儿童结节性硬化症合并癫痫的临床研究

A thesis submitted toZhengzhou Universityfor the degree of MasterClinical Research of Tuberous Sclerosis Complexcomplicated with Epilepsy in ChildrenBy：Yan SunSupervisor：ProfLi GaoPediactricsThe First Affilated Hospital of Zhengzhou UniversityMay 2013原创性声明IIIII I IIII I IIIIII IIII r IIlY231 4593本人郑重声明：所呈交的学位论文，是本人在导师的指导下，独立进行研究所取得的成果。除文中已经注明引用的内容外，本论文不包含任何其他个人或集体已经发表或撰写过的科研成果。对本文的研究作出重要贡献的个人和集体，均已在文中以明确方式标明。本声明的法律责任由本人承担。学位论文作者：忍和平乏 日期：少啦年穆碉；何日学位论文使用授权声明本人在导师指导下完成的论文及相关的职务作品，知识产权归属郑州大学。根据郑州大学有关保留、使用学位论文的规定，同意学校保留或向国家有关部门或机构送交论文的复印件和电子版，允许论文被查阅和借阅；本人授权郑州大学可以将本学位论文的全部或部分编入有关数据库进行检索，可以采用影印、缩印或者其他复制手段保存论文和汇编本学位论文。本人离校后发表、使用学位论文或与该学位论文直接相关的学术论文或成果时，第一署名单位仍然为郑州大学。保密论文在解密后应遵守此规定。学位论文作者：客抑 日期：叼弓年妙月多秒日摘要儿童结节性硬化症合并癫痫的临床研究研究生 孙艳导师 高丽郑州大学第一附属医院河南 郑州450052摘 要背景结节性硬化症(Tuberous sclerosis complex，TSC)属于神经皮肤综合征中的一种疾病，该病的发病率约为16000，其中散发患者约占23。1935年Gunther等发现该病为常染色体显性遗传性疾病，其显著的病理特征为多脏器错构瘤样增生，可损伤皮肤、脑部、肾脏、心脏等器官。研究发现首发(917)及初诊(946)患儿最常见的神经系统表现是癫痫发作，TSC患者的癫痫发作高峰期多在1岁以内，随着年龄增长，发作比例有下降趋势，但是对于不同首发年龄的TSC合并癫痫患儿的临床发作特点的研究尚不多。关于首发年龄不同患儿的发作类型分布、服药种类、初次脑电图异常情况、生长发育状况及皮肤损害特点的研究尚不足，对于散发性和具有家族史癫痫患儿的发作类型分布、药物治疗选择特点及TSC患儿皮肤损害与生长发育落后关系的研究有待进一步探索。目的探讨儿童结节性硬化症合并癫痫的临床特征。方法收集39例结节性硬化症合并癫痫患儿的临床资料，对患儿的癫痫发作、个人史、家族史、病程及药物治疗等进行回顾性分析。摘要职f甲耋口木1、39例TSC合并癫痫患儿癫痫发作的首发年龄为1月11岁，平均发病年龄为(201248)岁，中位年龄9月。其中01岁21例(538)、13岁8例(205)、35岁6例(154)、大于5岁4例(103)。2、TSC合并癫痫患儿中，具有家族史14 N(359)，散发患儿25例(641)；有皮肤损害表现23例(590)，有生长发育落后和(或)智能减退25例(641)。3、TSC合并癫痫患儿的抗癫痫药物治疗研究显示，单药、两种药物及三种以上药物治疗有效率分别为410、282、179。4、TSC合并癫痫患儿中，不同首发年龄的癫痫患儿发作类型分布(n2=5012，P=0082)、初次脑电图异常(Fisher确切概率法，P-0667)、服药种类(贮=1437，P=0488)、生长发育落后(Fisher确切概率法，P=0337)及皮肤损害(Fisher确切概率法，P=0469)的差异性比较无统计学意义。5、TSC合并癫痫患儿中，散发与具有家族史患儿发作类型分布的比较经统计学分析，具有显著性差异(贮=6520，P=0038)；在药物治疗方面上的差异性比较无统计学意义(Fisher确切概率法，P=0607)。6、TSC合并癫痫患儿皮肤损害与生长发育落后关系的研究显示，二者无相关性(贮=1400，P=0237)。7、TSC合并癫痫患儿中，不同发作频次患儿初次脑电图异常的比较经统计学分析，具有显著性差异(Fisher确切概率法，P=0008)：在药物治疗方案选择上的比较具有显著性差异(Fisher确切概率法，P=0029)。结论1在TSC合并癫痫患儿中，随着年龄的增加，癫痫发病患儿所占比例呈下降趋势；2在TSC合并癫痫患儿中，随着使用抗癫痫药物种类的增加，药物治疗有效率呈下降趋势；3在TSC合并癫痫患儿中，具有家族史患儿的全身性发作比例高于散发患儿；散发患儿的局灶性发作比例高于具有家族史患儿：关键词：儿童；结节性硬化症；癫痫IIAbstractClinical Research of Tuberous Sclerosis Complex complicated withEpilepsy in ChildrenPostgraduate：Sun YanTutor Professor：Gao LiThe First Affilated Hospital of Zhengzhou UniversityZhengzhou China 450052AbstractBackground and Obj ectiveTuberous sclerosis(Tuberous sclerosis complex，TSC)iS aneurocutaneous syndromeThis disease iS an autosomal dominant geneticdisease by Gunther in 1 935，there is a significant pathological features ofmultiple organ hamartoma like hyperplasia，it can damage the skin，brain，kidneys，heart and other organs and SO onThe incidence of the diseaseiS about 16000sporadic patients accounts for about 23，the study foundthat seizures among the children with the first(917)and newlydiagnosed(946、)is the most common neurological manifestations，the。of the TSC patients is1 than 1 rearthebiggerpeakof seizures age among the patients IS lessnan 1 year me tuggerthe TSC patients，the onset of a downward trend in the proportion ofrelatively smallerbut for different starting age of tuberous sclerosis withepilepsy clinical episodes proportionThe starting age children withseizure type distribution，medication species，growth and developmentstatus，initial starting age with newly diagnosed seizure type distributioncharacteristic EEG abnormalities，skin lesions characteristics andsporadic and familial epilepsy in children，children with epilepsy age，IIIAbstractskin damage and growth retardation relationship is still insufficientOhi ectiveExplore the clinical features of tuberous sclerosis in children with epilepsyMethodsCollect clinical data of 39 patients with tuberous sclerosis with epilepsy inchildren with seizures in children，such as personal history,family history,course ofdisease and drug therapy were retrospectively analyzedIksuits1、39 cases of children with seizures starting age were from lmonth to 11yearsold，with the average(201+248)years，a median age of 9 monthEljilepsy startingage 0 to 1 year of age，1 to 3 years old，3 to 5 years old，five over the age of onset ofthe respective proportions were 538，205，154，1032、In the Tuberous sclerosis children，359children had a genetic family history,641children had not family history of hereditary；590children had skindamageperformance of 641growth retardation or smart waning3、Single drug，two drugs and three or more drugs in the treatment efficiency were410，282，1794、Different starting age children of seizure types(贮=5012，P=0082)，medication species(贮=1437，P=0488)，growth retardation(P=0337)，the initialEEG abnormalities p-0667)and skin damage were no statistically significantdifference俨=0469)5、Dissemination in children with familial seizure types was statisticallysignificant(贮=6520，P=0038)，medication(P=0607)difference was notstatistically significant6、 Skin lesions in children with growth retardation was no correlation(贮=1400，P=0237)IVAbstract7、Daily attack group and choose an auspicious day in finding out the abnormalEEG(P=0029)and the application of drug treatment programs(P=0008)wasdifferentConclusion1、Epileptic children starting age is gradually increasing，the epileptogenesisproportion may decreasing2、With the gradual increase of the number of species of antiepileptic drugs，medication efficient downward trend may relate to the severity of the disease inchildren，the use of three or more medications may be refractory epilepsy in children3、Generalized seizures in children with famil