Differences in Levodopa Response for Progressive and Non-Progressive Micrographia in Parkinson's Disease.

Background: Micrographia, one element of the dysgraphia of Parkinson's disease (PD), may be classified according to the presence or absence of a decremental pattern. The decremental form, progressive micrographia, is an expression of the sequence effect seen generally in bradykinesia. Its responsiveness to levodopa has not been evaluated kinematically. Objectives: Aim of this study is to investigate the difference in levodopa response for progressive and non-progressive micrographia. Methods: Twenty-four PD patients and 24 age-matched repeatedly wrote the letter e on a computerized digital tablet. PD patients performed the task two times, in a defined off state and again after levodopa. Scripts were classified as progressive micrographia (PDPM) or non-progressive micrographia (PDNPM) depending on whether a 10% decrement was seen between the first and final characters of a line of lettering. Results: While levodopa produced a similar response on the MDS-UPDRS motor scale for the two groups, the effect on the two types of micrographia was different. While writing speed improved significantly in both groups after levodopa, the responses were over twofold greater for PDNPM. Moreover, the decremental features of PDPM-in size, speed, and pen-pressure-were largely unaltered by a levodopa dose. Conclusions: Progressive micrographia is less responsive to levodopa. Our findings agree with research showing that the sequence effect of bradykinesia is relatively resistant to medication. Yet we did not find a weaker overall levodopa motor benefit. Caution is needed in the interpretation of such micrographia measurements for estimating drug responses.

A Kinematic Study of Progressive Micrographia in Parkinson's Disease.

Progressive micrographia is decrement in character size during writing and is commonly associated with Parkinson's disease (PD). This study has investigated the kinematic features of progressive micrographia during a repetitive writing task. Twenty-four PD patients with duration since diagnosis of <10 years and 24 age-matched controls wrote the letter "e" repeatedly. PD patients were studied in defined off states, with scoring of motor function on the Unified Parkinson's Disease Rating Scale Part III. A digital tablet captured x-y coordinates and ink-pen pressure. Customized software recorded the data and offline analysis derived the kinematic features of pen-tip movement. The average size of the first and the last five letters were compared, with progressive micrographia defined as >10% decrement in letter stroke length. The relationships between dimensional and kinematic features for the control subjects and for PD patients with and without progressive micrographia were studied. Differences between the initial and last letter repetitions within each group were assessed by Wilcoxon signed-rank test, and the Kruskal-Wallis test was applied to compare the three groups. There are five main conclusions from our findings: (i) 66% of PD patients who participated in this study exhibited progressive micrographia; (ii) handwriting kinematic features for all PD patients was significantly lower than controls (p < 0.05); (iii) patients with progressive micrographia lose the normal augmentation of writing speed and acceleration in the x axis with left-to-right writing and show decrement of pen-tip pressure (p = 0.034); (iv) kinematic and pen-tip pressure profiles suggest that progressive micrographia in PD reflects poorly sustained net force; and (v) although progressive micrographia resembles the sequence effect of general bradykinesia, we did not find a significant correlation with overall motor disability, nor with the aggregate UPDRS-III bradykinesia scores for the dominant arm.

Effect of levodopa on handwriting tasks of different complexity in Parkinson's disease: a kinematic study.

Levodopa treatment does improve Parkinson's disease (PD) dysgraphia, but previous research is not in agreement about which aspects are most responsive. This study investigated the effect of levodopa on the kinematics of writing. Twenty-four patients with PD of less than 10 years duration and 25 age-matched controls were recruited. A practically defined off state method was used to assess the levodopa motor response, measured on the Unified Parkinson's Disease Rating Scale Part III. The kinematic features for six handwriting tasks involving different levels of complexity were recorded from PD patients in off and on states and from the control group. Levodopa is effective for simple writing activities involving repetition of letters, denoting improved fine motor control. But the same benefit was not seen for copying a sentence and a written category fluency test, tasks that carry memory and cognitive loads. We also found significant differences in kinematic features between control participants and PD patients, for all tasks and in both on and off states. Serial testing of handwriting in patients known to be at risk for developing PD might prove to be an effective biomarker for cell loss in the substantia nigra and the associated dopamine deficiency. We recommend using a panel of writing tasks including sentence copying and memory dependence. Dual-task effects may make these activities more sensitive to early motor deficits, while their weaker levodopa responsiveness would cause them to be more stable indicators of motor progression once symptomatic treatment has been commenced.

Efficacy of Guided Spiral Drawing in the Classification of Parkinson's Disease.

BACKGROUND: Change of handwriting can be an early marker for severity of Parkinson's disease but suffers from poor sensitivity and specificity due to inter-subject variations. AIM: This study has investigated the group-difference in the dynamic features during sketching of spiral between PD and control subjects with the aim of developing an accurate method for diagnosing PD patients. METHOD: Dynamic handwriting features were computed for 206 specimens collected from 62 Subjects (31 Parkinson's and 31 Controls). These were analyzed based on the severity of the disease to determine group-difference. Spearman rank correlation coefficient was computed to evaluate the strength of association for the different features. RESULTS: Maximum area under ROC curve (AUC) using the dynamic features during different writing and spiral sketching tasks were in the range of 0.67 to 0.79. However, when angular features ($\boldsymbol{\varphi }$ and ${\boldsymbol{p}_{\boldsymbol{n}}}$) and count of direction inversion during sketching of the spiral were used, AUC improved to 0.933. Spearman correlation coefficient was highest for ϕ and ${\boldsymbol{p}_{\boldsymbol{n}}}$. CONCLUSION: The angular features and count of direction inversion which can be obtained in real-time while sketching the Archimedean guided spiral on a digital tablet can be used for differentiating between Parkinson's and healthy cohort.

Distinguishing Different Stages of Parkinson's Disease Using Composite Index of Speed and Pen-Pressure of Sketching a Spiral.

The speed and pen-pressure while sketching a spiral are lower among Parkinson's disease (PD) patients with higher severity of the disease. However, the correlation between these features and the severity level (SL) of PD has been reported to be 0.4. There is a need for identifying parameters with a stronger correlation for considering this for accurate diagnosis of the disease. This study has proposed the use of the Composite Index of Speed and Pen-pressure (CISP) of sketching as a feature for analyzing the severity of PD. A total of 28 control group (CG) and 27 PD patients (total 55 participants) were recruited and assessed for Unified Parkinson's Disease Rating Scale (UPDRS). They drew guided Archimedean spiral on an A3 sheet. Speed, pen-pressure, and CISP were computed and analyzed to obtain their correlation with severity of the disease. The correlation of speed, pen-pressure, and CISP with the severity of PD was -0.415, -0.584, and -0.641, respectively. Mann-Whitney U test confirmed that CISP was suitable to distinguish between PD and CG, while non-parametric k-sample Kruskal-Wallis test confirmed that it was significantly different for PD SL-1 and PD SL-3. This shows that CISP during spiral sketching may be used to differentiate between CG and PD and between PD SL-1 and PD SL-3 but not SL-2.