Neuromyelitis optica spectrum disorders

Abstract

Objective:To (1) determine the value of the recently proposed criteria of neuromyelitis optica (NMO) spectrum disorder (NMOSD) that unify patients with NMO and those with limited forms (NMO/LF) with aquaporin-4 immunoglobulin G (AQP4-IgG) antibodies; and (2) investigate the clinical significance of the serologic status in patients with NMO.Methods:This was a retrospective, multicenter study of 181 patients fulfilling the 2006 NMO criteria (n = 127) or NMO/LF criteria with AQP4-IgG (n = 54). AQP4-IgG and myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) antibodies were tested using cell-based assays.Results:Patients were mainly white (86%) and female (ratio 6.5:1) with median age at onset 39 years (range 10–77). Compared to patients with NMO and AQP4-IgG (n = 94), those with NMO/LF presented more often with longitudinally extensive transverse myelitis (LETM) (p < 0.001), and had lower relapse rates (p = 0.015), but similar disability outcomes. Nonwhite ethnicity and optic neuritis presentation doubled the risk for developing NMO compared with white race (p = 0.008) or LETM presentation (p = 0.008). Nonwhite race (hazard ratio [HR] 4.3, 95% confidence interval [CI] 1.4–13.6) and older age at onset were associated with worse outcome (for every 10-year increase, HR 1.7, 95% CI 1.3–2.2). Patients with NMO and MOG-IgG (n = 9) had lower female:male ratio (0.8:1) and better disability outcome than AQP4-IgG-seropositive or double-seronegative patients (p < 0.001).Conclusions:In patients with AQP4-IgG, the similar outcomes regardless of the clinical phenotype support the unified term NMOSD; nonwhite ethnicity and older age at onset are associated with worse outcome. Double-seronegative and AQP4-IgG-seropositive NMO have a similar clinical outcome. The better prognosis of patients with MOG-IgG and NMO suggests that phenotypic and serologic classification is useful.

Immunotherapies in neuromyelitis optica spectrum disorder: efficacy and predictors of response

“…Third, we found a decreased attack risk with increasing age. This suggests that the shorter time to disability milestones in elderly reported in the literature 38 is rather driven by worse attack outcome than by higher attack rates. In accordance with this hypothesis, we found a lower remission rate with increasing age in the NEMOS cohort in our previous study.…”

Immunopathogenesis in Myasthenia Gravis and Neuromyelitis Optica

“…Most patients are seropositive for Ig G against aquaporin-4 (AQP4-IgG) ( 13 – 16 ), which is the most abundant water channel protein in astrocytes throughout the CNS ( 17 , 18 ). Approximately 5–10% of patients are seropositive for antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) ( 19 – 21 ), and a few patients are dual-positive for both antibodies ( 22 , 23 ). The prevalence and incidence of NMO/NMOSD are approximately 3.9–10 and 0.07–0.73 per 100,000, respectively, the median age of onset is 35–37 years and the female-to-male ratio is approximately 8–9:1 ( 24 ).…”

Pattern Recognition of the Multiple Sclerosis Syndrome

“…In up to 40% of cases, transverse myelitis can be the presenting manifestation of NMOSD [ 97 , 98 ] The presence of a LETM almost always evokes the diagnosis of AQP4-NMOSD. However, LETM has been associated with other inflammatory diseases of the CNS such as ADEM, MS, overlap syndromes (e.g., Sjogren’s and NMO), sarcoidosis, antiphospholipid syndrome, vasculitis [ 99 ], Behcet’s disease, and paraneoplastic syndrome, in addition to non-inflammatory etiologies such as intramedullary tumors, dural arteriovenous fistula, Alexander’s disease, metabolic and compressive myelopathies and spinal cord infarction [ 100 , 101 ].…”

“…The association of the MOG antibody in inflammatory demyelinating diseases to other autoantibodies (e.g., thyroid, celiac, antinuclear antibodies, Sjogren’s, glomerular basement membrane) has been reported in several papers [ 22 , 43 , 53 , 55 ], but this association is less commonly found in comparison to AQP4-NMOSD. Double seropositivity of AQP4 and MOG antibodies in NMOSD and its limited forms was found by ELISA techniques [ 201 ], by cell-based assays [ 62 , 98 , 202 ], and in a single patient with gastric cancer and NMO [ 53 ]. Known to be rare, these cases present clinically with severe deficits because of recurrent optic neuritis or bilateral optic neuritis and simultaneous transverse myelitis.…”