2. Academic Validation
  3. Clinical features, pathogenesis, and treatment of myasthenia gravis: a supplement to the Guidelines of the German Neurological Society

Clinical features, pathogenesis, and treatment of myasthenia gravis: a supplement to the Guidelines of the German Neurological Society

  • J Neurol. 2016 Aug;263(8):1473-94. doi: 10.1007/s00415-016-8045-z.
Nico Melzer 1,  Tobias Ruck 2,  Peter Fuhr 3,  Ralf Gold 4,  Reinhard Hohlfeld 5,  Alexander Marx 6,  Arthur Melms 7,  Björn Tackenberg 8,  Berthold Schalke 9,  Christiane Schneider-Gold 4,  Fritz Zimprich 10,  Sven G Meuth 2,  Heinz Wiendl 2
Affiliations

Affiliations

  • 1 Department of Neurology, University of Münster, Albert-Schweitzer-Campus 1, 48149, Münster, Germany. [email protected].
  • 2 Department of Neurology, University of Münster, Albert-Schweitzer-Campus 1, 48149, Münster, Germany.
  • 3 Department of Neurology, University of Basel, Basel, Switzerland.
  • 4 Department of Neurology, University of Bochum, Bochum, Germany.
  • 5 Institute of Clinical Neuroimmunology, Ludwig-Maximilians-University Munich, Munich, Germany.
  • 6 Institute of Pathology, University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany.
  • 7 Department of Neurology, University of Erlangen, Erlangen, Germany.
  • 8 Department of Neurology, University of Marburg, Marburg, Germany.
  • 9 Department of Neurology, University of Regensburg, Regensburg, Germany.
  • 10 Department of Neurology, Medical University of Vienna, Vienna, Austria.
PMID: 26886206 DOI: 10.1007/s00415-016-8045-z
Abstract

Myasthenia gravis (MG) is an autoimmune antibody-mediated disorder of neuromuscular synaptic transmission. The clinical hallmark of MG consists of fluctuating fatigability and weakness affecting ocular, bulbar and (proximal) limb skeletal muscle groups. MG may either occur as an autoimmune disease with distinct immunogenetic characteristics or as a paraneoplastic syndrome associated with tumors of the thymus. Impairment of central thymic and peripheral self-tolerance mechanisms in both cases is thought to favor an autoimmune CD4(+) T cell-mediated B cell activation and synthesis of pathogenic high-affinity autoantibodies of either the IgG1 and 3 or IgG4 subclass. These autoantibodies bind to the nicotinic acetylcholine receptor (AchR) itself, or muscle-specific tyrosine-kinase (MuSK), lipoprotein receptor-related protein 4 (LRP4) and agrin involved in clustering of AchRs within the postsynaptic membrane and structural maintenance of the neuromuscular synapse. This results in disturbance of neuromuscular transmission and thus clinical manifestation of the disease. Emphasizing evidence from clinical trials, we provide an updated overview on immunopathogenesis, and derived current and future treatment strategies for MG divided into: (a) symptomatic treatments facilitating neuromuscular transmission, (b) antibody-depleting treatments, and

Keywords

Myasthenia gravis; Pathogenesis; Treatment guidelines.

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