Epidemiology of aquaporin‐4 autoimmunity and neuromyelitis optica spectrum

Abstract

Objective Neuromyelitis optica and its spectrum disorders (NMOSD) are inflammatory demyelinating diseases (IDD) with a specific biomarker, aquaporin-4-IgG. Prior NMO/NMOSD epidemiological studies are limited by lack of aquaporin-4-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 two 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 aquaporin-4-IgG seroincidence and seroprevalence (sera collected in 80–84% of IDD) among patients with IDD diagnosis in Olmsted County, USA (82% white [Caucasian]) and Martinique (90% black [Afro-Caribbean]). Aquaporin-4-IgG was measured by M1-isoform-fluorescent-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 in Martinique than Olmsted County (16% vs 1.4%; p<0.01). The onset age (median, 35–37 years) and female:male distribution (8–9:1) were similar across both populations; 60% of prevalent cases were either blind in one eye, dependent on a gait aid or both. Interpretation This study reports the highest prevalence of NMO/NMOSD in any population (10/100,000 in Martinique), estimates it affects 16,000–17,000 in the USA (higher than previous predictions) and demonstrates it disproportionately affects blacks.

Incidence and prevalence of NMOSD in Australia and New Zealand

“…These studies included methodologies likely to have a high pick up rate for cases of NMOSD through multiple healthcare sources and national databases19 or systematic serological testing of all possible cases 18. Relatively small sample sizes mean that these higher prevalence figures could represent statistical random variation (the number of affected cases in the recent USA study was only six) 18. Conversely, it is likely the results presented here are an underestimate.…”

“…There are two studies with significantly higher estimates of prevalence18 19 and one of these also has a significantly higher estimate of incidence 19. These studies included methodologies likely to have a high pick up rate for cases of NMOSD through multiple healthcare sources and national databases19 or systematic serological testing of all possible cases 18. Relatively small sample sizes mean that these higher prevalence figures could represent statistical random variation (the number of affected cases in the recent USA study was only six) 18.…”

Multiple Sclerosis Mortality by Race/Ethnicity, Age, Sex, and Time Period in the United States, 1999–2015

“…In addition, disparities in mortality rates between racial and ethnic groups should raise questions about particular characteristics in these groups, including MS phenotypes and even alternate diagnosis that can lead to higher morbidity and mortality like neuromyelitis optica (NMO) spectrum disorders, for example [30]. Flanagan et al [31] recently reported a disproportionately higher prevalence of NMO/NMOSD affecting blacks compared to whites, introducing the possibility of misdiagnosing MS in this population. Whether there are differences in the clinical course of MS between these populations could also be relevant given that primary progressive MS has been associated with faster time to death from disease onset [32].…”

Ring-enhancing spinal cord lesions in neuromyelitis optica spectrum disorders

“…All incident myelitis cases in the Olmsted county21 population-based database of inflammatory demyelinating diseases (n=30) from 2003 to 2011 who concurrently or subsequently met 2011 diagnostic criteria for MS were studied 22. Ascertainment of these patients using the Rochester epidemiology project medical records linkage system has been described previously 21.…”

“…Ascertainment of these patients using the Rochester epidemiology project medical records linkage system has been described previously 21. The 30 MS myelitis attacks involved the cervical cord (n=14 (46.5%)), thoracic cord (n=11 (36.5%)) or both (n=5 (17%)).…”