西罗莫司治疗儿童结节性硬化症合并癫痫的临床研究

祝雪芬 陈泽 华虞 郭胜

[摘要] 目的 探討西罗莫司治疗儿童结节性硬化症合并癫痫的疗效及安全性。 方法 选取2015年5月～2018年6月于我院确诊的结节性硬化症合并癫痫患儿144例，随机分为实验组和对照组各72例，实验终末最后入组106例，其中实验组58例，对照组48例，实验组予西罗莫司联合抗癫痫药物治疗，对照组予常规抗癫痫药物治疗。观察两组治疗24周、48周后的临床疗效，观察西罗莫司的不良反应及安全性。 结果 治疗24周、48周后实验组总有效率分别为70.69%、79.31%，脑电图好转率分别为72.41%、77.59%;对照组总有效率分别为33.33%、52.08%，脑电图好转率分别为37.50%、47.92%，差异有统计学意义（P<0.05）。实验组的口腔溃疡发生率相对较高，两组患者的其他不良反应发生率比较，差异无统计学意义（P>0.05）。 结论 西罗莫司治疗儿童结节性硬化症合并癫痫具有良好的临床疗效，且安全性好，不良反应少。

[关键字] 西罗莫司;儿童结节性硬化症;癫痫;临床疗效

[中图分类号] R725.9          [文献标识码] B          [文章编号] 1673-9701（2020）15-0062-04

Clinical study of sirolimus in children with tuberous sclerosis complicated with epilepsy

ZHU Xuefen   CHEN Zehua   YU Guosheng   LIU Zhanli

Department of Pediatrics， Hangzhou First People's Hospital， Zhejiang University of Traditional Chinese Medicine，  Hangzhou   310006， China

[Abstract] Objective To investigate the efficacy and safety of sirolimus in the treatment of tuberous sclerosis complicated with epilepsy in children. Methods A total of 144 children with tuberous sclerosis and epilepsy diagnosed in our hospital from May 2015 to June 2018 were randomly divided into the study group and the control group， with 72 cases in each group. At the end of the study， 106 cases were included， with 58 cases in the study group and 48 cases in the control group. The study group was given sirolimus combined with antiepileptic drugs， and the control group was given conventional antiepileptic drugs. The clinical efficacy of the two groups after 24 weeks and 48 weeks of treatment， the adverse reactions and safety of sirolimus were compared between the two groups. Results After 24 weeks and 48 weeks of treatment， the total effective rate in the study group was 70.69% and 79.31%， respectively， and the EEG improvement rates were 72.41% and 77.59%， respectively; while the total effective rate in the control group was 33.33% and 52.08%， respectively， and the EEG improvement rates were 37.50% and 47.92%， respectively， and the differences were statistically significant（P<0.05）. The incidence of oral ulcers in the study group was relatively high， and there was no significant difference in the incidence of other adverse reactions between the two groups（P>0.05）. Conclusion Sirolimus has remarkable efficacy in treating tuberous sclerosis complicated with epilepsy in children， and has higher safety and fewer adverse reactions.

[Key words] Sirolimus; Childhood tuberous sclerosis; Epilepsy; Clinical efficacy

结节性硬化症（tuberous sclerosis complex，TSC）是一种任何年龄均可发病、多个器官系统损害的常染色体显性遗传性神经皮肤综合征。婴幼儿和儿童期的主要临床特征包括典型的皮肤病变、癫痫发作以及心脏、大脑、肾脏错构瘤等[1-2]。其中，癫痫发作是导致儿童严重脑损伤及智力障碍的主要病因之一[3]。本病的主要发病机制为TSC1或TSC2基因突变，导致哺乳动物雷帕霉素靶蛋白（mammalian target of rapamycin，mTOR）通路功能异常[4-5]。西罗莫司作为mTOR通路的免疫抑制剂，目前用于TSC合并癫痫的治疗，具有减小TSC病变结节大小，改善皮肤症状，减少癫痫发作等良好的临床效果[6-8]。但目前国内对西罗莫司治疗TSC的临床研究和经验不多，此外，西罗莫司在14岁以下儿童中的安全性和疗效尚不明确。……