An autoimmune disease resulting from an abnormality in neuromuscular transmission, characterized by a fluctuating degree of muscle weakness. Myasthenia gravis is a chronic autoimmune neuromuscular disorder (see illustration) characterized by varying degrees of weakness and excessive fatiguability of voluntary muscle. The weakness is usually aggravated by activity, and there is partial or complete restoration of strength after a period of rest or the administration of anticholinesterase medications. See also: Autoimmunity; Muscle; Muscular system; Muscular system disorders; Nervous system (vertebrate); Nervous system disorders; Neurobiology; Synaptic transmission
It has been shown that the basic defect in myasthenia gravis is a reduction in the number of acetylcholine receptor sites in the postsynaptic membrane of the neuromuscular junction (see illustration). It also has been shown that many myasthenic patients often have serum immunoglobulins that partially block acetylcholine receptors. In fact, myasthenic changes can be produced in mice by the injection of serum immunoglobulin from myasthenic patients. The antiacetylcholine receptor antibody is thought to originate in the thymus gland, and the antigenic stimulus is believed to be the acetylcholine receptors in the myoid cells in the thymus gland. See also: Acetylcholine; Antibody; Antigen; Immunoglobulin; Thymus gland
In myasthenic individuals, abnormalities have been demonstrated in the thymus gland and skeletal muscle. There is an increased incidence of thymoma (a tumor that affects the thymus gland) in myasthenia gravis. In contrast, in those without a thymoma, hyperplasia of the germinal centers is a common finding in the thymus gland. See also: Tumor
Muscle from myasthenic persons shows variable histologic findings. In some individuals, muscle is completely normal. In others, collections of lymphocyte-like cells are present in otherwise normal muscle. In still others, patterns suggesting neurogenic atrophy or a myopathy are found. However, a simplification of the secondary synaptic clefts and a widening of the primary synaptic cleft of the motor end plate have been demonstrated by electron microscopy.
Although the disease affects young women more commonly and usually in the third decade of age, it can occur in either sex at any age. In approximately 10% of those affected, myasthenia gravis is associated with a thymoma, and the prognosis in such individuals tends to be worse. In the majority of persons, weakness affects muscles of the head, neck, and limbs (generalized myasthenia); however, in some, the weakness is restricted to the muscles of the eyes (ocular myasthenia), in which case the disease is usually benign. Fifteen percent of babies born of myasthenic mothers have symptoms requiring treatment at birth, but these symptoms are transient and disappear in a few weeks (neonatal myasthenia).
The muscles most often affected in generalized myasthenia are those of the eyes, with ptosis and double vision (diplopia); of mastication, swallowing, and speech; and of respiration. Limb muscles are also frequently affected. Initially, the affected muscles have normal or nearly normal strength. However, with repeated use, progressive weakness develops. Thus, ptosis and diplopia become worse as the day progresses, speech becomes slurred and nasal with continued conversation, or the individual may be unable to finish eating because of increasing difficulty with chewing and swallowing. These symptoms are often only partially reversed with rest. In some individuals, myasthenia gravis is a life-threatening illness because of respiratory weakness. See also: Respiratory system disorders
The diagnosis of myasthenia gravis is based on the demonstration of increasing muscle weakness with exertion, and reversal of the weakness after the administration of anticholinesterase drugs.
The standard treatment for myasthenia gravis has been the use of long-acting anticholinesterase agents; thymectomy and immunosuppressive drugs are reserved for those individuals with generalized myasthenia that does not respond sufficiently to anticholinesterase agents. In those individuals with significant persistent symptoms, plasmapheresis (a medical procedure that removes some plasma from the blood) has also become another mode of treatment. When a thymoma is detected, thymectomy is mandatory.
Persons being treated with anticholinesterase drugs may develop periods of severe muscle weakness with respiratory paralysis. These paralytic periods may result from inadequate dosage (myasthenic crisis) of these agents or from overmedication (cholinergic crisis) with these agents; most commonly, though, they appear to result from development of resistance to the drugs. See also: Drug resistance