Please note this is an updated version of an earlier post:
More than 2.3 million people around the world have been diagnosed with Multiple Sclerosis (MS) and the large majority of those are over the age of 20. MS is not contagious but some inherited genetic characteristics influence risk of developing the disease. There is evidence that things going on in people’s lives and bodies when they are younger could influence the likelihood of them being diagnosed with this chronic and unpredictable disease of the central nervous system. Professor Scott Montgomery and colleagues from the University of Örebro and Karolinska Institutet in Sweden and University College London has spent two decades researching some of the possible causes and consequences of MS. Here he shares some of his latest findings including a new study showing that glandular fever really is a risk factor for subsequent MS.
Multiple sclerosis is a disease of the central nervous system (CNS), which is made up of the brain, spinal cord and optic nerves. Damage to the CNS due to demyelination (destruction of the myelin insulation around nerve cells) interferes with the transmission of nerve signals between the brain and spinal cord and other parts of the body.
Most people with MS are diagnosed between the ages of 20 and 50, although children and older adults may develop it. Anyone may develop MS but genetic susceptibility plays a role and there are some patterns of risk. More than two to three times as many women as men develop MS and this sex difference has been increasing over the past 50 years.
Some of the things that our research linked to a diagnosis of MS include physical injury to the CNS such as concussion, and the role of different types of infection, as well as body composition as indicated by body mass index (BMI).
Periods of susceptibility
We have come to understand in recent years that there are ‘periods of susceptibility’ – in other words points in our lives when if certain things occur the likelihood of us being diagnosed with MS later on is increased. An extra complexity when studying periods of susceptibility associated with MS is that following exposure during these periods, it may take five to 10 years or even longer for the disease to be diagnosed. This is because the disease typically begins developing silently and slowly and becomes symptomatic when it can be diagnosed eventually. This is why people tend to have a higher rate of other diagnoses before MS is finally identified.
Findings from one piece of research looking at children and young people who experienced concussion showed that where this happened between the ages of 11 and 19 there was increased risk of an MS diagnosis later on, particularly if more than one episode of concussion was experienced, raising the risk of MS by 133%. It wasn’t the case for younger children and babies, as concussion before age 11 years was not associated with MS at all.
Using BMI and fitness information collected from 740,000 young men who between 1970 and 1992 were compulsorily assessed for conscription into military service between the ages of 16 and 19, we were able to see that nearly 1000 of the men we looked at were diagnosed with MS after the age of 20.
Although we had known for some time that being obese was linked with an increased risk of getting MS later on particularly among women, this research dug deeper and showed that for every extra point on the BMI scale, young men aged 16-20 faced an increased risk of being diagnosed with MS later on, even among those in the normal BMI range.
The reasons for this pattern of association are not entirely clear as risks associated with obesity such as low vitamin D levels and increased systemic inflammation are less likely to explain associations in those who are not overweight or obese.
As well as providing new evidence that BMI in adolescence is linked with MS risk in men, this work provided us with further indications that ages 11 to 20 years represent an important period of susceptibility when environmental exposures and personal characteristics may have some sort of role in initiating MS disease activity.
Other research has shown a link between contracting pneumonia in adolescence and an MS diagnosis later on and we wanted to see if there was a window of susceptibility in adolescence where other types of infections might prove important. We had to be cautious though, because infections can be a consequence of MS and it’s important to be clear what is causing what.
We started by looking to see if there were links between having a hospital-diagnosis of any infection before the age of 20 and the risk of an MS diagnosis later on.
Here we saw that several types of infection in adolescence are associated with increased MS risk (adding further support to identifying adolescence as an age-defined period of susceptibility). This was not explained by Epstein-Barr virus infection which has long been linked with MS risk. A new finding is that rare direct infection of the CNS during the teenage years increases MS risk by 180%.
Glandular fever ‘a trigger’
In our latest study we used Swedish register data on nearly 2.5 million people born between 1958 and 1994 to further understand how much individual susceptibility to infections explains their association with MS. To do this we compared siblings in the same family to help us understand the role of inherited genetic risk from parents and the family environment in childhood and adolescence.
We found that glandular fever (one of the infections most associated with MS risk) during the teenage years actually ‘triggers’ MS. Previously, scientists suggested that infections like glandular fever (also called infectious mononucleosis “mono” or “kissing disease”) might be worse in people who will go on to develop MS because their immune system is already different.
But our study showed a very different relationship. Glandular fever between ages 11 and 19 was associated with a significantly increased MS risk after age 20 years.
The new study also made it possible to look in greater detail at when an infection is more likely to trigger MS. Glandular fever in earlier childhood was less of a risk for MS than when it occurred after age 11 years. The highest risk for MS was seen for infections between ages 11 and 15 years (around the time of puberty), with the risk dropping with increasing age and almost completely disappearing by age 25. Changes in the brain and immune system as people age may help explain this.
Many who had the infection between ages 11 and 15 years did not have an MS diagnosis until after they were 30. This is because the damage to the brain caused by MS develops slowly until it makes someone sick enough to receive a diagnosis of MS.
COVID-19 and MS
Given the associations that we have seen with respiratory and other infections, we wonder whether in five to ten years we will see links between COVID-19 and MS, clearly a potentially important avenue for future research: but it should be noted that MS remains a relatively rare disease and the vast majority of those with serious infections in adolescence will not go on to develop MS. It is also important to understand that SARS-CoV-2 infections in adolescents tend to be mild, seldom requiring hospital care, unlike in older adults. As adolescence appears to represent the period of greatest susceptibility when serious infections (that result in hospital admission) are associated with subsequent MS, the on average relatively mild nature of SARS-CoV-2 infections in people of this age may make it less likely that these infections will be linked with subsequent MS.
For those who do develop MS, it is a serious disease also linked with an increased risk of other diagnoses particularly in young adulthood.
Better understanding patterns of risk may facilitate earlier diagnosis of MS and with modern treatment options, earlier treatment may result in less disease progress. We aim to improve our understanding of the processes that result in development of MS.