Predictors of relapse and disability in NMOSD, MOGAD, and double-seronegative demyelinating syndromes: an international multicenter retrospective cohort study

Background: This international multicenter retrospective cohort study investigated predictors of relapse, acute attack severity, and six-month disability in patients with AQP4-IgG-positive NMOSD, MOGAD, and double-seronegative demyelinating syndromes. Methods: We analyzed 238 patients (132 NMOSD, 69 MOGAD, 37 double-seronegative). Clinical features, CSF findings, and timing of acute and maintenance therapies were evaluated as prognostic markers. Results: In NMOSD, female sex, delayed initiation of acute therapy, need for plasma exchange, and inflammatory CSF changes were associated with greater disability at the nadir of the first attack. Older age and longer disease duration predicted higher six-month disability, while oral corticosteroid tapering was protective. Higher EDSS at onset was associated with poorer six-month recovery. No factor significantly predicted relapse. In MOGAD, optic neuritis at onset and early IVMP were associated with lower six-month disability and higher recovery rates, whereas post-IVMP corticosteroid tapering correlated with higher six-month disability. CSF pleocytosis correlated with favorable recovery. Higher EDSS at onset predicted worse six-month outcomes. Early initiation of maintenance therapy reduced relapse risk although overall use versus none was not statistically conclusive. In double-seronegative patients, short steroid tapers, elevated CSF glucose, antecedent infections or vaccinations, and delayed maintenance therapy were associated with worse six-month recovery though no independent predictors were confirmed in multivariable analyses. Conclusions: Prognostic factors differed across subgroups. NMOSD outcomes were influenced by age, disease duration, and steroid tapering; MOGAD outcomes by onset phenotype, early therapy, and maintenance treatment; and seronegative outcomes by treatment timing and immune antecedents. These findings emphasize early, tailored therapy and distinct subgroup-specific prognostic considerations in antibody-mediated and seronegative demyelinating disorders.