Earlier Postural and Cognitive Milestones in Parkinson's Disease with Comorbid Myasthenia Gravis

BACKGROUND: The coexistence of Parkinson's disease (PD) and myasthenia gravis (MG) is poorly characterized. Overlapping axial symptoms and fatigability may complicate diagnosis and interpretation of PD-related milestones. OBJECTIVES: The aim of the study was to characterize the phenotype of coexistent PD and MG (PD + MG) and explore differences in the timing of PD-related milestones compared to matched PD-only controls. METHODS: In this matched-cohort study, PD patients with serologically and/or electrophysiologically confirmed MG were retrospectively identified from clinical records and compared with sex-, race-, age-at-PD-onset-, disease-duration-matched PD (PD-only) controls prospectively assessed within the Cincinnati Cohort Biomarker Program. Disease milestones were Hoehn & Yahr (H&Y) ≥ 3 and Montreal Cognitive Assessment (MoCA) < 26. Time-to-event analyses used Kaplan-Meier and Cox proportional-hazards models adjusted for sex, race, age-at-PD onset, and disease duration. RESULTS: We identified 21 PD + MG patients with predominantly ocular MG and autoimmune diseases. Compared to 210 matched PD-only controls, postural instability (71% vs. 12%) and cognitive impairment (57% vs. 4.8%) were more prevalent (P < 0.001). Median time from PD onset to H&Y ≥ 3 and MoCA < 26 was shorter in PD + MG, with milestones documented at or near PD diagnosis, versus 5 and 7 years in controls (P < 0.001). PD + MG patients showed increased adjusted hazard ratios (HR) for H&Y ≥ 3 (HR: 10.6; 95% confidence interval [CI], 3.83-29.4; P < 0.001) and MoCA < 26 (HR: 35.3; 95% CI, 12.8-97.1; P < 0.001). CONCLUSIONS: PD + MG was associated with earlier documented postural and cognitive milestones than matched PD-only controls, although interpretation warrants caution given the retrospective ascertainment for PD + MG cases. Oculobulbar symptoms, disproportionate axial impairment, or fluctuating weakness should prompt investigation as potential indicators of concomitant MG.