Objective: The objective of this study was to examine whether handwriting abnormalities are present prior to clinically manifest chorea in Huntington’s disease (HD) and can serve as an early biomarker of transition to manifest illness.

Background: Prior research has demonstrated that measures of handwriting kinematics are sensitive to mild pre-clinical motor abnormalities stemming from other basal ganglia disorders. The presence of a biomarker early in the transition period in HD may help efforts to pharmacologically manage or delay onset.

Method: Thirty gene-positive pre-manifest (PM), 38 symptomatic HD, and 25 normal control (NC) subjects completed handwriting tasks consisting of circles, loops, sentences and spirals with a non-inking pen on a standard digitizing tablet. Multiple measures of pen stroke kinematics and pressure were extracted from these trials. The clinical status of each participant was characterized using the UHDRS and several disease burden scores.

Results: There were statistically significant differences between HD and NC subjects on several handwriting movement variables, including longer and more variable stroke durations, decreased smoothness, and increased and more variable pen pressures in HD over multiple handwriting tasks.  Among the more robust correlations between handwriting kinematics and clinical variables, we found significant positive associations between BOP and stroke duration, CAP and stroke duration, and UHDRS Total Motor Score and pen pressure variability.  With regard to predictive modeling, results from a backward stepwise analysis (based on kinematic and pen pressure scores from three handwriting tasks) led to a 7-factor model having 90% sensitivity in classifying PM subjects and 80% specificity in classifying NC subjects with an overall accuracy of 85.4% (F7,47=6.70; p<0.0001).

Conclusion: Handwriting kinematics can detect movement abnormalities in individuals at risk for HD prior to the onset of even mild motor dysfunction and may serve as a sensitive and objective quantitative measure of the clinical efficacy of existing and novel pharmacotherapies.

(Some data from this abstract was previously presented at the 2018 HSG Meeting in Houston, TX)

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MDS Abstracts - https://www.mdsabstracts.org/abstract/can-handwriting-movement-abnormalities-serve-as-an-early-biomarker-of-transition-to-manifest-huntingtons-disease/