By Jai S. Perumal, MD

Assistant Professor of Neurology, Weill Cornell Medical College

Dr. Perumal reports no financial relationships relevant to this field of study.

SYNOPSIS: A large study that reviewed longitudinally collected data from the national Swedish Patient Register found that head trauma in adolescents was associated with an increased risk of subsequent diagnosis of multiple sclerosis.

SOURCE: Montgomery S, et al. Concussion in adolescence and risk of multiple sclerosis. Ann Neurol 2017; Sept. 4. doi: 10.1002/ana.25036 [Epub ahead of print].

Multiple sclerosis (MS) is an inflammatory disorder of the central nervous system that is believed to be triggered by yet unknown environmental causes in a genetically susceptible individual. Several environmental factors have been investigated — vitamin D deficiency, infections including Epstein-Barr virus (EBV), cigarette smoking, and trauma, along with others.

Montgomery et al endeavored to systematically analyze longitudinally collected data from the national Swedish registry to look for a possible association between head injury in childhood and adolescence and risk of subsequent MS. This is the largest study yet that examined trauma before the age of 20 years and the risk of MS. All diagnoses of MS recorded in the Swedish patient registry between 1964 and 2012 were identified based on ICD codes. From these patients, those who were diagnosed with MS after the age of 20 years were identified and matched with 10 controls who did not have a diagnosis of MS for age, sex, and region of residence. In identifying those exposed to head trauma, the investigators only used those with a diagnosis of concussion alone. As a control group for trauma exposure, they selected patients with a diagnosis of limb fracture. Trauma exposures were divided further into a childhood group, in which the trauma occurred between birth and 10 years of age, and an adolescent group, in which trauma occurred between 11 and 20 years of age. The researchers included 7,292 MS patients in the study.

This study found that concussion in adolescence (age 11-20 years) was associated with a statistically significant risk of a subsequent diagnosis of MS, and there was a dose-dependent increase in the risk. The adjusted odds ratios (and 95% confidence intervals) were 1.22 (1.05-1.42; P = 0.008) for diagnosis of one concussion and 2.33 (1.35-4.02; P = 0.002) for diagnosis of two or more concussions. There was no association between limb fracture and subsequent risk of MS. The authors also found no association between childhood (birth to 10 years of age) concussion and risk of MS.

COMMENTARY

Why might there be an increased risk of MS associated with head trauma? Several possible mechanisms include: 1) release of myelin-specific antigens secondary to injury and the subsequent expansion of myelin-specific T cells; 2) release of pro-inflammatory cytokines that might be directly toxic to oligodendrocytes; and 3) neuroinflammation that remains sustained long after the injury. There are limitations to this study’s conclusions. A diagnosis of concussion could have resulted in increased neuro-vigilance that led to further investigations and an earlier diagnosis of MS, and confounding factors, such as a low level of education or socioeconomic status, which also might be a risk for both MS and trauma. A diagnosis of concussion alone was used in ascertaining a history of head trauma; other forms of head injury were excluded in the analysis. The authors found that although adolescent concussion was associated with an increased risk of MS, earlier childhood exposure was not. This could be a result of the small number of cases of childhood trauma that were included in the study, but it also could mean that time of exposure to trauma, as the immune system undergoes changes through adolescence, might play a more pivotal role in initiation of inflammation that leads to MS. The observation of increased risk of developing MS after trauma during adolescence is similar to observations in other studies investigating the risk of infection in adolescence, like EBV, and the subsequent diagnosis of MS.

Montgomery et al found a statistically significant association between concussion during adolescence and subsequent risk of MS. This association was even stronger when there was a history of multiple concussions. Based on these data, trauma should be considered one of the modifiable risks for MS and this observation warrants further study. The potential risk of MS from concussions, in addition to other detrimental effects of traumatic injury to the brain, should emphasize the importance of protecting the brain from any kind of injury, including sports injuries, and the wearing of protective gear should be mandatory.