妥泰对成人癫痫患者骨代谢及骨密度的影响

目的：探讨妥泰对成人癫痫患者骨代谢及骨密度的影响。方法选取70例服用妥泰半年以上的痫病患者作为研究组,同时选取50例未服用过任何抗癫痈药物的癫痈患者作为对照组。观察2组患者血清钙、磷、碱性磷酸酶以及甲状旁腺激素水平,此外观察2组患者腰2～4椎骨与左股骨颈、股骨大转子、Wards三角区骨密度。结果2组患者血清钙、磷、碱性磷酸酶以及甲状旁腺激素等水平,差异均无统计学意义（P＞0·05）;2组患者腰2、腰4、腰2～4椎骨与股骨大转子、Wards三角区骨密度,差异均有统计学意义（P＜0·05）。结论妥泰对成人癫痫患者骨代谢无明显影响,对骨密度有轻微影响。     

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。     

托吡酯对戊四氮致癫癎大鼠海马AQP4表达水平的影响

目的探讨托吡酯对戊四氮致癫癎大鼠海马AQP4表达水平的影响。方法将30只Wistar大鼠随机分为戊四氮致癫癎组、托吡酯干预组和正常对照组，每组各10只；癫癎模型点燃后在不同时相点灌注取材，通过HE染色观察大鼠海马神经元的变化，并应用免疫组化法检测大鼠海马AQP4表达水平。结果HE染色显示托吡酯干预组神经元变性和坏死较戊四氮致癫癎组明显减轻；免疫组化显示戊四氮致癫癎组在致癫癎后12hAQP4的表达显著增强，致癫癎后24h达高峰，托吡酯干预组在致癫癎后12h～36h各时相点AQP4表达水平均分别低于戊四氮致癫癎组相应时间点（P〈0．05）。结论托吡酯通过下调大鼠海马AQP4的表达可能参与了对大鼠海马神经元的保护过程。     

四川地区新型抗癫痫药物超说明书规定用药分析:一项对儿童患者的多中心调查研究

目的调查四川地区左乙拉西坦、托吡酯、奥卡西平和拉莫三嗪等新型抗癫癎药物在儿童癫癎患者中超说明书规定用药(超说明书用药)的现状及安全性,以为临床制定相关用药指南提供数据,并为临床用药提供参考。方法收集2010年7月-2011年11月于四川大学华西第二医院、成都市妇女儿童中心医院和四川省人民医院门诊接受抗癫癎药物治疗的儿童癫癎患者资料,统计此间应用抗癫癎药物的总病例数和服用4种新型抗癫癎药物的病例数。依据药品说明书适应证,判断使用新型抗癫癎药物的医嘱是否属于超说明书用药及其药物类型,并计算和分析超说明书用药发生率及药物不良反应。结果共854例癫癎患儿接受抗癫癎药物治疗,其中670例患儿服用4种新型抗癫癎药物中的一种或多种,超说明书用药者406例,占抗癫癎药物治疗总病例数的47.54%(406/854),约占新型抗癫癎药物治疗总病例数的60.60%(406/670)。与按说明书用药患儿相比,超说明书用药患儿年龄更小、单药使用比例更高、全面性发作和癫癎综合征患儿比例更高,其病例数比例分别为左乙拉西坦78.50%(157/200)、托吡酯79.81%(253/317)、奥卡西平21.32%(42/197)和拉莫三嗪33.33%(21/63);不同年龄、单药使用和各种发作类型中以左乙拉西坦和托吡酯超说明书用药现象更为突出。除失访病例外,超说明书用药组患儿以奥卡西平[16.67%(7/42)]不良反应发生率最高,其次分别为托吡酯[14.81%(36/243)]、左乙拉西坦[10.60%(16/151)]和拉莫三嗪[9.52%(2/21)],但是与按说明书用药组之间差异无统计学意义(χ~2=0.375、0.448、0.014、0.109,P=0.540、0.503、0.906、0.742)。结论在四川地区儿童癫癎患者中超说明书应用新型抗癫癎药物的发生率较高,其中以托吡酯和左乙拉西坦尤为突出,但新型抗癫癎药物在一定范围内超说明书用药仍具有较好的安全性和耐受性。     

抗癫癎药物应用指南Ⅱ:新型抗癫癎药物的药力和耐受性:难治性癫癎的治疗美国神经病学学会治疗学和技术评定分委会和质量标准分委会及美国癫癎协会报告

目的对有关7种用以治疗儿童和成人部分性和全面性难治性癫癎的新型抗癫癎药物(AEDs):加巴喷丁(gabapentin, GBP)、拉莫三嗪(lamotrigine,LTG)、托吡酯(topiramate,TPM)、噻加宾(tiagabine,TGB)、奥卡西平(oxcarbazepine,OXC)、左乙拉西坦(levetiracetam,LEV)和唑尼沙胺(zonisamide,ZNS)的药力(efficacy)、耐受性和安全性进行评估。方法由23位成人神经病学家、小儿神经病学家、癫癎病学家和药理学家组成的专家组,依据从1987年到2002年9月Medline,Current Contents和Cochrane上发表的相关文献和2003年以前的指南提供的证据进行循证医学评估。结果所有新型抗癫癎药物都适用于成人难治性部分性癫癎的添加治疗,加巴喷丁对混合性癎性发作有效,加巴喷丁、拉莫三嗪、托吡酯和奥卡西平对儿童难治性部分性癫癎有效。有限的证据还表明,拉莫三嗪和托吡酯对成人和儿童特发性全面性发作和Lennox-Gastaut综合征的添加治疗也有效。结论抗癫癎药物的选择要考虑癫癎发作和/或癫癎综合征的类型、患者的年龄...     

托吡酯加用治疗难治性部分性癫Xian发作的临床研究

目的观察托吡酯加用治疗癫癎难治性部分性发作的疗效.方法32例难治性部分性发作或继发性全身性发作癫癎患者,病程1年以上,一直服用一种或两种基础抗癫癎药物每月仍有≥4次以上的发作.托吡酯采用加量法,加量期8周,目标剂量为200mg·d-1,观察12周后进入延长期.结果32例病人经过治疗后,发作100%消失者5例(15.62%),发作≤75%13例(40.62%),发作≤50%11例(34.37%),无改善2例(6.25%),因不良反应而中断1例(3.13%).结论托吡酯是一种非常有效的新型抗癫癎药物.     

抗癫(癎)药物应用指南Ⅱ:新型抗癫(癎)药物的药力和耐受性:难治性癫(癎)的治疗美国神经病学学会治疗学和技术评定分委会和质量标准分委会及美国癫(癎)协会报告

目的 对有关7种用以治疗儿童和成人部分性和全面性难治性癫(癎)的新型抗癫(癎)药物(AEDs):加巴喷丁(gabapentin,GBP)、拉莫三嗪(lamotrigine,LTG)、托吡酯(topiramate,TPM)、噻加宾(tiagabine,TGB)、奥卡西平(oxcarbazepine,OXC)、左乙拉西坦(1evetiracetam,LEV)和唑尼沙胺(zonisamide,ZNS)的药力(efficacy)、耐受性和安全性进行评估.方法 由23位成人神经病学家、小儿神经病学家、癫(癎)病学家和药理学家组成的专家组,依据从1987年到2002年9月Medline,Current Contents和Cochrane上发表的相关文献和2003年以前的指南提供的证据进行循证医学评估.结果 所有新型抗癫(癎)药物都适用于成人难治性部分性癫(癎)的添加治疗,加巴喷丁对混合性(癎)性发作有效,加巴喷丁、拉莫三嗪、托吡酯和奥卡西平对儿童难治性部分性癫(癎)有效.有限的证据还表明,拉莫三嗪和托吡酯对成人和儿童特发性全面性发作和Lennox-Gastaut综合征的添加治疗也有效.结论 抗癫(癎)药物的选择要考虑癫瘌发作和/或癫(癎)综合征的类型、患者的年龄、合用的药物、药物的耐受性、安全性和药力等因素.循证医学评估结果提供了难治性癫(癎)患者的抗癫(癎)药物应用指南,但尚需更为有力的证据用以鉴定其在癫(癎)型或综合征中疗效.     

托吡酯加用治疗难治性部分性癫(疒间)发作的临床研究

目的:观察托吡酯加用治疗癫癎难治性部分性发作的疗效。方法:３２例难治性部分性发作或继发性全身性发作癫癎患者,病程１年以上,一直服用一种或两种基础抗癫癎药物每月仍有≥４次以上的发作。托吡酯采用加量法,加量期８周,目标剂量为２００ｍｇ·ｄ－１,观察１２周后进入延长期。结果:３２例病人经过治疗后,发作１００%消失者５例(１５．６２%),发作≤７５%１３例(４０．６２%),发作≤５０%１１例(３４．３７%),无改善２例(６．２５%),因不良反应而中断１例(２．１３%)。结论:托吡酯是一种非常有效的新型抗癫癎药物。     

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、丙戊酸对癫癎病人胰岛素及瘦素水平的影响

目的研究服用托吡酯、丙戊酸的癫癎病人的体重变化是否与胰岛素和瘦素水平的变化有关.方法用放射免疫方法检测142例癫癎病人的空腹胰岛素和瘦素水平.结果①托吡酯组(55例)与对照组(35例)比托吡酯组空腹胰岛素水平低于对照组(P=0.025),尤其是女性病人(P=0.040);两组空腹瘦素水平的差异无显著性(P=0.420),但男性的空腹瘦素水平均低于女性(对照组P=0.001,托吡酯组P=0.022).②丙戊酸组(24例)与对照组(28例)比两组空腹胰岛素水平的差异无显著性(P=0.368),但丙戊酸组肥胖病人的空腹胰岛素水平高于非肥胖病人(P=0.032);丙戊酸组空腹瘦素水平高于对照组(P=0.017),尤其是肥胖病人(P=0.011);丙戊酸组肥胖病人的空腹瘦素水平高于非肥胖病人(P=0.037).结论托吡酯可显著降低非肥胖女性癫癎病人的空腹胰岛素水平,对瘦素水平无显著性影响.丙戊酸对癫癎病人空腹胰岛素水平无明显影响;可显著增加癫癎病人的空腹瘦素水平,尤其是肥胖病人.     

The effect of topiramate monotherapy on bone mineral density and markers of bone and mineral metabolism in premenopausal women with epilepsy

Purpose: To investigate the effect of topiramate on bone mass and metabolism in premenopausal women with epilepsy. Methods: Thirty‐six women on long‐term (at least 1 year) topiramate monotherapy were compared with 36 women taking carbamazepine, 32 women taking valproate, and 36 age‐ and sex‐matched controls. Subjects completed bone mineral density (BMD) studies. Serum was analyzed for indices of bone metabolism. Key Findings: BMD Z‐scores, and serum 25‐hydroxyvitamin D and 1alpha,25‐dihydroxyvitamin D₃ concentrations did not differ among the groups. Serum calcium concentrations were significantly lower in patients receiving topiramate than in those receiving valproate, and in patients receiving carbamazepine than in those receiving valproate and controls. Patients taking topiramate had lower levels of parathyroid hormone compared with controls and those taking carbamazepine or valproate. Patients receiving topiramate had higher levels of bone‐specific alkaline phosphatase and osteocalcin when compared with controls and higher levels of C‐terminal telopeptide of type 1 collagen when compared with those taking carbamazepine or valproate. Patients receiving carbamazepine had higher levels of bone‐specific alkaline phosphatase compared with controls and those receiving valproate. Serum bicarbonate concentrations were significantly lower in patients receiving topiramate than in the other groups. Significance: Our results demonstrate that use of topiramate is associated with lower parathyroid hormone and bicarbonate concentrations along with mild hypocalcemia and increased bone turnover, which suggests that topiramate may have long‐term effects on bone.     

Effects of topiramate on cognitive function

OBJECTIVE: To explore the impact of topiramate on tests of intellect and other cognitive processes. METHODS: This was a retrospective study. The neuropsychological test scores of 18 patients obtained before and after the introduction of treatment with topiramate (median dose 300 mg) were compared with changes in test performance of 18 patients who had undergone repeat neuropsychological assessments at the same time intervals. Complaints of cognitive decline precipitated referral for reassessment in five cases in the topiramate treated group. The groups were matched for age and intellectual level at the time of the first assessment. Patients were assessed using the WAIS-R, tests of verbal and non-verbal memory, language, and perceptual processing. A subgroup of patients underwent a brief reassessment after the withdrawal or substantial reduction of topiramate. RESULTS: Repeat assessments in those taking topiramate were associated with a significant deterioration in many domains, which were not seen in the comparison group. The greatest changes were for verbal IQ, verbal fluency, and verbal learning (p<0. 001). Improvements in verbal fluency (p<0.05), verbal learning (p<0. 01), and digit span (p<0.001) were recorded in those patients who had topiramate withdrawn or reduced. CONCLUSIONS: In our patient group topiramate had a negative impact on cognition which was consistent with subjective complaints of patients. Tests requiring verbal processing seemed especially sensitive to the drug. A decline in verbal intellect (VIQ), a measure which has been considered by some to be insensitive to antiepileptic drug effects, was particularly striking. Caution is warranted in the interpretation of the findings due to methodological limitations of the study design. Further investigation of mediating factors such as serum concentrations, comedication, and other potential risk factors, however, is needed to enable appropriate targeting of treatment with this effective antiepileptic agent.     

A comparison of topiramate and acetazolamide on seizure duration and paired-pulse inhibition in the dentate gyrus of the rat

Topiramate is a relatively new antiepileptic drug with several putative anticonvulsant mechanisms. Among them is the ability to inhibit carbonic anhydrase, a property in common with the anticonvulsant acetazolamide. This study examined the effects of topiramate and acetazolamide on the duration of epileptiform activity and on paired-pulse inhibition in the dentate gyrus in urethane anesthetized adult Sprague–Dawley rats. Neither topiramate nor acetazolamide altered excitability in the dentate gyrus, as measured with input–output curves or induction of long-term potentiation. Topiramate increased paired-pulse inhibition, whereas acetazolamide had no effect. Both drugs dose-dependently blocked the lengthening of the duration of epileptiform activity compared to vehicle controls. These results indicate that topiramate has an anticonvulsant-related effect (increase in paired-pulse inhibition), which may contribute to its antiepileptic effect, that is not dependent on its ability to inhibit carbonic anhydrase.     

长期应用托吡酯、丙戊酸钠对于血脂水平的影响

目的 观察长期应用托吡酯、丙戊酸钠单药治疗对癫痫患者血脂水平的影响。 方法 连续入组长期单药应用丙戊酸钠控制良好的癫痫患者28例、单药应用托吡酯控制良好的癫痫患者30例,并选取健康对照60例,观察各组间血脂代谢指标的差异。 结果 丙戊酸钠组血清脂蛋白（a）水平显著高于托吡酯组（P<0.001）及健康对照组（P=0.003）,而总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、甘油三酯水平较其他两组无明显差异。托吡酯组的总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、脂蛋白（a）、甘油三酯水平较对照组均未有显著差异。 结论 长期单药应用丙戊酸钠有可能增加癫痫患者脂蛋白（a）的水平,而长期单药应用托吡酯对于血脂水平影响并不明显。     

Bone mineral density in adult patients treated with various antiepileptic drugs

There is considerable evidence suggesting, that older antiepileptic drugs (AEDs) and some of the newer ones decrease bone mineral density (BMD). However, there is only limited and conflicting data concerning the effect of levetiracetam on BMD. In this cross-sectional study we analysed data from 168 adult consecutive outpatients treated with AEDs for more than 2 years, and who underwent measurement of the BMD. We compared the incidence of decreased BMD among the patients treated with 6 different AEDs: carbamazepine (CBZ), oxcarbazepine (OXC), valproic acid (VPA), lamotrigine (LTG), topiramate (TPM) and levetiracetam (LEV). Among the patients on monotherapy, reduced BMD was present significantly most often in patients treated with LEV and those treated with OXC. In the group of patients on polytherapy there was no significant difference in the incidence of low BMD among patients treated with various AEDs. Our data suggest that patients on long-term treatment with LEV have a higher risk for affection of bone density.     

Open-label adjunctive topiramate in the treatment of bipolar disorders.

BACKGROUND: To preliminarily explore the spectrum of effectiveness and tolerability of the new antiepileptic drug topiramate in bipolar disorder, we evaluated the response of 56 bipolar outpatients in the Stanley Foundation Bipolar Outcome Network (SFBN) who had been treated with adjunctive topiramate in an open-label, naturalistic fashion. METHODS: In this case series, response to topiramate was assessed every 2 weeks for the first 3 months according to standard ratings in the SFBN, and monthly thereafter while patients remained on topiramate. Patients' weights, body mass indices (BMIs), and side effects were also assessed. RESULTS: Of the 54 patients who completed at least 2 weeks of open-label, add-on topiramate treatment, 30 had manic, mixed, or cycling symptoms, 11 had depressed symptoms, and 13 were relatively euthymic at the time topiramate was begun. Patients who had been initially treated for manic symptoms displayed significant reductions in standard ratings scores after 4 weeks, after 10 weeks, and at the last evaluation. Those patients who were initially depressed or treated while euthymic showed no significant changes. Patients as a group displayed significant decreases in weight and BMI from topiramate initiation to week 4, to week 10, and to the last evaluation. The most common adverse side effects were neurologic and gastrointestinal. CONCLUSIONS: These preliminary open observations of adjunctive topiramate treatment suggest that it may have antimanic or anticycling effects in some patients with bipolar disorder, and may be associated with appetite suppression and weight loss that is often viewed as beneficial by the patient and clinician. Controlled studies of topiramate's acute and long-term efficacy and side effects in bipolar disorder appear warranted.     

Clinical experience with topiramate dosing and serum levels in children 12 years or under with epilepsy.

Only a limited topiramate dosing range (5-9 mg/kg/day) is approved by the U.S. Food and Drug Administration (FDA). We reviewed our topiramate dosing (mg/kg/d) and corresponding serum levels (microg/mL) (n = 77) in 41 children who were treated to clinical response or tolerability. The patients were divided into older (6-12 years [n = 21]) and younger (< or = 5 years [n = 20]) groups. Topiramate was given as monotherapy (n = 9), with an enzyme-inducing antiepileptic drug (n = 16) (phebarbital, phenytoin, or carbamazepine), or as polytherapy (n =17) (another antiepileptic drug). In the older children, there was a good dosage to serum level correspondence. However, younger children on topiramate monotherapy or cotherapy with an enzyme-inducing antiepileptic drug had relatively lower serum levels, but the serum level was increased if they were on polytherapy without an enzyme-inducing drug. This study supports a wider dosing range (7-22 mg/kg/day) of topiramate and dosage escalation beyond the approved range. Serum levels are useful in guiding topiramate dosing, especially in young children.     

Prospective study of first-choice topiramate therapy in newly diagnosed infantile spasms

OBJECTIVE: This was a prospective open study to establish the efficacy, tolerability, and problems associated with the use of topiramate as first-choice drug in children with infantile spasms. METHODS: Open-label follow-up study, ranging from 24 to 36 months, of the cases of 54 patients with infantile spasms treated initially with topiramate as first-choice drug. RESULTS: Thirty-one patients (57.4%) were seizure free for more than 24 months; 9 patients were treated with topiramate alone and 22 patients with topiramate plus nitrazepam and/or valproate. In 44 cases (81.4%), the reduction of seizure frequency from baseline was greater than 30%, whereas in 10 cases (18.6%), there was poor or no response. The average dosage applied was 5.2 mg/kg per day (maximum dosage, 26 mg/kg per day; minimum dosage, 1.56 mg/kg per day). Adverse events occurred in 14 patients (26%). They included poor appetite leading to anorexia, absence of sweating, and sleeplessness. CONCLUSIONS: Topiramate proves to be an effective and safe first-choice drug not only as adjunctive but also as monotherapy of infantile spasms in children younger than 2 years.     

Ultrastructure of the blood-brain barrier of the gyrus hippocampal cortex in an experimental model of febrile seizures and with the use of a new generation antiepileptic drug--topiramate

The ultrastructure of the blood-brain barrier (BBB) of the gyrus hippocampal cortex in an experimental model of febrile seizures in rats and the effect of a new generation antiepileptic drug, topiramate, on the morphological status of this barrier were investigated. Advanced changes indicating a substantial increase in BBB permeability were observed in the animals with induced febrile seizures (FS), with approximately 2/3 of capillaries and perivascular astroglial processes being affected. Almost total occlusion of the capillary lumen was frequently seen, caused by damaged endothelial lining and by external pressure from markedly swollen perivascular astrocytic processes. Mitochondrial changes predominated among the abnormalities found in endoplasmic organelles of endothelial cells. Lesions in the BBB coexisted with damage to pyramidal neurons, mainly with features of aponecrosis ("dark neurons"). The study on topiramate seems to demonstrate its protective action on the BBB components of the ammonal cortex in the group receiving the drug as prevention, i.e. against febrile seizures. It was found to prevent marked BBB damage in over half of the capillaries. However, the application of topiramate directly after FS induction had no distinct beneficial effect on the structural BBB components.     

托吡酯对戊四氮诱导的癫痫大鼠海马神经元bc1-2、bax基因表达的调控

目的探讨托吡酯对戊四氮癫癎模型大鼠大脑的神经保护作用及可能的机制.方法成年雄性Wistar大鼠54只,随机分为正常对照组(6只);戊四氮组(24只);托吡酯预处理组(24只).癫癎发作后分别于6、12、48 h后处死取脑,进行HE染色和bcl-2、bax免疫组化染色.结果癎性发作后海马HE染色显示;戊四氮组CA1、CA3和DC区神经元变性及坏死较托吡酯预处理组显著.免疫组化染色显示托吡酯预处理组bcl-2 12和48 h在CA1、CA3和DC的表达强于戊四氮组,而bax在上述时段的表达则较戊四氮组弱.结论托吡酯具有一定的神经保护作用,推测可能与其增强大鼠海马神经元bcl-2基因表达,降低bax基因表达有关.