Seasonality of Initial Attack Onset in AQP4+ NMOSD, MOGAD, and MS: Observations from a US-based Multicenter Cohort
Shuvro Roy1, Georgios Gakis2, Philippe-Antoine Bilodeau3, Anastasia Vishnevetsky3, Mattia Wruble Clark3, Joao Vitor Mahler3, Yana Said2, Angeliki Filippatou2, Yishang Huang2, Yujie Wang1, Ellen Mowry2, Kathryn Fitzgerald2, Michael Levy3, Elias Sotirchos2
1Neurology, University of Washington, 2Neurology, Johns Hopkins University, 3Neurology, Mass General Brigham
Objective:
To assess the seasonal variation of initial attack onset in AQP4+NMOSD, MOGAD and MS.
Background:
Seasonal variation in attacks of central nervous system (CNS) neuroinflammatory conditions has been reported, including in different underlying conditions with distinct pathophysiology, including multiple sclerosis (MS), aquaporin-4 IgG seropositive neuromyelitis optica spectrum disorder (AQP4+ NMOSD) and myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD). However, reports regarding seasonal variation in MS, MOGAD and AQP4+NMOSD initial attack onset are conflicting.
Design/Methods:
This study included 318 AQP4+NMOSD, 420 MOGAD and 1,128 relapsing-onset MS participants, with initial attacks between January 2005 and May 2025, and documented month and year of disease onset. AQP4+NMOSD and MOGAD participants were included from 3 US centers, whereas MS participants were included from one center. Statistical analysis was performed using Friedman’s test and the Roger-modified Edward’s test to assess for a significant monthly variation in attack onset. 
Results:
Among MOGAD patients, onset attack peaks were observed in November, January and March, with overall consistent findings across all 3 sites, and analyses were consistent with a statistically significant monthly variation (p<0.01 by both methods). In MS, onset attack peaks were observed in January, March and April, with analyses of monthly variation revealing borderline statistical significance (p=0.05 by Edward’s test and p<0.05 by Friedman’s test). In AQP4+NMOSD onset attack peaks across the overall cohort were observed in February and March but this pattern was not consistent across the 3 sites and analyses did not reveal a statistically significant monthly variation (p=0.21 by Edward’s test and p>0.10 by Freidman’s test).
Conclusions:

Seasonal variation in initial attacks was prominent in MOGAD and to a lesser extent MS, but not detected in AQP4+NMOSD. This could reflect the more prominent influence of seasonally distributed environmental factors such as infectious triggers or vitamin D deficiency in initial MOGAD and MS presentations compared to AQP4+NMOSD.

10.1212/WNL.0000000000217184
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