title: Prognostic factors and disease course in aquaporin-4 antibody-positive patients with neuromyelitis optica spectrum disorder from the United Kingdom and Japan.
abstract: Neuromyelitis optica and neuromyelitis optica spectrum disorders have been recently associated with the disease-specific autoantibody aquaporin-4, thought to be pathogenic. Identifying this antibody has allowed the clinical phenotype to be broadened. It is clear that some patients with similar clinical features do not have this antibody and may have a different condition with different outcomes and prognosis. Previous clinical neuromyelitis optica and neuromyelitis optica spectrum disorder studies have included such patients. We investigated clinical outcomes and prognostic characteristics of 106 aquaporin-4 antibody-seropositive patients from the UK and Japan. We looked at predictors of disability outcomes, namely visual disability (permanent bilateral visual loss with visual acuity of <6/36 in the best eye), motor disability (permanent inability to walk further than 100 m unaided), wheelchair dependence and mortality. Data were collected largely retrospectively through review of case records. After median disease duration of 75 months, 18% had developed permanent bilateral visual disability, 34% permanent motor disability, 23% had become wheelchair dependent and 9% had died. Age at disease onset appeared to be an important predictor of disability type. Young-onset patients in the UK, but not the Japanese cohort, commonly presenting with optic neuritis, had a high risk of visual disability while older patients in both cohorts had a high risk of motor disability, regardless of their onset symptom. Genetic factors also appeared important. The UK cohort seemed to have more severe disease than the Japanese cohort, with more severe onset attacks, a higher relapse frequency and greater disability at follow-up, despite earlier immunosuppression. Moreover, within the UK cohort, there were important differences between ethnic groups, with Afro-Caribbean patients having a younger age at disease onset, more brain and multifocal attacks and higher likelihood of visual disability than Caucasian patients. Thus, age at disease onset and genetic factors are both likely to be important in determining clinical outcomes in aquaporin-4 disease. This has important implications for interpreting clinical neuromyelitis optica and neuromyelitis optica spectrum disorder studies, since clinical features and outcomes appear not to be generic across populations and may need to be tailored to individual groups. These factors need to be explored further in future prospective neuromyelitis optica and neuromyelitis optica spectrum disorder studies.
authors.affiliation: Nuffield Department of Clinical Neurosciences, West Wing, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK.
authors.forename: Joanna
authors.initials: J
authors.lastname: Kitley
authors.forename: M Isabel
authors.initials: MI
authors.lastname: Leite
authors.forename: Ichiro
authors.initials: I
authors.lastname: Nakashima
authors.forename: Patrick
authors.initials: P
authors.lastname: Waters
authors.forename: Benjamin
authors.initials: B
authors.lastname: McNeillis
authors.forename: Rachel
authors.initials: R
authors.lastname: Brown
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Takai
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takahashi
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Misu
authors.forename: Liene
authors.initials: L
authors.lastname: Elsone
authors.forename: Mark
authors.initials: M
authors.lastname: Woodhall
authors.forename: Jithin
authors.initials: J
authors.lastname: George
authors.forename: Mike
authors.initials: M
authors.lastname: Boggild
authors.forename: Angela
authors.initials: A
authors.lastname: Vincent
authors.forename: Anu
authors.initials: A
authors.lastname: Jacob
authors.forename: Kazuo
authors.initials: K
authors.lastname: Fujihara
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Palace
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000906:Antibodies / Q000097:blood*; D051401:Aquaporin 4 / Q000276:immunology*; D001766:Blindness; D003431:Cross-Cultural Comparison; D004185:Disability Evaluation; D018450:Disease Progression; D005006:Ethnicity; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007564:Japan / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009043:Motor Activity; D009422:Nervous System Diseases / Q000097:blood / Q000276:immunology / Q000473:pathology; D009471:Neuromyelitis Optica / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology / Q000276:immunology*; D012189:Retrospective Studies; D018709:Statistics, Nonparametric; D006113:United Kingdom / Q000453:epidemiology; D014792:Visual Acuity / Q000502:physiology
chemical_list: C496030:AQP4 protein, human; D000906:Antibodies; D051401:Aquaporin 4