左乙拉西坦对癫痫患儿认知和脑电图的影响

1引言癫痫（epilepsy）是大脑神经元突然异常过度或同步化活动所引起的发作性疾病,是神经系统常见疾病之一,其中2／3发生在儿童。     

青少年肌阵挛癫痫的临床、EEG与SPECT的研究

目的：探索青少年肌阵挛癫痫（JME）的临床、脑电图（EEG）和发作间期单光子发射断层扫描（SPECT）的特点.方法：总结40例JME病例的临床、EEG和 SPECT显像等资料.结果：年龄6～32岁.病程2周至19年,平均（4.12±3.95）年.病因：家族史7例.临床表现：有肌阵挛发作性抽动40例（100%）,兼有全面性强直阵挛发作36例（90%）,兼有失神发作12例（30%）.常规EEG检查13例,正常5例,异常8例 长程EEG监测27例（V-EEG 21例,AEEG 6例）均异常,总体异常35例（87%）.异常者中,广泛性31例（89%）,局灶性异常4例（11%） 多棘慢波31例（89%）,高波幅慢波2例（6%）.发作间期SPECT正常11例（28%）,异常29例（72%）.低灌注12例（41%）,高灌注17例（59%）.异常灌注部位41个,额叶占40%.影像学异常5%.结论： 有关JME的诊断,在把握好临床表现的基础上,长程EEG监测显得很重要,SPECT显像的额叶异常灌注灶的证据也具有重要意义.     

青少年肌阵挛性癫痫21例误诊分析

青少年肌阵挛性癫痫（juvenile myoclonic epilepsy,JME）是常见的特发性全面性癫痫（IGE）综合征之一,以肌阵挛发作为突出表现,占全部癫痫的5%～10%[1],对不典型表现者临床容易漏诊误诊.本研究回顾性分析我院癫痫专病门诊诊断的21例JME患者的临床表现、脑电图（EEG）特点、诱发因素、误诊原因及药物疗效,以提高临床对此类疾病的认识.     

青少年肌阵挛癫的预后及影响因素长期随访分析

目的：探讨青少年肌阵挛癫?的预后。方法：对42例青少年肌阵挛癫?患者进行3～19年长期随访,平均随访9．75年,回顾性分析该病的预后及其影响因素。结果：28例（67％）患者发作终止,21例无复发,其中无发作5年以上、10年以上分别为14例、4例。单纯肌阵挛发作（M J ）17例中,14例发作终止（82％）;MJ＋全面性强直阵挛发作（GTCS）14例中,9例发作终止（64％）;MJ＋失神发作（AS）7例中,4例发作终止（57％）;MJ＋单纯部分性发作（SPS）＋GTCS 4例中,3例未终止发作,1例发作减少。减药前脑电图正常者11例,2例复发（18％）;异常者17例,5例复发（29％）。结论：青少年肌阵挛癫?早期正确的诊断、正确应用抗癫?药物,预后较好,50％的患者发作终止并可长期停药。单纯MJ预后较好,MJ＋SPS＋GTCS、MJ＋AS预后较差。减药前脑电图正常者复发率低。     

左乙拉西坦治疗儿童癫痫的疗效及安全性观察

目的：研究左乙拉西坦对于不同类型癫痫患儿的临床疗效及其安全性。方法：将各种不同发作类型的64例癫痫患儿分为单药治疗组47例和添加治疗组17例。单药治疗组应用左乙拉西坦治疗,添加治疗组因之前用药未能控制癫痫发作进而添加左乙拉西坦进行联合治疗,观察两组治疗结果。结果：单药治疗组有效率为83％（39／47例）,添加治疗组为65％（11／17例）,两组总有效率比较差异无统计学意义（x2=1．48,P〉0．05）。部分性发作总有效率为85％（34／40例）,全面性发作总有效率为63％（15／24例）,二者比较差异有统计学意义（x2=4．23,P〈0．05）。此外,简单部分性发作、复杂部分性发作、部分性发作继发全面性发作、婴儿痉挛、强直阵挛发作以及肌阵挛发作的有效率均在60％以上。单药治疗组与添加治疗组不良反应均较少且轻微,差异无统计学意义（x2=0．05,P〉0．05）。结论：左乙拉西坦治疗儿童各型癫痫均有良好的疗效,不良反应少。     

肌阵挛失神癫痫的临床及神经电生理学研究

目的：提高对肌阵挛失神癫痫（EMA）的认识。方法：收集2005年3月至2011年6月确诊为EMA的患儿5例,对其临床及神经电生理特征进行回顾性分析。结果：5例患儿以2岁零4个月至5岁起病,平均起病年龄4岁。3例以肌阵挛失神（MA）为唯一或主要发作形式,2例以全身强直阵挛发作（GTCS）首发,分别于1年和3年后转变为MA;临床表现为频繁的双侧节律性肌阵挛抽动。EEG＋EMG联合检查可见在EEG双侧同步的3Hz节律性棘慢波放电的同时,同步的EMG记录可见3Hz肌阵挛电活动和逐渐增强的强直性肌肉收缩电位。过度换气试验及闪光刺激均易诱发脑电一临床发作。发作间期EEG均见全导棘慢波,2例双额区尤显。治疗主要为丙戊酸钠单药或联合其他抗癫痫药物,分别随访6个月至4年,5例均有效（4例发作控制,1例仍有些许发作伴学习困难）。结论：EMA是一种以MA为主要发作类型的儿童期癫痫综合征,EMA的诊断主要依赖于临床症状观察和EEG＋EMG记录,早期准确诊断,正确选用抗癫痫药物,有助于远期预后改善。     

左乙拉西坦治疗癫的疗效及安全性分析

目的：观察左乙拉西坦（LEV）单药和（或）添加治疗成人癫?的临床治疗效果及安全性,旨在为今后临床治疗方案的选择提供参考和借鉴。方法：前瞻性选取本院神经内科2010～2013年4年间收治的160例成人癫?患者,根据是否为新确诊患者分为2组：Ⅰ组为既往确诊患者给予LEV添加治疗,Ⅱ组为新诊断癫?患者开始即给予L EV单药治疗,对比两组患者临床疗效及不良反应。结果：Ⅰ组总有效率为85．8％,略低于Ⅱ组的87．5％,但差异无统计学意义（χ2＝0．0703,P＝0．7909）;各型癫?疗效比较差异亦无统计学意义（ P＞0．05）;Ⅰ组脑电图缓解率为48．1％,略低于Ⅱ组的53．3％（χ2＝0．1287,P＝0．7198）,均无1例脑电图加重;Ⅰ组不良反应发生率为29．2％略高于Ⅱ组的27．5％（χ2＝0．0407,P＝0．8402）,副作用均较轻微,未给予处理,于2～5周内缓解或消失。结论：L EV不管是单药还是添加治疗对各型成人癫?具有疗效,能显著改善患者脑电图,不良反应发生率低且症状轻微,持续时间短,患者耐受性好,可作为临床治疗成人癫?的首选药物之一。     

儿童肌阵挛癫痫临床和录像脑电图分析

目的：探讨儿童肌阵挛癫痫患儿的临床、脑电图（EEG）和治疗特点。方法：对35例肌阵挛癫痫患儿的临床表现、录像脑电图（V-EEG）及抗癫痫药物的治疗效果进行回顾性分析。结果：35例均有肌阵挛发作,以肌阵挛为唯一的发作形式9例,其它26例合并强直阵挛发作、强直发作、部分性发作等发作类型。30例患儿EEG可见全导棘慢波或多棘慢波暴发,5例患儿为局灶性异常。28例明确为癫痫综合征,以青少年肌阵挛性癫痫和Lennox-Gastaut综合征最常见。多数患儿对丙戊酸治疗有效。结论：肌阵挛癫痫以肌阵挛发作为主要表现,正确的诊断依靠详细的询问肌阵挛发作的病史和V-EEG检查结果,治疗应首选丙戊酸。     

伴有肌阵挛失神发作的癫痫1例报告

患儿，女，9岁。于一年前无明显诱因出现楞神、发呆，有时在楞神、发呆的同时出现发作性头颈部、双肩部节律性抖动，发作后不跌倒、不入睡，但自述不知。每月发作2～4次。睡眠中未曾注意到有无发作，但有时有尿床现象，未予重视和治疗。至今年3月，发作频繁(每天数次至     

青少年肌阵挛癫痫患者的大尺度脑网络研究

采用静息态功能性磁共振成像(rs-fMRI)数据探究青少年肌阵挛癫痫(JME)患者大尺度脑网络的变化。采集17例JME患者和15名正常志愿者的脑部静息态功能磁共振成像数据,两组均使用偏相关系数构建静息态脑网络。分别计算JME患者组与正常对照组的阈值,构建二值化脑网络。计算两组被试各个脑区的介数值,采用双样本t检验对比两组脑网络介数值的差异(Bonferroni 校正,P<0.01),找出介数值发生显著变化脑区。结果表明,偏相关系数构造的脑网络具有小世界属性。JME患者组脑网络中脑区的介数值相比正常对照组有显著性差异。与正常对照组相比,JME患者组介数值显著降低的脑区有2个,介数值显著升高的脑区有17个。其中属于默认模式网络(DMN)的脑区有8个,属于突显网络(SN)的脑区有5个。JME患者组介数值显著降低的脑区有右侧中央旁小叶和右侧后扣带回,介数值显著增高脑区主要是右侧背外侧额上回、左侧枕中回、右侧楔前叶和右侧舌回等。JME患者介数值发生显著改变的脑区主要属于默认模式网络和突显网络。可以推断出默认模式网络和突显网络内部脑区间连接发生改变,信息传递产生变化。由此可能会导致JME患者大脑功能发生改变,造成患者的认知能力与执行能力等功能受损。     

Lack of association between juvenile myoclonic epilepsy and GABRA5 and GABRB3 genes

Alpha5 and beta3 GABA_A receptor genes are major candidates for epilepsy, as they code for subunits of the most important human inhibitory neurotransmitter. Moreover, they are located within a region of the human genome previously implicated in disorders including epilepsy. We carried out an association study between dinucleotide repeat polymorphisms in these two genes and juvenile myoclonic epilepsy (JME). JME is the most common idiopathic epilepsy and is characterized by a complex mode of inheritance. We did not find significant differences between controls and patients for allele or genotype frequencies. Am. J. Med. Genet. 74:150–153, 1997. © 1997 Wiley-Liss, Inc.     

左乙拉西坦单药治疗老年癫癎的临床研究

目的：研究左乙拉西坦（LEV）治疗老年癫癎患者的临床疗效、安全性及对生活质量的影响.方法：采用前瞻性研究对42例不同类型老年癫癎患者（男24例,女18例;年龄60～82岁）,使用LEV单药治疗.LEV起始剂量：500 mg,每日2次,根据疗效调整剂量,比较不同发作类型老年癫癎患者的疗效、安全性及对生活质量的影响.结果：42例老年癫癎患者用LEV后无发作13例（31%）,显效9例（22%）,有效14例（33%）,无效6例（14%）,采用癫癎患者生活质量量表-31（QOLIE-31）评定,LEV治疗后在对发作的担忧、精力/疲乏、认知功能、药物影响及社会功能方面得分与治疗前比较差异有统计学意义（P〈0.05）,有7例（17%）出现与LEV可能有关的不良反应,其中嗜睡2例,急躁3例,注意力不集中、攻击行为各1例,上述不良反应均未经特殊处理,在1～2个月内自行消失,无1例因不良反应退出治疗.结论：LEV单药治疗各型老年癫癎均有疗效,显著减少发作频率,安全耐受性好,无明显认知毒性,能够提高老年癫癎患者的生活质量.     

Lissencephaly associated with cerebellar hypoplasia and myoclonic epilepsy in a Bedouin kindred: a new syndrome?

Clinico-radiological assessment of three mentally retarded members of a large Bedouin kindred showed lissencephaly, spastic paraparesis, myoclonic epilepsy and cerebellar hypoplasia. It seems that the familial association of lissencephaly/myoclonic epilepsy/cerebellar hypoplasia represents a new entity.     

Novel mutation in potassium channel related gene KCTD7 and progressive myoclonic epilepsy

Progressive myoclonic epilepsy (PME) is a heterogeneous group of epilepsies characterized by myoclonus, seizures and progressive neurological symptoms. The index patient was a 6-year old boy showing early-onset therapy resistant PME and severe developmental delay. Genome-wide linkage analysis identified several candidate regions. The potassium channel tetramerization domain containing 7 gene (KCTD7) in the 7q11.21 linkage region emerged as a suitable candidate. Sequence analysis revealed a novel homozygous missense mutation (p.R94W) in a highly conserved segment of exon 2. This is the second family with PME caused by KCTD7 mutations, hence KCTD7 mutations might be a recurrent cause of PME.     

婴儿严重肌阵挛癫痫钠离子通道SCNIA基因突变分析

目的 研究婴儿严重肌阵挛癫痫(severe myoclonic epilepsy of infancy,SMEI)患儿钠离子通道a1亚单位基因(sodium channel al subunit gene,SCNIA)突变筛查及遗传特征.方法 收集SMEI患儿23例及其家系成员的临床资料及外周血DNA,采用PCR扩增和DNA直接测序的方法筛查SCNIA基因的26个外显子的突变.结果 23例SMEI患儿中17例有SCNlA基因突变.基因突变率约为73.9%(17/23),其中8例为错义突变(F90S、I91T、A239T、W952G、T1210K,V1335M、V1390M、G1433E),3例为无义突变(R612X、W768X、w1408X),3例为缺失突变(A395fsX400、L556fsX557、V1778fsX1800),1例为插入突变(Y1241fsX1270),1例为剪切部位突变(IVS10+3A>G),1例为同义突变(K1492K),截断突变约占总突变的47.1%(8/17).13个突变位点(F90S、I91T、T1210K、V1335M、G1433E、R612X、W768X,A395faX400、L556fsx557、V1778fsXl800、Y1241fsXl270、IVS10+3A>G、K1492K)经相关检索未见报道.14例突变已证实为新生突变,其余3例突变尚不能确定突变来源.结论 SCNIA基因是SMEI患儿的主要致病基因,约一半为截断突变.SMEI患儿的SCNIA基因突变无热点,且多为新生突变.     

Evidence for clinical,genetic and biochemical variability in spinal muscular atrophy with progressive myoclonic epilepsy

Spinal muscular atrophy with progressive myoclonic epilepsy (SMA‐PME) is a recently delineated, autosomal recessive condition caused by rare mutations in the N‐acylsphingosine amidohydrolase 1 (acid ceramidase) ASAH1 gene. It is characterized by motor neuron disease followed by progressive myoclonic seizures and eventual death due to respiratory insufficiency. Here we report an adolescent female who presented with atonic and absence seizures and myoclonic jerks and was later diagnosed as having myoclonic‐absence seizures. An extensive genetic and metabolic work‐up was unable to arrive at a molecular diagnosis. Whole exome sequencing (WES) identified two rare, deleterious mutations in the ASAH1 gene: c.850G>T;p.Gly284X and c.456A>C;p.Lys152Asn. These mutations were confirmed by Sanger sequencing in the patient and her parents. Functional studies in cultured fibroblasts showed that acid ceramidase was reduced in both overall amount and enzymatic activity. Ceramide level was doubled in the patient's fibroblasts as compared to control cells. The results of the WES and the functional studies prompted an electromyography (EMG) study that showed evidence of motor neuron disease despite only mild proximal muscle weakness. These findings expand the phenotypic spectrum of SMA‐PME caused by novel mutations in ASAH1 and highlight the clinical utility of WES for rare, intractable forms of epilepsy.     

A newly identified locus for benign adult familial myoclonic epilepsy on chromosome 3q26.32-3q28

Benign Adult Familial Myoclonic Epilepsy (BAFME) is an autosomal dominant disorder characterized by adult-onset cortical tremor or action myoclonus predominantly in the upper limbs, and generalized seizures. We investigated a Thai BAFME family. Clinical and electrophysiological studies revealed that 13 were affected with BAFME. There were a total of 24 individuals studied. Genetic analysis by genome-wide linkage study (GWLS) was performed using 400 microsatellite markers and excluded linkage of the previous BAFME loci, 8q23.3-q24.1, and 2p11.1-q12.2. GWLS showed that the disease-associated region in our Thai family was linked to a newly identified locus on chromosome 3q26.32-3q28. This locus represents the fourth chromosomal region for BAFME.     

Juvenile myoclonic epilepsy in chromosome 6p12-p11: Locus heterogeneity and recombinations

We recently analyzed under homogeneity a large pedigree from Belize with classic juvenile myoclonic epilepsy (JME). After a genome wide search with 146 microsatellites, we obtained significant linkage between chromosome 6p markers, D6S257 and D6S272, and both convulsive and EEG traits of JME. Recombinations in two affected members defined a 40 cM JME region flanked by D6S313 and D6S258. In the present communication, we explored if the same chromosome 6p11 microsatellites also have a role in JME mixed with pyknoleptic absences. We allowed for heterogeneity during linkage analyses. We tested for heterogeneity by the admixture test and looked for more recombinations. D6S272, D6S466, D6S294, and D6S257 were significantly linked (Z_max > 3.5) to the clinical and EEG traits of 22 families, assuming autosomal dominant inheritance with 70% penetrance. Pairwise Z_max were 4.230 for D6S294 (θ_{m = f} at 0.133) and 4.442 for D6S466 (θ_{m = f} at 0.111). Admixture test (H₂ vs. H₁) was significant (P = 0.0234 for D6S294 and 0.0128 for D6S272) supporting the hypotheses of linkage with heterogeneity. Estimated proportion of linked families, α, was 0.50 (95% confidence interval 0.05–0.99) for D6S294 and D6S272. Multipoint analyses and recombinations in three new families narrowed the JME locus to a 7 cM interval flanked by D6S272 and D6S257. © 1996 Wiley-Liss, Inc.