Clinical electrophysiological features of cyclin-dependent kinase-like 5 gene induced developmental epileptic encephalopathy
贾晨露 1范淑慧 1杨海坡 1姜玉武 1王爽1
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作者信息
1. 北京大学第一医院儿童医学中心(北京 102627)
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摘要
目的 探讨细胞周期蛋白依赖性激酶样-5(Cyclin-dependent kinase-like 5,CDKL5)基因所致发育性癫痫性脑病(Developmental and epileptic encephalopathies,DEE)的临床及电生理特点.方法 回顾性分析2016年6月-2024年5月就诊于北京大学第一医院儿童医学中心的CDKL5相关发育性癫痫性脑病(CDKL5-DEE)患儿临床资料和系列视频脑电图(Video electroencephalography,VEEG).结果 共纳入16例CDKL5-DEE患儿,其中女13例、男3例.所有患儿均为CDKL5基因新生变异,其中错义变异6例、移码变异5例、无义变异4例、大片段缺失1例.起病年龄为出生后8天龄(d)～1岁(y)10月龄(m),中位年龄(85.94±95.76)d.起病时癫痫发作类型:强直发作4例[起病年龄10～52d,中位年龄中位年龄(25.5±15.84)d];局灶性发作5例[起病年龄8 d～8 m,中位年龄(77.76±85.97)d];癫痫性痉挛发作4例[起病年龄3 m～1 y 10 m,中位年龄(6.25±3.49)m;双侧强直-阵挛发作2例[起病年龄30～40 d,中位年龄(35.00±5.00)d)];局灶性发作并发癫痫性痉挛1例(起病年龄2 m).16例患儿共进行了 59次4 h VEEG监测.所有结果均为异常,其中背景正常26次、背景慢节律差25次、无背景8次;间期为后头部或局灶性放电16次、多灶放电19次、广泛性或伴局灶/多灶放电17次、高度失律7次;发作期监测到癫痫性痉挛发作33次、肌阵挛发作6次、局灶性发作5次、强直-阵挛发作2次、不典型失神发作2次、强直发作2次、肌阵挛序贯局灶性发作1次、局灶序贯成串痉挛1次、过度运动-强直-成串痉挛发作1次.6月龄以内的患儿背景均正常,随年龄增长,背景异常明显增多.发作间期2岁以内放电更多灶,2岁以后广泛性放电明显.结论 CDKL5-DEE癫痫发作起病早且药物难治.癫痫性痉挛是每个患儿均出现的发作类型,且持续时间长,随年龄增长全面性发作明显增多.脑电图特点为6月龄以内背景正常,随年龄增长背景及间期放电均具有恶化趋势.
Abstract
Objective To investigate the clinical electrophysiological characteristics of Cyclin-dependent kinase-like 5 gene induced developmental epileptic encephalopathy(CDKL5-DEE).Methods The clinical data and series of video EEGs of children with CDKL5-associated developmental epileptic encephalopathy(CDKL5-DEE)who were admitted to the Children's Medical Center of Peking University First Hospital from June 2016 to May 2024 were retrospectively analyzed.Results A total of 16 patients with CDKL5-DEE were enrolled,including 13 females and 3 males.All patients had de novo variants of CDKL5 gene,including 6 cases of missense variants,5 cases of frameshift variants,4 cases of nonsense variants,and 1 case of large fragment deletion.The age of onset was 8 days(d)after birth～1 year(y)and 10 months(m),and the median age was(85.94±95.76)days.Types of seizures at onset:4 cases of tonic seizures[age of onset 10-52 days,median age(25.5±15.84)days];There were 5 cases of focal seizures[age of onset 8 d～8 m,median age(77.76±85.97)d].There were 4 cases of epileptic spasmodic seizures[age of onset 3 m～l y 10 m,median age(6.25±3.49)m];There were 2 cases of bilateral tonic-clonic seizures[age of onset 30-40 days,median age(35.00±5.00)days];focal concurrent epileptic spasm seizures 1 case(age of onset 2 m).A total of 59 VEEG sessions were performed in the pediatric EEG room of Peking University First Hospital for 4 hours.All the results were abnormal,including 26 normal background,25 slow rhythm difference with background,and 8 no background.The interictal was 16 posterior or focal discharges,19 multifocal discharges,17 generalized or accompanied by focal/multifocal discharges,and 7 hypsarrhythmia;The ictal was 33 epileptic seizures,6 myoclonic seizures,5 focal seizures,2 tonic-clonic seizures,2 atypical absence seizures,2 tonic seizures,1 myoclonic sequential focal seizure,1 focal sequential epileptic spasm,and 1 hypermotor-tonic-spasms.The background of patients within 6 months of age was normal,and the background abnormality increased significantly with age.generalized discharges are evident after 2 years of age between seizures.Conclusion CDKL5-DEE seizures have an early onset and are refractory to medications.Epileptic spasms are the most common type of seizure in every patient and long-lasting,with generalized seizures increasing markedly with age.EEG is characterized by a normal background within 6 months.With the increase of age,the background and interictal discharges have a tendency to deteriorate.
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