妥泰对海人酸致癎大鼠海马神经元线粒体损伤的保护作用

目的观察海人酸（KA）诱导的癫痫持续状态（SE）、大鼠海马CA3区神经元线粒体超微结构的损伤及妥泰（TPM）的保护作用。方法用TPM干预。用KA诱导大鼠SE2h，并于癫痫终止后3h制作脑切片，用光镜观察神经元的大体损伤，并用电镜进一步观察线粒体的超微结构。结果KA组和TPM组大鼠均出现了线粒体超微结构的损伤，TPM组大鼠的损伤明显减轻。结论KA诱导的SE可导致海马神经元线粒体损伤，妥泰对此具有保护作用。     

Clinical Efficacy of New Antiepileptic Drugs in Refractory Partial Epilepsy: Experience in the United States With Three Novel Drugs

Summary: A number of new antiepileptic drugs (AEDs), including topiramate (TPM), felbamate (FBM), and gabapentin (GBP), are approved or believed to be close to approval for marketing in the United States. Key efficacy findings for these AEDs in refractory partial epilepsy were reviewed. Large and significant drug-placebo differences were observed with TPM in two large dose-finding trials conducted in the United States. The minimal effective dose of TPM in the population studied was determined to be approximately 200 mg/day, and doses above 600 mg/day produced good efficacy but little incremental benefit versus the lower dosages for the overall study population. FBM is active in partial epilepsy, although seizure reduction is less marked and drug interactions complicate the findings. GBP is also active in this population, but only the 1,800 mg/day dosage was significantly better than placebo with respect to percent re-sponders. It may be useful to explore higher dosage ranges for both FBM and GBP if they can be well tolerated.     

托吡酯对慢性癫(癎)大鼠海马碱性成纤维细胞生长因子表达的影响

目的研究托吡酯（TPM）对慢性癫痫大鼠海马碱性成纤维细胞生长因子（bFGF）表达的影响。方法制作戊四氮（PTZ）慢性癫痫点燃大鼠模型，分为PTZ组、TPM组及正常对照组，每组又以5d、10d、15d3个时间点各分为3小组。免疫组化法观察各组海马CAl、CA3区及齿状回bFGF表达，HE染色观察病理形态学改变。结果（1）行为学观察：PTZ组和TPM组在癫痫发作上无明显差别。（2）bFGF表达：①各组齿状回区bFGF表达：PTZ组和TPM组各时点表达不断增高，与正常对照组比较差异有统计学意义（均P〈0．01），尤以10d及15d时增高更明显，与5d时比较差异有统计学意义（均P〈0．05）。②各组CAl区bFGF表达：PTZ组各时点均有明显表达，且随时间延长而表达不断增高，各时点比较差异有统计学意义（均P〈0．01），与正常对照组比较差异有统计学意义（均P〈0．01）；TPM组在5d时与正常对照组比较差异有统计学意义（P〈0．01），而10d、15d时逐渐下降，接近正常对照组水平。③各组CA3区bFGF表达：5d时3组比较差异无统计学意义。但PTZ组和TPM组在10d时与正常对照组比较差异有统计学意义（P〈0．01），PTZ组在15d时和TPM组及正常对照组比较差异有统计学意义（均P〈0．01）。（3）病理形态学改变：PTZ组和TPM组的海马CAl、CA3区尤其是CAl区可见较多神经元发生变性和坏死，PTZ组更显著。结论PTZ点燃过程中海马bF-GF表达增高，尤其在CAl区，且随时间延长有表达不断增高的趋势。TPM可能通过减少海马神经元损伤而明显下调海马CAl、CA3区bFGF的表达。     

托吡酯和丙戊酸钠治疗特发性全面性强直阵挛发作的临床疗效比较

目的:探讨中等剂量托吡酯(商品名:妥泰)200mg对特发性全面性强直阵挛(GTCS)发作的疗效。方法:64例GTCS患者分成三组,妥泰单药治疗21例,妥泰联合丙戊酸钠治疗22例,另外21例采用丙戊酸钠治疗作对照。结果:妥泰单药组及联用药组治疗GTCS有效例数明显高于单用丙戊酸钠组,差异显著(P<0.05);同时单用妥泰组与联用丙戊酸钠组疗效相近(P>0.05)。结论:妥泰治疗GTCS疗效优于丙戊酸钠,且妥泰单一用药与联用丙戊酸钠治疗疗效相近。     

The Effect of Antiepileptic Drugs on Cognition: Patient Perceived Cognitive Problems of Topiramate versus Levetiracetam in Clinical Practice

Summary:  Introduction: Neurocognitive complaints may interfere with long-term antiepileptic drug (AED) treatment and are an important issue in clinical practice. Most data about drug-induced cognitive problems are derived from highly controlled short-term clinical trials. We analyzed such cognitive complaints for the two most commonly used AEDs in a clinical setting using patient perceived problems as primary outcome measure.
Method: All patients of the epilepsy center Kempenhaeghe that received topiramate (TPM) or levetiracetam (LEV) from the introduction to mid 2004 were analyzed using a medical information system, an automated medical file. Patients were analyzed after 6, 12, and 18 months of treatment.
Results: Four hundred and two patients used either TPM (n = 260) or LEV (n = 142); 18 months retention showed a statistically significant difference, revealing 15% more patients that continued LEV compared to TPM: 18 months retention 46% for TPM and 61% for LEV [F (1.400) = 3.313, p = 0.043]. Neurocognitive complaints accounted for a significant number of drug discontinuations and especially the high frequency of neurocognitive complaints in the first period of TPM treatment appeared to be significant different from LEV [F(2,547) = 3.192, p = 0.042]. In the remaining patients, the difference in neurocognitive complaints was not statistically significant.
Conclusion: cognitive complaints are common in TPM treatment and frequently lead to drug withdrawal. The impact of LEV on cognitive function is only mild. This leads to a much higher (15%) drug discontinuation rate for TPM compared to LEV.     

不同剂量托吡酯对癫癎大鼠临床发作与脑电活动的影响

目的:观察不同剂量托吡酯对癫癎大鼠临床发作及脑电活动的影响。方法:选取雄性健康Wistar大鼠60只制作杏仁核点燃模型,然后用托吡酯(分20、40、80 mg／kg三组)进行灌胃,记录用药后杏仁核后放电阈值、皮层及杏仁核后放电持续时间及大鼠双前肢抽动时间。结果:托吡酯灌胃后相同强度电刺激点燃大鼠所需刺激次数明显增加;托吡酯(40、80 mg／kg)灌胃后4 h,杏仁核后放电阈值升高、杏仁核及皮层后放电时程缩短、双前肢抽动时间缩短。结论:托吡酯可明显缩短杏仁核点燃大鼠癫 癎发作时间,缩短杏仁核及皮层后放电持续时间,升高杏仁核后放电阈值。     

Antiepileptic drug treatment in the nineties in The Netherlands.

In this review the state of the art of treating patients with epilepsy in the nineties in the Netherlands is presented. It describes general strategies for treatment with antiepileptic drugs and the history of development of the classical anticonvulsant drugs. Eight new drugs, including vigabatrin, lamotrigine, felbamate, oxcarbazepine, gabapentin, tiagabine, levetiracetam and topiramate are discussed. A review of their pharmacological and clinical properties is presented. Dutch experience with these drugs is included.     

托吡酯预防动物热性惊厥的实验研究

目的:观察托吡酯预防动物热性惊厥发作的疗效与毒副反应。方法:60只对热惊厥敏感的Wistar大鼠,随机分为两组,分别按4或8mg/(k·d)的剂量灌服托吡酯20d后,观察其热性惊厥敏感性改变情况和毒副反应。结果:Wistar大鼠用药后,在热水浴中发生惊厥的时间分别从(247.8±84.9)s、(243.4±99.4)s延长到(353.6±79.3)s、(329.2±78.1)s(t分别为3.07、3.59,P均<0.01);发生惊厥的持续时间分别从(283.0±112.3)s、(298.3±84.0)s缩短到(178.9±84.8)s、(230.3±74.0)s(t分别为3.33、4.18,P均<0.01);热惊厥发生程度也明显减轻,分别从2.9±0.9、2.7±0.7降低到1.8±0.9、1.3±0.9(t分别为4.89、6.65,P均<0.01);热惊厥控制率达95%(57/60,P<0.01);不良反应发生率虽然较高为65.0%(39/60),但表现轻微,而引起动物死亡等严重不良反应发生却只有16.7%(10/60),两者相比差异非常显著(χ2=29.1,P<0.01),而血常规和肝肾功均无异常改变。结论:托吡酯用于预防动物热性惊厥的发生具有剂量较小,疗效高,安全性较好等优点。     

托吡酯治疗儿童癫癎出现泌汗障碍的临床观察与随访

目的研究托吡酯治疗儿童癫癎时出现的泌汗障碍(少汗或无汗)及其对策.方法通过追踪随访了解泌汗障碍与托吡酯服用的时间、季节、剂量、加药速度等的关系,合用其他抗癫癎药的影响,以及出现泌汗障碍后的转归.结果泌汗障碍与托吡酯服用的时间、剂量、加药速度无相关性,不同患儿间存在很大差异,不受合并用药的影响,高温时节症状明显,减缓加药速度可增加易感患儿对泌汗障碍的耐受性.结论托吡酯治疗儿童癫癎时出现的泌汗障碍为托吡酯所致,停药后泌汗功能恢复正常,大部分患儿对其耐受性好,泌汗障碍为非器质性损伤.