Autoimmune AQP4 channelopathies and neuromyelitis optica spectrum disorders

Shannon R. Hinson, Vanda A. Lennon, Sean J. Pittock

Research output: Chapter in Book/Report/Conference proceedingConference contribution

36 Scopus citations


Neuromyelitis optica (NMO) spectrum disorders (SD) represent an evolving group of central nervous system (CNS)-inflammatory autoimmune demyelinating diseases unified by a pathogenic autoantibody specific for the aquaporin-4 (AQP4) water channel. It was historically misdiagnosed as multiple sclerosis (MS), which lacks a distinguishing biomarker. The discovery of AQP4-IgG moved the focus of CNS demyelinating disease research from emphasis on the oligodendrocyte and myelin to the astrocyte. NMO is recognized today as a relapsing disease, extending beyond the optic nerves and spinal cord to include brain (especially in children) and skeletal muscle. Brain magnetic resonance imaging abnormalities, identifiable in 60% of patients at the second attack, are consistent with MS in 10% of cases. NMOSD-typical lesions (another 10%) occur in AQP4-enriched regions: circumventricular organs (causing intractable nausea and vomiting) and the diencephalon (causing sleep disorders, endocrinopathies, and syndrome of inappropriate antidiuresis). Advances in understanding the immunobiology of AQP4 autoimmunity have necessitated continuing revision of NMOSD clinical diagnostic criteria. Assays that selectively detect pathogenic AQP4-IgG targeting extracellular epitopes of AQP4 are promising prognostically. When referring to AQP4 autoimmunity, we suggest substituting the term "autoimmune aquaporin-4 channelopathy" for the term "NMO spectrum disorders." Randomized clinical trials are currently assessing the efficacy and safety of newer immunotherapies. Increasing therapeutic options based on understanding the molecular pathogenesis is anticipated to improve the outcome for patients with AQP4 channelopathy.

Original languageEnglish (US)
Title of host publicationAutoimmune Neurology, 2016
EditorsSean J. Pittock, Angela Vincent
Number of pages27
ISBN (Print)9780444634320
StatePublished - 2016

Publication series

NameHandbook of Clinical Neurology
ISSN (Print)0072-9752
ISSN (Electronic)2212-4152


  • AQP4
  • Astrocyle
  • Demyelination
  • EAAT2
  • Multiple sclerosis
  • Neuromyelitis optica
  • Optic neuritis
  • Transverse myelitis
  • Water channel

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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