托吡酯治疗小儿癫痫104例临床研究

目的观察托吡酯添加或单一治疗小儿癫痫,特别是对癫痫部分性发作及继发性全身性发作、Lennox-Gastaut综合征(LGS)和West综合征的疗效和不良反应.方法对癫痫部分性发作或继发性全身性发作32例、LGS47例及West综合征25例病例中已应用传统抗癫痫药物治疗,但控制不理想的病例添加托吡酯治疗,而新诊断的病例应用托吡酯单一治疗,并进行开放性自身对照研究.治疗剂量一般由0.5～1mg*kg-1*d-1开始,每周增加0.5～1mg*kg-1*d-1.部分性发作及继发性全身性发作组平均剂量为(6.2±2.2)mg*kg-1*d-1;LGS组平均剂量为(7.4±3.5)mg*kg-1*d-1;West综合征组<6个月的患儿由12.5mg/d开始,≥6个月的患儿由25mg/d开始,每2～3d增加12.5～25mg/d,平均剂量为(8.1±4.1)mg*kg-1*d-1.结果(1)托吡酯治疗小儿癫痫104例,疗程均在6个月以上,总疗效为发作减少≥50%的患者80例(76.9%),发作停止42例(40.4%);(2)添加托吡酯治疗对卡马西平和丙戊酸钠的血浓度没有明显影响;(3)不良反应嗜睡18例(17.3%),反应淡漠7例(6.7%),思维缓慢3例(2.8%),纳差25例(24.0%),类暑热症8例(7.7%),体重下降12例(11.5%).结论托吡酯治疗部分性发作及继发性全身性发作、LGS和West综合征安全、有效,不良反应轻.     

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     

托吡酯添加治疗儿童难治性癫痫的开放性自身对照临床研究

目的 评价托吡酯添加治疗儿童难治性癫痫的疗效及安全性。方法 应用托吡酯对44例难治性癫痫患儿进行开放性自身对照临床研究,其中单纯部分性发作患儿14例次,复杂部分性发作患儿23例次,部分性发作继发全面性发作患儿16例次。于服药后6个月评价托吡酯的疗效和安全性,以及临床疗效与药物剂量关系。结果 托吡酯治疗总有效率为58.14％(25/43例次),以发作次数减少≥50％为界,单纯部分性发作患儿治疗总有效率为57.14％(8/14例次),复杂部分性发作63.64％(14/22例次),部分性发作继发全面性发作68.75％(11/16例次)。6例Lennox-Gastaut综合征患儿中仅2例有效。托吡酯治疗后的不良反应发生率为46.51％(20/43例次),主要为厌食(37.21％)和体重下降(27.91％)。托吡酯所致不良反应较轻微,部分患儿继续接受治疗可自行缓解。结论 尽管在服用托吡酯期间须行不良反应监测,但其作为添加剂治疗儿童难治性癫痫安全有效,且对患儿血尿常规、肝肾功能均无明显影响。     

托吡酯添加治疗儿童难治性癫痫的开放性自身对照临床研究

目的：评价托吡酯添加治疗儿童难治性癫痫的疗效及安全性。方法：应用托吡酯对44例难治性癫痫患儿进行开放性自身对照临床研究，其中单纯部分性发作患儿14例次，复杂部分性发作患儿23例次，部分性发作继发全面性发作患儿16例次。于服药后6个月评价托吡酯的疗效和安全性，以及临床疗效与药物剂量关系。结果：托吡酯治疗总有效率为58.14%（25/43例次）。以发作次数减少≥50%为界，单纯部分性发作患儿治疗总有效率为57.14%(8/14例次），复杂部分性发作63.64%(14/22你次），部分性发作继发全面性发作68.75%(11/16例次）。6例Lennox-Gastaut综合征患儿中仅2例有效。托吡酯治疗后的不良反应发生率为46.51%(20/43例次），主要为厌食（37.21%）和体重下降（27.91%）。托吡酯所致不良反应较轻微，部分患儿继续接受治疗可行自行缓解。结论：尽管在服务托吡酯期间须行不良反应监测，但其作为添加剂治疗儿童难治性癫痫安全有效，且对患儿血尿常规、肝肾功能均无明显影响。     

托吡酯多中心开放性添加治疗成人难治性癫痫部分性发作的临床观察

目的 评价托吡酯（topiramate,TPM)对难治性癫痫部分性发作的疗效及耐受性。方法 采用多中心开放性试验的方法对全国52家医院的431例病人进行托吡酯添加治疗。本研究包括8周基础期、8周加量期及12周稳定观察期。在8周基础期,病人虽用1－3种抗癫痫药治疗,但仍有每月至少4次的发作;在加量期,TPM开始量为25mg/d,持续1周,以后每周增加25mg/d,直到目标剂量达到200mg/d,维持此剂量12周为稳定观察期。结果 431例病人参加此项研究,其中癫痫发作频率减少≥50％者为326例（75．6％）,≥75％者为257例（59．6％）,减少100％者为91例（21．1％）。18例（4．2％）发作频率增加≥25％。就发作类型而言,癫痫发作频率减少 ≥50％者中,单纯部分性发作（SPS）为83．4％,复杂部分性发作（CPS）为74．4％,部分发作继发全身性发作为82．1％。未出现严重的副作用。结论 TPM对癫痫部分性发作伴有或不伴有继发全身性发作者有效,口服安全。     

丙戊酸钠、托吡酯诱导癫癎患者体重及血清瘦素水平的变化

目的观察丙戊酸钠、托吡酯诱导癫癎患者体重及血清瘦素水平的变化。方法40例女性癫癎患者按年龄、体重指数分层匹配进入丙戊酸钠、托吡酯治疗组,每组20例。在治疗前及治疗3个月后分别测定身高、体重及早晨空腹血清瘦素水平。结果9例经丙戊酸钠治疗者体重增加(≥4kg),血清瘦素水平[(13.2±3.6)ng/ml]高于治疗前[(7.4±3.0)ng/ml,P<0.01];6例托吡酯治疗者体重减轻(≥4kg),血清瘦素水平[(3.7±1.8)ng/ml]低于治疗前[(7.4±2.6)ng/ml,P<0·01]。结论经丙戊酸钠治疗体重增加者出现瘦素抵抗,经托吡酯治疗体重减轻者血清瘦素水平降低。     

托吡酯快速加量法治疗小儿癫痫临床观察

目的　观察托吡酯快速加量法治疗小儿癫痫时的疗效及不良反应。方法　对 30例符合1981年国际抗癫痫联盟的癫痫临床发作的分类与 1989年癫痫与癫痫综合征分类中的各型癫痫患儿在住院期间应用快速加量法给予托吡酯进行治疗。治疗剂量由小剂量开始 ,平均 1.0mg (kg·天 ) ,每2～ 3天增加 1.0mg kg ,平均 13天达目标剂量 [平均 4 .5mg (kg·天 ) ]至发作控制 ,同时观察疗效及副作用。结果　 (1)托吡酯快速加量法治疗住院小儿癫痫 30例平均加药时间 13天达平均剂量 4 .5mg (kg·天 ) ,其总疗效为发作完全控制 14例 (4 6 .7% ) ,发作减少≥ 75 % 9例 (30 % ) ,发作减少≥ 5 0 % 5例 (6 .7% )。(2 )发生不良反应总例数 8例 (2 6 .7% )。表现为食欲降低 5例 (16 .7% ) ;低热为 3例 (10 % ) ;嗜睡、困倦 2例 (6 .7% ) ;多动、兴奋 2例 (6 .7% ) ;部分有交叉。结论　应用托吡酯治疗住院的癫痫儿童时可以快速加量 ,可以很快达到有效控制 ,安全、不良反应小     

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。     

Topiramate: an experience in children with partial epilepsy

Topiramate (TPM) is a new drug currently used in Brazil. We verified the clinical responses to TPM in children under 15 years-old. We started with 12.5 mg/day (1-7 mg/kg/day) and the doses increased 12,5 mg each week. Eleven children were studied, 9 females and 2 males, from 3 to 14 years-old with partial epilepsy associated to different etiological factors. Only one patient had an intense abdominal pain. The patients had weekly or daily seizures and after began TPM 1 patient stayed free from seizures, 5 improved more than 75% in frequency, 1 patient improved more than 50% and 3 had no control. A good control of seizures was achieved with a low dose of TPM as monotherapy and add-on therapy with carbamazepine even in severe cases.     

Topiramate monotherapy in newly diagnosed epilepsy in children and adolescents

A double-blind, dose-controlled study evaluated topiramate as monotherapy in 470 patients with newly diagnosed (< or = 3 months) epilepsy or epilepsy relapse in the absence of therapy. In addition to having at least 2 lifetime-unprovoked seizures, patients had 1 or 2 partial-onset seizures or generalized-onset tonic-clonic seizures during a 3-month retrospective baseline. The trial included a large cohort (N = 151, 32%) of children and adolescents 6 to 15 years of age. Eligible patients were randomized to treatment groups in which topiramate was titrated to target maintenance dosages of either 400 mg/day (n = 77) or 50 mg/day (n = 74). Patients were followed for at least 6 months. Based on Kaplan-Meier analyses, the primary efficacy endpoint of time to first seizure favored the higher topiramate dose in both the overall population and the cohort of children/adolescents. The probability that children/adolescents remaining in the study were seizure free at 6 months was 78% in the 50-mg target dose group and 90% with the higher dose. At 12 months, the probability of being seizure free was 62% and 85%, respectively. The incidence of treatment-limiting adverse events was 4% in the 50-mg target dose group and 14% in the group assigned to 400 mg as a target dose. The most common adverse events, excluding typical childhood illnesses, were headache, appetite decrease, weight loss, somnolence, dizziness, concentration/attention difficulty, and paresthesia. As shown in this subset analysis, topiramate is effective and well tolerated as monotherapy in children and adolescents.     

Topiramate effects on plasma serotonin levels in children with epilepsy

Topiramate (TPM) is a new, effective and safe antiepileptic drug. TPM is also effective in treating a wide spectrum of conditions such as eating disorders and related anomalies, bulimia nervosa and other conditions in which serotonin (5-hydroxytryptamine, 5-HT) is involved pathogenetically. Plasma serotonin mainly derives from blood platelets, which represent a valid model of serotoninergic neurons. We measured plasma 5-HT levels in 12 children affected by epilepsy who underwent TPM therapy. Inclusion criteria were (i) age range 2-12 years, (ii) weight greater than 12 kg, (iii) no more than one antiepileptic drug used when TPM therapy was instituted, and (iv) a minimum study period of 3 months. After a mean period of 3 months of TPM treatment, a significant increase in mean plasma serotonin levels was observed with respect to the basal levels and those of a control group. There were no significant correlations between the changes in serotonin concentrations and the antiepileptic efficacy or doses of TPM used. TPM may influence serotonin metabolism in children affected by epilepsy. Further studies are needed to establish whether these serotonin plasma changes represent an epiphenomenon or indicate direct effects of TPM on the serotoninergic system.     

Topiramate for intractable childhood epilepsy.

To better define the efficacy and tolerability of the new anticonvulsant topiramate in pediatric patients, the clinical courses of 49 children with intractable seizures were monitored during topiramate therapy. The 80% of children who had complex partial seizures experienced better seizure control with topiramate than the 20% who had generalized seizures. Efficacy was greatest with doses between 2.5 and 7.5 mg/kg/day. More than half the children on topiramate experienced adverse effects which could interfere with learning at school, but 20% demonstrated increased alertness or improved behavior. Topiramate is effective and may be considered as part of the treatment pathway for complex partial seizures in children, although careful monitoring of cognitive function is required.     

Topiramate in frontal lobe epilepsy

BACKGROUND: Frontal lobe epilepsy (FLE) is a type of epilepsy that is difficult to treat and there are few studies about the use of topiramate (TPM). AIM OF THE STUDY: To evaluate the efficacy and tolerability of TPM monotherapy in FLE. METHODS: The study group consisted of 55 (33 male; 22 female) patients. TPM was administered as a first drug (n = 16) or converted after previous treatment (n = 39). All patients were followed every 3 months for at least 1 year. The patients were subdivided into two groups: 'newly diagnosed' patients and 'difficult-to-treat' patients. RESULTS: Overall, all patients completed the 1-year study. At the end of follow-up, 10 patients showed disappearance of seizures and 33 patients showed improvement in seizure frequency. In particular, among the newly diagnosed patients 6/16 patients showed complete cessation of seizures and 5/16 patients showed very good response; in the other group, 4/39 patients showed complete cessation and 4/39 patients showed a very good response. No patients of both groups had worsening of seizures. No treatment-limiting adverse events associated with TPM were reported. CONCLUSIONS: TPM is effective in newly diagnosed patients with FLE; TPM can be considered for the treatment of FLE.     

Topiramate: efficacy and tolerability in children according to epilepsy syndromes

To evaluate the efficacy and tolerability of topiramate (TPM) as add-on therapy in children less than 12 years of age with refractory epilepsy, according to epilepsy syndromes, we conducted an open, prospective, pragmatic and multicenter study in France. Efficacy was assessed, especially according to epilepsy syndromes, as well as tolerability. We included 207 children (41 of whom were less than 4 years of age). TPM was effective (responders with >50% decrease in seizure frequency) in 50% of 128 patients with partial epilepsy, and in 44% of 79 patients with generalized epilepsy. In case of generalized epilepsy, responders more frequently had generalized symptomatic epilepsy, severe myoclonic epilepsy and myoclono-astatic epilepsy, whereas response rate was mild in both infantile spasms and Lennox-Gastaut syndrome (LGS). Improvement was well maintained in all patients during the treatment period (median 5.6 months). Seizure frequency/severity increased (worsening) in 13% of patients with partial epilepsy and 17% with generalized epilepsy (particularly in those with infantile spasms), and resulted in withdrawal of TPM for 8%. The most frequently reported adverse events were moderate neurobehavioral and gastrointestinal disorders. Adverse events led to withdrawal of TPM from 13.5% of patients. Children less than 4 years of age had particularly good tolerability. Results confirm that TPM is effective and well tolerated in children under 12 years of age in a broad range of epilepsy syndromes, including refractory partial epilepsy, and symptomatic and myoclonic generalized epilepsy. Use of TPM should be considered in children under 4 years of age, and slow and progressive titration is important.     

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。