Explaining Multiple Sclerosis (MS)

Although multiple sclerosis (MS) was first diagnosed in 1849, the earliest known description of a person with possible MS dates from fourteenth century Holland. 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 "multiple sclerosis" 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 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.

These findings indicate a strong role for an environmental factor in the cause of MS. It is possible that, at the time of or immediately following puberty, patients acquire an infection with a long latency period. Or, conversely, people in some areas may come in contact with an unknown protective agent during the time before puberty. Other studies suggest that the unknown geographic or climatic element may actually be simply a matter of genetic predilection and reflect racial and ethnic susceptibility factors.

Periodically, scientists receive reports of MS "clusters." The most famous of these MS "epidemics" took place in the Faeroe Islands north of Scotland in the years following the arrival of British troops during World War II. Despite intense study of this and other clusters, no direct environmental factor has been identified. Nor has any definitive evidence been found to link daily stress to MS attacks, although there is evidence that the risk of worsening is greater after acute viral illnesses.

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.

The Immune System

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.

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. Through intensive research efforts, scientists are unraveling the complex secrets of the malfunctioning immune system of patients with MS.

Investigators are also looking for abnormalities or malfunctions in the blood/brain barrier, a protective membrane that controls the passage of substances from the blood into the central nervous system. It is possible that, in MS, components of the immune system get through the barrier and cause nervous system damage.

Scientists have studied a number of infectious agents (such as viruses) that have been suspected of causing MS, but have been unable to implicate any one particular agent. Viral infections are usually accompanied by inflammation and the production of gamma interferon, a naturally occurring body chemical that has been shown to worsen the clinical course of MS. It is possible that the immune response to viral infections may themselves precipitate an MS attack. There seems to be little doubt that something in the environment is involved in triggering MS.

Genetics

In addition, increasing scientific evidence suggests that genetics may play a role in determining a person's susceptibility to MS. Some populations, such as Gypsies, Eskimos, and Bantus, never get MS. Native Indians of North and South America, the Japanese, and other Asian peoples have very low incidence rates. It is unclear whether this is due mostly to genetic or environmental factors.

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.

For identical twins, the likelihood that the second twin may develop MS if the first twin does is about 30 percent; for fraternal twins (who do not inherit identical gene pools), the likelihood is closer to that for non-twin siblings, or about 4 percent. The fact that the rate for identical twins both developing MS is significantly less than 100 percent suggests that the disease is not entirely genetically controlled. Some (but definitely not all) of this effect may be due to shared exposure to something in the environment, or to the fact that some people with MS lesions remain essentially asymptomatic throughout their lives.

These studies strengthen the theory that MS is the result of a number of factors rather than a single gene or other agent. Development of MS is likely to be influenced by the interactions of a number of genes, each of which (individually) has only a modest effect. Additional studies are needed to specifically pinpoint which genes are involved, determine their function, and learn how each gene's interactions with other genes and with the environment make an individual susceptible to MS. In addition to leading to better ways to diagnose MS, such studies should yield clues to the underlying causes of MS and, eventually, to better treatments or a way to prevent 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.

In addition, twenty percent of the MS population has a benign form of the disease in which symptoms show little or no progression after the initial attack; these patients remain fully functional. A few patients experience malignant MS, defined as a swift and relentless decline resulting in significant disability or even death shortly after disease onset. However, MS is very rarely fatal and most people with MS have a fairly normal life expectancy.

Studies throughout the world are causing investigators to redefine the natural course of the disease. These studies use a technique called magnetic resonance imaging (MRI) to visualize the evolution of MS lesions in the white matter of the brain. Bright spots on a T2 MRI scan indicate the presence of lesions, but do not provide information about when they developed.

Because investigators speculate that the breakdown of the blood/brain barrier is the first step in the development of MS lesions, it is important to distinguish new lesions from old. To do this, physicians give patients injections of gadolinium, a chemical contrast agent that normally does not cross the blood/brain barrier, before performing a scan. On this type of scan, called T1, the appearance of bright areas indicates periods of recent disease activity (when gadolinium is able to cross the barrier). The ability to estimate the age of lesions through MRI has allowed investigators to show that, in some patients, lesions occur frequently throughout the course of the disease even when no symptoms are present.

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.

However, women with MS who are considering pregnancy need to be aware that certain drugs used to treat MS should be avoided during pregnancy and while breast feeding. These drugs can cause birth defects and can be passed to the fetus via blood and to an infant via breast milk. Among them are prednisone, corticotropin, azathioprine, cyclophosphamide, diazepam, phenytoin, carbamazepine, and baclofen.

Unfortunately, between 20 and 40 percent of women with MS do have a relapse in the three months following delivery. However, there is no evidence that pregnancy and childbirth affect the overall course of the disease one way or the other. Also, while MS is not in itself a reason to avoid pregnancy and poses no significant risks to the fetus, physical limitations can make child care more difficult. It is therefore important that MS patients planning families discuss these issues with both their partner and physician.

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 retrobulbar or 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.

Most people with MS also exhibit paresthesias, transitory abnormal sensory feelings such as numbness, prickling, or "pins and needles" sensations; uncommonly, some may also experience pain. Loss of sensation sometimes occurs. Speech impediments, tremors, and dizziness are other frequent complaints. Occasionally, people with MS have hearing loss.

Approximately half of all people with MS experience cognitive impairments such as difficulties with concentration, attention, memory, and poor judgment, but such symptoms are usually mild and are frequently overlooked. In fact, they are often detectable only through comprehensive testing. Patients themselves may be unaware of their cognitive loss; it is often a family member or friend who first notices a deficit. Such impairments are usually mild, rarely disabling, and intellectual and language abilities are generally spared.

Cognitive symptoms occur when lesions develop in brain areas responsible for information processing. These deficits tend to become more apparent as the information to be processed becomes more complex. Fatigue may also add to processing difficulties. Scientists do not yet know whether altered cognition in MS reflects problems with information acquisition, retrieval, or a combination of both. Types of memory problems may differ depending on the individual's disease course (relapsing-remitting, primary-progressive, etc.), but there does not appear to be any direct correlation between duration of illness and severity of cognitive dysfunction.

Depression, which is unrelated to cognitive problems, is another common feature of MS. In addition, about 10 percent of patients suffer from more severe psychotic disorders such as manic-depression and paranoia. Five percent may experience episodes of inappropriate euphoria and despair--unrelated to the patient's actual emotional state--known as "laughing/weeping syndrome." This syndrome is thought to be due to demyelination in the brainstem, the area of the brain that controls facial expression and emotions, and is usually seen only in severe cases.

As the disease progresses, sexual dysfunction may become a problem. Bowel and bladder control may also be lost.

In about 60 percent of MS patients, heat--whether generated by temperatures outside the body or by exercise--may cause temporary worsening of many MS symptoms. In these cases, eradicating the heat eliminates the problem. Some temperature-sensitive patients find that a cold bath may temporarily relieve their symptoms. For the same reason, swimming is often a good exercise choice for people with MS.

The erratic symptoms of MS can affect the entire family as patients may become unable to work at the same time they are facing high medical bills and additional expenses for housekeeping assistance and modifications to homes and vehicles. The emotional drain on both patient and family is immeasurable. Support groups and counseling may help MS patients, their families, and friends find ways to cope with the many problems the disease can cause.

Treatment

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.

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. To date, clinical studies have not been able to confirm benefits from dietary changes; in the absence of any evidence that diet therapy is effective, patients are best advised to eat a balanced, wholesome diet.

MS is a disease with a natural tendency to remit spontaneously, and for which there is no universally effective treatment and no known cause. These factors open the door for an array of unsubstantiated claims of cures. At one time or another, many ineffective and even potentially dangerous therapies have been promoted as treatments for MS. A partial list of these "therapies" includes: injections of snake venom, electrical stimulation of the spinal cord's dorsal column, removal of the thymus gland, breathing pressurized (hyperbaric) oxygen in a special chamber, injections of beef heart and hog pancreas extracts, intravenous or oral calcium orotate (calcium EAP), hysterectomy, removal of dental fillings containing silver or mercury amalgams, and surgical implantation of pig brain into the patient's abdomen. None of these treatments is an effective therapy for MS or any of its symptoms.

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