左乙拉西坦单药治疗小儿癫癎的疗效和安全性随访研究

目的：评价左乙拉西坦(LEV)单药治疗小儿癫癎的疗效和安全性。方法：对该院2007年3月至2008年3月LEV单药治疗的32例癫癎患儿进行开放性自身对照随访研究,起始量每日10 mg/kg,每1周增加上述剂量1次,3~4周增加至维持剂量每日20～60 mg/kg,平均剂量为每日35 mg/kg。结果：LEV 单药治疗32例,失访1例,其余随访均在3个月以上。 80.6%（25/31）患儿发作减少≥50%,70.9%（22/31）患儿无发作,16.1%（5/31）患儿因发作控制不满意或者加重而停药。不良反应包括情绪异常19.4%（6/31）,乏力6.5%（2/31）,嗜睡6.5%（2/31）,皮疹3.2%（1/31）。上述不良反应均为一过性,在1～4 周内自然消失或者减量后消失,未导致停药,未发现过敏以及血液、肝、肾功能异常等严重不良反应。结论：LEV用于癫癎患儿（包括<4岁的婴幼儿）的部分性发作及全身性发作的单药治疗,疗效肯定、安全性好,是一个很有希望的用于儿童单药治疗的广谱抗癫癎药。     

左乙拉西坦单药或联合用药治疗婴儿癫长程保留率的回顾性分析

目的分析左乙拉西坦(LEV)单药或联合用药治疗婴儿癫的长程保留率。方法回顾性分析2006年7月至2007年6月应用LEV治疗的婴儿癫患儿的临床资料。结果 60例服用LEV的癫患儿,部分性发作20例,全面性发作19例,癫综合征21例,其中难治性癫21例。23例LEV单药治疗,37例以LEV作为添加药物联合治疗。LEV首剂量10 mg/kg·d,每日2次口服,每周加量10 mg/kg,加量调整直至取得最佳疗效和耐受性。LEV治疗6个月、1年、2年、3年及4年的保留率分别为95.0%、75.0%、60.0%、51.7%和38.3%。最主要停药原因为缺乏疗效(43.2%)。COX回归模型提示,病程1个月(RR=2.91,95%CI:1.16~7.30)及难治性癫(RR=2.30,95%CI:1.22~4.32)是患儿停药的危险因素(P均0.05)。患儿服药后发作频率较基线水平明显减少(P0.01)。至随访结束,23例未停药患儿中,有效率100%,完全缓解率69.57%。主要不良反应为倦怠乏力(56.0%),其余为睡眠增多、烦躁不安等。结论 LEV单药或联合用药治疗婴儿癫具有较好的长程保留率、良好的疗效及耐受性。     

奥卡西平治疗儿童癫(癎)的临床随访研究

目的 探讨奥卡西平治疗儿童癫(癎)部分性发作及难治性癫(癎)的临床疗效和安全性.方法 2005-2006年上海新华医院小儿神经科收治癫(癎)患者52例,其中新诊断和未经治疗癫(癎)部分性发作患者37例为单药治疗组;15例为既往经2种以上抗癫(癎)药正规治疗,发作仍未控制者为添加治疗组.起始剂量5～10 mg/(kg·d),每日2次口服,每5～7 d,增加5～10 mg/(kg·d),目标剂量20～40 mg/(kg·d).观察期为6个月至2年,进行自身对照开放性研究,观察其疗效、安全性及依从性,分析剂量与不同年龄及疗效的关系.结果 单药治疗组有效率为(控制+显效+有效)89.19%,控制率为67,57%,退出率为2.70%;难治组有效率为46.67%,控制率为13.33%,退出率为26.67%.共5例退出,1例因皮疹退出,4例因发作未能控制而退出.小于4岁患儿的平均剂量较年长儿显著增高(P＜0.05).发作减少50%以上的病例的平均剂量较发作减少50%以下者显著增高(P＜0.05).21.15%的病例发生不良反应,包括困倦、头晕、乏力、皮疹等,无低钠血症发生.结论 奥卡西平治疗儿童部分性癫(癎)疗效显著,对难治性癫(癎)的也有一定的疗效,临床应用依从性良好,不良反应较少,安全性好.     

左乙拉西坦治疗儿童癫(癎)51例自身对照研究

目的 研究左乙拉西坦(Lev)作为添加治疗不同类型儿童癫(癎)的临床疗效和安全性.方法 采用前瞻性研究51例不同类型耐药性癫(癎)患儿(男37例,女14例;平均年龄8.7岁)使用Lev作为添加治疗(发作形式包括复杂局限性发作20例,局限性发作继发全面性发作4例,强直-阵挛发作10例,强直发作1例,肌阵挛发作6例,眼肌痉挛型2例,Lennox-Gastaut综合征2例,婴儿痉挛症4例,不能分类的癫(癎)性脑病2例),原抗癫(癎)药继续服用.Lev起始剂量为20 mg/(kg·d),分2次服用,每2周增加10 mg/(kg·d),维持剂量30～40 ms/(kg·d).以治疗前3个月的发病频率为基础,平均随访6.8个月,观察发作频率变化及不良反应.6例分别因无效、发作加重、不能耐受终止Lev治疗.采用SPSS 14.0软件比较癫(癎)患儿Lev治疗前后发作频率的差别.结果 有效13例,占25.5%;显效9例,占17.6%;无发作16例,占31.4%;无效8例,占15.7%;加重5例,占9.8%.Lev治疗前后发作频率改变有统计学意义(P<0.005).结论 Lev作为添加治疗对于儿童各型癫(癎)均有疗效,尤其对于复杂局限性发作、肌阵挛发作等具有较好治疗效果,且不良反应轻,是一种安全性好,疗效佳的抗癫(癎)新药.     

左乙拉西坦对癫癎患者脑电电持续状态及认知的改善

目的 探讨左乙拉西坦(LEV)对癫癎患者脑电电持续状态及认知的影响.方法 选取8例EEG伴有睡眠期电持续状态(ESES)的癫癎患儿.其中良性癫癎伴中央颞区棘波(BECT)7例、获得性癫癎性失语(LKS)1例.8例患儿均应用LEV治疗,LEV起始剂量为10 mg· kg-1,每1～2周增加10 mg·kg-1,直至目标剂量40 ～60 mg·kg-1.例2同时予甲泼尼龙15 mg·kg-1冲击3d停4d,冲击2个疗程后改为泼尼松口服.分别在治疗前及治疗2周、4周及0.5a行视频脑电图监测.EEG疗效判断:棘慢波指数从85％减至50％以下为显效,有减少但仍在50％以上为有效,无变化为无效.并同时用韦氏儿童智力量表对这些患儿治疗前及治疗4周时进行神经心理评估.结果 治疗2周,患儿临床发作均得以控制,其中5例BECT患儿EEG棘慢波完全消失,其余3例患儿EEG棘慢波电压较前降低、数量较前减少;治疗4周,所有患儿的EEG恢复正常,临床无发作,LKS患儿语言较前好转.治疗4周,患儿的语言智商、操作智商及总智商均较治疗前有明显改善.随访0.5a,仅LKS患儿在随访2个月出现EEG恶化,且语言未完全恢复正常,余患儿病情及EEG均无反复.结论 LEV对局限性发作伴ESES的癫癎患者的EEG及认知有改善作用,对LKS患儿有短期疗效.     

左乙拉西坦治疗小儿癫(痫)100例疗效与安全性随访观察

目的 观察左乙拉西坦(LEV)单药或添加治疗不同类型小儿癫(痫)的临床疗效和安全性.方法 选取100例于山西省儿童医院小儿神经内科专科门诊2008年8月-2010年10月收治的应用LEV单药或添加治疗的癫(痫)患儿为研究对象,采用开放性自身对照随访研究方法.LEV给药起始剂量为10mg?kg-1 ?d-1,分2次口服,每周增加上述剂量1次,3～4周增加至目标剂量20～40 mg?kg-1?d-1,随访6 ～.24个月,以发作频率减少的百分率作为疗效判定标准,观察治疗前后发作频率变化、脑电图改变,并记录治疗过程中不良反应的发生情况,以评价其安全性.结果 入选癫(痫)患儿100例,失访4例.发作完全控制49例(占51.0％)；有效27例(占28.1％)；无效17例(占17.8％)；加重3例(占3.1％).总有效率为79.1％.脑电图明显改善者8例.14例(14.6％)患儿出现包括情绪异常,7例(7.3％)出现乏力,6例(6.3％)出现嗜睡,1例(1.0％)出现皮疹等不良反应.未发现严重过敏及血液系统抑制、肝肾功能异常等不良反应.2例因不良反应停药.结论 LEV治疗小儿各种类型癫(痫)具有良好的疗效和安全性,是一个值得推广的广谱抗癫(痫)药物.     

左乙拉西坦对儿童睡眠中癫癎性电持续状态的影响

目的：探讨左乙拉西坦（levetiracetam, LEV）治疗儿童睡眠中癫癎性电持续状态(ESES)的疗效。方法：对2009年8月至2011年3月首诊的27 例ESES患儿使用LEV状况进行分析,并最少随访6个月。结果：27例ESES患儿起病年龄为9个月至9岁7个月,起病早期81%的患儿为局限性运动发作。23例为ESES确诊后加用LEV治疗,其中19例为良性癫癎伴中央颞区棘波（BECT）患儿,4例为非BECT的ESES患儿。LEV 开始治疗年龄为1岁8个月至11岁9个月, 随访时间为7~19个月。LEV控制发作有效率为82%,改善脑电图（EEG）情况有效率为78%。LEV控制临床发作效果优于改善EEG效果（P<0.05）。另4例患儿于ESES前已加用LEV治疗,其中2例临床发作得到控制或EEG有明显改善。结论：LEV在控制临床发作和改善脑电图放电方面均有一定疗效。     

生酮饮食治疗难治性癫(癇)的初步观察

目的观察生酮饮食治疗小儿难治性癫癎的疗效及其安全性。方法选择15例难治性癫癎患儿用合适中国人膳食习惯的生酮饮食方案进行治疗。随访其依从性、临床发作频率及不良反应。结果12例（80%）坚持治疗1个月,其中10例（87.5%）癫癎发作减少〉50%;10例（66.6%）坚持治疗3个月,其中8例（80%）癫癎发作减少〉50%;5例（33.3%）坚持治疗6个月以上,其中5例（100%）癫癎发作减少均〉50%,4例（80%）癫癎发作减少〉90%,3例（60%）癫癎发作完全控制。1例已随访2年以上,发作减少〉90%。10例出现轻重不一的不良反应（恶心、呕吐、腹泻、便秘、低血糖、高血脂、肝功能受损）,经对症治疗后均可缓解。结论适合中国人膳食习惯的生酮饮食方案治疗小儿难治性癫癎有效而安全。其疗效与发作类型无明显关系。     

左乙拉西坦治疗小儿癫100例疗效与安全性随访观察

目的观察左乙拉西坦(LEV)单药或添加治疗不同类型小儿癫的临床疗效和安全性。方法选取100例于山西省儿童医院小儿神经内科专科门诊2008年8月-2010年10月收治的应用LEV单药或添加治疗的癫患儿为研究对象,采用开放性自身对照随访研究方法。LEV给药起始剂量为10 mg.kg-1.d-1,分2次口服,每周增加上述剂量1次,3～4周增加至目标剂量20～40 mg.kg-1.d-1,随访6～24个月,以发作频率减少的百分率作为疗效判定标准,观察治疗前后发作频率变化、脑电图改变,并记录治疗过程中不良反应的发生情况,以评价其安全性。结果入选癫患儿100例,失访4例。发作完全控制49例(占51.0%);有效27例(占28.1%);无效17例(占17.8%);加重3例(占3.1%)。总有效率为79.1%。脑电图明显改善者8例。14例(14.6%)患儿出现包括情绪异常,7例(7.3%)出现乏力,6例(6.3%)出现嗜睡,1例(1.0%)出现皮疹等不良反应。未发现严重过敏及血液系统抑制、肝肾功能异常等不良反应。2例因不良反应停药。结论 LEV治疗小儿各种类型癫具有良好的疗效和安全性,是一个值得推广的广谱抗癫药物。     

左乙拉西坦联合短程氯硝西泮治疗儿童Rolandic良性癫癎睡眠中癫癎电持续状态的效果

目的 探讨左乙拉西坦（LEV）联合短程氯硝西泮（CZP）治疗儿童Rolandic 癫癎（BECCT）睡眠中癫癎电持续状态（ESES）的效果。方法 采用24 h 便携式动态脑电（AEEG）或3 h 视频脑电（VEEG）监测,以非快速动眼（NREM）睡眠期出现持续广泛性棘慢波发放占整个NREM 期的85% 以上作为ESES 的诊断标准,回顾分析15 例（男9 例,女6 例）诊断为ESES 的BECCT 患儿临床表现及脑电图特点。患儿在口服LEV[20~40 mg/（kg · d）] 基础上联合2 个月短程CZP,并随访6~18 个月。结果 15 例患儿早期给予LEV 单药治疗过程中复查EEG 无改善或同时有癫癎发作,继而给予联合治疗（LEV+ 短程CZP）;治疗后第1、6 个月复查,14 例患儿EEG 放电明显减少（仅Rolandic 区少量放电）或消失,发作完全控制,1 例随访过程中ESES复发并癫癎发作2 次,重复上述联合治疗方案后第1、6 个月复查,EEG 正常范围,再次随访8 个月无发作。结论 LEV 联合短程CZP 对BECCT 患儿ESES 的控制相对理想、副作用少。     

Long-term use of Levetiracetam in patients with severe childhood-onset epilepsy

OBJECTIVE: To assess the efficacy and tolerability of Levetiracetam (LEV) in children and adolescents with refractory epilepsy with a special interest in the long-term retention rate. METHOD: One hundred and twenty-nine patients (83 male, 46 female; mean age 10.6 years/range: 6 months-39 years 9 months) were included in a prospective, open-label, add-on trial of LEV for up to 3 years. All patients had severe forms of epilepsy starting before the age of 10 often accompanied by mental retardation. Primary outcome measures were changes in seizure frequency after 6 months on the medication with LEV, with initial responders (>50% seizure reduction). Further objective was the retention rate of LEV therapy after 3 years defined as percentage of patients still taking LEV. RESULTS: Thirty-five patients (27.1%) were initial responders of which 5 became seizure free. The average maximum LEV dosage was 39.8 mg/kg/day (range: 6-70 mg/kg/day) with no difference responders vs. no responders. The retention rate for responders after 3 years was 22.5%. The rate of side effects was 39.8% in all patients, with the most frequent side effects being fatigue (12.5%), aggressiveness (7.8%) and gastrointestinal disorders (13.3%). CONCLUSIONS: Our study in patients with refractory epilepsy suggests that our initial responders were very likely to be still taking LEV after 3 years. We therefore consider treatment with LEV in this special group of patients with refractory epilepsy a promising therapeutic option, because of its favourable tolerance profile, the option of fast titration and the absence of drug interactions.     

Long-term use of zonisamide in refractory childhood-onset epilepsy.

This open label study examined the long-term efficacy and safety of zonisamide as adjunctive therapy in mentally retarded and multiple-handicapped patients with severe childhood-onset epilepsy. The study included 24 patients (mean age 12.5 years, range 2-40 years) which had different severe epilepsy syndromes (75% focal, 12.5% generalized, 12.5% refractory status epilepticus) refractory to at least 6 (median 10) anti-epileptic drugs. All patients were followed for at least 18 months after beginning of zonisamide treatment. Mean duration of zonisamide therapy was 55 weeks (range 5-168 weeks) and mean maintenance dosage was 7.7 mg/kg/day (range: 4-16 mg/kg/day). The patients received an average of 1.9 (range 1-3) concomitant antiepileptic drugs. The initial response rate defined as a > or =50% reduction of seizure frequency after 8 weeks was 58.3% (14 of 24 patients). Four of 14 initial responders developed loss of efficacy during long-term treatment. The retention rate after 18 months was 41.7% (10 of 24 patients). One patient (4.2%) became completely seizure-free after initiation of zonisamide treatment and remained seizure-free for the entire observation period of 18 months. Overall, zonisamide was well tolerated. Side effects were observed in 46% of patients and were mild to moderate. They mostly occurred during titration and subsided in maintenance dosing. Only in two patients (8.3%) zonisamide therapy was discontinued due to side effects (loss of appetite). No serious side effects were observed. These results are similar to the findings of Japanese studies suggesting that long-term use of adjunctive zonisamide therapy may be beneficial for treating mentally retarded, multiple handicapped patients with highly refractory childhood-onset epilepsy.     

Add-on levetiracetam in children and adolescents with refractory epilepsy: Results of an open-label multi-centre study

PURPOSE: To study the efficacy and tolerability of add-on levetiracetam in children and adolescents with refractory epilepsy. METHODS: In this prospective multi-centre, open-label, add-on study, 33 children aged 4-16 years (median 8.5 years) with epilepsy refractory to at least two antiepileptic drugs were treated with levetiracetam in addition to their present treatment regimen with a follow-up of 26 weeks. The starting dose of 10 mg/kg/day was increased with 2-week steps of 10 mg/kg/day, if necessary, up to a maximum dose of 60 mg/kg/day. RESULTS: Retention rate was 69.7% after 26 weeks on a median levetiracetam dosage of 22 mg/kg/day. Four children dropped-out because levetiracetam was ineffective, four because seizure frequency increased and/or seizures became more severe, and two because they developed aggressive behaviour. Compared to their baseline seizure frequency, 13 children (39.4%) had a >50% seizure reduction 12 weeks after initiation of levetiracetam, and 17 children (51.5%) at 26 weeks. At 26 weeks, nine children (27.3%) had been seizure-free for at least the last 4 weeks, terminal remission ranged from 0 to 187 days (mean 46 days). Levetiracetam was effective in both partial and primary generalized seizures, but had most effect in partial seizures. Most reported side effects were hyperactivity (48.5%), somnolence (36.4%), irritability (33.3%) and aggressive behaviour (27.3%). Severity of most side effects was mild. Five children had a serious adverse event, which all concerned hospital admissions that were not related to levetiracetam use. CONCLUSION: Levetiracetam proved to be an effective and well-tolerated add-on treatment in this group of children with refractory epilepsy.     

Clinical experiences with topiramate in children with intractable epilepsy.

At a tertial referral epilepsy centre 39 children were consecutively enrolled in an open add-on study with topiramate (TPM). All children had intractable epilepsy; the mean seizure frequency was 36 per month, and 31 children were treated with polypharmacy. All but five children were mentally retarded. The initial dose of TPM was 0.5-1 mg/kg daily, slowly titrated with 1-3 mg/kg daily every second week with an estimated target dose of 10 mg/kg daily. At latest follow-up 19 children continued on TPM, three (8%) were seizure-free, eight (21%) had a seizure reduction of more than 50% and eight (21%) improved their general condition. Mean follow-up was 13 months (range 9-36 months). Seizure reduction was seen in focal as well as generalized epilepsies. Adverse effects were reported in 21 cases (54%), weight loss and sedation being most frequent. The mean steady state dose in the children continuing on TPM was at latest follow-up: 14 mg/kg daily (< 5 years), 10 mg/kg daily (5-7 years), 5.8 mg/kg daily (8-17 years). The corresponding plasma level varied from 3 to 45 mumol/litre, and a significant correlation between the daily dose in mg/kg and the plasma level was found. Two patients with progressive myoclonus epilepsy are described separately; one had a dramatic general improvement. It is concluded that TPM seems to be a promising new broad-spectrum anti-epileptic drug, which is efficacious even in epilepsy syndromes, intractable to other new anti-epileptic drugs such as vigabatrin and lamotrigine.     

Open-label, long-term safety study of zonisamide administered to children and adolescents with epilepsy

BACKGROUND: Zonisamide is licensed in the EU and USA for the adjunctive treatment of partial-onset seizures in adults but there are few data about its use in children. AIMS: To assess the long-term safety and efficacy of zonisamide in children and adolescents. METHODS: Zonisamide-na?ve patients (n=109, aged 3-15 years, weight >or=12.5 kg) with a clinical diagnosis of epilepsy (>or=4 seizures/month, receiving 1-2 antiepileptic drugs [AEDs] daily) received zonisamide once or twice daily in an open-label trial. The starting dose was 1mg/kg/day, increased by 2 mg/kg/day every 1-2 weeks at the investigator's discretion to an initial maximum of 12 mg/kg/day. The occurrence of adverse events (AEs) was the primary safety measure. Efficacy was measured via the reductions in seizure frequency and via investigator- and carer-rated global assessment ratings. RESULTS: The mean dose received was 8.5 mg/kg/day. Of the 109 children, 52 (48%) completed 15 months' treatment. Treatment-related AEs, mostly mild-to-moderate in severity, were reported by 58 patients. Seven patients discontinued due to treatment-related AEs. Serious AEs (pancreatitis, decreased sweating, and vertigo) were reported by three patients. A significant (p=0.033) median reduction in 'all seizure' frequency of 2.60 seizures per week was observed. Additionally, a significant (p=0.029) median reduction of 1.80 seizures/week in 'complex partial' seizures was reported. Improvements in investigator- and carer-rated global assessments were noted. CONCLUSIONS: Zonisamide treatment was generally well tolerated and was associated with significant reductions in seizure frequency in this pediatric population with a variety of both partial and generalized medically refractory epilepsy syndromes.     

Efficacy and safety of lacosamide in infants and young children with refractory focal epilepsy

BackgroundLacosamide is effective and well-tolerated antiepileptic drug (AED) in both children and adults.AimThis multicentric, prospective study investigates the efficacy and safety of lacosamide adjunctive therapy in children aged less than four years presenting with refractory focal seizures.MethodsLacosamide was added to the baseline therapy at a starting dose of 1–2 mg/kg/day and titrated to the final dose, ranging from 7 to 15.5 mg/kg/day. Efficacy was evaluated after a three-month period of therapy. When possible, we compared the initial efficacy and the retention after a minimum of 12 months of lacosamide, with regard to loss of efficacy (defined as the return to the baseline seizure frequency).ResultsTwenty-four children were enrolled in the study. Mean age was 2.7 years. After a minimum three-month period of lacosamide add-on therapy, ten (42%) patients were responders (more than a 50% decrease in seizure frequency), of whom 4 (17%) became seizure free. Retention rate, after a minimum of 12 months of lacosamide, was evaluated in a group of 18 patients. In the latter group, eight patients (44%) were initial responders (three of whom seizure free). After 12 months of follow-up, four of them (22%) maintained the improvement, 2 (11%) of whom remained seizure free. A loss of efficacy was observed in 4 of the initial responders (50%). Adverse events were seen in 8 (33%) patients.ConclusionWe conclude that lacosamide is an effective and a well-tolerated antiepileptic drug in an etiologically wide range of focal seizures. Therefore, lacosamide might represent a possible therapeutic option in infants and young children affected by uncontrolled focal epilepsy.     

Usefulness of perampanel with concomitant levetiracetam for patients with drug-resistant epilepsy

Purpose

The purpose was to evaluate the efficacy of treatment and the occurrence of aggression-related adverse events among children receiving perampanel (PER) with concomitant levetiracetam (LEV).