Myelitis‐Predominant Aggressive Phenotype: Unveiling Unique Patterns of Late‐Onset Neuromyelitis Optica Spectrum Disorders

OBJECTIVE: The objective of this study was to compare clinical features and prognosis of late-onset neuromyelitis optica spectrum disorder (LO-NMOSD, onset age ≥60 years) with adult-onset NMOSD (AO-NMOSD, onset age 18-59 years), and to provide insights for individualized management in elderly patients. METHODS: Data from 748 patients with NMOSD (diagnosed according to the 2015 International Panel for NMO Diagnosis criteria) in the China National Registry of Neuro-Inflammatory Diseases (CNRID) were analyzed. Patients were stratified into AO-NMOSD (18-59 years, n = 617) and LO-NMOSD (≥ 60 years, n = 131). Demographics, clinical manifestations, imaging, treatments, and outcomes were compared using appropriate statistical methods including Kaplan-Meier survival curves and Cox proportional hazards regression. RESULTS: LO-NMOSD showed distinct traits: a lower female predominance (76.34% vs 86.55%), higher transverse myelitis (TM) incidence at onset (57.36% vs 40.17%), elevated annualized relapse rate (ARR; 0.52 ± 0.03 vs 0.38 ± 0.01), and accelerated disability (median Expanded Disability Status Scale [EDSS] 4.75 vs 3.0). TM-predominant relapses (39 of 45, 86.67% in LO vs 96 of 148, 64.86% in AO) contributed significantly to disability. Kaplan-Meier analysis showed LO-NMOSD had a higher risk of relapse (hazard ratio [HR] = 1.932, 95% confidence interval [CI] = 1.427-2.615), disability (HR = 3.192, 95% CI = 1.932-5.274) and reaching visual acuity (VA) ≤20 of 30 (HR = 3.523, 95% CI = 1.585-7.828). Cox regression confirmed that onset age ≥60 years was an independent risk factor for relapse (HR = 2.05, 95% CI = 1.60-2.59), disability (HR = 3.16, 95% CI = 2.14-4.62), and reaching VA ≤20 of 30 (HR 3.26, 95% CI = 1.83-5.48). INTERPRETATION: LO-NMOSD is characterized by myelitis-predominance with recurrent spinal cord involvement, high risk of relapses, and severe disability. It thus underscores the need for heightened clinical attention, with rigorous monitoring that balance safety and efficacy for elderly patients with NMOSD. ANN NEUROL 2026;99:1139-1151.