Myasthenia Gravis.

Myasthenia gravis is an autoimmune disease in which antibodies bind to acetylcholine receptors or to functionally related molecules in the postsynaptic membrane at the neuromuscular junction. The antibodies induce weakness of skeletal muscles, which is the sole disease manifestation.1-3 The weakness can be generalized or localized, is more proximal than distal, and nearly always includes eye muscles, with diplopia and ptosis.2 The pattern of involvement is usually symmetric, apart from the eye involvement, which is often markedly asymmetric and involves several eye muscles. The weakness typically increases with exercise and repetitive muscle use (fatigue) and varies over the course of a day and from day to day, often with nearly normal muscle strength in the morning. With an annual incidence of 8 to 10 cases per 1 million persons and a prevalence of 150 to 250 cases per 1 million,4 myasthenia gravis and its various subgroups are the major diseases that affect the neuromuscular junction. The Lambert– Eaton myasthenic syndrome and neuromyotonia are additional, rare, presynaptic autoantibody disorders characterized by skeletal-muscle dysfunction.5 Congenital myasthenic syndromes and toxin-induced conditions (e.g., botulism) can also affect the neuromuscular junction and lead to muscle weakness. This review focuses on new diagnostic tests for myasthenia gravis, updated treatment algorithms, and individualization of therapy according to biomarkers. The diagnosis of myasthenia gravis is confirmed by the combination of relevant symptoms and signs and a positive test for specific autoantibodies.6 Antibodies against acetylcholine receptors, muscle-specific kinase, and lipoprotein receptor– related protein 4 (LRP4) are specific and sensitive for the detection of myasthenia gravis, define disease subgroups, and point to pathogenic variations among these subgroups. The localization of the antigens at the neuromuscular junction and in skeletal muscle is shown in Figure 1. The disease-inducing potential of the antibodies depends on the epitope, binding pattern, IgG subclass, antibody cross-linking capacity, antibody concentration, and access of antibody to the muscle end plate.7 In antibody-negative cases, neurophysiological tests and a characteristic response to therapy secure the diagnosis.8 An ice-pack test that reverses ptosis supports the diagnosis. Thymic status should be determined by means of mediastinal imaging.9 The main value of such imaging is to detect a thymoma; this imaging is neither sensitive nor specific for the identification of thymic hyperplasia. Supplementary antibody tests can provide further help in characterizing the thymus.10 Symptomatic, immunoactive, and supportive approaches to therapy have a very good effect, and the prognosis regarding muscle strength, functional abilities, quality of life, and survival is generally good.11,12 Therapy should be aimed at full or nearly full pharmacologic remission (i.e., the absence of myasthenic symptoms and signs while the patient is receiving therapy). From the Department of Clinical Medicine, University of Bergen, and the Department of Neurology, Haukeland University Hospital — both in Bergen, Norway. Address reprint requests to Dr. Gilhus at the Department of Neurology, Haukeland University Hospital, 5021 Bergen, Norway, or at nils . gilhus@ uib . no.