title: Epidemiology of aquaporin-4 autoimmunity and neuromyelitis optica spectrum.
abstract: OBJECTIVE
  Neuromyelitis optica (NMO) and its spectrum disorders (NMOSD) are inflammatory demyelinating diseases (IDDs) with a specific biomarker, aquaporin-4-immunoglobulin G (AQP4-IgG). Prior NMO/NMOSD epidemiological studies have been limited by lack of AQP4-IgG seroprevalence assessment, absence of population-based USA studies, and under-representation of blacks. To overcome these limitations, we sought to compare NMO/NMOSD seroepidemiology across 2 ethnically divergent populations.
  
  
  METHODS
  We performed a population-based comparative study of the incidence (2003-2011) and prevalence (on December 31, 2011) of NMO/NMOSD and AQP4-IgG seroincidence and seroprevalence (sera collected in 80-84% of IDD cases) among patients with IDD diagnosis in Olmsted County, Minnesota (82% white [Caucasian]) and Martinique (90% black [Afro-Caribbean]). AQP4-IgG was measured by M1 isoform fluorescence-activated cell-sorting assays.
  
  
  RESULTS
  The age- and sex-adjusted incidence (7.3 vs 0.7/1,000,000 person-years [p < 0.01]) and prevalence (10 vs 3.9/100,000 [p = 0.01]) in Martinique exceeded that in Olmsted County. The AQP4-IgG age- and sex-adjusted seroincidence (6.5 vs 0.7/1,000,000 person-years [p < 0.01]) and seroprevalence (7.9 vs 3.3/100,000 [p = 0.04]) were also higher in Martinique than Olmsted County. The ethnicity-specific prevalence was similar in Martinique and Olmsted County: 11.5 and 13/100,000 in blacks, and 6.1 and 4.0/100,000 in whites, respectively. NMO/NMOSD represented a higher proportion of IDD cases in Martinique than Olmsted County (16% vs 1.4%; p < 0.01). The onset age (median = 35-37 years) and female:male distribution (5-9:1) were similar across both populations; 60% of prevalent cases were either blind in 1 eye, dependent on a gait aid, or both.
  
  
  CONCLUSIONS
  This study reports the highest prevalence of NMO/NMOSD in any population (10/100,000 in Martinique), estimates it affects 16,000 to 17,000 in the USA (higher than previous predictions), and demonstrates it disproportionately affects blacks. Ann Neurol 2016;79:775-783.
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN.
authors.forename: Eoin P
authors.initials: EP
authors.lastname: Flanagan
authors.affiliation: Department of Neurology, Fort-de-France University Hospital Center, Pierre Zobda Quitman Hospital, Fort-de-France, Martinique, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Cabre
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Weinshenker
authors.affiliation: Department of Epidemiology, Mayo Clinic, Rochester, MN.
authors.forename: Jennifer St
authors.initials: JS
authors.lastname: Sauver
authors.affiliation: Department of Biostatistics, Mayo Clinic, Rochester, MN.
authors.forename: Debra J
authors.initials: DJ
authors.lastname: Jacobson
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN.
authors.forename: Masoud
authors.initials: M
authors.lastname: Majed
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN.|Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.|Department of Immunology, Mayo Clinic, Rochester, MN.
authors.forename: Vanda A
authors.initials: VA
authors.lastname: Lennon
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN.
authors.forename: Claudia F
authors.initials: CF
authors.lastname: Lucchinetti
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN.|Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
authors.forename: Andrew
authors.initials: A
authors.lastname: McKeon
authors.affiliation: Department of Neurology, Massachusetts General Hospital and Brigham and Women's Hospital, Boston, MA.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Matiello
authors.affiliation: Bakirkoy Prof Mazhar Osman Training and Research Hospital, Istanbul, Turkey.
authors.forename: Nilifur
authors.initials: N
authors.lastname: Kale
authors.affiliation: Department of Neurology, Mayo Clinic, Scottsdale, AZ.
authors.forename: Dean M
authors.initials: DM
authors.lastname: Wingerchuk
authors.affiliation: Department of Biostatistics, Mayo Clinic, Rochester, MN.
authors.forename: Jay
authors.initials: J
authors.lastname: Mandrekar
authors.affiliation: Neurology Research, Mayo Clinic, Rochester, MN.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Sagen
authors.affiliation: Department of Biostatistics, Mayo Clinic, Rochester, MN.|Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
authors.forename: James P
authors.initials: JP
authors.lastname: Fryer
authors.affiliation: Olmsted Medical Center, Rochester, MN.
authors.forename: Angala Borders
authors.initials: AB
authors.lastname: Robinson
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN.|Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Pittock