Concussion before, not after, EBV infection may boost MS risk

Concussions during adolescence may increase the risk of developing multiple sclerosis (MS), but only if the concussion occurs before the individual has infectious mononucleosis, a condition caused by infection with Epstein-Barr virus (EBV), according to a new study.

The findings suggest that a concussion occurring before a person is infected with EBV may trigger inflammation or other changes in the brain that alter how the brain responds to the virus. If EBV infection happens after that injury, this altered environment could ultimately help set the stage for the disease in people who are already susceptible to MS.

“This national register-based cohort study found that concussion before IM [infectious mononucleosis] during adolescence is a risk factor for subsequent MS, while concussion that occurred after IM is not,” researchers wrote in the study, “Concussion is associated with multiple sclerosis if it occurs before infectious mononucleosis,” which was published in Brain Communications. 

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MS risk more than doubled when concussions occurred prior to mono

The causes of MS are not fully understood, but several risk factors have been identified. Infection with EBV is one of the most well-established MS risk factors, and some evidence has suggested that MS can only develop in people who have already been infected with this virus.

EBV is best known as the virus that causes infectious mononucleosis, colloquially known as mono. The virus also can cause nonspecific childhood infections, and the vast majority of humans have been infected by the time they reach adulthood. But even though almost everyone has been infected with EBV at some point, only a small number will go on to develop MS, for reasons that aren’t fully clear.

Some studies have suggested that people who experience concussion or other brain injuries during childhood or adolescence are at higher risk of developing MS later in life. In this study, researchers wanted to explore the relationship between concussions, EBV, and future MS risk. Specifically, the researchers wondered if the timing of concussions relative to EBV infection affects MS risk later in life.

To find out, the scientists used national registries in Sweden to identify data for more than 37,000 people who developed mono between the ages of 11 and 20. The scientists noted that they focused specifically on people with a documented history of adolescent mono because, as a general rule, this specific type of infection only occurs in people who weren’t infected with EBV as young children. As such, if someone gets mono as a teen, that’s probably the first time they were ever infected with EBV.

Concussion-related inflammation may alter the [brain] environment, increasing the possibility that a subsequent primary EBV infection triggers an inappropriate immune response … leading to development of MS among susceptible individuals.

Among the people in the data set, 1,474 had a documented concussion prior to the onset of mono, and 1,171 had concussions that occurred after they developed mono. Using statistical analyses, the researchers compared the risk of adulthood MS in people with concussions before or after mono against the risk in people who had mono but did not have a history of concussion in adolescence.

Results showed that, when concussions occurred prior to mono, the risk of adulthood MS was more than doubled. However, individuals who got a concussion after getting mono had similar MS risk compared with people who had mono but never had a concussion.

Based on these findings, the researchers speculated that an early concussion might cause changes in the brain, setting the stage for an atypical EBV infection later on that ultimately results in MS. By contrast, if the concussion occurs after EBV infection, any changes in the brain may not matter in terms of MS risk.

“Concussion-related inflammation may alter the [brain] environment, increasing the possibility that a subsequent primary EBV infection triggers an inappropriate immune response … leading to development of MS among susceptible individuals,” the scientists concluded.

The researchers noted that, even though this study included data on thousands of people, less than 200 individuals actually developed MS in adulthood. This small number of cases means the statistical analyses need to be interpreted cautiously, and follow-up research will be needed to verify the findings, they added.

“The results are statistically significant and biologically plausible, but a chance finding is always possible, so replication is important,” they wrote.