Myasthenia Gravis

In myasthenia gravis, weakness occurs when the nerve impulse to initiate or sustain movement does not adequately reach the muscle cells. This is caused when immune cells target and attack the body's own cells (an autoimmune response). This immune response produces antibodies that attach to affected areas, preventing muscle cells from receiving chemical messages (neurotransmitters) from the nerve cell.

The cause of autoimmune disorders such as myasthenia gravis is unknown. In some cases, myasthenia gravis may be associated with tumors of the thymus (an organ of the immune system). Patients with myasthenia gavis have a higher risk of having other autoimmune disorders like thyrotoxicosis, rheumatoid arthritis, and systemic lupus erythematosus.

Myasthenia gravis affects about 3 of every 10,000 people and can affect people at any age. It is most common in young women and older men.

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 benign 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.

Some or all of these factors (developmental, genetic, infectious, and thymic) may interact to create the autoimmune reaction.

The earliest symptoms of MG often result from weakness of the extraocular muscles, which control eye movements. Symptoms involving the eye (ocular symptoms) include double vision (diplopia), especially when not gazing straight ahead, and difficulty raising the eyelids (ptosis). A person with ptosis may need to tilt their head back to see. Eye-related symptoms remain the only symptoms for about 15% of MG patients. Another common early symptom is difficulty chewing and swallowing, due to weakness in the bulbar muscles, which are in the mouth and throat. Choking becomes more likely, especially with food that requires extensive chewing.

Weakness usually becomes more widespread within several months of the first symptoms, reaching their maximum within a year in two-thirds of patients. Weakness may involve muscles of the arms, legs, neck, trunk, and face, and affect the ability to lift objects, walk, hold the head up, and speak.

Symptoms of MG become worse upon exertion, and better with rest. Heat, including heat from the sun, hot showers, and hot drinks, may increase weakness. Infection and stress may worsen symptoms. Symptoms may vary from day to day and month to month, with intervals of no weakness interspersed with a progressive decline in strength.

"Myasthenic crisis" may occur, in which the breathing muscles become too weak to provide adequate respiration. Symptoms include weak and shallow breathing, shortness of breath, pale or bluish skin color, and a racing heart. Myasthenic crisis is an emergency condition requiring immediate treatment. In patients treated with anticholinesterase agents, myasthenic crisis must be differentiated from cholinergic crisis related to overmedication.

Pregnancy worsens MG in about one third of women, has no effect in one third, and improves symptoms in another third. About 12% of infants born to women with MG have "neonatal myasthenia," a temporary but potentially life-threatening condition. It is caused by the transfer of maternal antibodies into the fetal circulation just before birth. Symptoms include weakness, floppiness, feeble cry, and difficulty feeding. The infant may have difficulty breathing, requiring the use of a ventilator. Neonatal myasthenia usually clears up within a month.

Diagnosis of Myasthenia Gravis

Myasthenia gravis is often diagnosed accurately by a careful medical history and a neuromuscular exam, but several tests are used to confirm the diagnosis. Other conditions causing worsening of bulbar and skeletal muscles must be considered, including drug-induced myasthenia, thyroid disease, Lambert-Eaton myasthenic syndrome, botulism, and inherited muscular dystrophies.

MG causes characteristic changes in the electrical responses of muscles that may be observed with an electromyogram, which measures muscular response to electrical stimulation. Repetitive nerve stimulation leads to reduction in the height of the measured muscle response, reflecting the muscle's tendency to become fatigued.

Blood tests may confirm the presence of the antibody to the acetylcholine receptor, though up to a quarter of MG patients will not have detectable levels. A chest x ray or chest computed tomography scan (CT scan) may be performed to look for thymoma.

Treatment of Myasthenia Gravis

While there is no cure for myasthenia gravis, there are a number of treatments that effectively control symptoms in most people.

Edrophonium (Tensilon) blocks 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 standard 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 response to pyridostigmine and thymectomy are not adequate. Drugs include corticosteroids such as prednisone, and the non-steroids azathioprine (Imuran) and cyclosporine (Sandimmune).

Plasma exchange may be performed to treat myasthenic crisis or to improve 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 for myasthenic crisis. 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.

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).

Prognosis of Myasthenia Gravis

Most people with MG can be treated successfully enough to prevent their condition from becoming debilitating. In some cases, however, symptoms may worsen even with vigorous treatment, leading to generalized weakness and disability. MG rarely causes early death except from myasthenic crisis.

Prevention of Myasthenia Gravis

There is no known way to prevent myasthenia gravis. Thymectomy improves symptoms significantly in many patients, and relieves them entirely in some. Avoiding heat can help minimize symptoms.