Effectiveness of Intra-thecal Methotrexate in Refractory Anti-N-methyl-d-aspartate Receptor Encephalitis

Abstract

Background Anti-N-methyl-d-aspartate receptor encephalitis is one of the most common autoimmune encephalitis for which first- and second-line therapies have been recommended following international consensus. However, some refractory cases do not respond to the first- and second-line therapy and require further immune-modulatory therapies such as intra-thecal methotrexate. In this study, we reviewed six confirmed cases of refractory anti-N-methyl-d-aspartate receptor encephalitis from two tertiary centers in Saudi Arabia that required escalation of treatment and received a six-month course of intra-thecal methotrexate. The aim of this study was to evaluate the effectiveness of intra-thecal methotrexate as immunomodulatory therapy for refractory anti-N-methyl-d-aspartate receptor encephalitis. Methods: We retrospectively evaluated six confirmed cases of refractory anti N-methyl-d-aspartate receptor encephalitis who did not improve after first- and second-line therapy and received monthly intra-thecal methotrexate treatment course for six consecutive months. We reviewed patient demography, underlying etiologies, and compared their modified Rankin score prior to receiving intra-thecal methotrexate and six months after completing the treatment. Results: Three of the six patients showed a marked response to intra-thecal methotrexate with a modified Rankin scale of 0–1 at 6-month follow-up. None of the patients experienced any side effects during or after intra-thecal methotrexate treatment, and no flareups were observed. Conclusion: Intra-thecal methotrexate may be a potentially effective and relatively safe escalation option for immunomodulatory therapy of refractory anti- N-methyl-d-aspartate receptor encephalitis. Future studies on intra-thecal methotrexate -specific treatment regimens may further support its utility, efficacy, and safety in treating refractory anti- N-methyl-d-aspartate receptor encephalitis.