Is being asymmetric a bad thing? Insights from a longitudinal observational study on STN-DBS Parkinson's disease

Motor asymmetry is a characteristic feature of Parkinson's disease (PD); however, its definition and long-term evolution and clinical implications remain unclear.

Assess the trajectory of motor asymmetry at 3 and 5 years post-STN-DBS, as well as its impact on axial symptoms and quality of life (QoL).

Utilizing data from the PREDISTIM cohort, which includes over 500 patients and is representative of a large advanced PD population, we analyzed motor asymmetry (defined as the difference between right and left appendicular motor scores) at 1, 3, and 5 years following STN-DBS. Absolute and normalized (normalization based on global motor severity) asymmetry were quantified using MDS-UPDRS III scores in the Stim ON/Med ON state. Axial symptoms and QoL were assessed using the axial subscore and PDQ-39, respectively. Statistical analyses included mediation models to explore the interplay between asymmetry, motor severity, and clinical outcomes.

Normalized motor asymmetry decreased over time, despite an increase in absolute asymmetry and overall motor severity. Higher normalized asymmetry was associated with lower axial scores and better QoL. Mediation analyses confirmed that the relationship between motor asymmetry, axial scores, and QoL was largely associated with overall motor severity.

These findings suggest that a higher normalized motor asymmetry in advanced PD stage reflects an appendicular phenotype, which is associated with better QoL. Its reduction over time corresponds to increased axial involvement.