To identify the risk factors associated with the relapse rate in patients with DSNMOSD.

Double Seronegative Neuromyelitis Optica Spectrum Disorder (DSNMOSD) is a rare subset of NMOSD that is characterized by a negative test against Aquaporin 4 (AQP4) IgG and Myelin Oligodendrocyte Glycoprotein (MOG) IgG.

This is a multicenter retrospective study of cases of DSNMOSD at the MassGeneralBrigham and the Hospital University of Sao Paulo. Patients were included if they (1) met the diagnostic criteria for Seronegative NMOSD according to the 2015 International Panel for NMO Diagnosis (IPND) and (2) tested negative for AQP4-IgG and MOG-IgG at least once. Patients were excluded if they had an alternative diagnosis. To examine the association of the different clinical and paraclinical factors on relapses, we calculated the incidence rate ratio (IRR) using a Poisson regression analysis.

A total of 37 relapsing DSNMOSD patients were analyzed. In a univariate Poisson regression analysis, being female and of non-Caucasian race was predicted to have a higher rate of relapse (IRR 1.63, 95%CI 1.1-2.6; p= 0.034) and (IRR: 1.60, 95% CI 1.10-2.35; p=0.017), respectively. Simultaneous optic neuritis (ON) and transverse myelitis (TM) at onset resulted in a lower IRR of 0.04 (95%CI 0.01-0.13; p <0.001). After adjusting for sex, race, laterality of ON, and use of disease-modifying therapy, age at onset at ≥40 years old was associated with higher rate of relapses (IRR 2.10, 95% CI 1.23-3.51; p = 0.006), while initial clinical manifestations of TM only (IRR 0.47, 95%CI 0.22-0.97; p=0.043) and simultaneous ON and TM (IRR 0.05, 95% CI 0.10-0.21; p <0.001) were linked to low relapse rates when compared to ON only.

Later age onset (≥40 years old) and patients presenting with TM only and simultaneous ON and TM at onset significantly influence the relapse rate observed in DSNMOSD.