托吡酯单药治疗初诊成人癫(癎)的临床研究

托吡酯(Topiramate,TPM,商品名妥泰,Topamax)是一种新型抗癫(癎)药物,于1995年开始在临床应用.国内关于TPM作为添加治疗难治性癫(癎)的报道较多,未见TPM单药治疗新诊断成人癫(癎)的报道,我院癫(癎)中心于2008-12-2010-12采用TPM单药治疗新诊断成人癫(癎)患者10例,对其进行了开放性自身对照临床研究,观察和评价其临床有效性和安全性.     

托吡酯单药治疗癫癎的临床观察

目的观察托吡酯(TPM)单药治疗癫癎的临床疗效和不良反应.方法应用TPM治疗64例癫癎患者,平均日剂量为138 mg,服药6～36个月,将每例患者治疗最后3个月的发作次数与基础期比较,并观察记录其不良反应.结果本组总有效率为78.1%,其中控制率为42.2%.不良反应的发生率为70.3%,中枢神经系统的不良反应占57.1%,多数较轻微且持续时间较短.10例(15.6%)因治疗无效、不良反应或经济等原因终止治疗.结论 TPM长期单药治疗癫癎疗效明显,耐受性好,较为安全.     

托吡酯长期治疗儿童癫(癎)部分性发作疗效及耐受性的观察

目的观察托吡酯长期治疗儿童癫(癎)部分性发作的疗效、耐受性及安全性.方法对86例癫(癎)部分性发作的患儿给予托吡酯加用或单药治疗,起始剂量为0.5～1.0 mg/(kg·d),分2次口服,每周增加0.5～1.0 mg/(kg·d),经过8周加量期及18个月稳定期,观察其疗效、耐受性及安全性.结果 86例患儿完成加量期后,总有效率为61.6%,控制率为37.2%.稳定期6、12及18个月时总有效率分别为68.6%、81.9%及86.4%,控制率分别为46.5%、59.0%及60.5%,稳定期12及18个月时总有效率及控制率与加量期比较差异有显著性(均P<0.05).不良反应多发生在治疗初期,为一过性轻～中度嗜睡、厌食等.在稳定期18个月时仍有78例(90.7%)坚持服用托吡酯.结论托吡酯对儿童癫(癎)部分性发作的长期治疗,具有较高的疗效及较好的安全性与耐受性.     

托吡酯治疗老年继发性癫癎患者的临床观察

目的观察及评价托吡酯对老年性继发性癫癎患者的临床疗效和安全性。方法收集2007年1月~2008年12月神经内科门诊患者中60岁以上老年继发性癫癎患者40例,只给予托吡酯治疗,而且未服用其它任何抗癫癎药物,于3、6、12个月进行随访,评价托吡酯的临床疗效和安全性。结果 40例患者的有效率均在80%以上。无1例患者发生重度不良反应。结论托吡酯治疗老年继发性癫癎患者有效且安全。     

丙戊酸和托吡酯对癫(癎)患儿游离肉毒碱的影响

目的探讨丙戊酸(VPA)和托吡酯(TPM)对癫癎患儿游离肉毒碱的影响。方法35例癫癎患儿,年龄6～8岁,男20例,女15例,其中12例予VPA单药治疗,11例予TPM单药治疗,12例予VPA及TPM联合治疗6～8个月。15例健康儿童作为正常对照组。测定血浆游离肉毒碱的浓度。结果VPA组血浆游离肉毒碱的浓度明显低于对照组及TPM组,VPA-plus- TPM组与VPA组比较差异无显著性,TPM组与对照组比较差异无显著性。结论VPA可降低癫癎患儿血浆游离肉毒碱水平,而TPM对血浆游离肉毒碱无明显影响。     

托吡酯添加治疗难治性癫癎的临床观察

目的　观察添加托吡酯对难治性癫的临床效果与副作用。方法　对 18例难治性癫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 5 0 % ,其中显效率达 2 2 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 5 2 6%。结论　加用TPM治疗难治性癫安全有效。     

托吡酯治疗癫癎的长期疗效观察

目的观察托吡酯治疗不同类型癫癎的长期疗效及安全性.方法采用开放性试验的方法,给予115例不同类型癫癎患者托吡酯单药或添加治疗,6个月后进行疗效评定,1年和2年时计算控制率和托吡酯保留率,记录不良反应.结果 (1) 6个月时总有效率单药治疗组为83.9%,添加治疗组为66.1%,对各型癫癎均有一定疗效,各组间发作控制率和总有效率比较差异无显著性;(2)稳定期儿童组有效剂量为(105.72±48.28) mg/d,成人组为(176.36±62.81) mg/d;(3)控制率1年为40.0%,2年为28.7%;保留率1年为67.8%,2年为46.1%;(4)34例(29.6%)出现不良反应,为轻、中度的中枢神经系统症状以及厌食和体质量减轻.结论托吡酯是较好的广谱抗癫癎药物,长期应用仍有较好的疗效和安全性.     

抗癫(癎)药物对认知功能的影响

癫(癎)是脑部神经元异常放电高度同步化活动所引起的,由不同症状和体征组成的短暂性临床现象.其特点是脑部持续存在的导致癫(癎)反复发作的易感性,以及由于这种疾病引起的神经生物、认知、心理和社会功能障碍等方面的后果.     

癫(癎)患者认知功能影响因素的研究

目的:研究癫患者认知功能的影响因素。方法:对166例癫患者进行认知评定。认知评定工具:听觉词语测验、逻辑记忆测验、数字符号转换测验、Stoop字色干扰测验、连线测验、言语流畅性测验、Rey-Osterrieth复杂图片测验及Boston命名测验。影响因素与认知功能评分之间采用一元线性相关及多元逐步回归分析。结果:患者年龄、性别、文化程度、起病年龄、病程、发作频率、发作持续时间、全身强直阵挛发作(GTCS)、复杂部分性发作(CPS)及抗癫药物数量与患者的认知功能有相关性。结论:癫患者的起病年龄与其认知损害成正比,病程越长对癫患者的认知损害越明显,原发或继发全身性强直阵挛发作与言语功能损害、复杂部分性发作与言语记忆损害之间的关系密切,用药种类与记忆、注意力以及精神运动能力的损害有关。     

托吡酯治疗难治性癫癎的疗效观察

目的　评价托吡酯 (TMP)添加治疗难治性癫的疗效和其不良反应 ,以及对原服用AEDS 血中浓度的影响。方法　采取开放性试验的方法对 80例难治性癫进行添加托吡酯治疗 ,观察其疗效。结果　托吡酯作为添加治疗难治性癫总有效率5 8 6% ,对单纯部分性发作有效率 66 7% ,复杂部分性发作 2 5 % ,且完全控制率 12 9% ,不良反应均与CNS有关 ,多为一过性。但儿童的无汗、体重减轻 ,持续时间长。原服用AEDS 血中浓度在添加托吡酯前后无明显变化。结论　托吡酯治疗难治性癫有效 ,但要注意用药量的个体化。     

丙戊酸钠对成人癫痫患者认知功能的影响

目的了解丙戊酸钠对成人癫痫患者认知功能的影响。方法采用简易精神状态评定量表,分别于治疗前及治疗6个月、1年、2年、3年对74例接受丙戊酸钠治疗的成人癫痫患者认知功能进行评价,并选同期健康体检者85例作为对照组。结果癫痫组丙戊酸钠血药浓度均在正常浓度范围。简易精神状态评定量表评分：在干预前,癫痫组11项得分均低于对照组（P〈0.01）;在干预后6个月、1年、2年、3年,癫痫组11项得分均低于对照组（P〈0.05）;癫痫组自身与治疗前比较,11项得分均增高（P〈0.05）,但随时间延长无进一步改善趋势（P〉0.05）;癫痫组治疗前后原发性和继发性癫痫患者间比较无差异（P〉0.05）。结论成人癫痫患者存在认知功能下降,丙戊酸钠具有改善癫痫患者认知功能的作用。     

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。     

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。     

Topiramate in patients with juvenile myoclonic epilepsy

BACKGROUND: Topiramate is a broad-spectrum agent effective against primarily generalized tonic-clonic seizures (PGTCS) as well as partial-onset seizures. Juvenile myoclonic epilepsy is one of the most common idiopathic generalized epilepsies, with most patients experiencing PGTCS. OBJECTIVE: To evaluate topiramate as add-on therapy in patients with juvenile myoclonic epilepsy. DESIGN: Post-hoc analysis of a patient subset from 2 multicenter, double-blind, randomized, placebo-controlled, parallel-group trials. SETTING: Eighteen centers in the United States; 10 centers in Europe; 1 center in Costa Rica (primary trials). PATIENTS: A total of 22 patients with juvenile myoclonic epilepsy participating in placebo-controlled trials assessing topiramate (target dose, 400 mg/d in adults) in inadequately controlled PGTCS. MAIN OUTCOME MEASURE: Reduction of PGTCS. RESULTS: A 50% or more reduction of PGTCS in 8 of 11 topiramate-treated patients (73%) and 2 of 11 placebo-treated patients (18%) (P = .03). Reductions in myoclonic, absence, and total generalized seizures were also observed, although topiramate vs placebo differences did not achieve statistical significance. CONCLUSION: As a broad-spectrum agent, topiramate is an effective option for patients with juvenile myoclonic epilepsy.     

伽玛刀对药物难治性癫疒间病人认知功能的影响

目的探讨伽玛刀治疗对药物难治性癫疒间认知功能的影响。方法回顾性分析41例行伽玛刀治疗的药物难治性癫疒间病人的临床资料,根据Engel分级评价癫疒间发作控制情况,瑞文标准推理能力测验（SPM）评价病人的认知功能,并分析影响认知功能的可能因素。结果治疗后达EngelⅠ级3例,EngelⅡ级9例,EngelⅢ级17例,EngelⅣ级12例。治疗后SPM评分较术前提高13例,下降4例,无明显变化24例。治疗前智商值为73.3±18.9,治疗后为77.3±19.8,两者差异显著（P＜0.05）;治疗后颞叶癫疒间与非颞叶癫疒间的认知功能差异无统计学意义（P＞0.05）;而EngelⅠ～Ⅲ级与EngelⅣ级病人认知功能差异有统计学意义（P＜0.05）。结论伽玛刀可部分改善癫疒间病人认知功能,是治疗药物难治性癫疒间的安全、有效方法,具有良好应用前景。     

拉莫三嗪对癫(癎)患者认知功能与生活质量的影响

目的 评价拉莫三嗪对癫(癎)患者认知功能以及生活质量的影响.方法 对91例新诊断的癫(癎)患者给予拉莫三嗪治疗,并在用药前及用药16周后进行认知功能评定及生活质量调查.认知功能评定工具包括听觉词语测验、逻辑记忆测验、数字符号转换测验、Stroop字色干扰测验、连线测验、言语流畅性测验、韦氏积木测验、数字广度测验及Boston命名测验;生活质量调查采用患者生活质量评定量表-31(QOLIE-31).结果 癫(癎)患者应用拉莫三嗪治疗16周后与用药前比较,各项得分均有提高,其中以即刻与延迟词语记忆、情景记忆、执行功能、空间知觉能力以及言语命名功能方面改善显著.生活质量方面,QOLIE-31量表的7个测评方面及1个总体健康评价中,6项分值在用药后较用药前有所提高,其中"对癫(癎)的担心"(38.81±16.06,16周后45.68±15.18,P＜0.01)、"总体生活质量"(59.12±13.50,16周后64.99±13.33,P＜0.01)、"社会功能"(64.59±25.14,16周后69.41±22.70,P＜0.05)以及"总体自身健康评价"(71.18±13.73,16周后76.75±11.30,P＜0.01)4项的得分差异有统计学意义.结论 拉莫三嗪单药治疗新诊断癫(癎)患者可在短期内改善其认知功能,并提高生活质量.     

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.     

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.