Seasonal patterns of relapse and disability in Danish MS patients: A population-based cohort study

Background: The importance of environmental risk factors in the onset of multiple sclerosis (MS) has been studied extensively. Similarly, a growing number of studies address the importance of environmental factors, including seasonality, for ongoing activity of established disease. Specifically, past research demonstrates higher rates of relapse activity in summer months among individuals with MS. Our study adds to the existing literature on seasonality of disease relapse by analysing a large population-based and virtually complete cohort of patient with relapsing and remitting MS (RRMS) in an area of temperate climate. Methods: The Danish Multiple Sclerosis Registry includes follow-up for all patients receiving disease modifying treatment from 1996?2020, with near-complete registration of all relapses and their dates. We compared the observed and expected numbers of relapses for each calendar month and calculated month-specific annualized relapse rates (ARR) using Poisson regression. In addition, we analysed seasonal variation in disability as measured by the Expanded Disability Status Scale (EDSS). Results: From 1996 to 2020 we followed 13,575 MS patients treated with disease modifying therapy (4165 men and 9410 women) for a total of 82,187 person years and 134,593 control visits. The mean age at entry was 41.1 years with standard deviation 10.9 years. We recorded 16,083 relapses throughout the observation period, and for 15,728 of the relapses the date of onset was known. Relapses were unevenly distributed by calendar month (p < 0.00001). The most prominent deviation was a paucity of relapses in July in which the ARR was 0.166 compared with mean of 0.191 for the whole year. Otherwise, the ARR formed a plateau slightly above mean during the spring months. Mean EDSS was slightly higher in autumn (2.78) than in spring (2.74), but there was no difference between winter and summer; p < 0.0001. Conclusion: In contrast with previous studies, we observed a nadir of relapses in July among Danish patients with RRMS. This finding may be related to increased exposure to sunlight in the summer, particularly during vacation when outdoor recreational activities are more frequent and potential exposure to infections is decreased. Confirmation of this in future studies is warranted.