生酮饮食治疗对儿童Dravet综合征快速进展期患者的临床分析  

The clinical analysis of ketogenic diet therapy in children with rapidly progressive Dravet syndrome

作　　者：倪燕 周水珍 张赟健 李奕洁 龚晓妍 卢忠英 王艺 郁莉斐 NI Yan;ZHOU Shuizhen;ZHANG Yunjian;LI Yijie;GONG Xiaoyan;LU Zhongying;WANG Yi;YU Lifei(Department of Neurology,National Children’s Medical Center,ChIldren’s Hospital of Fudan University,Shanghai 201102,China)

机构地区：[1]复旦大学附属儿科医院神经科,上海201102

出　　处：《癫痫杂志》2022年第6期517-523,共7页Journal of Epilepsy

基　　金：中国抗癫痫协会癫痫科研基金(CX-B-2021-06)。

摘　　要：目的 探讨生酮饮食治疗(Ketogenic diet treatment,KDT)对儿童发育性癫痫性脑病Dravet综合征(Dravet syndrome,DS)快速进展期的临床疗效及安全性。方法 回顾性分析2011年—2021年于复旦大学附属儿科医院进行KDT的所有患儿的临床资料,<6岁作为疾病快速进展期的判断标准,对符合标准的DS患者进行临床特点、基因检测结果及KDT疗效和安全性分析。结果 32例患者符合疾病快速进展期标准,其中男22例、女10例。起病平均年龄为(5.69±2.10)月龄。所有患者具有多种发作表型,合理抗癫痫发作药物治疗下仍每月发作。KDT保留率3、6、12、≥24个月分别为93.8%(30/32)、87.5%(28/32)、53.1%(17/32)、34.4%(11/32)。KDT有效率3、6、12、≥24个月分别为76.7%(23/30)、75.0%(21/28)、70.6%(12/17)、54.5%(6/11)。KDT后癫痫持续状态(Status epilepticus,SE) 3个月减少100%、6个月减少71%、 12个月减少86%。KDT 12个月后,14例患者出现疗效降级。KDT 3个月后75.0%患者脑电图背景活动改善,54.5%患者痫样放电减少,78.6%患者认知功能改善。KDT启动初期62.5%(20/32)患者存在一过性不良反应,包括腹泻、呕吐、乏力、嗜睡、低血糖、代谢性酸中毒,未发现中长期不良反应。结论 KDT是DS的一种有效安全的治疗方案,在疾病快速进展期进行KDT能有效控制癫痫发作,减少SE发生率,缩短SE持续时间。随着KDT疗程延长,部分患者出现癫痫发作疗效降级现象。KDT能有效改善异常脑电图。疾病进展期进行KDT可改善患者认知功能。建议DS患者在疾病早期进展阶段尽早进行KDT。Objective To explore the efficacy and safety of ketogenic diet therapy(KDT) in the rapidly progressive stage of childhood developmental epileptic encephalopathy Dravet syndrome(DS). Methods The clinical data of all patients who added KDT in the Children’s Hospital of Fudan University from 2011 to 2022 were retrospectively collected, and the age of <6 years was used as the criterion for the rapid progression of the disease. The clinica data, genotype and the efficacy of KDT were analyzed in DS patients who met the criteria. Results A total of32 patients met the criteria for rapid disease progress, including 22 males and 10 females. The age at onset was(5.69±2.10)months. All patients had multiple seizure phenotypes and monthly seizures despite reasonable Antiseizure medications treatment. After 3, 6, 12, and ≥24 months, 93.8%(30/32), 87.5%(28/32), 53.1%(17/32), 34.4%(11/32) remained on the KDT, while 76.7%(23/30), 75.0%(21/28), 70.6%(12/17), 54.5%(6/11) showed >50% reduction in seizure. Status epileptius(SE) was reduced by 100% at 3 months, 71.0% at 6 months, 86.0% at 12 months. After 12 months, 14 patients experienced efficacy degradation. After 3 months, the EEG background rhythm showed improvement in 75.0% patients, interictal epileptic discharges was decreased in 54.5% patients and cognitive function was improved in 78.6% patients. At the initial stage of KDT, 62.5%(20/32) patients had transisent adverse reactions, including diarrhea, vomiting, fatigue, lethargy,hypoglycemia, and metabolic acidosis, but no mid-and long-term adverse reactions were found. Conclusion KDT is an efficective and safe treatment for DS. KDT can effectively control seizures, reduce the incidence of Status SE and shorten the duration of SE. With the prolongation of the KDT course, some patients experienced a degraded effect. KDT can improve abnormal EEG and cognitive function in DS patients. Pharmoco-resistant DS patients are suggested to receive KDT in the early stage of disease progression.

关 键 词：DRAVET综合征 生酮饮食 难治性癫痫 癫痫持续状态 

分 类 号：R742.1[医药卫生—神经病学与精神病学]