Myasthenia gravis

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.[1]Sanders DB, Wolfe GI, Benatar M, et al. International consensus guidance for management of myasthenia gravis: executive summary. Neurology. 2016 Jul 26;87(4):419-25. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4977114/ http://www.ncbi.nlm.nih.gov/pubmed/27358333?tool=bestpractice.com

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.