Symptom onset lateralization and bilaterality in Parkinson's disease: Clinical implications of motor and non-motor profiles

Background

Although motor symptom asymmetry is a hallmark of Parkinson's disease (PD), the clinical relevance of symptom-onset laterality—particularly with respect to handedness and bilateral onset—remains underexplored.

Objective

To determine how symptom-onset patterns—right vs. left, dominant vs. non-dominant, and bilateral vs. unilateral—relate to motor and non-motor clinical features in PD.

Methods

We retrospectively analysed 460 PD patients. Onset side and handedness were recorded from history; standardised assessments included MDS-UPDRS, HY, NMSS, and PDQ-39. Multivariate logistic regression identified independent correlates of onset side.

Results

Right-sided onset predicted higher ON-state motor burden (MDS-UPDRS Part 3; OR = 1.48, 95 % CI 1.05–2.09, p = 0.025). A similar association was seen for dominant-side onset (OR = 1.46, 95 % CI 1.04–2.06, p = 0.029). Bilateral onset—observed in 4 % of the cohort yet often excluded from prior studies—displayed a distinct profile: akinetic-rigid phenotype (OR = 2.13, p = 0.008), HY stage ≥3 (OR = 2.40, p = 0.025), and greater mood/cognition burden on the NMSS (OR = 2.36, p = 0.022). Conversely, bilateral onset was inversely related to OFF-state MDS-UPDRS Part 3 scores (OR = 0.31, p = 0.029).

Conclusions

Symptom-onset lateralization in PD carries clinically meaningful implications. Dominant-side onset signals higher residual motor impairment despite dopaminergic therapy, whereas bilateral onset marks a more advanced, non-tremor–dominant phenotype with prominent mood–cognition involvement. Systematic inclusion of bilateral cases and consideration of handedness enhance patient stratification and may inform prognostic counseling and therapeutic planning.