托吡酯治疗癫痫的临床观察

目的:本文观察应用托吡酯(妥泰)治疗癫痫的效果及安全性。方法:57例癫痫病人给予口服托吡酯,观察不同发作类型、年龄、用药方法、病程长短及影像改变与疗效的关系。结果:托吡酯对部分性、全面性发作及婴儿痉挛均有效,不良反应较轻。结论:托吡酯是一广谱、安全、有效的新型抗癫痫药物。     

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。     

托吡酯添加治疗对难治性癫痫的临床观察

目的 观察添加托吡酯（TPM）对难治性癫痫（IE）的临床效果与安全性。方法 观察IE15例,以加用TPM前1个月的发作频率为基准,按规定添加TPM,并与加TPM后稳定期3个月中最后1个月的发作频率进行比较,比观察疗效,同时观察副作用。以测原用抗癫痫药（AED）治疗前后的血浓度,协助观察患者用药的依从性。结果 患者用药依从性好,有效率为42.1％－46.7％。对多型癫痫发作有效。副反应轻至中度,且多为一过性。结论 加用TMP治疗IE是安全有效的选择方法之一。     

托吡酯对癫痫大鼠海马神经细胞凋亡的保护作用

目的　探讨托吡酯对癫痫发作大鼠海马神经元凋亡的影响及其可能的机制。方法　采用戊四氮致痫模型 ,大鼠癫痫发作后连续给予托吡酯 80mg/ (kg·d)和 4 0mg/ (kg·d) ) ,共 14d。以TUNEL方法标记DNA片段 ,原位检测海马CA1和CA3区的神经细胞凋亡。结果　各组大鼠海马CA1、CA3区均出现TUNEL阳性细胞。对照组 ,海马CA1、CA3区TUNEL阳性细胞数分别为 (35 .83± 4 .5 8)个和(36 .83± 3.87)个 ;4 0mg/ (kg·d)托吡酯组分别为 (31.5 2± 3.4 3)个和 (32 .35±4 .6 9)个 ;80mg/ (kg·d)托吡酯组为 (2 1.17± 3.0 6 )个和 (2 1.16± 3.87)个。 80mg/ (kg·d)托吡酯组与对照组比较存在显著差异(P<0 .0 0 1) ,4 0mg/ (kg·d)托吡酯组TPM组与对照组相比无显著差异 (P >0 .0 5 )。结论　TPM对癫痫发作后神经元凋亡具有一定的保护作用     

托吡酯加用及单用治疗老年癫痫发作的临床观察

目的 观察加用及单用托吡酯二种方式治疗老年癫痫患者的临床疗效和副反应，探讨单用托吡酯更快、更有效的给药方式。方法 老年癫痫患者124人，分为加用组（A组）：52例患者，在服用卡马西平或苯妥英钠的基础上加用托吡酯25 mg／d，增量25 mg／周至200 mg／d；单药组：72例患者按初始剂量及加量速度不同又分为M1、M2、M3组，M1组患者托吡酯25 mg／d，增量25 mg／周至200 mg／d；M2组患者托吡酯初始剂量50 mg／d，增量25 mg／周至200 mg／d，M3组患者托吡酯初始剂量50 mg／d，增量25 mg／3 d至200 mg／d。结果 各组患者托哟酯总有效率分别为加用组82．7％，单药组初始剂量25 mg／d组82．6％，初始剂量50 mg／d，增量25 mg／周组84．0％，初始剂量50 mg／d，增量25 mg／3 d组70．8％，加用组和M1、M2组单用托吡酯总有效率比较无明显差异（P＞0．05）。发生率比较高的副反应为感觉异常、食欲差和头痛。结论 可单用托吡酯并给予较大初始剂量（50 mg／d），以25 mg／周速度增量治疗老年癫痫。     

托吡酯添加治疗难治性癫痫临床观察

托吡酯的结构与现在的抗癫痫药完全不同 ,是一种在1982年由johnson实验室首先合成的一种可以替代的单糖类抗癫痫药。主要通过阻滞电压激活钠通道 ,在某种GABA受体上增强GABA的活性 ,或者通过阻滞红藻氨酸AMPA型谷氨酸受体起作用 ,其碳酸酐酶的弱抑制作用与某些副作用有关。主要用于顽固性部分性发作的添加治疗 ,部分性发作继发全面性强直 -阵挛发作 (generalizedtonic -clonicseizure ,GTCS)的治疗 ,也可单药治疗。我院自 2 0 0 0年 4月开展了应用托吡酯添加治疗难治性癫痫 ,疗效显著而副作用较少 ,现报道如下。1　资料与方法1.1　一…     

托吡酯添加治疗难治性癫痫的临床观察

目的 观察添加托吡酯对难治性癫痫的临床效果与副作用。方法 对18例难治性癫痫患者，加用TPM后观察其发作频率并与加用前进行比较。计算总有效率，同时进行临床疗效和副作用观察。结果 病人加用托吡酯后总有效率为50%。其中显效率达22.2%(3例未再发作），副反应以胃肠道反应及神经系统症状为主，发生率为52.6%。结论 加用TPM治疗难治性癫痫安全有效。     

托吡酯治疗难治性癫痫的疗效观察

目的：临床临床观察托吡酯（TPM）对难治性癫的疗效和安全性。方法：观察总结21例难治性癫痫病人，在原来应用抗癫痫药物（AEDs）种类及剂量不变的基础上，另增添TPM后3个月与治疗前1个月，癫痫发作频度进行个体自身比较。结果：完全被控制率38．1％，好转率33．3％，总有效率71．4％，不良反应轻微。结论：TPM治疗各类难治性癫痫的疗效显著，安全性好。     

妥泰单药治疗部分性癫痫的疗效观察

目的 观察妥泰单药治疗部分性癫痫病人的疗效及安全性。方法 对30例部分性癫痫患者应用妥泰单药治疗20周,于治疗前观察并记录基础发作频率,剂量从25mg/d开始,每周增加25mg,共8周,达有效剂量或200mg/d后维持治疗12周,并观察癫痫发作频率变化及不良反应等。结果 发作完全控制16例（53．3％）,发作减少≥75％6例（20％）,发作减少≥50％2例（6．7％）,发作减少＜50％6例（20％）。病程短者治疗效果较好。首次接受抗癫痫药物治疗者发作完全控制比例明显高于经治过的病人。治疗过程中无严重不良反应。结论 妥泰单药治疗对控制单纯部分发作及复杂部分性发作均有良好的效果,且耐受性、安全性好。     

托吡酯长期治疗对成年癫疒间患者血清甲状腺激素水平的影响

目的 探讨托吡酯(TPM)长期治疗对成年癫疒间患者血清甲状腺激素水平的影响.方法 用化学发光分析法测定成年癫疒间组患者(32例)TPM治疗前、后的血清甲状腺激素水平,并与健康对照组(40人)进行比较. 结果治疗前成年癫疒间组患者甲状腺激素水平与健康对照组比较无统计学意义(均P>0.05);TPM治疗后3个月、6个月、12个月及24个月的甲状腺激素水平与治疗前及健康对照组比较差异亦无统计学意义(均P>0.05).结论 TPM短期与长期治疗对成年癫疒间患者的甲状腺激素水平没有影响.     

托吡酯对癫癎患者骨代谢的影响

目的探讨长期服用托吡酯对成人癫癎患者骨代谢的影响及其可能机制。方法将长期服用抗癫癎药治疗的成人癫癎患者,分为单独服用非肝酶诱导剂托吡酯组、单独服用肝酶诱导剂(卡马西平、苯巴比妥等抗癫癎药物)组,服药疗程均>6个月。并设健康成人为对照组;对各组进行骨密度测定,检测骨形成的特异性指标(骨碱性磷酸酶),骨吸收的特异性指标(尿中脱氧吡啶啉),同时检测血钙、血磷含量及24小时尿钙尿磷的排泄量及血中甲状旁腺激素含量。结果肝酶诱导剂组及托吡脂组均表现不同程度的骨代谢异常,生化指标改变早于骨密度改变。托吡酯主要通过增加尿钙尿磷的排泄量,促进机体钙的丢失,其次还通过减少骨质形成,综合影响了骨质代谢。结论托吡酯与肝酶诱导剂类抗癫癎药物相比,导致骨量减少较轻,但同样影响骨代谢。早期加强钙的摄入,可以预防骨质疏松的发生。     

Topiramate: effect on EEG interictal abnormalities and background activity in patients affected by focal epilepsy

PURPOSE: To evaluate the effects of topiramate (TPM) on interictal epileptiform abnormalities (IEA) and background activity by means of a computerized EEG analysis, in adult patients affected by focal epilepsy, with or without secondarily generalization, treated with TPM as adjunctive therapy or monotherapy. METHODS: Twenty-four patients affected by symptomatic or cryptogenic focal epilepsy underwent long-term video-EEG recording before and after TPM addition (mean dose 175+/-25 mg per day). RESULTS: TPM addition induced a significant reduction of both partial and secondarily generalized tonic-clonic (SGTC) seizures; treatment responder patients (seizure reduction > or = 50%) were 19 out of 24 patients (79.1%), of whom 5 were seizure-free. Quantitative analysis of IEA showed a significant decrease in the mean number of spikes/10 min during TPM therapy ( 4.2+/-4.2 versus 2.2+/-4.4; P<0.003 ). The analysis of spatial distribution of interictal spikes showed that such reduction was more evident at the level of the epileptogenic area rather than on the spreading component. Statistical analysis revealed only a significant decrease of mean relative power of alpha band in the EEG spectral content, recorded at rest in a group of 18 out of 24 epileptic patients during TPM therapy. In addition, during TPM treatment we observed a significant reduction in alpha reactivity without any important changes of alpha indexes (peak frequency and median frequency). CONCLUSION: These findings suggest that TPM has a strong inhibitory effect on IEA, probably acting on the generating processes, and, if used at low dosage and gradually titrated, seems to have only mild interferences with EEG background activity.     

托吡酯单用及添加治疗癫痫302例临床分析

目的　观察托吡酯添加和单药治疗癫痫的临床疗效及不良反应 ,并探讨单药治疗的理想给药模式。方法　入组患者分为 3组 ,A组 10 2例采用托吡酯添加治疗 ,B组 2 0 0例采用托吡酯单药治疗 ,按初始剂量及加量速度不同 B组又分为 B1组、B2组。B1组 10 5例 ,妥泰初始剂量 2 5 mg/ d,增量 2 5 m g/ w至 2 0 0 m g/ d;B2组 95例 ,妥泰初始剂量 5 0 mg/ d,增量 5 0 m g/ w至 2 0 0 m g/ d。维持治疗 12周。记录发作情况及不良反应。结果　 A组总有效率及控制率分别为 6 0 .8%、2 4 .5 % ,B组总有效率及控制率为 76 .8%、4 1.5 % ,两组疗效差异有显著性意义 (P<0 .0 5 )。 B1组总有效率及控制率分别为 77.9%、4 1.9% ,B2组总有效率及控制率分别为 75 .8%、4 0 .0 % ,两组疗效差异无显著性意义 (P>0 .0 5 )。托吡酯对各型部分性发作及强直 -阵挛性发作的疗效差异无显著性意义 (P>0 .0 5 )。B2组不良反应高于 B1组 ,差异有显著性意义 (P<0 .0 5 )。结论　托吡酯添加及单药治疗癫痫具有良好的疗效 ,对发作频率较低的患者宜选用小剂量起始缓慢加量的治疗方法 ,对发作频率较高的患者可考虑予较大起始剂量并以较快速度加量以尽快控制发作     

Topiramate increases brain GABA, homocarnosine, and pyrrolidinone in patients with epilepsy

OBJECTIVE: To measure the effects of topiramate on brain gamma-aminobutyric acid (GABA) in patients with epilepsy. BACKGROUND: Topiramate is a new antiepileptic medication with multiple putative mechanisms of action. In a recent meta-analysis of the newer antiepileptic drugs, topiramate was the most potent. Homocarnosine and pyrrolidinone are important metabolites of GABA with antiepileptic actions. METHODS: In vivo measurements of GABA, homocarnosine, and pyrrolidinone were made of a 14-cm3 volume in the occipital cortex using 1H spectroscopy with a 2.1-Tesla magnetic resonance spectrometer and an 8-cm surface coil. Twelve patients (eight women) with refractory complex partial seizures were studied while using topiramate. Nine epilepsy-free, drug-free volunteers served as control subjects. RESULTS: Topiramate increased mean brain GABA, homocarnosine, and pyrrolidinone concentrations in all patients. In paired measurements, brain GABA increased by 0.7 micromol/g (SD 0.3, n 7, 95% CI 0.4 to 1.0, p < 0.01). Homocarnosine increased by 0.5 micromol/g (SD 0.2, n 7, 95% CI 0.3 to 0.7, p < 0.001). Pyrrolidinone increased by 0.21 micromol/g (SD 0.06, n 7, 95% CI 0.16 to 0.27, p < 0.01). In two additional patients, GABA, homocarnosine, and pyrrolidinone increased after they were switched from vigabatrin to topiramate. CONCLUSIONS: Topiramate increased brain GABA, homocarnosine, and pyrrolidinone to levels that could contribute to its potent antiepileptic action in patients with complex partial seizures.     

Topiramate on the quality of life in childhood epilepsy

This study evaluated the effect of topiramate (TPM) on the quality of life (QOL) in childhood epilepsy, using the Korean quality of life in childhood epilepsy (K-QOLCE) questionnaire. An open label, prospective, observational study of the families of 664 children with epilepsy from 41 centers was conducted. The parents completed the K-QOLCE at the baseline visit and again 6 months after starting TPM treatment. The parents reported the seizure frequency at both assessment dates. Statistically significant improvements in all K-QOLCE domains except social functioning were found at 6 months after starting TPM treatment from the baseline-scores (P < 0.05). However, improved QOL scores were not dependent on the reduction in seizure frequency. TPM significantly improved QOL in children with epilepsy, suggesting its potential clinical benefits.     

Topiramate in clinical practice: long-term experience in patients with refractory epilepsy referred to a tertiary epilepsy center

For the treatment of patients with chronic refractory epilepsies, information about the long-term efficacy and safety profile of any new antiepileptic drug is crucial. Topiramate has been proven to be effective in patients with refractory chronic partial epilepsies in short-term controlled clinical trials, but the long-term retention, long-term efficacy, and long-term side-effect profile have not been sufficiently investigated. We analyzed all patients who had been treated with topiramate in the Epilepsy Centre Kempenhaeghe from the introduction of the drug in the spring of 1993 up to a final assessment point in mid-2002. In total, 470 patients were identified. The data show that the clinical dose achieved was about 200mg/day, reached after approximately 6 months of treatment. Further dose escalation in the survivors was slow, with a mean dose of about 300 mg/day after 24 months of treatment. Mean titration dose is 25mg/week, but titration strategy is mostly individual and responds to patient complaints. With respect to seizure frequency, 10-15% of the patients were seizure-free at the 6-month evaluation; 4 patients achieved a 2-year remission. Retention rate was 53% after 1 year, 45% after 2 years, 38% after 3 years, and 30% after 4 years. At 4 years, almost 70% of the patients had discontinued topiramate. The main reason was adverse events, which accounted for about 65% of the discontinuations. Behavioral side effects were dominant, with mental slowing (27.6%), dysphasia (16.0%), and mood problems (agitation: 11.9%) being the most frequently reported side effects. In about 10% of the patients side effects led to discontinuation despite the obvious favorable effects on seizure frequency. Comparisons between the patients who discontinued topiramate treatment and those who continued topiramate showed that discontinuation was associated with comedication (vigabatrin and lamotrigine). Our conclusion is that TPM is associated with a high incidence of side effects in clinical practice, affecting long-term retention. Meaningful prognostic factors that may help us in clinical decision making, i.e., to prevent the side effects or to help us identify those at risk, have not been found.