Exploring the Association Between Parkinson’s Disease and Multiple Sclerosis: A Meta-analytic Overview
Yagya Adhikari1, Jamir Pitton Rissardo1, Sangam Shah2, Omar Elmandouh1, Ana Leticia Fornari Caprara1, Ian M. Walker1
1Cooper University Hospital, 2Youth for TPNW
Objective:
To evaluate the bidirectional relationship between Parkinson’s disease (PD) and multiple sclerosis (MS), including neuromyelitis optica spectrum disorder (NMOSD), using population-based studies and meta-analytic methods.
Background:
PD and MS are traditionally considered distinct neurological disorders, but emerging evidence suggests potential overlapping mechanisms. Clarifying their temporal associations may provide insight into shared pathophysiology and inform clinical practice.
Design/Methods:
A systematic review of the PubMed database was conducted to identify population-based studies examining the temporal association between PD and MS, including NMOSD. Studies were included if they reported incidence data for MS following PD (PD→MS), PD following MS (MS→PD), or PD following NMOSD. Nine eligible studies were identified. A meta-analysis was performed on five studies with complete comparator data using a random-effects model (DerSimonian-Laird estimator), with risk ratio (RR) as the summary measure. Subgroup analyses were conducted for each direction of association. Publication bias was assessed using Egger’s test, Begg’s test, trim-and-fill method, and fail-safe N calculations (Rosenthal, Orwin, and Rosenberg approaches).
Results:
Three studies evaluated PD→MS, five assessed MS→PD, and one examined NMOSD→PD. The overall random-effects RR was 1.58 (95% CI: 0.17–2.99). Subgroup analysis showed a RR of 1.74 (95% CI: −0.81 to 4.31) for PD→MS, 2.01 (95% CI: 1.34 to 2.68) for MS→PD, and 0.79 (95% CI: −0.03 to 1.62) for NMOSD→PD. Heterogeneity was low (I² = 1%), although Cochran’s Q was significant (Q = 80.5, p < 0.0001). No publication bias was detected. Rosenthal’s fail-safe N was 51, Orwin’s was 5, and Rosenberg’s was 28, indicating robustness of the findings.
Conclusions:
Meta-analytic evidence suggests a potential bidirectional association between PD and MS, with a stronger link observed from MS to PD. Findings appear robust against publication bias but are limited by heterogeneity and missing comparator data.
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