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 the anticholinesterase inhibitor pyridostigmine and immunotherapy (a corticosteroid or other immunosuppressant). Thymectomy is required if thymoma is present. Thymectomy has also been shown to be effective in people with generalized MG without thymoma who are AChR antibody positive.
Newer therapies for patients with generalized MG with AChR antibodies include eculizumab, efgartigimod alfa, and ravulizumab.
Approximately 15% to 20% of patients with MG experience a myasthenic crisis, an exacerbation necessitating mechanical ventilation and acute treatment with intravenous immune globulin or plasma exchange.
Many patients with MG enjoy good quality of life and normal lifespan due to advances in diagnosis and in immunosuppressive and immunomodulatory treatment. However, some patients have a significant burden of disease.
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 or repetitive 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 strength 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
mild to moderate disease (class I to III)
severe (class IV or V) or refractory disease
- Lambert-Eaton myasthenic syndrome (LEMS)
- Penicillamine-induced myasthenia gravis
- International consensus guidance for management of myasthenia gravis: 2020 update
- Practice advisory: thymectomy for myasthenia gravis (practice parameter update)
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