Definition

Myasthenia gravis, a chronic disease of the neuromuscular junction, is manifested by increasing skeletal muscle weakness, fatigability on effort, and at least partial restoration of function after rest.

Incidence

In the United States at least one in 7500 people have myasthenia gravis. In individuals younger than 50 years, the ratio of women to men with the disease is 3 to 2; however, in those older than 50 years, the disease is equally distributed between the sexes. Myasthenia gravis can begin spontaneously at any age, but it occurs most frequently between the ages of 30 to 40 years. The onset may be abrupt or insidious, and the course is fluctuating, marked by periods of exacerbation and remission. Spontaneous remissions that do occur sometimes persist for years.

Pathophysiology

Electron microscopic examination of the neuromuscular junction of the patient with myasthenia gravis shows a decrease in the number of functional postsynaptic ACh receptors (AChRs). The AChR lesion appears to be caused by immune-mediated destruction, blockage, or inactivation. The prejunctional ACh pool is normal.

Myasthenia gravis is a prototype autoimmune disease. Circulating antibodies react with myoneural AChR proteins, leading to varying degrees of dysfunction. Anti-AChR antibodies (immunoglobulin G [IgG]) are found in the sera of 85% to 90% of patients with myasthenia gravis, but the antibody level does not necessarily correlate with the severity of the disease. Most patients in clinical remission continue to show elevated serum levels of AChR antibodies.

The initiating stimulus for the production of anti-AChR IgG antibodies is unclear. A genetic cause or induction by microbial antigens has been postulated. The thymus gland seems to play a central role in the pathogenesis.

Pregnancy exacerbates the symptoms of myasthenia gravis in 40% of pregnant women with the disease; however, other patients with the disease experience remission or no change in symptoms during pregnancy. Anti-AChR antibodies that pass across the placenta may produce transitory symptoms of weakness in approximately 10% to 15% of infants born to mothers with myasthenia gravis. Signs of weakness (difficulty with breathing, ptosis, facial weakness) in the affected infant are usually present within the first few hours after birth. The condition lasts as long as 21 days, mirroring the half-life of the IgG antibodies.

Clinical manifestations

The clinical hallmarks of myasthenia gravis include a generalized muscle weakness, which improves with rest, and an inability to sustain or repeat muscular contractions. Enhanced effort produces enhanced weakness. The severity of myasthenia gravis can range from mild (slight ptosis only) to severe (respiratory failure). Environmental, physical, and emotional factors seem to affect the disease process, although unpredictably.

Mouth, eyes, pharynx, proximal limb, and shoulder girdle musculature are most often affected. Visual symptoms (ptosis and diplopia) from extraocular muscle weakness occur in more than 50% of patients with myasthenia gravis. The disease is restricted to the extraocular muscles in 20% of patients. Sensation and cognition are not affected by the disease process.

Thymus gland abnormalities are detectable in about 75% of patients with myasthenia gravis. Other autoimmune disorders, such as thyroid disease, collagen vascular diseases, polymyositis, and RA, occur more frequently in patients with myasthenia gravis. Myocarditis may complicate myasthenia gravis, especially in patients with thymomas. Microscopic lesions of myasthenic cardiac muscles are similar to skeletal muscle lesions, indicating a common pathogenesis. The myocardial inflammation produces dysrhythmias, particularly atrial fibrillation and atrioventricular block.