Neuromyelitis optica and the evolving spectrum of autoimmune aquaporin-4 channelopathies

Raffaele Iorio, Sean J. Pittock

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Water channels are a recognized "novel" target for central nervous system, inflammatory, autoimmune, demyelinating diseases, and represent an evolving spectrum of disorders termed neuromyelitis optica (NMO) spectrum disorders (SD). These disorders should now be considered under the umbrella term "autoimmune aquaporin-4 channelopathy". NMOSD represent the first multiple sclerosis (MS)-like disease for which a specific antigen has been identified - the astrocytic water channel aquaporin-4 (AQP4). MS lacks a distinguishing biomarker. This discovery represents a seismic shift from historic emphasis on the oligodendrocyte and myelin to the astrocyte. The NMO of today represents a relapsing spectrum of disease, not necessarily restricted to the optic nerves and spinal cord, that is different from the monophasic disorder in which near simultaneous bilateral optic neuritis and transverse myelitis occur, as was originally described by Devic. Recent clinical, radiological and pathological findings have documented brain involvement in NMO spectrum disorders, particularly in children. Most patients with NMOSD have brain abnormalities on magnetic resonance imaging, and these are consistent with MS in up to 10% of patients. Others have lesions in areas that highly express AQP4 including the circumventricular organs accounting for intractable nausea and vomiting, and the syndrome of inappropriate antidiuresis as presenting symptoms or heralds of relapse. Diencephalic involvement might explain recently recognized sleep disorders and endocrinopathies. Continued progress in our understanding of the immunobiology of AQP4 autoimmunity necessitates continuing revision of the clinical diagnostic criteria for NMO spectrum disorders. As the clinical spectrum broadens, the importance of highly specific assays that detect pathogenic AQP4-immunoglobulin G targeting extracellular epitopes of AQP4 cannot be overemphasized.

Original languageEnglish
Pages (from-to)175-187
Number of pages13
JournalClinical and Experimental Neuroimmunology
Volume5
Issue number2
DOIs
Publication statusPublished - 2014

Fingerprint

Channelopathies
Aquaporin 4
Neuromyelitis Optica
Multiple Sclerosis
Aquaporins
CNS Demyelinating Autoimmune Diseases
Transverse Myelitis
Optic Neuritis
Oligodendroglia
Brain
Optic Nerve
Myelin Sheath
Autoimmunity
Astrocytes
Nausea
Vomiting
Epitopes
Spinal Cord
Immunoglobulin G
Biomarkers

Keywords

  • aquaporin
  • multiple sclerosis
  • Neuromyelitis optica
  • optic neuritis
  • transverse myelitis
  • water channel

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Immunology
  • Clinical Neurology
  • Immunology and Microbiology (miscellaneous)

Cite this

Neuromyelitis optica and the evolving spectrum of autoimmune aquaporin-4 channelopathies. / Iorio, Raffaele; Pittock, Sean J.

In: Clinical and Experimental Neuroimmunology, Vol. 5, No. 2, 2014, p. 175-187.

Research output: Contribution to journalArticle

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