左乙拉西坦单药治疗80例成人癫癎的疗效及安全性

目的：评价左乙拉西坦单药治疗各种类型成人癫癎的疗效和安全性.方法：80例各类型新诊断的成人癫癎患者,口服左乙拉西坦治疗,随访1年,观察治疗后患者癫癎发作次数变化及不良反应发生率.结果：左乙拉西坦单药治疗成人癫癎的总有效率为75.0%;对部分性发作可能更为有效,有效率为77.08 %;不良反应发生率为16.3%.因疗效不佳退出为18.75%.结论：在单药治疗成人癫癎中,左乙拉西坦是一种安全有效的抗癫药物,且对部分性和全面性癫癎发作均有效.     

左乙拉西坦单药治疗脑梗死后迟发性癫癎的临床观察

目的:观察左乙拉西坦对老年脑梗死后迟发性癫癎的疗效和安全性。方法:左乙拉西坦单药治疗新诊断的老年脑梗死后迟发性癫癎18例,起始剂量250mg,每日2次。根据疗效调整剂量,每日最大量不超过3000mg。观察癫癎发作的频率、类型及不良反应。结果:18例迟发性癫患者应用左乙拉西坦500～1500mg·d-1后有16例(88.9%)未再有癫癎发作。3例(16.7%)有嗜睡,2例(11.1%)有头昏表现,不良反应总发生率为27.8%(5/18例)。上述不良反应均未经特殊处理,在l～2个月自行消失,无一例因不良反应退出治疗。结论:左乙拉西坦是治疗老年缺血性脑卒中后迟发性癫安全、有效,而且耐受性良好的药物。     

左乙拉西坦添加治疗儿童难治性部分性癫痫疗效的Meta分析

目的系统评价左乙拉西坦添加治疗儿童难治性部分性癫痫的疗效和耐受性。方法计算机检索1998年1月-2017年1月Cochrane图书馆、PubMed、EMbase、中国知网中国期刊全文数据库和万方及中国生物医学文献数据库,并手工检索相关杂志,RevMan 5.3统计软件进行Meta分析。结果根据Cochrane 5.0.2版随机对照临床试验质量评价标准,纳入4项随机对照临床试验共498例受试者(左乙拉西坦组268例、安慰剂对照组230例)。Meta分析结果显示,左乙拉西坦组部分性癫痫发作频率减少≥50%的病例数高于对照组[OR=2.940,95%CI(1.99,4.34),P0.000 01];完全不发作病例明显高于对照组[OR=5.310,95%CI(2.49,11.32),P0.000 01]。左乙拉西坦组失访率与安慰剂对照组之间差异无统计学意义[OR=0.760,95%CI(0.32,1.82),P=0.54]。药物不良反应中嗜睡[OR=2.57,95%CI(1.36,4.86)]及精神行为改变[OR=2.54,95%CI(1.56,4.14)]与左乙拉西坦组显著相关(P0.05),其他不良反应与左乙拉西坦组无显著相关。结论现有Meta分析显示,左乙拉西坦添加治疗难治性部分性癫痫的疗效与安慰剂组相比效果显著。左乙拉西坦添加治疗儿童难治性癫痫部分性发作有确切的疗效,且长期治疗效果稳定,有良好的安全性,保留率较高,可在临床进一步推广使用。     

左乙拉西坦添加治疗对青年癫(癎)患者生活质量影响的研究

目的 评价新型抗癫(癎)药物左乙拉西坦添加治疗青年难治性部分性癫(癎)患者的疗效,以及对患者生活质量的影响.方法 30例诊断明确的部分性发作青年患者随机分为左乙拉西坦组和吡拉两坦组,计算左乙拉西坦治疗第12周末时治疗有效率;依据癫(癎)生活质量量表-31分别评价两组患者在左乙拉西坦剂量维持期(12周)和开放性治疗期(12周)的生活质量.结果 治疗第12周末时,左乙拉西坦组治疗有效率(43.75%,7/16)高于吡拉两坦组(35.72%,5/14;Fisher精确概率法:P=0.031),生活质最明显改善(与基线比较:t=3.905.P=0.001).治疗第24周末时,两组患者生活质量较治疗前均显著改善(左乙拉西坦组:t=4.940,P:0.021;吡拉西坦组:t=2.575.P=0.023).结论 左乙拉两坦作为抗癫(癎)药的添加治疗药物,能够显著减少青年难治性部分性癫(癎)患者的发作频率,快速有效地提高患者生活质量.     

左乙拉西坦添加治疗难治性部分性发作癫痫疗效的Meta分析

目的系统评价左乙拉西坦添加治疗难治性部分性发作癫癎的疗效和药物安全性。方法计算机检索1998年1月-2010年12月Cochrane图书馆、MEDLINE、EMbase、社会科学引文索引、维普中文科技期刊、中国知网中国期刊全文数据库和中国生物医学文献数据库,并手工检索相关杂志,由两名研究者独立进行质量评价及数据分析,RevMan 5.0统计软件进行Meta分析。结果根据Cochrane5.0.2版随机对照临床试验质量评价标准,纳入11项随机对照临床试验共1981例受试者(左乙拉西坦组1192例、安慰剂对照组789例)。Meta分析结果显示,左乙拉西坦组每周部分性癫癎发作频率减少≥50%的病例数高于对照组(1000 mg/d:OR=2.990,P=0.000;2000 mg/d:OR=3.870,P=0.000;3000 mg/d:OR=3.440,P=0.000);每周发作频率减少≥75%的病例明显高于对照组(1000 mg/d:OR=3.130,P=0.000;2000 mg/d:OR=5.060,P=0.000;3000 mg/d:OR=4.730,P=0.000);完全不发作病例明显高于对照组(1000 mg/d:OR=5.080,P=0.001;2000 mg/d:OR=4.420,P=0.050;3000 mg/d:OR=4.150,P=0.000)。左乙拉西坦组失访率与安慰剂对照组之间差异无统计学意义(P>0.05)。治疗期间常见药物不良反应包括嗜睡、头晕、乏力、鼻咽炎、精神行为异常等,两组精神行为不良反应方面存在异质性(P=0.360,I~2=8.000%)。结论现有证据显示,左乙拉西坦添加治疗难治性部分性发作癫癎的疗效与安慰剂组相比效果显著,保留率高;药物安全性应注意其所引起的精神行为异常。     

左乙拉西坦和丙戊酸钠对青少年肌阵挛癫痫单药治疗的疗效比较

目的比较左乙拉西坦(levetiracitam,LEV)和丙戊酸钠(sodium valproate,VPA)对青少年肌阵挛癫痫(Juvenile Myoclonic Epilepsy,JME)单药治疗的疗效。方法选取60例青少年肌阵挛癫痫患者,随机分为2组,每组30例,分别给予左乙拉西坦和丙戊酸钠单药治疗,比较治疗后2组肌阵挛发作(myoclonic seizure,MS)、全面性强直阵挛发作(generalized tonic-clonic seizure,GTCS)和脑电图(electroencephalogram,EEG)改善情况。结果 (1)肌阵挛发作改善情况:左乙拉西坦组总有效率为79.31%,丙戊酸钠组总有效率为85.71%(χ2=0.049,P0.05);(2)全面性强直阵挛发作改善情况:左乙拉西坦组总有效率为89.65%,丙戊酸钠组有效率为82.14%(χ2=0.669,P0.05);(3)脑电图改善情况:左乙拉西坦组总有效率为72.41%,丙戊酸钠组总有效率为75.00%(χ2=0.049,P0.05);(4)不良反应:左乙拉西坦组不良反应发生率为6.90%,丙戊酸钠组为25.00%(χ2=6.02,P0.05)。结论青少年肌阵挛癫痫是一种需要长期治疗甚至终生治疗的疾病,故选择治疗药物时不仅需要考虑疗效,长期服用药物的毒副作用也不容忽视。左乙拉西坦和丙戊酸钠对青少年肌阵挛癫痫单药治疗有相同的疗效,且左乙拉西坦不良反应发生率较丙戊酸钠小(P0.05),故左乙拉西坦可作为治疗青少年肌阵挛癫痫的首选一线药物。     

左乙拉西坦添加治疗肌阵挛-失张力癫癇4例报道

目的：探讨左乙拉西坦添加治疗肌阵挛-失张力癫癇（MAE）的有效性及安全性。方法：回顾分析4例左乙拉西坦添加治疗的MAE病例,并结合国外相关文献分析其有效性和安全性。结果：4例MAE患者添加左乙拉西坦治疗后癫癇发作均明显减少,其中3例完全无发作,最长无发作时间达6个月,并且无明显不良反应。结论：左乙拉西坦添加治疗MAE可能是一较好的治疗方案。     

左乙拉西坦添加治疗对学龄期难治性癫痫患儿认知功能与生活质量的影响

目的探讨左乙拉西坦添加治疗对学龄期难治性癫痫患儿认知功能与生活质量的影响。方法选取2013.1~2016.1在我院接受治疗的110例难治性癫痫患儿作为研究组,选取110例正常儿童作为对照组,用癫痫儿童生活质量量表(QOLCE)对研究组和对照组进行生活质量的评估和比较。患儿接受左乙拉西坦治疗8个月后,再次进行评估,与治疗前进行对比;同时比较四种不同癫痫类型患儿的治疗效果。结果简单部分性发作、复杂部分性发作、部分性继发全面性发作以及无法分类四种类型癫痫总有效率分别为90.9%、93.8%、85.7%和85.7%;研究组患儿身体各项评分均低于对照组,治疗后8个月研究组各项评分比治疗前有明显提高,其中社会功能以及认知功能得分提高幅度最为明显(P0.05)。结论使用左乙拉西坦治疗难治性癫痫患儿可以有效改善患儿的认知功能和生活质量。     

在中国使用左乙拉西坦和卡马西平单药治疗部分性癫痫发作的比较:一项开放性、非劣效性试验的主要结果

目的针对≥16岁、新诊断或最近诊断为部分性癫痫发作的中国患者,比较左乙拉西坦和速释卡马西平(CBZ-IR)单药治疗的疗效。方法在Ⅲ期、随机分配、开放性试验N01364(NCT01954121)中,患者按1∶1的比例随机分配接受左乙拉西坦1 000 mg/d或CBZ-IR 400 mg/d,记录6个月无癫痫发作的患者比例及患者保留率、首次癫痫发作的时间、因不良事件或缺乏疗效导致首次癫痫发作/中止试验的时间、安全性和耐受性。结果在对符合方案集进行的分析中,接受左乙拉西坦治疗的186例患者中有88例(47.3%),接受CBZ-IR治疗的171例患者中有117例(68.4%)达到6个月无癫痫发作;校正后绝对差值为-22.9%(95%CI:-33.1%,-12.6%),其下限低于非劣效性界值-20%。左乙拉西坦组的患者保留率为48.4%,CBZ-IR组为70.2%。对于评估期首次癫痫发作时间,左乙拉西坦与CBZ-IR的风险比为2.686(95%CI:1.838,3.927);对于因不良事件或缺乏疗效导致首次癫痫发作/中止试验的时间,风险比为2.338(95%CI:1.629, 3.356)。使用...     

左乙拉西坦治疗儿童难治性癫痫临床疗效及对血清lgA、lgG和lgM水平的影响

目的探讨左乙拉西坦治疗儿童难治性癫痫的临床疗效及对其血清免疫球蛋白水平的影响。方法本院2015年1月至2017年1月收治的70例难治性癫痫患儿作为研究对象,根据随机数字表法将其分为两组,观察组38例给予左乙拉西坦治疗,对照组32例给予卡马西平治疗,用药6个月时统计临床疗效,并对比两组用药前后血清免疫球蛋白(lgA、lgG和lgM)水平、发作频率,并统计不良反应发生情况。结果 (1)观察组总有效率为94.74%,与对照组的81.25%比较显著提高(P0.05);(2)观察组治疗后癫痫发作频率为(5.14±2.32)次/月,与对照组的(8.14±2.78)次/月比较显著减少(P0.05);(3)观察组治疗后的lgA、lgG、lgM水平均较对照组显著降低(P0.05);(4)观察组不良反应发生率为10.53%,与对照组的21.88%比较显著降低(P0.05)。结论对于儿童难治性癫痫,给予左乙拉西坦治疗具有疗效确切、用药安全的优点,在显著减少疾病发作频率的同时,还能改善患儿免疫水平,值得推广。     

Levetiracetam monotherapy for primary generalised epilepsy.

PURPOSE: To evaluate the efficacy of levetiracetam in cases of refractory primary generalised epilepsy. METHODS: Three patients with refractory primary generalised epilepsy were treated with levetiracetam monotherapy; one with absence seizures, myoclonic jerks and generalised tonic-clonic (GTC) seizures one with myoclonic jerks and GTC seizures, and one with only GTC seizures. All three patients had generalised spike wave on the EEG and had failed at least three antiepileptic drugs (AEDs) before trying levetiracetam. RESULTS: All three patients tolerated levetiracetam well and became seizure free for at least 6 months. Therapeutic doses of levetiracetam ranged from 1250 to 3000 mg/day. CONCLUSION: Levetiracetam, a new AED with a novel mechanism(s) of action, should be considered for patients with refractory primary generalised epilepsy.     

Correlation Between Efficacy of Levetiracetam and Serum Levels Among Children With Refractory Epilepsy

BackgroundLevetiracetam is used as adjunctive therapy in various types of seizures. Studies evaluating the effect of levetiracetam on children with refractory epilepsy are scarce. The aim of this study was to evaluate the correlation between serum concentration of levetiracetam and either efficacy or tolerability in children with refractory epilepsy, and to determine the value of levetiracetam blood level monitoring.MethodsMedical records of 50 children with refractory epilepsy treated with levetiracetam and regularly followed at Assaf Harofeh Medical Center were retrospectively reviewed. Trough serum levetiracetam concentration was determined using high-performance liquid chromatography and correlated with the administered dose and clinical report.ResultsNo correlation between levetiracetam serum levels and clinical efficacy, tolerability or administered dosage was found. The average dose of levetiracetam was 43.7 ± 20.0 (range 14-100) mg/kg/day and the average serum concentration was 16.0 ± 9.5 (range 2.5-38.5) μg/mL. Forty-five patients (95%) had more than a 50% reduction of seizure frequency, with 22 (44%) patients becoming seizure-free for at least 6 months. Adverse events related to levetiracetam were reported in 15 (30%) patients. No correlation between serum concentrations and adverse events was found. These results were not affected by gender, age, type of seizure, and other drugs.ConclusionsDetermination of serum concentration is not needed in all children treated with levetiracetam. Serum concentrations may be valuable either in patients with refractory epilepsy for compliance evaluation or in patients with satisfactory control of seizures for determination of their therapeutic baseline.     

Efficacy and tolerability of 1000-4000 mg per day of levetiracetam as add-on therapy in patients with refractory epilepsy

The aim of this study was to determine the efficacy and tolerability of 1000-4000 mg/day of levetiracetam (LEV, Keppra) as add-on treatment for refractory epilepsy. This was a dose-escalation study of 29 patients with refractory epilepsy. Patients received placebo for 4 weeks (baseline) followed by levetiracetam 1000 and 2000 mg per day each for 2 weeks, and then 3000 and 4000 mg per day each for 4 weeks. Primary efficacy was assessed by seizure frequency (number/week). Tolerability was assessed by adverse events, laboratory parameters, clinical evaluations, and electrocardiogram. All the study periods were completed by 27 of the 29 patients. A substantially lower median seizure frequency was observed at all levetiracetam dosing periods (1000 mg per day, 1.0 seizures per week; 2000 mg per day, 1.5 seizures per week; 3000 mg per day, 1.0 seizures per week; 4000 mg per day, 0.75 seizures per week) compared with the placebo treatment (2.06 seizures per week). In addition, 22-33% of these patients were seizure free during treatment with levetiracetam compared with only 14% with placebo. Levetiracetam was well tolerated. The most common adverse events were somnolence and asthenia; frequency and severity increased with increasing doses of levetiracetam. Levetiracetam in doses from 1000 to 4000 mg per day is effective. Somnolence and asthenia were more frequent with the highest dose, suggesting that 4000 mg per day may be the upper limit in some patients, although individual susceptibility to somnolence was variable.     

Assessment of a dose–response relationship of levetiracetam

The aim of this study was to assess the relationship between levetiracetam dose and both efficacy and safety in adult patients with refractory partial epilepsy. Dose–response relationships for levetiracetam efficacy were evaluated using pooled data from three trials including adults with refractory partial epilepsy. Two were randomized, double-blind, placebo-controlled, parallel-group trials in which doses of 1000–3000 mg/day of levetiracetam were administered as adjunctive therapy. The third consisted of the two parts of a crossover randomized, double-blind study in which levetiracetam (1000 or 2000 mg/day) or placebo was added to ongoing therapy. Data from each part of the crossover trial were included as if it was an independent parallel-group study. A fourth randomized double-blind trial was added for the safety evaluation. It included data from adults receiving placebo or 2000 mg/day of levetiracetam as adjunctive therapy for refractory partial seizures. The combined analysis showed an increasing effect with increasing dose. The responder rates (≥50% reduction in seizures) for placebo and levetiracetam 1000, 2000, and 3000 mg/day were 13.1%, 28.5%, 34.3%, and 41.3%, respectively. The respective values for seizure freedom were 0.8%, 4.7%, 6.3%, and 8.6%. There was no evidence of a dose–response relationship with regard to adverse events, including those (asthenia, dizziness, somnolence) most commonly associated with this antiepileptic drug. Patients who do not become seizure-free at the lowest recommended levetiracetam dose (1000 mg/day) should be titrated to 2000 or 3000 mg/day to provide the greatest opportunity for efficacy with little or no increased risk for adverse events.     

Effects of intermittent levetiracetam dosing in a patient with refractory daily seizures

Some epilepsy patients quickly develop resistance to antiepileptic drugs (AEDs). We report a case of a patient with refractory epilepsy with daily seizures who initially responded to levetiracetam daily therapy, but then returned to baseline seizure frequency. However, when levetiracetam was given once weekly, the patient had significantly fewer seizures on the day of and after administration. These results suggest a useful treatment strategy for patients with refractory epilepsy who have developed resistance to AEDs.     

Exceptional response to brivaracetam in a patient with refractory idiopathic generalized epilepsy and absence seizures

Brivaracetam is currently indicated as adjunctive therapy for patients with focal‐onset seizures with or without secondary generalization. However, it has been suggested that it could provide broad‐spectrum efficacy given its similarity to levetiracetam and based on the results from preclinical studies and others of patients with generalized epilepsy. We present the case of a woman with refractory idiopathic generalized epilepsy and absence seizures with dramatic response to brivaracetam. Our report supports a consideration of treatment with this new antiepileptic drug on a case‐by‐case basis in patients with refractory generalized epilepsy, while we await further studies on this topic.     

Epilepsy in Angelman syndrome: A questionnaire-based assessment of the natural history and current treatment options

Purpose:   Angelman syndrome (AS) commonly presents with epilepsy (>80%). The goal of this study was to examine the natural history and various treatments of epilepsy in AS in a large population.
Methods:   A detailed electronic survey containing comprehensive questions regarding epilepsy in AS was conducted through the Angelman Syndrome Foundation.
Results:   There were responses from 461 family members of individuals with AS, of whom 86% had epilepsy (60% with multiple seizure types), the most common being atonic, generalized tonic–clonic, absence, and complex partial. Partial-onset seizures only were reported in 11% of those with epilepsy. Epilepsy was most common among those with maternal deletions and unknown subtypes, with catastrophic epilepsies present in only these two subtypes. These epilepsies were refractory to medication, with only 15% responding to the first antiepileptic drug (AED). The most commonly prescribed AED were valproic acid and clonazepam, but lamotrigine and levetiracetam appeared to have similar efficacy and tolerability.
Discussion:   This is the largest study to date assessing epilepsy in AS. Although epilepsy in AS is considered a generalized epilepsy, there was a high prevalence of partial seizures. There are few previous data regarding the use of newer AED in AS, and the results of this study suggest that these newer agents, specifically levetiracetam and lamotrigine, may have efficacy similar to that of valproic acid and clonazepam, and that they appear to have similar or better side-effect profiles. Nonpharmacologic therapies such as dietary therapy and vagus nerve stimulation (VNS) also suggest favorable efficacy and tolerability, although further studies are needed.     

Efficacy and tolerability of levetiracetam in children aged 10 years and younger: a clinical experience.

Levetiracetam is a new anti-epileptic drug that is currently not licensed for use in children. Studies in adults suggest that it may be a useful adjunctive treatment both in partial onset and generalised epilepsy. A retrospective case notes review of 26 children age 10 years and under with refractory epilepsy was undertaken to evaluate the efficacy and safety of the drug. The drug appeared to be most effective in children with partial onset seizures and least effective in those with myoclonic seizures. Sixty-one percent of patients showed a good response to levetiracetam with at least a 50% reduction in seizure frequency with two of these 26 children with previously refractory epilepsy becoming seizure-free. Levetiracetam was also found to be well-tolerated with very few reported side-effects.     

Levetiracetam in patients with refractory epilepsy: results of the SKATE trial in Austria, Germany and Switzerland.

PURPOSE: To further evaluate the safety, efficacy and optimal dose of levetiracetam (LEV) in daily clinical practice among patients with uncontrolled partial epilepsy with or without secondary generalization. METHODS: In this phase IV, open-label, 16-week community-based study, 178 at least 16-year-old patients with refractory focal epilepsy were treated with 1000, 2000 or 3000 mg levetiracetam as adjunctive therapy. All patients started with 500 mg LEV b.i.d. (1000 mg/day); the dose was adjusted in 2-week intervals up to 1500 b.i.d. (3000 mg/day) depending on seizure control and tolerability. The main objectives were the adverse events, the percentage reduction in partial and total seizure frequency per week from baseline and the retention rate, defined as the percentage of patients taking LEV at the end of the 16-week treatment period. RESULTS: Of the 178 patients who took at least one dose of LEV 151 completed the study. Thus, the retention rate (number of patients taking LEV at the end of the 16-week treatment period) was 84.8%. Most frequently reported adverse events were asthenia, dizziness, headache, nausea, somnolence and hostility; the majority of these events were of mild to moderate intensity. The seizure-free rate of the ITT population with focal seizures was 16.7%, for all seizures 16.6%; the median reduction of focal seizure frequency was 47.6%, and 46.5% for all seizures. The 50% responder rate was 46.6% for focal seizures and 45.1% for all seizures. CONCLUSION: Add-on treatment with LEV in patients with refractory partial epilepsy was safe and effective in this study.     

Levetiracetam may be more effective for late-onset partial epilepsy

BACKGROUND: Many agents are available for treating epilepsy; however, population studies have failed to show overall differences in efficacy for a given seizure type. Clinical experience suggests that certain individuals will respond to a given agent while others with the same seizure type will not. OBJECTIVES: To examine a population of patients who received one of the newer antiepileptic drugs, levetiracetam, and to identify those who had either a dramatic improvement or a significant worsening of seizures. METHODS: Retrospective medical record review of patients with refractory epilepsy. RESULTS: Patients who responded well to levetiracetam therapy were older at the onset of epileptic seizure than those who did not (mean [SD] age, 51 [5] vs 27 [3] years; P<.05). This was also true of the subset of patients who had localization-related epilepsy. Patients with temporal lobe onset were likely to do well whereas patients with frontal lobe onset were not. CONCLUSIONS: These results suggest that certain subpopulations may be particularly likely to respond to levetiracetam therapy. These need to be confirmed in a larger prospective trial; however, looking for specific characteristics of patients who respond to certain drugs may lead to useful guidelines for drug choices in treating epilepsy.