Myasthenia gravis is an autoimmune disorder that impairs communication between nerves and muscles, resulting in episodes of muscle weakness.
Myasthenia gravis is more common among women. It usually develops in women between the ages of 20 and 40. However, the disorder may affect men or women at any age. Rarely, it begins during childhood.
Nerves communicate with muscles by releasing a chemical messenger (neurotransmitter), which interacts with receptors on muscles (at the neuromuscular junction) and stimulates muscles to contract. In myasthenia gravis, the immune system produces antibodies that attack one type of receptor on the muscle side of the neuromuscular junction—the receptors that respond to the neurotransmitter acetylcholine. As a result, communication between the nerve cell and the muscle is disrupted. What causes the body to attack its own acetylcholine receptors—an autoimmune reaction—is unknown. According to one theory, malfunction of the thymus gland may be involved. In the thymus gland, certain cells of the immune system learn how to differentiate between the body and foreign substances. The thymus gland also contains muscle cells (myocytes) with acetylcholine receptors. For unknown reasons, the thymus gland may instruct the immune system cells to produce antibodies that attack the acetylcholine receptors. People may inherit a predisposition to this autoimmune abnormality. About 65% of people who have myasthenia gravis have an enlarged thymus gland, and about 10% have a tumor of the thymus gland (thymoma). About half of thymomas are cancerous (malignant).
Some people with myasthenia gravis do not have antibodies to acetylcholine receptors but have antibodies to an enzyme involved in the formation of the neuromuscular junction instead. These people may require different treatment.
The disorder may be triggered by infections, surgery, or use of certain drugs, such as nifedipine or verapamil (used to treat high blood pressure), quinine (used to treat malaria), and procainamide (used to treat abnormal heart rhythms).
Neonatal myasthenia develops in 12% of babies born to women who have myasthenia gravis. Antibodies against acetylcholine receptors, which circulate in the blood, may pass from a pregnant woman through the placenta to the fetus. In such cases, the baby has muscle weakness that disappears several days to a few weeks after birth. The remaining 88% of babies are not affected.
Episodes of worsened symptoms (exacerbations) are common. At other times, symptoms may be minimal or absent.
The most common symptoms are
The weakness disappears when the muscles are rested but recurs when they are used again. Weakness is less severe in cooler temperatures.
In 40% of people with myasthenia gravis, the eye muscles are affected first, but 85% eventually have this problem. In 15% of people, only the eye muscles are affected, but in most people, the whole body is affected. Difficulty speaking and swallowing and weakness of the arms and legs are common. Hand grip may alternate between weak and normal. This fluctuating grip is called milkmaid's grip. Neck muscles may become weak. Sensation is not affected.
When people with myasthenia gravis use a muscle repetitively, the muscle usually becomes weak. For example, people who once could use a hammer well become weak after hammering for several minutes. However, muscle weakness varies in intensity from minute to minute, hour to hour, and day to day, and the course of the disease varies widely.
About 15 to 20% of people with myasthenia gravis have a severe episode (called myasthenia crisis) at least once in their life. It is sometimes triggered by an infection. The arms and legs may become extremely weak, but even then, they do not lose sensation. In some people, the muscles needed for breathing weaken. This condition is life threatening.
Doctors suspect myasthenia gravis in people with episodes of weakness, especially when the eye or facial muscles are affected or when weakness increases with use of the affected muscles and disappears with rest. Because acetylcholine receptors are damaged, drugs that increase levels of acetylcholine can be used to help confirm the diagnosis. Edrophonium, injected intravenously, is most commonly used. People are asked to exercise the affected muscle until it tires. Then they are given the drug. If it temporarily and quickly improves muscle strength, myasthenia gravis is a possible diagnosis.
Other tests can also help with the diagnosis. Because coolness and rest lessen weakness due to myasthenia, doctors may apply an ice pack to the person's eyes or ask the person to lie quietly in a dark room for a few minutes with eyes closed. If weakness lessens, doctors suspect myasthenia gravis.
Other diagnostic tests are needed to confirm the diagnosis. They include electromyography (stimulating muscles, then recording their electrical activity) and blood tests to detect antibodies to acetylcholine receptors and sometimes the other antibodies present in people with the disorder. Blood tests are also done to check for other disorders. Computed tomography (CT) or magnetic resonance imaging (MRI) of the chest is done to assess the thymus gland and to determine whether a thymoma is present.
Drugs may be used to help improve strength quickly or to suppress the autoimmune reaction and slow progression of the disorder.
Drugs that increase the amount of acetylcholine, such as pyridostigmine (taken by mouth), may improve muscle strength. Long-acting capsules are available for nighttime use to help people who experience severe weakness or difficulty swallowing when they awaken in the morning. Doctors must periodically adjust the dose, which may have to be increased during episodes of weakness. However, doses that are too high can cause weakness that is difficult to distinguish from that caused by the disorder. Also, the effectiveness of these drugs may decrease with long-term use. Increasing weakness, which may be due to a decrease in the drug's effectiveness, must be evaluated by a doctor with expertise in treating myasthenia gravis.
Common side effects of pyridostigmine include abdominal cramps and diarrhea. Drugs that slow the activity of the digestive tract, such as atropine or propantheline, may be needed to counteract these effects.
To suppress the autoimmune reaction, doctors may also prescribe a corticosteroid, such as prednisone, or a drug that inhibits the immune system (immunosuppressant), such as mycophenolate mofetil, cyclosporine, or azathioprine. These drugs are taken by mouth. Most people need to take a corticosteroid indefinitely. If the dose is too high when the corticosteroid is started, symptoms may worsen initially, but improvement occurs within a few months. The dose is then reduced to the minimum that is effective. Corticosteroids, when taken for a long time, can have moderate or severe side effects. Thus, azathioprine may be given so that the corticosteroid can be stopped or its dose reduced. With azathioprine, improvement takes about 18 months.
When drugs do not provide relief or when a myasthenic crisis occurs, immune globulin or plasma exchange (see Blood Transfusion:Special Blood Donation Procedures) may be used. Immune globulin (a solution containing many different antibodies collected from a group of donors) may be given intravenously once a day for 5 days. Over two thirds of people improve in 1 to 2 weeks, and effects may last for several months. In plasma exchange, toxic substances (in this case, abnormal antibodies) are filtered from the blood.
If a thymoma is present, the thymus gland must be surgically removed to prevent the thymoma from spreading. Even if no thymoma is present, removing thymus tissue appears to be beneficial.
Last full review/revision September 2012 by Michael Rubin, MDCM