a fairly robust model, with these 4 significant var-
reported a disturbance in processing of visual inputs. Nevertheless, iables (Total Functional Capacity, UPDRS part I, PDQ-33, and EQ-
the role of more elaborated cognitive processes need to be 5D) explaining about 68.8% of the variance of the BDI score 5-
determined. year change.
Methods: Seventeen healthy subjects, 14 PD patients without VH Conclusions: Worse baseline BDI scores, even in the absence of
and 15 PD patients with minor VH participated in the study. None depression, are associated with a decline in multiple measures of

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


disease severity and symptomatology in PD. Change in the BDI at 5 baseline, post-test, and 1-month follow-up. Paired t-tests examined
years was associated with the change in UPDRS Part I and QOL differences in outcomes by time point.
measures, rather than motor and cognitive measures. Results: Treatment delivery, feasibility, and acceptability data
reflected strong interventionist adherence, expected attrition, and high
patient satisfaction. Apathy, depression, and QoL significantly improved
140 post-treatment with medium to large effects and clinically meaningful
Psychiatric and psychosocial outcome after bilateral deep brain changes. Improvements in apathy and depression were maintained at
stimulation of the globus pallidus pars interna and subthalamic follow-up. Response to treatment was associated with higher baseline
nucleus for advanced Parkinsons disease executive function, novelty seeking, and self-awareness.
J.A. Boel, V.J.J. Odekerken, G.J. Geurtsen, B. Schmand, D.C. Cath, Conclusions: A promising manualized intervention designed to
target self-generational deficits common in PD is presented. Prelimi-
M. Figee, R.J. de Haan, P.R. Schuurman, R.M.A. de Bie, The
nary results showed improved motivation, mood, and QoL in PD
NSTAPS Study Group (Amsterdam, Netherlands)
through a telehealth intervention. A randomized controlled trial is
Objective: To assess psychiatric and psychosocial outcome 12 needed to further investigate the efficacy of the PAL program.
months after bilateral deep brain stimulation (DBS) of the globus
pallidus pars interna (GPi) and subthalamic nucleus (STN) for
advanced Parkinsons disease. 142
Background: Concerns have been raised regarding the psychiat- Problematic mobile gaming: A previously unreported impulse
ric side-effects of DBS, especially STN DBS. The effects on mood control disorder
and behaviour could be the deciding factors in the choice between
E.A. Byrd, N.B. Galifianakis, C.A. Racine (San Francisco, USA)
the two targets (GPi vs. STN).
Methods: We randomly assigned patients to receive either GPi Objective: To present a case of dopaminergic medication-
DBS (n565) or STN DBS (n563). Standardized psychiatric and psy- induced problematic mobile gaming, a previously unreported impulse
chosocial questionnaires were assessed at baseline and after 12 control disorder (ICD) behavior.
months. Patients and study assessors were masked to treatment allo- Background: ICDs are a known side effect of dopaminergic
cation. We performed between-group, within-group, and descriptive medications used in the treatment of Parkinsons disease (PD), esti-
analyses. mated to occur in 10-40% of individuals with PD. Previous studies
Results: No differences were found between GPi DBS and STN have largely focused on the following behaviors: pathological gam-
DBS on psychiatric evaluation investigating, mania, mood, personal- bling, hypersexuality, hobbyism/punding, compulsive eating and
ity, and affect. Within-group comparisons showed small, but statisti- excessive spending. Recent reports have also described problematic
cally significant changes on several measures in both groups. Mania internet use, but our case extends ICD behavior into excessive gam-
scores and positive affect decreased after GPi DBS. Positive affect ing on mobile devices.
scores decreased after STN DBS. Descriptive analyses indicated Methods: Single case report.
slight changes in work status, social participation, and social rela- Results: A 64-year-old woman with a 5 year history of PD who
tions. Marital satisfaction of patients and partners remained relatively was taking levodopa and pramipexole presented with an ICD that
stable after GPi DBS and STN DBS. manifested primarily as playing a video game on her mobile device
Conclusions: We found neither clinically relevant differences in for 2-4 hours per day. She spent $600/month on within-app pur-
psychiatric and psychosocial outcome between GPi DBS and STN chases, which allowed her to continue playing after running out of
DBS, nor any relevant within-group differences before and after DBS. 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
141 had moved in with her. However, 10 months later on return visit she
The Parkinsons active living (PAL) program: A behavioral had started playing another mobile game, spending $800-900/month.
intervention targeting apathy in Parkinsons disease She was again treated by deleting the game. Tapering her dopamine
L.C. Butterfield, C.R. Cimino, R.D. Salazar, C.S. Lee, W.E. Haley, J. agonist was not possible in this case due to painful foot dystonia and
Sanchez-Ramos, M.S. Okun, D. Bowers (Gainesville, FL, USA) truncal dystonia that was minimally responsive to botulinum toxin.
Conclusions: To our knowledge, this is the first report of prob-
Objective: (1) To develop protocol materials to facilitate treat- lematic mobile gaming, an ICD behavior with several unique charac-
ment delivery, (2) to determine ease of training interventionists, (3) teristics which may lead to potentially serious financial
to assess feasibility, acceptability, and estimated effect of a 6-week, consequences. First, mobile games are exquisitely designed with
primarily telephone-based activity scheduling/monitoring intervention entertaining graphics, music, and sometimes subtle within-app pur-
on reducing apathy in non-demented, apathetic Parkinsons (PD) chasing options to maximize game use and profit. Perhaps more
patients. importantly, smart phones and other mobile devices are ubiquitous,
Background: Apathy, reflecting motivation and self-initiation which makes problematic mobile gaming readily available in almost
impairment, is common in PD and associated with a host of negative any time and place. This ubiquity, combined with the fact that gam-
associates, including reduced cognitive and daily functioning, treat- ing does not usually have the stigma associated with gambling and
ment compliance, and quality of life, and increased caregiver stress. other ICDs, make this behavior an important new ICD to actively
While some studies have evaluated pharmacologic approaches to screen with our PD patients. Furthermore, currently available ques-
treating apathy, few have evaluated non-pharmacologic approaches. tionnaires and scales do not address this behavior.
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) 143
An interventionist manual outlining treatment protocol and a patient Relation between farmachological treatment and impulse control
workbook were created. 2) Interventionists were trained and eval- disorder in patients with Parkinsons diseases of recent diagnose
uated for protocol adherence. 3) A one-arm uncontrolled trial was H. Duran Meza, D. Santana Vargas, D. Trejo Martnez (M exico
conducted to estimate treatment effect on self-rated apathy, depres- City, Mexico)
sion, ADLs, QoL, and caregiver burden. Intervention consisted of
one in-person Planning Session to identify and schedule tailored Objective: Identify the relation between pharmachological treat-
goals, and 6 weekly phone sessions. Outcomes were assessed at ment and the presence of Impulse Control Disorder.

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


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

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


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

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


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

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


been paid to diagnosis of the psychotic disorder. Results suggest that order and Stroke, National Institute of Health (NIND and NIMH) criteria
patients who meet the formal diagnosis of psychotic syndrome make was used to assess Parkinsons associated psychosis. Psychotic symptoms
up a separate category with more psychopathological symptoms, sleep and depression were rated using Brief psychosis rating scale (BPRS) and
disorders and low cognitive performance. This result is clinically Patient Health Questionnaire 9 (PHQ9) score respectively.
important for diagnostic criteria, with therapeutic and prognostic Results: 49.3% patients had one or more co morbid psychiatric dis-
implications. 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
152 score (median score 2.5 Vs 2, p value 0.0001). Daily living was signifi-
Cognitive and psychometric properties of drug-induced cantly more impaired among patients with psychotic symptoms. These
Parkinsonism and Parkinsons disease patients had significantly higher daily dose requirement of dopaminer-
gic drugs. Psychotic symptoms were more frequent in Postural Instabil-
J.S. Kim, J.M. Kim (Cheongju-si, Korea)
ity/gait difficulty (PIGD) variant of PD patients.
Objective: To investigate the cognitive and psychiatric aspects of Conclusions: Psychiatric disorders are prevalent among patients
drug-induced Parkinsonism(DIP) and Parkinsons disease(PD). with relatively severe PD. Patients with PIGD variant of PD had a
Background: DIP is the second most common cause of Parkin- higher risk of having psychiatric disorders as compared to tremor
sonism after PD and can be clinically indistinguishable from idio- dominant (TD) variant.
pathic PD, especially in early stages. Among clinical manifestations,
cognitive and psychiatric features that distinguish degenerative from
pharmacologic Parkinsonism are needed. 154
Methods: The sample consisted of consecutive patients who ful- Relationship between cognition and the self-assessment of the
filled the clinical criteria for DIP and PD. General characteristics psychological symptom in PD
include medication history were obtained. The clinical severity was
A. Kumon, Y. Kobayashi, M. Saruwatari, N. Kawashima, K.
evaluated at first visit and after 6 months based on the activities of
Hasegawa (Sagamihara, Japan)
daily living, score on the Unified Parkinsons disease Rating Scale,
and the Hoehn and Yahr scale. The patients cognitive state were Objective: Investigate to clarify the relationship between cogni-
evaluated with the mini-mental state examination (MMSE), the Mon- tion and self-assessment of depression in patients with Parkinsons
treal Cognitive Assessment (MoCA), Clinical Dementia Rating scale, disease (PD).
and mood disorders were screened by Hamilton Depression Rating Background: In patients with PD, depression is one of the most fre-
(HAM-D) scale, Hamilton Anxiety Rating scale, Sheehan disability quent psychiatric symptoms and examined by several subjective scales.
scale, and Liebowitz Social Anxiety Scale. But it is known there were the cases that those patients have difficulty in
Results: Over 12 months, a total of 114 were included. Fifty one self-assessment of the symptom or state such as posture and volume of
patients (44.7%) were DIP patients, and 63 (55.3%) were PD patients. voice. Based on the results of our previous study about apathy, it is likely
The patients with DIP showed significantly lower educational level. In to indicate a similar tendency in psychiatric symptoms.
addition, the number of comorbidities and taking medications were Methods: Subjects were 124 patients with PD (male:
more in DIP patients than PD. The score of MMSE and MoCA were female=60:64, mean age 68.6 years old, MMSE24, HAMD<7),
also lower in DIP patients who committed more errors than PD patients who had been examined frontal lobe function, everyday memory and
on orientation and executive functions. In addition, higher HAM-D subjective depression using FAB, RBMT, SDS, BDI-II.
scores were associated with DIP patients. Results: Subjects were divided into two groups according to
Conclusions: These findings suggested that cognitive impairment and results tendency of SDS and BDI. 88 subjects whose results showed
depression are common among DIP patients than PD. In addition, lower same tendency were discrepancy (-) group. Other 38 subjects whose
educational level and disorientation, various comorbidities and many kinds results showed different tendency were discrepancy (1) group. Com-
of medical pills might affect the drug induced medical problems. 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
153 higher than in discrepancy (1) group (13.8 6 2.3) (p5 .032).
Neuropsychiatric disorders in idiopathic Parkinsons disease Conclusions: In 31% of PD patients maintaining a certain level of
cognitive function and without obvious depression, the results of self-
M.U. Kulsum, A. Dutt, S. Choudhuri, S.S. Anand, C. Sengupta, B.
Mondal, P. Chatterjee, H. Kumar (Kolkata, India) assessment of depression differed depending on the scale being used. And
the difference related to not everyday memory but frontal lobe function.
Objective: 1. To study prevalence of various psychiatric disor- In PD patients, even though they have no problems with everyday mem-
ders in patients with PD. ory, we should carefully evaluate results of subjective scale of depression.
2. To compare the prevalence of psychiatric disorders in Tremor Hereafter we will investigate other factors affecting the difference.
dominant (TD) variant of PD with that in postural instability gait dif-
ficulty (PIGD) variants of PD.
Background: Psychiatric and behavioral symptom associated with 155
Parkinsons disease (PD) is a frequently encountered problem which Psychotic symptoms in Thai patients with Parkinsons disease:
may affect the quality of life of PD patients. By reason of inadequate Prevalence and associated factors
accessibility of reports in this ethnic population; we intended to assess
P. Lolekha, K. Kulkantrakorn (Pathumthani, Thailand)
the frequency and determinants of PD associated psychiatric disorders.
Methods: In this cross sectional study conducted in a Movement Dis- Objective: To determine the prevalence and associated factors of
order and psychiatry Out Patient Department, we have evaluated 150 neuropsychiatric symptoms in Thai Parkinsons disease (PD)
patients with PD (diagnosed by UK Brain Bank Criteria) on socio- patients.
demographic and clinical profile. The PD symptoms were objectively quan- Background: Hallucinations, Sense of Presence (SoP) and delu-
tified using Unified Parkinsons disease Rating Scale (UPDRS), Modified sions are frequent neuropsychiatric symptoms that reduce quality of
Hoehn and Yahr staging and Schwab and England activities of daily living life of PD patients. While the pathophysiology of these neuropsychi-
scale. Cognitive assessment was done by Mini Mental state examination atric phenomena is not well understood, it is commonly believed as
(MMSE). The Mini International Neuropsychiatric Interview was used to a side-effect of dopaminergic treatment in combination with the
screen for psychiatric illness and the National Institute for Neurological dis- underlying brain pathology of PD patients.

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


Methods: One-hundred and thirty patients with PD were included less of age, sex, race group, or screening MMSE score. There was
in the study. Demographic and clinical variables were recorded, no worsening of Parkinsonism as measured by UPDRS II1III, and
including Schwab & England Activity of Daily Living (SE-ADL the adverse event profile was virtually identical to placebo.
scale), UPDRS motor score, Hoehn & Yahr stage (H&Y), Levodopa Conclusions: Pimavanserin appears effective, safe and well-
Equivalent Dose (LED), Thai Mental State Examination (TMSE), tolerated for PDP based on individual study data (previously pub-
and Thai Geriatric Depression Scale-15 (TGDS-15). Hallucinations, lished) and in this pooled analysis of Phase 3 placebo-controlled
SoP and delusions were assessed by Thammasat University Non- data.
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), 157
and delusions (20%, n526). Among the patients with psychotic Othello syndrome in a Parkinsons disease patient with dementia
symptoms, 21% (n59) had isolated hallucinations, 7.1% (n53) had initiating Donepezil therapy: A case report
isolated SoP, and 18.6% (n58) had isolated delusions. Auditory hal- O.A. Molokwu, I.O. Onwuekwe, A.C. Nwabueze (Enugu, Nigeria)
lucinations were found in 7.7% (n59) and all were combined with
visual hallucinations. The psychotic symptoms in PD patients were Objective: To report a case of Othello syndrome in a Parkinsons
significantly associated with poorer SE-ADL scale, lower TMSE disease patient with dementia following commencement of
score, higher TGDS-15 score, higher TU-NMSQuest score, advanced Donepezil.
age, higher H&Y stage, and higher UPDRS motor score. Multiple Background: Psychiatric presentations such as depression, delu-
linear regression analysis showed severe cognitive impairment, sional disorders etc. have been described in patients with Parkinsons
depression, anxiety disorder and advanced disease stage were the disease (PD). Othello syndrome (OS) describes a psychiatric condi-
most significant factors for psychotic symptoms in PD. Duration of tion characterized by morbid jealousy in which the sufferer holds a
PD, type of antiParkinsonian medication and LED were not signifi- strong delusional belief of spousal or sexual partners infidelity with-
cantly associated with these symptoms. out having any significant proof to back up such claim.The causes of
Conclusions: Hallucinations, SoP and delusions are common in OS cuts across psychiatric illness, alcoholism, drug abuse, neurologi-
Thai PD patients and are likely to be multifactorial in origin. cal illness including PD and/or in association with its drug treatment
Advanced disease stage, cognitive impairment, depression and anxi- etc. Few case reports have described the occurrence of OS in PD
ety disorder are the most significant factors of psychotic symptoms patients.OS impacts negatively on marital relationship and increases
in Thai PD patients, regardless of disease duration, type and dosage caregiver strain. OS increases the risk for violence and aggression
of antiParkinsonian medication. towards spouse which if not tackled may lead to suicide and/or
Methods: We report a case of Othello syndrome in a PD patient
156 who was initiating treatment with Donepezil for recently diagnosed
Efficacy and tolerability of pimavanserin in PD psychosis: dementia and to review literature on the condition.
Analysis of an integrated phase 3 placebo-controlled dataset Results: A 62 year old man who was diagnosed of PD with
dementia and was commenced on Donepezil. About a week there-
R. Mills, J.H. Friedman, W. Ondo, R. Pahwa, K. Black, K. Chi-
after, he developed morbid jealousy associated with delusional belief
Burris, H. Williams (San Diego, CA, USA)
that his wife was having an affair with his bosom friend. He engaged
Objective: Pooling of efficacy data across studies can provide a in confirmatory behaviors such as checking his wifes phone call list
more precise estimate of overall treatment effect, treatment effect for and messages. He was aggressive sometimes, then later became
endpoints measured infrequently, and variation of effect across sub- depressed.The temporal association with initiation of Donepezil
groups of interest. A pooled analysis of two Phase 3, placebo- tended to suggest that the OS was an adverse drug reaction (ADR).
controlled studies was conducted to further evaluate the efficacy of However,Naranjo score for ADR probability was 2 which implies a
pimavanserin in PD Psychosis (PDP). The dataset comprised 268 N. probable ADR.He was admitted into the ward and did haemogram,
American subjects who received once-daily blinded treatment for up liver function test, biochemical panel test which were unremarkable.
to 6 weeks. CT scan done showed age related brain atrophy. He was reviewed
Background: Psychosis is common in PD and increases with dis- by the psychiatrist and was tried on some neuroleptics and antide-
ease duration. It is associated with increased morbidity/mortality, pressants with minimal improvement. He was later discharged on
complicates management of motor symptoms and often leads to request by the relatives and was lost to follow up.
long-term care placement. Pimavanserin is a potent, selective 5- Conclusions: Prompt recognition and treatment of Othello syn-
HT2A inverse agonist being developed as a first-line treatment for drome is imperative in other to prevent the untoward knock-on nega-
PDP. tive effect on marital relationship and patient outcome. while
Methods: Pooling is appropriate only for homogeneous popula- checkmating the increased risk of violence against partner, suicide
tions, where the same treatment duration, comparator and treatment and/or homicide seen in this condition.
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- 158
treated subjects. Effect of dopaminergic medication on BOLD fMRI in
Results: Pimavanserin 40mg demonstrated a 6.21-point improve- Parkinsons disease patients with visual hallucinations during a
ment in psychosis at Week 6 as measured by blinded, independent visuoperceptual task
raters using the PD-adapted Scale for Assessment of Positive Symp-
A.J. Muller, C. OCallaghan, J.M. Shine, S.J.G. Lewis (Sydney,
toms (SAPS-PD; primary change from baseline analysis [MMRM]). Australia)
The treatment difference was 2.87 points over placebo (p<0.001)
and was clinically meaningful. Pimavanserin 40mg also showed stat- Objective: To investigate neural mechanisms affected by dopami-
istically greater benefit over placebo on all SAPS supportive meas- nergic Parkinsons disease (PD) medications during visual misper-
ures and sensitivity analyses as well as on CGI-Severity, CGI- ception events in patients with visual hallucinations (VH).
Improvement (CGI-I), CGI-I responder analysis, SCOPA-nighttime Background: Although VH are extremely common in PD, their
sleep and daytime wakefulness measures, and caregiver burden score. neural mechanisms remain poorly understood. First line of treatment
Results were consistent across all subgroups of interest, showing of VH in PD usually involves a reduction of dopaminergic medica-
greater improvement with pimavanserin 40mg over placebo, regard- tion dose; however the direct effects of dopaminergic medication on

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


the neurobiology underlying hallucinatory events has yet to be (CI), 1.432 to 14.617; p 5 0.010] and dementia significantly corre-
established. lated with HY stage 5/3 (OR, 5.304; 95% CI, 1.327 to 22.948;
Methods: We performed functional MRI combined with the p 5 0.018).
Bistable Percept Paradigm (BPP), a visuoperceptual task capable of Conclusions: Our results suggest that among patients with PD,
eliciting visual misperceptions in patients with VH. All 15 patients the presence of hallucination, dementia, and delusions may be related
reported VH and were assessed in a randomised order both on their to UI, HY stage, and Dys, respectively.
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- 160
ated with correct perceptions on the task versus visual mispercep- Parkinsons disease psychosis (PDP): Characteristics of the PDP
tions, in both the ON and OFF states. Correction for multiple patient in clinical practice
comparisons was performed by controlling FWE<0.05, with 20-
J. Norton, D. Fredericks, R. Suresh, R. Mills (San Diego, CA, USA)
voxel extent threshold.
Results: Misperceptions were associated with significantly differ- Objective: To characterize the typical PDP patient across a vari-
ent neural activity patterns in the ON versus OFF states. These ety of dimensions.
included a significant increase of activation in the right parietal lobe, Background: PDP is a prevalent neuropsychiatric manifestation
and left inferior parietal lobe, cuneus, precuneus and dorsal posterior with lifetime prevalence in Parkinsons disease (PD) patients of up
cingulate area. A significant decrease of activation was shown in the to 50%. The PDP patients care is complex due to the need to not
left superior frontal gyrus. Behaviourally, there was no difference in only manage the symptoms of Parkinsons but also a variety of non-
the amount of misperceptions experienced in the ON and OFF states, motor issues, including psychosis.
although patients exhibited significantly higher levels of mispercep- Methods: 214 physicians (132 neurologists, 37 psychiatrists, and
tions on the BPP compared to established performance in healthy 45 primary care physicians) were asked to participate in a question-
age matched controls (p < .01). naire on PDP patients. Patients with Schizophrenia, Schizo-affective
Conclusions: Whilst behavioural results did not show significant disorder or Bipolar disorder were ruled out. Patient records were
differences within patients, these results indicate that dopaminergic required to include:
medication mediates neural activity associated with hallucinatory 2 records for patients currently being treated with an
events. The left-lateralised inferior parietal lobule, precuneus, and antipsychotic.
dorsal posterior cingulate regions potentially implicate dopaminergic 1 record for patients currently being treated with either an anti-
modulation of the default mode network during visual misperceptions psychotic, anti-depressant or anti-dementia agent.
in PD with VH; a network normally involved in introspection and 1 record for patients managed through modification of PD
self-referential tasks. The present results have implications for the medications.
understanding and management of VH in PD. 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
159 majority of PDP patients were living at home and being managed in
Investigation of factors associated with distinct psychiatric an office setting (54%), while 19% were in a long term care setting.
symptoms in patients with advanced Parkinsons disease 89% had some type of caregiver support, typically by an unpaid
K. Nakahara, R. Kurisaki, T. Sakamoto, K. Yi, T. Yamashita, K. caregiver. The reported psychotic symptoms varied, with 50% report-
ing hallucinations, 33% delusions, 33% lack of impulse control, 32%
Uekawa, Y. Ando (Uki, Japan)
paranoia, and 25% aggressive behavior. In 60% of the PDP patients,
Objective: To investigate factors associated with individual psy- the onset of psychotic symptoms developed at an average age of 67
chiatric symptoms in patients with advanced Parkinsons disease and within 4 years of initial PD diagnosis. The PDP patient typically
(PD). had more severe PD and a higher incidence of comorbidities, partic-
Background: Psychiatric symptoms are serious complications in ularly Alzheimers disease and renal dysfunction. Additionally, 71%
patients with advanced PD. of PDP patients suffered from sleep disorders.
Methods: Ninety-nine patients with PD who had Hoehn and Conclusions: The PDP patient is typically older and has a signifi-
Yahr (HY) scale scores 3 were treated as outpatients or inpatients cant number of comorbidities adding to the complexity of their treat-
in our institute between April 1 and November 30, 2013. Among ment. Current literature suggests that PDP patients suffer primarily
these, seven patients who underwent stereotactic brain surgery or had from hallucinations within the latter half of the first decade after
insufficient data were excluded from the study. diagnosis; however, this study found that delusions, impulse control
Based on the medical interviews and examinations performed by issues, paranoia and aggressive behavior are also common and occur
neurologists, relationships between psychiatric symptoms (hallucina- earlier in the course of the disease. Because of the severity of these
tion, dementia, depression, delusion) and other clinical parameters symptoms treatment should be considered earlier.
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- 161
tion of PD, 9.8 6 6.3 years; and mean HY stage, 3.9 6 0.8 (stage 3: Risk factors for psychosis in patients with Parkinsons disease
46 patients, stage 4: 25 patients, stage 5: 21 patients). Psychiatric M.S.G. Rocha, R.G. Borges, C.D.M. Costa, M.O. Oliveira, S.M.D.
symptoms were diagnosed in 36 patients (39.1%); of these 19 had
Brucki, F.F. Godinho, P.C. Gordon (Sao Paulo, Brazil)
hallucinations; 18, dementia; 10, depression; and 5, delusion. Uni-
variable logistic regression analysis revealed that the presence of hal- Objective: The aim of this study is to evaluate risk factors, par-
lucination significantly correlated with the duration of PD, urinary ticularly sleep alterations and dementia, associated with psychosis
incontinence (UI), and dyskinesia (Dys); presence of dementia signif- diagnosis in PD.
icantly correlated with duration of PD, HY stage, and UI; and delu- Background: Parkinsons disease (PD) patients frequently present
sion significantly correlated with Dys. Depression did not correlate psychotic symptoms that have been associated with old age, duration
with other clinical parameters. Multivariable logistic regression anal- of PD, and cognitive impairment. Depression and sleep abnormalities
ysis (explanatory variable: every item showing a significant differ- are also related to these factors.
ence by each analysis) revealed that hallucination significantly Methods: This is a cross-sectional evaluation of 94 consecutive
correlated with UI [Odds ratio (OR), 4.489; 95% confidence interval patients from a Movement Disorders clinic. A neurologist performed

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


clinical evaluation. Behavioral questionnaires were applied by a psy- B: 35 6 22). There were no differences in the rest of scales except
chiatrist, who used structured interview with both patient and care- for HADS (A: 5 6 3.9, B: 6 6 4.4), although these scores were below
giver to define psychosis diagnosis (PC) in accordance with DSM-4 clinical significance.
criteria. Clinical evaluation included UPDRS, sleep scales (SCOPA- Conclusions: The incidence of ICD was similar with the different
sleep, Epworth and REM sleep behavior disorder), quality of life DAs. Rotigotine was more frequently associated with gambling and
(PDQ-39), depression (Beck Inventory), and NINDS criteria for psy- less with hobbyism than pramipexole and ropinirole but the severity
chosis in PD. Subjects underwent a formal neuropsychological evalua- of all ICDs was not different among groups.
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); 163
individuals with PC had significant differences (p<0.01) in relation Left temporal lobe focal EEG abnormalities in Parkinsons
to patients without PC in relation to diurnal sleep quality (SCOPA- disease with visual hallucinations
Sleep), more severe diurnal hyper somnolence (Epworth scale), G.J. Schwartz, M.L. Gordon (Stony Brook, NY, USA)
worse quality of life (PDQ39), and more severe depression. Demen-
tia was significantly higher between PC patients (84.6%) than those Objective: To describe electroencephalography (EEG) abnormal-
without psychosis (24.5%). There was no significant difference in ities in a cohort of Parkinsons disease (PD) patients with visual hal-
severity of REM sleep behavior disorder between groups. Logistic lucinations (VHs).
regression analysis, including age, sex, PD duration, UPDRS total Background: The cause of VHs in PD remains poorly under-
score, Hoehn & Yahr stage, daily levodopa equivalent dosage, Beck stood. While dopaminergic medications have been implicated, there
depression inventory score, sleep scales scores, and postural instabil- is a growing body of evidence suggesting that VHs may be a mani-
ity gait disorder score, showed that only dementia and Epworth score festation of the underlying disease itself. One study has suggested
were independently associated with PC in PD (p50.002 for demen- that left hemispheric dysfunction in particular is associated with VHs
tia, and p50.016 for Epworth score). in PD. Furthermore, the phenomenology of temporal lobe ictal hallu-
Conclusions: Our data show that the presence of dementia and diur- cinations resembles those of VHs in PD.
nal somnolence are strongly associated with PC in PD and reaffirm that, Methods: We conducted a retrospective chart review of PD patients
in most patients, psychotic symptoms are probably part of a full spectrum with VHs, who had routine EEGs available for review. This cohort of
of dementia associated with PD, and not an isolated syndrome. 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.
162 Results: Forty nine EEGs were available for review in 28 patients
Incidence and severity of impulse control disorders in with PD and VHs. The male:female ratio was 1.5:1, the average age
Parkinsons disease patients treated with dopamine agonists was 79 years, and Parkinsonian motor signs were right-predominant in
M.C. Rodrguez-Oroz, R. Ribacoba Montero, A. Rojo-Sebastian, A. 70% (p 5 0.10 by Chi-square). The mean duration of PD, dopaminer-
Sesar Ignacio, M. Delgado-Alvarado, B. Ares Pensado (San Sebas- gic pharmacotherapy, and VHs was 10, 8 and 3 years, respectively.
Formed VHs were present in all patients, although 11% had elemen-
tian, Spain)
tary VHs as well. They were predominantly diurnal, although in 14%
Objective: Evaluate the incidence and severity of Impulse Con- of patients they were only hypnopompic. At least one abnormal EEG
trol Disorders (ICDs) among Parkinsons disease (PD) patients was found in 85% of patients: generalized background slowing in
treated with dopamine agonists (DAs). 79%, intermittent delta activity in 21%, and focal temporal lobe spikes
Background: Chronic use of DAs is often associated with side or sharp-waves in 14%. Lateralized focal EEG abnormalities were
effects among which ICDs are common. detected in 17% (n 5 5), all of which appeared in the left temporal
Methods: An observational, descriptive, cross-sectional study was lobe. The probability of lateralized abnormalities occurring exclusively
conducted in 4 hospitals in Spain. A total of 159 patients treated on the left by chance alone would be less than 4% (p 5 0.03).
with ropinirole, pramipexole or rotigotine were consecutively Conclusions: We found left temporal lobe focal EEG abnormal-
recruited, 53 patients in each treatment arm. Patients with PD on ities in a subset of PD patient with VHs, findings which are consist-
treatment with a DA for a minimum of 2 years or less if an ICD ent with a potential for left temporal lobe epileptogenicity.
occurred were eligible to participate. Demographic and clinical data Furthermore, in this cohort of PD patients with VHs, we found a dis-
of patients, previous history of DAs and treatment at the time of the proportionate number of those with left hemisphere-predominant Par-
study and when an ICD occurred were collected. Clinical features kinsonism. These findings suggest that left temporal lobe dysfunction
were evaluated using the following scales: Hoenh and Yarh Scale, may predispose to VHs in PD.
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- 164
pital Anxiety and Depression Scale (HADS) and Parkinsons disease Limitations of the BDI-II in PD evaluation: Concordance with
questionnaire (PDQ-8). Patient analysis sets: pramipexole-ropinirole the GDS-30
(group A) and rotigotine (group B).
M.J. Sollman, I. Ul Haq, S.S. Kramer, J.F. Cook, J.G. Hesse, M.S.
Results: 151 patients were analysed: pramipexole (51), ropinirole Siddiqui, A.W. Laxton, S.B. Tatter (Winston Salem, NC, USA)
(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 Objective: To evaluate diagnostic utility and operating character-
groups A and B respectively (p50.62). QUIP questionnaire showed istics of the BDI-II in Parkinsons disease (PD) patients undergoing
more gambling and less hobbyism (p<0.05) in group B (gambling A neuropsychological assessment as part of routine care or Deep Brain
4% and B14%; hobbyism A 37% and B 20%) without differences in Stimulation surgery (DBS) evaluation.
the (QUIP-RS) between the groups. No differences in incidence of Background: The presence of Depression in PD has relevance to
ICDs were seen for different cumulative doses of DA Patients in QOL (Jones et al., 2014), suicidal ideation, and DBS planning. A
group A were younger and had less years of evolution of the disease high estimated prevalence of minor or major depression in PD (20-
(age: A: 67 6 8.9 and B: 70 6 8.3; years of disease: A: 8 6 5.1 and 45%) suggests strong need for routine screening. Tremendous
B: 10 6 5.3). UPRDS and PDQ-8 scores were higher in group B research has supported use of the BDI-1a as a screening instrument
(UPDRS II: A: 12 6 6.0, B: 16 6 8.3; UPDRS III: A: 19 6 9.6, B: in this population. Less knowledge is available about the BDI-II,
28 6 13.4; UPDRS IV, A: 2 62.3, B: 3.5 6 2.9; PDQ-8: A: 27 6 18, while very similar to its predecessor (see Inoue et al., 2010).

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


Methods: We examined concordance between the BDI-II and GDS- 166

30, another well-validated measure of depression that places significantly
less emphasis on somatic symptoms (Ertan et al., 2015; Schrage et al., Dopaminergic medication increases risky choice via decreasing
2007). Participants were 204 PD-positive, well-educated older adults loss aversion in depressed but not in non-depressed Parkinsonian
(mean education 14 [SD=2.9] years) undergoing full neuropsychological patients
evaluation as a part of routine care or DBS work-up(71%). The Interna- M. Timmer, G. Sescousse, P. Piray, R. Esselink, R. Cools (Nijmegen,
tional Parkinson and Movement Disorder Society (MDS) Task Force- Netherlands)
recommended score of 9/10 (Schrage et al., 2007) was used for the GDS- Objective: To investigate dopaminergic drug effects on loss aver-
30, and published cut score of 14/15 was used for the BDI-II. sion defined as the relative weighting of gains and losses during
Results: In the overall sample, 33.0% of patients screened positive risky choice in depressed and non-depressed patients with Parkin-
with the GDS-30 compared to only 6.7% with the BDI-II, despite its sons disease (PD).
inclusion of somatic symptoms. Concordance in 120 patients adminis- Background: Dopaminergic medication is known to trigger undesir-
tered both screens suggests a BDI-II sensitivity of .71 and a specificity of able side effects such as impulse control disorders (ICDs) in patients
1.0 (GDS-30 5 28.3%, BDI-II 5 8.3%, hit rate 5 .80). The rate of detec- with PD. However, these side effects only occur in a subgroup of
tion was not grossly different in the subset of 86 pre-DBS patients patients, presumably reflecting an underlying vulnerability related to ven-
(26.7% versus 5.8%). The sample had similar prevalance of apathy tral striatal function. Depression, which is associated with ventral striatal
(30%) as found in other studies (e.g., Zahodne et al., 2012). Maximizing dysfunction, is a frequent non-motor symptom of PD. Here we hypothe-
sensitivity of the BDI-II while maintaining adequate specificity required size that it might constitute a vulnerability factor for developing ICDs
a cut score of < 4 in this sample (AUC=.915, Sn=1.0, Sp 5 .826). following dopaminergic medication, eventually leading to risky behavior.
Conclusions: Our data suggest the BDI-II grossly underestimates Methods: Depressed and non-depressed PD patients performed a
the likelihood of current minor or major Depression in PD patients well-established gambling task designed to measure loss aversion during
using validated cut scores. This does not appear to be due to presen- risky choice. Dopaminergic drug effects on loss aversion were investi-
tation management of pre-DBS patients. Lowering the BDI-II cut gated using a within-subject design, in which patients were assessed on
score to maximize sensitivity was not a reasonable solution in this two occasions - once after taking their normal dopaminergic medication
sample. The GDS-30 is felt to be additionally beneficial in offering (ON) and once after withdrawal of their medication (OFF).
two questions of hopelessness. Results: Dopaminergic medication induced differential effects on
loss aversion in depressed and non-depressed PD patients. While
165 there was no clear drug effect on loss aversion in non-depressed PD
patients, dopaminergic medication significantly reduced loss aversion
Brain regions associated with neuropsychiatric symptoms in (i.e. increased risky choice) in currently depressed PD patients. Fur-
patients with Parkinsons disease: An analysis of cerebral blood thermore, the degree to which medication reduced loss aversion cor-
flow using 123I-iodoamphetamineSPECT related with current depression severity and with drug effects on
H. Tachibana, K. Kawabata, T. Yamanishi, H. Nishimura, T. depression scores. Medication-related reductions in loss aversion
Tokunaga, T. Nakajima (Nishinomiya, Japan) were greater in more severely depressed patients and in patients who
exhibited greater medication-related decreases in depression scores.
Objective: To analyze correlations between rCBF and neuro- Conclusions: Dopaminergic medication increases risky choice via
psychiatric symptoms such as cognitive impairment, depression, apa- decreasing loss aversion in depressed but not in non-depressed PD
thy, and anxiety. patients. These data suggest that side effects of dopaminergic medi-
Background: Mental impairments and neuropsychiatric symp- cation in the domain of risky choice might differ between depressed
toms can appear in patients with Parkinsons disease (PD), which and non-depressed PD patients.
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. 167
Methods: Thirty-three patients with PD (mean age, 71.7 years)
underwent brain SPECT using 123I-iodoamphetamine.SPECT images Withdrawn by Author
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 POSTER SESSION 2
correlation between rCBF and clinical parameters, the statistical
results were expressed as Z score on surface projections maps. PD Monday, June 15, 2015
patients completed the Beck Depression Inventory 2nd edition (BDI- 12:3014:00
II),the State-Trait Anxiety Inventory (STAI), and Starksteins Apathy Coronado Ballroom
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 Parkinsons disease: Clinical trials,
27.4, 17.0, 17.4 and 49.4, respectively. The mean values of duration pharmacology and treatment
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, 168
parietal and occipital cortices, precuneus, posterior cingulated cortex Repeated intravenous amantadine infusions in advanced
and cerebellum. Correlations in similar areas were observed between Parkinsonism: The preliminary Tel-Aviv Medical Center
rCBF and AS scores. In the STAI score, negative correlations were experience
found in bilateral parieto-temporo-occipital cortices, medial part of M. Abu Snineh, T. Nussbaum, A. Hindi, A. Rosenberg, J. Knaani, A.
frontal cortex and cerebellum. Ezra, N. Giladi, T. Gurevich (Tel Aviv, Israel)
Conclusions: Present results suggest that there are some differen-
ces in associated brain regions among these major neuropsychiatric Objective: To summarize our experience with repeated intrave-
symptoms and cognitive impairment in PD patients. nous Amantadine in patients with advanced Parkinsonism.

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


Background: Few studies have examined the effect of intrave- of local provider (n51), and technology incompatibility (n52). Partic-
nous amantadine infusions in advanced Parkinsonism. ipants mean age is 65, mean disease duration is 8 years (range 1-22),
Methods: The medical files of 30 patients were reviewed. They and 51% are women. The 29 telemedicine participants are younger
received IVAM once every 3-4 weeks in the setting of neurological (mean 63) than the 32 usual care participants (mean 67) (p<0.05),
day care service. Patients and caregivers participated in a structured while gender distribution and disease duration are similar (p>0.05).
interview on clinical global impression of changes scale (CGICS) To date, 27 telemedicine visits have been completed, 93% as
regarding various symptoms. Treatment was initiated by a loading scheduled. Median visit duration is 51 minutes, 42 (82%) of which
dose of 200/400 mg for 5 days followed by a once every 2-3 weeks are spent with investigators. Participants report spending 120 minutes
dosage of 200/400 mg depending on the duration of treatment effect. (median) away from home for their last in-person appointment, 30
Results: Thirty patients (12 females) participated in the study. (25%) with a provider. All participants report being very satisfied
Nineteen had PD, 5 had multiple system atrophy (MSA) Parkinsonian or satisfied with the care, comfort, and overall experience of tele-
type, 3 had MSA cerebellar type, 2 had vascular Parkinsonism, and 1 medicine. Video quality remains a limitation: for 38% of initial tele-
had diffuse Lewy body disease. Their mean age was 73.27 6 9.67 medicine visits, investigators were highly unsatisfied (14%) or
years, average disease duration 5.5 6 4.8 years, and H&Y score unsatisfied (24%) with their ability to perform the MDS-UPDRS
3.16 6 0.87. The average levodopa dose was 1051 6 1782 mg. The motor assessment. However, 21 visits (78%) were rated highly sat-
mean IVAM treatment duration was 22.9 6 11.26 months. Most isfactory or satisfactory overall by investigators.
(76%) of the patients reported an improvement in tremor and rigidity, Conclusions: Participants are highly satisfied with telemedicine
and an improvement in stability and falling reduction (79%). visits. Investigators are modestly satisfied, but connection quality
An unexpected significant improvement of constipation was remains a challenge. Future results of participant-reported and blinded
reported by 4 patients (20%, p =0.012). Overall 91% of the patients outcomes will enable comparison of telemedicine care to usual care.
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- Pharmacokinetics, safety and tolerability of sub-lingually
sion and urinary complaints. administered APL-130277 compared to subcutaneous
Conclusions: The results of this retrospective open-label study apomorphine in healthy volunteers
indicated that repeated IVAM were effective and safe in patients A. Agro, J. Dubow, L. Toong-Chow, A. Giovinazzo (Toronto,
with Parkinsonism. Controlled double blind studies for exclusion of Canada)
a placebo effect are warranted.
Objective: To evaluate the pharmacokinetics, safety and toler-
ability of 2 doses of Sub-lingually administered APL-130277 (APL)
169 compared to subcutaneous apomorphine (SC Apo) in healthy
A randomized controlled trial of telemedicine for Parkinsons volunteers.
disease (Connect.Parkinson) in the United States: Interim Background: Parkinsons disease (PD) patients suffer from a
assessment of investigator and participant experiences variety of Off episodes as the disease progresses. These consist of
M.A. Achey, C.A. Beck, D.B. Beran, C.M. Boyd, P.N. Schmidt, A.W. wearing off, delayed-On or dose failures, sudden Offs and morning
Willis, S.S. Riggare, R.B. Simone, K.M. Biglan, E.R. Dorsey, J. akinesia. The only acute and effective rescue medication for these
Off episodes is apomorphine administered subcutaneously. Easier
Aldred, J. Ayan, M.T. Bull, J. Carter, K. Duderstadt, B. Dunlop,
to administer rescue treatments are needed. APL is a soluble film
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, strip of apomorphine delivered sub-lingually, designed to deliver
S.A. Parashos, I.H. Richard, L.C. Shih, M.A. Spindler, C. Wielinski, apomorphine rapidly through absorption from the oral cavity.
Methods: This was a single-center, Phase 1 trial in healthy vol-
C. Zadikoff (Rochester, NY, USA)
unteers that assessed the single-dose pharmacokinetics, safety and
Objective: The Connect.Parkinsons study aims to assess the fea- tolerability of APL administered to two cohorts (10mg and 15 mg)
sibility, efficacy, impact on quality of care, and value to patients and in a cross over design as compared to 2 mg and 3 mg of SC Apo
families of home telemedicine visits for Parkinsons disease (PD). (10 mg APL received 2 mg SC Apo and 15 mg APL received 3 mg
Background: This is the first national randomized comparative of SC Apo). Subjects were dosed with APL film strip on the under-
effectiveness study of telemedicine for PD. side of the tongue with the drug layer facing the bottom of the
Methods: Participants are recruited via PD community website and tongue. Subjects were pre-medicated with 3 days of domperidone,
social media outreach, e-mails to advocacy groups, and outreach to pri- which was continued during treatment.
mary care providers in underserved areas. Participants are randomly Results: The mean Cmax, Tmax, T1/2 and AUC for APL 10 mg
assigned to usual care or usual care plus 4 telemedicine visits with a (N=13), APL 15 mg (N=12), SC Apo 2 mg (N=13) and SC Apo
specialist. Primary outcomes include feasibility, measured by percent- 3 mg (N=12) are outlined in Table 1. Mean plasma levels are pre-
age of telemedicine visits completed, and efficacy, measured by change sented in Figure 1. The time spent above 3 ng/ml (the typical plasma
in PDQ-39. Secondary outcomes include blinded MDS-UPDRS scores. level for a patient to go from Off to On) was longer for APL
Here we report preliminary enrollment, retention, and satisfaction. compared to SC Apo and the number of subjects reaching the mini-
Results: As of January 2015, 87 people (44% of 200 planned) are mal toxic concentration (8.5 ng/ml) was lower for APL compared to
enrolled and 61 (70%) have been randomized. Four have withdrawn, SC Apo.
due to disappointment at randomization to control (n51), preference [figure1]

TABLE 1. Mean Pharmacokinetics of APL-130277 and SC Apomorphine

Dose Cmax (ng/ml) Tmax (min) T1/2 (min) AUCLast (min*ng/ml) AUCinf (min*ng/ml)
APL-130277 10 mg 5.45 34.2 56.5 509 543
SC apomorphine 2 mg 9.78 20.4 42.1 597 612
APL-130277 15 mg 8.02 39.2 54.7 804 854
SC apomorphine 3 mg 16.2 26.7 40.1 996 1022

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


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

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


Results: Eleven subjects were dosed with APL and two with pla- the frequency of dance therapies, the effects of different music gen-
cebo. The mean Cmax was 11.2 ng/ml, Tmax was 41.5 minutes, t1/2 res, participant satisfaction with therapy, socialisation, or retention of
was 62.2 minutes, AUCLast was 1102 min*ng/ml, and AUCinf was improvements associated with therapeutic dance intervention. More-
1204 min*ng/ml. The mean plasma concentration over time is pre- over there was little information about the advantages of caregiver
sented in Figure 1. It took approximately 7 minutes to reach the min- participation on the therapy, which may be closely correlated with
imum threshold concentration necessary to achieve efficacy in participant compliance. Therefore, more research is needed to com-
patients (3 ng/ml). A concentration greater than this threshold was prehensively evaluate these aspects of dancing programs.
maintained for 154 minutes. [figure1] Conclusions: There was emerging evidence that dance therapy is
Incidence of adverse events reported with APL 25 mg are pre- safe and feasible for people with mild to moderately severe PD, with
sented in Table 1. The events were mostly mild to moderate in beneficial effects on walking speed, freezing and health related qual-
severity, except for dizziness, which was reported to be severe in ity of life in some individuals.
three subjects. No serious adverse events occurred.
Incidence of Adverse Events with APL 25 mg in 2 or more Efficacy of safinamide in early Parkinsons disease: Results of
Subjects pooled analysis
Type of AE N(%) N=11 R. Anand, R.D. Hartman, V. Lucini, E. Forrest, R. Giuliani, M.
McBride (St. Moritz, Switzerland)
Any AE 11(100)
Objective: Analyses were performed to determine if the signifi-
Related AE 11(100)
Dizziness 9(82) cant benefits noted with safinamide as an add-on to early-stage PD
Sleepiness 9(82) patients in three DA-agonist monotherapy (ESPD) trials extend to
multiple measures of clinical relevance in pooled data analyses.
Nausea 4(36)
Background: Safinamide (50 and 100mg/day) add-on to DA-
Vomiting 4(36)
Feeling Cold 2(18) agonist monotherapy given in non-fluctuating patients (Studies 009,
Hypotension 2(18) 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
Conclusions: APL 25 mg administered sub-lingually demon- were assigned to a treatment group based on the randomized targeted
strates a favorable PK profile to support a rapid and sustained effect dose (placebo; safinamide 50 or 100 mg/day). The difference
for the relief of OFF episodes in Parkinsons disease patients. between treatment groups was compared using Mixed Model
Time to reach a minimum efficacious concentration was under 10 Repeated Measures (MMRM) and Analysis of Covariance
minutes and apomorphine levels were maintained above this concen- (ANCOVA) for continuous measures (UPDRS I, II, III, II1III and
tration for over 2.5 hours. Although dopaminergic AEs were rela- I1II1III) and logistic regression (chi-square test) for categorical
tively high in healthy volunteers, these are expected to be lower in ones (improvements of  30%, 40%, 50% in UPDRS III,  20% and
PD patients already on dopaminergic medications and with impaired 30% in UPDRS II1III, and improvement in CGI-Change [CGI-C]).
dopamine production. APL-130277 may offer easy to use, rapid, on- Results: The pooled analyses included 649 patients on safinamide
demand management of Off episodes in PD patients. and 349 on placebo without significant differences between treatment
groups in demographics, disease characteristics (PD duration, Hoehn
172 &Yahr stage, UPDRS scores, CGI-S, dosage/type of DA-agonist).
Therapeutic dancing for people with Parkinsons disease: A Statistically significant improvements were noted for the MMRM
systematic review of its effects on mobility and quality of life and ANCOVA analyses for safinamide 100mg/day, compared with
placebo, for the mean change (LS diff vs. placebo) in UPDRS Sec-
L.C. Aguiar, M.E. Morris (Melbourne, Australia)
tions II (-0.5, p50.0011), III (-1.2, p50.0003), II1III (-1.6,
Objective: This systematic review evaluated studies on the out- p50.0001) and I1II1III (-2.0, p50.0035). A significantly (p<0.05)
comes of different dance genres for mobility and quality of life in PD greater proportion of patients in both safinamide group met each of
(1). The emphasis was on walking speed, freezing and participant the above responder criteria. The percentages of patients meeting the
wellbeing. The feasibility and safety of trials were also examined (2). most stringent responder criteria were:  50% in UPDRS III [50 mg:
Background: Therapeutic dancing has recently been advocated 11.4% (p50.027), 100 mg: 14.4% (p50.003), Pbo: 7.6%];  30% in
as an effective adjunct to conventional physical therapies for people UPDRS II1III [50 mg: 25.4% (p50.005), 100 mg: 29.3%
living with Parkinsons disease (PD). (p50.003), Pbo: 20.1%]; and any improvement in CGI-C [50 mg:
Methods: Studies were identified through a detailed search of online 45.5% (p50.018), 100 mg: 48.2% (p50.016), Pbo: 39.6%].
databases including CINHAL (1982-2014), Medline (1922-2014), Sco- Conclusions: Pooled analyses of safinamide studies in patients on
pus (1996-2014), Web of Science (2002-2014), Embase (2007-2014), DA-agonist monotherapy demonstrated statistically significant and
PEDro (1999-2014) and the Cochrane Library (1996-2014). Parkinsons clinically relevant benefits for motor symptoms, activities of daily
disease, Paskinson*, Parkinsonism, dance, dance therapy, dance genres, living, and global evaluation for both the 50 and 100mg/day doses
safety, feasibility, quality of life. Two independent investigators (LA & compared with DA-agonist monotherapy.
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 174
improving motor performance, mobility and balance in some people Early onset and duration of effect of safinamide in patients with
living with PD. Dancing also had a positive impact on quality of life motor fluctuations
and adherence to physical activity over the long term. Dancing may
R. Anand, R.D. Hartman, V. Lucini, E. Forrest, R. Giuliani, M.
improve freezing of gait, walking speed and participant wellbeing in McBride (St. Moritz, Switzerland)
some individuals However, just a few studies described thoroughly
the evaluations of these outcomes. Little was reported on the effects Objective: To determine the onset of efficacy of safinamide on
of partnered versus non-partnered dancing, the use of different dance key efficacy measures by analysis of the data at all study visits in
genres in mixed dancing classes, efficacious scheduling of therapy, both the 016 and SETTLE studies.

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


Background: Safinamide add-on to levodopa in fluctuating patients Objective: To evaluate the efficacy of Levodopa-Carbidopa Intes-
demonstrated significant superiority over standard of care in the 24- tinal Gel (LCIG) in a subgroup of advanced Parkinsons disease
week studies 016 and SETTLE on the primary (ON Time without trou- (PD) patients of relatively younger age and shorter disease duration.
blesome dyskinesia) and secondary (OFF Time, UPDRS III) measures. Background: LCIG is a long-term treatment option for advanced
Study 016/018 also demonstrated persistence of benefit for 2 years. PD patients. The efficacy and safety of LCIG in <60 year-old
Methods: The two studies differed in the visit schedules and dos- advanced PD patients with <10 years of disease have not been
ing. In Study 016 patients were randomized to fixed doses of 50 or reported.
100mg/day of safinamide or placebo; in the SETTLE patients were Methods: This 24-month prospective, observational study of
randomized to placebo, or a starting dose of safinamide 50 mg/day that LCIG included 374 patients with advanced PD at 75 centers in 18
was increased to 100 mg/day not earlier than 2 weeks. Additionally, the countries. A post-hoc subgroup analysis was conducted on safety and
first assessment visit for 016 and SETTLE was at Week 4 and Week 2, efficacy data collected on/before 3rd January 2014 from patients who
respectively. These differences precluded data pooling for determining were <60 years old with <10 years of disease at baseline. Efficacy
both onset of efficacy and duration of benefit. Analyses (t-tests) were and quality of life (QoL) were evaluated by the mean change from
performed to determine the change in ON and OFF Time in baseline to 12 months (12M) on the Unified Parkinsons disease Rat-
safinamide-treated patients compared to placebo (ITT population). ing Scale (UPDRS) part II, III, IV (items 32 and 39), Non-Motor
Results: In both studies 016 (n5669) and SETTLE (n5559), the Symptoms Scale (NMSS) total score and 8-item Parkinsons disease
mean ON and OFF Time at baseline were comparable among all treat- Questionnaire (PDQ-8) total score. Adverse drug reactions (ADR)
ment groups. Statistically significant differences between safinamide were evaluated throughout the study. Baseline was the first visit
and placebo were evident at all post-baseline visits for ON and OFF before the start of LCIG infusion.
Time. The first post-baseline assessment visit at Week 2 for SETTLE Results: There were 28 (8.2%) patients in the subgroup of
showed a highly statistically significant (p50.0003) increase in median patients who were <60 years old with <10 years of disease, 15
ON Time of 1 hr for safinamide, compared with 30 min for placebo, (53.6%) of which completed 12M of the study. At baseline, this
and a decrease in median OFF time (p<0.0001, 1 hr for safinamide and subgroup had a mean (SD) age of 52.5 (5.7) years, 6.1 (1.9) years
30 min for placebo). Similarly, in Study 016 the first post-baseline disease duration, and 19 (67.9%) were male. At baseline this sub-
assessment visit at Week 4 showed a statistically significant (p50.017) group had mean (SD) levodopa dose of 914.0 (396.0) mg and a
increase in median ON Time [40 min for safinamide (50 and 100 mg/ higher level of off time and lower level of UPDRS sections II and
day) compared with 20 min for placebo], and a decrease in median III scores relative to the total population (Table 1).[ref1] There were
OFF Time (p<0.01, 45 min for safinamide and 15 min for placebo). significant decreases from baseline to 12M in hours of off time and
Onset of efficacy for the UPDRS III was first noted at Week 4. NMSS total score, and no significant changes in hours of dyskinesia
Conclusions: Safinamide was associated with statistically signifi- or QoL scores. In this subgroup, there were 12 (42.9%) patients with
cant benefit already at the first assessment (Week 2 or 4) for ON and 1 ADR, 5 (17.9%) with 1 serious ADR, and 1 (3.6%) who dis-
OFF Time. These rapid improvements in patients on standard of care continued due to an ADR.
suggest that safinamides dual mechanism produces benefits that will Conclusions: Although the sample sizes were limited, LCIG
be appreciated by patients, caregivers and physicians. 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

Efficacy and safety of levodopa-carbidopa intestinal gel in
patients with less than 10 years of Parkinsons disease Interim Efficacy of rotigotine at different stages of Parkinsons disease
results from the GLORIA long-term registry symptom severity and disability: Post hoc analysis according to
A. Antonini, K.R. Chaudhuri, L. Bergmann, A. Yegin, K. Onuk, W. baseline Hoehn & Yahr staging
Poewe (Venice, Italy) M. Asgharnejad, L. Bauer, F. Woltering (Raleigh, NC, USA)

Motor and Non-Motor Efficacy Measures in a Relatively Early Disease

Subgroup and Total Population of Advanced Parkinsons disease Patients

Earlier Disease Sub-

Total Population at Earlier Disease group(b) Change from
BL (n5343)(a) Subgroup(b) at BL (n526) Baseline at 12M
Efficacy and Quality of Mean 6 SD Mean 6 SD n Mean 6 SD
Life Assessments
Unified Parkinsons disease
Rating Scale (UPDRS):
Part II (activities of daily living score) 16.3 6 9.9 11.4 6 7.5 12 -2.7 6 6.4
Part III (motor score) 24.5 6 11.9 18.0 6 9.8 14 -4.9 6 9.2
Part IV item 32 (hours of dyskinesia/day) 4.4 6 3.8 4.3 6 4.7 11 -1.5 6 3.1
Part IV item 39 (hours of off time/day) 6.0 6 3.2 8.0 6 3.3 10 -6.7 6 2.2***
Non-Motor Symptom Scale 69.2 6 42.1 76.3 6 40.3 13 -32.9 6 46.5*
(NMSS) total score
8-item Parkinsons disease 46.5 6 18.7 44.2 6 18.2 12 13.8 6 32.1
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.

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


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

Objective: To investigate the efficacy of rotigotine transdermal (HY stage 1) to increasing symptom severity and disability (HY
patch across different stages of Parkinsons disease (PD) symptom stage 4). These data support the use of rotigotine across the progres-
severity and functional disability. sive stages of PD.
Background: The efficacy of rotigotine has been demonstrated in 1. Goetz CG, et al. Mov Disord. 2004;19:1020-8.
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 177
five-point staging scale that provides an estimate of clinical function Adverse effects of amantadine in patients of Parkinsons disease-
in PD (motor symptom severity and relative level of disability); it A cross sectional study
ranges from 1: unilateral involvement, minimal/no functional disabil-
K. Bahrani, V. Goyal, G. Shukla, M. Vanathi, M. Behari (New Delhi,
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- Objective: To evaluate the adverse effects of amantadine in
tine 8 mg/24h) or advanced-PD (SP511, SP515, SP650, SP921; patients of Parkinsons disease with special reference to corneal
rotigotine 16 mg/24h), with maintenance phase 7 weeks. Data endothelial toxicity.
from the studies were pooled, and patients stratified according to HY Background: In outpatient door consultation, some patients com-
stage at baseline (HY stage 1, 2, 3, or 4). For each HY stage, change plain of visual problems on changing dose of amantadine. Anti-
from baseline to end of maintenance is reported for Unified Parkin- cholinergic drugs also cause visual blurring and are usually co-
sons disease Rating Scale (UPDRS) II1III total score, and UPDRS prescribed, which creates problem that which drug is causing visual
II and III subscores. P-values are exploratory only. symptoms. Amantadine can rarely cause corneal endothelial cell
Results: Data were available for 2363 patients: HY stage 1, degeneration leading to visual loss, which is partially reversible.
n5274; HY 2, n51304; HY 3, n5692; HY 4, n593. Compared to Methods: A total of 120 Parkinsons patients with 90 patients on
patients at a lower HY stage, patients at higher HY stages were gen- amantadine (6 months) & 30 amantadine nave Parkinsons patients
erally older, had a longer time since PD diagnosis, more likely to be along with 30 age and gender-matched healthy controlswere enrolled.
receiving levodopa (and at higher doses), and higher baseline The amantadine treated group was divided into 3 sub-groups accord-
UPDRS II1III total scores (Table 1). Rotigotine improved UPDRS ing to daily dosage of amantadine, with 30 subjects in each subgroup
II1III total score vs placebo for each individual HY stage (p<0.01 on 200 mg/300 mg/400 mg of amantadine daily.
for all individual HY stages) (Table 2). Similar results were observed Endothelial indices were compared between Parkinsons patients
for UPDRS II and III subscores (p<0.01 for individual HY stages). on amantadine (6 months), amantadine nave Parkinsons patients
Conclusions: This post hoc analysis suggests that rotigotine & age-gender matched healthy controls. Other signs & symptoms of
transdermal patch is efficacious in patients with PD across the stages amantadine induced pedal edema, livedoreticularis (LR), visual hallu-
of the disease from mild symptoms/minimal functional disability cinations were also screened.

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


Outcome Measures: Endothelial cell density, Coefficient of varia- 179

tion, Hexagonality, proportion of Parkinsons patients with pedal
edema/livedoreticularis on amantadine. A study of the pharmacological chaperones targeting
Results: The amantadine group had lower ECD (mean 6 SD; glucocerebrosidase mutations in human fibroblast models of
2584.78 6 350.95 vs. 2707.37 6 220.68, p50.07), lower hexagonality Parkinsons disease
(mean 6 SD; 45.23 6 6.55 vs. 47.87 6 7.45, p50.06) & larger coeffi- M. Beavan, S.Y. Yang, K.Y. Chau, R. Shahar-Golan, D. Hughes, A.
cient of variation (mean 6 SD; 43.27 6 9.35 vs. 41.50 6 6.07, Mehta, A. Schapira (London, United Kingdom)
p50.33) compared with amantadine nave Parkinsons patients. Sub- Objective: We have extended our investigation into the efficacy
group on high dose amantadine (400 mg) had significantly lower of existing pharmacological chaperones (PC) for manipulating the
ECD (p50.01)& lower %Hex (p50.001) as compared to low dose activity of glucocerebrosidase enzyme (GCase), and their potential to
amantadine (200 mg & 300 mg) group. Among the subgroups of reverse the underlying molecular events in the pathogenesis of Par-
Parkinsons patients on amantadine with peripheral adverse effects,all kinsons disease (PD).
the subgroups had nearly equal number of patients with pedal edema Background: After aging, the most important risk factor known
& livedoreticularis. for the development of PD is certain mutations of the glucocerebrosi-
Conclusions: Amantadine is more likely to have effect on corneal dase gene (gba).
endothelial cells in a dose dependent manner when used long term. Methods: Human skin fibroblast cultures from individuals carry-
Our study is the first of its kind to show dose-dependent toxicity of ing heterozygous N370S (n 5 5) or L444P (n55) gba mutations,
amantadine in patients of Parkinsons disease from tertiary care hos- with and without PD, and those with mutation-negative idiopathic
pital in INDIA. 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-
178 phagic proteins were characterized.
Results: We observed a 50-70% decrease in GCase activity, 50%
R ) in
The effect of the Lee Silverman voice treatment (LSVT V lower GBA levels and 50% gba expression in fibroblasts obtained
Filipino Parkinsons disease patients: A pilot study from the heterozygous gba mutation carriers, associated with bio-
J.M.P. Bautista, C.K.A. Cuadro, R.D.G. Jamora (Quezon City, chemical abnormalities including defective localization of GBA and
Philippines) lysosomal autophagy. Optimised treatment of skin fibroblast cultures
with ambroxol and isofagomine resulted in significant restoration of
Objective: The primary aim is to determine the effect of GCase activity, GBA protein and gba gene expression in all cell
LSVTV R in the Filipino Parkinsons disease (PD) patient based on
lines, and correction of GBA localization. Autophagic compromise
two measured parameters: vocal intensity and length of time of associated with the pathogenesis of PD was identified and we are in
sustained phonation. Another objective of this study is to corre- the process of assessing the influence upon drug treatment.
late the subjects clinical PD profile to their response to Conclusions: We have demonstrated that the PC ambroxol and
treatment. isofagomine are able to modulate GCase function. It is unclear
Background: As much as 89% of PD patients develop voice whether the treatment alone may be able to overcome all biochemi-
and speech disorders. This is characterized by decreased vocal cal defects due to mutations in gba, due to the limitation of fibro-
intensity, monotonous speech, and imprecise articulation, collec- blasts as a model for interrogating the complete pathway in PD.
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- 180

tively new in the Philippines with very few certified LSVT speech Yoga versus resistance training in Parkinsons disease: A 12-
pathologists. No studies have yet been done on LSVT and the Fili- week pilot feasibility study
pino PD patient.
D. Bega, D. Corcos, J. Stein, D. Victorson, C. Zadikoff, B.
Methods: This is a cross-sectional study of PD patients in a sin-
Jovanovic, T. Simuni (Chicago, IL, USA)
gle institution in the Philippines. All records of PD patients inde-
pendent of disease and speech disorder severity who completed the Objective: To explore the safety and feasibility of a 12-week
LSVT course were retrieved. Data on vocal intensity and length of biweekly course of gentle Iyengar yoga in patients with PD, and to
time of sustained phonation at different vocal pitches were measured collect pilot data on efficacy compared to resistance exercise.
at baseline and during all 16 sessions of LSVT. Baseline data and Background: Yoga is a mind-body intervention which may
the mean of all sixteen sessions were compared and statistically address the motor and non-motor needs of patients with Parkinsons
analyzed. disease (PD). Despite the wide utilization of yoga there is little evi-
Results: From 9 PD patients referred for LSVT, only 7 patients dence in support of its use.
completed the whole course of 16 sessions. For vocal intensity, 5 Methods: Prospective randomized controlled single blinded study
out of 7 subjects showed louder vocal intensity compared to base- in patients with mild to moderate PD (H&Y stage 1-3). Patients
line on at least 1 vocal pitch. The remaining 2 out of the 7 subjects selected a site in downtown Chicago or the suburbs and were
did not show any improvement in vocal loudness on any of the 3 randomized 1:1 to yoga or resistance classes within each site. Groups
vocal pitches. For the length of time of sustained phonation, 5 out were matched for age, gender, and disease severity. Assessments
of 7 subjects were noted to have significantly longer sustained pho- were performed at screening and after the final session. Safety and
nation on at least 1 vocal pitch. The remaining 2 subjects failed to attendance data was collected by phone every 3 weeks. The main
show any improvement from their baseline time on any of the three exploratory outcome measures were change in Timed-Up-And-Go
pitch levels. (TUG), UPDRS part III, and PDQ-39.
Conclusions: Among Filipino PD patients who completed the Results: 23 patients were screened and 17 were eligible (11
LSVT, majority showed significant improvement in either vocal downtown, 6 suburbs). Demographics of the groups were similar,
intensity or in length of time of sustained phonation. Significant with mean age of the cohort 67.3 (SD 9.8) years, and mean UPDRS
improvement was seen more on the patients habitual pitch com- III score of 24.2 (SD 7.0). There were 3 withdrawals (2 yoga, 1
pared to lower or higher pitch levels. Most improvement was also resistance) unrelated to the intervention. There were no major
seen in patients with mild PD and mild speech disorder. This adverse events. 16% of yoga classes were missed compared to 8% of
implies that LSVT may have most benefit in this category of PD resistance classes (p50.04). Significantly more classes were missed
patients. at the downtown campus compared to the suburbs (14.8% vs 7.5%).

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


Upon completion of the trial both groups improved on mean TUG Friedman, M. Brys, R.M. Gilbert, A. Di Rocco (New York City, NY,
time, UPDRS score, and PDQ-39 score compared to baseline, USA)
although the standard deviations for all values were wide and none
of the between-group differences was statistically significant. With Objective: To explore clinical and electrophysiology outcomes of
the exception of 1 subject in each group, participants stated that they low frequency repetitive Transcranial Magnetic Stimulation (rTMS)
benefited from the intervention, and they would have continued the of two prefrontal stimulation targets in patients with PD.
intervention beyond 12 weeks. Background: rTMS trials showed promising results improving
Conclusions: The feasibility of a 12-week group yoga interven- motor symptoms of PD with a class-I trial reporting motor improve-
tion in a cohort with mild-moderate PD was somewhat limited, with ment with low frequency (LF) rTMS over the supplementary motor
better attendance seen for resistance classes. The suburban location area (SMA). Neurophysiology (NPh) studies suggest that motor cor-
was associated with significantly better compliance. Pilot exploratory tex excitability in PD is abnormal and can be modulated with rTMS;
outcome data suggest comparable improvement in motor and non- particularly LF rTMS over dorsal premotor cortex (PMd) can nor-
motor outcome measures in both groups, but a larger study powered malize motor excitability abnormalities. Optimizing rTMS treatment
to detect these differences is needed. Feasibility data will need to be strategies is challenging and NPh may help with understanding the
taken into account in designing such a study. TMS effects and optimizing design of novel rTMS treatment
Methods: 8 PD patients with H&Y score of 2 or 3 participated in
181 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-
Clinical predictors of functional decline in early treated treatment. The stimulation targets included either active rTMS over
Parkinsons disease: NET-PD LS1 cohort PMd and SMA (PMd1SMA group), or realistic sham on PMd and
D. Bega, S. Kim, Y. Zhang, J. Elm, J. Schneider, R. Hauser, A. active rTMS on SMA (SMA group). UPDRS III was used to mea-
Fraser, T. Simuni, On Behalf of the NET-PD LS1 Investigators (Chi- sure motor outcomes. Cortical silent period (SP), short interval intra-
cago, IL, USA) cortical inhibition and intra-cortical facilitation measures were used
to asses NPh outcomes.
Objective: Current data regarding predictors of functional decline Results: No significant adverse effects reported. At week 4 post-
in Parkinsons disease (PD) are largely based on studies of de novo treatment, UPDRS III decreased in both groups, in PMd1SMA
populations at baseline, often limited to the use of motor outcomes group from 30.25 (sd=12.7) to 24.5 (sd=11.4); in SMA group from
which fail to capture the full scope of the disease. We aimed to 30.0 (sd=6.7) to 24.5 (sd=5.3), both approaching significance [p <
determine the clinical predictors of decline in early treated PD as 0.1]; magnitude of decrease was greater in PMd1SMA group but
defined by a novel multi-domain outcome measure. did not reach significance. Neurophysiology results revealed a trend
Background: Clinical predictors of functional decline in PD are towards a significant difference [p < 0.1] between both groups SP
prognostically important in the absence of validated biomarkers of at week 4 post-treatment (prolongation of SP in the PMd1SMA
disease progression. Older age at disease onset and PD symptom group and shortening of SP in the SMA group). Other NPh results
subtype have been identified as the strongest predictors of more rapid were not significant. [figure2]
rate of progression. Conclusions: Both rTMS interventions were well tolerated and
Methods: We used data from NINDS Exploratory Trials in Par- improved UPDRS motor scores. Improvement was sustained up to
kinsons disease Long-Term Study 1 (NET-PD LS1), a large multi- four weeks post-treatment. Combined PMd1SMA rTMS prolonging
center cohort of early treated PD patients followed for 5-7 years. SP may indicate increased activity of inhibitory circuits in this group
Decline was defined by a global outcome metric that consists of the which may reflect a more effective intra-cortical modulation by LF
following 5 domains of disability, quality of life, motor and cogni- rTMS (as SP is abnormally shorter in PD patients). Larger studies
tive impairment: Schwab and England ADL scale (S&E), Parkin- are needed to better define the effects of prefrontal LF rTMS on NPh
sons disease Quality of Life Scale (PDQ-39), Unified Parkinsons measures and potential clinical interactions in PD.
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.

Prefrontal repetitive transcranial magnetic stimulation in
Parkinsons disease: Pilot study of motor and neurophysiology
M.C. Biagioni, G.S. Dacpano, S. Agarwal, K.R. Sticklor, W.R. Small,
Fig. 1. (182).
J.N. Chimienti, P. Kumar, A. Loggini, J.Y. Singleton-Garvin, E.R.

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


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,
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
Fig. 2. (182). 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
183 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
Utilizing remote blood pressure monitoring in a phase III clinical professionals.
drug trial for Parkinsons disease Methods: The SDM intervention will be tested in clinical prac-
R.A. Biemiller, K.J. Andrzejewski, M.T. Bull, K. Helles, B. Greco, D. tice. The aim is to select 40 patients; 20 after introducing the SDM
Oakes, T. Simuni, K.M. Biglan (Rochester, NY, USA) intervention, and 20 according to usual care. At baseline, the usual
DMP is followed and the patient will receive care as usual. After
Objective: To determine the feasibility of remote blood pres- this, professionals will get a theoretical and hands-on training in
sure monitoring in a phase III clinical trial for Parkinsons SDM and use of the online DA. With the next 20 patients, they will
disease. work according to the SDM intervention.
Background: Orthostatic hypotension is common in Parkinsons Feasibility of this intervention will be measured in both patients
disease (PD). Clinical trials for PD have used home blood pressure and professionals by means of questionnaires, interviews, observa-
(BP) monitoring for participant safety and enrollment eligibility. tions of the DMP and logging behavior of the online decision aid.
Monitoring typically involves patients keeping a home log, which is Results: Important outcomes will be the level of SDM in the con-
presented at interim in-person visits to research staff for review. sultations and informed preference as a measure of the quality of
These home logs may be subject to inaccuracies due to errors in decision making.
transcribing results or non-compliance. This has the potential to Conclusions: The results of this project will inform the imple-
impact study validity and participant safety. mentation of the new SDM approach, which could be evaluated in a
Safety, Tolerability, and Efficacy Assessment of Isradipine for larger RCT in clinical practice. Our long-term goal is to create equal
Parkinsons disease (SteadyPD3) is a phase III double-blinded accessibility to all advanced therapies and offer patients the opportu-
study of isradipine, a dihydropiridine calcium channel antagonist, nity to actively participate in this complex medical decision. This
as a potential neuroprotective agent in PD. Given the mechanism should reduce the under treatment of patients with advanced PD and
of isradipine, STEADYPD3 requires frequent BP monitoring prior improve treatment compliance.
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 185
capture and analysis and has the potential to improve validity and Designing a decision aid for patients in advanced Parkinsons
safety of the trial. disease (PD): The user test experiences
Methods: Participants in SteadyPD3 take twice-daily orthostatic
B.R. Bloem, M.J. Faber, F.A.P. Nijhuis, D.L.M. Radder (Nijmegen,
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 Objective: To optimize a newly developed decision aid (DA) for
monitored by the research team. The database tags all BP readings patients with PD in the advanced stage, we conducted a user test
outside the prespecified safety range for review. We report on our with PD patients. The aim was to test the DA on 1) quality of the
initial findings on the feasibility and challenges of remote BP information; and 2) ease of use.
monitoring. Background: For many PD patients, it eventually becomes diffi-
Results: SteadyPD3 began enrollment in November 2014. It has cult to manage motor complications with adjustments in oral medica-
enrolled 29 and screened 46 patients who have utilized the remote tion. For these patients, Deep Brain Stimulation, Continuous
BP units and have successfully transmitted to the online database. Duodenal Levodopa Infusion and Continuous Subcutaneous Apomor-
The main complications have been: spurious readings due to patient phine Infusion are the cornerstones for therapeutic management. The
error, extra reported readings from researchers instructing patients on choice for one of the treatments is an individual decision, based on
the use of the units and an excessive amount of BP reads that require patients personal preferences and values. The notion that the
dedicated personnel to review. patients perspective and participation in decision making is needed
Conclusions: Remote blood pressure monitoring in an ongoing for a quality decision, was the starting point for us to develop a
Phase III trial of PD has been feasible. Remote BP monitoring has SDM intervention comprising a DA and a training for professionals.
the potential to increase safety and validity in PD studies but will Methods: For testing the DA, 25 patients were approached, of
require further testing. which 19 responded. All participants received a personal login code,

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


testing the DA for one week. Afterwards, the patients received an PWR!MovesV R can benefit motor, cognitive, and non-motor symp-

evaluation questionnaire. Four of them were interviewed at home to toms of PD.

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 187
treatments (68%)). Less than half (47%) rated the information on the
effects of the treatments as good. Patients judged the language as Treatment of apomorphine-induced skin reactions: A pilot study
comprehensible (95%) and the length of the DA (68%) and quantity R.W.K. Borgemeester, G.F.H. Diercks, M.F. Jonkman, T. van Laar
of information (63%) were optimal. Patients felt that the DA offered (Groningen, Netherlands)
well-balanced information about the specific treatments (88%). All
Objective: To evaluate the efficacy of four treatment strategies,
participants would use the DA if they were faced with the choice
including massage, dilution of apomorphine, treatment with topical
(100%). Moreover, patients provided several instructions for improv-
hydrocortisone, and pre-treatment with subcutaneous administration
ing the DA, particularly to include more experiences of patients that
of hydrocortisone, in Parkinsons disease (PD) patients with
underwent one of the treatments, and to include practical information
apomorphine-induced skin reactions.
about how the devices are used at home.
Background: Apomorphine-induced skin reactions (i.e. erythema,
Conclusions: Patients rated the DA as a useful tool in making
swelling and/or subcutaneous nodule formation) are a common side-
the decision and as easy to use. Obviously, it differs per patient how
effect of continuous subcutaneous apomorphine infusion. However,
much information they wish to receive. Therefore patients have
the pathogenesis of apomorphine-induced skin reactions is poorly
access to the information pages for both patients and professionals,
understood, which explains the absence of proven treatment
allowing patients in need of more information to read the more
extensive scientific knowledge for professionals. We have incorpo-
Methods: An open-label, sequence-fixed, cross-over study with
rated the feedback into a new version of the DA, which will be
four treatment arms including local massage, dilution of the apomor-
tested in a feasibility study.
phine concentration from 0.5% to 0.25%, topical hydrocortisone 1%
and pre-treatment with subcutaneous 10 mg hydrocortisone, was
186 designed in 20 patients being treated with subcutaneous infusion of
apomorphine. Each treatment arm started after a wash-out period of
Short-term benefits of a progressive aerobic exercise and skill 2 weeks. The efficacy of each treatment was evaluated after 2 weeks
acquisition program for people with mild to moderate by determining patient satisfaction, local erythema and nodule size,
Parkinsons disease in a community group setting as well as skin tissue characteristics. Two skin biopsies were taken
E.E. Borchers, E. Ferrigni, K. Krauss, B.G. Farley (Tucson, AZ, after each treatment modality, at 2 sites, consisting of 1 site 3 days
USA) after infusion and another site 14 days after apomorphine infusion.
Results: Massage and dilution of apomorphine seem to have a
Objective: To examine the short-term effects of a progressive
good effect on the nodule formation of apomorphine, whereas the
aerobic exercise and skill acquisition program conducted at The Par-
hydrocortisone creme was less effective as compared with the subcu-
kinsons Wellness Recovery Gym (PWR!GymV R ), a community based
taneous pre-treatment with hydrocortisone. Several biopsies showed
exercise center devoted to improving quality of life for people with
an allergic component as well, consisting of eosinophils.
Parkinsons disease (PD).
Conclusions: To our knowledge, this is the first study examining
Background: Progressive aerobic exercise has been shown to
various treatment strategies in apomorphine-induced skin reactions in
improve endurance, gait, balance, and executive function as well as
PD. Local treatment with massage, dilution of apomorphine and pre-
decrease fatigue and depression in people with Parkinsons disease
treatment with subcutaneous hydrocortisone are effective measures in
(PD). Prior research suggests that vigorous aerobic exercise in com-
reducing the skin problems associated with apomorphine. Therea-
bination with skill acquisition augmented with feedback improves
bove, anti-allergic drugs like anti-histamines might play a role in the
function and can mediate brain health and repair mechanisms in peo-
treatment of apomorphine-induced skin reactions in the future.
ple with PD. Limited research has been done on the effectiveness of
this type of exercise program implemented in a community group
Methods: Sixteen members of the PWR!GymV R with mild to 188
moderate PD participated for 7 weeks. Volunteers provided individu- Long-term evaluation of 24 hour ambulatory blood pressure
alized education and feedback regarding perceived effort based on monitoring in patients with Parkinsons disease and symptomatic
the Modified Borg scale correlated with heart rate. Group 1, which neurogenic orthostatic hypotension treated with droxidopa
included 8 participants with moderate stage PD, exercised 3 times
S. Brillman, S. Husain, S.H. Isaacson (Boca Raton, FL, USA)
per week with total cardio times increasing from 30 to 40 minutes.
Group 2, which included 8 participants with mild to moderate stage Objective: To determine if the effect of droxidopa on clinical
PD, exercised 3 times per week with total cardio times increasing symptoms and systolic blood pressure are durable.
from 40 to 50 minutes. Both groups utilized treadmills and stationary Background: Neurogenic Orthostatic Hypotension due to auto-
bicycles followed by various PWR!MovesV R for skill acquisition for nomic dysfunction in Parkinsons disease (PD) not uncommonly
the remaining time to total a one hour class. complicates clinical management. Treatment options are limited, due
Results: Preliminary findings suggest improvements in motor and both to limited symptomatic efficacy in some patients and to
cognitive assessments as well as non-motor symptoms associated increases in supine hypertension (sHTN) in others. Studies using
with PD. The majority of participants improved in the 6 Minute droxidopa to raise standing systolic blood pressure (sSBP) in patients
Walk Test, 2 Minute Walk Test, Timed Up and Go, and 5 Times Sit with PD and nOH have identified short term improvement in symp-
to Stand suggesting benefits in the domains of endurance and func- toms and in sSBP, but clinical durability beyond 1-2 weeks has been
tional mobility. Improvements were also found in verbal fluency and limited by study design and other factors.
trailmaking tasks. In addition, subjects reported less fatigue, Methods: Droxidopa, a synthetic precursor converted to norepi-
improved sleep quality, better mood, less pain, and higher quality of nephrine, was administered to five patients with PD and symptomatic
life after participating in this program. nOH. During routine clinic visits, patients were assessed with 24
Conclusions: These findings suggest that a 7 week progressive hour ambulatory blood pressure monitoring (ABPM) Orthostatic
aerobic group exercise and skill acquisition program based upon the Hypotension Questionnaire Question #1 (OHQ-Q1) before and 3-6
Modified Borg scale at high-intensity intervals and the month after beginning treatment with droxidopa.

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


Results: Retrospective analysis of baseline ABPM demonstrated Objective: To determine efficacy and duration of benefits of
marked fluctuations in sSBP in all treated patients, and overnight motor and prefrontal cortex high frequency rTMS on motor and
sHTN. After treatment with droxidopa, most patients had a reduction mood symptoms of PD.
in the number of sSBP lower than 90mmHG measurements on 24 Background: Several studies suggest that high frequency rTMS
hour ABPM at the post-treatment assessments. Improvement in (HF rTMS) to the motor cortex improves motor symptoms of PD
OHQ-Q1 (lightheadedness/dizziness) was also. However, fluctuations and HF rTMS to left dorsolateral prefrontal cortex (DLPFC)
in ABPM sSBP measurements and in OHQ-Q1 persisted among improves depression. Yet, there are no appropriately powered, sham
patients at all timepoints. controlled studies targeting depression and motor dysfunction con-
Conclusions: In this cohort of patients treated with droxidopa for currently despite the frequent co-morbidity.
symptomatic NOH, efficacy and imrpoved s-SBP was maintained Methods: 71 PD subjects with motor dysfunction and depression
months after beginning treatment. Variabilty in blood pressure and despite optimized medication treatment consented to participation
symptoms persist though, pointing to an underlying difficulty in the and were randomized in this multicenter, double-blind, sham-con-
clinical assessment of patients with PD and autonomic dysfunction. 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
Chemogenetic inhibition of the subthalamic region of state at baseline, at 1 week and at 1, 3 and 6 months post treatment.
Parkinsonian mice improves motor function Hamilton Depression (HAM-D) scale was used for depression out-
L. Broom, T. Samardzic, A. Worley, C. Joanne, O. Yo, D.K. Simon, come and UPDRS III for motor outcome.
C.B. Saper, V. VanderHorst (Boston, MA, USA) Results: 59 subjects completed the treatment, 46 subjects (78%)
completed all study visits (real M1-sham DLPFC n513, real
Objective: To test whether chemogenetic inhibition of the subtha- DLPFC-sham M1 n510, real M11DLPFC n521, double sham
lamic region improves motor function in a Parkinsonian mouse model. n515). There was a significant, sustained decrease in HAM-D in all
Background: Deep brain stimulation is an effective treatment of study participants regardless of stimulation status (p<0.001), while
motor symptoms in Parkinsons disease (PD). Chemogenetic UPDRS III improved transiently (p50.03) and reverted to baseline
approaches provide an alternative without limitations of hardware and by month 6. As compared to sham stimulation, no change in UPDRS
unintended stimulation of fiber tracts. One such approach makes use III or HAM-D was found 1 month post treatment completion in par-
of Ivermectin (IVM) channels, which are mutated nematode glutamate ticipants receiving real TMS (p5ns). Similarly, no study group dif-
gated chloride channels that can be delivered locally via microinjec- ference was shown when all study visits were analyzed (rANOVA,
tion of an adeno-associated viral vector (AAV). IVM channels are p5ns).
inert in mammals due to a mutation, but can be specifically and rever- Conclusions: Multifocal M1 and/or DLPFC HF rTMS was no
sibly targeted by the drug IVM, leading to inhibition of transfected better than sham stimulation for motor or mood symptoms of PD.
neurons. We apply this strategy to the subthalamic region (STN), Sustained improvement of depression, regardless of stimulation sta-
which is overactive in PD, to assess the feasibility of this approach to tus, points to universal benefit from study participation or from a
ameliorate motor function in an acute Parkinsonian mouse model. perceived intervention. Transient improvement of UPDRS III indi-
Methods: We placed micro-injections of AAV10-CMV-IVM-GFP cates strong placebo response (perhaps related to salient electrical
into the STN region of male C57Bl6J mice. Following transfection, sham stimulation) precluding further conclusions regarding multi-
we injected vehicle or IVM i.p. to assess the effect of inhibition of target rTMS efficacy. Better understanding of sham rTMS response
the STN region on motor function. We did this first in the intact CNS in this particular population may help in the design of future efficacy
and following injection of 6-hydroxydopamine (6OHDA) into the sub- studies.
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- 191
try to visualize GFP1 transfected neurons in the STN region and tyro-
Effect of antidepressants on the motor symptoms of Parkinsons
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 H. Calderon, R. Llorens-Arenas, D. Pi~ na-Fuentes, A. Cervantes-
region in non-lesioned mice induces small enhancements of motor Arriaga, M. Rodriguez-Violante (Mexico City, Mexico)
performance such as an increase in gait speed. Following 6OHDA- Objective: To evaluate the effect of antidepressants in the motor
induced dopaminergic cell loss and worsening of motor performance, symptoms of Parkinsons disease.
inhibition of the STN region results in marked improvements of motor Background: Depressive syndromes occur in an average of 40%
function. The effects are reversible and dose dependent. of patients with Parkinsons diseaseDepressive. However, they are
Conclusions: These findings represent a proof of concept for this often not identified.
novel technology to ameliorate motor function in a Parkinsonian Depression and anxiety disorders are the most common neuro-
mouse model. The results demonstrate its potential as a treatment in psychiatric syndromes in people with PD.
PD and other neurological conditions that involve an imbalance in To date, few studies have evaluated the effect of antidepressant
neural circuitries. treatment on motor symptoms in patients with Parkinsons disease
(PD) and results have been controversial.
190 Methods: A longitudinal analytical study was conducted. Patients
were evaluated and divided into two groups: non-depressed (con-
No benefit from multifocal repetitive transcranial magnetic trols), and untreated depression. The diagnosis of depression was
stimulation on motor and mood symptoms of Parkinsons disease based on the DSM-IV. Treatment with SSRI was initiated in patients
compared to sham stimulation: Results of the MASTER-PD with depression. Patients were assessed 10 weeks after the start of
study antidepressants; no adjustment was made antiParkinsonian drugs dur-
M. Brys, M. Biagioni, S. Agarwal, G. Dacpano, P. Kumar, E. ing this time. All patients were evaluated with the MDS-UPDRS.
Pirraglia, Z. Gray, D.K. Simon, A. Wu, H. Fernandez, R. Chen, A. Other scales applied were: NMSS (scale non-motor symptoms of
Wagle Shukla, J.S. Lou, A. Di Rocco, A. Pascual-Leone (New York, PD) and PDQ8 (scale of quality of life PD), HAM-D (Hamilton
NY, USA) depression Scale, HAS (Hamilton anxiety Scale), LARS (scale

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


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

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


Results: The results showed improvement after treatment, accord- Methods: This post-hoc analysis of pooled data from the pivotal
ing to media score for the Group I e II TUG (p50,01), 6 min walk Phase III trials 016 and SETTLE evaluated the effects of safinamide
(p50,00) and BBS (p50,00), Mini BESTest (p50,00),PRT (p50,00) vs. placebo on individual cardinal symptoms of PD during the ON
NFOG-Q (p5 0,01) only to Group I. phase (bradykinesia, rigidity, tremor, postural stability, gait) and the
Conclusions: The MC physiotherapy programme proposed in this mean change from baseline in daily OFF time in subgroups of
study connected to medicine was effective to minimize FoG in PD patients who were receiving levodopa alone or concomitant treat-
and postural instability. 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
194 medications).
Results: Compared to placebo, safinamide 100 mg/day signifi-
The impact a belt adaptation in walker stabilize on gait cantly improved bradykinesia, rigidity tremor and gait, and signifi-
measures and falls in Huntingtons disease (HD) and Parkinsos cantly reduced mean daily OFF time when used as adjunct therapy
disease (PD) in all subgroups of patients considered without increasing the rate of
T.T.C. Capato, M.S. Haddad, R. Guimar~ aes, J. Tornai, M.R. adverse events nor the risk to develop troublesome dyskinesia.
Goncalves, M.E.P. Piemonte, E.R. Barbosa (S~
ao Paulo, Brazil) Conclusions: Safinamide was an effective and safe drug when
used as add-on therapy in mid- to late-stage fluctuating PD patients:
Objective: Examine the effects a belt Adaptation in Walkers Sta-
improvements were seen in OFF time and in almost all cardinal
bilizer (BAWS) on Gait Measures and falls in HD and PD.
symptoms in subjects with wearing-off phenomena, despite they
Background: Gait and postural instability disturbs lead to bal-
were receiving an optimized dopaminergic treatment regimen, with-
ance loss and falls in individuals with HD e PD. The slowness of
out deteriorating their motor complications.
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 196
prescribed to prevent falls, but their efficacy is unknown. However,
there are no evidence-based guidelines available to prescribe and rec- 24 hour levodopa-carbidopa intestinal gel may reduce falls from
ommendations of adaptations. unresponsive freezing of gait in Parkinsons disease
Methods: Were assessed 05 subjects with HD moderate and 10 F.C.F. Chang, D.S.Y. Tsui, N. Mahant, N. Wolfe, S.D. Kim, A.D. Ha,
PD (H&Y 3-4) as they walked 3 conditions (without AD, Walker J.M. Griffith, M. Drury, V.S.C. Fung (Westmead, Australia)
Stabilizer and BAWS). Demographic information, UHDRS and
Objective: We report ongoing data on a prospective, open label
UPDRS motor scores, and fall history (FES-I) data were obtained
study of 24 hour levodopa-carbidopa intestinal gel (LCIG), as treat-
from ambulatory patients with a diagnosis of HD and PD who were
ment for levodopa-unresponsive freezing of gait (u-FOG) and falls in
examined by physical therapists at our Movement Disorders Clinic.
Parkinsons disease (PD).
Gait and Balance parameters was assessed by TUG, 6 min walk,
Background: FOG associated with PD is a challenging phenom-
Mini BESTest, Push and Release Test (PRT). We used a BAWS
enon, in terms of pathophysiology and treatment. Off period FOG
placed in low back region to provide a proprioceptive cue to the
is treated with increased dopaminergic therapy whereas u-FOG is not
patients. It also acts as a security belt.
responsive to levodopa or deep brain stimulation.
Results: In AD condition, there were differences in gait velocity
Methods: Patients with u-FOG documented with an oral dose
and balance parameters between the HD and PD and slowness in
cycle of levodopa were commenced on continuous 24 hour infusion
both groups. In Walker Stabilizer conditions to HD and PD there
through the LCIG pump with the night-time rate at 50 to 80% of
were a significant improvement in gait velocity and balance scores in
daytime infusion rate. Patients with u-FOG underwent baseline, 3, 6,
comparison between without AD. The higher differences were shown
9, 12 and 18 month gait assessments, video-taped examination and
with BAWS on 6 min walk, TUG and Mini BESTest. These scores
FOG questionnaire. The change in falls frequency were recorded and
shown with BAWS show decreased fall risk in HD and PD.
Friedmans test was used to test for statistical significance for varia-
Conclusions: Walker Stabilizer can be very helpful for moderate
bles up to 9 months, using SPSS 22.0, defined as p < 0.05.
HD and PD patients. BAWS can reduce falls when used as a pro-
Results: 7 patients participated, their mean age 67.4 1/- 8.3 with
prioceptive cue. BAWS selection, training and adjustments should be
duration of PD 18.21/-9.1 years. The falls frequency reduced after
considered and conducted by a physicaltherapist. More researches
24 hour LCIG (p50.048) at 3, 6 and 9 months compared to baseline.
are necessary to evaluate the effects on freezing in PD.
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
195 to baseline and two subjects had transient dyskinesia or postural
Efficacy of safinamide as adjunct therapy in mid- to late-stage hypotension. One subject withdrew from the study following persis-
fluctuating Parkinsons disease patients: Post-hoc analyses of 016 tent visual hallucinations. Otherwise it was well tolerated without
and SETTLE trials side effects.
Conclusions: Our study provides additional evidence that 24 hour
C. Cattaneo, E. Bonizzoni, R. La Ferla, M. Sardina (Bresso (Milan),
Italy) LCIG infusion reduces motor complications in PD. We offer a novel
therapy that may reduce falls associated with u-FOG due to PD.
Objective: To investigate the clinical effects of safinamide vs. However, a larger prospective study is needed for confirmation.
placebo on cardinal symptoms of Parkinsons disease and on motor
fluctuations in defined patient subgroups using pooled data from
studies 016 and SETTLE. 197
Background: Safinamide, a unique molecule with a novel mecha- Antecollis associated with Parkinsons disease improved
nism of action (dopaminergic and non-dopaminergic), resulted safe following apomorphine therapy
and effective in two double-blind, placebo-controlled, 6-months trials F.C.F. Chang, N. Mahant, V.S.C. Fung, D.S.Y. Tsui, Z. Aldaajani, R.
(016 and SETTLE) when used as add-on therapy in patients with idi- Adam, M.A. Hely (Wentworthville, Australia)
opathic Parkinsons disease (PD) and motor fluctuations, treated with
stable doses of levodopa alone or in combination with other anti- Objective: We report improvement in antecollis in a Parkinsons
Parkinsons drugs. disease (PD) patient following subcutaneous apomorphine therapy.

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


Background: Antecollis is dystonia of the neck resulting in and selegiline, while the mean LEDD was significantly higher in
excessive forward flexion, often associated with dysphagia. It is asso- cases taking amantadine (982.6 6 453.8 vs. 527.9 6 315.3 mg/day,
ciated with later stage of PD and is often refractory to medical and p<0.001).
botulinum toxin therapy. Conclusions: This study provides a systematic analysis of mean
Results: We report a 70 year old lady with idiopathic PD diag- LEDD in a large cohort of Taiwanese patients with PD. Moreover,
nosed 12 years ago. She presented with unilateral levodopa respon- our survey shows that the LEDD is positively correlated with the
sive hand tremor with akinesia and rigidity. 12 months ago, during duration and severity of PD, and is affected by the different pattern
treatment with levodopa 600 mg daily, pramipexole ER 3 mg daily, of use of anti-Parkinsonian medications. The comparison of mean
she developed acute antecollis over 24 hours after a fall with minor LEDD between different ethnic populations are worth for the further
head injury. Reduction in pramipexole to 2.25 mg daily made no dif- assessment.
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- 199
mal neck extensor strength. There was no rigidity and minimal bra- Relationship of vitamin B12 status to baseline clinical condition
dykinesia in the extremities. Administration of oral medication via and outcomes in a large, early Parkinsons disease cohort
nasogastric tube was ineffective. An apomorphine challenge was per- (DATATOP)
formed after pre-treatment with domperidone. There was acute C.W. Christine, P. Auinger, A. Joslin, R. Green, PSG DATATOP
improvement in hand function, rigidity and mobility without speech Investigators (San Francisco, CA, USA)
or neck posture improvement. However, neck posture started to
improve 4 hours post apomorphine. Apomorphine was commenced Objective: To determine the prevalence of low vitamin B12 sta-
regularly at 2mg subcutaneous injections 3 times a day. This was tus and its association with cognitive and motor outcomes in early
well tolerated with mild generalized dyskinesia and no hallucina- Parkinsons disease (PD).
tions. At 2 and 4 months followup, the patient had significant Background: Previous studies have identified relationships of
improvement in swallowing and resolution of antecollis. She was low vitamin B12 levels with neurological features including neuropa-
able to feed, transfer herself and play the piano again and gained 8 thy and cognitive impairment in moderately advanced PD. We
kilograms. She had presence hallucinations at night with retained sought to determine the prevalence of low vitamin B12 status in
insight. At 7 months followup she had recurrence of antecollis and early PD and whether low B12 was associated with greater
dysphagia which improved following cessation of pramipexole and morbidity.
commencement of an apomorphine 16 hour daytime infusion with Methods: We measured vitamin B12 and methylmalonic acid
nocturnal rotigotine patch therapy. (MMA) levels using 680 of the baseline serum samples from the
Conclusions: Apomorphine therapy may be an useful treatment DATATOP cohort of patients with early, untreated PD. Low B12
for antecollis in PD. 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
198 (UPDRS scores) and cognitive assessments (Symbol Digits Modal-
Analysis of daily dose of dopaminergic replacement therapy in ities Test and Selective Reminding Test) at baseline and follow-up,
patients with Parkinsons disease: Experience of a medical center calculated as an annualized rate of change for those who participated
in Taiwan for 9 months to 2 years. T-tests and chi-square tests were used to
compare outcomes between subjects who were deficient to those
Y.Y. Chang, T.K. Lin, Y.F. Chen, C.S. Su, M.Y. Lan, Y.F. Chen
who were non-deficient.
(Kaohsiung, Taiwan)
Results: A B12 level <184 pmol/l was present in 12.8% of sub-
Objective: To study the anti-Parkinsonian medication patterns jects at baseline and 5% had B12 levels <157 pmol/l (regardless of
and investigate the association between the levodopa equivalent daily MMA levels). Fifteen (2%) were B12 deficient. Using either the
dose (LEDD) and the various clinical variables in patients with Par- threshold of B12 <184pmol/l (82 subjects) or MMA >400 nM (27
kinsons disease (PD). subjects), we found lower scores in the selective reminding test for
Background: The pharmacological treatment of PD is individual- these groups at baseline. We also found greater clinical deterioration
ized based on motor symptom severity, non-motor symptoms, and (measured by the annualized increase in total UPDRS and motor
benefits and side effects of the medications. Here we analysed data scores) in those with baseline B12 levels <184 pmol/l. No associa-
on the anti-Parkinsonian treatment and clinical characteristics of PD tions were found between baseline B12 status and baseline sensory,
patients treated by Movement Disorder specialists. gait, or stability outcomes as measured by individual UPDRS items.
Methods: A territary care medical center cross-sectional survey Conclusions: In this cohort of early PD subjects, 1 in 8 subjects
was conducted over a defined period. Information on patient demo- had low B12 status. Moreover, low B12 status was associated with
graphics and clinical features including age, age at PD onset, disease both baseline cognitive defects and more rapid rate of progression of
duration, and modified Hoehn and Yahr (H-Y) stage, and LEDD of impairment as measured by the UPDRS. These changes occurred in
anti-Parkinsonian medications was obtained from the patients medi- the absence of sensory or gait changes, suggesting that serum tests
cal records. may be necessary to detect low B12 status. Our data raise the possi-
Results: During the study period, a total of 244 PD patients (156 bility that prevention or early correction of low B12 status may slow
male, mean age 67.48 6 10.79 years, range from 3092 years) were the onset of disability in PD. Supported by MJFOX Foundation,
included. The mean LEDD in the study population was Grant 8646.
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- 200
able. The most frequently administered drugs were L-dopa (89.3%), Do late-stage Parkinsons disease patients still respond to
dopamine agonists (DA) (70.9%), entacapone (49.2%), amantadine levodopa?
(27.9%), selegiline (15.6%), and anticholinergics (13.5%). Besides, M. Coelho, M. Fabbri, D. Abreu, L. Guedes, N. Goncalves, M.M.
the most frequent pattern was a combination of L-dopa and DA Rosa, J.J. Ferreira (Lisbon, Portugal)
(66.8%), followed by L-dopa monotherapy (18.4%), DA monother-
apy (4.1%), and other dopaminergic drugs (2.0%) respectively. There Objective: Our aim was to study the response to a levodopa test
was no difference in mean LEDD with the use of anticholinergics in a late stage PD (LSPD) population.

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


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


Conclusions: Although both rehabilitation programs mainly Results: We observed that 33% of patients showed improvement
induced comparable effects on TMS, only NR-MI showed a signifi- of gait and balance after TDCS. All selected patients showed expres-
cant improvement of FoG, suggesting a different mechanisms of sive gait changes following TDCS and MCS, in a follow-up of 4-18
intervention between the two treatments. NR-MI appears to be an mo. [figure1]The benefit of MCS was similar to the best response
interesting suitable rehabilitation strategy to treat FoG in PD observed after TDCS which occurred 1-3hrs after the session and
patients. 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-
203 ity provides continuos stimulation, responses are more stable and
lasting. TDCS could be an efficient trial.
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) 204
Objective: To evaluate the benefit of Epidural Motor Cortex Eight years experience with continuous intraduodenal levodopa
Stimulation (MCS) in Parkinsonian patients who presented improve- infusion in Parkinsons disease
ment of freezing of gait (FOG) and balance after transcranial motor
O. De Fabregues, J. Dot, A. Abadia, J. Hernandez, M. Ibarria, A.
cortex stimulation (tDCS).
Ferre, C. Puiggros, J.R. Armengol, M. Quintana, J. Alvarez-Sabin
Background: Gait disturbances such as freezing of gait (FOG),
(Barcelona, Spain)
balance and apraxia are challenging symptons in advanced advanced
Parkinsons disease (PD), generally resistant to conventional drug Objective: To describe our experience of 8 years in the manage-
and non-drug treatment, can generate loss of autonomy and traumatic ment of continuous intraduodenal infusion of levodopa (CIDLI) treat-
complications. Recently, researches have been directed toward these ment for Parkinsons disease (PD).
devastating symptoms. Traditional deep brain stimulation have been Background: CIDLI is a new treatment for advanced PD that has
proved worthless and Pedunculopontinous Nucleus Stimulation, pro- demonstrated to improve motor fluctuations. Long-term therapy com-
posed as a new potential target, still havent been widely accepted for plications and their management and its effect on sleep, cognition
its risks and lack of predictors. Few reports suggested improvement and behavior and impact in patients quality of life and caregiver
of bradykinesia and gait after MCS. Lately, the possibility of cortex burden are not well established.
modulation with tDCS have leaded to new perspectives and non- Methods: Open and prospective study in patients with advanced
invasive approaches. Many authors reported changes in gait and PD with disabling motor fluctuations treated with CIDLI. Motor
motor skills after these modalities. We report the benefit MCS in 4 scale and patient diaries were used to evaluate the motor condition.
patients who presented improvement after tDCS and submitted to Adverse events and action taken to solve them were collected.
MCS. Quality of sleep subgroup (sG): evaluated with Epworth scale,
Methods: We selected 12 PD patients, who presented motor fluc- fatigue scale, Pittsburg quality of sleep questionnaire, Beck depres-
tuations, severe gait disturbances, and who showed insufficient sion scale, and Hamilton anxiety scale, and overnight polysomnogra-
improvement after levodopa trial (30%). All patients were submitted phy study.
tDCS, 4 weekly sessions, with 2mA, during 30. Neuropsychological assessment sG: evaluated with a specific neu-
Patients who presented improvement of Gait, balance and brady- ropsychological battery for cognitive assessment by the same neuro-
kinesia were considered to underwent Surgical Epidural Motor Cor- psychologist at the same environmental conditions.
tex Stimulation (MCS) of the left hemisphere. Improovement of gait Health status, quality of life and caregiver burden sG: evaluated
was considered as remission of FOG, step larger than a foot, 5 m with quality of life questionnaire in PD (PDQ-39), health status ques-
walking time, and improove in posture and balance. Patients were tionnaires (EQ-5D and EQ-VAS), global clinical impression scale
assessed preoperatively and 3 months after surgery. (CGI) and caregiver burden questionnaire (Zarit Burden index).

Fig. 1. (203).

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


Assessments at baseline, week 1, three, six, twelve months and Objective: (1) To provide an effective approach for monitoring
one, two, three, four, five, six, seven and eight years. of Parkinsons disease (PD) patients bradykinesia, (2) to systemati-
Results: Thirty patients were included (17M/13F) with advanced cally and objectively identify the clinical effects on the bradykinesia
PD. Mean age was 68.5 years (range 54-79) and the mean duration of 15 PD patients undergone Subthalamic deep brain stimulation
of the disease was of 13.8 years (range 7-23). (STN-DBS) over successive programming sessions.
Patients showed a significant and sustained motor improvement Background: Clinical scale based follow-up of patients under-
with increase of time ON to more than 80% of their waking time, going STN-DBS has shown inconsistent effect on bradykinesia in
and a mean decrease of 5.2 h in OFF time, without deterioration PD patients. However, quantitative assessment of STN-DBS effects
or with a tendency to an improvement of non-motor disorders stud- on bradykinesia has not been done.
ied. With improvement in the quality of life and reduction of the Methods: Fifteen PD patients and 15 healthy controls are
caregiver burden, despite several complications and adverse events recruited. The study has been approved by the local ethics commit-
most of low and moderate severity, and some serious related to PEG, tee. Each patient is assessed pre-operatively and followed for 6
to the infusion system or to the treatment itself. All the patients months post-operatively. At each visit, we test three DBS settings
selected maintained the treatment except 5. Five patients in CIDLI with enough time between the sessions. The settings are pre-defined
treatment died by not related cause with the treatment. and cover the whole range of device settings in common practice.
Conclusions: We confirm CIDLI as a treatment with sustained The settings are randomized for each patient. The patients are
efficacy, where the correct management requires the organization of recorded in the lab environment while wearing a motion capture suit.
a multidisciplinary team. A variety of features are extracted from the data to quantify
Results: Currently there are 15 patients enrolled in this study
205 and preliminary analysis has been performed for 3 patients who
have finished all the 9 lab visits as well as 3 healthy controls. We
The efficacy and safety of coenzyme Q10 in preventing the analyze forearm angular displacement during a hand pronation-
progression of early Parkinsons disease: A meta-analysis supination task. The extracted features are: standard deviation
R.C. De Roxas, R.D.G. Jamora (Manila, Philippines) (STD), range of motion (ROM), angular velocity (Vel), and vari-
Objective: The objective of this study is to assess and summarize ability in terms of time (Time_Var) and amplitude (Amp_Var).
the available evidence on the efficacy and safety of Coenzyme Q10 We define a new bradykinesia index which considers all the fea-
administration in the prevention of the progression of early Parkin- tures: B-Index 5 sqrt(STD*ROM*Vel/Time_Var*Amp_Var). Our
sons disease. analyses reveal that increasing the frequency of stimulation (volt-
Background: Coenzyme Q10, also known as Ubiquitone, is a age and pulse width fixed) generally decreases the B-Index.
substance now being used as a dietary supplement in many countries Increasing the pulse width (voltage and frequency fixed) does not
including the Philippines. It has also been the focus of several generally cause a consistent effect on the B-Index. Increasing the
researches as treatment for several diseases including Parkinsons voltage (frequency and pulse width fixed) increases the B-Index.
disease. Several studies have shown that Coenzyme Q10 inhibits On average, the B-Index of healthy controls is higher than the
mitochondrial dysfunction in Parkinsons disease, hence delaying its patients.
progression. Conclusions: We conclude that our method provides an effective
Methods: This is meta-analysis of randomized controlled trials approach to quantify PD patients bradykinesia after DBS surgery
on the use of Coenzyme Q10 in Parkinsons disease. A literature which overcomes some of the shortcomings of the other studies. We
search in several databases was conducted for relevant studies. Three show that our approach form an accurate tool to compare the slow-
randomized controlled trials met the inclusion criteria. The efficacy ness of movement of PD patients and healthy people.
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. Efficacy of IPX066, an extended-release formulation of
The Review Manager Software was utilized for the meta-analysis. carbidopa-levodopa, in advanced Parkinsons disease patients
Results: Compared to Placebo, treatment of CoQ10 did not show with troublesome dyskinesia
any significant difference in the mean scores of the UPDRS mental R. Dhall, L. Struck, R. Rubens, V. Shah, S. Gupta (Phoenix, AZ,
and ADL scores. Interestingly, the UPDRS motor score showed a USA)
significant difference between Coenzyme Q10 and placebo, but no
significant difference when a subgroup analysis between high-dose (- Objective: Evaluate the efficacy of IPX066 in advanced Parkin-
4.03 [-15.07-7.01], p-value= 0.47, I2=67%, P for heterogeneity=0.08) sons disease (PD) patients with troublesome dyskinesia.
and low-dose Coenzyme Q10 (0.53 [-0.89-1.94], p-value= 0.47, Background: IPX066 is an extended-release formulation of
I2=34%, P for heterogeneity=0.22) was done. Overall, there was no carbidopa-levodopa (CD-LD) designed to provide a rapid increase in
significant difference in the total UPDRS score (0.68 [-0.61-1.97], p- plasma LD concentrations similar to immediate-release CD-LD, but
value= 0.30, I2=0%, P for heterogeneity=0.70). The most common with sustained stable concentrations to allow a dosing interval of
side effects of the use of Coenzyme Q10 are anxiety, back pain, every 6 hours. IPX066 has demonstrated improvements in PD motor
headache, sore throat, nausea, dizziness and constipation. symptoms in early and advanced PD.
Conclusions: CoQ10 treatment was found to be safe with only Methods: IPX066 was administered for 13 weeks in a
minimal side effects but it did not show any significant difference in double-blind, parallel-group study vs. immediate-release CD-LD
the mean scores of the UPDRS total and component scores in (IR) in advanced PD patients (randomized N=393). This post-
patients with Parkinsons disease. 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
206 included patient diaries and Unified Parkinsons disease Rating
Scale (UPDRS) Parts II (activities of daily living) 1 III (motor
The impact of electrical parameters on bradykinesia of score).
Parkinsons disease patients after deep brain stimulation surgery Results: At baseline, these patients had a mean (SD) on time
M. Delrobaei, S. Tran, G. Gilmore, K. Ognjanovic, K. McIsaac, M. with troublesome dyskinesia of 1.7 (1.3) hr and 1.9 (1.6) hr, and
Jog (London, ON, Canada) 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


groups, respectively. Baseline UPDRS Parts II1III scores were 30.3 Cohens effect size) and Schwab and England (0,03 Cohens effect
(14.9) for IPX066 and 34.1 (14.8) for IR. At the end of the 13-week size).
treatment period, IPX066 treatment produced a significantly greater Conclusions: Our results suggest that this intensive rehabilita-
improvement in UPDRS Parts II1III scores (-4.9 [10.5] points) com- tion program had a high adherence level and appears to be feasi-
pared to IR, which worsened by 11.6 (10.4) points (P<.001). ble for these individuals with moderately severe PD. Our results
IPX066 treatment also produced a greater decrease in off time also suggest that the most responsive outcome measure for an
(-1.4 [2.8] hr) compared to the IR group (-0.7 [2.9] hr), although this intervention with these characteristics is the MDS-UPDRS
was not statistically significant (P=.13). Both groups showed less (Part III).
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 209
UPDRS Parts II1III scores and numerically greater improvement in
off time after treatment with IPX066 compared to IR. These Onset and duration of clinical effect of IPX066, an extended-
improvements were not accompanied by increased on time with release formulation of carbidopa-levodopa, in advanced
troublesome dyskinesia in either treatment group. Parkinsons disease
A. Ellenbogen, R.A. Hauser, N.B. Modi, A. Hsu, S. Khanna, S. Gupta
(Bingham Farms, MI, USA)
208 Objective: Compare the onset and duration of clinical effect of
Feasibility study of an intensive multi-strategy rehabilitation IPX066 to immediate-release (IR) carbidopa-levodopa (CD-LD) and
program for Parkinsons disease CD-LD 1 entacapone (CL1E) in patients with advanced Parkinsons
J.M. Domingos, V. Canica, C. Godinho, A. Pinho, D. Guerreiro, J.J. disease (PD).
Ferreira (Torres Vedras, Portugal) Background: IPX066 is an extended-release, multiparticulate
capsule formulation of CD-LD designed to provide a rapid increase
Objective: To assess the feasibility of an intensive multi-strategy in plasma LD concentrations similar to IR CD-LD, but with sus-
rehabilitation program for individuals with Parkinsons disease (PD) tained stable concentrations to allow dosing every 6 hours. IPX066
and to evaluate the responsiveness of multiple outcome measures has demonstrated improvements in PD motor symptoms in early and
that could be candidates to be applied on confirmatory trials. advanced PD.
Background: Increasing research suggests that intensive reha- Methods: IPX066 and CL1E were compared in a double-blind
bilitation programs can provide both short and long-term benefits crossover study; IPX066 and IR CD-LD were compared in an open-
to individuals with PD. Given the variety of rehabilitation pro- label randomized crossover study. The Unified Parkinsons disease
grams that exist, the true acceptability to these programs is still Rating Scale (UPDRS) Part III (motor score), Investigator Dyskinesia
limited. Assessment (IDA; rating of off time and on time with or without
Methods: We conducted an exploratory feasibility study in indi- dyskinesia), and finger tapping (taps/min) were assessed after a sin-
viduals diagnosed with idiopathic PD. Feasibility was assessed by gle dose of IPX066 or the comparator. Outcomes were assessed pre-
level of adherence to the program. Participants were recruited from a dose and at 30 min (tapping, IDA) or hourly (UPDRS) intervals after
Movement Disorders Unit (Campus Neurol ogico Senior - CNS) dosing. The time at which patients crossed a threshold of improve-
based on their balance and gait impairments. Participants were ment in finger tapping [10, 15, 20%] and UPDRS Part III [2.5, 5, 7,
assessed with the MDS -UPDRS (part III), Pull-test, Timed-up and 11 units] were used to determine the onset and duration of clinical
go (TUG) and Balance Berg scale, and Schwab & England Scale. effect. Time to on and duration of on without troublesome dys-
Our intervention consisted of at least 2 hour individual physiotherapy kinesia (on with no or non-troublesome dyskinesia) were analyzed
sessions per day, 3 times a week for at least 4 weeks. The program for the IDA.
consisted of practicing gait and balance multitask activities with dif- Results: For IPX066 vs. CL1E, a subset of 32 patients under-
ferent kinds of motor and cognitive tasks progressively introduced. went pharmacodynamic assessment (of 91 randomized in the larger
Focused attention and multitasking was also explored with resistance study); 27 patients were enrolled for IPX066 vs. IR CD-LD. Time to
training using plurisports adapted to PD, such as boxing, dancing on and duration of on using a threshold of 15% increase from
and swimming. baseline in tapping, and an 11 point improvement in UPDRS were
Results: The participants included 6 woman and 7 men, mean similar to values obtained on the IDA, and are shown in Table 1.
age of 72.5, Hoehn and Yahr stages 2 to 4 and with a mean disease The pattern of improvements was similar using other improvement
duration of 7 years. Every participant completed the program with thresholds. [figure1]
no relevant adverse effects and according to the protocol. The out- Conclusions: The onset of clinical effect for IPX066 was rapid,
comes with larger effect size were the MDS-UPDRS (Part III) (with similar to that for IR CD-LD and CL1E. The duration of effect for
0,78 Cohens effect size); Berg balance scale (0,25 Cohens effect IPX066 was substantially longer than that for either IR CD-LD or
size); Timed Up and Go (0,25 Cohens effect size); Pull test (0,07 CL1E.

Fig. 1. (209).

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


210 Results: IPX066 significantly improved off time (P<.0001)

and UPDRS II1III scores (P<.03) compared with the active con-
TDCS and gait training for hypokinetic gait disorders: A pilot trols in the overall studies. In both studies, numerical improve-
study ments from baseline in UPDRS Parts II1III and off time were
T. Emara (Cairo, Egypt) seen with IPX066 vs. the comparator in each disease severity
Objective: Different gait training protocols usually improve gait subgroup. In the larger ADVANCE-PD study, the improvements
speed by 0.1 m/sec. Our objective was to test whether applying in off time were significantly greater for IPX066 vs. IR CD-
Transcranial Direct Current Stimulation (TDCS) with gait training LD in the more severe off (P<.0001) and in both the more
may help achieve better gains in walking speed. (P=.02) and less severe (P=.0001) UPDRS subgroups. Greater
Background: Gait problems in patients with Parkinsons improvements in UPDRS II1III were also seen with IPX066 in
disease or vascular Parkinsonism are often resistant to medical the more severe off (P=.0002) and UPDRS (P=.0001) sub-
treatments. groups; the approximate 2-fold improvement by IPX066 compared
Methods: Nine patients with PD or vascular Parkinsonism were to IR CD-LD in the less severe off (P=.13) and UPDRS
recruited. 12 20-minute sessions of Anodal TDCS at Cz that were (P=.18) subgroups did not reach significance, possibly due to a
followed by gait training sessions within a period of 4 weeks were lower score range (floor effect). For both studies, IPX066 did not
applied. 10 mts walking speed at self selected pace was measured at worsen on time with troublesome dyskinesia compared to active
baseline and at the end of the treatment period. Other outcome controls in any subgroup (P>.11).
measures included degree of assistance (1-7 score similar to the Conclusions: Across disease severity subgroups, IPX066 con-
functional independence measure grading), number of falls, and sistently improved UPDRS Part II1III and off time vs. the
functional category according to walking speed (difficult in-home active controls without significantly worsening troublesome
ambulation less than 0.2 m/s; in-home ambulation 0.2-0.4 m/s, lim- dyskinesia.
ited community ambulation 0.4-0.8 m/s; community ambulation
more than 0.8 m/s). No change of medications was allowed during 212
the study period.
Results: Six cases with PD (5 males and one female) and three Impact of tDCS in Parkinsons disease on mood, cognition, and
male patients with vascular Parkinsonism with mean age of 68.1 1/- motor deficits: A randomized, double-blinded, placebo-controlled
4.5 and mean duration of illness of 7.5 1/- 2.3 yrs were recruited. trial
There was a significant change in gait speed (baseline 0.291/- R.A. Falconer, S.L. Rogers, Y. Torres-Yaghi, P. Turkeltaub, F. Pagan
0.17 m/s, post 0.561/-0.23 m/s; p50.0001), and degree of assistance (Washington, DC, USA)
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 Objective: Evaluate the potential for bifrontal transcranial direct
in their functional category of walking speed, all of them had a start- current stimulation (tDCS) to improve mood, cognitive and motor
ing speed of less than 0.4 m/s. functioning in patients with Parkinsons disease.
Conclusions: TDCS may augment the effects of gait training in Background: tDCS has demonstrated ability to temporarily
patients with hypokinetic gait disorders. The effect is particularly enhance cognitive, motor and affective functions of the brain. Prior
clear in those with low starting walking speed and results in a func- studies have shown definable improvement in post-stroke patients.
tional change of walking ability in those cases. A larger RCT is cur- This study seeks to examine whether these benefits translate to neu-
rently underway to validate these results and to monitor the rodegenerative conditions. An open-label trail showed potential for
sustainability of this improvement. 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.
211 Pre-stimluation testing included the following: UPDRS, Becks Depres-
The influence of baseline disease severity on the efficacy of sion Screen (BDS), MOCA, and speech assessments. Participants in the
IPX066, an extended-release formulation of carbidopa-levodopa, treatment arm were then given tDCS treatments daily for 10 days. These
in advanced Parkinsons disease daily treatments involved 2mA current administered in a bifrontal mon-
tage for 30 minutes, designed to facilitate frontal lobe integration at the
A.J. Espay, G. Liang, K. Sharma, R. Rubens (Cincinnati, OH, USA)
prefrontal cortex. Participants in the placebo-controlled arm received a
Objective: Evaluate whether the clinical efficacy of IPX066 is brief, 15-second stimulation to mimic treatment, but no other therapy.
influenced by baseline disease severity in clinical trials of advanced After completion of the 10 days, a post-test battery was completed for
Parkinsons disease (PD), using post hoc subgroup analyses. comparison. We will complete 1 month post-follow-up with testing and
Background: IPX066 is an extended-release formulation of a full delayed intervention to the placebo group.
carbidopa-levodopa (CD-LD) designed for a rapid increase in plasma Results: Regarding mood, the treatment arm experienced a 65%
LD concentrations (similar to immediate-release [IR] CD-LD), but improvement on average in BDS, compared to 22% in the placebo
with sustained stable concentrations to allow dosing every 6 hours. group. For cognition, the treatment group saw a 36% improvement
IPX066 has demonstrated improvements in motor symptoms in early on average in MOCA score, compared to 4% in placebo group.
and advanced PD. Regarding motor functioning, the treatment group saw a 24%
Methods: IPX066 was tested in advanced PD in two random- improvement on average in UPDRS, compared to an average decline
ized, double-blind, active comparator-controlled Phase 3 studies of 13% in the placebo group. When comparing treatment and pla-
(ADVANCE-PD: IPX066 vs. IR CD-LD for 13 weeks, N=393; cebo, improvement was consistently greater in the treatment arm by
ASCEND-PD: IPX066 vs. CD-LD1entacapone using a 2-week per a difference of 43% (BDS), 32% (MOCA) and 37% (UPDRS).
period crossover, N=91). Subgroups were dichotomized into more Conclusions: With 10 days of tDCS stimulations to the bifron-
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 and motor scoring that was not reflected in the placebo arm.
UPDRS Part II1III (activities of daily living 1 motor score: 32, Although low sample size is a limitation to this study, the noted
ADVANCE-PD; 30, ASCEND-PD). The changes from baseline in improvement in the treatment arm compared to placebo arm is
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 Parkinsons community and should propel further tDCS studies in
subgroup. PD.

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


213 egies and external cues are typically used to circumvent freezing
Leg rest tremor response to acute dopaminergic challenge Methods: In this case series study, we investigated the effects of
predicts long term Parkinsons disease diagnosis a task-specific learning principled approach that targeted each per-
S. Fari~
na, M. Wilken, P. Morisset, D. Cerquetti, M. Rossi, M. sons unique triggers directly. In addition to specificity of training,
Merello (Buenos Aires, Argentina) other learning principles were integrated into the program including:
Objective: To evaluate leg rest tremor (LRT) response to acute feedback, intensity through high effort and dosage (5 days; 3 hours/
dopaminergic challenge and its relationship to subsequent long term day), and progressive difficulty by manipulating environment, bal-
Parkinsons disease (PD) diagnosis. ance requirements, distractors, and variability of practice. Attentional
Background: LRT can be an early sign of PD and other Parkin- strategies and external cues were integrated to enhance learning by
sonisms, such as multiple system atrophy and vascular Parkinsonism. allowing for greater success during the practice of complex multi-
Its predictive value for PD clinical diagnosis has not been described. tasking conditions. The study was held in a community setting with
Methods: A retrospective review of medical records from a small group boot camp approach to take advantage of social/
patients with a short-onset Parkinsonism that were submitted to acute emotional interactions shown to impact learning and quality of life.
levodopa challenge for clinical prediction of sustained long-term Results: 5/6 subjects showed improvement in the FOG question-
dopaminergic response between November 1999 and August 2014. naire and objective measures including dual tasking conditions.
Data was collected on demographics, levodopa response (a modifica- These improvements were related to QoL for 4/5 subjects. One sub-
tion of UPDRS-III or MDS-UPDRS-III 30% was considered a pos- ject with mild FOG did not show improvement on any FOG
itive test and a reduction in at least one point in LRT subscore was outcomes.
considered a positive response of LRT), clinical manifestations and Conclusions: We will report on the trends across 6 individuals
final clinical diagnosis after at least one-year follow-up. and discuss the implication to future studies and real world
Results: A total of 778 patients were evaluated, of which 75 implementation.
(10%) patients presented LRT. Fifty four (72%) had responsive LRT,
of which 41 (76%) showed a positive response to levodopa acute 215
challenge and 49 (65%) fulfilled all UKPDSBB criteria at one-year
follow-up. Of the 21 (28%) non-responsive LRTs, only one (5%) Preliminary report investigating the benefits of neuroplasticity-
showed a total positive response to acute levodopa challenge and a principled community-based exercise programs for people with
final PD diagnosis, whereas 20 (95%) had negative response to acute Parkinsons disease
challenge, of which 6 (30%) received a PD diagnosis at one-year fol- B.G. Farley, A. Okurily, J. Bazan-Wigle, K. Moynahan (Tucson, AZ, USA)
low-up (false negatives). A responsive LRT to acute levodopa chal-
lenge obtained a sensitivity of 88%, a specificity of 74% with a Objective: Report preliminary short-term benefits on mobility of
positive and negative likelihood ratio for a final clinical PD diagnosis ongoing community-based group exercise programs that implement
of 3.3 and 0.2, respectively. Multivariate analysis revealed the pres- progressive aerobic training and Parkinsons disease (PD) specific
ence of limb bradykinesia (p<0.0001) and the total UPDRS/MDS- skill acquisition forms of training for people of varying disease
UPDRS-III response to levodopa acute challenge (p5<0.0001) were severity.
independent factors related to LRT response. No PD patient had iso- Background: Progressive aerobic training and skill acquisition
lated (without any akineto-rigid feature) LRT, whereas 5 out of 19 have emerged as forms of practice for people with PD that are capa-
(26%) presented LRT without arm or leg rest tremor. LRT magni- ble of not only improving function, but capable of mediating brain
tude response to levodopa was significantly higher than hand rest health and repair mechanisms. Translating neuroplasticity-principled
tremor (p50.033). research protocols effectively, thereby counteracting inactivity, is a
Conclusions: LRT, although infrequent, can be an early sign of challenge. The Parkinsons Wellness Recovery Gym (PWR!GymV R)

PD. It was frequently accompanied with hand rest tremor, but offers ongoing specialty group classes and intensive therapies for
showed a greater magnitude response to levodopa than the latter. Its people with Parkinsons disease of varying severity in a community
positive response to acute levodopa challenge has a high sensitivity center.
and moderate specificity for PD diagnosis. 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
214 varies across groups from most (HIIT, N=13) to moderate (Circuit,
Benefits of task-specific learning-principled practice to improve N=12) to least (MOVES, N=10). Measurements are collected at
freezing of gait for individuals with Parkinsons disease in a initial intake and 6 months thereafter. All classes meet for 1 hour
small group community setting. A case series study 2-3x/week and target 20 of progressive aerobic training plus 20 of
a functional amplitude-focused training program called
B.G. Farley, K.M. Hamilton, A.B. Messer, K. Greene, L. Rankin
(Tucson, AZ, USA) PWR!MovesV R.

Results: MOVES/Circuit both improved in 10 m self-selected

Objective: To examine the benefits of task-specific learning-prin- walking (12%) and stand to floor transfer time (17-24%). All
cipled practice to improve freezing of gait (FOG) for individuals groups improved in backward walking (14-23%) and timed up/
with Parkinsons disease (PD) in a small community setting. go (TUG) in motor dual task conditions (14%). MOVES
Background: FOG is one of the most disabling symptoms of showed greatest change in TUG in both dual task conditions
advanced stage PD and is associated with frequent falls and reduced (motor/cognitive) interference. Circuit was the only group to
quality of life (QoL). Researchers and clinicians define FOG as: An show meaningful improvements in 6 walk endurance (16%)
episodic inability to generate effective stepping most commonly and 10 m fast walking (12%). HIIT showed least improvement
experienced during turning and step initiation, but also when faced on all measures.
with spatial and time constraints, stress, and distraction. Despite the Conclusions: The least challenging class showed the greatest
multifactorial nature of FOG, task-specific training has not yet been improvement on functional mobility outcomes. Backward walking
applied to counteract the multiple motor/cognitive/emotional triggers and dual task TUG were most sensitive across groups. Data may
that lower threshold for the occurrence of FOG and that may interact reflect need for more sensitive clinical mobility outcomes, differen-
and deteriorate synergistically. In addition, learning principles of ces in specificity of training across exercise classes, and need for bet-
practice have not been applied to task specific antifreeze exercises. ter clinical criteria to predict an individuals response to
Instead, more general gait and balance training with attentional strat- manipulations of fitness/learning principles of training.

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


216 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
Initiating intrajejunal infusion of levodopa/carbidopa intestinal again on the following two days, in order to refine the optimal LCIG
gel: An outpatient model dosage as well as to taper off oral drugs. [figure1]
A. Fasano, L.W.C. Liu, Y.Y. Poon, A.E. Lang (Toronto, ON, Results: To date, five patients (including 1 with levodopa-
Canada) responsive multiple system atrophy, 1 female, age: 61.8 6 8.1 years,
Objective: To describe our experience with an outpatient-model disease duration: 10.0 6 2.6 years) have received the treatment suc-
for levodopa/carbidopa intestinal gel (LCIG) treatment in patients cessfully and safely with the proposed outpatient model. None
with Parkinsons disease. needed the nasojejunal test-phase. All patients reported an improve-
Background: Although there are no published procedural guide- ment of motor fluctuations (on average by 59.7 6 15.3%). One
lines on the best model to deliver intrajejunal infusion of LCIG treat- patient suffered from a stoma infection treated with topical
ment, patients are generally hospitalized and switched from their antibiotic.
conventional pharmacotherapy to LCIG through a percutaneous Conclusions: Our model is characterized by a delay between the
endoscopic gastrostomy (PEG) with jejunal tube (PEG-J). PEG-J procedure and initiating the LCIG to allow the fistula track to
Methods: We propose the nasojejunal test phase for patients mature, thus possibly reducing PEG site related complications, fre-
whose potential clinical benefit is uncertain. Patients undergo endo- quently reported in clinical trials. We believe that there is no
scopic PEG/PEG-J placement as outpatients, are sent home 1-2 hours urgency to start LCIG following the PEG-J procedure, as is often
after and seen by the gastroenterologist the following day to examine encouraged in the full inpatient model in order to expedite patients
the PEG insertion site and to adjust the bumper position against the stay in the hospital.
abdominal wall as necessary. A minimum of two weeks later, 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.

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
Fig. 1. (216). regarded as safe.

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


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.

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


TABLE 2. multivariate analysis of risk factors for wearing-

variables P value ratio (OR)
Duration of L-dopa treatment 0.003* 1.024
Disease Duration at assessment 0.241 0.994
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
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)
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
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
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)
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


50mg-OPC group (65.2% [p=0.0028]). OPC and ENT were generally with either 25mg- or 50mg-OPC resulted in a significant reduction
safe and well tolerated. of daily OFF-time (1.56 h [p=0.0106] 25mg-OPC and -1.94 h
Conclusions: Opicapone, particularly 50mg-OPC, was effective [p<0.0001] 50mg-OPC vs. -0.97 h Placebo) and increase in the ON-
in reducing OFF-time in PD patients with a favourable profile com- time without troublesome dyskinesia (1.43 h [p=0.0083] 25mg-OPC
pared to ENT. 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]).
220 Conclusions: OPC is effective in reducing OFF-time and increas-
Safety and tolerability of opicapone in the treatment of ing ON-time without troublesome dyskinesia.
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, Number-needed-to-treat analysis of droxidopa in patients with
Portugal) symptomatic neurogenic orthostatic hypotension
C. Francois, G.J. Rowse, R.A. Hauser, L.A. Hewitt (Deerfield, IL,
Objective: Evaluate the safety of opicapone (OPC) in patients
with Parkinsons disease (PD) and motor fluctuations across phase
III studies. Objective: To evaluate the safety and efficacy of droxidopa vs
Background: OPC, a novel once-daily peripheral COMT inhibi- placebo for the treatment of symptomatic neurogenic orthostatic
tor, has shown to be effective in reducing OFF-time in PD patients hypotension (NOH) in terms of the number needed to treat (NNT)
with motor fluctuations. and number needed to harm (NNH).
Methods: Patient-level data of matching treatment arms of Background: Droxidopa is a norepinephrine prodrug recently
BIPARK I and II studies was integrated (placebo, 25mg-OPC and approved to treat symptomatic NOH caused by primary autonomic
50mg-OPC). Both were multicentre, 14 to 15-week double-blind, failure (Parkinsons disease, multiple system atrophy, and pure auto-
randomised, placebo- and active-controlled studies and had similar nomic failure), dopamine b-hydroxylase deficiency, and nondiabetic
designs and measurement instruments. Safety was assessed by inci- autonomic neuropathy. To date, safety and efficacy of droxidopa
dence of treatment-emergent adverse events (TEAEs), changes in have been studied in 6 multicenter, phase 3 trials ranging from 2
laboratory values, ECGs and vital signs. weeks to 2 years in duration and involving >600 patients.
Results: The pooled safety set included over 750 patients Methods: Safety and efficacy data were pooled from 2 phase 3
(N=257, 244 and 265 for placebo, 25mg- and 50mg-OPC). Dopami- trials: NOH301 and NOH306. To calculate the NNT, outcome
nergic events and other PD symptoms were the most commonly assessed was the response rate of Item 1 of the Orthostatic Hypoten-
reported TEAEs: dyskinesia (18.3% OPC vs. 6.2% placebo), consti- sion Symptom Assessment (OHSA) showing improvement 50% or
pation (5.7% vs. 1.9%), insomnia (5.1% vs. 1.6%) and dry mouth 2 units at Week 1; to calculate the NNH, outcomes assessed were
(4.7% vs. 1.2%). No dose relationship was observed for the majority adverse events (AEs) with >5% frequency, AE rate leading to drop-
of TEAEs. Serious AEs were reported for few patients: 4.3% placebo out, and AEs related to falls. NNT and NNH were calculated as the
and 3.5% OPC. One death (pneumonia) occurred in the placebo reciprocal of the risk difference for placebo vs droxidopa. Likelihood
group. There were no reports of severe diarrhea, myocardial infarc- to be helped or harmed (LHH) was calculated as NNH/NNT.
tion, prostate cancer, melanoma or any serious hepatic event in OPC Results: Based on pooled OHSA Item 1 results, the NNT was
groups. Impulse control disorders were reported by <1% of OPC- significant for improvement 50% (5; 95% CI: 311) and 2 units
treated patients. No relevant differences compared to placebo were (5; 95% CI: 48). The NNH was dependent on outcome assessed. Of
observed for laboratory parameters, vital signs or ECG readings. the AEs occurring >5% (headache, dizziness, nausea, fatigue, and
Conclusions: OPC is safe and well tolerated with no apparent hypertension), the NNH ranged from 23 to 302 and was significant
association to known safety concerns of other anti-PD drugs, particu- only for pooled incidence of hypertension (28; 95% CI: 1695). For
larly other COMT inhibitors. 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
221 dropouts due to AEs, the NNH was 34 (NOH301: 84; NOH306: 24)
Efficacy of opicapone as adjunctive therapy to levodopa in and NNT of 5 (responder week 1 OSHA >2 or 50% improvement);
patients with Parkinsons disease and motor fluctuations: therefore, LHH was calculated as 34/5=6.8.
Analysis of pooled phase III studies Conclusions: Droxidopa is 6.8 times more likely to achieve
response than result in a discontinuation because of an AE compared
J. Ferreira, A. Lees, A. Santos, N. Lopes, R. Costa, C. Oliveira, R.
with placebo.
Pinto, T. Nunes, J.F. Rocha, P. Soares-da-Silva (S. Mamede do
Coronado, Portugal)
Objective: Evaluate the efficacy of opicapone (OPC) in patients 223
with Parkinsons disease (PD) and motor fluctuations across phase Impact of reduction in falls for patients with PD and NOH: Post
III studies. hoc economic analyses of phase 3 clinical trial data on droxidopa
Background: OPC is a novel once-daily potent and long-acting C. Francois, R.A. Hauser, H. Kaufmann, S. Heritier, L.A. Hewitt, R.
peripheral COMT inhibitor under investigation for PD.
Owen, B. Rive, G.J. Rowse (Deerfield, IL, USA)
Methods: Patient-level data of matching treatment arms of
BIPARK I and II studies was integrated (placebo, 25mg-OPC and Objective: To estimate the impact of droxidopa therapy on total
50mg-OPC). Both were multicentre, 14 to 15-week double-blind, costs in patients with Parkinsons disease (PD) and neurogenic ortho-
randomised, placebo- and active-controlled studies and had similar static hypotension (NOH) while considering the observed reduction in
designs and measurement instruments. The primary efficacy variable the number of falls experienced by patients and droxidopa drug cost.
was the change from baseline in absolute OFF-time based on Background: NOH results from inadequate noradrenergic
patients diaries. Key secondary measure was the OFF- and ON-time response to postural change. It is known to be a substantial risk fac-
responder rates ( 1 hour). tor for falls in patients with PD. Droxidopa is a norepinephrine pro-
Results: The pooled efficacy set included over 750 subjects (pla- drug recently approved to treat symptomatic NOH caused by
cebo n5255, 25mg-OPC n5241, 50mg-OPC n5262). Treatment primary autonomic failure (PD, multiple system atrophy, and pure

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


autonomic failure), dopamine beta-hydroxylase deficiency, and non- gained. ICERs per avoided fall with no or minor injury and per
diabetic autonomic neuropathy. avoided fall with moderate or major injury were $1559 and $24,866,
Methods: Cost offset due to a reduction in falls was estimated respectively. Main drivers were the distribution of falls by severity,
using a retrospective, piggyback design of randomized controlled fear of fall-related inputs, and costs due to injuries.
trial data and published data. Patients with PD in a phase 3 study Conclusions: Droxidopa is a cost-effective option compared with
underwent double-blind titration up to 2 weeks with droxidopa, fol- the SoC in US clinical practice for the treatment of NOH.
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 225
care, and costs from a systematic review of falls data in people 60 Medical near-miss events in hospitalized patients with
years old living in the community, we calculated the average cost/ Parkinsons disease, using a nationwide online open database in
fall/treatment to estimate the potential cost reduction during 10 Japan
weeks of droxidopa therapy vs placebo. T. Furuya, K. Takahashi, A. Miyake, T. Kimura, Y. Ito, T. Sasaki, N.
Results: Droxidopa treatment over 10 weeks was associated with Araki, T. Yamamoto (Saitama-ken, Japan)
significantly fewer falls per patient-week vs placebo and with fewer
fall-related injuries. The estimated average costs of falls per patient Objective: To investigate medical near-miss events in hospital-
were $4,573 for droxidopa vs $11,813 for placebo. This results in a ized patients with Parkinsons disease (PD) in Japan, using a nation-
cost reduction of $7,239. The average droxidopa drug cost was wide online open database provided by the Japan Council for
$10,108. Thus the net cost of droxidopa therapy was $2,869. Sensi- Quality Health Care (JCQHC).
tivity analyses with more conservative estimates of cost of falls or Background: Complex medication regimens are often prescribed
number of falls increased the net costs to $6,640 and $7,457, to manage PD symptoms. For PD inpatients, safety and adherence to
respectively. a regular PD medication schedule are important in achieving optimal
Conclusions: This simple model indicates that droxidopa could symptom control. Only a few studies have investigated medical near-
reduce falls for PD patients with symptomatic NOH, limiting the miss events in hospitalized PD patients.
financial impact of droxidopa therapy to $2,869 over 10 weeks of Methods: A division of JCQHC has undertaken a project to col-
treatment. Inclusion of other potential benefits on functioning, quality lect medical near-miss/adverse event information in Japan, and the
of life, and associated costs related to negative consequences of fear collected information and all anonymous individual reports can be
of falling may further decrease the overall cost. accessed on JCQHCs website ( A total of
39,379 medical near-miss events were recorded in this database
between January 2010 and November 2014.
224 Results: We performed a retrospective analysis and identified 131
Cost effectiveness of droxidopa in patients with neurogenic cases related to PD inpatients, among which 119 incorrect medication
orthostatic hypotension: Post hoc economic analysis of phase 3 administrations (90.8%) were included. We found three major catego-
trial data ries associated with inappropriate medications: incorrect time (40
cases), dose omission (30 cases) and preparation errors (12 cases).
C. Francois, R.A. Hauser, J. Dorey, E. Kharitonova, S. Aball
ea, L.A.
The causes of incorrect medications were a lack of confirmation by
Hewitt (Deerfield, IL, USA)
medical staff, and drug regimen complexity/polypharmacy. The medi-
Objective: To develop a cost-effectiveness (CE) model to esti- cal staff involved in these cases were nurses (113 cases), pharmacists
mate the impact of droxidopa vs the standard of care (SoC) in terms (12 cases) and others (6 cases). The number of cases related to an
of US costs and quality-adjusted life-years (QALYs). extra dose of PD medication (with the exception of after each meal)
Background: Neurogenic orthostatic hypotension (NOH) is was 21. The incorrect medication time details were as follows: right
caused by autonomic dysfunction in which there is an inadequate after waking up (6 cases), at bed time (2 cases) and others (13 cases).
noradrenergic response upon standing. Droxidopa is a norepinephrine The numbers of errors in each PD drug category were 50 cases of L-
prodrug that is FDA approved to treat symptomatic NOH. Orthostatic dopa, 12 cases of dopamine agonists, eight cases of selegiline and
falls in blood pressure can lead to serious injuries, limited daily four cases each of entacapone/amantadine/anti-cholinergic drugs. In
activities, and decreased quality of life, and represent a significant two cases, the daily replacement of a transdermal patch was skipped.
economic burden on the US healthcare system. Contraindicated medications were ordered for two patients.
Methods: A Markov model was used to predict risk of falls and Conclusions: Although adherence to complex PD medication
impact of NOH symptom improvement. Probabilities of falls and schedules during hospitalization entails various challenges, collabora-
treatment responses were from randomized controlled trials tion for the confirmation of medication administration by interdisci-
(NOH306A and NOH306B) with Parkinsons disease patients who plinary medical staff can improve outcomes and help safeguard
underwent 2-week, double-blind placebo or droxidopa dose titration, against the disruption of PD patients prescribed medication sched-
followed by 8 weeks of double-blind maintenance treatment. The ules at home.
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- 226
ues, and injury-related costs were from published studies. Model out- Pharmacokinetic profile of ND0612L (levodopa/carbidopa for
comes included the number of falls (total and by severity), number subcutaneous infusion) in patients with moderate to severe
of QALYs, and costs (total, treatment acquisition, fall-related, and Parkinsons disease
NOH management). The primary CE measures were the incremental
N. Giladi, Y. Caraco, T. Gurevich, R. Djaldetti, Y. Cohen, O.
CE ratios (ICERs), calculated as the difference in costs between the Yacobi-Zeevi, S. Oren (Tel Aviv, Israel)
two treatment groups divided by the differences in falls and number
of QALYs. Outcomes were assessed over a 12-month period, based Objective: To characterize the pharmacokinetic profile of
on a treatment duration of 6 months. ND0612L in PD patients with motor fluctuations.
Results: Droxidopa patients had fewer falls in each severity cate- Background: The symptomatic efficacy of continuous levodopa/
gory and a higher number of QALYs. Estimated droxidopa costs for carbidopa (LD/CD) delivery in PD patients with motor fluctuations is
6 months were $30,112, and estimated cost savings due to falls were well known. However, intrajejunal infusion systems are associated
$14,574 over 12 months. From a payer perspective, droxidopa was with tolerability concerns, and poor LD solubility has prevented devel-
cost-effective vs the SoC with an ICER of $47,001 per QALY opment as a subcutaneously deliverable formulation. ND0612L is a

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


proprietary liquid formulation of LD/CD that enables subcutaneous touches the ground again. Gait cycle improved from PD pre-
administration of LD/CD to achieve steady levodopa plasma levels. operative baseline (Pre-op: M=1.11 sec, 6 months: M=1.04 sec).
Methods: This was a Phase II randomized, placebo-controlled, Double support time decreased from Pd pre-operative baseline (Pre-
double-blind, two-period study of ND0612L in PD patients with op: M=.30 sec, 6 months: .26 sec), which better represents control
motor response fluctuations. During Period-1 (14 days), 30 patients data (M=.28 sec).
received their optimized current oral treatment (dose reductions per- Conclusions: Preliminary data analysis suggests DBS intervention
mitted), and were randomized (2:1) to adjunct ND0612L or placebo. may improve gait over a 6 month period post-operatively. Further
During Period-2 (7 days), 16 patients were offered open-label analysis, up to 1 year post-operation, will better elucidate the long-
ND0612L and were randomized to ND0612L monotherapy or term efficacy of DBS intervention on gait. Our method provides the
ND0612L plus oral entacapone. first objective and quantitative measure of long-term gait variances
Results: Patients treated with adjunct ND0612L had their plasma in PD patients undergoing DBS treatment.
LD concentrations consistently maintained above a mean (6SD) of
800 6570ng/ml, as well as a lower peak-to-trough ratio and fluctua- 228
tion index vs. placebo. Exploratory efficacy analysis showed that
ND0612L treatment reduced OFF time by a mean6SD of Switch form immediate release pramipexole to extended release
2.42 6 2.62h and 2.13 6 2.24h from baseline according to in-clinic pramipexole: Experience from a tertiary referral center
and home diaries, respectively (vs. 0.41 6 2.62h and 1.39 6 2.33h S.I. Gul, M. Kuzu, O. Herdi, S. Tezcan, N.F. Mercan, C.M.
with placebo). ND0612L also improved sleep quality (17.1 6 17.58 Akbostanci (Ankara, Turkey)
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 Objective: To evaluate the safety and efficacy of switch from
from baseline vs 1.78 611.10 with placebo), and global impression immediate release pramipexole (pex) to extended release pramipex-
(90% of the patients had improved CGI-C scores vs. 36% in pla- ole (pex-ER).
cebo). All 16 patients chose to continue to Period-2 in which plasma Background: Since the avalibility of pex-ER in our country
LD levels were maintained at a mean of 550 6 79ng/ml with about a year ago, we could reach satisfactory information from the
ND0612L monotherapy and 800 6144ng/ml with ND0612L plus files of 69 patients (26 females, 38%) who had switched from pex to
oral entacapone. In these patients, the oral LD intake was reduced by pexER.
a median of 80%, with 3 of 16 patients completely discontinuing Methods: We documented pre and post switch pramipexole and
oral LD therapy. levodopa-equivalent doses of other antiParkinsonian medication, and
Conclusions: These data suggest that subcutaneous continuous analyzed the frequency and nature of reported adverse effects.
delivery of LD/CD with ND0612L, provides relatively stable LD lev- Results: Mean age of patients was 63,3 (range 44-88), and mean
els with reduced variability compared with oral LD. Efficacy findings disease duration was 7,1 years (range 1-27). The other drugs were
are also promising and warrant further study. 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%).
227 Switch from pex to pexER was uneventful in 59 (92,2%) patients.
Adverse events reported in five (7,2%) patients were ankle swelling
Deep brain stimulation and the effect on gait in Parkinsons (two patients), nausea (one patient), dyskinesia (one patient), hyper-
disease sexuality (one patient), and psychosis (one patient). Problems
G. Gilmore, M. Delrobaei, S. Tran, K. Ognjanovic, M. Jog (London, resolved with further medication change in two patients. Three
ON, Canada) patients preferred to went back to pex.
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. Pre and post switch pramipexole and levodopa-equivalent doses
Background: Gait impairments contribute to PD patient falls and of the patients.
reduced quality of life. Specifically, it remains unclear whether PD Pre-Switch Post-Switch
gait improves or worsens with DBS intervention over a long-term. Dose (mg/day) Dose (mg/day) p
Currently gait changes are monitored using the UPDRS, which is
subjective and qualitative in nature. An objective and quantitative Pex to Pex-ER 2,5 (SD 1,3) 3,1 (SD 1,2) ,00
assessment of gait, using kinematic technology, will allow the clini- Levodopa-Equivalent 653,2 (SD 498,2) 719,1 (SD 562,9) ,00
cian to more effectively determine whether gait is affected by DBS. Dose
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 Conclusions: Great majority of patients (92,2%) switched from
healthy age-matched controls will be used. Patients are assessed one three times daily pex to once daily pex-ER uneventfully. A slight
week pre-operatively and then up to one year post-operatively. Dur- increase in pramipexole daily dose, tailored according to patients
ing each programming visit the patient is monitored by a clinician, symptomatic needs, resulted in an increase in post-switch levodopa
and their device is adjusted if required. The patients gait is captured equivalent doses. Our experience is compatible with previously
using the PKMAS gait analysis carpet. The carpet assesses various reported studies.
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. 229
Results: Seven of the total patients (N=15) have completed the 6 Effect of medical cannabis in Parkinsons disease: Survey of
month session. Preliminary data has shown an improvement in patient experiences
important areas of gait performance up to 6 months post-operatively. T. Gurevich, L. Bar Lev Chleider, A. Rosenberg, J. Knaani, Y.
Stride length (Pre-op: M=94.56 cm, 6 months: M=113.32 cm) and Baruch, R. Djaldetti (Tel Aviv, Israel)
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 Objective: To assess the effect of cannabis treatment in patients
time from when one foot touches the ground to when the same foot with Parkinsons disease (PD).

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


Background: Medical cannabis is now widely used for improv- Results: Pre-Post LSVT LOUD findings indicated 1) less glottal
ing the quality of life of patients with various neurological disorders. incompetence and no significant change in supraglottal hyperfunction
Methods: A telephonic survey was conducted on PD patients 2) significant improvements in EGGW, aerodynamic and perceptual
granted medical cannabis treatment licenses from the Israel Ministry measures 3) decreased supraglottic hyperfunction.
of Health and who had received at least 2 months of treatment prior Conclusions: The results of these studies and our clinical experi-
to the interview. The structured questionnaire contained epidemiolog- ence demonstrate that when providing LSVT LOUD treatment cor-
ical questions and items about the effects of cannabis on different rectly, the result is a voice with normal healthy loudness that is not
symptoms. hyperfunctional and is of good quality.
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 231
participate, 20 could not be reached by phone, 4 had passed away. Integrated cardiovascular safety profile of droxidopa
The mean duration of cannabis treatment was 16.8 6 18.9 R.A. Hauser, W.B. White, G.J. Rowse, L.A. Hewitt (Tampa, FL,
months, the mean daily dose - 1.1 6 0.9 grams. The consumption USA)
methods were smoking (n524 [61%]), oil (n56 [15.3%]), smoking
1oil (n54 [10.2%]) and vaporizer (n51 [3%]). Nine patients (23%) Objective: To evaluate the cardiovascular (CV) safety profile of
discontinued treatment due to lack of effect or side effects. Thirty droxidopa in patients with symptomatic neurogenic orthostatic hypo-
patients (76.9%) reported a positive impact of cannbis on their gen- tension (NOH).
eral condition and mood, 25 (64%) reported improvement in pain Background: Droxidopa is a norepinephrine prodrug recently
and rigidity, 22 (59%) reported decrease in tremor and improved approved to treat symptomatic NOH caused by primary autonomic
quality of sleep. The most common reported side effects were cough- failure (PD, multiple system atrophy [MSA], and pure autonomic
ing due to smoking (n59), hallucinations (n56), restlessness (n56) failure [PAF]), dopamine b-hydroxylase deficiency, and nondiabetic
and confusion (n55). autonomic neuropathy. It is thought that droxidopa raises blood pres-
Conclusions: Subjective improvement of motor and non-motor sure (BP) by causing vasoconstriction.
symptoms was reported by most of the survey responders. However, Methods: CV safety data were integrated from 5 trials (N=666)
a significant number of patients had no improvement or experienced of patients with symptomatic NOH and diagnoses of PD, MSA,
side effects on short-term treatment. The long-term safety profile of PAF, dopamine b-hydroxylase deficiency, or nondiabetic autonomic
medical cannabis in PD patients is still undetermined. The results of neuropathy. Two were short-term, double-blind, randomized,
this retrospective open-label study require confirmation in a double placebo-controlled trials (RCTs) in patients with autonomic failure; a
blind study to exclude the placebo effect and to assess longer-term third RCT was in patients with PD randomized to 2-week, double-
safety of cannabis use in PD. 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
230 short-term studies. Adverse event (AE) rates were adjusted for treat-
LSVT LOUD voice treatment: Training normal healthy loudness ment duration and calculated by the number of events per patient per
with good quality year of mean exposure.
A.E. Halpern, L.O. Ramig, E. Peterson (Denver, CO, USA) Results: A total of 307 (46%) patients enrolled in any one of the
trials had a preexisting CV disorder at baseline; the most common
Objective: The target voice in LSVT LOUD is normal loudness diagnoses (n [%]) were arrhythmia (235 [35.3%]), coronary artery
with healthy voice quality, not shouting or vocal hyperfunction. This disease (164 [24.6%]), and hypertension (116 [17.4%]). In the trial
poster will present a review of a series of data sets which demon- in PD patients, over the entire 10 weeks the rates of CV-related AEs
strate healthy vocal loudness Post LSVT LOUD. Group data will were 0.17 and 0.24 for patients randomized to placebo and droxi-
include 1) physiological measures of laryngeal videostroboscopic 2) dopa, respectively; the event rates were nominally higher during
glottographic and aerodynamic tasks, as well as listener perceptual titration vs maintenance for placebo (0.65 vs 0.07) but similar during
data. 3) A case study of Pre supraglottic hyperfunction that was titration vs maintenance for droxidopa (0.30 vs 0.29). The rates of
reduced Post LSVT LOUD will be presented. LSVT LOUD strat- cardiac-related treatment-emergent AEs (TEAEs) were nominally
egies for achieving a normal loudness, good quality voice will be higher in droxidopa vs placebo patients who had a preexisting CV
discussed. disorder (0.34 vs 0.16); similarly, the rates of BP-related TEAEs
Background: LSVT LOUD is a voice and speech treatment that were nominally higher in droxidopa vs placebo patients with a preex-
was developed for Parkinsons disease (PD), and has applications to isting CV disorder (1.11 vs 0.62). There were no CV-related AEs
other neurological disorders. Over 20 years of research data have during 1 to 2 weeks of double-blind treatment in the short-term tri-
demonstrated the efficacy of this treatment (e.g., Ramig et al, 2001). als. In the long-term extensions, the event rate was 0.13.
LSVT LOUD targets the hallmark PD voice symptoms of decreased Conclusions: There were nominal, modest increases in CV-
loudness, hoarseness, and breathiness. A key component of LSVT related AE rates with droxidopa vs placebo; event rates in the long-
LOUD is training individuals to achieve normal loudness with a term extension was low.
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 232
loudness levels is incorporated into the treatment to address this sen- Efficacy of rasagiline in early Parkinsons disease: A meta-
sory mismatch. analysis of data from the TEMPO and ADAGIO studies
Methods: Data were collected on individuals with PD, Pre-Post R.A. Hauser, V. Abler, E. Eyal (Tampa, FL, USA)
LSVT LOUD. 1) Laryngeal videostroboscopic data were collected
on 13 individuals. The randomized studies were rated by 4 judges. 2) Objective: To evaluate the efficacy of rasagiline 1 mg/day versus pla-
Glottographic (EGGW) and aerodynamic measures were collected to cebo in a pooled population of patients with early Parkinsons disease (PD).
investigate the mechanism of change. Blinded listener perceptual rat- Background: TEMPO and ADAGIO were both Phase III studies
ings of hoarseness and breathiness were used to assess changes in that evaluated the symptomatic efficacy of rasagiline versus placebo
voice quality. 3) Laryngeal videostroboscopic data were collected on in patients with early PD.
an individual with PD pre/post LSVT LOUD who exhibited Pre Methods: Both studies recruited early, untreated patients with
supraglottic hyperfunction. early PD who were randomized to placebo, rasagiline 1mg/day or

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


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.
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


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.

Fig. 1. (233).

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

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


TABLE 1. Effect of hippotherapy on Parkinsons disease



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.

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


Objective: To gather data about rotigotine use for the treatment 1 to 4 units at week 1; more patients also had improvement 4
of Parkinsons disease (PD) in a tertiary Movement Disorder clinic units at weeks 4 and 8. The increase in standing SBP was signifi-
in Canada after 1 year of clinical availability. cantly greater in droxidopa patients vs placebo at week 1 (treatment
Background: Rotigotine is a dopamine agonist that binds prefer- difference: 6.8 mmHg; P=.007), but not at week 8 (treatment differ-
entially to dopamine D3 > D4 > D2 > D1 receptors, in addition to ence: 3.0 mmHg; P=.276). In 303, mean changes from baseline in
alpha-2B adrenoceptors and serotonin 7 (5-HT7) receptors. Rotigo- OHSA Item 1 score were -4.0, -3.9, -3.7, and -3.9 units at 1, 3, 6,
tine is available as a transdermal patch that provides constant plasma and 12 months, respectively. Increases in standing SBP were sus-
levels throughout the day and thus offers the theoretical advantage of tained: 13.7, 14.0, 10.4, and 12.3 mmHg at 1, 3, 6, and 12 months,
reducing peaks and troughs associated with conventional dopamine respectively. In both trials, headache (306: 13.2%; 303: 13.7%) and
replacement therapies. Rotigotine was administered to early- and dizziness (306: 9.6%; 303: 7.8%) were common treatment-emergent
late-stage PD patients and was effective at reducing Parkinsonian adverse events (TEAEs). Most TEAEs were mild or moderate in
disability in controlled clinical trials. Reported adverse events intensity and considered unrelated to study drug.
include nausea, exacerbation of dyskinesia and impulse-control disor- Conclusions: Clinically relevant improvements in OHSA Item 1
der. Rotigotine was approved by Health Canada in 2013 and has score and standing SBP were consistent and durable with long-term
been commercially available in the country for about 1 year. Rotigo- droxidopa treatment. Droxidopa had a good safety profile and was
tine was not approved for reimbursement by Regie de lAssurance well tolerated.
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- 240
scribed population of PD patients with the results gathered in the Effect of droxidopa on fear of falling
controlled trials that led to rotigotine approval by regulatory S. Isaacson, C. Francois, G. Peng, G.J. Rowse (Boca Raton, FL,
agencies. USA)
Methods: Patients referred to the Andre Barbeau Movement Dis-
order Clinic with idiopathic PD to whom rotigotine was prescribed Objective: To assess the impact of droxidopa on the fear of fall-
were enrolled in this retrospective and observational study. ing in patients with Parkinsons disease (PD) and symptomatic neu-
Results: PD patients were administered rotigotine up to 8 mg/24h rogenic orthostatic hypotension (NOH) by a post hoc analysis of the
as monotherapy or in combination with rasagiline and/or L-3,4- falls diary.
dihydroyxphenylalanine (L-DOPA). Rotigotine improved Parkinso- Background: Symptomatic NOH results from autonomic failure
nian disability and was well tolerated in most cases. Adverse events in which there is an inadequate noradrenergic response to postural
reported by patients include impulse-control disorder, nausea and change. NOH is associated with an increased incidence of falls, and
local skin erythema, and led to drug discontinuation in some cases. studies suggest that some patients may severely limit their movement
Details regarding patients characteristics, rotigotine titration, and and activity due to high levels of anxiety resulting from previous
clinical rating of Parkinsonism with the Unified Parkinsons disease falls. Droxidopa is a norepinephrine prodrug recently approved to
Rating Scale will be presented at the conference. treat symptomatic NOH caused by primary autonomic failure (PD,
Conclusions: One year after its commercialisation in Canada, multiple system atrophy, and pure autonomic failure), dopamine
rotigotine remains seldom prescribed, mostly because of cost issues. beta-hydroxylase deficiency, and nondiabetic autonomic neuropathy.
However, the drug appears to be beneficial to patients who can Methods: Patients underwent up to 2 weeks of double-blind titra-
afford and tolerate it. 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
239 subsequently asked whether they had a fear of falling. To account
Durability of effect with long-term droxidopa treatment in for the intensity of the fear of falling, the cumulative number of fear
patients with symptomatic NOH of falls was calculated over the 8-week treatment period.
Results: A total of 62 and 58 patients reported a fall on placebo
S. Isaacson, G. Liang, J.P. Lisk, G.J. Rowse (Boca Raton, FL, USA)
and droxidopa, respectively; of these, 61 on placebo and 56 on drox-
Objective: Evaluate the long-term efficacy and safety of idopa completed the fear of falls question. More patients on droxi-
droxidopa. dopa reported no fear of falls (57% vs 43%, droxidopa vs placebo;
Background: Neurogenic orthostatic hypotension (NOH) results not significant); the total number for the cumulative fear of falls was
from insufficient noradrenergic response to orthostatic challenge. lower in patients on droxidopa (137) vs placebo (249). The correla-
Droxidopa is a norepinephrine prodrug approved to treat sympto- tion between the number of falls and fear of falls was 0.58 (Spear-
matic NOH caused by primary autonomic failure (PD, multiple sys- man correlation coefficient, P<0.001), suggesting that factors in
tem atrophy, and pure autonomic failure), dopamine beta- addition to falls affect the fear of falling.
hydroxylase deficiency, and nondiabetic autonomic neuropathy. Conclusions: These preliminary results suggest a potential effect
Methods: In Study 306, 225 patients with PD were randomized of droxidopa in reducing the fear of falling. However, caution is
to 2-week, double-blind placebo or droxidopa dose titration, followed warranted due to the small sample size and the post hoc nature of
by 8-week double-blind treatment (100600 mg TID). Study 303 the analysis.
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. 241
Efficacy measures included changes in the Orthostatic Hypotension Analysis of the incidence of supine hypertension with droxidopa
Symptom Assessment (OHSA) Item 1 score and standing systolic S. Isaacson, W.B. White, G.J. Rowse, L.A. Hewitt (Boca Raton, FL,
blood pressure (SBP). USA)
Results: In 306, OHSA Item 1 score was consistently improved
with droxidopa; relative to baseline, scores were -2.5, -2.2, and -2.3 Objective: To evaluate the incidence of supine hypertension in
units at weeks 1, 4, and 8, respectively. Mean change from baseline patients with symptomatic neurogenic orthostatic hypotension (NOH)
to week 1 was significantly greater with droxidopa vs placebo (treat- receiving droxidopa.
ment difference: -1.2 units; P=.008) with a trend favoring droxidopa Background: Droxidopa is a norepinephrine prodrug that is FDA
at week 8 (treatment difference: -0.8 units; P=.077). Responder anal- approved to treat symptomatic NOH. Its mechanism of action likely
ysis demonstrated that significantly more patients had improvements raises standing systolic blood pressure (SBP) by causing

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


vasoconstriction. As supine hypertension is common in patients with ure during the 7 day L-dopa period. Overall, the most common AEs
NOH, it is important to understand to what degree droxidopa might were nausea, dizziness & orthostatic hypotension (most AEs were
affect supine BP. mild/moderate & occurred during APO titration); no serious AEs
Methods: Data from 3 randomized, phase 3 trials that enrolled occurred.
patients with symptomatic NOH (N=666) were examined. In 2 stud- Conclusions: In patients with delayed TTO after the first morning
ies, patients with autonomic failure underwent open-label dose titra- oral L-dopa dose, subcutaneous injections of APO provided a robust
tion with droxidopa; dose titration was followed by 1-week washout motor improvement that was rapid, reliable and safe. Dose failures
and 1-week, double-blind treatment (study 1) or 7-day, open-label were significantly reduced and global impression and quality of life
treatment and 14-day, randomized withdrawal (study 2). In study 3, scales also improved. APO was generally well tolerated. Non-oral
patients with Parkinsons disease (PD) underwent double-blind dose delivery may improve motor fluctuations by avoiding GI dysfunction
titration followed by 8-week, double-blind maintenance treatment. that can delay L-dopa absorption.
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 243
after 3 minutes of standing. Severe, sustained supine hypertension
was defined as SBP >180 mmHg at all 3 supine measurements dur- Safety of sublingual APL-130277 for the treatment of OFF
ing the OST. Patients with supine SBP >180 mmHg at screening episodes in patients with Parkinsons disease
were not eligible for these trials. S. Isaacson, J. Dubow, B. Dzyngel, T. Bilbault, A. Giovinazzo, A.
Results: In the 2 studies of autonomic failure patients, the inci- Agro (Boca Raton, FL, USA)
dence of severe, sustained supine hypertension at end of study was
nominally higher in the droxidopa-treated group (study 1: 4.9%; Objective: To evaluate the safety of single treatments of APL-
study 2: 14.0%) vs placebo-treated group (study 1: 2.5%; study 2: 130277 in 19 patients with Parkinsons disease.
5.9%). In the study in PD patients (study 3), the incidence of supine Background: Parkinsons disease (PD) patients suffer from a
hypertension was nominally higher during titration in the droxidopa- variety of predictable and unpredictable OFF episodes throughout the
vs placebo-treated groups (2.6% vs 1.9%) but generally decreased disease duration. OFF periods reflect end-of-dose wearing off,
over the course of the study, with no patients observed to have delayed time-to-ON, dose failures, and morning akinesia. The only
severe, sustained supine hypertension at week 4 or week 8. Across approved acute, intermittent treatment of OFF episodes is apomor-
all studies, the incidence of sustained supine SBP >200 mmHg was phine administered subcutaneously. Treatments that are easier to
extremely low (<0.1%) in the droxidopa-treated groups. administer, convenient, and available on-demand are needed. APL-
Conclusions: In patients with symptomatic NOH who did not 130277 (APL) is a soluble film strip of apomorphine that is delivered
have severe, sustained supine hypertension at screening, the inci- sub-lingually, designed to rapidly deliver apomorphine through
dence of sustained supine hypertension with droxidopa treatment was absorption from the oral cavity mucosa.
nominally higher than placebo but did not increase over time. 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:
242 at least one OFF episode per day,  2 hours of total daily OFF time,
and predictable OFF episodes in the morning. Subjects were pre-
Efficacy of apomorphine subcutaneous injections for the medicated for 3 days with trimethobenzamide, which was continued
management of morning akinesia in Parkinsons disease during the study. Subjects presented to the clinic in the morning
S. Isaacson, M. Lew, W. Ondo, F. Pagan (Boca Raton, FL, USA) OFF state and were initially administered APL 10 mg. If a satisfac-
Objective: This multicenter, two-phase, open-label study assessed tory response was not seen, the dose of APL was increased in 5 mg
the effect of subcutaneous injection of apomorphine (APO) on first increments until a clinically meaningful ON was achieved, to a max-
dose time-to-on (TTO) in Parkinsons disease (PD) patients with imum dose of 30 mg.
morning akinesia. Results: 19 subjects received a total of 77 doses of APL, at doses
Background: Patients with PD & motor fluctuations often have ranging 10-30 mg. Overall, 13 (68.4%) patients experienced an AE,
delayed TTO after a dose of oral L-dopa. Delayed TTO can be due with most experiencing mild AEs (Table 1). The most common AEs
to gastrointestinal (GI) factors impairing L-dopa absorption, includ- were dizziness (7/19, 36.8%), somnolence (6/19, 31.6%), nausea (4/
ing delayed gastric emptying or competitive effects of protein. Deliv- 19, 21.1%) and yawning (3/19, 15.8%) (Table 2). There were no AEs
ery of non-oral (ie subcutaneous) medication may provide a more of dyskinesia. One patient experienced mild orthostatic hypotension.
rapid and predictable response by avoiding the GI system. Early One patient had a serious AE of dysphagia deemed not related to
morning off periods are common, and delayed TTO after the 1st APL by the Investigator. No subjects discontinued due to AE.
morning L-dopa dose can result in a prolonged period of morning Conclusions: Sublingual APL was safe and well tolerated in PD
akinesia, delaying the onset of L-dopa response. patients with OFF episodes. The most common AEs were mild or
Methods: Subjects who reported morning akinesia at a clinic visit moderate, and are commonly associated with dopaminergic medica-
recorded their TTO following each morning dose of L-dopa for 7 tions and/or apomorphine. No discontinuations occurred due to AEs
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- TABLE 1. Overview of AEs with APL-130277
out intolerable AEs. Subjects then recorded their TTO following
each morning dose of APO for 7 days. Mean TTO represented the N=19 n (%)
primary efficacy variable comparing APO treatment period vs base- Any AE 13 (68.4)
line L-dopa period. Safety and tolerability were also assessed. Mild AE 13 (68.4)
Results: The full analysis set included 88 subjects. Mean TTO Moderate AE 4 (21.1)
reduced from 60.86 6 18.11 minutes after L-dopa to 23.72 6 14.55 Severe AE 2 (10.5)
minutes after APO (p<0.0001). Significant improvements were also Any Related* AE 11 (57.9)
found in PGI, CGI, & EQ-5L-3D scales. Dose failures (defined as Any Serious AE 1 (5.3)
>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%) *Deemed certainly, probably, or possibly related to APL by the
diary entries following APO. Over 40% of subjects had a dose fail- Investigator

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


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


TABLE Continued Objective: To examine the choice of first symptomatic drug treat-
ment in Parkinsons disease (PD) during two years, 2005 and 2012
Motor Persistence based on the Finnish nationwide prescription register.
Diagonal movements Background: Evaluation of prescription patterns in early PD
Medium targets -0.4479 -0.4761 have shown that Levodopa and dopamine agonists are the most
Small targets -0.4214 -0.4853 favored drugs as monotherapy and that the drug preferences are
Sinusoidal movements influenced by the age of the patient. Studies also suggest that initial
Medium targets -0.6119 -0.5547 drug choices are at least moderately in adherence with recommenda-
Small targets -0.5038 -0.5668 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
Data on PD subjects only; Values are Pearson correlation values 2005 (n51,436) and 2012 (n51,607), were identified from a Finnish
(Pearson R); mRS 5 modified Rankin Scale; PDQ- nationwide register of special reimbursements for medication costs.
39 5 Parkinsons disease QoL Questionnaire. Results arranged Data on their PD drug purchases (ATC codes N04) during 2003
by increasing level of task-movement complexity (i.e., diagonal, 2006 and 20102013 were obtained from the national Prescription
sinusoidal; linear not shown) and by decreasing target size (large register, also maintained by the Social Insurance Institution of
not shown); Bold numbers represent strong correlation based on Finland.
predefined criteria (>|0.40|) Results: Overall, levodopa was the most common initial drug in
PD. Levodopa was started as the first drug in more than 80% of the
Conclusions: PMATT may be a helpful tool to measure fine cases in patients aged over 74 years. Dopamine agonists and MAO-
motor deficits in early stages of PD and could be developed as a tool B inhibitors predominated among patients aged < 60 years and the
to detect pre-clinical motor deficits in individuals at risk of PD. frequency of both drug classes decreased with advancing age. Signif-
PMATT is easily scalable to large trials and for use in field studies icant changes in the choice of the first drug occurred from the year
with centralized data collection. 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-
246 nists increased.
Medication information needs of patients with Parkinsons Conclusions: The choices of the first drug in PD show significant
disease age and time period related variation. The patterns of prescription of
T. Ker
anen, H. J
arvinen, K. Laitinen (Helsinki, Finland) the first drug in PD suggest that guidelines have an impact in clinical
Objective: To survey medication information needs of patients
with Parkinsons disease (PD) using the database of the Kuopio
Medicines Information Centre (KMIC). 248
Background: Medical treatment in PD is challenging due to the Effect of action observation combined with motor training on
age range of the patients, common co-morbidities and complexity of learning of reach-to-grasp actions in individuals with Parkinsons
PD drug regimens. Patient centered information on drugs may reduce disease
the risk of drug related adverse effects which have detrimental
effects on the quality of life of PD patient. S. Khacharoen, J. Tretriluxana, A. Pisarnpong, P. Chaiyawat
Methods: The data was collected from requests concerning PD (Nakhon Pathom, Thailand)
drugs received at the KMIC during 17.8.2002-14.4.2012. Almost all Objective: To determine the effects of action observation com-
inquiries to the KMIC service are made via telephone but the service bined with reach-to-grasp (RTG) training on learning of RTG actions
can be also reached by fax, e-mail and web form. In the KMIC, the in Parkinsons disease (PD).
inquiries and responses are documented electronically. For the pur- Background: There were findings indicating that action observa-
poses of this study only inquiries concerning the ATC-class N04 tion combined with motor training enhanced prehensile execution in
(anti-Parkinsons drugs), made by PD patients or their relatives, were individuals with stroke and PD. PD individuals also have the
included. impaired RTG planning, kinematics and coordination. It is still ques-
Results: Majority of the inquiries concerned levodopa (n5158), tionable if action observation combined with motor training could
pramipexole (n585) and selegiline (n558). The most common areas improve these impairments.
of interests were drug interactions (n5214), dosage and the use of a Methods: In Pre-training test, 16 PDs were evaluated planning
PD drug (n567) and adverse effects (n564). Interaction issues con- (measured by reaction time (RT)), kinematics and coordination dur-
cerned mostly drug-drug interactions (n5205), especially possible ing performing RTG to avoid the barrier. The kinematics were
interactions between concurrent use of an antipsychotic and a PD movement time (MT), maximum velocity (Vmax), maximum aper-
drug or the combination of levodopa and selegiline. Most common ture (Amax). The coordination of RTG were correlation coefficient
adverse effects mentioned were nausea, vomiting or other gastroin- (rmax) from cross correlation analysis between transport velocity and
testinal symptoms, hypotension, motor symptoms, hallucinations, aperture size, and associated time lag (Tmax). They were also tested
fatigue, and somnolence or falling asleep. unimanual items of the Wolf Motor Function test (WMFT). Conse-
Conclusions: This study emphasized three areas in which PD quently, they were allocated into action observation (AO) or Placebo
patients need more guidance on: drug interactions, dosage and the (P) groups. Participants in AO groups were asked to observe hand
use of drug and adverse effects. A telepharmacy service, such the action for 6 minutes alternate with physical training which using
KMIC described here, can supplement the education of given by similar tasks as in WMFT for 4 observation blocks. For P groups,
other healthcare professionals. participants were asked to train as in AO group but observe the natu-
ral landscape instead of hand action. After training, all participants
247 were tested under alll RTG actions immediately in Post-training
test and 45 minutes later in Retention test.
The choice of first symptomatic drug treatment in Parkinsons Results: AtPost-training test, there was a significant decrease in
disease MT and total time of WMFT in both groups. Moreover, the WMFT
T. Keranen, L.J. Virta (Helsinki, Finland) time was different between the 2 groups. However, the decreased

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


tmax was shown only in the AO group. At Retention test, RT, MT Methods: In this study, acute treatment effects of istradefylline
and Tmax decreased continuously until reached significant level were evaluated in two monkey models of PD (i) the gold-standard
when compared to Pre-training test only in AO group. The WMFT MPTP-treated macaque model of Parkinsonian and dyskinetic motor
time could be decreased when compared to Pre-training testin both symptoms and (ii) the chronic low dose (CLD) MPTP-treated maca-
groups. However, the WMFT time was different between the 2 que model of cognitive (working memory and attentional) deficits.
groups. Moreover, there was a diffrence in the rmax between the 2 Results: Istradefylline treatment with optimal L-DOPA enhanced
groups. motor activity but exacerbated dyskinesia. When combined with sub-
Conclusions: These results indicate that action observation com- optimal L-DOPA, istradefylline treatment alleviated PD disability to
bined with the motor training enhance the learning of RTG planning, a similar extent to the optimal dose of L-DOPA alone, while main-
kinematics, co-ordination and function in individuals with PD. 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
249 (60 mg/kg) prevented cognitive impairment induced by a therapeutic
Medications reconciliation in hospitalized Parkinsons disease dose of L-DOPA.
patients Conclusions: These data support the clinical use of istradefylline
as an adjunct treatment to a sub-threshold dose of L-DOPA in
Y. Kianirad, M. Marvanova, T. Simuni (Chicago, IL, USA)
patients with PD. Such a treatment strategy would help reduce
Objective: To determine the frequency of prescribing errors of adverse motor and cognitive complications associated with an opti-
PD medication in hospitalized PD patients. mal dose of L-DOPA, while maintaining a desired anti-Parkinsonian
Background: Parkinsons disease (PD) patients are hospitalized effect.
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 251
in an advanced stage of PD when a complex regime with multiple The effects of clinically used anti-Parkinsonian drugs on whole-
PD medications is needed requiring frequent administration. body kinematics in the MPTP-treated macaque model of
Methods: We conducted a single-center, retrospective study of Parkinsons disease: Therapeutic validation of a translational
PD patients followed in the Movement Disorder clinics at Northwest- platform for Movement Disorder research
ern University who were admitted for at least one night between W.K.D. Ko, I. Vollenweider, L. Baud, Q. Li, Y. Jianzhong, G.
August 2013 to August 2014. Electronic medical records were
Courtine, E. Bezard (Manchester, United Kingdom)
reviewed by a neurology resident.
Results: 103 PD patients (37 Females, mean age of 72.7 (SD Objective: To assess the functional impact of anti-Parkinsonian
10.6), PD duration 4.6 (2.8) were admitted between August 2013 to drugs on gait, posture and limb dysfunction in MPTP-treated maca-
August 2014. Of these patients, 3 were not on any PD medications, ques using biomechanical analyses and objective statistical
one was on DUODOPA trial. 45 patients (45.45%) remained on their procedures.
home PD medications regimen and for the rest of 54 patients Background: Anti-Parkinsonian treatment therapies are often
(54.54%), home medications were modified (29 (39%) medications developed in preclinical studies that utilise animal models of Parkin-
discontinuation, 22 (30%) change in dose, 15 (20%) change of fre- sons disease but translation into clinical benefit remains uncommon.
quency, 8 (11%) change of dosage form). The reasons for medica- A major contributing factor to this predicament is an inconsistency
tions changes were the following: not documented in 30 (41%), 28 in methodological approaches between preclinical and clinical
(38%) inaccurate home medication documentation by medical staff, research. There is a lack of consensus on measures for rating motor
7 (11%) unavailable or none formulary medication, 4 (5%) pharmacy performance and defining useful experimental endpoints.
error and 4 (5%) due to medical reason (NPO, mental status, Methods: We employ the experimental platform of whole-body
dysphagia). kinematic analyses in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Conclusions: There was a high rate of unintended changes of PD (MPTP)-treated macaques, the gold-standard model for Parkinsonian
medications in this cohort of hospitalized PD patients. The data sup- motor symptoms, for evaluating clinically used anti-Parkinsonian
port importance of on-going staff education and development of agents. Animals were trained to perform unconstrained locomotor
standardized protocols for administration of PD medications in the tasks, following which pharmacological treatments were tested in the
hospital setting. same conditions.
Results: These unbiased quantitative analyses of motor function
during unrestricted movement allowed mechanistic identification of
250 clinically effective treatments against Parkinsonian motor disabilities
An evaluation of istradefylline treatment on motor and cognitive (i.e. L-DOPA, pramipexole, ropinirole, amantadine and istradefyl-
disabilities in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine line). The high resolution of these analyses dissociates specific clus-
(MPTP)-treated macaque models of Parkinsons disease ters of motor control parameters that are improved from those that
W.K.D. Ko, Q. Li, Y. Jianzhong, E. Pioli, E. Bezard (Manchester, remain affected. For example, L-DOPA enhanced movement velocity
United Kingdom) and stride length during walking, but had no effect on stance dura-
tion or foot elevation.
Objective: To assess the motor and cognitive function in MPTP- Conclusions: These recording methodologies and analytical tools
treated macaques following acute administration of istradefylline for assessment of motor control capacities are readily transferable to
(60-100 mg/kg) combined with optimal or sub-optimal doses of L- a clinical setting, offering an efficient and reliable avenue for pre-
DOPA. dicting/evaluating therapeutic benefit of novel treatments. This meth-
Background: Istradefylline (KW-6002), an adenosine A2A recep- odological approach, which has been validated in human patients,
tor antagonist used adjunct with L-3,4-dihydroxyphenylalanine (L- bridges the gap between preclinical and clinical research. Together,
DOPA), increases ON-time in patients with Parkinsons disease these tools support (i) greater translational efficacy of novel thera-
(PD). However, an effective combined drug treatment strategy for peutic interventions and (ii) objective fine-tuning of existing drug
reducing dyskinesia and cognitive impairments commonly associated treatments used in patients with Parkinsonian or other neuro-motor
with a therapeutic dose of L-DOPA remains to be determined. disorders.

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


252 Detectable Change for these measures. Results were not maintained
at one month follow up. No statistically significant changes noted on
The impact of levodopa-carbidopa intestinal gel on health-related the PDQ-39.
quality of life in Parkinsons disease Conclusions: We found that a 12 week, twice weekly, 60 minute
N. Kov  G. Deli, E. Bosny
acs, Z. Aschermann, P. Acs, ak, J. Janszky, supervised group-based exercise program based on the PWR!TM
S. Komoly (P ecs, Hungary) Framework induced changes in functional mobility among individu-
Objective: Our aim was to assess the improvement in quality of als with PD. However, these changes were not sustained one month
life of PD patients treated with LCIG at University of Pecs. after the intervention. These findings suggest that there is a need for
Background: The levodopa/carbidopa intestinal gel (LCIG) ther- ongoing community exercise programs specific to individuals with
apy can improve the severe fluctuations associated with advanced PD.
Parkinsons disease (PD).
Methods: Eighteen PD patients were evaluated (age: 69.5 6 4,7 254
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 Withdrawn by Author
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- 255
motor symptoms (PD Sleep Scale 2nd version: PDSS-2, Epworth Parkinsons disease evaluation of range of motion t