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Neuromyelitis optica should be classified as an astrocytopathic disease rather than a demyelinating disease
Author(s) -
Fujihara Kazuo,
Misu Tatsuro,
Nakashima Ichiro,
Takahashi Toshiyuki,
Bradl Monika,
Lassmann Hans,
Takano Rina,
Nishiyama Shuhei,
Takai Yoshiki,
Suzuki Chihiro,
Sato Douglas,
Kuroda Hiroshi,
Nakamura Masashi,
Fujimori Juichi,
Narikawa Koichi,
Sato Shigeru,
Itoyama Yasuto,
Aoki Masashi
Publication year - 2012
Publication title -
clinical and experimental neuroimmunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.297
H-Index - 15
ISSN - 1759-1961
DOI - 10.1111/j.1759-1961.2012.00030.x
Subject(s) - neuromyelitis optica , multiple sclerosis , demyelinating disease , optic neuritis , pathology , myelin basic protein , aquaporin 4 , myelitis , transverse myelitis , myelin , medicine , glial fibrillary acidic protein , autoantibody , demyelinating disorder , immunology , central nervous system , antibody , immunohistochemistry , spinal cord , psychiatry
Neuromyelitis optica ( NMO ) is characterized by severe optic neuritis and transverse myelitis. The relationship of NMO to multiple sclerosis ( MS ) has long been debated, but NMO has been classified as a demyelinating disease. Since the discovery of an NMO ‐specific autoantibody to aquaporin 4 ( AQP 4), a dominant water channel in the central nervous system densely expressed on end‐feet of astrocytes, the clinical, magnetic resonance imaging and laboratory findings to distinguish NMO from MS have been clarified. Furthermore, pathological studies showed an extensive loss of immunoreactivities to astrocytic proteins, AQP 4 and glial fibrillary acidic protein ( GFAP ), and perivascular deposition of immunoglobulins and activated complements with a relative preservation of the staining of myelin basic protein ( MBP ) in acute NMO lesions, but not in MS . In support of these pathological findings, the GFAP levels in the cerebrospinal fluid ( CSF ) during acute exacerbation of NMO are remarkably elevated compared with MBP and neurofilament, whereas the CSF ‐ GFAP in MS is not different from those in controls. Additionally, recent experimental studies have convincingly shown that AQP 4 antibody is pathogenic in causing astorocytic destruction and dysfunction in vitro , ex vivo and in vivo . These findings strongly suggest that damage of astrocytes is far more severe than those of myelin and neurons, and that autoimmune astrocytopathy is the primary pathology in NMO . Based on these accumulated data, we propose that NMO should be classified as an astrocytopathic disease rather than a demyelinating disease.