Myasthenia gravis Health Article

Definition

Myasthenia gravis is an autoimmune disease that causes muscle weakness.

Description

The name myasthenia gravis literally means "grave muscle weakness". Myasthenia gravis (MG) affects the neuromuscular junction, interrupting the communication between nerve and muscle, and thereby causing weakness. A person 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.

Genetic profile

Myasthenia gravis is not inherited directly nor is it contagious. It is usually considered sporadic, meaning that it occurs by chance. One to four percent of cases are familial, which means they occur more than once in a family. Predisposition in a family to develop myasthenia gravis may be due to autoimmunity in general.

Demographics

About 36,000 people in the United States are affected by MG; roughly 14 people per 100,000. It can occur at any age, but is most common in women under age 40, and in men who are over 60. Occasionally the disease is present in more than one person in a family.

Signs and symptoms

Myasthenia gravis is an autoimmune disease, meaning 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 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 over-medication.

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, poor muscle tone, 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.