Objective: To explore differences in movement control between PRKN-PD and gene-negative YOPD patients using a structured handwriting task.

Background: Idiopathic Parkinson’s disease (IPD) symptoms are caused by progressive accumulation of cortical Lewy bodies and the loss of striatal dopaminergic afferents arising from the midbrain substantia nigra pars compacta (SNc). PRKN-related parkinsonism is pathologically different to IPD, characterised by few or no Lewy bodies and SNc degeneration limited to its ventral tier (Doherty et al., 2013).

The striatum is spatially organised into functionally distinct but integrated regions. Each region communicates with separate cortical areas and function via corticostriatal loops. The sensorimotor loop governs automatic (habitual) movements and the associative loop controls outcome-dependent, goal-directed movements (Redgrave et al., 2010).

In IPD, automatic movements become impaired first. Functional imaging studies show recruitment of goal-directed cortical regions as a compensatory strategy to preserve movements, albeit in a less economical and more effortful fashion. As SNc degeneration and Lewy body burden progresses, this plasticity predictably fails(Ballanger and Boulinguez, 2024). As PRKN-PD patients do not have Lewy bodies and lose only the ventral SNc, they may be able to compensate and continue to move better even late in disease. We hypothesised that handwriting, as a lifetime habit, could be used to interrogate differences in corticostriatal loop function and movement control in PRKN-PD patients.

Method: 47 native English speakers (29 gene-negative YOPD, 18 PRKN-PD, matched for motor symptom duration) transcribed 40 words onto a digital tablet under four conditions: signature (automatic), English, Polish and Greek (goal-directed). We analysed kinematic and spatiotemporal variables using SPSS.

Results: We found across all language conditions group differences in mean stroke velocity (p = 0.034) and stroke length (p=0.007). We expect further analysis to reveal differences in performance between language conditions.

Conclusion: This handwriting task is a useful and non-invasive method for delineating motor differences between PRKN and gene-negative IPD. It could provide a window into pathophysiological differences at a corticostriatal level and help us understand human movement control.

References: Ballanger, B., Boulinguez, P., 2024. Motor compensation in Parkinson’s disease: an empirical challenge with clinical implications. Brain 147, 3648–3650. https://doi.org/10.1093/brain/awae328
Doherty, K.M., Silveira-Moriyama, L., Parkkinen, L., Healy, D.G., Farrell, M., Mencacci, N.E., Ahmed, Z., Brett, F.M., Hardy, J., Quinn, N., Counihan, T.J., Lynch, T., Fox, Z.V., Revesz, T., Lees, A.J., Holton, J.L., 2013. Parkin Disease: A Clinicopathologic Entity? JAMA Neurol. 70, 571–579. https://doi.org/10.1001/jamaneurol.2013.172
Redgrave, P., Rodriguez, M., Smith, Y., Rodriguez-Oroz, M.C., Lehericy, S., Bergman, H., Agid, Y., DeLong, M.R., Obeso, J.A., 2010. Goal-directed and habitual control in the basal ganglia: implications for Parkinson’s disease. Nat. Rev. Neurosci. 11, 760–772. https://doi.org/10.1038/nrn2915

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MDS Abstracts - https://www.mdsabstracts.org/abstract/handwriting-in-prkn-pd-a-study-of-movement-control/