Myasthenia gravis and myasthenic syndromes.

More than a decade ago myasthenic symptoms were observed in rabbits immunized with acetylcholine receptor (AChR) [119] and AChR deficiency was found at the neuromuscular junction in human myasthenia gravis (MG) [36]. By 1977 the autoimmune character of MG and the pathogenic role of AChR antibodies had been established by several measures. These included the demonstration of circulating AChR antibodies in nearly 90% of patients with MG [87], passive transfer with IgG of several features of the disease from human to mouse [149], localization of immune complexes (IgG and complement) on the postsynaptic membrane [30], and the beneficial effects of plasmapheresis [20, 123]. Substantial subsequent progress has occurred in understanding the structure and function of AChR and its interaction with AChR antibodies. The relationships of the concentration, specificities, and functional properties of the antibodies to the clinical state in MG have been carefully analyzed, and the mechanisms by which AChR antibodies impair neuromuscular transmission have been further investigated. The clinical classification of MG has been refined, the role of the thymus gland in the disease has been further clarified, and new information has become available on transient neonatal MG. The prognosis for generalized MG is improving, but there is still no consensus on its optimal management. Novel therapeutic approaches to MG are now being explored in animal models. Recognition of the autoimmune origin of acquired MG also implied that myasthenic disorders occurring in a genetic or congenital setting had a different cause. As a result, a number of congenital myasthenic syndromes have come to be recognized and investigated. Finally, an acquired disorder of neuromuscular transmission different from MG, the Lambert-Eaton myasthenic syndrome, has also been shown to have an autoimmune basis. In this syndrome, active zone particles of the presynaptic membrane are direct or indirect targets of the pathogenic autoantibodies.