MS

This essay was written by Kamalini Trentham and was first published in the 1999 Mill Hill Essays.

There are approximately eighty-five thousand people in the United Kingdom who suffer from Multiple Sclerosis (MS). MS can affect people at any age but it is most common in young adults, first symptoms usually appearing during their early twenties and thirties. More women than men are affected; for every three women with MS there are only two men.

MS is a condition that affects the Central Nervous System which consists of the brain and the spinal cord. The brain has often been compared to a computer but it is a lot more sophisticated in its performance and seems to have unlimited capacity to process information. The spinal cord is the cable, no more than an inch thick, through which information is received by the brain from all parts of our bodies and commands are sent through our nerves. The brain, the spinal cord and all other nerves are made up of cells called neurons. Neurons, like all cells contain a nucleus, which contains the genetic information. Each neuron has several branching structures called dendrites which detect signals, and a long arm-like structure called an axon which passes the signal on. Axons can be very long and branch at the end, each axon branch making contact with another neuron creating a network. Nerves have a protective insulating coating, or sheath, of a material called myelin, which is necessary for them to work in this way. Any damage to the Central Nervous System, whether it is to the nerve cell or to the myelin sheath, will stop the transfer of messages carried by the nerves and produce disease symptoms. In MS, the nerves in the Central Nervous System are stripped of their myelin coating.

The unpredictable nature and course of the disease is one of the most difficult aspects of MS for people to cope with. In nearly eighty-five percent of patients, MS initially takes a relapsing / remitting course. An attack or relapse during which faulty nerves work incorrectly is followed by almost complete recovery, a remission. The relapse may last for hours, days or months and may be mild or severe. During the remission, to an onlooker, a person with MS may seem perfectly normal and complaints of sudden fatigue may be hard to believe – in fact, in the early history of MS it was referred to as a ‘faker’s disease’. The remission period can vary tremendously too, from a few months to many years. In this phase of MS, referred to as the Relapsing/Remitting phase, nerves which have lost their myelin coat can produce another one and recover their proper activities.

Around one in five of the people with the Relapsing/Remitting form of MS not only recover all their functions resulting in little or no sign of disability but they stay in remission for as many as fifteen years or more. Another quarter continue in Relapsing/Remitting stage with some disability accumulating after each relapse. A further two in five go on to the next phase in which the remissions last for very short periods and eventually stop and the disease enters a progressive phase. This is called Secondary Progressive MS. The remaining fifteen percent of people with MS have the Primary Progressive form also known as chronic progressive, where there is no Relapsing/Remitting phase and symptoms and disability worsen from the onset. Even in Primary Progressive MS the course can be unpredictable, as it can level off or progress at variable rates, even in the same individual.

Symptoms vary from person to person depending on the body function affected by the damaged area of the Central Nervous System. Impaired balance, blurred or double vision, control and frequency of bladder and bowel functions, speech and swallowing and sexual functions can all be affected. Some people with MS suffer from pain and muscular spasms. Most people only experience a few of these symptoms at any one time. However nearly everyone with MS suffers from chronic fatigue even when they are in the remission phase.

Many of the symptoms of MS are not specific and there is no one single test for the disease. Most diagnostic routines begin with physical examination to test any abnormalities in the nerve pathways. Both motor and sensory pathways are tested. The time taken for the brain to receive and interpret sights and sounds is measured and Cerebro-spinal fluid that surrounds the brain and the spinal cord may be removed by lumbar puncture to check for specific antibodies. However, before MS can be confirmed, all other causes which give rise to similar symptoms must be eliminated. The arrival of Magnetic Resonance Imaging has been of tremendous value to neurologists in diagnosing MS, as areas of demyelination can be seen during an imaging scan. Magnetic Resonance Imaging has proved to be an invaluable tool not only for diagnostic purposes but also for monitoring clinical trials of new drugs. Since there are other diseases that also result in demyelination of nerves, Magnetic Resonance Imaging alone is not a sufficient basis for a definite diagnosis. A neurologist will usually only confirm MS after the patient has had at least two attacks separated by at least a month, each lasting for at least twenty-four hours and involving at least two different areas of the Central Nervous System.

What causes MS is not yet known, but it appears to be neither infectious nor hereditary. There is evidence to indicate a role for geographical and environmental factors as well as genetic susceptibility in its onset. Epidemiological studies have identified geographical clusters of MS and also provide the bulk of the evidence for environmental factors. MS is more prevalent in temperate climates and northern latitudes. Even within the British Isles, for example, there are regional variations in the number of people with MS. For every person with MS in southern England there are two in north-east Scotland. There are data, which suggest that individuals who move from a low-risk area to a high-risk area are more likely to increase their risk if they move after the age of fifteen. Some scientists suspect that the environmental factor may be a virus, but most do not consider that a single virus is responsible. However, there is strong evidence that although MS is not a genetic disease, there is a genetic susceptibility, which means that people who have certain genes may be more likely to suffer from MS. Much of this evidence comes from observations that there are several ethnic groups that have no incidence of MS. Some of the studies, which have followed the migration of such groups into geographic areas where the incidence of MS is high, have found that they remain free of the disease.

Research has shown that MS is an autoimmune disease. Our body’s immune defence system is highly developed, very sophisticated and extremely efficient. During the development of the foetus, the immune system learns to recognise all parts of the body, which it is to protect. In addition, control mechanisms are set within the system to make sure that it does not turn upon itself. The concept of protecting self and destroying non-self , that is anything foreign to itself, is a central feature of the immune system. It fights off invasion by enemies, which may come in many forms like viruses and bacteria, or parasites like malaria, and protects the organs of the body from their attack. In an autoimmune disease the system fails and it begins to consider parts of itself as foreign and launches an attack on them.

The autoimmune nature of MS has been long established. Although the brain is continually supplied with nutrients through the circulating blood, no blood cells cross through the walls of the blood vessels into the brain. The blood-borne cells of the immune system have, therefore, not been exposed to nerve cells during the crucial period when the distinction between self and non-self is established. In MS, a breach in the barrier between blood and brain brings, for the first time, the white blood cells of the immune system into direct contact with the myelin coats of nerve cells. Not having encountered myelin before, the white blood cells regard it as foreign and launch an attack stripping the nerve fibres of their protective myelin sheath. Demyelinated fibres are unable to carry out their function of carrying messages from the Central Nervous System to the rest of the body, and the symptoms of MS result. As yet, there is no cure for MS, but in the last decade, there have been tremendous advances in intervention to change the course of progression of the disease and in its management. In addition, rehabilitation plays an important role in helping people with MS to lead as full a life as possible.

Cure and prevention is the ultimate dream of both researchers and sufferers alike. A cure will require two criteria to be met. Firstly, remyelination of demyelinated axons necessary for them to recover their lost functions and secondly, control of the immune system to stop it attacking the new myelin.

Although a complete cure may seem a dream, there is much cause for optimism. There are many strategies that are being investigated currently and a breakthrough may come not only from research on MS, but also from research on other related neurological disorders. Many promising treatments are still in the experimental stages or are undergoing clinical trials. One of the approaches has been to try to repair the damaged blood-brain barrier, another is to re-educate the immune system so that it recognises myelin as self and does not attack it. Then there are attempts to remyelinate the axons. Myelin is produced by highly specialised cells called oligodendrocytes. Unfortunately, an adult brain has a limited supply of these cells and the cells themselves only have a limited life when they are actively producing myelin. In the relapsing-remitting stage of MS, these cells produce myelin for the nerve fibres faster than the cells of the immune system break it down. As the disease advances, the production of myelin cannot keep pace with its destruction. This results in an incomplete recovery of the affected function and MS moves into the progressive phase. Neurons that have been stripped of their myelin protection for long periods may eventually die. This has serious implications for people with primary or secondary progressive MS. For them to be cured and recover their lost functions there will have to be a way of either regenerating or transplanting new nerve cells.

History is full of successes in the medical application of basic immunological research; from the first vaccine developed by Jenner for smallpox to Salk’s polio vaccine to the immune suppression for organ transplantation. Even the safety of such routine procedures as blood transfusion is based on an understanding of the immune system. So how has this understanding of the immune system been exploited for MS? Most current ways of slowing the progression of MS are based on immunotherapy. 1996 saw MS much highlighted in the British media when beta interferon, under the trade name Betaferon, was granted a licence for the treatment of the Relapsing/Remitting form. Interferons are proteins that play an important role in regulating the immune system and in the body’s defences, especially against viruses. They were discovered in 1956 by Alick Isaacs and Jean Lindenmann at the National Institute for Medical Research. Three types of interferons have now been identified, alpha, beta and gamma. Gamma interferon has been shown to contribute to the destruction of myelin but Beta interferon has therapeutic effects by blocking the action of gamma interferon and dampening down the immune system.

Although beta interferon has only a modest effect on the severity and number of relapses in the Relapsing/Remitting form of MS, it is the only drug currently licensed for treatment. A modest start, but a start none-the-less, towards the final goal. There are many other exciting approaches to therapy currently under investigation. Experimental trials to re-educate the immune system in Secondary Progressive MS have shown very encouraging results. Such treatments will stop progression, but lost functions will not be repaired. Perhaps given earlier in the course of the disease when the loss of function is minimal, this may be as good as a cure. Drugs to repair the damaged blood-brain barrier are also undergoing trials. Attempts to stimulate the regrowth of nerve cells and their remyelination are currently being made to repair spinal injuries caused accidentally by falls and crashes. Such approaches may also have direct benefit to people with MS It is very likely that a combination of such treatments will be necessary to contain the damage and restore lost function. If the progress of the last decade is anything to go by, this will hopefully not be a dream for long.

 

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