MS ExplainedThe possible causes of MS

Almost 150 years after the condition was first described, the cause of MS remains a mystery. There has been a great deal of research looking for the solution to this problem and a number of theories have held sway as to what triggers MS.

During this period, speculation on the cause of the condition has included:

acute fevers or exposure to damp or cold
blood clots or poor circulation in the brain
environmental poisons
dietary factors such as a food allergy or food intolerance
mercury leakage from dental amalgam fillings

Research has failed to prove any of these theories and it is now widely believed that MS is an autoimmune disease.

Autoimmune disease

An autoimmune disease is one in which the immune system, which should only target invading germs, turns on the body's own tissues. Other autoimmune conditions include diabetes mellitus type 1, in which the insulin making cells of the pancreas are destroyed, or rheumatoid arthritis, where the immune system attacks the joints and organs such as the lungs and skin. In the case of MS, the immune system attacks myelin, the substance covering and protecting nerves in the central nervous system.

The reason for this reaction is unknown but it is thought that the genetic make up of some people means that MS can be triggered by something in the environment, possibly an infectious agent or agents. In response to the infection, some cells from the immune system come into contact with the central nervous system and attack myelin, mistaking it for the invading agent.

Genetics

It is important to state that MS is not hereditary and the majority of people who develop MS have no previous family history of the condition. However, there is a higher, but still small, risk of developing MS for someone with a relative with the condition.

The risk of developing MS

In the general population in the UK, the risk of developing MS is about 1 in 700. Studies have shown that the risk for first degree relatives (parents, children, siblings) of someone with MS is about 1 in 40. For second degree relatives (cousins, uncles/aunts, nephews/nieces) it is around 1 in 100.

It is worth putting MS in context with other conditions.

1 in 9 women will develop breast cancer
1 in 14 men will develop prostate cancer
1 in 26 people has some form of diabetes
1 in 85 people has some form of dementia
1 in 240 people live with disabilities caused by stroke
1 in 500 people have Parkinson's disease
1 in 700 people have multiple sclerosis

Whilst the rate of MS within families indicates that there is a genetic factor involved in developing the condition, studies of identical twins show that genes are not the whole story. Identical twins have exactly the same genetic make up. If MS were solely dependent on genes, it would be expected that if one identical twin developed the condition, so would the other. Studies have shown that rather than this 100% risk, the actual risk of developing MS for the identical twin of someone with MS is about 1 in 4.

Which genes are involved in MS?

Genetic research has started to identify conditions such as cystic fibrosis that result from variations in a single gene. This is not the case with MS and it is believed that the interaction of a number of genes determines whether or not an individual is susceptible.

In 2007 two new genes were identified as contributing to the risk of MS, bringing the total known to three. The scale of the problem is shown by the fact that researchers suggest there might be more than a hundred genes that contribute to an individual's risk of MS. On its own, each gene raises the MS risk by a negligible amount. However, if an individual has enough of these genes, the combined effect will make them susceptible to MS.

A major reason why the identification of genes has been so slow is that none of those associated with MS is unique to people with the condition. For instance, one of the recently discovered genes, called IL7R, is carried by nine out of ten people in the general population. However, researchers are confident that new and better tools will mean that further genes will be indentified over the next few years.

External factors

Whilst a specific combination of genes can mean that an individual is at risk of developing MS, this in itself does not cause the condition. There is believed to be some other external or environmental factor. When people with a particular genetic make up are exposed to this, it triggers their body to react in a way that starts the development of MS, although it may be years before any symptoms become apparent. Many people believe that this trigger is probably an infection of some sort.

Infection

From the early days of MS there has been research into the role of an infection or infections in the onset of MS. Initial work looked into the theory that MS was directly caused by an infectious agent, but 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 common infections have been investigated, including chicken pox, measles, mumps, canine distemper and several herpes viruses.

When someone is infected with a virus or bacteria, the immune system creates antibodies to help it fight off the invasion. The antibodies remain in the blood to help fight off further infections. Researchers can identify antibodies in the blood that indicate the infections to which someone has been exposed.

It is also not yet clear if there is a particular virus or combination of viruses that might trigger MS, or if this varies from person to person. A challenge with this type of research is that most adults carry evidence of common infections, even if their immune system managed to prevent any symptoms developing.

For example, a virus that has recently been investigated is the Epstein Barr virus, which causes glandular fever. As children have a lower level of exposure to some infections, researchers in Canada compared exposure to the Epstein Barr virus in a group of children with MS and a control group who did not have the condition. They found that 83% of the MS group had been infected compared to 42% of the controls. Whilst this suggests that the Epstein Barr virus might have a role in the development of MS for some people, almost one in five of those with MS had no evidence of exposure.

Vitamin D

The role of vitamin D as a protective agent against the development of MS has also been the focus of research.

Vitamin D is manufactured by the skin when it is exposed to sunlight. Studies of the geographical distribution of MS support the link between lack of sunlight exposure, consequent lack of vitamin D production, and the development of MS.

A review of blood samples taken from US military personnel found that levels of vitamin D in people who subsequently developed MS were lower than levels in people without the condition. This effect only seemed to occur in samples from white people, and was not demonstrated in the smaller set of samples from black or Hispanic people.

Another study found that amongst sets of identical twins, where only one of the twins had MS, the twin who had engaged in less outdoor activity as a child and had been less exposed to sunlight was the twin more likely to have developed MS.

Although these results suggest a protective effect for people without the condition, there is currently no evidence of the effect of vitamin D in people who already have MS.