Myasthenia gravis and the neuromuscular junction

Curr Opin Neurol. 2013 Oct;26(5):459-65. doi: 10.1097/WCO.0b013e328364c079.

Abstract

Purpose of review: Myasthenic disorders are a well characterized group of diseases of the neuromuscular junction. Their pathogenesis is diverse, including genetic and autoimmune mechanisms. We review recent findings on risk factors, pathogenesis and treatment of autoimmune myasthenia gravis.

Recent findings: Better knowledge of congenital myasthenia has led to the development of efficient diagnostic algorithms that have therapeutic implications. New epidemiological and genetic risk factors have been identified and are considered to play a role in the development of myasthenia gravis. The study of the role of innate immunity in myasthenia gravis has identified relevant pathways to explain myasthenia gravis causes. The description of the pathogenic role of IgG4 anti-MuSK antibodies has revealed heterogeneous immune mechanisms that should lead to more specific therapies. Rituximab seems to be particularly effective in MuSK myasthenia gravis, and eculizumab arises as an option in refractory AChR myasthenia gravis. Therapeutic algorithms need to be tailored to each myasthenia subtype.

Summary: Increasing knowledge about the environmental and genetic risk factors and basic immunopathogenesis of myasthenia gravis, including the role of innate immunity, regulatory T cell impairment and autoantibody heterogeneity, is providing a rationale for treatment with new biological agents. Current immunotherapies in myasthenia gravis undoubtedly provide benefits, but also cause side-effects. Controlled trials are, therefore, needed to confirm initial results from pilot studies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoantibodies / immunology
  • Autoantibodies / metabolism
  • Humans
  • Myasthenia Gravis / genetics
  • Myasthenia Gravis / immunology
  • Myasthenia Gravis / therapy*
  • Myasthenic Syndromes, Congenital / metabolism
  • Myasthenic Syndromes, Congenital / therapy
  • Neuromuscular Junction / genetics
  • Neuromuscular Junction / immunology*
  • Neuromuscular Junction / metabolism
  • Receptors, Cholinergic / immunology
  • Receptors, Cholinergic / metabolism
  • Risk Factors

Substances

  • Autoantibodies
  • Receptors, Cholinergic