Researchers Report Gains Against Muscle-Wasting Disease

Myasthenia gravis is muscle weakness, pure and simple, weakness down to the very fiber of a human being. Eyelids droop because the muscles that hold them up grow weak. Eyes cross because the muscles guiding them can no longer bear that burden. Arms and legs grow heavy and useless. Chewing, even swallowing, becomes a monumental effort. At its worst, the disease can even halt a person's breath. This is what can happen to people who contract myasthenia gravis, an autoimmune disease that likely affects two to three people per every 10,000 in the United States. While it strikes all ethnic groups and both men and women, it most often affects women under 40 and men over 60. Myasthenia gravis results when the immune system attacks the body's neuromuscular junctions, the places where nerve impulses are transferred to muscles. The muscles misfire, growing weaker and weaker with continued use, according to the National Institutes of Health. But the encouraging news is that, despite the debilitating and potentially deadly symptoms, myasthenia gravis is no longer a fatal disease. "In most cases, we can improve patients to where they are living a full life, from a social and employment standpoint. And life expectancy is not affected by myasthenia gravis in the vast majority of patients, unlike 30 to 40 years ago," said Dr. Gil Wolfe, associate professor of neurology at the University of Texas Southwestern Medical School in Dallas. That belies the disease's name, which is Latin and Greek in origin and literally means "grave muscle weakness." Symptoms can vary from person to person but always involve some form of muscle weakness, said Dr. Robert Ruff, director of neurology at the Cleveland Veterans Affairs Medical Center. "The most common manifestations are drooping of the eyelids, double vision, difficulty speaking with slurred or difficult-to-understand speech," Ruff said. "People can also get asymmetric or generalized muscle weakness in the limbs, swallowing mechanism, and muscles associated with breathing." When electrical impulses travel down a healthy nerve, the nerve endings normally release a neurotransmitter substance called acetylcholine, according to the National Institute of Neurological Disorders and Stroke. The substance travels through the neuromuscular junction and binds to receptors, which activate and generate a muscle contraction. In myasthenia gravis, antibodies interfere with or destroy the receptors for acetylcholine at the neuromuscular junction, preventing the muscle contraction from occurring. The disease is highly unpredictable and episodic, which has become one of the best ways to separate myasthenia gravis from other neuromuscular disorders. "Other disorders are more constant and fixed, while the symptoms in MG can fluctuate even from hour to hour," said Wolfe, who's also the Dr. Bob and Jean Smith Foundation Distinguished Chair in Neuromuscular Disease Research at the University of Texas Southwestern Medical School. The most serious health risk from the disease comes when it causes the voluntary muscles that control breathing to stop working, in what is known as a "myasthenia failure" or "myasthenia crisis." These are common among myasthenia gravis patients, but rarely fatal, Wolfe said. The victims survive by being put on a respirator until the crisis has passed. In patients whose respiratory muscles are weak, these crises can be triggered by infection, fever, an adverse reaction to medication, or emotional stress, according to the National Institutes of Health. "One in every four to five patients will go into myasthenia crisis," Wolfe said, adding that the disease's effect on the swallowing mechanism also poses serious health risks and can cause aspiration or pneumonia. While there's no cure for myasthenia gravis, there are treatments that can improve the efficiency of neuromuscular communications, thus relieving many of the symptoms, Ruff said. Drugs that suppress the immune system are one proven therapy, he said. Medications like Novantrone, prednisone, cyclosporine and azathioprine keep the body from interfering with the chemical receptors controlling muscle contractions. "With good immunosuppressive treatment, for many patients, the disease can be arrested or slowed," Ruff said. Other medications like neostigmine and pyridostigmine help improve neuromuscular transmission and increase muscle strength. Another treatment involves removal of the thymus gland, Ruff said. The thymus gland, which lies in the upper chest beneath the breastbone, plays an important role in the development of the immune system in early life. In adults with myasthenia gravis, the thymus gland is abnormal. Scientists believe the abnormal gland might give incorrect instructions to developing immune cells, turning the body against the neuromuscular junction by attracting receptor sites, Ruff said. "It's believed that removal of the thymus gland basically removes the signal that tells the body to produce antibodies against this receptor," he said. Thymectomy has been found to improve symptoms in more than 70 percent of patients. "Source":[ http://www.healthday.com/view.cfm?id=533699]

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