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THU0501 Efficacy and safety of methotrexate as maintenance therapy for children with anti–n-methyl-d-aspartate receptor (NMDAR) encephalitis: experience of a single center

Background Autoimmune-mediated encephalitis (A-ME) in children remains as a diagnostic and therapeutic challenge (1). These patients have a 12% risk of relapse, which is usually more severe (2). We previously proposed the therapy with methotrexate (MTX) for this condition (3), and we are offering now additional data on its potential benefits. Objectives To describe the outcome of children with A-ME receiving MTX for at least one year after stabilization of symptoms. Methods In this retrospective study we recruited 11 patients (7 females) with A-ME, a mean age of 7.5 years (range 8 months - 14 years), and with a median follow up of 22 months. In all cases, anti-NMDAR antibodies (subunit NR1) were detected in the CSF. Data from these patients were collected by consulting medical records. Relapse of encephalitis was defined as new onset of symptoms occurring after at least 2 months of remission, in the absence of other CNS disease. Results Patients presented with seizures (n=10), behavioral changes (n=11), psychosis (n=11), speech problems (n=10), and autonomic/breathing dysregulation (n=9). Patients were initially treated with methylprednisolone pulses (n=11), rituximab (n=6), intravenous immunoglobulins (n=4), cyclophosphamide (n=3) and MTX (n=11). Complete remission was observed in all cases, and maintenance therapy with MTX (10 mg/m2 BSA) was started in all them, with gradual tapering until it was stopped. Interestingly, no relapses have been observed in any case during the mean follow up. One patient had mild oral ulcers and other showed mild elevation of liver enzymes; both events remitted after discontinuing the treatment for a couple of weeks. Conclusions Since relapses in patients with A-ME are a relatively frequent, the immunosuppressive therapy to prevent them is fully justified (4). Moreover, MTX therapy in pediatric patients is safe and usually well tolerated (3,5,6). The recommended dose is less than 15 mg/m2 BSA or 1 mg/kg, with a maximal dose of 40 mg and with folic acid supplementation. In this regard, our study suggests that MTX administration (10 mg/m2 BSA) during at least one year is a viable and effective therapy for maintenance treatment of A-ME. Accordingly, we did not detect relapses in the 11 patients studied with a median follow up time of 22 months and with an acceptable safety profile. References AlHakeem AS, et al. Neurosciences (Riyadh). 2017;22:67–68. Titulaer MJ, et al. Lancet Neurol. 2013;12:157–165. Bravo-Oro A, et al. Rev Neurol. 2013;57:405–410. Lin JJ, et al. Pediatr Neurol. 2014;50:574–80. Weibel L, et al. Br J Dermatol. 2006;155:1013–20. Li SC, et al. Arthritis Care Res. 2012;64:1175–1185. Disclosure of Interest None declared