The Mechanism Behind Myasthenia

Myasthenia gravis is an autoimmune disease, meaning that it develops from within the body’s own defense system. In fact, due to remarkable advances over the past 25 years, it is the best understood of all the autoimmune diseases. In this type of condition, a person’s immune system, which normally fights germs and other invaders, produces antibodies that attack his or her own cells. Myasthenia gravis results when the body’s defenses mistakenly produce antibodies that attack the acetylcholine receptors on skeletal (voluntary) muscles.

To understand how myasthenia causes problems, we must start with how nerves and muscles interact. To move any muscle—to breathe, swallow, speak, smile, or look in any direction—your nerves must transmit a signal to that muscle. An electrical impulse traveling down the motor nerve releases the neurotransmitter acetylcholine. The muscle receives this chemical signal in a specialized area, below the nerve, that is tightly packed with acetylcholine receptors. When the acetylcholine released from the nerve combines with the receptor on the muscle, a new electrical impulse is initiated within the muscle, which causes the muscle to contract.

If something interferes with the signal’s transmission from nerve to muscle, the result is weakness and fatigue. In myasthenia, the problem is that antibodies attack the acetylcholine receptors, leaving too few of them available to receive the signal. The brain itself is not involved in myasthenia gravis, and the body’s mechanisms for initiating movement at the level of the brain and spinal cord are intact. Even the peripheral nerves remain healthy. Only the acetylcholine receptors on the skeletal muscles are abnormal.

As we have learned more about myasthenia gravis, we have come to recognize it in more people. About 1 in every 7,000 individuals has the condition, and the rate may even be three times that. Females often develop it in their teens and twenties, while in men it usually appears in the fifth to eighth decades. However, myasthenia can occur at any age.

Why some people’s immune systems erroneously attack their acetylcholine receptors is not clear. The answer in many cases seems to be related to the thymus gland, a lymph gland located under the breastbone that serves its main function during early development. About three quarters of all people with myasthenia have abnormalities of the thymus gland. Eighty-five percent of these show evidence of overactivity (hyperplasia) of the gland, and the other 15 percent have tumors there. We therefore suspect that the immune system’s error may originate in the thymus gland.

Myasthenia may also occur in association with other autoimmune diseases, such as thyroiditis, lupus, and certain blood diseases. This suggests a more generalized error by the immune system in distinguishing between “self,” which should not be attacked, and “nonself,” which could represent a threat.

It is rare for myasthenia to be inherited. However, similar disorders of nerve-to-muscle transmission do have a genetic component. These are termed congenital myasthenic syndromes, and they are extremely rare.