Multiple sclerosis (MS) is usually diagnosed between the ages of 20 and 50. Some genes put a person at risk for this central nervous system disease, but researchers are still trying to understand the triggers. My colleagues and I have been studying these triggers for many years. Our previous research found that pneumonia in adolescence is associated with an increased risk of MS, so we decided to investigate whether other types of infection are associated with the condition.
However, we had to be careful, as infections can be a result of MS rather than the other way around. It can also be five to ten years, or even longer, between the onset of the disease process and a person showing the first symptoms, which include numbness and tingling, stiffness, difficulty balancing, vision problems and fatigue. We therefore had to take extra measures to be sure that infections occurred before any MS-related disease became apparent.
For our study, published in the journal Brain, we used health records for almost 2.5 million people born in Sweden between 1970 and 1994. Just over 4,000 of them were diagnosed with MS after the age of 20. Among this group, 19% had an infection diagnosed in hospital between birth and ten years and 14% between 11 and 19 years.
We found that most infections before the age of 11 were not associated with a later diagnosis of MS. In contrast, infections diagnosed in a hospital (indicating that they are relatively serious) between the ages of 11 and 19 were consistently associated with an increased risk of developing MS.
Not all types of infections were associated with subsequent MS, but a striking finding is that infections of the central nervous system (brain and spinal cord) increased the risk of MS in particular. This makes sense, because we believe that inflammation of the central nervous system can start the autoimmune process (when a person’s immune system attacks a part of the body) that causes MS.
Respiratory infections in adolescence were also associated with MS, which increased the risk by 51%. We believe that in some cases, infection and inflammation in the lungs can lead to immune activation in other parts of the body, including the central nervous system, which increases the risk of inflammation there. This may explain how a lung infection can initiate the MS disease process. Alternatively, the infectious agent may have a more direct effect on the brain.
Epstein-Barr virus (EBV) infection has long been associated with MS, so it was important to ensure that the results were not due to EBV infection being associated with other types of infections. After excluding people who had ever had the acute form of EBV infection, known as glandular fever, the results for the other infections remained, emphasizing the importance of different types of infections in adolescence as MS risks.
To make it even more certain that infections during adolescence were likely to precede the initial asymptomatic development of MS, we repeated the analysis but only looked at MS that was diagnosed after the age of 25. The increased risk of MS in connection with infections in adolescence remained for infections of the central nervous system and lung infections. There were at least five years between infection and MS diagnosis – and usually longer – indicating that the disease progresses slowly until there is sufficient damage to the brain for symptoms of multiple sclerosis to develop.
Period of increased sensitivity
Our study provides further evidence that adolescence is a period of increased sensitivity to exposures linked to MS risk and that it can take many years between exposure and MS diagnosis. These results help us better understand the types of exposures that may increase the risk of MS. It may be worth considering MS as a potential diagnosis in someone who has neurological symptoms if they had a serious infection during adolescence.
The next step in our research will be to further investigate whether people who are genetically susceptible to developing MS are more likely to have a more pronounced immune response to infections that increase the likelihood of hospitalization.
Several but not all types of infections are associated with MS, especially those that can cause inflammation in the central nervous system. Only a few people who have relatively serious infections during adolescence will continue to have MS (in most cases much lower than 1%), as other factors, including genetic susceptibility, are also needed for the disease to develop.
Author: Scott Montgomery – Honorary Professor, Epidemiology, UCL