Myasthenia gravis

Myasthenia gravis (MG) is a chronic autoimmune disorder of the post-synaptic membrane at the neuromuscular junction in skeletal muscle.

MG is characterised 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-fibre 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 generalised MG without thymoma who are AChR antibody positive.

Newer therapies for patients with generalised MG with AChR antibodies include complement C5 inhibitors and neonatal Fc receptor (FcRn) antagonists.

Approximately 15% to 20% of patients with MG experience a myasthenic crisis, an exacerbation necessitating mechanical ventilation and acute treatment with intravenous immunoglobulin 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.

MG is a chronic autoimmune disorder of the post-synaptic 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 [2]Ruff RL, Lisak RP. Nature and action of antibodies in myasthenia gravis. Neurol Clin. 2018 May;36(2):275-91. http://www.ncbi.nlm.nih.gov/pubmed/29655450?tool=bestpractice.com [3]Narayanaswami P, Sanders DB, Wolfe G, et al. International consensus guidance for management of myasthenia gravis: 2020 update. Neurology. 2021 Jan 19;96(3):114-22. https://n.neurology.org/content/96/3/114.long http://www.ncbi.nlm.nih.gov/pubmed/33144515?tool=bestpractice.com

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 generalised muscle weakness to respiratory failure requiring mechanical ventilation.