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

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.

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.

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.

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).

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.