Enterovirus Encephalitis in People With Multiple Sclerosis on Ocrelizumab

OBJECTIVES: Anti-CD20 therapies for multiple sclerosis (MS) are highly effective at preventing disease activity. Recognizing infectious complications of these therapies is essential. METHODS: Three MS centers shared deidentified clinical data on persons with MS (pwMS) receiving ocrelizumab who developed enterovirus encephalitis. RESULTS: Five pwMS (4 with relapsing-remitting MS, 1 with secondary progressive MS) on ocrelizumab were identified. At diagnosis, the median age was 34 years (range, 30-57), the median MS duration was 5 years (range, 2-13), and the median ocrelizumab exposure was 3 years (range, 2-7). Four had young children who were recently ill, including 2 with hand, foot, and mouth disease. MRI brain revealed new nonenhancing T2 hyperintensities in the thalamus (2), substantia nigra (2), cerebellum (2), and pons (1). All had CSF pleocytosis (median, 57/mcL; range, 33-175). Enterovirus was detected by reverse-transcription PCR in CSF (4) and blood (2). Hypogammaglobulinemia was present in 4 patients tested; 1 also had neutropenia. Three received IV immunoglobulin. At follow-up (median, 7 months; range, 3-15), 1 patient had fully recovered and 4 had residual symptoms (cognitive, 1; gait impairment, 3). DISCUSSION: Enterovirus encephalitis is a rare but serious complication in pwMS receiving ocrelizumab; hypogammaglobulinemia may increase risk. Clinician awareness and prompt testing may improve outcomes.