Outcome and risk of recurrence in a large cohort of idiopathic longitudinally extensive transverse myelitis without AQP4/MOG antibodies

Background Longitudinally extensive transverse myelitis (LETM) is classically related to aquaporin (AQP4)-antibodies (Ab) neuromyelitis optica spectrum disorders (NMOSD) or more recently to myelin oligodendrocyte glycoprotein (MOG)-Ab associated disease. However, some patients remain negative for any diagnosis, despite a large work-up including AQP4-Ab and MOG-Ab. Data about natural history, disability outcome, and treatment are limited in this group of patients. We aimed to (1) describe clinical, biological, and radiological features of double seronegative LETM patients; (2) assess the clinical course and identify prognostic factors; and (3) assess the risk of recurrence, according to maintenance immunosuppressive therapy. Methods Retrospective evaluation of patients with a first episode of LETM, tested negative for AQP-Ab and MOG-Ab, from the French nationwide observatory study NOMADMUS. Results Fifty-three patients (median age 38 years (range 16-80)) with double seronegative LETM were included. Median nadir EDSS at onset was 6.0 (1-8.5), associated to a median EDSS at last follow-up of 4.0 (0-8). Recurrence was observed in 24.5% of patients in the 18 following months, with a median time to first relapse of 5.7 months. The risk of recurrence was lower in the group of patients treated early with an immunosuppressive drug (2/22, 9%), in comparison with untreated patients (10/31, 32%). Conclusions A first episode of a double seronegative LETM is associated to a severe outcome and a high rate of relapse in the following 18 months, suggesting that an early immunosuppressive treatment may be beneficial in that condition.