$Unique_ID{BRK04014} $Pretitle{} $Title{Multiple Sclerosis} $Subject{Multiple Sclerosis MS Demyelinating Disease Disseminated Sclerosis Amyotrophic Lateral Sclerosis (ALS) Charcot-Marie-Tooth Disease Dejerine-Sottas Disease Friedreich's Ataxia Guillain-Barre Syndrome Chronic Inflammatory Demyelinating Polyneuropathy Leukodystrophy } $Volume{} $Log{} Copyright (C) 1984, 1985, 1986, 1987, 1988, 1989, 1990, 1991, 1992, 1993, National Organization for Rare Disorders, Inc. 15: Multiple Sclerosis ** IMPORTANT ** It is possible that the main title of the article (Multiple Sclerosis) is not the name you expected. Please check the SYNONYMS listing to find the alternate name and disorder subdivisions covered by this article. Synonyms MS Demyelinating Disease Disseminated Sclerosis Insular Sclerosis Information on the following diseases can be found in the Related Disorders section of this report: Amyotrophic Lateral Sclerosis (ALS) Charcot-Marie-Tooth Disease Dejerine-Sottas Disease Friedreich's Ataxia Guillain-Barre Syndrome Chronic Inflammatory Demyelinating Polyneuropathy Leukodystrophy General Discussion ** REMINDER ** The Information contained in the Rare Disease Database is provided for educational purposes only. It should not be used for diagnostic or treatment purposes. If you wish to obtain more information about this disorder, please contact your personal physician and/or the agencies listed in the "Resources" section of this report. Multiple Sclerosis is a chronic disorder of the central nervous system (CNS) that causes the destruction of the covering (myelin sheath) over the nerves. The course of this disease is variable; it may advance, relapse, remit, or stabilize. The demyelinating plaques or patches scattered throughout the central nervous system interfere with the ability of the nerves to communicate (neurotransmission) and can cause a wide range of neurological symptoms. Symptoms The symptoms of Multiple Sclerosis may vary greatly. Some people may have visual impairment (including blind spots), double vision (diplopia), or involuntary rhythmic movements of the eyes (nystagmus). People with Multiple Sclerosis may also experience impairment of speech, numbness or tingling sensation in the limbs and difficulty walking. Dysfunction of the bladder and bowel may also be present. Multiple Sclerosis is rarely fatal; the average life expectancy is 93 percent of that of the general population. One in 5 Multiple Sclerosis patients experience one attack, followed by little or no advance in the disorder. Two-thirds of patients can walk independently 25 years after diagnosis. Approximately 50 percent of those with Multiple Sclerosis pursue most of the activities they engaged in prior to their diagnosis. In some cases, however, paralysis of different severities may make it necessary to use a cane, crutches, and other aids while walking. In a very small number of cases, the disease accelerates and may result in life-threatening complications. Causes The exact cause of Multiple Sclerosis is not known. An autoimmune association, possibly in a viral or environmental setting, has been suggested. Autoimmune disorders are caused when the body's natural defenses (antibodies, lymphocytes, etc.), against invading organisms suddenly begin to attack perfectly healthy tissue. The human T-lymphotropic virus (HTLV-1) has been proposed as another possible cause. The HTLV-1 virus is a retrovirus that has been associated with other central nervous system disorders and certain blood malignancies. An hereditary predisposition has been suggested, but it seems that other factors need to be present as well. A genetic predisposition means that a person may carry a gene for a disease but it may not be expressed unless something in the environment triggers the disease. It has been proposed that a Multiple Sclerosis "susceptibility gene" (MSSG) exists. There is, as yet, no definite genetic pattern that can be discerned. Studies have shown that the siblings of a person with Multiple Sclerosis are at a 10 to 15 percent higher risk of developing the disorder than the general population, whose risk is 0.1 percent. A Canadian study indicated that the daughters of mothers with Multiple Sclerosis have a 5 percent risk of developing the disease. This may be accounted for the by an immune system that may or may not foster the development of the disorder (histocompatible antigens). A 1989 Australian study implied that a virus carried by cats might be responsible. Approximately 7 percent of domestic cats have been shown to have a demyelinating disease that closely resembles Multiple Sclerosis. Both infected cats and patients have been tested and shown to be carrying a morbillivirus (a virus that resembles the measles virus). More research is needed to determine whether this virus has a role in Multiple Sclerosis and if it can be transmitted from cats. Affected Population Multiple Sclerosis affects approximately 58 in every 100,000 people, numbering around 130,000 individuals. The disorder may appear at any age, although the diagnosis is most often made between 20 and 40 years of age. Multiple Sclerosis is more common in Caucasian Americans than in Americans of African or Oriental heritage. In a few ethnic societies (Eskimos, Bantus and American Indians), Multiple Sclerosis is rare or absent. This may hint at a genetic link to this disorder. Multiple Sclerosis seems to occur more often the moderate regions (temperate climates) of the world. Related Disorders Symptoms of the following disorders can be similar to those of Multiple Sclerosis. Comparisons may be useful for a differential diagnosis: Amyotrophic lateral sclerosis (ALS) is a disease of the motor neurons that send signals to the skeletal muscles. It generally affects both the upper and the lower muscle groups and results in the progressive weakness and wasting away of the muscles involved. There are several varieties of Amyotrophic Lateral Sclerosis. The early symptoms may include slight muscular weakness, clumsy hand movements and difficulty performing fine motor tasks. Weakness in the legs may result in clumsiness and tripping, and a slowing of speech may also be present. Other symptoms may include muscle stiffness and coughing. (For more information on this disorder, choose "Amyotrophic Lateral Sclerosis" as your search term in the Rare Disease Database). Charcot-Marie-Tooth Disease (also known as CMT Disease) is a hereditary neurological disorder characterized by muscle weakness and atrophy, primarily in the muscles of the legs. Symptoms of Type I Charcot-Marie-Tooth Disease usually begin in middle childhood or teenage years with a deformity of the foot characterized by a high arch and hyperextension of the toes (gampsodactyl or claw-foot). This produces a "stork leg" deformity. With time, Charcot-Marie-Tooth disease spreads to the upper extremities and produces a "stocking-glove" pattern of diminished sensitivity. There is a decrease in the sensitivity to vibration, pain and temperature. (For more information on this disorder, choose "Charcot-Marie-Tooth Disease" as your search term in the Rare Disease Database). Dejerine-Sottas Disease is a rare progressive hereditary disorder that causes the enlargement of the peripheral nerves and the loss of myelin. This results in a burning or tingling sensation in the limbs, generalized muscle weakness and the loss of coordination in the hands and forearms. Weakness in the back of the legs eventually spreads to the front of the legs resulting in difficulty and pain when walking. Mild vision problems may also be present. (For more information on this disorder, choose "Dejerine-Sottas Disease" as your search term in the Rare Disease Database). Friedrich's Ataxia is a progressive hereditary disorder that affects the neuromuscular system. It is generally diagnosed in childhood or adolescence. There are slow degenerative changes of the spinal cord and the brain that affect speech and motor coordination. These changes may produce an unsteady walk or numbness and weakness in the arms and legs. The legs generally become progressively weaker resulting in a staggering, lurching walk or trembling when standing still. (For more information on this disorder, choose "Friedreich's Ataxia" as your search term on the Rare Disorder Database). Guillain-Barre Syndrome (Acute Idiopathic Polyneuritis) is a rare rapidly progressive polyneuropathy. Although the exact cause is not known, a gastrointestinal virus or respiratory infection precedes the onset of the syndrome in almost half the cases. The myelin sheath that covers the nerves is damaged and results in muscle weakness. The symptoms may include a burning or tingling sensation in the feet followed by weakness of the legs. Eventually the torso, upper limbs and face may be affected. (For more information on this disorder, choose "Guillain-Barre Syndrome" as your search term in the Rare Disease Database). Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) is a rare disorder in which there is swelling of the nerve roots and the destruction of the covering (myelin sheath) over the nerves. This causes weakness, paralysis and impairment of motor function especially in the limbs. Symptoms may include burning, numbness or tingling of the hands and feet or the arms and legs. Reflexes may be weakened or absent, and the muscles of the face may become weak. Other symptoms may include difficulty in walking and respiratory problems. (For more information on this disorder, choose "Chronic Inflammatory Demyelinating Polyneuropathy" as your search term on the Rare Disease Database). Leukodystrophy is the name given to a group of very rare, progressive, metabolic, genetic diseases that affect the brain, spinal cord and often the peripheral nerves. Each of the leukodystrophies will affect one of the chemicals that make up the myelin sheath that covers the nerve fibers or it may affect the white matter of the brain. Most of the leukodystrophies are present at birth but some may appear more slowly over time and even into adulthood. Leukodystrophy causes the patient to have problems with movement, vision, hearing, feeling and thinking. This can result in difficulty walking, stiffness, a "floppy" feeling in the muscles, paralysis or convulsions. (For more information on this disorder, choose "Leukodystrophy" as your search term on the Rare Disease Database). Therapies: Standard Multiple Sclerosis has no known prevention or cure. Common treatments may include the administration of ACTH (adrenocorticotropic hormone), prednisone or other corticosteroid drugs to help reduce the severity of recurrent attacks. These drugs do not slow down or stop the progression of this disorder. A wide variety of drugs are prescribed to treat symptoms. These may include muscle relaxants and anticonvulsants to help reduce muscle spasms. Antidepressants, aspirin or acetaminophen may also help ease pain. Physical therapy and exercise programs (especially aquatic or water therapy) may be of value in some patients. Therapies: Investigational Research into the treatment of Multiple Sclerosis is vigorously underway. The drug cyclophosphamide is being tested and some patients experience temporary beneficial effects. Maintenance booster shots of cyclophosphamide are now being tested to see if these effects can be prolonged. Beta-interferon injections given directly into the spinal canal (intrathetically) appear to cut the rate of progressive recurrent episodes in half for some Multiple Sclerosis patients in experimental trials. Other trials are underway using blood plasma replacement (plasmapheresis) in Multiple Sclerosis. This procedure is a method for removing unwanted substances (toxins, metabolic substances and plasma parts) from the blood. Blood is removed from the patient and blood cells are separated from plasma. The patient's plasma is then replaced with other human plasma and the blood is transfused back into the patient. This therapy is still under investigation to analyze side effects and effectiveness. More research is needed before plasmapheresis can be recommended for use in all but the most severe cases of Multiple Sclerosis. Also under study is the use of monoclonal antibodies, alpha-interferon, amantadine, and the anti-gout drug colchicine for use in the treatment of Multiple Sclerosis. A two-year clinical trial of the orphan drug copolymer I (COP-1), a synthetic polypeptide developed in Israel indicated that in fifty patients with relapsing-remitting Multiple Sclerosis the average number of attacks per patient was significantly lower for the group treated with copolymer I. An International trial of several hundred patients is currently underway. This orphan drug is manufactured by Lemmon Pharmaceuticals, P.O. Box 904, Sellersville, PA, 18960. This drug is currently available under a "Treatment IND" to patients who are not in a clinical trial. Contact Lemmon Pharmaceuticals for more information. Intravenous injection of 4-aminopyridine is also being studied in the hope that this drug may be capable of improving conduction in demyelinated nerve pathways. Twelve Multiple Sclerosis patients were treated at Rush Medical College in Chicago with 4-aminopyridine. Of the twelve patients treated, ten showed varying degrees of improvement in vision, eye movement, coordination and walking. These effects lasted for about four hours. More study of this drug is needed to determine its safety and find a way to prolong its effects. Studies of hyperbaric oxygen treatment for Multiple Sclerosis has led to the conclusion that it is not helpful in the management of this disorder. Researchers working with specific antibody treatments (monoclonal antibodies) are trying to find a way to halt disease progression in Multiple Sclerosis patients. These antibodies may block the autoimmune process of Multiple Sclerosis, and appear to have caused no adverse effects in initial clinical testing. One promising candidate is an antibody to the immune response antigen, which may interrupt the symptoms of the disorder but leave the immune system intact. Chimeric M-T412 (Human Murine) IgG monoclonal Anti-CD4 is one of these new antibody treatments being tested. It is manufactured by Centocor, Inc., 244 Great Valley Parkway, Malvern, PA, 19355. Another biologic agent being tested for the treatment of Multiple Sclerosis is Myelin, developed by Autoimmune, Inc., 75 Francis St., Boston, MA, 02115. Other research is aimed at immune suppressing drugs. Recent research, however, on the use of Cyclosporine (an immune suppressant prescribed for organ transplant patients to avoid rejection of a transplanted organ) has indicated that the therapeutic dose required for Multiple Sclerosis patients is much to high. This can lead to unacceptable side effects. The orphan drug Betaseron is being tested on patients with a relapsing and remitting form of Multiple Sclerosis. Betaseron is manufactured by Triton Biosciences. More research is needed to determine if Betaseron (a form of beta-interferon) will be a safe and effective treatment for Multiple Sclerosis. Infusion of the drug Baclofen by a surgically implanted pump is being studied by scientists for the treatment of spasticity associated with Multiple Sclerosis. Infusion of the drug directly into the spinal space, rather than oral administration, seems to provide patients with better relief of spasticity and may improve muscle tone for longer periods of time. Smaller quantities of Baclofen seem to be needed when it is infused rather than given orally. More research is needed to provide evidence of the safety and effectiveness of this type of Baclofen administration. Alpha interferon has been used experimentally on people with Multiple Sclerosis. Preliminary evidence suggests that alpha interferon may delay attacks, leading to progressively fewer attacks of Multiple Sclerosis in some people. Radiation treatments are being used experimentally to reduce tissues that produce T cells (cells that are produced in the bone marrow and mediate immune responses) in Multiple Sclerosis patients. Lymphoid irradiation is directed at the spleen and lymph nodes in the neck, armpit, chest, abdomen and groin. Elan Drug Co., is testing EL-970 as a treatment for Multiple Sclerosis. It is hoped that this drug may improve nerve conduction in a number of Multiple Sclerosis patients, increasing their visual and motor abilities. EL-970 was licensed from Rush-Presbyterian-St. Lukes Medical Center in Chicago. Researchers at the University of Pennsylvania are studying the use of Photopheresis as a treatment for Multiple Sclerosis. Photopheresis has been used to treat other types of diseases such as cancer and skin problems. In this method of treating the blood, the drug 8-MOP is given to the person orally. Then the blood is removed and radiated with ultraviolet light, and then returned to the body. The patient does not receive radiation, but the treated blood's cell structure is altered to stimulate the immune system. It is hoped that this may lead to an increase the body's defense against Multiple Sclerosis. Clinical trials are underway to study the role of T-cell receptor repertoire in Multiple Sclerosis. Interested persons may wish to contact: Dr. David H. Mattson University of Rochester 601 Elmwood Ave., Box 605 Rochester, NY 14642 (716) 275-7854 This disease entry is based upon medical information available through February 1993. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder. Resources For more information on Multiple Sclerosis, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 The National Multiple Sclerosis Society maintains over 120 chapters throughout the United States which provide direct services to people with MS and their families, including occupational and physical therapy, support groups, clinics, and professional and public education. Information about chapters can be obtained from the national office. National Multiple Sclerosis Society, National Headquarters 733 Third Ave. New York, NY 10017-3288 (212) 986-3240 (800) 624-8236 NIH/National Institute of Neurological Disorders & Stroke (NINDS) 9000 Rockville Pike Bethesda, MD 20892 (301) 496-5751 (800) 352-9424 References MENDELIAN INHERITANCE IN MAN, 10th Ed.: Victor A. McKusick, Editor: Johns Hopkins University Press, 1992. Pp. 317-318. CECIL TEXTBOOK OF MEDICINE, 19th Ed.: James B. Wyngaarden, and Lloyd H. Smith, Jr., Editors; W.B. Saunders Co., 1990. Pp. 2196-2102. INTRATHECAL BACLOFEN FOR SEVERE SPASTICITY, R.D. Penn, et al.; New Eng J Med (June 8, 1989, issue 320 (23)). Pp. 1517-1521. TREATMENT OF MULTIPLE SCLEROSIS WITH HYPERBARIC OXYGEN. RESULTS OF A NATIONAL REGISTRY, E.P. Kidwell et al.; Arch Neurol (Feb. 1991; 48(2)): Pp. 195-199. THE SUPRASPINAL ANXIOLYTIC EFFECT OF BACLOFEN FOR SPASTICITY, S.R. Hinderer; Am J Med Rehabil (Oct. 1990; (69(5)): Pp. 254-258. HIGH DOSE ORAL BACLOFEN: EXPERIENCE IN PATIENTS WITH MULTIPLE SCLEROSIS, G.D. Ehrlich et al.; Neurology (March 1991; (41(3)): Pp. 335-43.