Neuromyelitis optica spectrum disorders: Comparison according to the phenotype and serostatus

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.

Figure 1. Kaplan-Meier estimation of time to neuromyelitis optica (NMO) conversion and development of motor disability

(A) Months from onset to develop NMO according to the onset attack type: patients with optic neuritis, and those with longitudinally extensive transverse myelitis (LETM) aged <30 years, converted earlier than patients with LETM aged >30 years or with brainstem syndrome (p < 0.001). (B) Months from onset to use a cane (Expanded Disability Status Scale [EDSS] score 6.0) by age at disease onset: older patients were significantly more likely than younger patients to develop motor disability over time (p < 0.001). (C) Years from onset to use a cane by antibody status in NMO patients: at 5 years after onset, 26% of aquaporin-4 immunoglobulin G (AQP4-IgG)–positive patients, 19% of double-seronegative patients, and none of the myelin oligodendrocyte glycoprotein (MOG)–IgG-positive patients were expected to need a cane to walk (EDSS score 6.0) (p = 0.089). EDSS score 6.0 = intermittent or unilateral assistance required to walk 100 meters with or without resting. ON = optic neuritis.