Majed, Masoud

AbstractTo determine whether CSF leucine‐rich glioma‐inactivated 1(LGI1)‐IgG titer, index or IgG subclass has prognostic significance, we tested serum and CSF specimens collected concomitantly from 39 seropositive patients. LGI1‐IgG index was elevated (>1) in 21 patients (54%), suggesting intrathecal synthesis. Patients with worse outcome at last follow‐up (modified Rankin Scale >2) had significantly higher index (median 6.57 vs. 0.5, P = 0.048) compared to those with better outcome. Higher CSF LGI1‐IgG4 subclass‐specific titer and index correlated with worse outcome (P < 0.005 for both). These data suggest that evidence of intrathecal LGI1‐IgG synthesis may correlate with neuronal injury and warrant consideration of aggressive immunotherapy.

ObjectiveNeuromyelitis 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.MethodsWe 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.ResultsThe 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.InterpretationThis 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