Neuromuscular Junction Disorders

Myasthenia gravis is an autoimmune disease caused by antibody attack directed at the acetylcholine or MuSK receptors, which are clustered at post-synaptic muscle fiber endplates in striated muscles. This interferes with transduction of nerve signals to the appropriate muscles. This results in weakness of the muscles involved, causing problems with eyelid opening, double vision, speech, swallowing, and breathing difficulties, as well as arm and leg weakness. Depending on the muscles involved and the degree of involvement, difficulties vary from mild to life-threatening. Therapy is directed at reducing the effects of the antibody attack by prolonging the duration of transmitter availability or reducing the amount of antibody produced. Occasionally there are crises consisting of severe and occasionally abrupt disease worsening associated with respiratory failure. The patient in crisis must be intensively supported, while therapy to reduce antibody levels, and possibly other immune system elements, is undertaken. With proper care, nearly all patients regain normal function. Lambert-Eaton syndrome is usually seen in the setting of cancer, particularly small cell cancer of the lung. One-third of patients develop this problem on an autoimmune basis. In patients with underlying neoplasms, therapy is directed at the neoplasm. In patients whose disease is autoimmune mediated, therapy is directed at reducing antibody production or levels.