托吡酯对癫痫患者认知功能的影响

目的 评价托吡酯对癫痫病人认知功能的影响。方法 对2001年首次来我院癫痫门诊确诊的26例癫痫患者中12例用托吡酯单药治疗,14例用其他传统的抗痫药物治疗,6个月后对两组对象进行智力测定。托吡酯组还另行测定治疗前后的智力变化。结果 14例用传统抗痫药物治疗组6个月后平均IQ值为(89.64±11.37)分,12例用托吡酯治疗组6个月后平均IQ值为(81.83±17.51)分,两组比较P值<0.05,差别有统计意义;用托吡酯组治疗前智力测定平均IQ值为(87.50±16.78)分,治疗6个月后平均IQ值为(81.83±17.51)分,前后比较P值<0.05,差别也有统计意义。结论应用托吡酯治疗癫痫确实会影响患者的认知功能,使患者的智商(IQ)下降。     

传统抗癫疒间药物与托吡酯对成年癫疒间患者生活质量影响的对比研究

目的 探讨传统抗癫癎药物(AEDs)与托吡酯(TPM)对成年癫癎患者生活质量(QOL)的影响。方法 102例临床确诊的成年癫癎患者随机分为AEDs组和TPM组,井用QOL IE-30表对102例癫癎患者和62名正常人(对照组)进行评定。结果 AEDs组较对照组QOL明显降低(P<0.05),表现惧怕发作,对日常生活不满意,情绪差,精力不足,认知功能下降,对长期服用抗癫癎药物的顾虑较多,社交、工作受限等;而TPM组的QOL虽然低于对照组(P<0.05),但在前5项的评分中明显高于AEDs组(P<0.05)。TPM组的发作频率明显低于AEDs组(P<0.05)。发作频率对癫癎患者QOL的影响较大,癫癎发作越频繁,QOL越差。结论 成年癫癎患者的QOL较正常人显著降低,TPM能提高癫癎患者的QOL,其改善QOL的作用主要是通过控制发作实现的。因此,合适的药物控制癎性发作是提高癫癎患者QOL的关键。     

托吡酯对癫痫患者认知功能影响的Meta分析

目的以事件相关电位P300或智商为观察指标运用Meta分析的方法综合评价托吡酯对癫痫患者认知功能的影响。方法通过计算机文献检索,根据纳入和排除标准收集所有关于托吡酯对癫痫患者认知功能影响的研究文献,应用RevMan4.2软件对符合要求的研究结果进行Meta分析。结果共有相关文献8篇纳入分析(托吡酯起始剂量0.5mg/kg/d,维持剂量小于300mg/d)。Meta分析结果表明,癫痫患者应用托吡酯治疗后P300潜伏期显著延长(WMD=-25.60,95%CI[-43.07,-8.14],假设检验z=2.87,P=0.004),P300波幅差异无统计学意义(P=0.30),总智商、语言智商、操作智商得分显著下降(P0.001)。结论托吡酯小剂量、缓慢加量、低维持剂量治疗癫痫,仍能引起认知功能受损。     

托吡酯对癫痫大鼠认知功能及海马组织中NCAM的mRNA表达影响

目的研究托吡酯（TPM）对癫痫大鼠认知功能的影响以及使用TPM后大鼠海马组织中神经细胞粘附分子（NCAM）的mRNA表达变化。方法将大鼠随机分成生理盐水（NS）组、癫痫（EP）组、癫痫＋托吡酯治疗1周（TPM1周）组和癫痫＋托吡酯治疗4周（TPM4周）组,建立匹罗卡品诱导癫痫大鼠模型和TPM干预模型,观察大鼠的行为学改变,通过Morris水迷宫实验测试大鼠的学习记忆能力,并通过Real—TimePCR检测大鼠海马组织中NCAM的mRNA表达水平。结果EP组大鼠的逃避潜伏期大于NS组,原平台象限游泳时间百分比小于NS组,海马NCAM的mRNA表达水平高于NS组（P〈0．01）;TPM1周组和TPM4周组大鼠的逃避潜伏期大于EP组,原平台象限游泳时间百分比小于EP组,海马NCAM的mRNA表达水平低于EP组（P〈0.01）;TPM4周组大鼠的逃避潜伏期大于TPM1周组,原平台象限游泳时间百分比小于TPM1周组,海马NCAM的mRNA表达水平低于TPMI周组（P〈0.05）。结论大鼠产生癫痫持续状态后认知功能明显下降,海马NCAM的mRNA表达上调;使用大剂量TPM短期治疗后其认知功能进一步下降,海马NCAM的mRNA表达受抑,且下降与受抑程度与TPM的持续使用时间有关。     

托吡酯单药治疗155例癫痫的疗效观察

近年来我们应用托吡酯(TMP)对155例癫痫患者进行单药治疗，取得较好的疗效，现报告如下。     

托吡酯对癫痫患者脑电活动的影响

脑电图（EEG）在癫痫诊断及治疗方面具有重要意义。托吡酯（TPM）是一种新型抗癫痫药物，本研究采用TPM治疗癫痫患者并观察其对脑电活动的影响。     

托吡酯添加治疗难治性癫痫的临床研究

目的观察托吡酯作为添加药物治疗难治性癫痫的疗效、用药方法、剂量及副作用.方法采用开放性试验的方法对50例难治性癫痫患者(其中成人30例,小儿20例)进行添加托吡酯治疗,观察其疗效.结果托吡酯作为添加药物治疗难治性癫痫,总有效率达58%,22%的患者发作停止.对复杂部分性发作有效率达69%,对其他发作类型亦有一定疗效.本组中成人的疗效好于儿童.平均有效剂量成人为(123.9±47.9)mg/d,小儿为(3.6±1.2)mg·kg     

托吡酯治疗难治性癫痫的疗效观察

目的　评价托吡酯 (TPM)单药治疗难治性癫痫 (IE)的疗效及其不良反应。方法　选择 5 6例各种类型发作的 IE患者给予 TPM单药治疗 ,前 8周为调整期 ,后 8周为稳定期 ,总观察期 16周。每 2周观察 1次 ,疗效评估每 4周 1次。并对不同时期 TPM剂量与癫痫发作次数作相关分析以及观察不良反应。结果　 5 6例患者 (15例因多种原因中途退出者不含在内 ) TPM剂量 2 41.6 7± 75 .6 6 m g/ d(15 0～ 6 0 0 m g/ d)。调整期随着 TPM剂量增加患者癫痫发作频率逐渐减少 ,呈显著相关性 (r=0 .6 32 7,P<0 .0 0 0 1) ;稳定期 TPM剂量不增加而患者癫痫发作次数继续减少 ,相关性呈现下降趋势 (r=0 .5 92 1,P<0 .0 0 1;r=0 .40 44 ,P<0 .0 1)。全组有效率为 73.2 1% ,包括 6例完全不发作者。治疗初期 18例患者出现一过性轻度不良反应 ,治疗中未见病情恶化者。结论　托吡酯能有效减少难治性癫痫临床发作 ,较佳疗效时间窗在第 12～ 16周。     

托吡酯抗癫痫治疗对糖代谢的影响

目的观察癫痫患者服用托吡酯后血糖、胰岛素、胰岛素抵抗指数等变化,评估托吡酯对于抗癫痫治疗的临床意义及局限性。方法回顾性分析2014-06—2016-05我院神经内科门诊及住院的78例癫痫患者临床资料,随机分成2组,托吡酯组40例给予托吡酯治疗,丙戊酸钠组38例给予常规的丙戊酸钠治疗,分别于治疗前和治疗后3个月、6个月检测2组糖代谢指标差异及不良反应发生情况。结果 2组治疗后体质量、胰岛素、IR、瘦素及脂联素比较差异有统计学意义(P0.05)。托吡酯不良反应发生率为12.5%,显著低于丙戊酸钠组的23.7%,差异有统计学意义(P0.05)。结论 (1)癫痫患者葡萄糖代谢存在异常,抗癫痫药物对癫痫患者糖代谢存在影响;(2)托吡酯与丙戌酸钠均会导致癫痫患者糖代谢指标出现不同程度的下降或升高,故两种药物是否可作为理想药物尚待进一步研究,建议临床合理选用抗癫痫药物,尽可能减少药物不良反应。     

抗癫(痫)药物对癫(痫)病人事件相关电位P300的影响

目的:评价托吡酯(topiramate,TPM)与拉莫三嗪(lamotrigine,LTG)对癫痫患者认知功能的影响.方法:60例新确诊癫痫患者随机分为两组:TPM单药治疗组32例,LTG单药治疗组28例;用药前及用药2个月后分别检测事件相关电位(event related potentials,ERP) P300的潜伏期(ms)及波幅(μV),并比较两种药物对P300的影响.结果:TPM治疗后,患者P300潜伏期延长、波幅降低,与治疗前相比,差异有显著意义(P＜0.01),与对照组(未用药的24名正常人)相比,差异有显著意义(P＜0.01),与LTG相比,差异有统计学意义(P＜0.05),LTG治疗组P300潜伏期延长、波幅降低,但与治疗前相比和与对照组相比,差异均无统计学意义(P＞0.05).结论:TPM与LTG都是控制癫(痫)发作较理想的新型抗癫(痫)药物,服用治疗剂量范围内TPM对患者P300产生较明显的影响,而LTG对癫(痫)患者P300影响较小.服用TPM可能导致癫(痫)患者出现认知功能障碍,而服用LTG对癫(痫)患者的认知功能不仅没有损害,甚至可能有一定的改善作用.     

新型和传统抗癫痫药治疗新诊断癫痫患者的评价

目的评价新型和传统抗癫痫药(AEDs)单药治疗新诊断癫痫患者的疗效及安全性。方法前瞻性收集143例新诊断癫痫患者,分为卡马西平(CBZ)、丙戊酸钠(VPA)、托吡酯(TPM)和拉莫三嗪(LTG)治疗组,其中CBZ用于癫痫部分性发作,VPA用于癫痫全面性发作,而TPM和LTG用于各种类型癫痫发作,至少观察1年。采用生存分析Kaplan-Meier法比较治疗后癫痫初次发作时间、治疗失败时间,同时比较各组患者达"6月、1年无发作"比例和药物不良反应。结果 4组AEDs单药治疗后至癫痫初次发作时间、治疗失败时间的差异均无统计学意义(P0.05);CBZ、VPA、TPM和LTG组"6月无发作"率分别为80%、78%、87.9%、63.3%(均P0.05);"1年无发作"率分别为70%、66%、66.7%、50%(均P0.05)。TPM组不良反应率为63.3%,高于CBZ组(20%)、VPA组(24%)(均P0.01),而LTG组不良反应率为16.7%,与CBZ、VPA组相当(均P0.05)。结论从疗效和安全性综合考虑,新型AEDs治疗癫痫并不优于传统AEDs,其中TPM轻、中度不良反应还明显高于传统AEDs。     

Effects of topiramate versus other antiepileptic drugs on the cognitive function of patients with epilepsy

BACKGROUND: Only very large dose of topiramate has neurotoxicity, indicating that topiramate has low neurotoxicity and high safety. The residual rate of topiramate is affected by many cognitive-related adverse effects. Patients who take topiramate often accompany with thought slowness, difficulty in finding words, dyscalculia, blunt reaction, attention decreasing, memory deterioration, etc. OBJECTIVE: To compare the effects of topiramate with traditional anti-epileptic drugs (including carbamazepine and Valproic acid (VPA) on cognitive function of patients with epilepsy. DESIGN: Observational experiment, self-control and intergroup comparison. SETTING: Sichuan Academy of Medical Science. PARTICIPANTS: Eighty-seven inpatients and outpatients with newly diagnosed epilepsy who received preliminary diagnosis and follow-up in the Department of Neurology, Sichuan People's Hospital between January 2004 and June 2006 were involved in this survey. They were diagnosed according to disease history and electroencephalogram (EEG). The onset type was diagnosed following the definition of epilepsy and epileptic syndrome in 1989 International Anti-epileptic League. The involved patients and their relatives were informed of detection and therapeutic regimen. The patients were assigned into two groups according to table of random digit: traditional antiepileptic drugs group (AEDs group, n =44) and topiramate (TPM) group (n =43). METHODS: ①Among the patients in AEDs group, carbamazepine was the first choice for 21 patients with partial seizures or partial secondarily generalized seizures, and VPA for 23 patients with generalized seizures. The initial dose of carbamazepine was 300 mg/d, and that of VPA was 500 mg/d. Patients in the TPM group took TPM with the initial dose of 25 mg/d, increased by 25 mg/d each week to target dose 150 mg/d within 8 weeks. ② Curative effect was graded into 4 degrees: markedly effective, effective, ineffective and aggravated. Total effective rate was calculated. ③ Cognitive function of patients was tested before and 6 months after administration by using Wechsler Adult Intelligence Scale(WAIS) or Wechsler Intelligence Scale for Children (WISC, Chinese edition), (Higher scores indicated better cognitive function), Stroop color word interference, test of memory of past numbers, test of telling the names of fruits and vegetables within 1 minute (Shorter time for reading word, telling color and memory of past numbers demonstrated better cognitive function. Less errors in reading words, telling colors and memory of past numbers, numbering and telling the names of fruits and vegetables within 1 minute indicated better cognitive function), etc. totally 22 items. ④ t test and paired t test were used for measurement data. MAIN OUTCOME MEASURES: Clinical curative effects and adverse reactions as well as neurological tests. RESULTS: Eighty-four pationts praticipated final analysis and 3 dropped out. ① Inthe AEDS group and TPM group, total effective rate was 86% and 99%, respectively. ② In the AEDs group, there were no significant changes in the scores of each test of WIS before and after treatment (P > 0.05). In the TPM group, total IQ, word scores, verbal IQ and digit span scores were significantly decreased （t =2.097–4.423，P < 0.05–0.01）.Following treatment, the time for reading word and telling color for patients in the AEDs group was prolonged in Stroop color interference test（t =–2.304，–2.454，P < 0.05）, and time for reading word and memory of past numbers for patients in the topiramate group was significantly prolonged （t =–3.054，2.272，P < 0.01，0.05）. ③There were no significant differences in scores of WIS before and after treatment in AEDs group and TPM group (P > 0.05). Following treatment, verbal IQ, word scores, total IQ, digit span of patients in the TPM group were significantly lower than those in the AEDs group（t =2.052–3.297，P < 0.05–0.01）.There were no significant differences in Stroop color word interference, memory of past numbers and telling the names of fruits and vegetables within 1 minute before and after treatment in AEDs group and TPM group (P > 0.05). CONCLUSION: ① Moderate and small doses of both TPM and AEDs may lead to mild cognitive function impairment of patients, mainly presenting delayed reaction and decreased sensitivity. ②TPM mainly influences attention, language comprehension ability and fluency, while AEDs cause delayed reaction easily, but influence executive function mainly.     

Effects of topiramate versus other antiepileptic drugs on the cognitive function of patients With epilepsy

BACKGROUND： Only very large dose of topiramate has neurotoxicity, indicating that topiramate has low neurotoxicity and high safety. The residual rate of topiramate is affected by many cognitive-related adverse effects. Patients who take topiramate often accompany with thought slowness, difficulty in finding words, dyscalculia, blunt reaction, attention decreasing, memory deterioration, etc. OBJECTIVE： To compare the effects of topiramate with traditional anti-epileptic drugs （including carbamazepine and Valproic acid （VPA） on cognitive function of patients with epilepsy. DESIGN： Observational experiment, self-control and intergroup comparison. SETTING： Sichuan Academy of Medical Science. PARTICIPANTS： Eighty-seven inpatients and outpatients with newly diagnosed epilepsy who received preliminary diagnosis and follow-up in the Department of Neurology, Sichuan People＇s Hospital between January 2004 and June 2006 were involved in this survey. They were diagnosed according to disease history and electroencephalogram （EEG）. The onset type was diagnosed following the definition of epilepsy and epileptic syndrome in 1989 International Anti-epileptic League. The involved patients and their relatives were informed of detection and therapeutic regimen. The patients were assigned into two groups according to table of random digit： traditional antiepileptic drugs group （AEDs group, n =44） and topiramate （TPM） group （n =43）. METHODS： （1）Among the patients in AEDs group, carbamazepine was the first choice for 21 patients with partial seizures or partial secondarily generalized seizures, and VPA for 23 patients with generalized seizures. The initial dose of carbamazepine was 300 mg/d, and that of VPA was 500 mg/d. Patients in the TPM group took TPM with the initial dose of 25 mg/d, increased by 25 mg/d each week to target dose 150 mg/d within 8 weeks. （2） Curative effect was graded into 4 degrees： markedly effective, effective, ineffective and aggravated. Total effective rate was calculated. （3） Cognitive function of patients was tested before and 6 months after administration by using Wechsler Adult Intelligence Scale（WAIS） or Wechsler Intelligence Scale for Children （WISC, Chinese edition）, （Higher scores indicated better cognitive function）, Stroop color word interference, test of memory of past numbers, test of telling the names of fruits and vegetables within 1 minute （Shorter time for reading word, telling color and memory of past numbers demonstrated better cognitive function. Less errors in reading words, telling colors and memory of past numbers, numbering and telling the names of fruits and vegetables within 1 minute indicated better cognitive function）, etc. totally 22 items. （4） t test and paired t test were used for measurement data. MAIN OUTCOME MEASURES： Clinical curative effects and adverse reactions as well as neurological tests. RESULTS： Eighty-four pationts praticipated final analysis and 3 dropped out. （1） Inthe AEDS group and TPM group, total effective rate was 86% and 99%, respectively. （2） In the AEDs group, there were no significant changes in the scores of each test of WIS before and after treatment （P 〉 0.05）. In the TPM group, total IQ, word scores, verbal IQ and digit span scores were significantly decreased （ t =2.097 - 4.423, P 〈 0.05 - 0.01 ） .Following treatment, the time for reading word and telling color for patients in the AEDs group was prolonged in Stroop color interference test （ t = - 2.304, - 2.454, P 〈 0.05 ）, and time for reading word and memory of past numbers for patients in the topiramate group was significantly prolonged （ t = - 3.054, 2.272, P 〈 0.01, 0.05 ）. （3）There were no significant differences in scores of WIS before and after treatment in AEDs group and TPM group （P 〉 0.05）. Following treatment, verbal IQ, word scores, total IQ, digit span of patients in the TPM group were significantly lower than those in the AEDs group （t =2.052 - 3.297, P 〈 0.05- 0.01 ） .There were no significant differences in Stroop color word interference, memory of past numbers and telling the names of fruits and vegetables within 1 minute before and after treatment in AEDs group and TPM group （P 〉 0.05）. CONCLUSION： （1） Moderate and small doses of both TPM and AEDs may lead to mild cognitive function impairment of patients, mainly presenting delayed reaction and decreased sensitivity. （2）TPM mainly influences attention, language comprehension ability and fluency, while AEDs cause delayed reaction easily, but influence executive function mainly.     

Comparative cognitive effects of levetiracetam and topiramate in intractable epilepsy

Aim: Anti‐epileptic drugs (AED) may cause cognitive impairment. Because intractable epilepsy (IE) represents a distinct group, the purpose of the present study was to study the comparative cognitive effects of the two efficacious AED, levetiracetam (LEV) and topiramate (TPM), on IE. Methods: This was a non‐randomized, blinded cognitive assessment and parallel design. The cognitive effects of LEV and TPM on 79 demographically comparable patients with IE were assessed at baseline (T1) and after 1 year of treatment (T2) using the Cognitive Abilities Screening Instrument. Results: Forty patients took TPM and 39 took LEV. At T1, seizure frequency, number of AED, and epilepsy duration were not significantly different. There were no significant differences in cognition between the two groups at T1 or T2. T2 orientation scores were lower than T1 scores in the TPM group (P < 0.05). In the TPM subgroup with T1 cognitive abnormalities, T2 scores for recent memory improved (P < 0.05). Conclusion: For patients with IE, LEV might preserve cognition, TPM's effects for patients with baseline cognitive abnormalities are worth observation.     

75例癫痫患者认知功能与影响因素分析

目的了解癫痫患者认知功能状况变化及影响因素。方法应用简明精神状况量表(MMSE)对75例癫痫患者进行认知功能评定,以年龄、性别、受教育程度相匹配的75例健康者志愿者作为正常对照。并分析相关影响因素。结果与对照组相比,癫痫患者MMSE评分明显下降(P0.01)。癫痫患者认知功能障碍与初发年龄、发作频率、发作类型及用药种类多少具有明显相关性。结论癫痫患者存在认知功能下降,初发年龄、发作频率、发作类型及用药种类影响患者认知功能。     

癫(癎)患者认知功能障碍及其影响因素的分析

目的 探讨癫(癎)患者认知功能障碍及其影响因素.方法 采用韦氏儿童智力量表及成人智力量表对125例癫(癎)患者的认知功能进行测定,并分析年龄、发作类型、癫(癎)综合征类型、病因、发作频率、严重程度、脑电图改变、服用药物及家族史等因素对其的影响.结果 癫(癎)患者认知功能障碍发生率为18.4%,儿童(27.8%)高于成人(14.6%).癫(癎)组儿童和成人患者总智商(F7Q)、操作智商(PIQ)和言语智商(VIQ)、言语理解因子(VCF)、知觉组织因子(POF)和记忆/注意不分心因子(MF)显著低于相应的正常对照组(均P<0.01).多因素回归分析显示,发作程度越严重、服用药物的数量越多,智商越低,全面发作对智商的影响最明显.结论 癫(癎)患者存在明显的认知功能障碍,发作严重程度、服药数量,发作形式是影响其认知功能的独立危险因素.     

颞叶癫痫患者情绪及认知功能研究

目的调查颞叶癫痫(TLE)患者情绪及认知功能状况,分析相关的临床影响因素。方法对30例颞叶癫痫患者以及30例年龄、性别和受教育程度无差异的健康对照进行信息采集、神经心理学量表调查和统计学分析。结果与对照组相比,TLE组中出现焦虑情绪个体比例更高(P0.01);MoCA、WAIS-RC知识、TMT_B以及BDST评分较低,差异具有统计学意义(P0.05)。病程、癫痫家族史与MoCA评分及起病年龄与WAIS-RC知识评分之间均具有线性回归关系(决定系数分别为R~2=0.325和R~2=0.137,P0.05)。结论 TLE患者群体相较于正常人群更容易出现焦虑情绪,并且可出现整体智能、短时记忆、远期记忆能力、注意力和执行控制能力下降。对TLE患者,尤其对病程长、起病早和有家族史的患者,早期进行神经心理学评估将有利于及早发现认知功能损伤,实行有效干预。     

托吡酯单药治疗癫痫的临床和动态脑电图研究

目的:观察新型抗癫痫药托吡酯(妥泰)单药治疗癫痫的临床疗效和24h动态脑电图(AEEG)变化。方法:用开放性自身对照临床实验,对38例癫痫患者给予托吡酯单药治疗,比较用药前和用药后20周时癫痫发作频率变化、药物不良反应和AEEG的变化。结果:托吡酯单药治疗癫痫总有效率81.58%,不良反应较小;AEEG痫样放电率治疗前73.68%降至治疗后39.47%,有显著统计学差异(P<0.01),异常慢波治疗前26.32%,增加至治疗后55.26%,有显著统计学差异(P<0.01)。结论:托吡酯单药治疗癫痫有效,未见明显不良反应,并可使AEEG痫样放电减少和慢波活动增加。