Myasthenia Gravis and Congenital Myasthenic Syndromes

Emma Ciafaloni, MD Muscle and Neuromuscular Junction Disorders p. 1767-1784 December 2019, Vol.25, No.6 doi: 10.1212/CON.0000000000000800
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PURPOSE OF REVIEW Myasthenia gravis (MG) is an autoimmune neuromuscular disease that causes fluctuating weakness in ocular, bulbar, and limb muscles and can, in 15% of cases, cause myasthenic crisis, a neurologic emergency characterized by respiratory failure. Although infrequent, MG needs to be promptly recognized and treated because the potential for improvement and remission is very high. The diagnosis of MG can be challenging and delayed because of the fluctuating nature of muscle weakness and the overlap of signs and symptoms with other neuromuscular diseases.

This article reviews the importance of prompt recognition of the typical signs and symptoms, best tests to confirm the diagnosis, currently available acute and chronic treatment modalities, the role of thymectomy, and the natural history of the disease. Special consideration related to the diagnosis and management in women during pregnancy and in children will also be reviewed. This article also includes an overview of congenital myasthenic syndromes.

RECENT FINDINGS Recent significant efforts in standardizing and improving the care of patients with MG have occurred, as well as new momentum in developing new drugs for patients with MG who do not adequately respond to currently available treatments. The number of clinical trials and drugs in development for MG is steadily increasing. Eculizumab has been recently approved by the US Food and Drug Administration (FDA) for adult patients with generalized MG who are acetylcholine receptor–antibody positive, based on the REGAIN (Safety and Efficacy of Eculizumab in Refractory Generalized Myasthenia Gravis) study, a phase 3, randomized, double-blind, placebo-controlled, multicenter trial. An international, multicenter, randomized trial comparing thymectomy plus prednisone with prednisone alone has demonstrated that thymectomy improves clinical outcome in patients with nonthymomatous MG. Clinical care guidelines have been published, and the recommendations for clinical research standards and the Myasthenia Gravis Foundation of America MGFA clinical classification published in 2000 have become widely accepted by the clinical and research community of MG experts.

SUMMARY MG is a highly treatable disease with many effective treatment modalities available and with a natural history that continues to improve thanks to better diagnostic tests and effective drugs. The diagnosis and management of patients affected by MG can be highly rewarding for any neurologist as most patients are able to live normal lives if treated appropriately. Nevertheless, future research is needed to address unresolved clinical issues, such as when and how to discontinue immunosuppressive medications in patients in remission, the role and timing of thymectomy in children, and better treatment options for refractory patients.

Address correspondence to Dr Emma Ciafaloni, MD, 601 Elmwood Ave, PO Box 673, Rochester, NY 14642, Emma_Ciafaloni@URMC.Rochester.edu.

RELATIONSHIP DISCLOSURE: Dr Ciafaloni has received personal compensation for serving on advisory boards and speakers bureaus and/or as a consultant for Avexis, Inc; Biogen; Medscape; Pfizer Inc; PTC Therapeutics; Sarepta Therapeutics; and Strongbridge Biopharma plc. Dr Ciafaloni has received research/grant support from Biogen, the Centers for Disease Control and Prevention, CureSMA, the Muscular Dystrophy Association, the National Institutes of Health, Orphazyme, the Parent Project Muscular Dystrophy, the Patient-Centered Outcomes Research Institute, PTC Therapeutics, Santhera Pharmaceuticals, Sarepta Therapeutics, and the US Food and Drug Administration. Dr Ciafaloni has received royalties from Oxford University Press and personal compensation from Medlink for editorial duties.

UNLABELED USE OF PRODUCTS/INVESTIGATIONAL USE DISCLOSURE: Dr Ciafaloni reports no disclosure.

© 2019 American Academy of Neurology.