Management of childhood epilepsy

Epilepsy is a common childhood neurological morbidity needs careful evaluation, relevant investigations and precise therapy with appropriate antiepileptic drugs for optimal duration. Majority of childhood epilepsy remits with antiepileptic drugs and should be managed in the community. Practising Pediatricians must counsel the family for possible etiology of epilepsy, compliance during treatment and possible outcome. It is important to distinguish pseudo seizures and nonepileptic events from true epilepsy, as this would reduce the burden of unwanted medication. It is also equally important to enable ourselves to recognize early predictors of intractability and refer them to appropriate referral units. Epilepsy is a social and an economic burden for the family. Preventive strategies by improved perinatal care, prevention and managemnt of neuro infections and infestations which will mitigate epilepsy burden in the community are essential. In this context it is important to familarize appropriate and relevant use of investigations. Inappropriate antiepileptic drug usage is common in the community and drug therapy should be rationalized. Epilepsy management requires a close interaction between the patient, family and the treating physician and a concerted effort is essential.     

Efficacy of antiepileptic drugs in the era of pharmacogenomics: A focus on childhood

BackgroundIn recent years advances in the field of pharmacogenomics have expanded the concept for more individualized treatments. Our aim is to provide literature data about the relationship between genetic polymorphisms and efficacy of antiepileptic drugs in children.MethodsPubmed was used as the main medical database source. Only original research papers were considered. No year-of-publication restriction was placed. Quality of evidence was assessed according to American Academy of Neurology guidelines.ResultsA total of 12 cross-sectional and case–control studies fulfilled our selection criteria. ABCB1 gene was associated with drug responsiveness in 2 out of 6 studies and ABCC2 gene in 1 out of 1 studies. SCN1A gene was also associated with seizure control in 4 out of 5 studies. Cytochrome P450 genes were found to significantly affect drug responsiveness in 2 out of 4 studies, while polymorphisms of uridinediphosphateglucuronosyltransferaseUGT2B7 gene predisposed to drug-resistance in 1 out of 2 studies.ConclusionVariability in genes coding for sodium channels, drug transporters and cytochrome P450 enzymes can have a significant impact on response to antiepileptic drugs. Larger prospective studies with better stratification of samples are needed to shed light on these associations.     

奥卡西平的不良反应

奥卡西平(oxcarbazepine, OXC)是一种新型抗癫癎药物,由于其耐受性好,药物间的相互作用少,在临床得到越来越广泛的应用,但其毒副作用仍不可忽视。OXC 的不良反应以中枢神经系统和消化系统多见,如:疲劳、嗜睡、复视、头晕、恶心、呕吐等;皮肤不良反应主要为皮疹;长期服用OXC 还可能引起低钠血症。本文搜集国内外近十年有关OXC 不良反应的文献,并对其进行归纳分析,旨在为OXC 的临床合理用药提供参考。     

Treatment of epilepsy in childhood

OBJECTIVE: Due to the development of new antiepileptic drugs, epilepsy treatment has presented substantial progress in the last decade. In spite of presenting more adequate profile, these drugs have not shown better efficiency in seizure control than the traditional drugs. The objective of this revision is to provide up-to-date data for the treatment of epilepsy in childhood and the role of the new antiepileptic drugs. SOURCES: Bibliographic review has been performed at Medline for the last 10 years, and the most pertinent papers and abstracts presented in International Epilepsy Meetings were selected. SUMMARY OF THE FINDINGS: The new antiepileptic drugs could be indicated in the treatment of some specific epileptic syndromes. Serious side effects have been described with the use of these drugs. CONCLUSIONS: The traditional drugs must be considered as the primary choice in the treatment of ordinary epilepsy.     

Treatment of Lennox-Gastaut Syndrome (LGS)

Lennox-Gastaut Syndrome (LGS) is a severe form of epilepsy that usually starts in early to mid childhood and is characterized by multiple seizure types, abnormal electroencephalogram with slow spike-and-wave discharges and cognitive problems. Numerous approaches are currently used to treat LGS, including use of conventional antiepileptic drugs (most commonly sodium valproate, lamotrigine and topiramate), other drug interventions (corticosteroids and intravenous immunoglobulin) and nonpharmacologic treatments (ketogenic diet, corpus callosotomy and vagus nerve stimulation). Rufinamide is the most recent antiepileptic drug to have shown efficacy in the treatment of LGS.Despite the variety of therapeutic options, there have been only five double-blind, placebo-controlled clinical trials of antiepileptic drugs in LGS and none of these were head-to-head comparison trials. The evidence supporting the use of available treatments for LGS is, therefore, not robust. Here, we review the evidence supporting the use of specific therapies in LGS and provide recommendations on how to set appropriate treatment goals, select treatments and minimize polypharmacy. A suggested treatment algorithm is presented and discussed. Sodium valproate is recommended for first-line therapy; if seizures persist, alternative interventions should be trialed on an individually tailored basis.     

Neurodevelopmental outcome in full-term newborns with refractory neonatal seizures

Aim: This retrospective study describes the prognosis of full‐term newborns with refractory neonatal seizures, comparing the need for treatment with two versus three or more antiepileptic drugs. Methods: We reviewed our database (January 2002–December 2007) to include newborns with refractory neonatal seizures and abnormal electroencephalogram. Group A consisted of 17 newborns with two antiepileptic drugs. Group B consisted of 29 newborns with three or more antiepileptic drugs. Outcome was determined at 2 years of age using the Dutch Bayley Scales of Infant Development or a neurodevelopmental classification scheme. Results: Group A and group B were comparable regarding to a variety of demographic and aetiologic factors. Thirteen newborns died before 2 years of age and one was lost to follow‐up. Normal development at 2 years of age was found in 50% and 5% for group A and B, respectively. Severe neurodevelopmental delay at 2 years of age was found in 30% and 68% for group A and B, respectively. Conclusion: The number of antiepileptic drugs probably reflects increased seizure burden and is – in that way – related to poor outcome. This may be useful information for early prediction of adverse neurological outcome in the first days of life.     

癫(癎)的免疫学研究进展

癫(癎)为临床常见综合征,近年来,关于癫(癎)的免疫学发病机制已逐渐被人们所认识,包括体液免疫和细胞免疫两个方面.体液免疫异常主要包括细胞因子、自身抗体及免疫球蛋白等的变化,细胞免疫异常则表现为淋巴细胞亚群、淋巴细胞增殖带及NK细胞等的变化.除外周血的异常,癫(癎)患者的脑脊液检查也可发现各项免疫指标的变化.抗癫癎药物...     

儿童癫癎对药物反应性与多药耐药基因MDR1C3435T多态性的相关性研究

目的:探讨汉族癫癎患儿MDR1基因单核苷酸多态性（C3435T）与对抗癫癎药物反应的相关性。方法：214例癫癎患儿根据对抗癫癎药物的反应性分为耐药组和对药物反应良好组,提取外周血基因组DNA,用PCR-RFLP的方法即多聚合酶链反应（PCR）扩增后继以限制性内切酶片断长度多态性（RFLP）分析,对不同药物反应性与基因型频率、等位基因频率结果进行分析。结果：214例可明确分型的病例中,对药物反应良好的有164例,耐药的有50例 。两组病例的等位基因频率比较和基因型频率相比较,均未发现差异有显著性。结论：该研究未能反映汉族儿童C3435T基因多态性与癫癎病例对药物反应之间的相关性。［中国当代儿科杂志,2007,9（1）：11-14］     

Successful treatment of antiepileptic drug hypersensitivity syndrome with intravenous immune globulin

Intravenous immune globulin (IVIG) has proved beneficial for severe immunologically related cutaneous adverse reactions. We report a child with severe antiepileptic drug hypersensitivity syndrome who was successfully treated with IVIG. IVIG should be considered in the pharmacologic armamentarium of severe antiepileptic drug hypersensitivity syndrome. antiepileptic drugs, hypersensitivity, immune globulin.     

癫痫患儿红细胞免疫功能的研究

目的 探讨红细胞免疫粘附功能与癫痫发作的关系。方法 采用酵母菌花环试验法对７０例癫痫患儿及３０例健康儿童（对照组）进行红细胞（Ｃ３ｂ（ＲＢＣ－Ｃ３ｂ）受体花环率及红细胞免疫复合物ＲＢＣ－ＩＣ）花环率检测,并进行比较。结果（１）癫痫组ＲＢＣ－Ｃ３ｂ受体花环率明显地姐;ＲＢＣ－ＩＣ花环率明显高于对照组;（２）使用抗癫痫药物组患儿ＲＢＣ－Ｃ３ｂ受体花环率明显高于未使用抗癫痫药物组,ＲＢＣ－ＩＣ花环率两组     

口服抗癫癎药物治疗儿童热性惊厥的临床与脑电图分析

目的：了解有癫癎高危因素的热性惊厥患儿应用丙戊酸钠与托吡酯口服治疗4年的临床与脑电图改变情况。方法：对2004~2005年的132例有应用抗癫癎药物指征的热性惊厥患儿给予丙戊酸钠与托吡酯口服治疗,每半年随访一次病情变化、血常规和肝肾功能;每一年随访一次睡眠脑电图,共随访4年。结果：随访时间1~10年,丙戊酸钠口服液单药治疗110例,长期控制率为98.2%,95例已停药,10例正处在减药过程中。托吡酯单药治疗13例,均发作控制,顺利停药。无一例出现血常规和肝肾功能异常表现。治疗后睡眠脑电图恢复正常者102例,出现局灶性改变者8 例,两侧同步性棘慢波4例,3 Hz棘慢波及多棘慢波2例。结论：对于癫癎高危因素的热性惊厥患儿,早期使用抗癫癎药物丙戊酸钠或托吡酯,疗效确切,无明显不良反应。抗癫癎药物治疗后大部分患儿睡眠脑电图恢复正常。     

小儿癫痫及抗癫痫治疗血脂水平的监测及其临床意义

目的　探讨小儿癫痫及抗癫痫治疗血脂水平的变化。方法　对６０ 例癫痫患儿服药前、后血脂水平进行测定。结果　癫痫本身对血脂水平无影响;卡马西平可使血清总胆固醇（ＴＣ）、甘油三酯（ＴＧ）、高密度脂蛋白胆固醇（ＨＤＬ－ Ｃ） 及低密度脂蛋白胆固醇（ＬＤＬ－ Ｃ） 水平升高,且随时间延长,差异更为明显;丙戊酸钠对血脂无影响。结论　小儿癫痫治疗期间应动态监测血脂水平,如血脂有动态增高趋势应密切观察,并可适当调整饮食。     

儿童难治性癫痫抗癫痫药物治疗策略

难治性癫痫往往需要多种药物联合治疗。因此,熟悉抗癫痫药物的作用机制和药代动力学主要特点, 按照发作类型和综合征进行选药, 注意加量速度和剂量, 避免严重药物不良反应, 对于最大限度减少患儿发作、 改善认知功能、 减少不良反应、 提高患儿生活质量, 有着非常重要的意义。     

草果知母汤抗癇性的临床观察及实验研究

目的　从临床观察和动物实验两方面研究草果知母汤 (CGZMT)的抗疒间 性。方法　通过对 17例癫疒间患儿药效学观察 ,评价CGZMT的临床疗效。利用小鼠最大电休克发作 (MES)模型、大鼠听源性发作 (AGS)癫疒间模型、小鼠戊四唑阈值发作试验 (MST) ,研究CGZMT的抗疒间 性。结果　临床观察显示 :总有效率 6 4 7% ,单服中药与中西药合用的抗疒间 性无显著性差异 (P >0 0 5 )。CGZMT对小鼠MES的拮抗作用及用药 2周对大鼠AGS的抗疒间 性均与苯巴比妥 (PB)相似 (P >0 0 5 ) ;对MST疗效弱 ,但与氯硝西泮 (CZP)合用抗惊厥率达 85 % ,疗效优于模型组 (P <0 0 1)。结论　CGZMT有肯定的抗疒间 性 ,对强直 阵挛性发作疗效优于失神发作 ,无明显毒副作用。对于失神发作 ,CGZMT与CZP有较强的协同作用     

Newer anti-epileptic drugs

During the past few years, a number of drugs have been added to the anti-epileptic arsenal. This review focusses on five of these drugs which have undergone extensive trials: Vigabatrin, Lamotrigine, Gabapentin, Felbamate and Oxcarbazepine. Some of these antiepileptic drugs appear to be helpful for treatment of catastrophic childhood epilepsies. Vigabatrin appears promising in children with infantile spasms who do not respond to ACTH or Prednisolone. Children with Lennox-Gastaut syndrome may respond to treatment with lamotrigine or Vigabatrin. Gabapentin and vigabatrin have proved to be effective in refractory partial seizures. Oxcarbazepine, a ketoderivative of carbamazepine, is as effective as Carbamazepine but has a better safety profile. Lesser neurotoxicity and fewer drug interactions is another advantage with these drugs. However monitoring is required to determine the long term safety with their usage. These drugs have a definite role in childhood epilepsies refractory to conventional antiepileptic drugs.     

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??Intractable epilepsy often requires a combination of drugs. To reduce the seizures in children?? minimize the side effects of drugs?? and improve the patient’s quality of life?? it is very important to be familiar with the main mechanisms and pharmacokinetics of antiepileptic drugs?? and correctly choose drugs according to the types of seizure and syndrome. Also every time to add a new drug?? it must consider the dosage and speed of titration of the drug to avoid serious adverse effects.     

婴儿恶性游走性部分性癫癎综合征研究进展

婴儿恶性游走性部分性癫癎综合征是在婴儿期发病的一种严重的癫癎性脑病,1995年由Coppola等首次报道,目前世界共有近80例报道,国内暂无报道.目前该综合征病因不明,早期诊断困难,传统抗癫癎药物疗效不佳.该文就婴儿恶性游走性部分性癫癎综合征可能的病因、临床特点、诊断、治疗进行综述.     

癫癎患儿共患注意缺陷多动障碍的临床分析

目的：评估癫癎患儿共患注意缺陷多动障碍（ADHD）的共患率,探讨引起癫癎患儿共患ADHD的相关危险因素。方法：选取符合癫癎和癫癎综合征诊断标准、年龄在6～15岁的患儿256例,调查癫癎患儿与ADHD的共患率及危险因素。结果：192例患儿完成系统评定。ADHD的共患率为42.2%。首次发作年龄越早,抗癫癎药物治疗时程越长及多种抗癫癎药物联合应用者癫癎共患ADHD的共患率越高;Lennox-Gastaut 综合征和全身强直-阵挛发作型癫癎及脑电图提示多病灶起源的癫癎患儿ADHD共患率较高。结论：ADHD在癫癎患儿中的共患率较高。癫癎患儿共患ADHD相关的危险因素包括：癫癎的首次发作年龄、癫癎发作类型、癫癎综合征的类型、脑电图特征及抗癫癎药物的使用。     

Lacosamide in children with refractory status epilepticus. A multicenter Italian experience

ObjectiveStatus epilepticus (SE) is considered a life-threatening medical emergency. First-line treatment with antiepileptic drugs (AEDs) consists of intravenous benzodiazepines followed by phenytoin. SE is considered refractory (RSE) when unresponsive to standard doses of the first two AEDs. Scarce evidence is available to support specific guidelines for the management of RSE in either adults or children. This study aimed to assess the efficacy and tolerability of intravenous (iv) lacosamide (LCM) in children affected by RSE.MethodChildren with RSE who were treated with ivLCM were included in the study. Efficacy was defined as the cessation of seizures after administration of ivLCM, with no need for any further antiepileptic drug. All patients had been unsuccessfully treated following standard protocols before ivLCM was administered.ResultsEleven children entered the study (mean age: 9.4 years). Etiology was symptomatic in 7 patients (63%). RSE was convulsive (focal or generalized) in 6 patients and nonconvulsive in 5. The mean initial bolus dose of LCM was 8.6 mg/kg. The drug, which was used as a fourth or later option, was effective in stopping RSE in 45% of patients, with seizures terminating within 12 h in three children. No serious adverse events attributable to LCM were reported.ConclusionsLCM might be an effective and well-tolerated AED in children with RSE.     

甲基丙二酸血症患儿治疗前后的脑电图监测

目的观察甲基丙二酸血症(MMA)患儿治疗前后脑电图的变化,探讨其对MMA疗效评估的意义。方法对2000—2005年在首都儿科研究所确诊为MMA的26例患儿采用16导视频脑电图仪检查,并将治疗前后的脑电图结果进行对比分析。结果(1)脑电图结果:异常16例(16/26,62%),主要为高峰节律紊乱、慢波背景、癎样放电等;正常10例(10/26,38%)。(2)惊厥发作:16例脑电图异常患儿中12例(12/16,75%)有惊厥发作,主要为痉挛样、强直-阵挛发作,病程1个月至4年。(3)转归:脑电图异常伴惊厥发作的12例患儿中,11例发作停止、脑电图改善(正常7例,异常慢波活动4例);1例死于感染后多脏器功能衰竭,其脑电图由高峰节律紊乱转为放电持续状态;11例患儿惊厥控制2~6个月后停用抗癫癎药,随诊1~5年无发作。4例脑电图异常无惊厥发作患儿,3例随诊中无发作,脑电图无改善,1例脑电图持续低电压死亡。10例脑电图正常患儿中1例随诊中脑电图有棘波发放,无临床发作。结论(1)对婴幼儿难治性癫癎伴有智力低下者应进行病因学诊断;(2)脑电图是了解MMA患儿脑功能的客观指标之一,无惊厥发作的MMA患儿亦应进行脑电图的检测;(3)脑电图是评估病因治疗疗效的客观指标之一;(4)合并癫癎的MMA患儿在病因治疗的同时应辅以抗癫癎药物治疗,疗程个体化。