Mono- or Polypharmacotherapy in Institutionalized Epileptic Children with Severe Mental Retardation?

ABSTRACT. Nine severely mentally retarded patients with severe epilepsy who were living in an institution were studied during a three-year period by a multi-disciplinary team. A seizure rate serum level chart was made for each patient. It served as the basis for monthly discussions in the team about medication changes. Drug plasma concentrations were monitored monthly. Statistical comparisons between seizure frequency on different drug regimens were made by χ² test. Withdrawal of all medication was possible in one case and reduction to monotherapy in two cases. In the remainder of the patients a combination of two or three anticonvulsants gave the best clinical effect. We thus found polypharmacotherapy necessary for some severely retarded patients with epilepsy. Our multidisciplinary approach and chart monitoring system has many advantages and is valuable for the medical care and drug treatment of this patient category.     

全面性癫癎伴热性惊厥附加症一家系随访分析

目的探讨全面性癫伴热性惊厥附加症(GEFS )的临床意义。方法回顾性分析GEFS 一家系的临床发作情况,作详细体格检查。进行脑电图、24 h动态脑电监测,部分患者作头颅CT检查。结果先证者Ⅳ12,以抽搐频发3 d入院,生后8个月开始高热惊厥(FS)。此次发作为无热性频发全面性强直-阵挛发作。该家系5代共36人。其中有14例患者;男8例,女6例;年龄4岁5个月~82岁,除Ⅰ2发作类型不详外,Ⅱ2、Ⅲ1、Ⅲ4、Ⅲ6、Ⅳ1、Ⅳ11、Ⅳ17、Ⅴ2为FS,Ⅳ2、Ⅳ12、Ⅳ13、Ⅳ14为FS ,Ⅴ1为FS 和失神发作。除Ⅳ13、Ⅳ14目前予丙戊酸镁治疗外,其他患者已减量停药或未用药,均无发作。全家系成员智能发育、全身及神经系统检查均正常。3例行头颅CT检查,均正常。结论GEFS 为常染色体显性遗传性疾病,具有显著遗传异质性和表型异质性。认识该综合征对诊断和鉴别诊断儿童时期癫具有重要的临床意义。     

全面性癫痫伴热性惊厥附加症一家系随访分析

目的探讨全面性癫痫伴热性惊厥附加症（GEFS^＋）的临床意义。方法回顾性分析GEFS^＋一家系的临床发作情况，作详细体格检查。进行脑电图、24h动态脑电监测，部分患者作头颅CT检查。结果先证者Ⅳ12以抽搐频发3d入院，生后8个月开始高热惊厥（FS）。此次发作为无热性频发全面性强直一阵挛发作。该家系5代共36人。其中有14例患者；男8例，女6例；年龄4岁5个月～82岁，除Ⅰ2发作类型不详外，Ⅱ2、Ⅲ1、Ⅲ4、Ⅲ6、Ⅳ1、Ⅳ11、Ⅳ17、Ⅴ2为FS，Ⅳ2、Ⅳ12、Ⅳ13、Ⅳ14为FS^＋，Ⅴ1为FS^＋和失神发作。除Ⅳ13、Ⅳ14。目前予丙戊酸镁治疗外，其他患者已减量停药或未用药，均无发作。全家系成员智能发育、全身及神经系统检查均正常。3例行头颅CT检查，均正常。结论GEFS^＋为常染色体显性遗传性疾病，具有显著遗传异质性和表型异质性。认识该综合征对诊断和鉴别诊断儿童时期癫痫具有重要的临床意义。     

全面性癫癎伴热性惊厥附加症家系GABRB2基因测序研究

目的对全面性癫伴热性惊厥附加症(GEFS )侯选基因GABRB2进行测序研究。方法设计GABRB2外显子-内含子交界处内含子引物,采用PCR直接测序法,对一GEFS 家系GABRB2编码区全部11个外显子进行测序分析。结果患儿GABRB2基因外显子2,mRNA第133个碱基发现一新的C/G多态性。结论该家系未发现GABRB2基因编码区的突变;所显示的mRNA的单个碱基多态性对以后其他癫家系的连锁分析及GABRB2 mRNA、基因功能研究均有重要意义。     

全面性癫痫伴热性惊厥附加症6家系SCN1B基因突变筛查

目的探讨全面性癫痫伴热性惊厥附加症家系SCN1B基因突变情况。方法共收集GEFS＋家系6个,采集40份外周血,并取健康对照组外周血50份。提取基因组DNA,设计7对引物,进行聚合酶链反应（PCR）扩增,琼脂糖凝胶电泳,选取符合条件的PCR产物进行聚丙烯酰胺凝胶电泳,进行单链构象多态性分析,对个别PCR产物进行双向测序。结果6个先证者和50名健康对照进行SCN1B的5对外显子筛选时,均未发现异常带出现。6个先证者的PCR产物测序结果与基因组序列相比对,也未发现碱基改变。结论全面性癫痫伴热性惊厥附加症是一种复杂综合征,本组家系中未发现SCN1B基因突变,GEFS^＋具有遗传异质性。     

全面性癫伴热性惊厥附加症电压门控钠离子通道基因的研究进展

全面性癫伴热性惊厥附加症(GEFS+)是国际抗癫联盟新近提出的一种新的癫综合征。在家系分析的基础上,目前GEFS+的遗传学研究主要集中在基因定位方面,研究表明GEFS+与编码电压依赖性Na+通道(SCN)基因突变有关。现就GEFS+与SCN1B、SCN2B、SCN1A、SCN2A基因突变的关系进行综述,旨在提高对本病的认识。     

全面性癫伴热性惊厥附加症2家系GABRG2基因突变分析

目的收集2个全面性癫伴热性惊厥附加症(GEFS+)家系,分析中国人GEFS+的遗传特点。并对2个GEFS+家系进行GABRG2基因突变检测,以期发现新的突变位点。方法对参与本研究的2个GEFS+家系成员在知情自愿的情况下参与调查、体检和血样本采集。另取20名健康体检儿童作为对照。对先证者及患者和健康对照组GABRG2基因全部9个外显子进行测序。将患者基因组各外显子片段测序结果与GenBank中的正常序列和健康对照组外显子片段测序结果通过互联网(BLAST)进行比对分析。结果 GEFS+2个家系成员共40份外周血中均未发现K289M、R43Q、Q351X、IVS6+2T→G、R139G、W390X等6种已知突变位点,仅在外显子5第40碱基处发现1个已知C/T多态性。结论 GABRG2基因很可能不是我国汉族人群GEFS+家系主要的致病基因,其与国外报道的GEFS+的主要致病基因存在种族及地域差异。     

癫痫和热性惊厥患儿脑脊液生长抑素的变化

目的探讨癞痫(EP)和热性惊厥(FC)患儿脑脊液(CSF)生长抑素(SS)含量及其与EP和FC发病机制关系。方法采用放射免疫法(RIA)测定EP和FC患儿CSF中SS含量。结果EP组CSF中SS水平(139.59±45.95)ng/L明显高于FC组(89.71±37.51)ng/L和对照组(77.31±37.10)ng/L(P均<0 05);FC组CSF中sS水平(89 71±37 51)ng/L与对照组比较无显著性差异(P>0.05);严重组EP和FC患儿CSF中SS水平与普通组比较均无显著性差异(P均>0.05)。结论SS参与EP发作,可能有致EP发作作用,而与FC的惊厥发作无关。     

Severe Mental Retardation in Jordanian Children

ABSTRACT. The etiology of severe mental retardation has not previously been studied in Jordan. In a group of 203 mainly severely mentally retarded children born 1975–1985, we found the etiology to be related to two main factors: (1) sequele from high perinatal morbidity or meningitis in infancy leading to a combination of severe mental retardation and cerebral palsy; (2) a high degree of intermarriage and a high frequency of retarded siblings indicating that genetic causes of MR are common. The results underscore the importance of further development of antenatal and perinatal care, especially for poor people and the need of genetic councelling.     

全面性癫(癎)伴热性惊厥附加症家系SCN1A及GABRG2基因突变筛查

目的 探讨全面性癫(癎)伴热性惊厥附加症(GEFS+)家系SCN1A及GABRG2基因突变情况.方法 收集8个GEFS+家系中包括先证者在内符合GEFS+临床表型的生存患者共31例,健康对照组100例,均为汉族.采集外周血提取DNA,设计合适引物特异性扩增SCN1A及GABRG2基因组全部外显子序列,应用PCR产物直接测序方法进行突变筛查.结果 全部GEFS+患者在SCN1A及GABRG2基因均未发现迄今已报道的所有已知突变.然而,在家系E先证者的SCN1A基因第1外显子发现了新核苷酸多态性(SNP) c.69G>A,呈杂合子变异,密码子由GCG序列突变为GCA,属同义突变;随后在2/100例健康对照人群中也证实存在.另外,在GABRG2基因的翻译起始密码前发现1个新SNP c.-14delA,表现为cDNA序列的第-14号核苷酸A缺失变异,未参与氨基酸的表达;该变异存在于所有GEFS+患者及92/100例健康对照者中.结论 SCN1A基因发现的1个新SNP(c.69G>A)虽未引起氨基酸改变,但可能通过影响mRNA的稳定性,从而改变受体蛋白的功能.GABRG2基因发现的新SNP(c.-14delA)是我国人群高频SNP,并非GEFS+致病的潜在因素.该新发现的2个碱基多态性丰富了SNP数据库,为癫(癎)易感多态位点的研究提供了候选位点.SCN1A及GABRG2基因很可能不是我国南方汉族GEFS+家系的主要致病基因,证实GEFS+具有明显的遗传异质性.     

纳洛酮对高热惊厥大鼠海马神经元c-fos表达的影响

目的　观察不同剂量纳洛酮对高热惊厥大鼠海马神经元c fos表达的影响 ,进一步探讨纳洛酮对高热惊厥脑损伤的干预作用。方法　利用热水浴惊厥模型诱导生后 1 5dSD大鼠发生 7次热性惊厥 ,期间两治疗组大鼠每次惊厥一出现立即腹腔注射纳洛酮 (分别为 1mg/kg ,2mg/kg) ,而惊厥对照组大鼠仅腹腔注射等量生理盐水 ,利用免疫组织化学方法及Western印迹法对c fos基因的表达产物在海马中的分布情况进行定性及半定量分析。结果　接受纳洛酮治疗的大鼠海马神经元c fos表达较惊厥对照组明显降低 ,主要降低部位在齿状回及海马CA3区 ;且这种作用具有剂量依赖性 ,2mg/kg的纳洛酮较 1mg/kg的纳洛酮更为明显地下调c fos表达。结论　应用纳洛酮能明显抑制高热惊厥后c fos蛋白在海马神经元的表达 ,提示其具有减轻惊厥后兴奋毒性损伤的作用 ,亦提示惊厥发作时阿片肽表达变化的机制可能与海马c fos表达的调节机制之间存在相互作用关系。     

Febrile convulsions

Febrile convulsions are the commonest form of seizure under the age of 2, occurring in 2–4% of children in the UK. The majority occur between 12–18 months and are more common in those with a family history. The aetiology is multi-factorial, although most episodes occur in children with viral infections. In most children the seizure will have self-resolved prior to coming to hospital and the child may be back to normal. No investigation or treatment is necessary. However, it is important to appreciate that for parents who have witnessed the episode, it will have been extremely distressing and frightening. In addition, there are many myths and misconceptions held by parents particularly in relation to the association with fever and further episodes, as well as the concerns surrounding longer term outcomes. Reassurance and clear advice given by clinicians is therefore one of the most important aspects to management. This review gives a practical approach to management for clinicians and enables them to give informed and up to date guidance to parents, thus allowing them to feel confident about how to manage their child at home if they were to have further episodes, as well as providing reassurance about the harmless nature of febrile convulsions.     

The Pattern of Childhood Epilepsy with Mental Retardation in Nigeria

Of 580 epileptic children, 353 males and 227 females, seen at the Paediatric Neurology Clinic of the University of Nigeria Teaching Hospital Enugu, from 1985 to 1987, 18 per cent were mentally retarded, a much higher prevalence rate than in the general population. Nine different seizure types were seen, with generalized tonic-clonic seizures (grand mal) leading in frequency. The highest incidence of mental retardation occurred among the children with infantile spasms (51 per cent). For all the seizure types, there was a long delay in seeking medical attention (mean interval, 1.7 years). The mean interval for epileptics with mental retardation was even higher (2.77 years). Factors found to increase the chances of an epileptic child having mental retardation include episodes of status epilepticus, early age at onset of seizures, and long delay before presentation to hospital for treatment. There is need for increased efforts aimed at the elimination of these factors and also for a well organized programme to educate the population about the nature of epilepsy, and the importance of compliance with the treatment schedule.     

全面性癫癎伴热性惊厥附加症家系γ-氨基丁酸A型受体γ2亚单位基因研究

目的研究全面性癫癎伴热性惊厥附加症(GEFS )患者的γ-氨基丁酸A型受体γ2亚单位(GABRG2)基因分布。方法对10个家系先证者的GABRG2基因进行体外扩增及测序分析。结果发现一核苷酸多态位点,未发现已报道的突变。结论GABRG2基因突变在我国北方汉族人分布并不普遍。     

全面性癫(癎)伴热性惊厥附加症家系γ-氨基丁酸A型受体γ2亚单位基因研究

目的研究全面性癫痫伴热性惊厥附加症（GEFS＋）患者的γ-氨基丁酸A型受体γ2亚单位（GABRG2）基因分布。方法对10个家系先证者的GABRG2基因进行体外扩增及测序分析。结果发现一核苷酸多态位点,未发现已报道的突变。结论GABRG2基因突变在我国北方汉族人分布并不普遍。     

Rett's Syndrome: Prevalence and Impact on Progressive Severe Mental Retardation in Girls

ABSTRACT. The prevalence of Rett's syndrome was studied in a part of southwestern Sweden comprising five counties and the city of Gothenburg. In a population of 315469 children and adolescents, 6-17 years of age, 10 cases were detected, all girls. The corresponding prevalence was 0.65/10000 girls, i.e. about twice that of phenylketonuria (PKU) in the same area. As progressive brain disorders/metabolic diseases together constitute 5-6 % (1.5-2.0/10000 children) of the aetiologies among severely mentally retarded persons of this age group in central Sweden, it can be concluded that within this group Rett's syndrome should be considered as an aetiological factor to think of in females. This syndrome might well be responsible for one-fourth to one-third of such cases among girls.     

反复热性惊厥过程中γ-氨基丁酸B受体对气体信号分子一氧化碳的影响

目的探讨γ氨基丁酸B受体(GABABR)对热性惊厥(FS)大鼠一氧化碳(CO)/血红素氧合酶(HO)系统表达的影响。方法SD大鼠32只随机分为对照组、FS组、FS baclofen组、FS phaclofen组,每组各8只。采用热水浴诱导大鼠FS,隔日诱导1次,共10次。采用双波长分光光度计法测定大鼠血浆CO含量;用原位杂交观察GABABR和HO1mRNA表达情况;用免疫组织化学方法观察GABABR和HO1蛋白表达情况。结果FS baclofen组CO含量高于FS组,同时HO1表达也较FS组增强;而FS phaclofen组CO含量低于FS组,同时HO1表达也较FS组减弱。FS baclofen组和FS phaclofen组与FS组相比,差异均有显著意义(P均<0.05)。结论反复FS过程中,GABABR的改变可影响CO/HO1系统的表达。     

Benign Childhood Epilepsy with Centro-Temporal Spikes: Evolution of Seizure Types

Evolution of the seizure types according to age in 20 outpatients with benign childhood epilepsy with centro-temporal spikes (BECT) was studied. BECT satisfied the following criteria: 1) normal intelligence, 2) central and/or mid-temporal spikes with normal background activities on the interictal EEG recordings, and 3) partial and/or generalized seizures in sleep. The patients were divided into two groups according to the clinical course; P (n = 10): patients with only (n = 6) or predominantly (n = 4) partial seizures, G (n = 10): those with only (n = 7) or predominantly (n = 3) generalized seizures. No difference in the age at onset was noted between the two groups. There were also no indications that the seizures tend to generalize at a younger age or remain partial at an older age. Therefore, age is not important in the evolution of partial to generalized seizures in BECT.     

Testicular Dysgenesis and Mental Retardation in Two Incompletely Masculinized XY-Siblings

ABSTRACT. Aberrations of fetal sexual development were studied in two retarded phenotypic female 46, XY dysgonadal sisters from a consanguineous marriage. Endocrine evaluation revealed an inadequate response of plasma-testosterone to human chorionic gonadotropin (hCG) stimulation and a normal response to adrenocorticotropic hormone (ACTH) administration. At exploratory laparotomy dysgenetic testes and remnants of the Müllerian and of the Wolffian duct were found. Loss of testicular function, resulting in male pseudohermaphroditism (MPH), can occur at different times during intrauterine development, resulting in a variety of clinical manifestations. A thorough evaluation is warranted in all patients in order to reach a correct diagnosis which is of importance for appropriate gender assignment and genetic counseling.