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Myasthenia Gravis +mI-us-!thE-nE-u-!gra-vus

by Michael Rubin, MDCM

Myasthenia gravis is an autoimmune disorder that impairs communication between nerves and muscles, resulting in episodes of muscle weakness.

  • Myasthenia gravis results from malfunction of the immune system.

  • People usually have drooping eyelids and double vision, and muscles become unusually tired and weak after exercise.

  • Tests using an ice pack or rest to see whether weakness lessens, electromyography, and blood tests help confirm the diagnosis.

  • Some drugs can improve muscle strength rapidly, and others can slow progression of the disorder.

Myasthenia gravis is more common among younger women and older men. It usually develops in women between the ages of 20 and 40 and in men between the ages of 50 and 80. 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—see Overview of Neuromuscular Junction Disorders) 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 these thymomas are cancerous (malignant).

Myasthenia gravis also often occurs in people with other autoimmune disorders, such as rheumatoid arthritis and disorders that cause the thyroid gland to become overactive (autoimmune hyperthyroidism).

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

  • 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

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.

Symptoms

Episodes of worsened symptoms (exacerbations) are common. At other times, symptoms may be minimal or absent.

The most common symptoms are

  • Weak, drooping eyelids

  • Weak eye muscles, which cause double vision

  • Excessive weakness of affected muscles after they are used

The weakness disappears when the muscles are rested but recurs when they are used again. Weakness is less severe in cooler temperatures.

In 50% 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.

Myasthenia crisis

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.


Diagnosis

  • Tests using an ice pack or rest

  • Electromyography

  • Blood tests

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 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, including thyroid disorders.

After myasthenia gravis is diagnosed, 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.

Treatment

  • Pyridostigmine or a similar drug

  • A corticosteroid or a drug that inhibits the immune system

  • Sometimes intravenous immune globulin or plasma exchange

  • Often removal of the thymus gland

Drugs may be used to

  • Help improve strength quickly

  • Suppress the autoimmune reaction and slow progression of the disorder

Drugs to help improve strength quickly

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. This effect is called cholinergic crisis.

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.


Treatments to suppress the autoimmune reaction

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 several weeks. 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, intravenous immune globulin (IVIG) or plasma exchange (see ) 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. It contains antibodies that help control the immune system and stop the autoimmune reaction that causes myasthenia gravis. 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. Improvement after plasma exchange is similar to that after taking immune globulin.


Other treatments

If a thymoma is present, the thymus gland must be surgically removed to prevent the thymoma from spreading. Removal may result in remission or enable doctors to reduce the dose of the corticosteroid.

Sometimes doctors remove the thymus even if there is no thymoma, but whether this treatment is effective is not clear.


Drugs Mentioned In This Article

  • Generic Name
    Select Brand Names
  • CALAN
  • QUALAQUIN
  • No US brand name
  • ADALAT CC, PROCARDIA
  • MESTINON
  • ATROPEN
  • RAYOS
  • NEORAL, SANDIMMUNE
  • IMURAN