title: Loss of aquaporin-4 in active perivascular lesions in neuromyelitis optica: a case report.
abstract: Neuromyelitis optica (NMO) is clinically characterized by severe optic neuritis and transverse myelitis. In Japan, NMO has been named optic-spinal multiple sclerosis (OSMS) and it has been thought to be a subtype of multiple sclerosis (MS). However, several clinical and laboratory findings suggest NMO or OSMS is distinct from MS. Recently, the disease-specific antibody (NMO-IgG) was found in the serum from NMO patients, and its target antigen was identified as aquaporin-4 (AQP4) water channel protein which is mainly expressed in astroglial foot processes. However, the pathogenetic role of AQP4 in NMO remains unknown. We herein report a typical case of NMO in which immunohistochemical analysis showed a lack of AQP4 in the spinal cord lesions. The loss of AQP4 was evident in the central gray matter, especially in the perivascular lesions where immunoglobulins and complements were deposited, and glial fibrillary acidic protein (GFAP) staining was weak in those lesions. However, GFAP was strongly stained at the reactive astrogliosis surrounding the lesions. Myelin basic protein (MBP)-stained myelinated fibers were relatively preserved in the lesions where AQP4 was lost. In contrast to these NMO lesions, AQP4 was expressed predominantly in the gray matter in control spinal cords, and AQP4 was preserved in demyelinating MS lesions. Our findings suggest that astrocytic impairment associated with humoral immunity against AQP4 may be primarily involved in the lesion formation of NMO, and that the pathomechanisms of NMO are different from those of MS in which demyelination is the primary pathology.
authors.affiliation: Department of Neurology, Tohoku University School of Medicine, Sendai, Japan. misu@em.neurol.med.tohoku.ac.jp
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Misu
authors.forename: Kazuo
authors.initials: K
authors.lastname: Fujihara
authors.forename: Masashi
authors.initials: M
authors.lastname: Nakamura
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Murakami
authors.forename: Minoru
authors.initials: M
authors.lastname: Endo
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Konno
authors.forename: Yasuto
authors.initials: Y
authors.lastname: Itoyama
mesh_terms: D000328:Adult; D051401:Aquaporin 4 / Q000378:metabolism*; D001253:Astrocytes / Q000648:ultrastructure; D001808:Blood Vessels / Q000473:pathology; D003165:Complement System Proteins / Q000378:metabolism; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007150:Immunohistochemistry; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis; D009186:Myelin Sheath / Q000378:metabolism; D009471:Neuromyelitis Optica / Q000175:diagnosis* / Q000378:metabolism; D009901:Optic Nerve Diseases / Q000209:etiology; D013116:Spinal Cord / Q000098:blood supply / Q000378:metabolism*
chemical_list: C496030:AQP4 protein, human; D051401:Aquaporin 4; D005904:Glial Fibrillary Acidic Protein; D007074:Immunoglobulin G; D003165:Complement System Proteins