Citations

Objective A novel autoimmune central nervous system (CNS) disorder with glial fibrillary acidic protein (GFAP)‐IgG as biomarker was recently characterized. Here, 102 patients with GFAP‐IgG positivity are described. Methods The 102 included patients had: (1) serum, cerebrospinal fluid (CSF), or both that yielded a characteristic astrocytic pattern of mouse tissue immunostaining; (2) confirmation of IgG reactive with specific GFAP isoforms (α, ɛ, or κ) by cell‐based assays; and (3) clinical data available. Control specimens (n = 865) were evaluated by tissue (n = 542) and cell‐based (n = 323) assays. Results Median symptom onset age was 44 years (range = 8–103), and 54% were women. The predominant phenotype (83 patients; 81%) was inflammation of meninges, brain, spinal cord, or all 3 (meningoencephalomyelitis). Among patients, highest specificity for those phenotypes was observed for CSF testing (94%), and highest sensitivity was for the GFAPα isoform (100%). Rare GFAP‐IgG positivity was encountered in serum controls by tissue‐based assay (0.5%) or cell‐based assay (1.5%), and in CSF controls by cell‐based assay (0.9%). Among patients, striking perivascular radial enhancement was found on brain magnetic resonance imaging in 53%. Although cases frequently mimicked vasculitis, angiography was uniformly negative, and spinal imaging frequently demonstrated longitudinally extensive myelitic lesions. Diverse neoplasms encountered were found prospectively in 22%. Ovarian teratoma was most common and was predicted best when both N‐methyl‐D‐aspartate receptor–IgG and aquaporin‐4–IgG coexisted (71%). Six patients with prolonged follow‐up had brisk corticosteroid response, but required additional immunosuppression to overcome steroid dependency. Interpretation GFAPα‐IgG, when detected in CSF, is highly specific for an immunotherapy‐responsive autoimmune CNS disorder, sometimes with paraneoplastic cause. Ann Neurol 2017;81:298–309

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

ObjectiveTo compare longitudinally extensive myelitis in neuromyelitis optica spectrum disorders (NMOSD) and spinal cord sarcoidosis (SCS).MethodsWe identified adult patients evaluated between 1996 and 2015 with SCS or NMOSD whose first myelitis episode was accompanied by a spinal cord lesion spanning ≥3 vertebral segments. All NMOSD patients were positive for aquaporin‐4–immunoglobulin G, and all sarcoidosis cases were pathologically confirmed. Clinical characteristics were evaluated. Spine magnetic resonance imaging was reviewed by 2 neuroradiologists.ResultsWe studied 71 patients (NMOSD, 37; SCS, 34). Sixteen (47%) SCS cases were initially diagnosed as NMOSD or idiopathic transverse myelitis. Median delay to diagnosis was longer for SCS than NMOSD (5 vs 1.5 months, p < 0.01). NMOSD myelitis patients were more commonly women, had concurrent or prior optic neuritis or intractable vomiting episodes more frequently, had shorter time to maximum deficit, and had systemic autoimmunity more often than SCS (p < 0.05). SCS patients had constitutional symptoms, cerebrospinal fluid (CSF) pleocytosis, and hilar adenopathy more frequently than NMOSD (p < 0.05); CSF hypoglycorrhachia (11%, p = 0.25) and elevated angiotensin‐converting enzyme (18%, p = 0.30) were exclusive to SCS. Dorsal cord subpial gadolinium enhancement extending ≥2 vertebral segments and persistent enhancement >2 months favored SCS, and ringlike enhancement favored NMOSD (p < 0.05). Maximum disability was similar in both disorders.InterpretationSCS is an under‐recognized cause of longitudinally extensive myelitis that commonly mimics NMOSD. We identified clinical, laboratory, systemic, and radiologic features that, taken together, help discriminate SCS from NMOSD. ANN NEUROL 2016;79:437–447