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Myasthenia gravis

Abstract

Myasthenia gravis (MG) is an autoimmune disease caused by antibodies against the acetylcholine receptor (AChR), muscle-specific kinase (MuSK) or other AChR-related proteins in the postsynaptic muscle membrane. Localized or general muscle weakness is the predominant symptom and is induced by the antibodies. Patients are grouped according to the presence of antibodies, symptoms, age at onset and thymus pathology. Diagnosis is straightforward in most patients with typical symptoms and a positive antibody test, although a detailed clinical and neurophysiological examination is important in antibody-negative patients. MG therapy should be ambitious and aim for clinical remission or only mild symptoms with near-normal function and quality of life. Treatment should be based on MG subgroup and includes symptomatic treatment using acetylcholinesterase inhibitors, thymectomy and immunotherapy. Intravenous immunoglobulin and plasma exchange are fast-acting treatments used for disease exacerbations, and intensive care is necessary during exacerbations with respiratory failure. Comorbidity is frequent, particularly in elderly patients. Active physical training should be encouraged.

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Fig. 1: Structure of the neuromuscular junction.
Fig. 2: Structures of the main autoantigens in MG.
Fig. 3: Pathophysiology of MG at the neuromuscular junction.
Fig. 4: The process of normal immune tolerance.
Fig. 5: A simplified diagnostic algorithm for MG.
Fig. 6: Typical asymmetrical bilateral ptosis in a patient with MG.
Fig. 7: Treatment algorithms for chronic MG and acute MG exacerbations.

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All authors have contributed to and are responsible for all parts of the Review. The first draft was written by N.E.G. (Introduction, Epidemiology and Overview of Primer); S.T. (Mechanisms/pathophysiology); J.P. (Diagnosis, screening and prevention); A.E. (Management); T.M.B. (Quality of life); and J.J.G.M.V. (Outlook).

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Correspondence to Nils Erik Gilhus.

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Competing interests

N.E.G. has received speaker’s honoraria from Octapharma and Alexion and consulting honoraria from Argenx and Ra Pharma. S.T. has shares in the research and diagnostic laboratory Tzartos NeuroDiagnostics. A.E. was a member of the advisory board for Alexion and is a scientific award jury member for Grifols and a safety data monitor for UCB. J.P. has received travel support or honoraria from MerckSerono, Biogen Idec, Novartis, Teva, Chugai Pharma, Bayer Schering, Alexion, Roche, Genzyme, Medimmune, Eurimmune, MedDay, Abide and Argenx and grants from MerckSerono, Novartis, Biogen Idec, Teva, Abide and Bayer Schering. T.M.B. was a member of the steering committee for Argenx. The institution of J.J.G.M.V. (Leiden University Medical Centre) has received fees from Alexion, Argenx and Ra Pharma owing to consultations by J.J.G.M.V. and has received royalties for antibody tests.

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Gilhus, N.E., Tzartos, S., Evoli, A. et al. Myasthenia gravis. Nat Rev Dis Primers 5, 30 (2019). https://doi.org/10.1038/s41572-019-0079-y

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