A chronic autoimmune disorder of the post-synaptic membrane at the neuromuscular junction in skeletal muscle.
Characterised by muscle weakness that increases with exercise (fatigue) and improves on rest. Commonly presents with drooping eyelids, double vision, oropharyngeal and/or appendicular weakness, and shortness of breath.
Elevated serum acetylcholine receptor antibody titres or muscle-specific tyrosine kinase antibodies are present. Antibodies to 4 new autoantigens, low-density lipoprotein receptor-related protein (LRP4), agrin, collagen Q, and cortactin, located at the neuromuscular junction, have been identified. Clinical electrophysiology shows decremental response on repetitive nerve stimulation or increased jitter on single-fibre study.
Treatments include anticholinesterases and immunotherapy. Thymectomy may be required and has been shown to be effective in people with generalised myasthenia gravis who are acetylcholine receptor (AChR) antibody positive with no thymoma. It is not yet clear at which stages of myasthenia gravis, in which patients, and in what sequence in relation to other therapies that thymectomy in non-thymoma patients should be done. Eculizumab, a novel monoclonal antibody that inhibits complement activation, has shown clinical benefit in patients with resistant generalised myasthenia gravis and AChR antibodies.
Approximately 15% to 20% of patients may 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 immunosuppressive and immunodulatory treatment.
Myasthenia gravis (MG) is a chronic autoimmune disorder of the post-synaptic membrane at the neuromuscular junction (NMJ) in skeletal muscle. Circulating antibodies against the nicotinic acetylcholine receptor (AChR) and 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 generalised muscle weakness and respiratory failure requiring mechanical ventilation.
Parker Webber Chair in Neurology
Professor of Neurology
Professor of Immunology and Microbiology
Wayne State University School of Medicine
RPL is an unpaid member of the Medical Advisory Committee and the Research Committee of the Myasthenia Gravis Foundation of America. He has consulted for Gerson Lehman Group, in the form of two 1-hour conversations with clients of GLG on the state of current treatments in MG.
Dr Robert Lisak would like to gratefully acknowledge Dr Andrea Corse and Dr Ami Mankodi, previous contributors to this monograph. AC and AM declare that they have no competing interests.
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