Objective: To evaluate digital handwriting kinematics as a useful tool to quantify the acute motor response to dopaminergic treatment in patients with Parkinson’s disease (PD).

Background: Dysgraphia is a frequent manifestation of PD and reflects early deficits in fine motor function (1). Despite its impact on the life of PD patients, handwriting is rarely evaluated quantitatively and is only assessed through a single patient-reported item in the MDS-UPDRS (2). This assessment can be extended using digitizing tablets that distinguish PD patients from healthy controls (3), enable objective quantification of kinematic handwriting parameters, provide a sensitive approach to characterize PD dysgraphia, and detect dopaminergic-related changes in fine motor function (4).

Method: Twenty-six patients with PD were evaluated in a medication-OFF state after 18 hours of treatment withdrawal. Then, they received a single dose of inhaled levodopa (66 mg) and were reassessed 30 minutes later. Handwriting was recorded while participants wrote a standardized sentence on a digitizing tablet; 19 kinematic handwriting parameters were extracted and compared Intra-subject between OFF and ON states using paired test. The same handwriting parameters were correlated with the corresponding MDS-UPDRS III score using Spearman correlations.

Results: Several digital handwriting kinematic parameters changed significantly following levodopa inhalation. These changes paralleled clinical motor improvement, with MDS-UPDRS III scores decreasing from 22.77 ± 8.01 at OFF state to 15.35 ± 9.09 30 minutes after inhalation (p < 0.001). Pen contact time (t_down) and in-air time (t_up) were significantly reduced, indicating faster and more continuous writing movements. Pressure entropy also decreased significantly, suggesting improved motor control. Changes in handwriting parameters were not significantly correlated with MDS-UPDRS III scores; among then, Δt_down showed the closest-to-significance association (ρ = −0.34; p = 0.088).

Conclusion: Digital handwriting analysis is a non-invasive tool for quantifying PD dysgraphia and its response to dopaminergic treatment. It may provide a precise characterization of fine motor modulation and support clinical monitoring and treatment evaluation in PD. These findings suggest that digital handwriting analysis could be considered an objective digital biomarker.

References: 1. Letanneux A, Danna J, Velay JL, Viallet F, Pinto S. From micrographia to Parkinson’s disease dysgraphia. Movement Disorders. 2014;29(12):1467–1475.
2. (Goetz et al., 2008) MDS Goetz CG, Tilley BC, Shaftman SR, Stebbins GT, Fahn S, Martinez-Martin P, Poewe W, Sampaio C, Stern MB, Dodel R, Dubois B, Holloway R, Jankovic J, Kulisevsky J, Lang AE, Lees A, Leurgans S, LeWitt PA, Nyenhuis D, Olanow CW, Rascol O, Schrag A, Teresi JA, van Hilten JJ, LaPelle N; Movement Disorder Society UPDRS Revision Task Force. Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord. 2008 Nov 15;23(15):2129-70. doi: 10.1002/mds.22340. PMID: 19025984.
3. Diaz-Feliz L, Sanz-Cartagena P, Faundez-Zanuy M, Arbelo-Gonzalez J, Garcia-Ruiz P. Computerized assessment of handwriting in de novo Parkinson’s disease: a kinematic study. Parkinsonism & Related Disorders. 2024;126:107072
4. Eichhorn TE, Gasser T, Mai N, Marquardt C, Arnold G, Schwarz J, Oertel WH. Computational analysis of open loop handwriting movements in Parkinson’s disease: a rapid method to detect dopamimetic effects. Movement Disorders. 1996;11(3):289–297.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/digital-handwriting-analysis-a-useful-tool-to-quantify-acute-dopaminergic-response-in-parkinsons-disease/