Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Largo Daneo 3, 16132, Genoa, Italy.
Autoimmunology Laboratory, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
Neurol Sci. 2022 Nov;43(11):6441-6447. doi: 10.1007/s10072-022-06313-3. Epub 2022 Aug 11.
The immunotherapy strategy for autoimmune encephalitis is based on several types and schedules of both first- and second-line drugs. Failing to respond to the latter prompts the use of non-conventional rescue therapies, with higher risks of severe adverse effects. We report on a protocol that entails the use of intravenous immunoglobulin cycles to bridge the 4-month period that the second-line drug rituximab needs to exert its full therapeutic effects.
Three patients with NMDAR encephalitis who were non-responders to first-line treatments entered the study. The protocol consisted of six monthly cycles of intravenous immunoglobulins (IVIG, 0.4 mg/kg/die for 5 days), starting 1 month after the last rituximab infusion (1000 mg at days 0 and 15). Brain MRI and [F]-FDG-PET were performed at onset and at six and 18 months after onset.
In the three patients, substantial improvements of disability or complete recovery were achieved, without modifications over the 30-to-50-month follow-up. No adverse events nor laboratory test abnormalities were recorded. Imaging findings paralleled the favorable disease courses. Brain [F]-FDG-PET was more sensitive than MRI in detecting abnormalities.
Our observations suggest that the herein-described protocol might be used in patients with NMDAR encephalitis at risk for poor prognosis in the mid-term when they need to shift to rituximab. [18F]-FDG-PET confirmed to be a sensitive tool to detect the minimal brain lesions that can underlie isolated cognitive and psychiatric symptoms.
自身免疫性脑炎的免疫疗法策略基于多种类型和方案的一线和二线药物。对后者没有反应会促使使用非常规的抢救疗法,这些疗法有更高的严重不良反应风险。我们报告了一种方案,该方案涉及使用静脉注射免疫球蛋白循环来桥接二线药物利妥昔单抗发挥其全部治疗效果所需的 4 个月时间。
3 名抗 NMDAR 脑炎患者对一线治疗无反应,进入研究。该方案包括 6 个每月的静脉免疫球蛋白(IVIG,0.4mg/kg/die 连用 5 天)周期,从最后一次利妥昔单抗输注后 1 个月开始(第 0 和 15 天各 1000mg)。在发病时以及发病后 6 个月和 18 个月进行脑 MRI 和 [F]-FDG-PET 检查。
在这 3 名患者中,残疾程度显著改善或完全恢复,在 30 至 50 个月的随访中没有改变。未记录到不良反应或实验室检查异常。影像学发现与有利的疾病过程平行。脑 [F]-FDG-PET 比 MRI 更能敏感地检测到异常。
我们的观察结果表明,当需要转换为利妥昔单抗时,该方案可用于具有中期不良预后风险的抗 NMDAR 脑炎患者。[18F]-FDG-PET 证实是一种敏感的工具,可以检测到可能导致孤立认知和精神症状的微小脑病变。