以癫痫起病结节性硬化症患者的临床诊治及基因特点回顾性分析

Retrospective analysis of clinical diagnosis and treatment and genetic characteristics of patients with TRE(TSC-related epilepsy)

目的分析结节性硬化症(tuberous sclerosis complex,TSC)相关性癫痫(TSC-related epilepsy,TRE)患者的临床特点、基因特点、用药和手术预后效果,提高对TSC的认识,为临床诊治提供合理的方案。方法入组2014年11月-2019年11月我院癫痫中心诊治的10例TSC合并难治性癫痫患者,回顾性分析视频脑电图、影像学、病理学、基因特点以及治疗预后随访,结合相关文献,总结TSC继发癫痫的临床和基因特点。结果女性3例,男性7例;首次发作:3岁前4例,3~6岁5例,19岁1例,阵挛性发作5例、局灶性发作5例;视频脑电图示单侧癫痫样放电7例,双侧3例;影像学示单侧室管膜下或皮质下结节4例,双侧信号异常5例,1例患者Dandy-Walker畸形;4例手术患者病理学示脑组织切片6层结构消失,见未成熟神经元;基因检测示TSC1变异5例,TSC2变异5例,家系变异7例,4例手术患者均为无义突变;3例雷帕霉素治疗症状改善明显。结论TRE患者通常起病早、年龄小、男多于女,以阵挛性、局灶性发作为主。视频脑电图单侧癫痫样放电为著。影像学多为单侧或双侧室管膜下或皮质下结节。基因检测对治疗有参考意义,突变类型可能与脑组织病变程度和部位、放电起源部位有关,但脑电图记录的放电部位与影像学异常部位无明显相关性,因此当临床治疗不理想时应考虑完善基因检测。

Objective To improve the understanding and provide a reasonable plan for clinical diagnosis and treatment of TRE(TSC-related epilepsy,TRE),by analyzing the clinical and genetic characteristics of TRE as well as the treatment effect about medication and surgery.Methods We analyzed the video EEG,imaging,pathology,genetic characteristics,and treatment effect of 10 patients retrospectively.These patients with refractory epilepsy were diagnosed and treated by our epilepsy center from November 2014 to November 2019.The clinical and genetic characteristics of TRE were summarized.Results There were 3 females,7 males,4 patients with seizures before 3 years old,5 patients with seizures from 3 to 6 years old and 1 at 19 years old.There were 5 cases of spastic seizures and 5 cases of focal seizures.The Video EEG showed that 7 patients have epileptiform discharge site located on one side brain hemisphere and 3 patients about both side.Imaging results showed 4 cases of unilateral subventricular or subcortical nodules,5 cases of bilateral abnormalities,and 1 case of Dandy-Walker deformity.Pathology showed brain tissue section of 4 patients with six-story structure disappearance and immature neurons appearance.Genetic testing revealed 5 cases of TSC1 mutations,5 cases of TSC2 mutations,7 cases of family mutations,and 4 cases of surgical patients were nonsense mutations.The treatment effect about 3 patients of Rapamycin improved than before significantly.Conclusion TRE patients usually fall ill in early age,more males than females,mainly spastic and focal seizures.The Video EEG showed epileptiform discharge site located on one side brain hemisphere.Gene testing is useful for treatment.The type of mutation may be related to the degree and location of brain lesions and the origin of the discharge,but there is no significant correlation between the discharge site recorded on the EEG and the abnormal imaging site.Therefore,genetic testing should be considered when clinical treatment is not improvement.