Clinical observation of rituximab in three patients with anti-N-methyl-D-aspartate receptor encephalitis

Abstract

Objective To investigate the efficacy and safety of rituximab in the treatment of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Methods Three patients with anti-NMDAR antibodies in cerebrospinal fluid and serum hospitalized from May 2012 to July 2014 were retrospectively reviewed. The clinical syndrome, investigations, and therapeutic interventions by rituximab when first line immunotherapy failed were evaluated. Results All 3 patients were females with median age of 17 years (12, 17, and 22 years). One patient had ovarian teratoma. All 3 patients presented with psychiatric symptoms and movement disorders, 2 of which developed into a state of unresponsiveness. Brain magnetic resonance imaging of 2 patients was unremarkable, and 1 showed T2 and FLAIR hyperintensity among the areas of medulla, pons, caudex cerebri and callosum. Fluoro-2-deoxy-D-glucose-PET showed variable multifocal cortical and subcortical abnormalities that changed during the course of the disease. Electroencephalograms were abnormal in all patients, showing non-specific, slow, and disorganised activity, 1 showing extreme delta brush. The cerebrospinal fluid showed lymphocytic pleocytosis. All patients showed no response to treatment with first line immunotherapy (corticosteroids, intravenous immunoglobulin (400 mg·kg-1·d-1×5 d, 2-3 courses of treatment)). After the administration of rituximab, 1 patient responded slower, whereas the other 2 patients who recovered dramatically (375 mg/m2 every week for 3-4 weeks)continued immunosuppression with mycophenolatemofetil for 1 year. Relapse occurred in 1 patient when the immunotherapies discontinued 6 months later. During the treatment of rituximab, 2 patients had grade 3 infectious adverse events (hospitalization and intravenous administration of antibiotics). Conclusions Rituximab is effective for the patients with anti-NMDAR encephalitis who fail to respond to the first line immunotherapy. However the utility of rituximab is still a challenge due to the risk of infectious complications and off-label use. Key words: Anti-N-methyl-D-aspartate receptor encephalitis; Immunotherapy; Antibodies, monoclonal, murine-derived; Therapies, investigational; Infection