良性婴儿癫痫的临床特点及PRRT2基因突变检测

发布时间：2017-12-27 17:08

本文关键词：良性婴儿癫痫的临床特点及PRRT2基因突变检测　出处：《山东大学》2017年硕士论文　论文类型：学位论文

【摘要】：研究目的:良性婴儿癫痫(benign infantile epilepsy,BIE)是临床常见的儿童癫痫类型,总体预后良好,病程自限,曾被称为婴儿良性部分性癫痫。随着对该疾病的认识不断加深,临床诊断BIE的患儿2岁后仍有发作的病例报道逐渐增多,而且随着大家对高级神经活动的重视,发现了部分患儿出现一定程度的认知障碍、语言发育落后。关于该疾病的分子遗传学研究也不短取得新进展,有研究证实少数BIE的患儿存在PRRT2基因突变。为了能够在发病初期准确判断疾病预后、指导治疗,本文收集了 35例BIE的临床资料,对比分析其临床特点、脑电图改变、影像学、治疗效果等,并对患者进行PRRT2基因突变筛查,以寻求早期评估预后的客观指标。方法:1.收集2013年7月至2016年6月于山东省千佛山医院住院的35例BIE的临床资料,分析其性别,首次发病年龄,临床发作特点,脑电图检查、其他辅助检查及治疗等情况,并随访其预后转归。用Microsoft Excel进行数据分析:计量资料用均值±标准差、最大值、最小值表示;计数资料则用例数、百分数表示。2.收集患者外周血DNA,采用PCR扩增和Sanger测序的方法筛查PRRT2基因突变。结果:1.一般情况:35例患者中,男性18例(51.43%),女性17例(48.57%)。最小发病年龄为2月,最大发病年龄为1岁11月,平均发病年龄为10.72±6.746个月。其中在1岁以内发病者23例(65.71%),1岁～2岁发病者12例(34.29%)。所有患儿发病前后精神运动发育正常,无围产期高危因素,无外伤、中枢神经系统感染等其他情况所致脑损害。31例(88.57%)患儿无热性惊厥或癫痫家族史;4例有癫痫家族史。2.临床特点(1)丛集性35例患者中有18例(51.43%)发病初期存在丛集性发作,最多者11次/日。其余17例(48.57%)患儿为单次发作。(2)持续时间35例患儿病程中141次惊厥发作,其中43次(30.50%)持续时间1min,86次(60.99%)持续时间在1-3min,12次(8.51%)持续时间3-5min。(3)发作类型根据患儿家长描述发作时表现,发作类型有局灶性发作(6例,17.14%)、局灶性发作继发全面性发作(11例,31.43%)以及全面性发作(18例,51.43%)。3.脑电图(EEG):所有患儿至少完善一次视频脑电图检查,平均为2.1次。所有患儿脑电图背景活动正常。3例(8.57%)患者监测到共16次发作。异常放电均为局灶起源,1例患儿起源于右额区,1例起源于右侧中央、顶区,1例起源于枕区。15例(42.86%)患儿虽未监测到发作,但病程初期及随访期间睡眠期痫性放电持续存在,3例(8.57%)患儿在病程初发作间期脑电图正常,但随访过程中睡眠期出现痫性波发放,放电主要来源于单侧或双侧的中央、中线区,少部分来源于枕部及后颞区。其余14例(40%)患儿为正常脑电图。4.CT/MRI 30例患儿行颅脑CT(4例)或MRI(26例)检查,29例(96.67%)无异常,1例(3.33%)提示髓鞘发育不良。另外5例因检查失败家长拒绝。5.脑脊液检查12例患儿完善脑脊液检查。所有患儿脑脊液压力、常规、生化、培养等检测均未见异常。6.其他辅助检查入院后完善血尿便常规、肝肾功、心肌酶、电解质等生化检查。血常规及生化检查中血象轻度增高者3例;谷草转氨酶轻度增高者6例;CKMB轻度增高者9例;轻度低钠血症1例;余未见明显异常。35例患儿完善血糖检测,其中1例轻度增高,余未见异常。部分患儿同时伴有胃肠炎表现,5例患儿完善大便轮状病毒抗原检测,其中3例检测结果为阳性,2例阴性。7.PRRT2基因突变筛查结果实验对35例患者进行了 PRRT2基因测序,未筛查出PRRT2突变。8.治疗和随访15例患儿因初期发作不频繁,家长拒绝抗癫痫药物治疗,其中12例无复发,3例患儿复发后加用抗癫痫药物后均已控制,其中2例选择丙戊酸钠,1例左乙拉西坦。20例患儿首次就诊后即开始接受单药抗癫痫治疗。18例患儿在口服抗癫痫药物后1月内停止发作,其中1例在开始治疗后2周出现1次胃肠炎诱发惊厥,后未再复发。2例患儿在3岁后仍有惊厥发作,发作类型同前。患儿随访时间在5-36个月,平均时长16.7个月。多数患儿在3岁前停止发作。其中末次发作年龄=1岁者14例(40.00%),1岁～2岁者16例(45.71%);3例(8.58%)患者末次发作时间在2～3岁,2例(5.71%)患儿末次发作年龄3岁。随访期间患儿精神运动发育无明显异常。结论:(1)BIE具有自限性,总体预后良好,多数患者在抗癫痫治疗后短期内停止发作。(2)少数以BIE的临床表现起病的患儿,其临床经过并非呈良性、自限性,需要较长时间的抗癫痫药物治疗。(3)本组2例3岁后仍有癫痫发作的患儿起病年龄分别为1岁11月和1岁9月,较平均年龄偏大。(4)本组BIE患儿未检测到PRRT2基因点突变。
[Abstract]:Research purposes: benign infantile epilepsy (BIE) is a common type of childhood epilepsy. Its overall prognosis is good and its duration is limited. It has been called benign partial epilepsy in infants. With the deepening of the understanding of the disease, the number of children who have been diagnosed with BIE has increased gradually after the age of 2 years old. And with the attention of advanced nervous activity, a number of children developed a certain degree of cognitive impairment and language development. The molecular genetic study of the disease has also made new progress. Studies have shown that a small number of BIE children have PRRT2 gene mutations. In order to accurately determine the prognosis of the disease in the early stage of the disease and guide the treatment, this paper collected the clinical data of 35 cases of BIE, comparative analysis of the clinical characteristics, EEG, imaging, treatment, and patients with PRRT2 gene mutation screening, objective index to seek early prognosis assessment. Methods: 1.. The clinical data of 35 cases of BIE from July 2013 to June 2016 in Qianfo Hill Hospital of Shandong province were collected, and their gender, age of onset, clinical seizure characteristics, EEG examination, other auxiliary examinations and treatment were analyzed, and the prognosis of patients was followed up. Microsoft Excel is used for data analysis: the measurement data are expressed with mean standard deviation, maximum value and minimum value; count data are represented by use case number and percentage. 2. the peripheral blood DNA was collected and the PRRT2 gene mutation was screened by PCR amplification and Sanger sequencing. Results: 1. general cases: of the 35 patients, 18 were male (51.43%), and 17 (48.57%) were female. The minimum age of onset was February, the maximum age of onset was 1 years in November, and the average age of onset was 10.72 + 6.746 months. Among them, there were 23 cases (65.71%) and 12 cases (34.29%) from 1 to 2 years of age under 1 years of age. All the children had normal mental motor development before and after the onset of the disease. There was no high risk factors for perinatal period, no brain damage caused by other cases such as trauma and central nervous system infection. 31 cases (88.57%) had no febrile convulsion or family history of epilepsy; 4 had a family history of epilepsy. 2. of the clinical characteristics (1) of the 35 patients with cluster, 18 (51.43%) had a series of episodes at the beginning of the onset, with a maximum of 11 times per day. The remaining 17 cases (48.57%) were single episodes. (2) duration of seizures occurred in 35 children, including 43 (30.50%) duration 1min, 86 times (60.99%), duration 1-3min, 12 times (8.51%) duration 3-5min. (3) the types of seizures were described according to the parents' seizures. There were focal seizures (6 cases, 17.14%), focal attacks followed by generalized seizures (11 cases, 31.43%), and generalized seizures (18 cases, 51.43%). 3. electroencephalogram (EEG): all children had at least one video electroencephalogram at least once, averaging 2.1 times. The background activity of electroencephalogram in all children was normal. A total of 16 episodes were monitored in 3 (8.57%) patients. The abnormal discharge is the focal origin, 1 children originate in the right frontal area, 1 cases originate in the right central and top area, and 1 cases originate in the occipital region. 15 cases (42.86%) were not detected during the attack, but the course of initial and follow-up period of sleep epileptic discharge persisted, 3 cases (8.57%) patients in the early course of interictal EEG was normal, but the process of follow-up period of sleep epileptic wave discharge, discharge mainly from unilateral or bilateral central, midline area and a little from the occipital and posterior temporal area. The rest of the 14 cases (40%) were normal electroencephalogram. 30 cases of 4.CT/MRI were examined with craniocerebral CT (4 cases) or MRI (26 cases), 29 cases (96.67%) had no abnormality, 1 cases (3.33%) showed myelin dysplasia. The other 5 cases were rejected by the parents who failed to check. 5. cerebrospinal fluid examinations were performed in 12 cases, and the cerebrospinal fluid examination was perfected. No abnormality was found in all children's cerebrospinal fluid pressure, routine, biochemical, and culture. 6. other auxiliary examination after admission to improve the routine hematuria, liver and kidney work, myocardial enzymes, electrolytes and other biochemical tests. 3 cases of blood routine and biochemical examination in 6 cases of mild increased; aspartate aminotransferase increased slightly; 9 cases of slightly increased CKMB; 1 cases of mild hyponatremia; no other abnormalities. 35 cases of children improved blood glucose test, of which 1 cases were slightly higher, and no abnormalities were found. Some of the children were accompanied by gastroenteritis, 5 cases improved the detection of stool rotavirus antigen, of which 3 cases were positive, 2 cases were negative. The 7.PRRT2 gene mutation screening test showed that the PRRT2 gene was sequenced in 35 patients, and the PRRT2 mutation was not screened. 8., 15 children with treatment and follow-up were not treated with antiepileptic drugs because of infrequent initial attacks, of which 12 cases did not recur. 3 cases were controlled after the use of antiepileptic drugs after recurrence. 2 of them were valproate and 1 left Ne Laci Staw. 20 cases of children began to receive single drug antiepileptic treatment after the first visit. 18 cases were stopped after oral antiepileptic drugs in January, of which 1 cases had 1 gastroenteritis induced convulsions 2 weeks after the beginning of treatment, and no recurrence was found. 2 children at the age of 3 after a seizure, seizure types. The children were followed up for 5-36 months, with an average length of 16.7 months. Most of the children cease their seizures before the age of 3. Among them, the last attack age was =1 years old, 14 cases (40%), 1 to 2 years old 16 cases (45.71%), 3 cases (8.58%) patients had the last attack time in 2~3 years old, 2 cases (5.71%) children last attack age 2 years old. There was no obvious abnormal mental movement in the children during the follow-up period. Conclusion: (1) BIE is self limiting, and the overall prognosis is good. Most patients stop in the short term after antiepileptic treatment. (2) a few children with BIE clinical manifestations are not benign and self limiting, and need a long time of antiepileptic drugs. (3) the onset age of 2 children with epileptic seizures after 3 years of age was 1 year November and 1 year September, the average age was larger than the average age. (4) PRRT2 gene point mutation was not detected in children with BIE in this group.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R742.1

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