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ORIGINAL ARTICLE
Year : 2018  |  Volume : 131  |  Issue : 2  |  Page : 156-160

Utility and Safety of Intrathecal Methotrexate Treatment in Severe Anti-N-methyl-D-aspartate Receptor Encephalitis: A Pilot Study


1 Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
2 Department of Emergency, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
3 Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences; Center of Neuroscience, Chinese Academy of Medical Sciences, Beijing 100730, China

Correspondence Address:
Dr. Hong-Zhi Guan
Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0366-6999.222327

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Background: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a treatable autoimmune neurologic syndrome that occurs with or without tumor association. However, some severe cases are refractory to systemic immunotherapy. This pilot study aimed to evaluate the utility and safety of intrathecal methotrexate injection for severe patients with anti-NMDAR encephalitis who did not respond to first-line immunotherapy. Methods: Intrathecal injections with methotrexate and dexamethasone were performed weekly in four legible patients within consecutive 4 weeks. Cerebrospinal fluid (CSF) was collected at baseline and each time of intrathecal injection for identification of anti-NMDAR antibody titers. Results: Significant clinical improvement was observed in three patients associated with a stepwise decrease of CSF anti-NMDAR antibody titers (maximum: 1/320 to minimum: 1/10). After 2 months of follow-up, they were able to follow simple commands and had appropriate interactions with people (modified Rankin scale [mRS] of 0–2). At 12 months of follow-up, they all had returned to most activities of daily life (mRS of 0), and no relapses were reported. One patient showed no clinical improvement and died of neurologic complications. Conclusions: Intrathecal treatment may be a potentially useful supplementary therapy in severely affected patients with anti-NMDAR encephalitis. Further large cohort study and animal experiment may help us elaborate the utility of intrathecal injection of methotrexate and its mechanism of action.


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