Clinical and genetic analysis of two Chinese families with benign familial neonatal convulsions

Benign familial neonatal convulsions (BFNC) is a rare autosomal dominant inherited epilepsy syndrome. Two voltage-gated potassium channel genes, KCNQ2 and KCNQ3, have been identified as the genes responsible for BFNC. Here we report two Chinese families with clinical histories of typical BFNC. Using six microsatellite markers, two located at KCNQ2 locus and four at KCNQ3 locus, linkage analysis was performed in the two families, which excluded the linkage of BFNC to KCNQ3, but could not exclude the linkage to KCNQ2. Direct DNA sequencing of the KCNQ2 gene in the two families was performed, and two formerly unknown polymorphisms were identified, but no KCNQ2 mutation was found in the two families. Our study suggests the genetic heterogeneity in Chinese families with BFNC and proves the existence of a new gene locus for BFNC.     

Clinical and genetic analysis of two Chinese families with benign familial neonatal convulsions

Benignfamilialneonatalconvulsions(BFNC)is arareautosomaldominantinheritedepilepsysyn dromecharacterizedbyunprovokedpartialorgeneral izedseizures.Theseizuresusuallyoccurfromthesec onddayofbirthtothesixthmonthandremitsponta neouslyafterseveralweekstomonths.Mostindivid ualsareseizure freebytheageofsixmonths.The serumchemistryandneuroradiologicalexaminations,interictalelectroencephalogram(EEG),andpsy chomotordevelopmentareusuallynormal.However,10%to15%ofpatientshavetheriskofseizurere currencela…     

A single gene error of noradrenergic axon growth synchronizes central neurones

One strategy for deciphering inherited neurological disease is to examine the expression of individual genes controlling the assembly and physiology of specific cell groups within the developing mammalian central nervous system (CNS). This neurogenetic approach, using defined single-locus mutations arising on coisogeneic mouse strains, has recently been used to analyse a major class of neuronal membrane diseases involving abnormal excitability, the epilepsies, and to identify examples of hereditary variation in signalling properties at central synapses. An interesting mutation, the Tottering (tg) gene, causes a delayed onset, recessive neurological disorder in the mouse featuring a stereotyped triad of ataxia, intermittent myoclonus and cortical spike-wave discharges accompanied by behavioural absence seizures which resemble petit mal epilepsy. Axon branches of the locus coeruleus, a noradrenergic brain-stem nucleus, hyperinnervate specific target regions of the tg brain. The number of parent coerulean perikarya is unaffected, indicating a true proliferation of the terminal axonal arbor. With the exception of this unusually precise error of axonal growth, no other cytopathology has been identified in the tg brain. Here I present evidence that selective lesions of the central noradrenergic axons early in development limit the expression of the disease.     

实验性癫痫大鼠补体C3b受体的表达

目的：建立大鼠的实验性癫痫模型，探讨实验性癫痫大鼠补体C3b受体的表达，进一步揭示癫痫的免疫炎症机制．方法：采用皮下注射海仁酸方法建立实验性癫痫大鼠模型；采用免疫组织化学染色方法观察实验性癫痫大鼠补体C3b受体的表达．结果：给大鼠皮下注射海仁酸可成功地建立实验性癫痫大鼠模型，其大脑海马锥状细胞层可见到神经元的变性，并可见补体C3b受体的明显表达．结论：实验性癫痫大鼠大脑海马硬化发生过程中，存在着补体系统参与的免疫反应发生，并引起炎症反应、     

89次额叶癫痫发作期Video-EEG监测报告

利用ZN80 0 0型Video EEG监测系统对 10例额叶癫痫患者进行脑电和行为监测 ,旨在探讨额叶癫痫发作时的行为表现及脑电变化特征。结果表明 :额叶癫痫发作以运动症状为主 ,常于夜间发作 ,发作频繁而短暂。发作期EEG为额区癫痫样放电亦可为高幅慢波 ,与临床发作同步     

外伤后癫痫98例临床及预后分析

目的分析外伤后癫痫临床与预后,为PTE的合理诊治提供参考。方法回顾性分析98例外伤后癫痫患者的临床表现、药物治疗效果及预后。结果98例外伤后癫痫常见的表现为短暂的部分性发作,并常泛化为全身强直阵挛发作。一线抗癫痫药物治疗总有效率为77．5％。结论外伤后癫痫是局灶性癫痫中常见类型,正确地诊断、良好的依从性与规范化治疗可明显改善其预后。     

Cloning of cDNA for the glutamate-binding subunit of an NMDA receptor complex.

The amino acids L-glutamic and L-aspartic acids form the most widespread excitatory transmitter network in mammalian brain. The excitation produced by L-glutamic acid is important in the early development of the nervous system, synaptic plasticity and memory formation, seizures and neuronal degeneration. The receptors activated by L-glutamic acid are a target for therapeutic intervention in neurodegenerative diseases, brain ischaemia and epilepsy. There are two types of receptors for the excitatory amino acids, those that lead to the opening of cation-selective channels and those that activate phospholipase C (ref. 11). The receptors activating ion channels are NMDA (N-methyl-D-aspartate) and kainate/AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate)-sensitive receptors. The complementary DNAs for the kainate/AMPA receptor and for the metabotropic receptor have been cloned. We report here on the isolation and characterization of a protein complex of four major proteins that represents an intact complex of the NMDA receptor ion channel and on the cloning of the cDNA for one of the subunits of this receptor complex, the glutamate-binding protein.     

Control of neuronal fate by the Drosophila segmentation gene even-skipped

The central nervous system (CNS) contains a remarkable diversity of cell types. The molecular basis for generating this neuronal diversity is poorly understood. Much is known, however, about the regulatory genes which control segmentation and segment identity during early Drosophila embryogenesis. Interestingly, most of the segmentation and homoeotic genes in Drosophila, as well as many of their vertebrate homologues, are expressed during the development of the nervous system (for example, ref. 3). Are these genes involved in specifying the identity of individual neurons during neurogenesis, just as they specify the identity of cells during segmentation? We previously described the CNS expression of the segmentation gene fushi tarazu (ftz) and showed that ftz CNS expression is involved in the determination of an identified neuron. Here we show that another segmentation gene, even-skipped (eve), is expressed in a different but overlapping subset of neurons. Temperature-sensitive inactivation of the eve protein during neurogenesis alters the fate of two of these neurons. Our results indicate that the nuclear protein products of the eve and ftz segmentation genes are components of the mechanism controlling cell fate during neuronal development.     

动脉硬化性脑梗死继发性癫痫

动脉硬化性脑梗死继发性癫痫217例,梗死灶主要位于脑叶,提示痫性活动与皮层梗死密切相关,早发性痫性发作（发生于脑梗死2周内）为短暂性痫性发作,可能为脑代谢异常所致,一般仅临时用安定,预后好,晚发性痫性发作（发生于脑梗死2周后）可能为癫痫灶所致,半数病例需服抗癫痫药。     

肢带型肌营养不良一家系致病基因排除性定位

为了定位一个常染色体显性遗传肢带型肌营养不良家系的致病基因（ADLGMD）,采用13个荧光微卫星标记对收集到的一个包括4代33人的ADLGMD家系进行连锁分析,所选择的标记覆盖了3个已知ADL—GMD致病基因位点和4个已报道的致病基因定位区段．通过Linkage 5．1软件包计算连锁概率,各位点连锁分析所得的LOD值均小于-3,显示该家系致病基因与这7个位点均不连锁．该家系的肌营养不良症致病基因不在已知的位点内,很可能是一个新致病基因．     

A highly polymorphic locus very tightly linked to the Huntington's disease gene

The genetic defect in Huntington's disease (HD), an inherited neuropsychiatric disorder of unknown etiology, has not been defined. The discovery of linkage between HD and the DNA marker D4S10(G8) raised the possibility of isolating the disease gene on the basis of its chromosomal location, in addition to providing a limited presymptomatic test for the late onset disorder. But it has been difficult to isolate other DNA markers nearer to the HD gene, and this has hampered attempts to identify the disease locus and limited the applicability and accuracy of predictive testing. Recently, several new DNA markers from the region of the genome near the HD gene have been isolated using a directed cloning strategy. We describe here the characterization of one of these new markers, D4S95, a highly polymorphic locus which displays no recombination with the HD gene in the families tested. The high degree of polymorphism at this locus and its proximity to the HD gene make it extremely useful for predictive testing and as a new starting point for attempts to clone the disease gene.     

雌激素对戊四唑致痫大鼠海马内GABA和P38的影响

目的：分析月经性癫痫中，雌激素对大鼠海马内γ-氨基丁酸(γ-amiobutyric acid，GABA)和P38的影响，探讨雌激素促癫痫发作的作用机理。方法：利用去卵巢(ovaiectomized，OVX)SD大鼠，用雌激素替代疗法及戊四唑(petylenetetrazole，PTZ)致病，诱发大鼠癫痫发作，并采用免疫组织化学技术，对大鼠背侧海马不同脑区GABA和P38的免疫反应产物进行观察。结果：(1)GABA免疫组化检测结果显示，实验对照组(OVX NS PTZ)与空白对照组(OVX NS NS)相比及实验给药组(OVX E2 PTZ)与实验对照组相比，背侧海马门区内GABA免疫反应阳性神经元数目均显性减少。(2)P38免疫反应产物的观察：其免疫反应产物呈特征性点状或颗粒状。在CA1区始层和辐射层、CA3区透明层，空白对照组与实验对照组相比免疫反应强度无明显变化，实验给药组比实验对照组免疫反应增强。在齿状回分子层，3组的免疫反应强度无明显变化。结论：雌激素使海马门区GABA含量减少，从而降低了GABA对癫痫发作的抑制作用，增强了癫痫发作的敏感性。雌激素可使背侧海马CA1区始层和辐射层、CA3区透明层P38的表达增加(即使该区的突触密度增加)，从而增加了海马内兴奋性递质的释放，使海马内的兴奋性增强。     

脑卒中后癫痫50例临床研究

目的:探讨脑卒中后癫痫的临床特点,癫痫对脑卒中恢复期神经功能康复的影响.方法:50例脑卒中后继发癫痫患者进行发作部位、类型、治疗时间及效果等分析,并按病情轻、中、重三组进行功能康复评分.结果:脑卒中后癫痫发生率5.1%(50/980),其中早发癫痫72%(36/50),迟发癫痫28%(14/50);皮层病灶继发癫痫72%(36/50).皮层下病灶继发癫痫28%(14/50).早发癫痫中全身发作27例,部分性发作9例;迟发癫痫中全身发作4例,部分性发作10例.癫痫组神经功能缺损评分均差于对照组(P<0.05).结论:脑卒中后癫痫皮层病灶多见,早发癫痫以全身发作为主,迟发癫痫以部分发作为主.脑卒中合并癫痫患者的治疗效果差于对照组,抗癫痫治疗有利于神经功能康复.     

A crucial epileptogenic site in the deep prepiriform cortex

Antagonists of gamma-aminobutyric acid (GABA)- or glycine-mediated neurotransmission, muscarinic cholinergic agonists, and excitatory amino acids and their analogues are all considered to be potent chemoconvulsant agents. However, although systemic injections of these agents have been used to create experimental models of generalized epilepsy, there has been no identification of a specific locus at which any of these drugs act to initiate generalized seizures. We recently located a forebrain region from which seizures can be elicited by the GABA antagonist bicuculline, and now report that manipulations of excitatory amino acid transmission and cholinergic transmission can also elicit seizures from this site. Bilateral clonic seizures can be elicited after unilateral application of picomole amounts of bicuculline, kainic acid or carbachol and micromole amounts of glutamate. Local application of the GABA agonist muscimol prevents the appearance of seizures on subsequent microinjection of all convulsant agents examined, whereas local application of the muscarinic antagonist, atropine, only prevents seizures induced by carbachol. This region is therefore a site of action for the epileptogenic effects of neuroactive agents with diverse mechanisms of action; it may also represent a site at which GABA agonists could function therapeutically to control epileptogenesis.     

老年人癫痫与病因分析

探讨老年人癫痫的临床特点、病因和发病机理。方法：回顾分析了６２例老年癫痫患者的临床表现、ＣＴ、ＭＲＩ、ＥＥＧ、ＥＫＧ和血生化方面检查。结果：脑血管病是老年人癫痫常见的病因,其次为脑肿瘤、脑萎缩、心血管及糖尿病。３６例脑中风患者中,１２例在中风后２周内有癫痫发作,２４例在中风后２周后出现癫痫发作,５例脑出血和蛛网膜下腔出血病人在起病２４小时内出现癫痫发作。脑皮质梗塞和脑叶出血比皮层下和脑深部病变更易出现癫痫发作。对不同梗塞部位的观察发现,大脑中动脉供血区梗塞后癫痫的发生率高于大脑前动脉供血区梗塞。结论：对老年的癫痫病人应尽早做ＣＴ、ＭＲＩ、ＥＫＧ和血生化方面检查,明确病因和诊断,及时治疗。     

Kindling stimulation induces c-fos protein(s) in granule cells of the rat dentate gyrus

Alterations in neuronal gene expression have been proposed to account for permanent changes in brain function such as learning and memory. In particular, it has been suggested that protooncogenes such as c-fos may be rapidly induced in conditions that lead to neuronal plasticity and evoke permanent changes in the expression of effector genes. Concentrations of the c-fos proto-oncogene increase rapidly following depolarization-induced calcium influx in non-dividing neuronally differentiated PC 12 cells. Recently, the presence and induction of c-fos in the adult brain and spinal cord has been observed. Here we report that electrically-induced seizure activity, which leads to a permanent increase in the response of the brain to future seizures (kindling), rapidly and transiently increases c-fos protein-like immunoreactivity in the nuclei of granule cells in the rat dentate gyrus. These results suggest that c-fos protein is present within the nuclei of adult mammalian neurons, and could be involved in plastic changes in the nervous system associated with seizure activity.     

水稻紫色柱头突变体ps-5的遗传分析和分子定位

在水稻品种Nipponbare中发现一个紫色柱头突变体ps-5,整个生育期最显著的特点就是柱头紫色且子房较大.遗传分析表明该基因受1对隐性核基因控制,暂命名为ps.利用极端个体定位法把ps-5精细定位于第8染色体SSR标记LR41和LR43之间,ps-5基因距它们的遗传距离均为0.12cM,并与LR413共分离,LR41和LR43两标记间的物理距离约为125kb,为该基因的分子标记辅助选择和图位克隆奠定了基础.     

基于SVM分类器的癫痫脑电时空特征提取方法的研究

癫痫发作具有突发性和反复性,给患者的生命安全带来巨大隐患。为了给患者提供有效的预警,结合时间和空间两个维度,选取模糊熵和皮尔逊相关性作为特征参数,分别衡量时序信号复杂度和空间通道间的相关性; 利用F-score筛选出最优特征组合,既增加了预测的准确率又去除冗余信息; 利用支持向量机(support vector machine,SVM)分类器识别癫痫发作前期和发作间期的颅内脑电信号。为验证该特征的预测效果,进行了模糊熵或皮尔逊相关性单独作为特征参数的对比试验。实验结果表明,与单一特征相比,时空特征的预测效果更好,准确率高达91.26%,误报率仅为2.32%。该方法能有效提取癫痫特征信息,为癫痫的临床预警提供新思路。     

A neuronal clone derived from a Rous sarcoma virus-transformed quail embryo neuroretina established culture

Neuroretina (NR) is an evagination of the central nervous system (CNS) which is composed of photoreceptors, glial (Müller) cells and horizontal, bipolar, amacrine and ganglion neuronal cells. We describe here the usefulness of Rous sarcoma virus (RSV) in the establishment of a neuronal clone from quail embryo neuroretina. When primary cultures of chick and quail embryo neuroretina cells are transformed by RSV, neuronal markers such as ribbon synapses, choline acetyltransferase (CAT) and glutamic acid decarboxylase (GAD) specific activity are present. These RSV-transformed primary cultures can be established into permanent cell lines from which neuronal clones have been isolated. One of them, clone QNR/D, can generate tetrodotoxin(TTX)-inhibitable action potentials on electrical stimulation, has a high GAD activity and binds monoclonal antibodies raised against chick embryo neuroretina. The presence of these neuronal markers suggests that the QNR/D clone is derived from cells of the amacrine or ganglionic lineage. This is the first time that a neuronal cell clone of defined origin has been obtained from the CNS. The neuronal markers of the QNR/D clone are expressed at both the permissive and the non-permissive temperatures for transformation.