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Concussion is associated with multiple sclerosis if it occurs before infectious mononucleosis
Scott Montgomery1,2,3, Daniel Smith1,4, Lars Alfredsson5,6
1Clinical Epidemiology and Biostatistics, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro 703 62, Sweden.
Brain Communications
|August 5, 2026
Summary
Concussion before Epstein-Barr virus infection (infectious mononucleosis) in adolescence increases multiple sclerosis risk. Concussion after infection does not significantly alter this risk, suggesting timing is crucial for MS development.
Area of Science:
- Neurology
- Epidemiology
- Immunology
Background:
- Epstein-Barr virus (EBV) is strongly linked to multiple sclerosis (MS) pathogenesis.
- The timing of EBV infection relative to other exposures may influence MS risk.
- Concussion is a potential risk factor for MS, but its interaction with EBV timing is unclear.
Purpose of the Study:
- To investigate whether concussion occurring before or after infectious mononucleosis (IM), a proxy for primary EBV infection, differentially impacts MS risk in adolescents.
- To determine if the sequence of concussion and IM influences the likelihood of developing MS.
Main Methods:
- Utilized Swedish national health registers for individuals born 1980 onwards, with follow-up to 2023.
- Identified a cohort with IM between ages 11-20, excluding those with prior demyelinating disease.
- Employed Cox regression to analyze associations between concussion timing (before/after IM) and subsequent MS diagnosis, adjusting for relevant covariates.
Main Results:
- Concussion occurring before IM in adolescence was significantly associated with an increased risk of MS (aHR 2.23, 95% CI 1.24-4.03).
- Concussion occurring after IM was not significantly associated with altered MS risk (aHR 0.85, 95% CI 0.35-2.09).
- No statistically significant interaction effect was found for concussion timing and MS risk.
Conclusions:
- The findings suggest that concussion may facilitate MS development primarily when it occurs before primary EBV infection.
- Changes in the central nervous system environment due to concussion prior to EBV exposure might play a critical role in MS pathogenesis.
- Timing of environmental exposures relative to EBV infection is a key factor in understanding MS etiology.
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