生酮饮食、阿那白滞素及托珠单抗治疗急性期热性感染相关性癫痫综合征的疗效及安全性分析

刘伟; 邓泂; 桑田; 张捷

doi:10.13406/j.cnki.cyxb.003754

重庆医科大学学报 ›› 2025, Vol. 50 ›› Issue (03) : 293 -302. DOI: 10.13406/j.cnki.cyxb.003754

热性感染相关性癫痫综合征专题

生酮饮食、阿那白滞素及托珠单抗治疗急性期热性感染相关性癫痫综合征的疗效及安全性分析

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Efficacy and safety of ketogenic diet，anakinra，and tocilizumab in treatment of febrile infection-related epilepsy syndrome in the acute stage

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摘要

目的：采用Meta分析探讨生酮饮食治疗、阿那白滞素及托珠单抗治疗热性感染相关性癫痫综合征（febrile infectionrelated epilepsy syndrome,FIRES）的疗效和安全性。方法：以FIRES、生酮饮食治疗、阿那白滞素和托珠单抗为检索词，检索PubMed、Embase、Web of Science、Cochrane Library、Clini calttrials.gov、中国知网、万方和维普数据库，检索时限为建库至2024年12月13日。由2名评价者按照纳入与排除标准独立筛选文献并评价纳入研究的偏倚风险。采用Review Manager进行Meta分析。结果：在549项研究中，45例病例报告和病例系列符合入选标准，共有45篇回顾性研究，其中25篇、8篇、17篇文献分别被纳入生酮饮食治疗、托珠单抗、阿那白滞素组，分别有66例、8例、54例患者被纳入生酮饮食治疗、托珠单抗、阿那白滞素组，其中有3篇个案报道中3例患者均接受托珠单抗及阿那白滞素治疗。Meta分析结果显示，生酮饮食治疗、阿那白滞素和托珠单抗治疗FIRES急性期有效率分别为68%（95%CI=51%～85%,I²=71%,P<0.01）、57%（95%CI=35%～80%,I²=71%,P<0.01）、100%（95%CI,79%～100%,I²=0%,P=1.00），差异无统计学意义。生酮饮食治疗、阿那白滞素、托珠单抗组存活率分别为96%（95%CI=89%～100%,I²=0%,P=1.00）、96%（95%CI=89%～100%,I²=0%,P=1.00）、100%（95%CI=80%～100%,I²=0%,P=1.00）。生酮饮食治疗、阿那白滞素、托珠单抗组不良反应发生率为22%（95%CI=7%～37%,I²=81%,P<0.01）、19%（95%CI=2%～36%,I²=67%,P<0.01）、0%（95%CI=0%～21%,I²=0%,P=1.00）。结论：生酮饮食治疗、阿那白滞素和托珠单抗均可减少FIRES急性期癫痫发作频次，生酮饮食治疗、阿那白滞素治疗不良反应发生率相对较高，低血糖、感染等不良反应在治疗中可能常见。

Abstract

Objective To investigate the efficacy and safety of ketogenic diet，anakinra，and tocilizumab in the treatment of febrile infection-related epilepsy syndrome（FIRES） through a meta-analysis. Methods With FIRES，ketogenic diet，anakinra，and tocilizumab as search terms，the databases of PubMed，Embase，Web of Science，the Cochrane Library，Clinicalttrials.gov，CNKI，Wanfang Data，and VIP were searched for related articles published up to December 13，2024. Two reviewers independently screened the articles according to the inclusion and exclusion criteria and assessed the risk of bias of the studies included. Review Manager was used to perform the meta-analysis. Results Among the 549 studies，45 case reports and case series met the inclusion criteria，and there were 45 retrospective studies in total，among which 25，8，and 17 were included in the ketogenic diet group，the tocilizumab group，and the anakinra group，respectively，with 66 patients in the ketogenic diet group，8 in the the tocilizumab group，and 54 in the anakinra group. There were 3 case reports，in which all 3 patients were treated with tocilizumab and anakinra. The meta-analysis showed that in the treatment of FIRES in the acute stage，ketogenic diet，anakinra，and tocilizumab showed a response raet of 68%（95%CI=51%-85%，I²=71%，P<0.01），57%（95%CI=35%-80%，I²=71%，P<0.01），and 100%（95%CI=79%-100%，I²=0%，P=1.00），respectively，with no statistical differences between studies. The survival rate was 96%（95%CI=89%-100%，I²=0%，P=1.00） in the ketogenic diet group，96%（95%CI=89%-100%，I²=0%，P=1.00） in the anakinra group，and 100%（95%CI=80%-100%，I²=0%，P=1.00） in the tocilizumab group. The incidence rate of adverse reactions was 22%（95%CI=7%-37%，I²=81%，P<0.01） in the ketogenic diet group，19%（95%CI=2%-36%，I²=67%，P<0.01） in the anakinra group，and 0%（95%CI=0%-21%，I²=0%，P=1.00） in the tocilizumab group. Conclusion Ketogenic diet，anakinra，and tocilizumab can reduce the frequency of seizures in acute stage of FIRES，and ketogenic diet and anakinra treatment have a relatively high incidence rate of adverse reactions. Hypoglycemia and infection are adverse reactions commonly observed during treatment.