Objective: This study aimed to identify characteristic parkinsonism patterns across PD, MSA and PSP, and evaluate their utility in early differentiation.

Background: Parkinson’s disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP) are neurodegenerative disorders sharing overlapping parkinsonism features in early stages, posing significant challenges to differential diagnosis. Early and accurate discrimination among these entities is critical for tailored therapeutic interventions and prognostic stratification.

Method: A multicenter cohort of 297 patients (PD: n=130; PSP: n=105; MSA-P: n=62) underwent standardized assessments using the Movement Disorder Society Unified Parkinson’s Disease Rating Scale Part III (MDS-UPDRS-III) and levodopa challenge tests. Six motor subdomains were analyzed: tremor, bradykinesia-rigidity, axial symptoms, gait dysfunction, laterality, and dopaminergic responsiveness. Between-group differences were assessed via ANCOVA with disease duration. Softmax regression models were constructed for diagnostic classification.

Results: Distinct phenotypic trajectories emerged: PD exhibited milder motor deficits with prolonged disease duration, MSA-P demonstrated rapid disability progression (shortest survival), while PSP showed male predominance and later symptom onset. Axial symptom burden and gait dysfunction provided robust diagnostic discrimination. Post-levodopa axial improvement ≥30% strongly favored PD over atypical parkinsonism (APD, p<0.001). PSP-RS displayed predominant axial/gait involvement (68.7% of total MDS-UPDRS-III scores vs. 41.2% in PD, p<0.001) with minimal levodopa response. Tremor asymmetry (left-right difference >5 points) and lower limb sparing effectively distinguished PD from APD (AUC=0.89). Bradykinesia-rigidity severity correlated with global disability progression (r=0.76, p=0.003).

Conclusion: Quantitative analysis of parkinsonism patterns, PD, MSA-P, and PSP can be effectively distinguished.. Key indicators include: 1) axial symptom levodopa responsiveness for PD vs. APD; 2) axial/gait predominance for PSP; 3) asymmetric tremor and lower limb sparing for PD identification.

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Three Components Significantly Associated with PSP

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MDS Abstracts - https://www.mdsabstracts.org/abstract/differentiating-parkinsonism-and-related-diseases-by-specific-parkinsonism-patterns/