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.     

托吡酯治疗各型癫癎的疗效与安全性观察

目的 观察托吡酯（TPM)对成人和儿童各型癫痫的临床效果与安全性。方法 用开放性试验方法对100例癫痫患者进行了添加、添加转单药以及首诊单药的托吡酯治疗；以加用托吡酯前3个月的平均月发作频率为基准，与用托吡酯进入稳定期后的月平均发作频率进行比较，按常规计算发作减少百分比的中位值和有效率百分比。结果 托吡酯无论在添加治疗、添加转单药以及单药治疗上均有明显疗效。添加组70％患者的发作减少，添加转单药组发作减少者占78％，而单药组发作减少者占86％。其抗癫痫谱广，可用于单纯部分性发作伴或不伴全面性发作、复杂部分性发作伴或不伴全面性发作、婴儿痉挛以及Lennox—Gastaut综合征。托吡酯的不良反应以中枢神经系统最常见，但导致治疗中断的不良反应少见，本组仅3例因不良反应而中断治疗。结论 托吡酯是广谱抗癫痫药，疗效肯定，无耐药性，无严重不良反应，即既可用于添加治疗也可作为单药治疗。     

应用托吡酯治疗小儿难治性癫癎的临床研究

目的观察托吡酯治疗小儿难治性癫癎疗效、用药方法及副反应.方法采用开放性方法对31例小儿难治性癫癎患者进行单用或加用托吡酯治疗.观察其疗效及副反应.结果托吡酯治疗小儿难治性癫癎总有效率67.7%.38.7%患儿停止发作,对部分性发作疗效较好.其他类型发作亦有一定疗效.平均有效剂量为(4.0±1.8)mg@kg-1@d.副反应主要为体重减轻(16例,56.6%),神经系统症状,少汗或无汗,皮疹等,结论托吡酯对小儿难治性癫癎有良好疗效.     

托吡酯单药治疗癫(癎)疗效和脑电图观察

目的观察托吡酯（TPM）单药治疗癫癇的疗效及脑电图变化。方法49例临床及脑电图检查确诊为癫癇的病人，观察其单服TPM1个月、3个月及半年的疗效及脑电图。结果临床疗效服药半年33例控制发作。脑电图半年仅5例异常。结论TPM单药治疗癫癇疗效明显，脑电图改善快，脑电图可作为观察疗效、指导用药、调整剂量的有效方法。     

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.     

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。     

托吡酯单药治疗小儿癫癎45例疗效观察

目的 托吡酯(TPM)单药治疗儿科癫癎的疗效及安全性。方法 45例患儿入组,TPM目标维持剂量为2.5mg/(kg·d)。基础期1个月,记录癫癎发作次数;加药期2-3个月;稳定期3个月,坚持服用维持剂量,记录发作次数及不良反应。结果 45例患儿癫癎总有效率为82.2％,其中显效71.1％,无效17.7％,治疗各种类型癫癎有效率均>75％,不良反应率58％。多数短暂而轻微。结论 TPM单治小儿癫癎疗效明显,且较安全。     

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。     

托吡酯单药治疗癫疗效和脑电图观察

目的观察托吡酯(TPM)单药治疗癫的疗效及脑电图变化。方法49例临床及脑电图检查确诊为癫的病人,观察其单服TPM1个月、3个月及半年的疗效及脑电图。结果临床疗效服药半年33例控制发作,脑电图半年仅5例异常。结论TPM单药治疗癫疗效明显,脑电图改善快,脑电图可作为观察疗效、指导用药、调整剂量的有效方法。     

妥泰治疗难治性癫痫的临床疗效观察

目的 :观察妥泰 (TPM)单药对难治性癫痫 (RE)的临床疗效和安全性。方法 :RE4 1例 ,添加TPM治疗后逐渐撤去原服用的抗癫痫药物 ,而用TPM单药治疗。以添加TPM前 12周平均每 4周发作频率为基线 ,与评价前12周平均每 4周发作频率进行个体自身比较。按常规计算完全控制率和有效率。并进行临床观察和实验室检查。结果 :完全控制率 34 1% ,有效率 6 5 9%。不良反应 2 5例次 ,但绝大部分轻微 ,可自行消失。结论 :TPM对RE疗效显著 ,安全性好     

Daytime sleepiness in epilepsy patients receiving topiramate monotherapy

Summary: Purpose: Limited research has focused to date on objective neurophysiological evaluation of daytime sleepiness in patients treated with newer antiepileptic drugs (AEDs), especially when used as monotherapy. This study was aimed at assessing occurrence of daytime sleepiness in newly diagnosed, drug‐naïve patients with partial epilepsy receiving initial topiramate (TPM) monotherapy. Methods: Daytime vigilance was assessed in 14 consecutive, newly diagnosed and never medicated adult patients with focal epilepsy, receiving monotherapy with TPM. At baseline and 2 months after slowly titrated therapy with TPM, 200 mg/day, patients underwent the Multiple Sleep Latency Test (MSLT), visual simple and choice reaction times (VRT), and self‐rated their own degree of sleepiness with the Epworth Sleepiness Scale. A group of 14 age‐ and gender‐matched healthy volunteers served as controls. Results: At baseline, mean daytime sleep latencies on the MSLT were comparable in patients and in controls. Two months after TPM monotherapy, MSLT scores did not significantly change in patients as compared with pretreatment values. Accordingly, subjective daytime sleepiness and VRTs, which were comparable in controls and in untreated patients at baseline, did not change in patients after TPM monotherapy. Conclusions: Study results suggest that an initial short‐course monotherapy with TPM, 200 mg/day, does not impair daytime vigilance in newly diagnosed adult patients with partial seizures.     

Cognitive effects of low-dose topiramate monotherapy in epilepsy patients: A 1-year follow-up

The present study was conducted to evaluate the long-term effects of low-dose topiramate (TPM) monotherapy on the cognitive function of epilepsy patients. Forty-seven epilepsy patients received TPM, with target doses of 50, 75, and 100 mg/day. Cognitive tests were performed twice, at baseline and 1 year after starting medication. Thirty-six patients completed the follow-up neuropsychological tests. After a year of treatment, 16 patients (44%) complained of cognitive problems. Although it improved seizure frequency and EEG abnormalities, TPM had significantly negative effects on the digit span and verbal fluency tests. These cognitive effects were dose-related and significantly improved after withdrawal from TPM and substitution with older antiepileptic drugs. In conclusion, even at a low dose, TPM has long-term, negative effects on working memory and verbal fluency.     

Long-term efficacy and tolerability of topiramate as add-on therapy in refractory partial epilepsy: An observational study

Purpose:   To evaluate the long-term efficacy and tolerability of topiramate (TPM) as add-on therapy in patients with refractory partial epilepsy.
Methods:   This is a retrospective, single-center, long-term observational study. Patients fulfilling the criteria of medical intractability proposed by Berg et al. were entered into the study if they were newly prescribed TPM as add-on therapy between January 2000 and June 2002. The usual starting dosage of TPM was 50 mg/day and optimal-dose adjustments were made according to individual clinical responses. Efficacy and tolerability were analyzed every year during 5-year follow-up in the "intention-to-treat (ITT) population." Retention rate was estimated by Kaplan-Meyer analysis.
Results:   A total of 125 patients were included in the study and 107 patients (85.6%) were followed for 5 years. Retention rate was 87.2% at 1 year and 64% at 5 years. At the end of 5 years, the median seizure frequency reduction rate was 69.0% and responder rate was 43.2% in the ITT population. Cumulative seizure-free rate (SFR) was 30.4% and the terminal 1-year SFR was 12.8% in the ITT population (20.0% in completers) at 5-year follow-up. Adverse events (AEs) occurred in 39.2% of patients, including significant AEs leading to antiepileptic drug (AED) withdrawal in 14.4%. The most common AEs were anorexia (16.0%), weight loss (10.4%), and gastrointestinal symptoms (8.8%). Concomitant AEDs were reduced in 25.0% of the completers.
Discussion:   Low-dose and slow-dose escalation of TPM in add-on therapy for patients with refractory partial epilepsy is effective and well tolerated in long-term, individualized clinical practice.     

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。     

托吡酯对慢性癫痫幼鼠神经元保护作用的实验研究

目的 研究托吡酯(TPM)单药对慢性癫痫幼鼠损伤神经元的影响.方法 将3～4周龄雄性Wistar大鼠72只采用随机数字表法分为6组,每组各12只,A组:阴性对照组;B组:阳性对照组;C组:TPM低剂量组(20 mg/kg);D组:TPM中等剂量组(40 mg/kg);E组:TPM高剂量组(80 mg/kg);F组:合药组(TPM 40 mg/kg+丙戊酸钠200 mg/kg),其中B～F组为慢性癫痫组,于给药前腹腔注射戊四氮.连续用药2个月,观察幼鼠体重、行为学表现、血清神经元特异性烯醇化酶(NSE)及病理改变.结果 (1)E组对幼鼠体重的影响比C组、F组显著.(2)D组、E组戊四氮诱发痫性发作的时间延长,痫性发作的程度减轻.(3)TPM各剂量组NSE水平显著低于B组,F组与TPM单药组无差异.(4)E组海马组织神经元的退行性变和胶质细胞的增生程度减轻明显.结论 TPM可减轻幼鼠痫性发作后的神经损伤程度,且存在剂量效应,但与丙戊酸钠联合可削弱其神经保护作用.     

Efficacy of topiramate in children with refractory status epilepticus

PURPOSE: Status epilepticus (SE) is a life-threatening medical condition associated with significant morbidity and mortality that requires urgent medical intervention. Although several agents are available to treat SE, they occasionally fail to abort seizure activity. Topiramate (TPM) was anecdotally reported to be effective in adult patients with refractory SE. In this study, we evaluated the efficacy of TPM administered to children with this condition. METHODS: We retrospectively reviewed the pediatric SE database at the University of Michigan Medical Center and identified three children with refractory SE who were treated with TPM. Those children failed to respond to treatment with benzodiazepines, phenytoin, phenobarbital, midazolam, or pentobarbital. Additional treatment with TPM was administered by nasogastric tube. All patients were continuously monitored by 21-channel digital EEG machines, and the diagnosis of SE was made by a board-certified neurophysiologist. RESULTS: The ages of the three children were 4.5 months, 34 months, and 11 years. TPM was initiated at 2 mg/kg/day in two children and at 3 mg/kg/day in the third. The status was terminated in all three children within 24 h of maintenance therapy with TPM at 5-6 mg/kg/day. CONCLUSIONS: These results support the potential efficacy of TPM for children with refractory SE. Larger prospective series are needed to confirm those results.     

托吡酯与卡马西平治疗脑梗死后继发癫（癎）患者的疗效比较

目的 比较托吡酯与卡马西平治疗脑梗死后继发癫（癎）的临床疗效.方法 选取2011-05-2013-05我院收治的72例脑梗死后继发癫（癎）患者,采用随机对照方法分为观察组和对照组各36例.对照组在常规治疗基础上应用卡马西平,观察组在常规治疗基础上应用托吡酯,比较2组临床疗效、癫（癎）发作次数及不良反应.结果 观察组总有效率91.7%,对照组为80.6%,观察组总有效率显著高于对照组,差异有统计学意义（P〈0.05）;观察组3个月和6个月内癫（癎）发作次数均显著少于对照组,差异有统计学意义（P〈0.05）.结论 托吡酯治疗脑梗死后继发癫（癎）的临床疗效明显优于卡马西平,可有效降低癫（癎）的发作次数,且不良反应少,值得临床应用和推广.     

Efficacy and safety of topiramate in refractory epilepsy: a long-term prospective trial

The effects of topiramate in 15 patients with drug refractory partial epilepsy or Lennox-Gastaut syndrome were assessed in an open, add-on prospective study. After a follow-up of 14–21 months, six patients are still on topiramate (mean dosage 583 mg/day, range 400–800 mg/day), and nine have discontinued treatment because of adverse events (n=6), inefficacy (n=2) or poor compliance (n=1). Nine patients (69%) continued to have a 50% reduction in seizure frequency during the last two months of treatment, and one has been seizure-free for the last 19 months. The most common adverse events were somnolence, weight loss, mental slowing, fatigue, ataxia and irritability. Most of these events were reversible, but withdrawal of treatment was required in six cases as a result of ataxia (two patients), somnolence, metabolic acidosis, irritability or psychotic symptoms (one patient each). It is concluded that topiramate is a valuable agent for the long-term management of refractory epilepsy.

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Sommario Gli effetti di topiramato utilizzato in aggiunta alla terapia preesistente sono stati valutati nell'ambito di uno studio prospettico in aperto in 15 pazienti farmacoresistenti affetti da epilessia parziale o sindrome Lennox-Gastaut. Dopo un follow-up di 14–21 mesi, 6 pazienti sono tuttora in trattamento (posologia media di topiramato 583 mg/die, range 400–800 mg/die), mentre 9 hanno sospeso il farmaco a causa di eventi avversi (n=6), inefficacia (n=2) o scarsa compliance (n=1). Nove pazienti (69%) continuavano a presentare una riduzione di almeno il 50% della frequenza delle crisi durante gli ultimi 2 mesi di trattamento e un paziente è libero da crisi da 19 mesi. Gli eventi avversi più frequenti erano costituiti da sonnolenza, calo ponderale, rallentamento mentale, astenia, atassia e irritabilità. La maggior parte di questi eventi è risultata reversibile, ma in 6 pazienti si è resa necessaria la sospensione del trattamento a causa di atassia (2 casi), sonnolenza, acidosi metabolica, irritabilità e sintomi psicotici (1 caso ciascuno). Sulla base di questi dati, il topiramato può essere ritenuto un utile presidio nel trattamento a lungo termine dell'epilessia farmacoresistente.