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Myasthenia gravis (MG)

Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 25 February 2013, last major update December 2012
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● Defect in nicotinic acetylcholine receptor (AChR) present in subsynaptic membrane of neuromuscular junction (at motor end plate), due to circulating autoantibodies to receptor
● Acetylcholine receptor also present in normal thymus, in myoid type cells
● Thymus may contain ectopic germinal centers with B cells producing pathogenic anti-acetylcholine receptor antibodies (Ann N Y Acad Sci 2008;1132:135)


● May be due to T cells attacking myoid cells, then T cells induce B cells to produce autoantibodies; physiological connection with thymomas is unclear
● Two step hypothesis: hyperplastic medullary thymic epithelial cells are involved in provoking infiltration and thymic myoid cells (with intact AChR) are involved in germinal center formation (Am J Pathol 2007;171:893)
● MG patients have high number / ratio and abnormal distribution of thymic dendritic cells, which may be actively involved in pathogenesis (Zhonghua Yi Xue Za Zhi 2008;88:3349)
● Autoimmunity may be related to increased toll-like receptor 4 expression in thymus of some myasthenic patients (Am J Pathol 2005;167:129)

Clinical features

● 12% of MG patients have other autoimmune diseases, including Gravesí disease, rheumatoid arthritis
● MG patients with thymomas may have autoantibodies to titin or other striated muscle antigens
● 65% of patients have thymic hyperplasia, 25% normal thymus, 10% thymomas; risk factors for thymoma are males with initial MG symptoms age 50+ years
● Present or develops in 30-45% of patients with thymomas, usually months/years after excision of thymoma
● Lymphoid follicles in thymoma or adjacent thymus indicates higher risk for MG
● MG associated thymomas are morphologically similar to non-MG associated thymomas

Prognostic factors

● Mildest clinical outcome associated with normal thymus, most severe associated with thymoma (Clin Neurol Neurosurg 2012 Jul 5 [Epub ahead of print])


● Thymectomy (regardless of presence of thymoma)

Micro images

Thymic follicular hyperplasia

Differential diagnosis

Lambert-Eaton syndrome: muscle weakness due to antibodies to neuronal calcium channel

End of Mediastinum > Thymus > Myasthenia gravis (MG)

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