神经刺激技术在药物难治性癫痫中的治疗进展

癫痫是一种反复发作的慢性神经系统疾病,绝大多数(约70%)可通过使用抗癫痫药物控制发作,但仍有部分患者难以通过药物治疗控制,即难治性癫痫。通常,采用手术切除癫痫病灶进行治疗,但临床上仍有诸多难治性癫痫患者由于多种原因无法进行手术。对于这部分患者可选择神经刺激术进行治疗。神经刺激术的种类较多,具有相对靶向性、可调节性及持续性的特点。目前,主要用于治疗疼痛、运动障碍、震颤、癫痫等多种疾病。本文对神经刺激术治疗癫痫的相关研究进行综述。     

成人难治性部分发作性癫痫的药物治疗研究进展

正癫痫是神经科的常见疾病[1]。约50%的癫痫可用单一药物完全控制,15%~25%的癫痫通过更换或添加抗癫痫药物而治愈,但仍有20%~30%的癫痫无法用药物治疗控制[2]。目前,难治性癫痫的定义尚无统一的标准。我国学者认为难治性癫痫指应用抗癫痫药物正规治疗2年以上仍不能有效控制,且每月发作仍在4次以上,严重影响患者日常生活并经全面检查并无颅内占位或中枢神经系统病变[3]。本文     

儿童难治性癫痫的研究进展

癫痫是一种由多种病因引起的慢性脑部疾病,以神经元过度放电导致反复性、发作性和短暂性的中枢神经系统功能失常为特征。癫痫发作对儿童的生长发育、生活和学习造成了很大影响,同时也给家庭带来了困惑。大多数的癫痫是在儿童时期起病,随着临床实践、临床脑电图学、病因及发病机制以及诊断学水平的提高,尤其是医学影像学、分子遗传学技术的不断发展,儿童癫痫的诊断和治疗水平不断提高。大部分癫痫患儿经过正规治疗后可以达到控制或者症状缓解,仍有少部分难以得到有效控制或者出现复发,成为难治性癫痫。目前对儿童难治性癫痫的治疗方案有多种,主要包括药物治疗,外科手术治疗,神经调控,生酮饮食治疗以及基因治疗等。本文将对目前儿童难治性癫痫的研究进展作一综述。     

依达拉奉辅助治疗难治性癫痫的疗效及机制

目前,各家对难治性癫痫（refractory epilepsy）的定义大多是根据其发作频率和对抗癫痫药物治疗反应而定。Oxbury等将其认为是临床经过迁延,3种一线药物采用“最理想”的剂量单独或合并使用2年以上仍有癫痫发作。吴逊等将难治性癫痫定义为：频繁的癫痫发作至少每月4次以上,应用适当的一线抗癫痫药物正规治疗,药物稳态血浓度在有效治疗范围内,至少观察2年,仍不能控制发作且影响日常生活,[第一段]     

儿童难治性癫痫的手术治疗

癫痫是儿童神经系统常见疾病之一,其发病原因、临床表现及治疗原则较成人癫痫具有明显差异.随着抗癫痫药物的不断创新、扩展及人们对癫痫的深入研究,大多数癫痫患儿可以得到理想的控制,但仍有部分患者经药物治疗无效而成为难治性癫痫,是外科干预治疗的潜在目标.近年来手术治疗难治性癫痫的技术得到迅速发展,特别是针对儿童难治性癫痫的手术治疗取得重大突破.目前用于儿童癫痫的外科治疗方法主要有切除性手术、毁损性手术、阻断通路手术和神经调控手术等.     

迷走神经刺激术治疗药物难治性癫痫的价值

尽管目前癫痫的药物治疗已取得较大进展,但仍有20％～30％的患者对癫痫药物治疗反应差,部分癫痫发作难以有效控制,即所谓的药物难治性癫痫。癫痫病灶切除术是治疗药物难治性癫痫的有效方法,但并非所有患者均能找到确切病灶,而且部分患者手术后效果不佳。1988年,迷走神经刺激术(vagus nerve stimulation,VNS)开始应用于治疗药物难治性部分性癫痫,为药物难治性癫痫提供了一种新的治疗方法。     

24例难治性癫痫患者临床特点分析

难治性癫痫目前国内外仍没有统一的定义,通常指应用目前的抗癫痫药物、在有效的治疗期内、合理用药不能终止其发作或已被临床证实是难治的癫痫及癫痫综合征[1].对难治性癫痫的全面认识,包括其成因、临床表现、辅助检查及治疗史进行全面的总结分析,对临床医生更进一步认识难治性癫痫,对患者的规范治疗及改善预后有重要的意义.本研究通过对已行手术治疗的24例难治性癫痫患者临床特点总结分析,旨在为临床选择癫痫的手术适应证提供帮助.     

难治性癫痫动物模型研究进展

临床上大多数癫痫病人的发作都可获得满意的控制,但也有相当一部分病人虽经早期合理使用一线抗癫痫药物（AED）,仍不能较好控制发作而成为难治性癫痫。难治性癫病的病因复杂,既有先天性因素,又有后天环境因素。由于在病人身上研究难治性癫痫的发生机制比较困难,故目前主要通过建立难治性癫痫动物模型,探讨其形成和耐药机制以及筛选新的AED。一、难治性癫痫动物模型的选择标准【引l．模型的癫痫性发作应与人类癫痫的临床表现相似。临床上最常见的难治性痴痴包括复杂部分性发作、L规加时Gastaut综合征和婴儿痉挛症等,因此,模拟这…     

难治性癫痫与FDG-PET显像

难治性癫痫是指采用目前的抗癫痫药物进行正规的治疗，在有效治疗期内，通过多种努力仍不能控制其发作的癫痫。一般认为其病程应在3～4年以上，每月发作至少4次，经过长期系统抗癫痫药物的治疗不能控制其发作，并且因为频繁发作而影响病人的工作、学习和生活。本文就难治性癫痫的发病     

胼胝体切开术治疗难治性癫痫的价值

尽管目前癫痫治疗已取得较大进展,多数病人的癫痫发作经系统的药物治疗可得到控制,但仍有约20%～30%的病人对癫痫药物治疗反应差、癫痫发作难以控制,即所谓的难治性癫痫。胼胝体切开术能降低癫痫发作的频率及严重程度,可作为难治性癫痫治疗的一种外科手段。     

Advancing the medical management of epilepsy: disease modification and pharmacogenetics

Despite the recent development of new antiepilepsy drugs, a significant number of children are still unable to achieve seizure freedom without side effects. Understanding the factors behind individual variability in antiepilepsy drug tolerability and dose response and incorporating these factors into a treatment plan would represent an important advance in epilepsy pharmacotherapy. A more thorough understanding of the epileptogenic process may allow clinicians to select antiepilepsy drugs that interrupt or modify various steps in the epileptogenic progression (ie, disease modification). Additionally, advances in the understanding of human genetics may allow for selection of antiepilepsy drugs and dosage regimens based on a patient's clinical characteristics and genotype (ie, pharmacogenetics). This article focuses on these two areas of potential improvement in the medical treatment of patients with epilepsy. Such methods of tailoring antiepilepsy drug therapy would be preferable to the trial-and-error system that is currently used.     

Cognitive and behavioural assessment in clinical trials: when should they be done?

The issue of 'timing' of behavioural assessments in clinical trials can be approached in two different ways. Firstly the 'timing' during the process of drug development. As a rule, cognitive and behavioural side effects of antiepileptic drug treatment do not become an issue until the drug is marketed. At this stage a negative result has large marketing effects and this leads to a tendency to organise 'positive studies'('no-effect results'), that can be achieved by reducing power. A second approach is the 'timing' of cognitive assessment during a trial. The first and intuitive answer to the question 'when this should be done' is to perform assessments during an untreated baseline that is then compared with an endpoint during antiepileptic drug (AED) treatment. This is the 'gold standard design' for cognitive assessments in the majority of the cognitive trials. However, in patients with epilepsy, the behavioural drug effects are not independent from the effect of the epilepsy or the seizures. Recent studies have confirmed that the effect of uncontrolled seizures are often larger than the effects of drug treatment, leading to the so-called seizure confound, that is, adverse cognitive AED effects may be masked by beneficial effects of better seizure control. In such studies endpoint scores are thus improved, hiding possible negative drug effects. Other designs may have other limitations: e.g. in using adjunctive therapy the identification of the components of a treatment most responsible for any observed effects presents a difficult problem; in normal volunteers, exposure durations which are not representative of those in epilepsy patients on chronic treatment represent a major validity issue. We therefore consider the drug withdrawal study as the optimal design for assessing behavioural drug effects. In this design subjects are tested while still on medication and after withdrawal; larger gains in the epilepsy group relative to the controls are considered evidence for a reversible impairment, attributable to AED use.     

Ion channel dysfunction in pathogenesis of idiopathic epilepsies

Despite advances in diagnostics, the cause of epilepsy has still not been unequivocally determined in 60-65% of patients. In this group of patients, genetic factors probably play the main role. It is thought that genetic predisposition is responsible for the occurrence of so-called "idiopathic" forms of epilepsy in about 40% of patients. The genetic basis of epilepsy has been substantiated by numerous examples of familial forms of epileptic syndromes. Among these, autosomal dominant nocturnal frontal lobe epilepsy and juvenile myoclonic epilepsy can be mentioned. Mutations in the neuronal nicotinic acetylcholine receptor subunit genes are responsible for both these epilepsies. Recent advances in molecular genetics have provided the means for better understanding of human epileptogenesis at a molecular level, which facilitates clinical diagnosis and provides a more rational basis for therapy and prevention of this form of epilepsy.     

脑动静脉畸形患者癫痫间发作的相关因素分析

目的 探讨脑动静脉畸形并发癫痫间发作的相关危险因素以及癫痫间的合理预防措施。方法 回顾性分析286例脑动静脉畸形患者的临床及脑动静脉畸形基线资料。根据是否合并癫痫间发作分为癫痫间组和对照组。分析脑动静脉畸形患者并发癫痫间发作的危险因素,观察癫痫间组92例患者的发作类型及发作频率以及药物治疗反应情况。结果 癫痫间组与对照组畸形血管团的位置、畸形血管团直径、静脉引流方向等因素比较差异明显(P<0.05); 非条件多因素Logistic回归分析显示对脑动静脉畸形患者癫痫间发作有显著影响的因素为畸形团直径大于3 cm和由浅静脉或者浅深静脉共同引流(P<0.05)。经过抗癫痫间药物治疗,癫痫间组有69例患者癫痫间发作得到了完全控制,余患者发作频率均有不同程度减低。结论 畸形团直径大于3cm和由浅静脉或者浅深静脉共同引流是脑动静脉畸形患者并发癫痫间的危险因素; 脑动静脉畸形合并的癫痫间发作是一个相对良性过程,抗癫痫间药物对多数癫痫间患者治疗有效。     

Research progress of vagus nerve stimulation in the treatment of epilepsy

The International League Against Epilepsy (ILAE) defined drug‐resistant epilepsy (DRE) that epilepsy seizure symptoms cannot be controlled with two well‐tolerated and appropriately chosen antiepileptic drugs, whether they are given as monotherapy or in combination. According to the WHO reports, there is about 30%‐40% of epilepsy patients belong to DRE. These patients need some treatments other than drugs, such as epilepsy surgery, and neuromodulation treatment. Traditional surgical approaches may be limited by the patient's clinical status, pathological tissue location, or overall prognosis. Thus, neuromodulation is an alternative choice to control their symptoms. Vagus nerve stimulation (VNS) is one of the neuromodulation methods clinically, which have been approved by the Food and Drug Administration (FDA). In this review, we systematically describe the clinical application, clinical effects, possible antiepileptic mechanisms, and future research directions of VNS for epilepsy.     

Genetics of Epilepsy: An Overview

Studies of the genetics of epilepsy have, until recently, involved epidemiologic or segregation analyses of phenotypic characteristics of a number of seizure disorders. Technical advances in molecular biology involving gene mapping and gene identification have made it possible to examine the heritability of various epilepsy syndromes. Using “reverse genetics” or positional cloning, it is possible to identify an abnormal protein through gene isolation and cloning. Genes are localized through analysis of linkage to phenotypic markers (proteins) or DNA markers such as restriction fragment length polymorphisms, variable number of tandem repeats, and dinucleotides. Methods used to obtain DNA of interest involve digestion of genomic DNA with specific restriction endonucleases or amplification of DNA by polymerase chain reaction technology. Gel electrophoresis is the basis for the separation of different sized DNA. Inherited disorders for which a gene has been cloned or localized have highly penetrant, well-defined clinical phenotypes with no remissions and abundant clinical material. Genetic epilepsies, however, are variably penetrant age-dependent disorders with heterogenous clinical phenotypes. Despite these difficulties, three genetic epilepsies have been mapped to specific chromosomes: benign familial neonatal convulsions to 20q, juvenile myoclonic epilepsy to 6p, and Baltic progressive myoclonus epilepsy to 21q. Further progress in understanding genetic epilepsies will depend on better definition of syndrome phenotypes, isolation of the epilepsy gene(s), and identification of the abnormal protein(s).     

Epilepsy research: a window onto function to and dysfunction of the human brain

As one of the most common neurological disorders, epilepsy has devastating behavioral, social, and occupational consequences and is associated with accumulating brain damage and neurological deficits. Epilepsy comprises a large number of syndromes, which vary greatly with respect to their etiology and clinical features, but share the characteristic clinical hallmark of epilepsy-recurrent spontaneous seizures. Research aimed at understanding the genetic, molecular, and cellular basis of epilepsy has to integrate various research approaches and techniques ranging from clinical expertise, functional analyses of the system and cellular levels, both in human subjects and rodent models of epilepsy, to human and mouse genetics. This knowledge may then be developed into novel treatment options with better control of seizures and/or fewer side effects. In addition, the study of epilepsy has frequently shed light on basic mechanisms underlying the function and dysfunction of the human brain,     

Classification of seizures and epilepsy

The management of seizures and epilepsy begins with forming a differential diagnosis, making the diagnosis, and then classifying seizure type and epileptic syndrome. Classification guides treatment, including ancillary testing, management, prognosis, and if needed, selection of the appropriate antiepileptic drug (AED). Many AEDs are available, and certain seizure types or epilepsy syndromes respond to specific AEDs. The identification of the genetics, molecular basis, and pathophysiologic mechanisms of epilepsy has resulted from classification of specific epileptic syndromes. The classification system used by the International League Against Epilepsy is periodically revised. The proposed revision changes the classification emphasis from the anatomic origin of seizures (focal vs generalized) to seizure semiology (ie, the signs or clinical manifestations). Modified systems have been developed for specific circumstances (eg, neonatal seizures, infantile seizures, status epilepticus, and epilepsy surgery). This article reviews seizure and epilepsy classification, emphasizing new data.     

Update on pharmacogenetics in epilepsy: a brief review

Recent developments in the pharmacogenetics of antiepileptic drugs provide new prospects for predicting the efficacy of treatment and potential side-effects. Epilepsy is a common, serious, and treatable neurological disorder, yet current treatment is limited by high rates of adverse drug reactions and lack of complete seizure control in a significant proportion of patients. The disorder is especially suitable for pharmacogenetic investigation because treatment response can be quantified and side-effects can be assessed with validated measures. Additionally, there is substantial knowledge of the pharmacodynamics and kinetics of antiepileptic drugs, and some candidate genes implicated in the disorder have been identified. However, recent studies of the association of particular genes and their genetic variants with seizure control and adverse drug reactions have not provided unifying conclusions. This article reviews the published work and summarises the state of research in this area. Future directions for research and the application of this technology to the clinical practice of individualising treatment for epilepsy are discussed.