摘要
目的分析电压门控性钾离子通道(voltage-gated potassium channels,Kv)基因变异相关遗传性癫痫的基因型—表型特点,评价不同抗癫痫发作药物(anti-seizure medications,ASMs)的疗效。方法检索PubMed数据库,纳入符合纳排标准的患儿进行分析,并根据临床表现将患儿分为“良性”、“脑病”和其他表型3类。对患儿的变异基因、临床表现、药物疗效等进行描述性统计分析,采用Logistic回归探究治疗效果的影响因素。结果纳入474例患儿的数据进行分析。不同表型间变异基因、变异来源等方面有差异。临床特征方面,不同表型间的患儿在发病年龄、合并发育迟缓等方面也有显著差异。单药治疗方面,“良性”表型的患儿最常见的治疗选择是苯巴比妥,“脑病”表型的患儿最常见的治疗选择是钠通道阻滞剂(sodium channel blockers,SCBs)类药物,SCBs单药治疗的疗效均优于其他ASMs。对接受单药治疗的患儿进行多元Logistic分析,结果显示,患儿是否合并发育迟缓及是否应用SCBs是药物治疗疗效的显著影响因素。结论“良性”表型和“脑病”表型的Kv基因变异相关癫痫患儿在基因变异、临床表型和药物选择的多个方面存在差异。SCBs可能是单药治疗此类癫痫的推荐选择。
Aim To analyze the genotype-phenotype characteristics of voltage-gated potassium channels(Kv)associated genetic epilepsy and evaluate the efficacy of anti-seizure medications(ASMs).Methods PubMed database was searched and patients meeting the inclusion criteria were included for analysis.We divided the patients into“benign”,“encephalopathic”and other phenotypes according to the clinical characteristics.We performed descriptive statistical analysis of patients’mutated genes,clinical phenotype and drug efficacy,and used logistic regression to explore the influencing factors of treatment outcome.Results Data of 474 children were included for analysis.There were significant differences among different phenotypes in mutated genes,source of mutations and so on.In terms of clinical characteristics,there were also significant differences between patients with different phenotypes in age of onset,combined developmental delay and so on.In terms of monotherapy,phenobarbital was the most common treatment choice for children with“benign”phenotype,and sodium channel blockers(SCBs)were the most common treatment choice for children with“encephalopathy”phenotype,and the efficacy of SCBs monotherapy was superior to that of other ASMs.Multivariate Logistic analysis of the children receiving monotherapy showed that whether the children were combined with developmental delay and whether SCBs were used were significant factors influencing the efficacy of drug therapy.Conclusions Patients with the“benign”and“encephalopathic”phenotypes differ in several aspects of genetic variation,clinical characteristics,and drug selection.These results suggest that SCBs may be one of the recommended options for monotherapy.
作者
李若茗
张捷
陈超阳
魏然
周颖
崔一民
吴晔
LI Ruo-ming;ZHANG Jie;CHEN Chao-yang;WEI Ran;ZHOU Ying;CUI Yi-min;WU Ye(Dept of Pharmacy,Peking University First Hospital,Beijing 100034,China;Dept of Pharmacy,Administration and Clinical Pharmacy,School of Pharmaceutical Sciences,Peking University Health Science Center,Beijing 100191,China;Dept of Pediatrics,Peking University First Hospital,Beijing 100034,China;Institute of Clinical Pharmacology,Peking University First Hospital,Beijing 100034,China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2023年第6期1067-1073,共7页
Chinese Pharmacological Bulletin
基金
国家科技重大专项重大新药创制(No 2017ZX09304029-006-001)。
关键词
癫痫
儿童癫痫
遗传性癫痫
钾离子通道
抗癫痫治疗
钠通道阻滞剂
epilepsy
pediatric epilepsy
genetic epilepsy
potassium channels
antiepileptic therapy
sodium channel blockers
