Multiple Sclerosis Research

An unpredictable disease of the central nervous system, MS can range from relatively benign to somewhat disabling to devastating as communication between the brain and other parts of the body is disrupted.

The vast majority of patients are mildly affected, but in the worst cases MS can render a person unable to write, speak, or walk. A physician can diagnose MS in some patients soon after the onset of the illness. In others, however, physicians may not be able to readily identify the cause of the symptoms, leading to years of uncertainty and multiple diagnoses punctuated by baffling symptoms that mysteriously wax and wane.

During an MS attack, inflammation occurs in areas of the white matter* of the central nervous system in random patches called plaques . This process is followed by destruction of myelin , the fatty covering that insulates nerve cell fibers in the brain and spinal cord.

Myelin facilitates the smooth, high-speed transmission of electrochemical messages between the brain, the spinal cord, and the rest of the body; when it is damaged, neurological transmission of messages may be slowed or blocked completely, leading to diminished or lost function. The name "MS" signifies both the number (multiple) and condition (sclerosis, from the Greek term for scarring or hardening) of the demyelinated areas in the central nervous system.

No one knows exactly how many people have MS. It is believed that, currently, there are approximately 250,000 to 350,000 people in the United States with MS diagnosed by a physician. This estimate suggests that approximately 200 new cases are diagnosed each week.

Most people experience their first symptoms of MS between the ages of 20 and 40, but a diagnosis is often delayed. This is due to both the transitory nature of the disease and the lack of a specific diagnostic test-specific symptoms and changes in the brain must develop before the diagnosis is confirmed.

Although scientists have documented cases of MS in young children and elderly adults, symptoms rarely begin before age 15 or after age 60. Whites are more than twice as likely as other races to develop MS. In general, women are affected at almost twice the rate of men; however, among patients who develop the symptoms of MS at a later age, the gender ratio is more balanced.

MS is five times more prevalent in temperate climates-such as those found in the northern United States, Canada, and Europe-than in tropical regions. Furthermore, the age of 15 seems to be significant in terms of risk for developing the disease: some studies indicate that a person moving from a high-risk (temperate) to a low-risk (tropical) area before the age of 15 tends to adopt the risk (in this case, low) of the new area and vice versa. Other studies suggest that people moving after age 15 maintain the risk of the area where they grew up.

MS is a life-long chronic disease diagnosed primarily in young adults who have a virtually normal life expectancy. Consequently, the economic, social, and medical costs associated with the disease are significant. Estimates place the annual cost of MS in the United States in the billions of dollars.

Scientists have learned a great deal about MS in recent years; still, its cause remains elusive. Many investigators believe MS to be an autoimmune disease-one in which the body, through its immune system, launches a defensive attack against its own tissues. In the case of MS, it is the nerve-insulating myelin that comes under assault. Such assaults may be linked to an unknown environmental trigger, perhaps a virus.

To understand what is happening when a person has MS, it is first necessary to know a little about how the healthy immune system works. The immune system - a complex network of specialized cells and organs - defends the body against attacks by "foreign" invaders such as bacteria, viruses, fungi, and parasites. It does this by seeking out and destroying the interlopers as they enter the body. Substances capable of triggering an immune response are called antigens .

The immune system displays both enormous diversity and extraordinary specificity. It can recognize millions of distinctive foreign molecules and produce its own molecules and cells to match up with and counteract each of them. In order to have room for enough cells to match the millions of possible foreign invaders, the immune system stores just a few cells for each specific antigen. When an antigen appears, those few specifically matched cells are stimulated to multiply into a full-scale army. Later, to prevent this army from overexpanding, powerful mechanisms to suppress the immune response come into play.

T cells, so named because they are processed in the thymus, appear to play a particularly important role in MS. They travel widely and continuously throughout the body patrolling for foreign invaders. In order to recognize and respond to each specific antigen, each T cell's surface carries special receptor molecules for particular antigens.

T cells contribute to the body's defenses in two major ways. Regulatory T cells help orchestrate the elaborate immune system. For instance, they assist other cells to make antibodies , proteins programmed to match one specific antigen much as a key matches a lock. Antibodies typically interact with circulating antigens, such as bacteria, but are unable to penetrate living cells. Chief among the regulatory T cells are those known as helper (or inducer) cells. Helper T cells are essential for activating the body's defenses against foreign substances. Yet another subset of regulatory T cells acts to turn off, or suppress, various immune system cells when their job is done.

Killer T cells, on the other hand, directly attack diseased or damaged body cells by binding to them and bombarding them with lethal chemicals called cytokines. Since T cells can attack cells directly, they must be able to discriminate between "self" cells (those of the body) and "nonself" cells (foreign invaders). To enable the immune system to distinguish the self, each body cell carries identifying molecules on its surface. T cells likely to react against the self are usually eliminated before leaving the thymus; the remaining T cells recognize the molecular markers and coexist peaceably with body tissues in a state of self-tolerance.

In autoimmune diseases such as MS, the detente between the immune system and the body is disrupted when the immune system seems to wrongly identify self as nonself and declares war on the part of the body (myelin) it no longer recognizes.

In the population at large, the chance of developing MS is less than a tenth of one percent. However, if one person in a family has MS, that person's first-degree relatives-parents, children, and siblings-have a one to three percent chance of getting the disease.

Each case of MS displays one of several patterns of presentation and subsequent course. Most commonly, MS first manifests itself as a series of attacks followed by complete or partial remissions as symptoms mysteriously lessen, only to return later after a period of stability. This is called relapsing-remitting (RR) MS. Primary-progressive (PP) MS is characterized by a gradual clinical decline with no distinct remissions, although there may be temporary plateaus or minor relief from symptoms.

Secondary-progressive (SP) MS begins with a relapsing-remitting course followed by a later primary-progressive course. Rarely, patients may have a progressive-relapsing (PR) course in which the disease takes a progressive path punctuated by acute attacks. PP, SP, and PR are sometimes lumped together and called chronic progressive MS.

While there is no good evidence that daily stress or trauma affects the course of MS, there is data on the influence of pregnancy. Since MS generally strikes during childbearing years, a common concern among women with the disease is whether or not to have a baby. Studies on the subject have shown that MS has no adverse effects on the course of pregnancy, labor, or delivery; in fact symptoms often stabilize or remit during pregnancy.

This temporary improvement is thought to relate to changes in a woman's immune system that allow her body to carry a baby: because every fetus has genetic material from the father as well as the mother, the mother's body should identify the growing fetus as foreign tissue and try to reject it in much the same way the body seeks to reject a transplanted organ. To prevent this from happening, a natural process takes place to suppress the mother's immune system in the uterus during pregnancy.

Symptoms of MS may be mild or severe, of long duration or short, and may appear in various combinations, depending on the area of the nervous system affected. Complete or partial remission of symptoms, especially in the early stages of the disease, occurs in approximately 70 percent of MS patients.

The initial symptom of MS is often blurred or double vision, red-green color distortion, or even blindness in one eye. Inexplicably, visual problems tend to clear up in the later stages of MS. Inflammatory problems of the optic nerve may be diagnosed as retrobulbaror optic neuritis. Fifty-five percent of MS patients will have an attack of optic neuritis at some time or other and it will be the first symptom of MS in approximately 15 percent. This has led to general recognition of optic neuritis as an early sign of MS, especially if tests also reveal abnormalities in the patient's spinal fluid.

Most MS patients experience muscle weakness in their extremities and difficulty with coordination and balance at some time during the course of the disease. These symptoms may be severe enough to impair walking or even standing. In the worst cases, MS can produce partial or complete paralysis. Spasticity -the involuntary increased tone of muscles leading to stiffness and spasms-is common, as is fatigue. Fatigue may be triggered by physical exertion and improve with rest, or it may take the form of a constant and persistent tiredness.

Possible Symptoms of Multiple Sclerosis(MS)

There is no single test that unequivocally detects MS. When faced with a patient whose symptoms, neurological exam results, and medical history suggest MS, physicians use a variety of tools to rule out other possible disorders and perform a series of laboratory tests which, if positive, confirm the diagnosis.

Imaging technologies such as MRI can help locate central nervous system lesions resulting from myelin loss. MRI is painless, noninvasive, and does not expose the body to radiation. It is often used in conjunction with the contrast agent gadolinium, which helps distinguish new plaques from old. However, since these lesions can also occur in several other neurological disorders, they are not absolute evidence of MS. .

Can Multiple Sclerosis(MS) Be Treated?

There is as yet no cure for MS. Many patients do well with no therapy at all, especially since many medications have serious side effects and some carry significant risks. Naturally occurring or spontaneous remissions make it difficult to determine therapeutic effects of experimental treatments; however, the emerging evidence that MRIs can chart the development of lesions is already helping scientists evaluate new therapies.

In the past, the principal medications physicians used to treat MS were steroids possessing anti-inflammatory properties; these include adrenocorticotropic hormone (better known as ACTH), prednisone, prednisolone, methylprednisolone, betamethasone, and dexamethasone.

Immunotherapy

As evidence of immune system involvement in the development of MS has grown, trials of various new treatments to alter or suppress immune response are being conducted. Most of these therapies are, at this time, still considered experimental.

Results of recent clinical trials have shown that immunosuppressive agents and techniques can positively (if temporarily) affect the course of MS; however, toxic side effects often preclude their widespread use. In addition, generalized immunosuppression leaves the patient open to a variety of viral, bacterial, and fungal infections.

Remyelination

Some studies focus on strategies to reverse the damage to myelin and oligodendrocytes (the cells that make and maintain myelin in the central nervous system), both of which are destroyed during MS attacks. Scientists now know that oligodendrocytes may proliferate and form new myelin after an attack. Therefore, there is a great deal of interest in agents that may stimulate this reaction.

Diet

Over the years, many people have tried to implicate diet as a cause of or treatment for MS. Some physicians have advocated a diet low in saturated fats; others have suggested increasing the patient's intake of linoleic acid, a polyunsaturated fat, via supplements of sunflower seed, safflower, or evening primrose oils.

Other proposed dietary "remedies" include megavitamin therapy, including increased intake of vitamins B12 or C; various liquid diets; and sucrose-, tobacco-, or gluten-free diets.

Treatment

While some scientists look for therapies that will affect the overall course of the disease, others are searching for new and better medications to control the symptoms of MS without triggering intolerable side effects.

Many people with MS have problems with spasticity, a condition that primarily affects the lower limbs. Spasticity can occur either as a sustained stiffness caused by increased muscle tone or as spasms that come and go, especially at night.

It is usually treated with muscle relaxants and tranquilizers. Baclofen (Lioresal), the most commonly prescribed medication for this symptom, may be taken orally or, in severe cases, injected into the spinal cord.

Reference For Multiple Sclerosis(MS) Article

National Institute of Neurological Disorders and Stroke

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