托珠单抗治疗儿童热性感染相关性癫痫综合征2例并文献复习

doi:10.12372/jcp.2025.24e0426

摘要/Abstract

摘要：

目的报道托珠单抗在2例儿童热性感染相关性癫痫综合征（FIRES）患者中的应用，为治疗该病提供参考。方法回顾性分析我院儿童重症监护室于2023年收治的2例FIRES患儿的临床表现、诊疗过程及其对托珠单抗的治疗反应，并结合相关文献进行复习和讨论。结果 2例患儿对多种抗癫痫发作药物、麻醉剂、生酮饮食治疗及一线免疫治疗（大剂量甲基泼尼松龙、大剂量免疫球蛋白）无反应，使用托珠单抗进行二线免疫治疗后，癫痫发作得以控制，无不良反应。随访4~6个月，1例患儿再次癫痫发作。结论托珠单抗作为二线免疫治疗药物对FIRES有效，耐受性好，是一种具备潜力的治疗手段之一。

关键词: 热性感染相关性癫痫综合征, 托珠单抗, 细胞因子, 儿童

Abstract:

Objective To report the use of tocilizumab in 2 cases of children with febrile infection-ralated epilepsy syndrome (FIRES), and provide a reference for its therapeutic application. Methods A retrospective analysis was conducted on the clinical manifestations, diagnostic and treatment processes, and therapeutic responses to tocilizumab in two FIRES patients admitted to the pediatric intensive care unit of our hospital in 2023, and the relevant literatures were reviewed. Results Neither patient responded to multiple antiepileptic drugs, anesthetics, ketogenic diet therapy, or first-line immunotherapy (high-dose methylprednisolone and high-dose intravenous immunoglobulin). Following second-line immunotherapy with tocilizumab, epileptic seizures were effectively controlled without adverse reactions. After 4-6 months of follow-up, one patient experienced recurrence of epileptic seizures. Conclusions Tocilizumab demonstrates efficacy as a second-line immunotherapy for FIRES, with good tolerability, and represents a promising treatment option.

Key words: febrile infection-ralated epilepsy syndrome, tocilizumab, cytokine, child

中图分类号:

李凡, 黄先杰, 范亚珍, 赵建闯, 崔晨航, 郭芪良, 乔俊英. 托珠单抗治疗儿童热性感染相关性癫痫综合征2例并文献复习[J]. 临床儿科杂志, 2025, 43(7): 532-538.

LI Fan, HUANG Xianjie, FAN Yazhen, ZHAO Jianchuang, CUI Chenhang, GUO Qiliang, QIAO Junying. Tocilizumab treatment for febrile infection-related epilepsy syndrome in children: 2 cases report and literature review[J]. Journal of Clinical Pediatrics, 2025, 43(7): 532-538.

图/表 5

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表1

托珠单抗治疗FIRES病例文献复习"

病例	ASMs	麻醉剂	一线/二线免疫治疗	使用TCZ 距起病天数/d	TCZ剂量	TCZ后 IL-6水平 /pg·mL^-1	治疗效果	随访
1^[14]	VPA、LEV、LCS、PHT、PB	咪达唑仑、氯胺酮	PE/TCZ	21	4 mg·kg·次^-1，每周1次，共2次	血2.9	第二次后13 d，发作明显减少；语言运动恢复正常	急性期内癫痫发作，每月1~2次；3个月后发作更频繁，复查TL-6正常
2^[14]	LCS、LEV、PHT、CLB、TPM、VPA	咪达唑仑	IVMP，IVIG/TCZ	30	4 mg·kg·次^-1，每10天1次，共2次	血2.4	首剂后2~3天，发作明显减少，2~5次/天；语言、意识水平、运动正常	—
3^[17]	PHT、PER、LEV、VPA、LCS、CLB、PB	咪达唑仑、硫喷妥钠	IVMP，IVIG/TCZ	NA	4 mg·kg·次^-1，共2次，间隔时间不详	—	首剂后72小时，脑电和临床发作均停止，出院后应用4种ASMs	随访4月，癫痫未发作；mRS评分3分，在短期记忆、学习、执行功能方面轻度缺陷
4^[18]	LEV、PHT、PB、VPA、LCS、TPM、大麻二酚、劳拉西泮	咪达唑仑、氯胺酮、戊巴比妥	IVMP，IVIG/阿那白滞素、TCZ	20	12 mg·kg·次^-1，每2周1次，共4次	—	首剂后3天，发作减少，出院后应用5种ASMs	随访1年，每天发作0~1次；右侧颞叶内侧硬化；行为失调，注意力不集中
5^[19]	PB、VPA、TPM、LEV、PHT	咪达唑仑、戊巴比妥	IVMP，IVIG/TCZ、TAC、IT-DEX	36	8 mg·kg·次^-1，每周1次，共2次	血4.6，脑脊液1	发作暂时受抑制后复发，给予IT-DEX、再次IVMP，加TAC后好转	—
6^[7]	PB、VPA、LEV、TPM、OXC、LCS、CZP、PER、ZNS	异丙酚、咪达唑仑	IVMP，IVIG/TCZ	36	4 mg·kg·次^-1，每周1次，共2次	血正常	首剂应用后3天，发作减少50%以上，第二剂后10天，发作得到控制	3个月后再次发作，每月2~3次，随访10个月，mRS评分1分，智商76
7^[20]	LEV、VPA、TPM、PER、PB、GBP、CLB、VGB、RUF	咪达唑仑、异丙酚、硫喷妥钠、氯胺酮	IVMP，IVIG，PE/托法替尼、TCZ、阿那白滞素	51	前4次8 mg·kg·次^-1，每2周1次；后3次每月1次	下降，数值不详	首次应用后16天，显著临床和电反应，发作改善	最低意识状态，康复治疗
8^[21]	CZP、FPHT、LEV、PB、LCS	咪达唑仑、异丙酚、氯胺酮	IVMP，IVIG，PE/TCZ	17	4 mg·kg·次^-1，d17，d23	—	首剂后2天撤机，4天抽搐停止，10天脑电图背景活动正常，28天出院	1年后，每月局灶性发作，脑电图示左颞慢波。轻度注意力缺陷，神经心理评估正常

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