Department of Neurology, American University of Beirut Medical Center, Beirut, Lebanon.
Division of Neurology, Saint George Hospital University Medical Center, Beirut, Lebanon.
Front Immunol. 2024 Mar 6;15:1369587. doi: 10.3389/fimmu.2024.1369587. eCollection 2024.
Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is one of the most prevalent etiologies of autoimmune encephalitis. Approximately 25% of anti-NMDAR encephalitis cases prove refractory to both first- and second-line treatments, posing a therapeutic dilemma due to the scarcity of evidence-based data for informed decision-making. Intravenous rituximab is commonly administered as a second-line agent; however, the efficacy of its intrathecal administration has rarely been reported.
We report two cases of severe anti-NMDAR encephalitis refractory to conventional therapies. These patients presented with acute-onset psychosis progressing to a fulminant picture of encephalitis manifesting with seizures, dyskinesia, and dysautonomia refractory to early initiation of first- and second-line therapeutic agents. Both patients received 25 mg of rituximab administered intrathecally, repeated weekly for a total of four doses, with no reported adverse effects. Improvement began 2-3 days after the first intrathecal administration, leading to a dramatic recovery in clinical status and functional performance. At the last follow-up of 6 months, both patients remain in remission without the need for maintenance immunosuppression.
Our cases provide evidence supporting the intrathecal administration of rituximab as a therapeutic option for patients with refractory anti-NMDAR encephalitis. Considering the limited penetration of intravenous rituximab into the central nervous system, a plausible argument can be made favoring intrathecal administration as the preferred route or the simultaneous administration of intravenous and intrathecal rituximab. This proposition warrants thorough investigation in subsequent clinical trials.
抗 N-甲基-D-天冬氨酸受体（anti-NMDAR）脑炎是自身免疫性脑炎最常见的病因之一。约 25%的抗 NMDAR 脑炎病例对一线和二线治疗均无反应，由于缺乏循证数据来做出明智决策，因此存在治疗困境。静脉注射利妥昔单抗通常作为二线药物使用；然而，其鞘内给药的疗效鲜有报道。
我们报告了两例对常规治疗无效的严重抗 NMDAR 脑炎病例。这些患者表现为急性起病的精神病，进展为暴发性脑炎，伴有癫痫发作、运动障碍和自主神经功能障碍，对早期使用一线和二线治疗药物均无反应。两名患者均接受了 25mg 利妥昔单抗鞘内给药，每周重复一次，共 4 个剂量，无不良反应报告。首次鞘内给药后 2-3 天开始出现改善，导致临床状况和功能表现明显恢复。在最后一次 6 个月的随访中，两名患者均处于缓解期，无需维持免疫抑制治疗。
我们的病例提供了证据支持鞘内注射利妥昔单抗作为治疗难治性抗 NMDAR 脑炎的一种选择。鉴于静脉注射利妥昔单抗进入中枢神经系统的穿透有限，可以合理地认为鞘内给药是首选途径，或者同时进行静脉和鞘内利妥昔单抗给药。这一观点需要在后续的临床试验中进行深入研究。
