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.     

脑立体定向微创技术治疗颅内出血降低术后继发性癫癎发生率

目的观察立体定向微创技术治疗颅内出血术后继发性癫癎的发生率。方法：高血压性脑出血患者60例，平均年龄43．52岁，血肿量为30～50 mL，平均（38．33±2．8）mL。患者入院后随机分为立体定向微创治疗组及开颅血肿清除术组各30例，人院24 h内进行微创血肿清除术或开颅血肿清除术，2组患者均予常规药物治疗如降颅压、调节血压、止血、预防感染等。手术治疗后3、6、12个月时随访，以患者继发性癫癎发生率及美国国立卫生研究院卒中量表（NIHss）评分为指标，评估其神经功能恢复情况及继发性癫癎发生情况。结果：立体定向微创组3个时间段继发性癫癎的发生率分别为6．7％、10％、10％，NIHSS评分分别为（6．23±2．02）分、（5．50±2．21）分、（4．80±1．20）分；开颅血肿清除术组3个时间段继发性癫癎的发生率分别为60％、60％、53％，NIHSS评分分别为（10．18±2．20）分、（8．20±2．20）分、（7．43±2．22）分；2组间比较，继发性癫癎及NIHSS评分的差异有统计学意义（P〈0．01）。结论：立体定向微创治疗高血压性脑出血可以明显降低继发性癫癎发生率，改善患者神经功能，有利于并提高患者的生活品质。     

拉莫三嗪单药治疗老年癫癎效果分析

2009年3月～2012年9月我科用拉莫三嗪治疗老年癫癎50例,取得良好疗效,现报告如下。1资料与方法1．1病例选择2009年3月～2012年9月在我科门诊及住院确诊的老年癫痂患者50例,其中男性35例,女性15例,年龄60～83岁,平均（70．18±0．98）岁,病程1～30年,平均（5．48±0．95）年。发作类型：全身强直阵挛发作17例,复杂部分性发作19例,简单部分性发作4例,失神发作3例,部分发作继发全面性发作1例,植物性发作1例,部分性发作持续状态5例。入选标准：①按照国际抗癫癎联盟（ILAE）对癫癎发作及癫癎综合征的分类标准诊断为癫癎;②患者年龄≥60岁;③病程1年以上;④癫癎发作频率每年≥2次;⑤无严重肝、肾功能障碍;⑥无恶性肿瘤及变性病。排除标准：①对拉莫三嚷过敏者;②癫痫发作频繁无法计数者;③有精神障碍者。     

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。     

癫癎发作对大鼠海马感觉门控的影响

目的：观察癫癎发作对大鼠海马感觉门控的影响。方法：采用青霉素诱导的大鼠癫癎发作模型，将探测电极植入大鼠海马的CA1区，连续7天，记录大鼠海马的听觉诱发电位；采用条件—测试模式的双短音刺激（S1、S2），刺激间隔是500ms，观察大鼠癫癎发作前后S1和S2波的峰—峰值、潜伏期和N40的测试刺激／条件刺激（T／C）比的变化，并与对照组进行比较。结果：与生理盐水对照组相比，实验组大鼠第一天癫癎发作后S2的峰—峰值增大，差异有显著意义（P=0．043）。反复癫癎发作一周，实验组第二天以后每天癫癎发作后总的趋势是：S1的峰—峰值减小，与对照组相比差异有显著意义（P=0．01），N40的T／C比在癫癎发作后增大，差异具有显著意义（P=0．028）。结论：癫癎发作对大鼠海马感觉门控具有急性和潜在的慢性损害作用。     

醒脑静对戊四氮致癎大鼠行为学及脑电图的影响

目的：探讨中成药醒脑静（XingNaoJing,XNJ）对戊四氮慢性点燃癫癎大鼠行为学及脑电图的影响。方法：将健康雄性SD大鼠50只随机分成5组（每组10只）：正常对照组、单纯模型组、制模并药物干预的醒脑静组、苯巴比妥组及中西药合用（醒脑静＋苯巴比妥）组,观察分析醒脑静对戊四氮点燃癫癎大鼠首次出现发作时间、各阶段发作级别、发作潜伏期及持续时间和脑电图的影响。结果：醒脑静组首次出现癫癎发作时间较模型组延迟（P〈0．01）,发作级别降低（P〈0．05,P（0．01）,发作潜伏期明显延长（P（0．01）,发作持续时间明显缩短（P〈0．01）,癫癎发作波频率和波幅降低。醒脑静组与苯巴比妥组比较,差异无统计学意义（P〉0．05）。中西药合用组各指标与醒脑静单用组或苯巴比妥单用组比较差异均有统计学意义（P（0．05）。结论：醒脑静具有抑制戊四氮诱发癫癎的作用,与抗癫癎西药合用抗癫癎作用更强。     

难治性癫(癎)靶点学说研究进展

癫(癎)发病机制的研究在近30年内取得了极大的进展,尤其是在生理学和遗传学方面.1978年起,10种新型抗癫(癎)药物(antiepileptic drugs,AED):丙戊酸、托吡酯、拉莫三嗪、加巴喷丁、非氨酯、奥卡西平、氨己烯酸、唑尼沙胺、左乙拉西坦和普瑞巴林等在临床的应用,极大地改善了癫(癎)的治疗.但仍有约三分之一的癫(癎)患者在接受合理的药物治疗后,其发作不能终止,称之为难治性癫(癎)(refractory epilepsy,RE).     

儿童与成人起病的伴海马硬化的颞叶癫癎对比分析

目的对比分析儿童与成人起病组的伴海马硬化的颞叶癫癎（TLE-HS）患者临床特点的异同,以提高对该病的认识。方法：回顾性收集我院癫癎诊疗中心就诊的TLE-HS患者201例,依据患者起病年龄分成儿童起病组和成人起病组,收集病史、发作类型和频率、药物治疗、头部影像学、24 h视频脑电图（V—EEG）等临床资料,作对比分析。结果：儿童起病组较成人起病组伴热性惊厥（FS）史多、间断发作少,频繁发作多,差异均有统计学意义（P=0．013、0．013、0．013）;儿童起病组较成人起病组在发作间期EEG颞区以外癎样放电较多,差异有统计学意义（P=0．015）。两组患者在HS侧别、发作起源、发作类型、单用或联合用药、头部外伤史、脑炎史、家族史、精神发育迟滞、精神异常等方面比较差异均无明显统计学意义。结论：与成人起病组相比,儿童起病组伴FS史多,发作频率更高,这提示FS是导致癫癎患者更早起病的原因之一;儿童起病组发作间期EEG颞区以外癎样放电较多。     

拉莫三嗪添加治疗难治性癫(癎)的临床观察

目的:观察拉莫三嗪添加治疗难治性癫癎的疗效、用药方法、剂量及副作用。方法:对54例难治性癫癎患者进行添加拉莫三嗪治疗,观察其疗效。结果:拉莫三嗪添加治疗难治性癫癎,总有效率达83％,37例(69％)患者发作停止。对全面性发作有效率达83％,对部分性发作及部分性发作继发全面性强直阵挛性发作有效率达80％。平均有效剂量96．8±27．3mg／d,37例无发作病例平均剂量为77．8±17．5 mg／d。2例加量12．5 mg／d后发作加重,减量后控制良好。除1例发生轻微皮肤瘙痒外,无中枢神经系统及其他副作用,满意度为96％。结论:拉莫三嗪添加治疗难治性癫癎有良好疗效,副作用轻微,一天一次用药效果可靠,一般患者有效剂量在150mg／d内。     

克罗米酚的抗癫癎作用

目的:了解雌激素受体调节剂克罗米酚(clomiphene citrate,CC)对海人藻酸(kainic acid, KA)致癎大鼠癫癎发作行为的影响。方法:健康雌性SD大鼠40只,均行双侧卵巢切除术,术后第八天将动物随机分4组:茶油对照组(OIL组)、KA组、雌二醇(E2) KA组、E2 CC KA组,每组10只。 OIL组、KA组连续5天腹腔注射茶油;E2 KA组连续5天腹腔注射E2(20mg／kg,10mg／ml);E2 CC KA组连续5天腹腔注射E2和CC(2mg／kg,2mg／ml),最后一次打药结束1 h后,致癎各组大鼠(KA 组、E2 KA组、E2 CC KA组)经腹腔注射KA(10mg／kg,2mg／ml),OIL组腹腔注射生理盐水后,连续观察大鼠2 h的行为改变。记录癎样发作的潜伏期、出现重型发作的时间以及发作程度。结果:E2 CC KA组的癫癎发作潜伏期为61．75±19．04 min,较E2 KA组的潜伏期23．8±6．03 min延长,且出现重型癫癎发作的时间晚,为50．20±20．37 min,而E2 KA组出现重型癫癎发作时间平均为30．70 ±13．58 min,两组比较差异有显著意义(P<0．05)。致癎2 h后,致癎各组大鼠的癫癎发作Racine分级比较差异显著意义(P>0．05)。结论:CC有拮抗雌激素的致癎作用,延缓癫癎的发作。     

Quantitative Study of the Response to Genetic Selection of the Wistar Audiogenic Rat Strain (WAR)

To study the relationship between genetics and epilepsy, Wistar rats susceptible to audiogenic seizure were selected from the main breeding stock of the Ribeirão Preto School of Medicine at the University of São Paulo, Brazil, and inbred. The criteria for selection were the highest seizure severity index (SI) and shortest latencies of the first running fit (LI). Because behavioral response to sound stimulation (120 dB) at 70 to 78 days of age was very stable, SI and LI were evaluated within this age range. Analysis of 9450 observations in 1575 animals from the 3rd to 17th generations demonstrated significant effects of generation, parity, and litter on SI and of generation and litter on LI. The SI and LI averages were, respectively, 37.13 and 22.82 s in the 3rd generation and 83.06 and 7.84 in the 17th generation. Heritabilities of both characters were estimated, by maximum likelihood, as 0.37 ± 0.066 and 0.44 ± 0.059, respectively. Because a significant regression related individual breeding values for both SI and LI to generation number, we concluded that genetic selection has a positive impact on the traits analyzed. Therefore, the Wistar audiogenic rat (WAR) strain appears, as per the 17th to 20th generations of genetic selection to be an audiogenic rat strain suitable for epilepsy studies.     

The decreased susceptibility to the development of in vitro kindling-like state in hippocampal CA1 slices of rats sensitive to audiogenic seizures

The field excitatory postsynaptic potential (fEPSP) with the presynaptic fiber volley (PrV) and the population spike (PS) were recorded with two glass microelectrodes in stratum radiatum and stratum pyramidale of rat hippocampal CA1 slices, respectively, in response to electric stimulation of Schaffer collaterals/commissural fibers (SC/CF) containing glutamate as a neurotransmitter. Three components of the overall input-output function were taken: (1) PrV amplitude vs. intensity of stimulating current, (2) dendritic layer fEPSP slope vs. PrV amplitude and (3) PS amplitude vs. fEPSP slope. Three groups of rats were used: (1) normal male Wistar rats (control), (2) a strain of rats genetically-prone to audiogenic seizures (GPAS) and (3) GPAS rats 10 min after a single intense sound stimulus. Unlike hippocampal slices taken from normal Wistar rats, slices taken from GPAS rats were less susceptible to the development of the in vitro kindling-like state induced by the repeated 30 s applications (3 episodes) of [K⁺]_o up to 20 mM. Such short-term [K⁺]_o increases also did not induce the EPSP-spike transfer potentiation (E-S potentiation) in CA1 pyramidal neurons of audiogenic rats either. Furthermore, the presynaptic glutamatergic fibers of GPAS rats are less excitable to stimulating currents then that of normal Wistar rats. It is suggested that the resistance of audiogenic rat hippocampal CA1 slices to the development of long lasting epileptiform activity is a protective adaptive mechanism preventing the propagation of seizure activity into limbic structures.     

Influence of age and brief auditory conditioning upon experimental seizures in mice

Audio-sensitivity can be induced in strains of mice considered audio-resistant by exposure to a brief auditory stimulation (60 sec at 95 db) at a critical age. Mice that had been audio-conditioned were subjected to a battery of seizure-evoking procedures and the responses interpreted in terms of neurophysiological mechanism. The effect of maturation on the development of sound induced, chemoshock and electroshock convulsion threshold and pattern was also studied. The pattern of maximal seizures induced by electroshock, pentylenetetrazol, and sound are remarkedly similar at a given age. The threshold for low frequency electroshock and for minimal pentylenetetrazol decreased with increased age and weight. There was no significant difference in maximal electroshock seizure threshold with aging, but duration of the seizure pattern markedly changed with increased age. Audio-conditioning produced profound changes in the ontogeny of low frequency and chemoshock threshold, but maximal seizure threshold and pattern were unaffected. The audio-sensitized CF# 1 mice differ in several ways from littermate. The oscillator mechanism of the audio-sensitive mice is more easily discharged by electric and chemical stimulation, and there is an alteration in the neuro-ontogenic pattern, and a decreased growth rate.     

Increased severity of pentylenetetrazol induced seizures in leptin deficient ob/ob mice

Leptin modulates multiple ion channels making its net effect on brain excitability difficult to predict. One method of determining leptin's net effect on brain excitability is to examine brain excitability during chronic leptin deficiency. We compared the susceptibility of leptin deficient ob/ob and wild type mice to pentylenetetrazol (PTZ) induced seizures using continuous video electroencephalogram (EEG) recordings. We found that ob/ob mice were more likely to die and were more susceptible to generalized clonic and clonic-tonic seizures than wild type mice at submaximal PTZ doses. These findings suggest that chronic leptin deficiency in vivo increases seizure susceptibility.     

失张力发作患者的临床和脑电图表现5例报告

目的．观察失张力发作病人的临床和脑电图(EEG)表现。方法：对符合失张力发作诊断标准的5例病人进行临床观察和EEG检查。结果：5例病人表现为程度不同、发作频率不同的肌张力突然降低。持续时间较短，其中1例合并肌阵挛．1例病人有短暂的意识丧失。发作问期EEG多为非特异的双侧同步的多棘慢波。结论：失张力发作表现为突然的肌肉张力的丧失而倒地．可以合并其他发作形式，持续时间短暂。EEG为双侧对称的多发性多棘慢波。     

Predicting Severity of Disease‐Causing Variants

Most diseases, including those of genetic origin, express a continuum of severity. Clinical interventions for numerous diseases are based on the severity of the phenotype. Predicting severity due to genetic variants could facilitate diagnosis and choice of therapy. Although computational predictions have been used as evidence for classifying the disease relevance of genetic variants, special tools for predicting disease severity in large scale are missing. Here, we manually curated a dataset containing variants leading to severe and less severe phenotypes and studied the abilities of variation impact predictors to distinguish between them. We found that these tools cannot separate the two groups of variants. Then, we developed a novel machine‐learning‐based method, PON‐PS ( http://structure.bmc.lu.se/PON-PS ), for the classification of amino acid substitutions associated with benign, severe, and less severe phenotypes. We tested the method using an independent test dataset and variants in four additional proteins. For distinguishing severe and nonsevere variants, PON‐PS showed an accuracy of 61% in the test dataset, which is higher than for existing tolerance prediction methods. PON‐PS is the first generic tool developed for this task. The tool can be used together with other evidence for improving diagnosis and prognosis and for prioritization of preventive interventions, clinical monitoring, and molecular tests.     

反复听源性惊厥对大鼠各脑区葡萄糖摄取率的影响

采用~3H-2-脱氧葡萄糖(~3H-2-DG)定量方法研究大鼠听源性发作后各脑区葡萄糖摄取率的变化。实验动物每天在强声(115±5dB)刺激下诱导发作一次,共五次发作;对照动物为未经强声刺激的易感性大鼠。第六天,实验动物和对照动物都在安静的状态下测定其各脑区的糖代谢率。结果表明反复听源性发作之后,几乎所有的脑区都出现糖代谢率增高(p<0.05),其中下丘、上撖榄核、外侧丘系核、上丘增高更明显(p<0.01)。提示这些脑区可能与大鼠听源性发作的起源及传播途径有关。     

长程视频脑电图监测对非癫痫性发作诊断价值探讨

目的探讨长程视频脑电图监测在非癫痫性发作诊断中的应用价值。方法对48例酷似非癫痫性发作患者行24 h长程视频脑电图监测,将发作表现及同期的脑电图进行分析。结果 48例患者在监测中均出现临床发作,长程视频脑电图监测所有发作期脑电图均未见痫样放电。其中1例患者表现单个θ波发放,27例患者为肌电伪差或动作伪迹。13例患者在发作间期脑电图见单个尖波或慢波发放,35例患者为正常范围。结论长程视频脑电图监测可将非癫痫性发作的临床表现和同步脑电图结合起来,为非癫痫性发作的诊断提供重要的临床资料。     

18例复杂部分性癫痫发作患者同步录像脑电图监测报告

目的：探讨同步录像脑电图（Video-EEG）在复杂部分性癫痫发作诊断中的应用价值。方法：利用ZN8000型EEG仪对临床确诊的18例复杂部分性发作患者进行脑电和行为监测,监测时间2．5～28h平均用18.8h。结果：共监测到93次临床发作,睡眠中发作54次,清醒时发作39次,发作持续时间7～120s,平均34．8s。发作时的临床表现：双眼向前或向一侧凝视11例,头向一侧转动9例,一侧面部或肢体抽搐9例,行为或口咽自动症6例,精神症状5例,姿势性发作5例,对发作过程不能回忆15例。发作期EEG示癫病样放电（棘波、尖波、棘慢、尖慢综合波）12例,阵发性高幅慢波5例,未见异常1例,EEG异常率95％。发作间期EEG示中高幅阵发性慢波3例,阵发性痫样放电9例,未见异常6例,EEG异常率65％。结论：Video－EEG对复杂部分性癫痫发作有重要诊断价值,痫样放电与临床发作密切相关。