Myasthenia gravis
Description
Myasthenia gravis (MG) is an autoimmune disease that causes muscle weakness. It affects the neuromuscular junction, interrupting the communication between nerve and muscle, and thereby causing weakness. People with MG may have difficulty moving their eyes, walking, speaking clearly, swallowing, and even breathing, depending on the severity and distribution of weakness. Increased weakness with exertion, and improvement with rest, is a characteristic feature of MG.
About 30, 000 people in the United States are affected by MG. It can occur at any age, but is most common in women who are in their late teens and early twenties, and in men in their sixties and seventies.
MG has been associated with malignant thymoma , a disease in which cancer cells are found in the tissues of the thymus.
Causes
Myasthenia gravis is an autoimmune disease, meaning that it is caused by the body's own immune system.
In MG, the immune system attacks a receptor on the surface of muscle cells. This prevents the muscle from receiving the nerve impulses that normally make it respond. MG affects "voluntary" muscles, which are those muscles under conscious control responsible for movement. It does not affect heart muscle or the "smooth" muscle found in the digestive system and other internal organs.
A muscle is stimulated to contract when the nerve cell controlling it releases acetylcholine molecules onto its surface. The acetylcholine lands on a muscle protein called the acetylcholine receptor. This leads to rapid chemical changes in the muscle which cause it to contract. Acetylcholine is then broken down by acetylcholinesterase enzyme, to prevent further stimulation.
In MG, immune cells create antibodies against the acetylcholine receptor. Antibodies are proteins normally involved in fighting infection. When these antibodies attach to the receptor, they prevent it from receiving acetylcholine, decreasing the ability of the muscle to respond to stimulation.
Why the immune system creates these self-reactive "autoantibodies" is unknown, although there are several hypotheses:
- During fetal development, the immune system generates many B cells that can make autoantibodies, but B cells that could harm the body's own tissues are screened out and destroyed before birth. It is possible that the stage is set for MG when some of these cells escape detection.
- Genes controlling other parts of the immune system, called MHC genes, appear to influence how susceptible a person is to developing autoimmune disease.
- Infection may trigger some cases of MG. When activated, the immune system may mistake portions of the acetylcholine receptor for portions of an invading virus, though no candidate virus has yet been identified conclusively.
- About 10% of those with MG also have thymomas, or tumors of the thymus gland. The thymus is a principal organ of the immune system, and researchers speculate that thymic irregularities are involved in the progression of MG. A definite relationship exists between MG and thymoma: of patients with MG, 15% also have thymoma, and of patients with thymoma, 50% have MG.
Treatment
While there is no cure for myasthenia gravis, there are a number of treatments that effectively control symptoms in most people. Even though no rigorously tested treatment trials have been reported and no clear consensus exists on treatment strategies, MG is one of the most treatable immune disorders. Several factors require consideration before initiating treatment, such as the severity, distribution, and rapidity of the MG progression.
Edrophonium (Tensilon) is a drug used to block the action of acetylcholinesterase, prolonging the effect of acetylcholine and increasing strength. An injection of edrophonium rapidly leads to a marked improvement in most people with MG. An alternate drug, neostigmine, may also be used.
Pyridostigmine (Mestinon) is usually the first drug tried. Like edrophonium, pyridostigmine blocks acetylcholinesterase. It is longer-acting, taken by mouth, and well-tolerated. Loss of responsiveness and disease progression combine to eventually make pyridostigmine ineffective in tolerable doses in many patients.
Thymectomy, or removal of the thymus gland, has increasingly become a standard form of treatment for MG. Up to 85% of people with MG improve after thymectomy, with complete remission eventually seen in about 30%. The improvement may take months or even several years to fully develop. Thymectomy is not usually recommended for children with MG, since the thymus continues to play an important immune role throughout childhood.
Immune-suppressing drugs are used to treat MG if patient response to pyridostigmine and thymectomy is not adequate. These drugs include corticosteroids such as prednisone, and the non-steroids azathioprine (Imuran) and cyclosporine (Sandimmune).
Plasma exchange may also be performed to treat the condition or to strengthen very weak patients before thymectomy. In this procedure, blood plasma is removed
and replaced with purified plasma free of autoantibodies. It can produce a temporary improvement in symptoms, but is too expensive for long-term treatment. Another blood treatment, intravenous immunoglobulin therapy, is also used. In this procedure, large quantities of purified immune proteins (immunoglobulins) are injected. For unknown reasons, this leads to symptomatic improvement in up to 85% of patients. It is also too expensive for long-term treatment. There are indications that IVIg is an effective immunoglobulin for some categories of MG patients.
People with weakness of the bulbar muscles may need to eat softer foods that are easier to chew and swallow. In more severe cases, it may be necessary to obtain nutrition through a feeding tube placed into the stomach (gastrostomy tube).
Alternative and complementary therapies
No alternative therapies have been shown to be effective for the treatment of MG. Reports claiming that herbal remedies or alternative treatments alleviate or cure MG have not been corroborated by properly controlled clinical trials , which are required to evaluate the benefit of such treatments.
Among complementary MG therapies, prescription of low dose atropine can help relieve the cramping and diarrhea often caused by the drug Mestinon. Propantheline bromide (ProBanthine)is a drug similar to atropine, and it may also be prescribed to treat gastrointestinal discomfort. Caution must be taken not to take too much atropine because it cancels the beneficial effects of the anticholinesterase drugs. Ephedrine is sometimes also used with anticholinesterase therapy to strengthen the muscle tissue of MG patients.
Resources
BOOKS
Swash, Michael and Martin Schwarz. Neuromuscular Diseases: A Practical Approach to Diagnosis and Manage ment. Springer, 1997.
PERIODICALS
Davitt, B. V., G. A. Fenton, O. A. Cruz. "Childhood myasthe nia." Journal of Ophthalmic and Nursing Technology 19 (March-April 2000):74-81
Garg, R. K. "Myasthenia gravis." Journal of the Association of Physicians, India 46 (March 1998):286-93.
Bedlack, R. S., and D. B. Sanders. "How to handle myasthenic crisis. Essential steps in patient care." Postgraduate Medi cine 107 (April 2000):211-214.
Carrieri, P. B., E. Marano, A. Perretti, and G. Caruso. "The thymus and myasthenia gravis: immunological and neuro-physiological aspects." Annals of Medicine 31 (October 1999) Suppl 2:52-56
ORGANIZATION
Muscular Dystrophy Association. 3300 East Sunrise Drive, Tucson, AZ 85718. (520) 529-2000 or (800) 572-1717. <http:www.mdausa.org.> 29 June 2001.
Myasthenia Gravis Foundation of America. 222 S. Riverside Plaza, Suite 1540, Chicago, IL 60606. (800) 541-5454. <http://www.myasthenia.org> 29 June 2001.
Richard Robinson
Monique Laberge, Ph.D.
KEY TERMS
Antibody
—An immune protein normally used by the body for combating infection and which is made by B cells.
Atropine
—An alkaloid extract from belladonna.
Autoantibody
—An antibody that reacts against part of the self.
Autoimmune disease
—A disease caused by a reaction of the body's immune system.
Bulbar muscles
—Muscles that control chewing, swallowing, and speaking.
Immunoglobulin
—A protein substance produced by plasma cells which helps to fight infection.
Malignant thymoma
—A disease in which cancer cells are found in the tissues of the thymus, a small organ that lies under the breastbone.
Neuromuscular junction
—The site at which nerve impulses are transmitted to muscles.
Pyridostigmine bromide (Mestinon)
—An anti-cholinesterase drug used in treating myasthenia gravis.
Tensilon test
—A test for diagnosing myasthenia gravis. Tensilon is injected into a vein and, if the person has MG, their muscle strength will improve for about five minutes.
Thymectomy
—Removal of the thymus by surgery, radiation or chemical means
Thymus gland
—A small gland located just above the heart, involved in immune system development.
