Introduction

About two and a half million people worldwide have multiple sclerosis (MS). In the UK, there's a one in 400 chance that you may contract the disease during your lifetime. So it's time to look at possible new developments in what we know about the disease, and its treatment.

What goes wrong in MS

The main feature of MS is a patchy loss of the fatty sheath around the nerve fibers in the central nervous system (i.e. the brain and the spinal cord). Small areas of autoimmune inflammation¹ disable the cells responsible for making and maintaining these 'myelin' sheaths. Without their myelin sheaths the nerve fibers degenerate, and fibrosis, or sclerosis, occurs; hence the name multiple sclerosis.

Because the nerve fibers have lost their myelin sheaths, they can become super-sensitive and send a stimulus quite spontaneously, especially if their electrical properties are changed by extremes of temperature. That's why symptoms and signs of MS often appear after exercise or a hot bath. Sometimes 'cross-talk' between neighboring fibers occurs when this would not normally be the case, causing bizarre symptoms that may last a few minutes.

The actual symptoms experienced depend on where the lesions are within the central nervous system. For instance,

If the lesion is in the . . . .	The symptoms might be . . . . .
Cerebral hemispheres	Impaired mentality, epilepsy, depression
Optic nerve	Painful loss of vision in one eye
Cerebellum (the 'little brain')	Loss of balance & co-ordination, tremor
Brainstem	Double-vision, speech & swallowing difficulties, vertigo
Spinal cord	Weakness, stiff muscles, painful spasms, loss of bladder control, impotence, constipation
Other symptoms	Pain, fatigue, intolerance to temperature changes

Diagnosing MS

As there can be a wide variety of symptoms, MS is quite difficult to recognize in the early stages. However, it's important to try to make the diagnosis as soon as possible, as starting treatment early may improve the outcome considerably.

For a diagnosis of MS, the patient must have at least two episodes of symptoms, or a single episode accompanied by two typical lesions on magnetic resonance imaging (MRI).

The condition is 'sporadic' in 4 out of 5 cases. That's to say an episode of symptoms is followed by a symptomless period, known as a remission. One in 5 sufferers have what is known as progressive MS, in which the first symptom or group of symptoms persist and get worse, being later joined by other groups of symptoms. In these patients examination of the cerebrospinal fluid (CSF) and a test of electrical conduction between the eye and the brain (visual invoked potential, or VIP) can help with the diagnosis.

How the disease progresses

As with other autoimmune diseases, MS affects women at least twice as often as men. It usually starts between 20 and 40 years of age and episodes average occur about once a year, on average.

Although distressing and debilitating, MS does not normally shorten life; it's rarely the direct cause of death. Every-day activities are not affected in 25% of cases, and the average life expectancy from the time of diagnosis is at least 25 years.

About a third of all new cases occur after an infection of some kind, and infections in MS patients (e.g. a cold or 'gastric flu') can cause a relapse in about 10% of instances. Relapse is less likely during pregnancy, but they are more common after the baby is born. Injury or stress does not seem to affect the activity of the disease.

What causes MS?

It seems that heredity and the environment both play a part. The chances of a parent or child of an MS patient getting the disease is 2%, a brother or sister 3%, a non-identical twin 6%, and an identical twin 50-55%. However, no particular gene has been identified as being responsible, so far.

The environmental factors seem to be related to temperature. MS is commoner in northern Europe, the north part of North America, and Australasia. Occasional "epidemics" have been described in Iceland, the Orkneys and the Shetland Islands.

More recently, attention has focused on the possibility that infectious diseases trigger MS. A virus that causes a childhood infection called roseola (human herpes virus 6), Chlamydia infection, the Epstein-Barr virus (the cause of infectious mononucleosis) and the bacterium that causes Lyme disease are all possible candidates.

The fact that the progressive form of MS affects mostly older men, runs a worse course, and has distinct radiological changes, has led to some people thinking of it as a completely separate disorder.

Treatment approaches

Treatment is aimed at slowing the relapse rate, preventing disability, and managing the various symptoms of MS.

Two interferon drugs (beta-1a interferon and beta-1b interferon) are anti-viral agents, which is why they were used in MS in the first place. However, their use produces a 30% to 55% reduction in annual relapse rates. There are other drugs that can slow the relapse rate, but they are not as effective, and have more side effects.

The occurrence of disabilities is probably best prevented with steroids. This is because they are anti-inflammatory, and interrupt the cascade of inflammatory changes around the nerve fibers. They work well in the short-term, but aren't so successful in preventing permanent disability.

Fully developed neurological deficits can be improved a lot by intensive inpatient rehabilitation; various symptoms due to such deficits can usually be controlled fairly easily with the right specific drugs (e.g. muscle relaxants, antidepressants, laxatives, etc).

The authors of this review believe that much greater, long-lasting benefits may be achieved if treatment (such as interferon beta-1a) is started as soon as the diagnosis is made. To prove that point, however, long-term studies will be required. In the meantime, new approaches are being developed in the laboratory and tested in clinical studies.

Trying to restore myelin sheaths to the damaged nerve fibers is a feasible approach in animal models, but it has not been tried in humans, as yet. It will probably involve implanting nerve cells - cells taken from a nerve in the patient's arm or leg - or from a nerve to the nose. Optic nerve damage might be a good candidate for a test of this type of cellular transplantation.

Comment

Enormous research is being done to improve our understanding of the cause of MS, and to discover new, effective treatments. Clinical trials of new therapies will have to be long enough to be able to demonstrate real long-term benefits, so it may be some time before any really new treatment is generally available.