儿童热性感染相关性癫痫综合征的临床特征和预后分析

Clinical features and prognosis of febrile infection-related epilepsy syndrome in children

摘要

目的：研究热性感染相关性癫痫综合征（febrile inection-related epilepsy syndrome,FIRES）重要临床特征及治疗预后结局。方法：纳入2022年3月至2024年6月于北京大学第一医院住院治疗的15例FIRES患者，回顾性分析其临床特征、治疗方案和预后结局，并进行电话随访。结果：所有患者癫痫持续状态持续中位时间为15 d,93.3%(14/15)合并意识障碍，53.3%(8/15)合并呼吸衰竭并行气管插管术，86.7%(13/15)曾进入重症监护室治疗。7例患者于急性期同时行血、脑脊液白细胞介素（interleukin,IL）-1β、IL-2、IL-4、IL-5、IL-6、IL-8、IL-10、肿瘤坏死因子-α(tumor necrosis factor,TNF-α)等多种炎症因子检测，7例患者脑脊液炎症因子升高，且明显高于血清炎症因子水平。急性期80%(12/15)患者脑电图呈弥漫性慢波改变，46.7%(7/15)监测到游走性局灶性发作。急性期头颅磁共振成像（magnetic resonance imaging,MRI）表现为颞/岛叶皮质水肿（60%）、白质异常信号（33.3%）、屏状核征（13.3%）。慢性期MRI特征为脑沟加深（75%）、脑室扩张（33.3%）。急性期治疗包括丙种球蛋白、大剂量甲泼尼龙静滴（15例应用，2例有效）、生酮饮食（4例应用，1例有效）、托珠单抗（5例应用，3例有效）、阿那白滞素治疗（2例应用，1例有效）。截至末次随访时所有患者的中位病程为14.0(4～65)个月，仅2例患者癫痫发作完全控制，其余13例患者均存在难治性癫痫。93.3%的患者存在认知障碍。结论：FIRES病情急重，一线免疫治疗效果往往较差，托珠单抗、阿那白滞素可能对于部分患者急性期癫痫发作有效。

Abstract

Objective To investigate the important clinical features and prognosis of febrile infection-related epilepsy syndrome （FIRES）. Methods A retrospective analysis was performed for the data of 15 children with FIRES who were hospitalized and treated in Peking University First Hospital from March 2022 to June 2024，including clinical features，treatment regimens，and prognosis，and follow-up was performed by telephone. Results The median duration of status epilepticus was 15 days for all children. Of all 15 children，14（93.3%） were comorbid with disturbance of consciousness，8（53.3%） were comorbid with respiratory failure and underwent endotracheal incubation，and 13（86.7%） had been admitted to the intensive care unit. In the acute stage，7 children underwent the examination of various inflammatory factors in blood and cerebrospinal fluid，including interleukin（IL）-1β，IL-2，IL-4，IL-5，IL-6，IL-8，IL-10，and tumor necrosis factor-α，and all 7 children had significant increases in the levels of inflammatory factors in cerebrospinal fluid，which were significantly higher than the levels of inflammatory factors in serum. Of all 15 children，12（80%） had diffuse slow wave changes on electroencephalography，and migrating focal seizures were detected in 7 children（46.7%）. Cranial magnetic resonance imaging（MRI） manifestations in the acute stage included temporal and insular cortical edema（60%），abnormal white matter signal（33.3%），and claustrum sign（13.3%），and MRI features in the chronic stage included the deepening of cerebral sulci（75%） and ventricular dilatation（33.3%）. The treatment in the acute stage included intravenous drip of gamma-globulin and high-dose methylprednisolone in 15 children（effective in 2 children），ketogenic diet in 4 children （effective in 1 child），tocilizumab in 5 children（effective in 3 children），and anakinra in 2 children（effective in 1 child）. As of the last follow-up，the median duration of disease was 14.0 months（4-65 months） for all patients，and only 2 children achieved complete seizure control，while the remaining 13 children had refractory epilepsy. Cognitive impairment was observed in 93.3% of the children. Conclusion FIRES often has acute and severe conditions，and first-line immunotherapies often have a poor therapeutic effect. Tocilizumab and anakinra may be effective in some patients with seizures in the acute stage.

关键词

儿童 / 癫痫持续状态 / 热性感染相关性癫痫综合征

Key words

children / status epilepticus / febrile infection-related epilepsy syndrome

基金资助

中国抗癫痫协会癫痫基金“新锐酮学”研究资助项目(CX-B-2021-13)

北京亦城合作发展基金会罕见病科研课题资助项目(YCXJ-JZ-2023-017)