Myasthenia gravis (MG) is a chronic autoimmune disorder of the postsynaptic membrane at the neuromuscular junction in skeletal muscle.
MG is characterized by muscle weakness that increases with exercise (fatigue) and improves on rest. It commonly presents with drooping eyelids, double vision, oropharyngeal and/or appendicular weakness, and shortness of breath.
Elevated serum levels of antibodies against the acetylcholine receptor (AChR) or muscle-specific tyrosine kinase (MuSK) are usually present. Antibodies have also been identified to proteins located at the neuromuscular junction: low-density lipoprotein receptor-related protein 4 (LRP4), agrin, collagen Q, and cortactin. Patients with MG may have elevated levels of one or more of these antibodies.
Clinical electrophysiology shows decremental response on repetitive nerve stimulation or increased jitter on single-fiber study.
Treatments include anticholinesterases and immunotherapy. Thymectomy may be required for thymoma. Thymectomy has also been shown to be effective in people with generalized MG without thymoma who are AChR antibody positive. It is not yet clear at which stages of MG, in which patients, and in what sequence in relation to other therapies, that thymectomy in nonthymoma patients should be done.
Eculizumab, a monoclonal antibody that inhibits complement activation, has shown clinical benefit in patients with treatment-resistant generalized MG and AChR antibodies.
Approximately 15% to 20% of patients with MG experience a myasthenic crisis (exacerbation necessitating mechanical ventilation).
Most patients, but not all, enjoy good quality of life and normal lifespan due to advances in diagnosis and in immunosuppressive and immunomodulatory treatment.
Myasthenia gravis (MG) is a chronic autoimmune disorder of the postsynaptic membrane at the neuromuscular junction in skeletal muscle. Circulating antibodies against the nicotinic acetylcholine receptor (AChR) or associated proteins impair neuromuscular transmission.
Patients present with muscle weakness, which typically worsens with continued activity (fatigue) and improves on rest. Severity varies from isolated eye muscle weakness to generalized muscle weakness to respiratory failure requiring mechanical ventilation.
History and exam
Key diagnostic factors
- muscle fatigability
- facial paresis
- proximal limb weakness
- shortness of breath
- family history of autoimmune disorders
- genetic markers
- cancer-targeted therapy
1st investigations to order
- serum acetylcholine receptor (AChR) antibody analysis
- muscle-specific tyrosine kinase (MuSK) antibodies
- serial pulmonary function tests
Investigations to consider
- striational receptor antibody assays
- repetitive nerve stimulation
- single-fiber EMG
- CT of chest
severe disease (class IV and V, myasthenic crisis)
mild disease (class I and II)
moderate disease (class III)
severe disease (post-myasthenic crisis): no intolerance or contraindication to immunosuppressants
severe disease (post-myasthenic crisis): intolerance or contraindication to immunosuppressants
Robert P. Lisak, MD, FRCP (E), FAAN, FANA
Parker Webber Chair in Neurology
Professor of Neurology
Professor of Immunology and Microbiology
Wayne State University School of Medicine
RPL is an Advisory Board member for Argenx (developing a clinical trial for chronic inflammatory demyelinating polyneuropathy [CIDP]). RPL has worked with Alexion (testing a treatment for myasthenia gravis); Novartis (design of research related to primary progressive MS vs. secondary progressive MS); GLG Consulting, Putnam Consulting, Slingshot Consulting, Haven Consulting, Clearview Consulting, Alpha Sites Consulting, and Insights Consulting (providing insights on the current and future treatments of several neuroimmunologic diseases including MS, MG, Guillain-Barré syndrome, CIDP, and neuromyelitis optica spectrum disorder); and Teva Pharmaceuticals (two non-branded talks to patient groups about MS). RPL has presented several CME talks for companies with multiple sources of support (no direct payments to RBL). RPL has received clinical trial grants (no direct payments) for studies in myasthenia gravis (Alexion, Argenx, Ra Pharmaceuticals) and MS (Novartis, Teva, Genentech/Roche, Chugai). He has received royalties from Blackwell Press as an editors of a textbook International Neurology. RBL is an author of several papers cited in this topic.
Dr Robert Lisak would like to gratefully acknowledge Dr Andrea Corse and Dr Ami Mankodi, previous contributors to this topic. AC and AM declare that they have no competing interests.
Vern C. Juel, MD
Associate Professor of Medicine (Neurology)
VCJ declares that he has no competing interests.
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