Concussion in adolescence and risk of multiple sclerosis

Montgomery, Scott; Hiyoshi, Ayako; Burkill, Sarah; Alfredsson, Lars; Bahmanyar, Shahram; Olsson, Tomas

doi:10.1002/ana.25036

Cited by 45 publications

(28 citation statements)

References 27 publications

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“…Strengths of this study include standardised objective measurements of BMI, rather than self-report, at a critical MS risk period and a large sample size. However, unlike our previous study, 9 we did not have access to MS Register data, so we could not identify suspected symptomatic MS onset before age of 20 years. MS appears to have a long pre-clinical phase 10 and only exposures before pathogenesis initiation may add notably to MS risk, possibly reducing magnitude of associations.…”

Section: Discussionmentioning

confidence: 89%

Higher body mass index at ages 16 to 20 years is associated with increased risk of a multiple sclerosis diagnosis in subsequent adulthood among men

Hiyoshi

Brand

et al. 2020

Mult Scler

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Background: Evidence for the association between body mass index (BMI) and multiple sclerosis (MS) among men remains mixed. Objective and methods: Swedish military conscription and other registers identified MS after age of 20 years and BMI at ages 16–20 years ( N = 744,548). Results: Each unit (kg/m2) BMI increase was associated with greater MS risk (hazard ratio and 95% confidence interval = 1.034, 1.016–1.053), independent of physical fitness (1.021, 1.001–1.042). Categorised, overweight and obesity were associated with statistically significant raised MS risk compared to normal weight, but not after adjustment for physical fitness. Conclusion: MS risk rises with increasing BMI, across the entire BMI range.

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Section: Discussionmentioning

confidence: 89%

Higher body mass index at ages 16 to 20 years is associated with increased risk of a multiple sclerosis diagnosis in subsequent adulthood among men

Hiyoshi

Brand

et al. 2020

Mult Scler

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“…Moreover, we show anti-EBNA1 antibody reactivity in CSF, as has been described previously (27), with a high correlation with anti-ANO2 reactivity in CSF. There are several lifestyle and environmental factors associated with an increased risk of MS (4,28,29), including various aspects of virus infections. Many different infections have been claimed to be associated with MS but have in most cases been refuted.…”

Section: Discussionmentioning

confidence: 99%

Molecular mimicry between Anoctamin 2 and Epstein-Barr virus nuclear antigen 1 associates with multiple sclerosis risk

Tengvall

Huang

Hellström

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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147

125

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Multiple sclerosis (MS) is a chronic inflammatory, likely autoimmune disease of the central nervous system with a combination of genetic and environmental risk factors, among which Epstein-Barr virus (EBV) infection is a strong suspect. We have previously identified increased autoantibody levels toward the chloride-channel protein Anoctamin 2 (ANO2) in MS. Here, IgG antibody reactivity toward ANO2 and EBV nuclear antigen 1 (EBNA1) was measured using bead-based multiplex serology in plasma samples from 8,746 MS cases and 7,228 controls. We detected increased anti-ANO2 antibody levels in MS (P = 3.5 × 10−36) with 14.6% of cases and 7.8% of controls being ANO2 seropositive (odds ratio [OR] = 1.6; 95% confidence intervals [95%CI]: 1.5 to 1.8). The MS risk increase in ANO2-seropositive individuals was dramatic when also exposed to 3 known risk factors for MS: HLA-DRB1*15:01 carriage, absence of HLA-A*02:01, and high anti-EBNA1 antibody levels (OR = 24.9; 95%CI: 17.9 to 34.8). Reciprocal blocking experiments with ANO2 and EBNA1 peptides demonstrated antibody cross-reactivity, mapping to ANO2 [aa 140 to 149] and EBNA1 [aa 431 to 440]. HLA gene region was associated with anti-ANO2 antibody levels and HLA-DRB1*04:01 haplotype was negatively associated with ANO2 seropositivity (OR = 0.6; 95%CI: 0.5 to 0.7). Anti-ANO2 antibody levels were not increased in patients from 3 other inflammatory disease cohorts. The HLA influence and the fact that specific IgG production usually needs T cell help provides indirect evidence for a T cell ANO2 autoreactivity in MS. We propose a hypothesis where immune reactivity toward EBNA1 through molecular mimicry with ANO2 contributes to the etiopathogenesis of MS.

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“…Recently, a large case-control study in Sweden reported an increased risk of MS for one (OR 1.22 [1.05-1.42], p = 0.008) and 2 or more (OR 2.33 [1.35-4.04], p = 0.002) concussions during adolescence period [24]. No associations were observed for concussions during childhood [24]. The difference of effect by the age of injury was considered to be related to the severity of traumatic impact as well as the different immune response during the 2 periods.…”

Section: Discussionmentioning

confidence: 99%

Medical History and Multiple Sclerosis: A Population-Based Incident Case-Control Study

et al. 2018

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Background: Consistent evidence regarding the potential role of medical history in multiple sclerosis (MS) etiology is lacking. Objective: The association of medical history variables, that is, head injury and 9 autoimmune diseases with MS onset was investigated. Methods: This was a population-based incident case-control study in Iran with 547 incident cases and 1,057 general population controls (August 7, 2013 – February 17, 2015). Multiple logistic regression models were used for estimating the adjusted ORs. Results: Lifetime history of head trauma was not significantly associated with risk of MS after adjustment for well-known confounders (OR 1.24 [0.93–1.66, p = 0.14]). Similarly, there was no statistically significant association between cumulative numbers of head injury and MS (OR 1.02 [0.90–1.15, p = 0.79]). A history of autoimmune disease did not increase the risk of MS (p > 0.1). Similarly, the cumulative number of autoimmune diseases is not significantly associated with the risk of MS (p > 0.70). Conclusion: Lifetime histories of head trauma as well as 9 investigated autoimmune diseases are not associated with increased risk of MS.

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Concussion in adolescence and risk of multiple sclerosis

Cited by 45 publications

References 27 publications

Higher body mass index at ages 16 to 20 years is associated with increased risk of a multiple sclerosis diagnosis in subsequent adulthood among men

Higher body mass index at ages 16 to 20 years is associated with increased risk of a multiple sclerosis diagnosis in subsequent adulthood among men

Molecular mimicry between Anoctamin 2 and Epstein-Barr virus nuclear antigen 1 associates with multiple sclerosis risk

Medical History and Multiple Sclerosis: A Population-Based Incident Case-Control Study

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