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DOI 10.1007/s00415-013-6996-x
ORIGINAL COMMUNICATION
Received: 5 May 2013 / Revised: 3 June 2013 / Accepted: 4 June 2013 / Published online: 16 June 2013
Springer-Verlag Berlin Heidelberg 2013
Introduction
To date, clinical assessment remains the gold standard in
the diagnosis of Parkinsons disease (PD). In recent years,
an effort has been made to identify an objective biomarker
by organized initiatives such as the Parkinson Progression
Marker Initiative (PPMI) [1] and the Longitudinal and
Biomarker Study-Parkinsons disease [2] using varied
approaches including examination of blood, saliva, exhaled
breath [3], cerebrospinal fluid and neuroimaging. Finding a
biomarker is important not only for the diagnosis and follow-up of disease progression but also for testing of
potential neuroprotective interventions with the hope of
screening and preventing this disease [4, 5]. In striving for
a tool that will objectively diagnose PD, the US Food and
Drug Administration (FDA) recently approved the dopamine transporter (DAT) ligand [(123)I] ioflupane, with
single-photon emission computed tomography (SPECT,
DaTscan) for evaluating parkinsonian syndromes and for
distinguishing Parkinsons disease from essential tremor.
However, this testing modality exposes patients to radioactive material and does not distinguish Parkinsons disease from multiple system atrophy or corticobasal
degeneration [6].
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Subjects
Outcome Measures
Controls (n = 20)
PD (n = 20)
p value
61.66 10.00
61.18 9.11
NS
11 (55)
13.78 1.65
11 (55)
12.80 1.70
NS
NS
MMSE
30 0
29.88 0.33
NS
2 0.79
UPDRS
25.05 14.04
Disease duration
8.05 3.90
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Statistical analysis
MANOVA analyses were used to test for group differences
(controls vs. PD) across the computerized spatial, temporal
and pressure measures for each of the two writing tasks
2359
Results
Results of the MANOVAs for both the name writing
(F(6,32) = 6.72, Wilks Lambda = 0.442 p \ 0.001
g2 = 0.558) and address copying tasks (F(6,31) = 14.77,
Wilks Lambda = 0.259 p \ 0.001 g2 = 0.741), showed
significant group effects. The univariate ANOVAs indicated significant differences between the groups for several
measures of the name writing task and for all measures of
the address copying task. The means and standard deviations are presented in Table 2.
In order to further analyze the mean stroke duration,
t-tests were conducted for the mean stroke duration on
paper and in air for the address copying task. Mean
stroke duration on paper (controls 0.19 0.02 s vs. PD
0.27 0.10 s p = 0.001) and in air (controls
0.21 0.06 s vs. PD 0.38 0.15 s p \ 0.001) were significantly different between controls and PD patients.
For both tasks, compared with controls, PD participants
wrote significantly smaller letters, applying significantly
less pressure on the writing surface, and requiring significantly more performance time. The gap in the stroke
duration in air was more dramatic than the gap in the
Table 2 Kinematic measures
for writing tasks
Measures
Discussion
Using two simple short and routine writing tasks, PD
patients could be distinguished from healthy controls with
very high accuracy. None of the controls were categorized
as suffering from PD while one of the PD patients was
incorrectly categorized as being healthy. Thus, taken
together these two handwriting tasks had 95 % sensitivity
and 100 % specificity. Handwriting was chosen as a possible biomarker for PD based on previous reports of micrographia appearing many years before the diagnosis of
PD [19]. It is a noninvasive method that is easily performed. Hence, the sensitivity and specificity for the distinction of PD patients from healthy controls could allow a
quick and simple initial diagnosis in a non-specialist
Copying an address
Healthy mean
(SD)
Healthy mean
(SD)
PD mean (SD)
PD mean (SD)
Spatial measures
Stroke length (cm)
0.96 (0.40)
0.60 (0.34)*
0.75 (0.14)
0.53 (0.16)**0
0.32 (0.11)
0.18 (0.07)**
0.23 (0.04)
0.17 (0.04)**0
0.47 (0.16)
0.36 (0.25)
0.35 (0.07)
0.27 (0.07)**0
0.16 (0.04)
0.21 (0.09)
0.20 (0.04)
0.32 (0.12)**
Velocity (cm/sec)
5.18 (1.26)
3.10 (1.30)**
4.86 (0.96)
2.67 (0.91)**
783.55 (149.04)
591.77 (160.98)**
788.61 (146.59)
603.29 (164.08)**
Temporal measures
Pressure measures
Pressure
(Non-scaled units
01,024)
* p \ 0.05, ** p \ 0.01
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2360
Loading
0.496
Copying an address
Copying an address
-0.477
0.422
Copying an address
0.392
Copying an address
-0.389
-0.219
0.183
-0.143
123
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