GATOR1复合体突变相关脑皮质发育畸形所致儿童药物难治性癫痫的手术疗效观察

Surgical efficacy of drug-resistant epilepsy in children caused by GATOR1 complex mutation-associated malformation of cortical development

目的 观察接受手术治疗的GATOR1复合体突变相关脑皮质发育畸形(MCD)所致药物难治性癫痫患儿的疾病特征和手术疗效.方法 回顾性分析2015年1月至2020年12月北京大学第一医院儿童癫痫中心手术治疗的35例GATOR1复合体突变相关MCD所致药物难治性癫痫患儿的临床资料,总结并分析其遗传学特点、临床特征、手术方式及疗效.术后3、6、12个月及之后每年于门诊复查.以癫痫控制(Engel分级Ⅰ级)情况评估手术疗效.采用Kaplan-Meier法绘制患儿的术后癫痫控制曲线,采用log-rank检验比较携带不同基因突变患儿的手术疗效.结果 35例患儿中,DEPDC5突变25例(71.4%),NPRL2突变4例(11.4%),NPRL3突变6例(17.2%);病变累及额叶最为常见(23例,65.7%),而累及枕叶者最为少见(9例,25.7%).28例(80%)患儿直接接受根治性手术;7例(20%)患儿接受立体定向射频热凝(RFTC)治疗后均复发,其中1例继续口服药物治疗,另6例接受根治性手术治疗.34例接受根治性手术治疗的患儿中,局灶性切除术21例,离断术13例;术后病理学均诊断为MCD,以局灶性皮质发育不良(FCD)Ⅱa型为主(20例,58.8%).35例患儿的随访时间[M(Q1,Q3)]为32(21,44)个月.至末次随访,行根治性手术治疗的34例患儿中,27例(79.4%)癫痫控制;1例RFTC治疗后复发仅口服药物治疗的患儿,Engel分级为Ⅳ级.至末次随访,DEPDC5、NPRL2和NPRL3突变患儿的癫痫控制比例分别为22/25、3/4和2/6;log-rank检验结果显示,DEPDC5突变患儿的手术疗效优于NPRL2和NPRL3突变的患儿(P=0.006).结论 观察发现,接受手术治疗的GATOR1复合体突变相关MCD所致药物难治性癫痫患儿中携带DEPDC5突变者较多,病变主要累及额叶,病理学改变以FCD Ⅱa型最为常见;癫痫外科根治性手术是其有效治疗方法,其中DEPDC5突变者较NPRL2和NPRL3突变者疗效好.

ObjectiveTo observe the disease characteristics and surgical efficacy in children with drug-resistant epilepsy caused by GATOR1 complex mutation-associated malformations of cortical development(MCD).MethodsA retrospective analysis was conducted on the clinical data of 35 children with GATOR1 complex mutation-associated MCD who had drug-resistant epilepsy and underwent surgical treatment at the Pediatric Epilepsy Center of Peking University First Hospital from January 2015 to December 2020.The genetic characteristics,clinical features,surgical methods and efficacy were summarized and analyzed.Postoperative follow-up examinations were conducted at 3,6,12 months post operation and annually thereafter.Surgical efficacy was assessed based on the outcome of seizure control(Engel classⅠ).The postoperative seizure control curves of the patients were plotted using the Kaplan-Meier method,and the surgical efficacy of patients with different gene mutations was analyzed using the log-rank test.ResultsAmong the 35 children,25(71.4%)had DEPDC5 mutations,4(11.4%)had NPRL2 mutations,and 6(17.2%)had NPRL3 mutations.The most common affected lobe was the frontal lobe(23 cases,65.7%),while involvement of the occipital lobe was the least common(9 cases,25.7%).Twenty-eight(80%)children underwent radical surgery directly,and 7(20%)children received stereotactic radiofrequency thermocoagulation(RFTC)and experienced recurrence.Among them,1 child continued oral medication,and the remaining 6 children underwent radical surgery.Among the 34 children who underwent radical surgery,21 underwent focal resection,and 13 underwent disconnection surgery.The postoperative pathological diagnosis was MCD,predominantly focal cortical dysplasia(FCD)typeⅡa(20 cases,58.8%).The follow-up duration[M(Q 1,Q 3)]for the 35 children was 32(21,44)months.At the last follow-up,among the 34 children who underwent radical surgery,27(79.4%)achieved seizure control.One child treated with RFTC and medication only achieved Engel ClassⅣ.At the last follow-up,the seizure control rates for children with DEPDC5,NPRL2,and NPRL3 mutations were 22/25,3/4,and 2/6,respectively.The log-rank test showed that the surgical efficacy of children with DEPDC5 mutations was superior to those with NPRL2 and NPRL3 mutations(P=0.006).ConclusionsObservations indicate that among children with drug-resistant epilepsy caused by GATOR1 complex mutation-associated MCD who undergo surgical treatment,there is a higher prevalence of DEPDC5 mutations.The lesions mainly involve the frontal lobe,and the most common pathological change is FCD typeⅡa.Epilepsy surgery is an effective treatment method,with better efficacy observed in patients with DEPDC5 mutations compared to those with NPRL2 and NPRL3 mutations.