{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T14:53:27Z","timestamp":1785855207223,"version":"3.56.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":215,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100023670","name":"Nyckelfonden","doi-asserted-by":"publisher","award":["OLL-984743"],"award-info":[{"award-number":["OLL-984743"]}],"id":[{"id":"10.13039\/501100023670","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100023670","name":"Nyckelfonden","doi-asserted-by":"publisher","award":["OLL-1013159"],"award-info":[{"award-number":["OLL-1013159"]}],"id":[{"id":"10.13039\/501100023670","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>If Epstein\u2013Barr virus is essential for multiple sclerosis (MS) pathogenesis, there may be differences in MS risk for auxiliary exposures that occur before or after Epstein\u2013Barr virus infection. Infectious mononucleosis (IM) during adolescence typically represents the primary Epstein\u2013Barr virus infection, so can be used as a proxy marker, while concussion in adolescence is considered a separate non-essential risk factor for MS. The objective here was to examine if concussion before or after IM during adolescence is differently associated with MS risk. Using national Swedish health registers, among those born from 1980 with follow-up to 2023, we identified a cohort with IM between ages 11 and 20 years among people without a demyelinating disease diagnosis by age 20 years (n = 37 432), among whom 174 had a subsequent MS diagnosis. The median age (and interquartile range) at IM was 17.00 (15.52\u201318.59) years among those without MS and 16.66 (15.15\u201318.29) years among those with MS. In this cohort, between ages 11 and 20 years, there were 1474 episodes of concussion before IM and 1171 occurring afterwards. Associations between concussion and MS risk were estimated using Cox regression, with age as the underlying timescale and adjustment for age at IM, year of birth (both modelled as continuous measures using restricted cubic splines), sex and county. Notably, only concussion occurring before, but not after, IM was associated with increased MS risk producing adjusted hazard ratios (with 95% confidence intervals) of 2.23 (1.24\u20134.03; P = 0.008) for concussion before IM and 0.85 (0.35\u20132.09; P = 0.726) for concussion after IM. However, there is no statistically significant effect modification for MS with an interaction for concussion before and after IM of 1.60 (0.16\u201315.60; P = 0.685). Our findings suggest that changes in the environment of the CNS caused by concussion facilitate development of MS if present before primary Epstein\u2013Barr virus infection.<\/jats:p>","DOI":"10.1093\/braincomms\/fcag234","type":"journal-article","created":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T11:34:18Z","timestamp":1785670458000},"source":"Crossref","is-referenced-by-count":0,"title":["Concussion is associated with multiple sclerosis if it occurs before infectious mononucleosis"],"prefix":"10.1093","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6328-5494","authenticated-orcid":false,"given":"Scott","family":"Montgomery","sequence":"first","affiliation":[{"name":"Clinical Epidemiology and Biostatistics, School of Medical Sciences, Faculty of Medicine and Health, \u00d6rebro University , \u00d6rebro 703 62 ,","place":["Sweden"]},{"name":"Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet , Stockholm 171 77 ,","place":["Sweden"]},{"name":"Department of Epidemiology and Public Health, University College London , London WC1E 7HB ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Smith","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology and Biostatistics, School of Medical Sciences, Faculty of Medicine and Health, \u00d6rebro University , \u00d6rebro 703 62 ,","place":["Sweden"]},{"name":"Clinical Trials and Statistics Unit, Cancer Research UK, Sutton SM2 5GP ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Alfredsson","sequence":"additional","affiliation":[{"name":"Institute of Environmental Medicine, Karolinska Institutet , 171 77 Stockholm ,","place":["Sweden"]},{"name":"Centre for Occupational and Environmental Medicine , 13 65 Stockholm ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredrik","family":"Piehl","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, Karolinska Institutet , 171 77 Stockholm ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Olsson","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, Karolinska Institutet , 171 77 Stockholm ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2088-0530","authenticated-orcid":false,"given":"Ayako","family":"Hiyoshi","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology and Biostatistics, School of Medical Sciences, Faculty of Medicine and Health, \u00d6rebro University , \u00d6rebro 703 62 ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"2026080410175089100_fcag234-B1","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/s41586-022-04432-7","article-title":"Clonally expanded B cells in multiple sclerosis bind EBV EBNA1 and GlialCAM","volume":"603","author":"Lanz","year":"2022","journal-title":"Nature"},{"issue":"6578","key":"2026080410175089100_fcag234-B2","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1126\/science.abj8222","article-title":"Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis","volume":"375","author":"Bjornevik","year":"2022","journal-title":"Science"},{"key":"2026080410175089100_fcag234-B3","doi-asserted-by":"crossref","first-page":"107994","DOI":"10.1016\/j.ijid.2025.107994","article-title":"Seroepidemiology of maternal and childhood pathogen exposure in three European 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