Predictors for the severity of acute aquaporin-4 immunoglobulin G-seropositive neuromyelitis optica spectrum disorders: a prospective cohort study
Objective The study aimed to investigate risk factors for disease severity in acute aquaporin-4 (AQP4) -IgG-seropositive neuromyelitis optica spectrum disorders (NMOSD) patients. Methods This prospective cohort study enrolled 103 serum Aquaporin-4 Immunoglobulin G (AQP4-IgG)-positive NMOSD patients from the Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine, between April 2022 and June 2025. Among them, 60 cases were in the acute phase and 43 in the remission phase. Additionally, 25 age-and sex-matched healthy controls (HCs) were included. Clinical characteristics of all participants were evaluated, and blood samples were collected for laboratory testing. The Expanded Disability Status Scale (EDSS) score was used to assess the severity of the disease. Receiver operating characteristic (ROC) curve analysis was performed using EDSS ≥ 4 as the definition of severe disability. Results Our cohort study revealed significant differences (P < 0.05) in white blood cell (WBC) count, neutrophil (NEUT) count, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), systemic immune inflammation index (SII), systemic inflammation response index (SIRI), and serum complement levels among patients in the acute phase, those in the remission phase, and HCs. Multivariate regression analysis demonstrated that age (p = 0.01; OR = 0.06; 95% CI = 0.02–0.11), NLR (p = 0.018; OR = 0.24; 95% CI = 0.05–0.44), and complement 3 (C3) (p < 0.001; OR = 7.24; 95% CI = 3.77–10.72) were independent and significant risk factors for predicting the severity of disability (as assessed by the EDSS score) during the acute phase. Further ROC curve analysis demonstrated that C3 had strong predictive performance (AUC = 0.84), with high sensitivity and specificity at the optimal cut-off value. NLR showed limited overall discrimination (AUC = 0.62) but high specificity, suggesting a potential role as a rule-in marker. Age exhibited modest predictive value (AUC = 0.64), with an optimal cut-off of 45.5 years. Conclusion Older age at onset, a higher NLR, and elevated serum C3 levels may predict greater disability in AQP4-IgG-positive NMOSD patients during the acute phase. Early identification of these predictive indicators could help guide initial treatment decisions.