Almost 150 years after the condition was first recognised, the cause of multiple sclerosis remains a mystery. The theory that is widely held is that MS is an autoimmune disease - where the immune system, which should only target invading germs, turns on the body's own tissues. In the case of multiple sclerosis, the immune system attacks myelin, the fatty protein that covers nerves in the central nervous system.
The reason why the body reacts in this way is unknown, but it is thought that the genetic make up of some people means that MS can be triggered by an environmental factor, possibly an infectious agent or agents.
Although there are instances of several members of a family developing multiple sclerosis, MS is not hereditary and the majority of people who develop MS have no previous family history of the condition.
Studies of identical twins, who have exactly the same genetic make up, indicate that MS is not solely dependent on genes. If it were, it would be expected that were one identical twin to develop the condition, the other would also develop MS. Studies have shown that rather than this 1 in 1 risk, the actual risk for the identical twin of someone with MS is about 1 in 4.
This suggests that there is some other factor, or factors, that causes some people with a particular genetic make up to go on to develop MS. It is currently thought that one of the factors might be an infection.
In the early part of the twentieth century research was focused on the idea that multiple sclerosis was directly caused by an infectious agent. This work failed to find any positive results. Subsequent research, which still continues, has worked on the theory that, rather than being an immediate cause, an infection acts as a trigger which sets off a train of events in some people that develops into MS over a period of time.
A number of viruses have been investigated, including chicken pox, measles, mumps, canine distemper and a number of herpes viruses. Recent research has been looking at the Epstein Barr virus (EBV), a common virus that causes glandular fever in some people. However, if there is a particular virus or combination of viruses that trigger MS, they still have to be identified.
It is known that multiple sclerosis is more common in countries further from the equator. One explanation for this observation may be that a lower exposure to sunlight results in a higher incidence of MS.
Vitamin D is manufactured by the skin when it is exposed to sunlight. In theory, with lower sun exposure, there will be less vitamin D produced by the body. This has led to the hypothesis that low sunlight exposure and consequent low vitamin D production triggers the development of MS.
Studies are underway to investigate both the role of vitamin D as a protective agent against the development of MS and as a treatment for people with the condition.
Combination of factors
In 2011, a study suggested that the combined effect of exposure to the Epstein Barr virus and low levels of vitamin D could increase the risk of developing multiple sclerosis. Researchers studied hospital admissions in England in the seven years up to 2005 for people with MS and also people who had had glandular fever. They compared this with data on sunlight in the same period. Analysis of sunlight exposure explained 61% of the difference between high and low rates of MS across the country. The combined effect of sunlight and glandular fever meant that 72% of the variation could be explained.
There is increasing evidence that smoking is a significant risk factor in MS.
In 2009, an Italian vascular surgeon proposed the theory of chronic cerebrospinal venous insufficiency (CCSVI). He suggested that MS might be caused by the narrowing of veins in the brain leading to iron in the blood damaging the central nervous system. A number of research studies have investigated the association between venous insufficiency and MS. Whilst many of these demonstrate that CCSVI is not a cause of MS, debate remains as to whether it is a cause of MS symptoms, arises as a result of MS, or is completely unrelated to MS and just coincidental.
Many other factors may add to the risk of someone developing MS. This is a very active area of research but there are no clear answers so far.
- Annals of Neurology 1993;33(3):281-285. Summary A population-based study of multiple sclerosis in twins: update.
- Lancet Neurology 2007;6(9):773-781. Summary Clinical features and viral serologies in children with multiple sclerosis: a multinational observational study.
- Neurology 2011;76(16):1410-1414. Summary Relationship of UV exposure to prevalence of multiple sclerosis in England.
- PLoS One 2011;6(1):e16149. Full article Smoking and multiple sclerosis: an updated meta-analysis.
- Canadian Medical Association Journal 2011:183(16):e1203-e1212. Full article Association between chronic cerebrospinal insufficiency and multiple sclerosis: a meta-analysis.
Last updated: 8 August 2014
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