Diagnostic biomarkers for differentiating AQP4-IgG- negative NMOSD from other nervous system autoimmune disorders: a retrospective study

Background and objective: The clinical manifestations of neuromyelitis optica spectrum disorders (NMOSD) overlap with those of other central nervous system (CNS) disorders, making differential diagnosis based on symptoms alone difficult. This study aimed to identify distinguishing indicators of aquaporin-4 (AQP4) IgG-negative NMOSD and assess their diagnostic value. Methods: We analyzed four groups: 85 patients with AQP4-IgG-negative NMOSD, 192 with AQP4-IgG-positive NMOSD, 547 with other nervous system autoimmune disorders (e.g., multiple sclerosis, Guillain-Barré syndrome, and viral and autoimmune encephalitis), and 269 healthy controls matched for sex, age, and BMI.A diagnostic model was established using clinical, biochemical, and cerebrospinal fluid (CSF) variables. The dataset was divided into training and internal validation cohorts, and model performance was further assessed through external validation using an independently collected dataset obtained during the same study period. Results: We enrolled 1,093 participants. The AQP4-IgG-negative NMOSD group showed: higher diplopia incidence (35.29% vs. 17.19% in positive NMOSD, 17.18% in controls; P