LAUSR

BACKGROUND At present, patients positive for aquaporin-4 antibody (AQP4-Ab) or myelin oligodendrocyte glycoprotein antibody (MOG-Ab) are diagnosed as neuromyelitis optica spectrum disorder (NMOSD) and MOG-Ab-associated diseases, respectively. However, some patients who meet the diagnostic criteria for NMOSD and show demyelination of the central nervous system cannot be clearly classified. METHODS We performed a prospective cohort study to evaluate the clinical characteristics and prognoses of double-seronegative patients with NMOSD. RESULTS A total of 594 patients were included in the cohort, including 26 patients with MOG-Ab, 517 with AQP4-Ab, and 51 with double seronegativity. Compared to AQP4-Ab-positive patients, double-seronegative patients experienced less severe clinical attacks (51.0% vs. 78.1%; Pcorr < 0.01), either visual (23.5% vs. 42.6%; Pcorr = 0.024) or motor attacks (39.2% vs. 59.8%; Pcorr = 0.015), and had a better median Expand Disability Status Scale (EDSS) score at the last follow-up (2.0 vs. 3.0; Pcorr = 0.012) and a lower proportion of disability (11.8% vs. 30.9%; Pcorr = 0.015). Furthermore, lower risks of visual and motor disability were also observed by Kaplan-Meier analyses (P = 0.031 and 0.038, respectively). Both the MOG-Ab and double-seronegative groups had lower frequencies of severe clinical attacks, especially motor attacks, better EDSS scores at the last visit, and a lower proportion of disability than was found in the AQP4-Ab group (all P values and corrected P values <0.05). CONCLUSIONS In patients who met the diagnostic criteria for NMOSD, compared with AQP4-Ab-seropositive patients, double-seronegative and MOG-Ab-seropositive patients had less severe clinical attacks and better prognoses, including lower EDSS scores and a lower proportion of disability.