In a retrospective cross-sectional analysis of 184 PD patients (44 with STN-DBS), levodopa administration—independent of DBS status—was associated with increased motor asymmetry and higher axial-to-appendicular ratios, with a larger AAR change observed in the STN-DBS cohort.

The study has moderate translational value because it informs clinical trial endpoint selection and patient stratification by showing that dopaminergic therapy can reshape motor phenotype, but it offers limited mechanistic targets or direct therapeutic leads for drug discovery.

BACKGROUND: Motor asymmetry and axial symptoms represent partially distinct dimensions of the Parkinson's disease (PD) motor phenotype. Although subthalamic nucleus deep brain stimulation (STN-DBS) and dopaminergic therapy are known to influence motor presentation, the clinical expression of lateralized and axial motor domains under different treatment strategies remains incompletely characterized in real-world settings. OBJECTIVES: To compare motor asymmetry and axial involvement between PD patients treated with STN-DBS and those receiving medical therapy alone, and to examine OFF - ON levodopa-related modulation of these motor domains. METHODS: In this retrospective cross-sectional study, 184 consecutive PD patients (44 with STN-DBS and 140 without DBS) underwent standardized evaluations in medication 'OFF' and 'ON' states. Motor Asymmetry Index (MAI) and Axial-to-Appendicular Ratio (AAR) were calculated using MDS-UPDRS-III subscores. Between-group comparisons and within-group OFF - ON changes were analyzed, adjusting for disease duration and baseline motor severity. RESULTS: Unadjusted analyses showed lower MAI values in the STN-DBS group in the OFF state (p = 0.045), suggesting greater symmetry; however, this association was not significant after adjustment. Levodopa was associated with a consistent shift toward increased motor asymmetry and higher axial-to-appendicular ratios across both groups (all p < 0.01). The magnitude of AAR change was greater in the STN-DBS cohort. CONCLUSIONS: In this retrospective cross-sectional study, levodopa was associated with a shift in motor phenotype characterized by increased asymmetry and axial-to-appendicular burden, independent of DBS status. These findings suggest that dopaminergic therapy may reshape motor expression rather than uniformly improve motor function.