Characterizing double seronegative neuromyelitis optica spectrum disorder: A distinct subgroup or part of the continuum?

Abstract

Background: Neuromyelitis optica spectrum disorder (NMOSD) encompasses inflammatory demyelinating CNS conditions. Patients negative for aquaporin-4 (AQP4-IgG) and myelin oligodendrocyte glycoprotein (MOG-IgG) antibodies are classified as double seronegative (DN).

Objective: To characterize and compare the clinical, radiological, and therapeutic profiles of DN, AQP4-IgG+, and MOG-IgG+ patients.

Methods: Retrospective analysis of patients meeting 2015 NMOSD criteria, grouped by serostatus (AQP4-IgG+, MOG-IgG+, and DN). Demographic, clinical, and imaging data were compared.

Results: We analyzed 111 patients: 64 AQP4-IgG+, 31 DN, and 16 MOG-IgG+. At onset, AQP4-IgG+ patients were older than DN and MOG-IgG+ (49 ± 14 vs 41 ± 12 vs 35 ± 12 years, p < 0.0001). DN had more relapses in the first two years (p = 0.02) and higher EDSS (p < 0.001). Myelitis was common in DN and AQP4-IgG+, while optic neuritis in MOG-IgG+. Relapse rates were highest in AQP4-IgG+ (p < 0.001). Oligoclonal bands were more common in DN (39 %) than in AQP4-IgG+ (27.7 %) and MOG-IgG+ (25 %)(p < 0.0001). Area postrema lesions were more frequent in DN (p = 0.02). Rituximab was mainly used in AQP4-IgG+ and DN (p < 0.001), with lower failure in DN (4.8 % vs 18 %).

Conclusion: DN NMOSD shows distinct features but comparable disability to AQP4-IgG+ individuals. Conventional immunosuppressants seem effective, though further research is needed to clarify mechanisms and optimize treatment strategies.