multiple sclerosis

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Definition

Multiple sclerosis (MS) is a chronic autoimmune disorder affecting movement, sensation, and bodily functions. It is caused by destruction of the myelin insulation covering nerve fibers (neurons) in the central nervous system (brain and spinal cord).

Description

MS is a nerve disorder caused by destruction of the insulating layer surrounding neurons in the brain and spinal cord. This insulation, called myelin, helps electrical signals pass quickly and smoothly between the brain and the rest of the body. When the myelin is destroyed, nerve messages are sent more slowly and less efficiently. Patches of scar tissue, called plaques, form over the affected areas, further disrupting nerve communication. The symptoms of MS occur when the brain and spinal cord nerves no longer communicate properly with other parts of the body. MS causes a wide variety of symptoms and can affect vision, balance, strength, sensation, coordination, and bodily functions.

Multiple sclerosis affects more than a quarter of a million people in the United States. Most people have their first symptoms between the ages of 20 and 40; symptoms rarely begin before 15 or after 60. Women are almost twice as likely to get MS as men, especially in their early years. People of northern European heritage are more likely to be affected than people of other racial backgrounds, and MS rates are higher in the United States, Canada, and Northern Europe than in other parts of the world. MS is very rare among Asians, North and South American Indians, and Eskimos.

— Ruthan Brodsky

A chronic autoimmune disease of the central nervous system in which gradual destruction of myelin occurs in patches throughout the brain or spinal cord or both, interfering with the nerve pathways and causing muscular weakness, loss of coordination, and speech and visual disturbances.

Definition

Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system. The disease results in injury to the myelin sheath (the fatty matter that covers the axons of the nerve cells), the oligodendrocytes (the cells that produce myelin) and, to a lesser extent, the axons and nerve cells themselves. The symptoms of multiple sclerosis vary, depending in part on the location of plaques (areas of thick scar tissue) within the central nervous system. Common symptoms include weakness and fatigue, sensory disturbances in the limbs, bladder or bowel dysfunction, problems with sexual function, and ataxia (loss of coordination). Although the disease may not be cured or prevented at this time, treatments are available to reduce severity and delay progression.

Description

Multiple, or disseminated, sclerosis (MS) is a slowly progressive disease of the central nervous system (CNS), that comprises the brain and spinal cord. In 1868, French physician Jean-Martin Charcot (1825–1893) produced his lectures on "Sclerose en plaques," providing the first detailed clinical description of the disease. The cause of multiple sclerosis is unknown, and it cannot be prevented or cured. Great progress, however, is being made in treating and identifying underlying mechanisms that trigger the disease. The primary characteristic of MS is the destruction of myelin, a fatty insulation covering the nerve fibers. The end results of this process, called demyelination, are multiple patches of hard, scarred tissue called plaques. Another important feature in the disease is destruction of axons, the long filaments that carry electric impulses away from a nerve cell, which is now considered to be a major factor in the permanent disability that occurs with MS.

Multiple sclerosis is usually characterized by a relapsing remitting course in the early stages, with full or nearly full recovery initially. In the early stages, there may be little damage to axons. Over time, the disease enters an irreversible progressive phase of neurological deficit. Each relapse causes further loss of nervous tissue and progressive dysfunction. In some cases there may be chronic progression without remission or acute disease rapidly leading to death.

MS is a diverse disease. No two affected persons are the same and each will experience different combinations of symptoms with differing severity. The most common form is relapsing-remitting multiple sclerosis (RRMS), which affects 80–85% of people with MS. These patients develop disease relapses, often without a specific trigger, but possibly associated with infections. Disease relapses can last between 24 hours and several months, and the person may, or may not, completely recover. The disease is stable between relapses, although affected persons can have residual symptoms and disability.

After several years, the majority (70%) of persons with MS will develop secondary progressive multiple sclerosis (SPMS), whereby they experience a progressive neurological deterioration. They may still suffer from superimposed relapses. A subcategory of RRMS patients (around 20%) has benign MS. These patients have rare and mild relapses and a long course of disease with minimal or no disability. If patients have a steady neurological decline from the onset, without relapses, they are described as having primary-progressive multiple sclerosis (PPMS). This comprises approximately 15–20% of people with the disease

A fourth, rare type of MS is progressive-relapsing multiple sclerosis (PRMS), which is considered a variant of PPMS with similar prognosis. In patients with PRMS, there is a gradual neurological decline from the beginning. It is similar to PPMS, but has superimposed, acute relapses.

Demographics

According to the National Multiple Sclerosis Society, approximately 400,000 Americans acknowledge having MS, and every week about 200 people are diagnosed. Worldwide, MS may affect 2.5 million individuals. The usual age of onset is within the third and fourth decades, although the disease can begin in childhood and also above the age of 60 years. Overall, MS occurs more frequently in women than in men, and the female-to-male ratio is approximately of 2:1. This female predominance is less defined in patients with PPMS, which typically develops at a later age.

There is a variation in the worldwide distribution of MS, with the highest prevalence in the northern and central Europe, northern North America and southeastern

Australia. Clusters, or areas with more than the expected amount, occur. There are also racial differences, with a low prevalence in Asians and Africans or people of African descent, and a higher frequency in Caucasians, especially of northern European descendent. MS is rare between the equator and latitudes 30°–35° north and south. The prevalence of MS increases proportionally with increased distance from the equator. There is no satisfactory explanation of this phenomenon, although certain variables have been researched. These include environmental factors, such as climate, humidity, hours of daily sunshine, resistance to certain viruses, and even consumption of cow's milk.

Causes and symptoms

The causes of multiple sclerosis remain unknown, but it is widely accepted that susceptibility to MS is determined by a complex interaction between susceptibility genes and environment. The most popular current theory is that the disease occurs in people with a genetic susceptibility, who are exposed to some environmental assault (a virus or a toxin) that disrupts the blood-brain barrier, a protective membrane that controls the passage of substances from the blood into the central nervous system. Most researchers consider MS to be an autoimmune disease-one in which the body, through its immune system, launches a defensive attack against its own tissues. Immune factors converge in the nerve cells and trigger inflammation and an autoimmune attack on myelin and axons. Still, a number of disease patterns have been observed in MS patients, and some experts believe that MS may prove to be not a single disorder, but may represent several diseases with different causes.

Components of myelin such as myelin basic protein have been the focus of much research because, when injected into laboratory animals, they can precipitate experimental allergic encephalomyelitis (EAE), a chronic relapsing brain and spinal cord disease that resembles MS. The injected myelin probably stimulates the immune system to produce anti-myelin T-cells that attack the animal's own myelin.

Increasing scientific evidence suggests that genetics may play a role in determining a person's susceptibility to MS. No specific gene has been identified and it seems to have a mode of inheritance that involves multiple genes. Twin studies have shown an increased risk of 30% in identical twins, and around 5% in fraternal twins. First-degree relatives of a person with MS have a two or three percent increased risk, which, although small, is higher than in the general population. Further indications that more than one gene is involved in MS susceptibility comes from studies of families in which more than one member has MS.

Several research teams found that people with MS inherit certain regions on individual genes more frequently than people without MS. Of particular interest is the human leukocyte antigen (HLA) or major histocompatibility complex region on chromosome 6. HLAs are genetically determined proteins that influence the immune system. Another interesting candidate is CD24, which has shown to be essential for the induction of EAE in mice. CD24 is a cell surface protein with expression in a variety of cell types that can participate in the rise of MS, including activated T-cells.

An infectious cause of MS has been indicated by some studies as well as by similarities to infectious demyelinating diseases. However, infectious agents more likely shape the immune response that may induce the disease under special circumstances. Evidence is mounting that infection with the Epstein-Barr virus (EBV), which can cause mononucleosis, may also increase the risk of developing multiple sclerosis later in life. Researchers have shown that people with multiple sclerosis tend to carry higher levels of antibodies to the Epstein-Barr virus and that they seem to be at higher risk for the disease. Some of the immune cells that become programmed to attack the Epstein-Barr virus may begin to attack myelin as well.

Environmental factors, other than infectious agents, for which there is some evidence of an association with MS, include toxins, low sunlight exposure, diet factors, and trauma.

Almost any neurological deficit can occur in MS, but there are several signs and symptoms that are characteristic and their presence should suggest MS as a possible diagnosis, particularly in a young adult.

Vision disorders such as optic neuritis can occur. Optic neuritis (ON) is an inflammation of the optic nerve characterized by acute or subacute loss of vision usually in one, but occasionally in both eyes. The visual loss evolves over a period of hours or days. Vision returns to normal within two months, but may deteriorate in later years. Previous history of optic neuritis in a person who develops a neurological illness will strongly support the diagnosis of MS.

Cognitive (thought) impairment is thought to affect 40–70% of MS patients and can be present even in the early stages of MS. Approximately one-third of people with MS have some degree of memory loss. Other areas of cognitive function particularly affected in the MS patient include sustained attention, verbal fluency, and spatial perception. Dementia (loss of intellectual function) is often common in the latter stages of MS.

Many MS patients are temperature sensitive. In hotter weather or during a period of raised body temperature, their MS symptoms worsen. Most frequently, vision is affected and muscle weakness occurs.

About two-thirds of MS patients experience pain at some point during the course of the disease and 40% are never pain free. MS causes many pain syndromes; some are acute, while others are chronic. Some worsen with age and disease progression. Pain syndromes associated with MS are trigeminal (facial) pain, powerful spasms and cramps, optic neuritis pain, pressure pain, stiffened joints, and a variety of sensations including feelings of itching, burning, and shooting pain.

The Lhermitte's sign can occur, which is actually more of a symptom than a sign. A tingling or electric-like sensation down the back and legs is felt upon flexing the neck. The symptom is non-specific, but occurs more frequently in MS than in any other condition and provides an important clue to the correct diagnosis.

Urinary incontinence affects up to 90% of people with multiple sclerosis and usually occurs before major physical disability is apparent. Bladder problems are due to plaques in the spinal cord. If demyelination occurs in both controlling pathways, the bladder will neither store urine nor empty it properly. Constipation affects about 40% of people with MS. Bowel incontinence and urgency of defecation can also occur in about half of people with MS.

Fatigue is a common complaint in MS. Characteristics of fatigue include muscle weakness, coordination problems, ataxia, transient deafness, changes in taste or smell and numbness of the extremities. Spasticity occurs in up to 90% of MS patients and it can be painful and distressing. Spasticity is characterized by weakness, loss of dexterity, and the inability to control specific movements. It is usually more severe in the legs and torso.

Sexual dysfunction is common among people with multiple sclerosis. If MS damages the nerve pathways from the brain to the sexual organs via the spinal cord, sexual response can be directly affected. Physicians and people with MS often neglect to deal with this aspect of the disease, and both treatments and strategies for success are available.

Depression is common in MS; some studies show that over 50% of people with MS have depression at some point in their lifetime. There is also an increased risk of suicide. If depression is present, it should be treated prior to initiating MS therapy. Depression in those with MS is treated in the same way as the general population.

Diagnosis

MS diagnosis is based upon an individual's history of clinical symptoms and neurological examination. A qualified physician, often a neurologist, must thoroughly review all symptoms experienced by an individual to suspect MS. Other conditions with similar symptoms must be ruled out, often requiring various tests.

The diagnosis of MS is usually made in a young adult with relapsing and remitting symptoms referable to different areas of CNS white matter. Diagnosis is more difficult in a patient with the recent onset of neurological complaints or with a primary progressive clinical course.

Laboratory studies include blood work to exclude collagen vascular disease, infections (ie, Lyme disease, syphilis), endocrine abnormalities, vitamin B-12 deficiency, sarcoidosis, and vasculitis. The examination of cerebrospinal fluid (CSF) has been used to support the diagnosis of MS. The presence of myelin basic protein in the CSF of an MS patient may be highly suggestive of activity of the MS process, but its absence does not rule out active disease.

A newer neuroimaging technique, magnetic resonance spectroscopy (MRS), has been useful in following NAA (N-acetyl-aspartate) levels in patients with multiple sclerosis. NAA is an amino acid found in neurons and axons of the mature brain. In patients with relapsing-remitting MS, NAA levels are reduced, suggesting axonal loss; however, in patients with secondary progressive MS with more disability, the NAA levels are reduced more significantly. In fact, patients with MS had lower levels of NAA even in areas of the brain previously thought to be unaffected, when compared with levels in normal persons.

Magnetic resonance imaging (MRI) remains the imaging procedure of choice for diagnosing and monitoring disease progression in the brain and spinal cord. This test can show brain abnormalities in 90–95% of patients and spinal cord lesions in up to 75% of cases, especially in elderly patients. However, MRI alone cannot be used to diagnose MS. Evoked potential tests that measure how quickly and accurately a person's nervous system responds to certain stimulation have been the most useful neurophysiological studies for evaluation of MS.

At the onset, MS may be mistaken for other inflammatory diseases of the central nervous system, such as Behçet disease, antiphospholipid syndrome or acute disseminated encephalomyelitis (ADEM). Pseudotumoral MS may be reminiscent of lymphoma, other tumors (glial tumors), or infectious diseases (like Lyme disease, HTLV1 infection or abcess). Recurrent relapses of neurological impairment may also be mistaken for cavernomatosis. In most cases, MRI findings, cerebrospinal fluid analysis, evoked potentials, the association with systemic signs and the relapsing remitting nature of the disease allow physicians to exclude other diseases, and to arrive at a diagnosis of MS.

Treatment team

The multidisciplinary team usually includes specialists in neurology, urology, ophthalmology, neuropsychology, and social work.

Treatment

The three goals of drug therapy in the treatment of MS are management of acute episodes, prevention of disease progression, and treatment of chronic symptoms. Specific symptoms that may be treated include muscle spasticity, lack of co-ordination, tremor, fatigue, pain, bladder and bowel dysfunctions, sexual dysfunction and depression.

Exacerbations (episodes of worsening symptoms) can be defined as temporary flare-ups, sometimes referred to as attacks or relapses. Most relapses show a degree of spontaneous recovery, but treatment is offered for those relapses that have a severe impact on function. Steroids are the treatment of choice for relapses, usually methyl-prednisolone given orally or by intravenous infusion. Before starting steroids, infection should be excluded because steroids have immunosuppressant action and can exacerbate the infection.

Disease modifying treatments are aimed at slowing disease progression. The two current types of immunomodulatory agents used as a first line treatment are interferon beta and glatiramer acetate. Interferon beta has proved effective with RRMS and SPMS. There is currently no evidence for improvement with PPMS. Discontinuation of the treatment may be necessary because of intolerance to side effects, when a pregnancy is planned, or when it is no longer effective. Glatiramer is the appropriate treatment to reduce relapse frequency in patients with RRMS and it should not be used for both PPMS and SPMS. Stopping criteria for glatiramer are the same of interferon beta.

A number of treatments are available for managing MS chronic symptoms and complications, each one with specific drugs. Indeed, symptomatic treatment, along with supportive measures and rehabilitation, are a major part of the MS treatment.

Recovery and rehabilitation

When recovering from a symptom flare-up or learning to cope with a change in mobility, rehabilitation through physical therapy can be of great value training patients to improve mobility and to decrease spasticity and strengthen muscles. Some of those who have a physically demanding or highly stressful job may choose to make a career change, in which case vocational training is helpful.

Occupational therapy helps in assessing the patient's functional abilities in completing activities of daily living, assessing fine motor skills, and evaluating for adaptive equipment and assistive technology needs. Speech therapists assess the patient's speech, language, and swallowing and may work with the patient on compensatory techniques to manage cognitive problems.

Clinical trials

The National Institute of Neurological Disorders and Stroke (NINDS) is recruiting patients to evaluate the safety, tolerability, and effect of the drug Rolipram on MS. The NINDS is also recruiting patients with relapsing-remitting or secondary progressive multiple sclerosis to examine the safety and effectiveness of Zenapax (a laboratory-manufactured antibody) in treatment of MS. More information is available at the website: , a clinical trial service sponsored by the United States government.

Prognosis

It is generally very difficult to predict the course of MS. The disorder varies greatly in each individual, but most people with MS can expect to live 95% of the normal life expectancy. Some studies have shown that people who have few attacks in the first several years after diagnosis, long intervals between attacks, complete recovery from attacks, and attacks that are sensory in nature (i.e., numbness or tingling) tend to fare better. People who have early symptoms of tremor, difficulty in walking, or who have frequent attacks with incomplete recoveries, or more lesions visible on MRI scans early on, tend to have a more progressive disease course.

Special concerns

People with should avoid caffeine-containing beverage, which can actually be dehydrating. The diet should also be rich in fiber, particularly from whole grains, fruits and vegetables to increase digestive motility and reduce constipation. Maintenance of weight in the normal range is also desirable in order to diminishes stress on the joints and skeletal muscles.

Gait difficulty (difficulty with walking) may worsen during pregnancy, and assistive devices for walking or a wheelchair are useful at this time. During pregnancy, bladder and bowel problems may also be aggravated in women with MS who already have these dysfunctions.

Resources

BOOKS

O'Connor, Paul. Multiple Sclerosis: The Facts You Need. Firefly Books, 1999.

Warren, Sharon, and Kenneth Warren. Multiple Sclerosis. World Health Organization, 2001.

PERIODICALS

Myles, Mary L. "The ongoing battle against multiple sclerosis." Canadian Journal of Diagnosis (June, 2003): 108–117.

OTHER

"About MS." Multiple Sclerosis Association of America.http://www.msaa.com (February 12, 2004).

National Institute of Neurological Disorders and Stroke. NINDS Multiple Sclerosis Information Page.http://www.ninds.nih.gov/health_and_medical/disorders/multiple_sclerosis.htm (February 12, 2004).

National Multiple Sclerosis Society. Living with MS.http://www.nationalmssociety.org (February 1, 2004).

ORGANIZATIONS

The National Multiple Sclerosis Society. 733 Third Avenue, 6th floor, New York, NY 10017. (212) 986-3240 or (800) 344-4867; Fax: (212) 986-7981. nat@nmss.org. http://www.nationalmssociety.org.

Marcos do Carmo Oyama

Iuri Drumond Louro

A neuromuscular disorder that characteristically involves the destruction of myelin, the insulating material around nerve fibers. The onset of the disease is unusual in persons under 15 or over 60 years of age, and peak incidence is found in people in their 20s and 30s. Multiple sclerosis affects females more frequently than males by approximately 2:1. Distribution is worldwide, but there is an unusual relationship to latitude, with a much higher incidence at northern latitudes than near the Equator.

In multiple sclerosis, only the central nervous system is affected, but both incoming and outgoing processes may be disrupted. Common initial symptoms reflect this underlying disease mechanism. They include blindness in one eye due to disruption of the conduction of the nerve impulse through the optic nerve; weakness of one side of the body due to impairment of the downstream signals from the motor areas of the cerebral cortex through the spinal cord; difficulties with coordination related to problems with cerebellar function; and disturbances in sensation, such as tingling and numbness in an arm or a leg that is related to dysfunction of incoming sensory signals. Multiple sclerosis is a progressive disease, so that over time there is often an accumulation of new symptoms and problems.

In its classic form, the disease spreads both temporally and anatomically. Temporally, there may be a series of acute attacks, but between attacks a person may recover fully and remain well for some time. Anatomically, areas of disruption of myelin (demyelination) are scattered throughout the nervous system and spinal cord. Thus, symptoms depend upon what part of the nervous system is affected at any given time. The course of the disease is unpredictable.

The basic cause of the disease is not known. There clearly are genetic factors in that the incidence of the disease is 20 times higher in first-degree relatives than in the general population. However, other factors must be involved, including infection (presumably viral) or possibly an immunological mechanism. The prevailing hypothesis combines these two possible etiological mechanisms to suggest that some type of viral infection occurs early in life to alter the patient's immune system. Thus, the activity and progression of the disease are related to altered immune functions within the central nervous system. In keeping with this hypothesis, therapy is aimed at altering the immune status of the affected individual. See also Human genetics; Immunogenetics; Nervous system disorders.

A slowly progressive disease involving nerve degeneration; it may take many years to develop to the stage of paralysis, and it is subject to random periods of spontaneous remission. There is some evidence that supplements of polyunsaturated fatty acids slow its progression.

A progressive disease characterized by disseminated demyelination of nerve fibers of the brain and spinal cord. It begins slowly, usually in young adulthood, and continues throughout life with periods of exacerbation and remission. The first signs are paresthesias, or abnormal sensations in the extremities or on one side of the face. Other early signs are muscle weakness, vertigo, and visual disturbances.

Definition

Multiple sclerosis is a chronic, degenerative disease of the central nervous system (CNS). The CNS is comprised of the brain and the spinal cord. In the CNS, the nerves are covered by a protective layer called the myelin sheath. Myelin helps keep the nerve healthy. It also improves nerve conduction. In multiple sclerosis, inflammation causes the nerves to gradually lose this myelin cover. This repeated inflammation and erosion leads to scarring (sclerosis), which impairs the nerve's ability to conduct impulses. Eventually, even the nerves themselves are affected. Because the nervous system controls and coordinates a number of body functions, patients with MS gradually lose a variety of functions, including memory and the ability to see, speak or walk.

Description

Multiple sclerosis is a chronic debilitating disease that affects as many at 350,000 in the United States alone (2.5 million worldwide). Most patients are first diagnosed of the disease at age 20-40. However, the disease may appear as early as age 12 or as late as age 50. MS strikes women earlier in life. Women are also affected more frequently than men and whites more often than other races.

Causes & Symptoms

The causes of multiple sclerosis are still unknown, although many factorsare suspected. In the United States, whites are diagnosed with MS twice as often as blacks or Hispanics. Asians are the least affected. There is some consensus, however, that the following factors may contribute to the development of multiple sclerosis:

• Genetic heredity. Family members of multiple sclerosis patients have a 1 in 50 chance of having MS; the odds for people without an affected family member are 1 in 1,000. If an identical twin is diagnosed with MS, the remaining twin has a 1 in 3 chance of becoming affected as well. Recent research has shown that several autoimmune diseases, including MS, share a common genetic link. In other words, patients with MS might share common genes with family members that have other autoimmune diseases like systemic lupus, rheumatoid arthritis, and others.

• Viral infection. Most MS patients have high levels of antibodies to measles and other viruses. Therefore, multiple sclerosis may be the body's delayed immune reaction to viruses such as measles, Herpes simplex, rubella, and parainfluenza. A 2001 study also suggested that Epstein-Barr virus, the virus that causes mononucleosis, probably increases risk of MS.
• Autoimmune reaction. Scientists know that MS is an autoimmune disorder, an illness in which the body attacks its own myelin as if it were a foreign substance. Although research has identified which immune cells are responsible and how they are activated, no one knows what causes the immune system to begin this attack.
• Geography. Countries in the temperate zones (above 40°) such as Northern Europe, North America, Australia, and New Zealand have significantly higher incidence of multiple sclerosis than countries in the tropics. In the United States, people who live below the 37th parallel develop MS at a rate of 57–78 cases per 100,000 people. Those who live above the line have a prevalence rate of 110–140 cases per 100,000 people.
• Diet. Studies have shown that populations at high risk of developing multiple sclerosis tend to consume a lot of dairy products and animal fats. On the contrary, in countries such as Japan, people eat few dairy products but consume lots of fish, soy-rich foods, and seeds, which are good sources of essential fatty acids. The incidence rates in these countries are very low. Thus, essential fatty acid deficiency due to excessive consumption of saturated fats may contribute to the development of multiple sclerosis.

Diagnosis

In order to determine whether or not a patient has multiple sclerosis, doctors often rely on the Schumacher criteria:

• Patient's symptoms indicate neurological damage in more than one areas.
• Patient's symptoms have worsened for more than six months.
• There are at least two events (each lasting for more than one day) separated by at least one month.
• Neurological exam of the patient shows abnormal central nervous system function.
• Symptoms reflect damage in the white matter of the CNS only.
• Patient is older than 10 but less than 50 years old.
• Patient does not have stroke, lupus, or any disease that may have similar symptoms.

A diagnosis of multiple sclerosis is made when patient's symptoms fit Schumacher's criteria and neurological exams, MRI, and laboratory results also show corresponding abnormalities. In 2001, a panel convened by the National Multiple Sclerosis Society wrote new diagnostic criteria for MS, the first update in about 20 years. The new criteria formally recommend MRI and outline how doctors should use the results of tests like cerebral spinal fluid analysis.

MS symptoms vary significantly in terms of severity, intensity and duration. Sensory symptoms are the first warning signs. Many patients notice color distortion, blurred or double vision, and temporary blindness. Their senses of smell, hearing, touch, and taste are also affected. They experience muscle weakness and difficulty walking, as well as muscle spasms and numbness, tingling, or prickling ("pins and needles") sensations called paresthesias. As the disease progresses, sudden partial or complete paralysis of the arms or legs is common, as are an inability to speak clearly, move without tremors, or hear clearly. Mental functions are also affected. Patients can not concentrate or remember as clearly as before. They often become depressed. They may laugh or cry uncontrollably. As conditions worsen, they lose control of bodily functions. Some patients find that hot weather exacerbates their symptoms. Cold baths or air conditioning may help during these periods. There are also periods, called remissions, in which patients are free of symptoms; remission can be complete or partial.

While there is a rare, rapidly progressing form of MS that can be fatal in as little as a few days or weeks, MS generally affects the quality of life more than it diminishes life expectancy. Most patients can look forward to decades of life after diagnosis. Many are able to continue to live a relatively normal life for at least 20 years after onset, although some patients become disabled within a few months of being diagnosed. In addition, because MS patients are frequently forced into immobility

and spend a lot of time sitting in wheelchairs they are susceptible to such common complications of the disabled as urinary tract infections, skin ulcers, pneumonia, or pulmonary embolism (blood clot in the lung) in addition to side effects from prescribed drugs.

Treatment

Nutritional Therapy

Many multiple sclerosis patients follow a low-fat diet developed by Dr. Roy Swank, who recommends his diet to slow down disease progression. The following are his recommendations:

• Consume no more than 10 g of saturated fat per day.
• Limit polyunsaturated fat consumption to 50 g or less per day.
• Take 1 tbsp of cod liver oil per day to supplement essential fatty-acid intake. Cod liver oil is a good source of omega-3 fatty acid, one of the two essential fatty acids.
• Consume adequate amount of protein in the diet, preferably plant protein such as soy, beans, seeds, and nuts.
• Eat more fish, a good source of omega-3 fatty acid. Swank recommends having fish three or more times per week. Omega-3 fatty acid is believed to support myelin production and improve nerve function.

In addition to following the Swank diet, Dr. Michael Murray and Dr. Joseph Pizzorno, the authors of the book Encyclopedia of Natural Medicine also recommend the following nutritional supplements:

• Flaxseed oil. Murray and Pizzorno recommend replacing the fish oil in Swank's diet with flaxseed oil because the latter can provide both omega-3 and omega-6 fatty acids. Omega-6 fats, studies have shown, also help alleviate MS symptoms.
• Antioxidants such as selenium, vitamin C, and vitamin E. Patients with multiple sclerosis often have antioxidant deficiency.
• Vitamin B₁₂. MS patients often lack Vitamin B₁₂, and correcting this deficiency is believed to help decrease myelin destruction.

Exercise and Physical Therapy

Almost any form of exercise or movement therapy is beneficial for MS patients. For patients too weak to exercise alone, a massage or assisted physical therapy should be helpful to improve circulation to the limbs and promote well-being. Those that are less restricted may find t'ai chi, qigong, yoga, martial arts, conventional cardiovascular exercise, and/or water aerobics helpful.

Other Treatments

Other alternative treatments such as aromatherapy (body massage with rosemary or juniper essential oils) and hydrotherapy (hot or cold baths used to treat affected areas, also a program of exercise performed in water) may also improve muscle strength in MS patients. Chinese herbs, especially ginseng, are also helpful in managing the disease. Wearing a cooling vest may also help, according to a 2001 study. The vest cools patients (without affecting their temperatures) and also appears to promote production of white cell nitrous oxide, which may play a role in MS.

Allopathic Treatment

Standard treatment consists of an exercise program, diet modification, and medication. Three relatively new drugs may be prescribed: beta-interferon A (Avonex), which can limit the progressions of disability; beta-interferon-B (Betaseron), which reduces the number and severity of relapses; and Glatiramer acetate (Copaxone), which helps prevent relapse in patients with the relapsing-remitting (RR) type of MS. (These are patients who have a period of time with no or few symptoms [remission] following acute exacerbations [relapse] of disease.) All are administered by injection. These drugs have significant side effects including fever, tiredness, weakness, chills, muscle aches and inflammation at injection sites. Avonex may be better tolerated than Betaseron.

For symptomatic treatment of muscle spasm, Baclofen is most effective; its dosage must be carefully tailored to specific patient's needs. An implantable infusion pump that delivers the drug directly into the spinal cord can be used for patients with severe spasticity. Diazepam (valium) is sometimes given together with baclofen to increase its effectiveness. Alternative antispastic drugs are tizanidine and dantrolene. Steroids such as methylprednisolone and prednisone are also sometimes used to treat flare-ups.

Expected Results

Patients whose symptoms worsen quickly right after diagnosis, those who have significant impairment in muscle movement or brain functions at onset and who have very abnormal magnetic resonance imaging (MRI) results at the beginning have poor prognosis. On the other hand, patients who recover quickly after the initial symptoms or those who experience only sensory impairment for five years or more after diagnosis often are able to maintain work longer and live longer than those with chronic progressive multiple sclerosis.

Prevention

There is no way to prevent the onset of multiple sclerosis, though a diet low in saturated fat may be helpful.

Resources

Books

Burton Golberg Group. "Multiple Sclerosis." In Alternative Medicine: The Definitive Guide. Tiburon, CA: Future Medicine Publishing, Inc., 1999.

Holland, Nancy J., T. Jock Murray, and Stephen C. Rheingold. Multiple Sclerosis: A Guide for the Newly Diagnosed. New York, NY: Demos Vermande, 1996.

Murray, Michael T., and Joseph E. Pizzorno. "Multiple Sclerosis." In Encyclopedia of Natural Medicine. Revised 2nd ed. Rocklin, CA: Prima Publishing, 1998.

Rudick, Richard A. "Multiple Sclerosis and Related Conditions." In Cecil Textbook of Medicine, 21st ed. W.B. Saunders Company, 2000.

Periodicals

Acherio, Alberto, et al. "Epstein-Barr Virus Antibodies and Risk of Multiple Sclerosis: A Prospective Study." JAMA, The Journal of the American Medical Association. 286; no. 24 (December 26, 2001):3083-3086.

Moran, M. "Autoimmune Diseases Could Share Common Genetic Etiology." American Medical News. 44; no. 38: (October 8, 2001):38.

Vastag, B. "New Diagnostic Criteria for MS Issued." JAMA, The Journal of the American Medical Association. 286; no. 14 (October 10, 2001):1703.

"Wearing Colling Vest Helps Improve Symptoms." Pain and Central Nervous System Week. (October 6, 2001).

Organizations

Multiple Sclerosis Association of America (MSAA). 706 Haddonfield Road. Cherry Hill, NJ 08002-2652. (800) LEARN-MS (532-7667) Fax: (609) 661-9797. http://www.msaa.com.

Multiple Sclerosis Foundation, Inc. (MSF). 6350 North Andrews Avenue. Fort Lauderdale, FL 33309. (800) 441-7055 Fax: (954) 938-8708.

National Multiple Sclerosis Society (NMSS). 733 3rd Avenue. New York, NY 10017-3288. (800) 344-4867 or (212) 986-3240. http://www.nmss.org.

Other

Lazoff, Marjorie, MD. "Multiple Sclerosis." Emedicine.comhttp://www.emedicine.com/emerg/topic321.htm

[Article by: Mai Tran; Teresa G. Odle]

Multiple sclerosis (MS) is a disorder that affects primarily the myelinated white matter of the central nervous system (CNS), the brain, optic nerves, and spinal cord. There is no known cause. Myelin is the fatty sheath that insulates nerve fibers (axons). Partial or complete loss of myelin due to MS impairs nerve conduction through affected axons, producing symptoms and functional impairment referable to them. Thus, MS may produce mild to severe weakness, lack of coordination, disordered sensations, partial loss of vision, impaired control of bladder and bowel function, impaired cognition, or any combination of these effects.

Early in the course of the disorder, symptoms are often brief and transient—impaired function caused by a particular episode, or relapse, tends to improve, in what is called a "remission." Remissions may be partial or total. However, over the course of years, incomplete recovery from relapses may occur, leading to the accumulation of impaired function and producing some degree of disability in about 70 percent of affected individuals. Among those who become disabled, some do not experience improvement from the beginning. However, it is important to realize that, although it is a common cause of disability among young to middle-aged individuals, MS is very unpredictable in a particular person; it does not necessarily disable and it does not necessarily shorten life span appreciably.

The average age of occurrence of the first symptom(s) is thirty-three, but MS may show itself as early as childhood or as late as age sixty or beyond. It affects almost twice as many women as men, and primarily in men and women of predominantly or mixed Caucasian parentage. Approximately 350,000 people in the United States have MS, and it is estimated to affect about 3 million people worldwide. However, MS is rare among South and East Asians, and among blacks in Africa. These differences suggest that susceptibility to develop MS may be genetically determined. However, among identical twins where one has MS, no more than 50 percent of the unaffected twins will go on to develop MS. This lends support to the concept that an environmental trigger, perhaps a viral infection, acts in concert with the genetic setting to produce MS. Siblings and children of those with MS have a somewhat greater chance of developing MS, but no specific genetic pattern has been identified. It is likely that multiple genes are involved in conferring susceptibility.

The frequency of MS has been studied closely since the 1930s. However, despite improved diagnostic methods (and improved treatment), the incidence (number of new cases per year in the population) does not appear to have increased.

Even after many years of intensive research, the cause of MS remains elusive, and it is a challenging subject for research. The most widely accepted hypothesis at this time is that an infection triggers an autoimmune response in genetically susceptible individuals. Autoimmunity implies that the body's immune-defense system erroneously and inappropriately attacks normal tissues, in this case the myelin and/or the cell that synthesizes and supports myelin, the oligodendrocyte.

Diagnosing MS is often very challenging. To do so involves documenting the occurrence of two or more episodes of impaired function, occurring at different times, that are referable to CNS white matter, while excluding all other possible causes of the problems. The fact that MS affects primarily the CNS white matter makes it possible to visualize very accurately areas of inflammation and demyelination via magnetic resonance imaging (MRI). MRI is an invaluable aid to diagnosis, although the MRI picture alone is not sufficient to be certain of the diagnosis. MRI is also used to identify new relapses, and to quantify the number and size of past episodes. Similarly, the cerebrospinal fluid typically shows alterations that may support a diagnosis, but a diagnosis cannot be made without appropriate clinical history and neurological examination.

Even though its cause is still mysterious, treatments have been developed that have reduced the number of relapses by more than 30 percent. These agents include recombinant interferon beta (IFNß; particular brand names include Avonex, Betaseron, and Rebif) and glatiramer acetate (Copaxone), each of which is widely used. Laboratory and clinical studies of many other possible treatments are underway, which is a very hopeful indicator of more effective therapies to come in the future. In addition to these disease-modifying agents, treatment often includes the use of medications intended for purely symptomatic relief, as well as physical therapy and occupational therapy. The challenges posed by an uncertain clinical course, and by chronic disability among some individuals, makes psychological support a key part of management.

The National Multiple Sclerosis Society (http://nmss.org/), similar organizations in other countries, and the International Federation of Multiple Sclerosis Societies (http://www.who.int/ina-ngo/ngo/ngo076.htm) are excellent sources of further information about the disorder, ongoing research, and treatment.

(SEE ALSO: Environmental Determinants of Health; Genes; Genetic Disorders; Genetics and Health)

Bibliography

Burks, J. S., and Johnson, K. P., eds. (2000). Multiple Sclerosis: Diagnosis, Medical Management, and Rehabilitation. New York: Demos.

Paty, D. W., and Ebers, G. C., eds. (1998). Multiple Sclerosis. Philadelphia, PA: F. A. Davis.

— DONALD H. SILBERBERG

For more information on multiple sclerosis, visit Britannica.com.

A medical condition in which the myelin sheath gradually disappears around nerve cells, impairing the transmission of nerve impulses and resulting in sufferers gradually losing control over their muscles. Up until the 1980s, people with multiple sclerosis (MS) were generally advised that physical activity would exacerbate their condition and that they should live a quiet life. In 1970 an American international alpine skier, Jimmie Huega, following this advice began to deteriorate physically and mentally. In order to stem the deterioration, he decided to develop a cardiovascular endurance programme that included stretching and strengthening exercises. His programme helped him regain health within the constraints of MS. His results have inspired hundreds of other MS sufferers to incorporate exercise into their treatment at a non-profit making centre he established in Avon (Colorado USA). In 2005, the Jimmie Huega Center was continuing to help families living with MS minimize the impact of the disease through exercise and lifestyle changes.

A chronic disease of the central nervous system characterized by the hardening of patches of tissue in the brain and spinal cord. The cause of this disease has to do with damage to the sheathes of nerves, and there is no specific treatment. It occurs in varying degrees of severity and, in the worst case, can result in permanent paralysis.