title: Clinical spectrum of CNS aquaporin-4 autoimmunity.
abstract: OBJECTIVE
  Traditionally, neuromyelitis optica (NMO) was known to involve only the optic nerves and spinal cord. However, the discovery of highly specific anti-aquaporin-4 (AQP4) antibody for NMO enabled us to identify more diverse clinical manifestations. Here, we describe the demographic and clinical characteristics of patients who were anti-AQP4-antibody positive, represented by CNS AQP4 autoimmunity.
  
  
  METHODS
  In total, 388 consecutive patients with inflammatory demyelinating CNS diseases were tested for the anti-AQP4 antibody and 106 seropositive patients who were positive by ELISA or cell-based assay were included.
  
  
  RESULTS
  Ninety-seven patients were women, and 9 men. The median age at onset was 32 years. The median annualized relapse rate was 1.14 during the median follow-up of 7.0 years. When the 2006 revised diagnostic criteria for NMO were applied, 72% of patients met the criteria, and 28% had a limited form of NMO. Brain symptoms were observed in 51% of patients, and 24% of patients presented with brain symptoms as their first manifestation. Severe residual visual impairment or ambulatory disability was observed in 42% of patients. The median intervals to Expanded Disability Status Scale (EDSS) 6 and severe visual impairment in at least one eye were 12 and 11 years, respectively. A multivariate analysis revealed a delay of more than 4 years before appropriate immunotherapy was independently associated with reaching severe disability of more than EDSS 6.
  
  
  CONCLUSIONS
  The spectrum of neurologic manifestations and the disease course associated with CNS AQP4 autoimmunity is broader than previously recognized.
authors.affiliation: Department of Neurology, Research Institute and Hospital of National Cancer Center, Goyang, Korea.
authors.forename: S-H
authors.initials: SH
authors.lastname: Kim
authors.forename: W
authors.initials: W
authors.lastname: Kim
authors.forename: X F
authors.initials: XF
authors.lastname: Li
authors.forename: I-J
authors.initials: IJ
authors.lastname: Jung
authors.forename: H J
authors.initials: HJ
authors.lastname: Kim
mesh_terms: D000328:Adult; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D051401:Aquaporin 4 / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D015551:Autoimmunity; D001379:Azathioprine / Q000008:administration & dosage; D006233:Persons with Disabilities; D004334:Drug Administration Schedule; D042241:Early Diagnosis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016899:Interferon-beta / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D015999:Multivariate Analysis; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D009471:Neuromyelitis Optica / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology*; D011237:Predictive Value of Tests; D011239:Prednisolone / Q000008:administration & dosage; D011379:Prognosis; D056910:Republic of Korea; D000069283:Rituximab
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D051401:Aquaporin 4; D001323:Autoantibodies; D007166:Immunosuppressive Agents; D000069283:Rituximab; D016899:Interferon-beta; D011239:Prednisolone; D008942:Mitoxantrone; D009173:Mycophenolic Acid; D001379:Azathioprine