title: Aquaporin-4 antibody-positive cases beyond current diagnostic criteria for NMO spectrum disorders.
abstract: OBJECTIVE
  To analyze aquaporin-4 (AQP4) antibody-positive patients who do not fulfill the current diagnostic criteria of neuromyelitis optica (NMO) and NMO spectrum disorders (NMOSD).
  
  
  METHODS
  We used a cell-based assay (CBA) with AQP4-transfected cells to detect AQP4 antibody in 298 consecutive patients with inflammatory CNS disorders seen at Tohoku University Hospital from 2007 to 2012. The patients were diagnosed as NMO, NMOSD, multiple sclerosis, or others using the respective current diagnostic criteria. The seropositive samples by CBA were also tested using a commercial ELISA.
  
  
  RESULTS
  Seventy-two patients were AQP4 antibody positive. Among them, 18.1% (13/72) did not meet the NMO or NMOSD criteria (7 with monophasic optic neuritis, 2 with attacks restricted to the brainstem, and 4 with myelitis with less than 3 vertebral segments) and 84.6% (11/13) of these had only a single attack. The ELISA results were negative in 38.4% (5/13) of those patients, and they had lower antibody titers by CBA than patients with NMO/NMOSD. Although these patients had a shorter follow-up and few attacks, they shared some clinical features with NMO/NMOSD patients such as onset age, female predominance, presence of other autoantibodies, severe optic neuritis attacks, centrally located spinal cord lesions, persisting hiccups, and nausea or vomiting episodes.
  
  
  CONCLUSIONS
  AQP4 antibody-positive patients with single or recurrent attacks of optic neuritis, myelitis, or brain/brainstem disease not fulfilling the current criteria of NMO or NMOSD may not be uncommon, and they should also be included in the NMO spectrum.
authors.affiliation: Department of Neurology, Tohoku University School of Medicine, Sendai, Japan. douglas.sato@med.tohoku.ac.jp
authors.forename: Douglas Kazutoshi
authors.initials: DK
authors.lastname: Sato
authors.forename: Ichiro
authors.initials: I
authors.lastname: Nakashima
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takahashi
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Misu
authors.forename: Patrick
authors.initials: P
authors.lastname: Waters
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kuroda
authors.forename: Shuhei
authors.initials: S
authors.lastname: Nishiyama
authors.forename: Chihiro
authors.initials: C
authors.lastname: Suzuki
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Takai
authors.forename: Kazuo
authors.initials: K
authors.lastname: Fujihara
authors.forename: Yasuto
authors.initials: Y
authors.lastname: Itoyama
authors.forename: Masashi
authors.initials: M
authors.lastname: Aoki
mesh_terms: D000328:Adult; D000368:Aged; D051401:Aquaporin 4 / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000097:blood; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D009471:Neuromyelitis Optica / Q000175:diagnosis* / Q000276:immunology
chemical_list: C496030:AQP4 protein, human; D051401:Aquaporin 4; D001323:Autoantibodies; D015415:Biomarkers