抗癫药物的作用机制与用药

癫(癎)是一种常见病、多发病,药物治疗是最重要的手段.采用现代有效的抗癫(癎)药物,可使约80%患者的癫(癎)发作获得控制.然而,到目前为止仍无一种药物能控制所有发作类型或癫(癎)综合征.正确选择抗癫(癎)药物,是疗效的保证.除按照癫(癎)发作类型和综合征选择外,还要参考抗癫(癎)药物的作用机制.     

星形胶质在癫(癎)中的生物学机制研究进展

离子通道改变、神经递质及其受体调控异常、血脑屏障损伤、炎症、氧化应激损伤等均与癫(癎)发作有关.近年来通过对癫(癎)动物模型、癫(癎)患者尸体解剖或手术切除患者癫(癎)病灶的研究表明,星形胶质与癫(癎)的发生发展有一定的关系,但两者之间的因果关系一直没有定论.目前多数抗癫(癎)药物都是针对神经元,对患者的认知和脑功能都有一定的影响.因此,从星形胶质的角度去探讨癫(癎)的发病机制,有助于发现新的干预靶点以开发新型抗癫(癎)药物.     

对Lennox-Gastaut综合征的新认识

Lennox-Gastaut综合征(LGS)是一种在儿童期发病的严重癫(癎)性脑病.临床表现为多种癫(癎)发作形式、精神发育迟缓、脑电图弥漫的棘慢复合波.早期诊断困难,传统抗癫(癎)药物疗效不佳.近年来多种新抗癫(癎)药物用于LGS治疗,治疗观念及治疗效果评价也有所改变.文章就LCS诊断、治疗指南,以及一些新的认识进行综述.     

MicroRNA在癫癎中的研究进展

微小核糖核酸(MicroRNA, miRNA)是一类短链非编码RNA,主要通过控制信使RNA的翻译起到转录后水平的调节作用.癫癎是一种严重的、慢性的神经系统疾病,大多在儿童期发病.大脑在病理的情况下会表达独特的miRNA,并与癫癎的发生有关.miRNA拓展了研究者对于癫癎发生机制的认识,使其成为新的治疗靶点和有效的抗癫癎新药.该文介绍了与癫癎发生密切相关的几种miRNA在癫癎发生、发展中的作用.     

难治性癫(癎)的发病机制研究进展及前景展望

癫(癎)是儿童常见的神经系统疾病,近年来有关难治性癫(癎)发病机制的研究取得一些突破性进展.文章就难治性癫(癎)发病机制的研究现状进行综述,主要包括4个方面的内容,其中多药转运体表达增多可能导致进入脑组织的药物浓度降低是产生耐药的主要因素,文章重点阐述多药耐药基因和难治性癫(癎)的关系,并对难治性癫(癎)的进一步研究方向和临床应用前景提出新的思路.     

DNA甲基化在癫(癎)发病机制及治疗中的研究进展

DNA甲基化是重要的表观遗传修饰,通过DNA甲基转移酶完成,与多种表观遗传学调控机制相互作用,参与调控基因表达和细胞分化的过程.目前在癫(癎)研究中发现了大量DNA甲基化相关改变,其在癫(癎)发病中的作用愈见明显.该文就DNA甲基化在癫(癎)发病机制中的研究进展进行了系统的分析和综述,并阐述了其在癫(癎)治疗上的应用和前景.     

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.     

良性癫(癎)伴中央颞区棘波与其他类型癫(癎)偏头痛发生率的比较

目的 探讨良性癫(癎)伴中央颞区棘波(BECT)与其他类型癫(癎)和偏头痛是否有共同的发病基础.方法 2003年6月至2006年6月对山东大学齐鲁医院收治的BECT患儿采用配对队列研究,每l例BECT患儿(共53例入组)根据年龄和性别匹配1例隐源性或症状性部分发作性癫(癎)患儿和l例无癫(癎)发作患儿.向入组队列的患儿父母或直接监护人问卷或电话访谈,收集有关患儿家庭情况、偏头痛或偏头痛等位症信息.根据国际头痛协会(HIS-R)制定的修订版头痛分类标准,比较各队列组癫(癎)发作情况和偏头痛发生率之间的差异.结果 BECT组简单部分性发作比例较隐源性或症状性癫(癎)组高(P<0.01);在隐源性或症状性癫(癎)组中,15例(28.3%)为癫(癎)病灶在前额,12例(22.6%)癫(癎)病灶在颞叶,3例(5.7%)病灶在前颞,3例(5.7%)病灶在枕叶,1例(1.9%)病灶在顶叶,8例(15.1%)病灶在中央,11例(20.8%)为多灶性.5例(9.4%)曾行过癫(癎)外科手术.两癫(癎)发作组中偏头痛发生率差异没有统计学意义.但隐源性或症状性组癫(癎)发作后头痛较BECT组高(P<0.05).与无癫(癎)发作组相比,肯定型和可能型偏头痛发生率较高(P=0.05).隐源性或症状性癫(癎)中有8例头痛只发生在癫(癎)作后,而BECT组中无1例是这种情况.有先兆型偏头痛的在癫(癎)发作组中差异没有统计学意义,但和无癫(癎)相比,BECT组良性发作性眩晕发生率较高(P<0.05),运动性呕吐发生率也较高(P<0.01).其直系亲属中母亲91%而父亲53%有头痛病史.除了隐源性或症状性组中儿童母亲有先兆无偏头痛发生率较其他组高外,其余差异均无明显统计学意义.结论 癫(癎)和偏头痛发病机制之间可能存在共同的易患基础,癫(癎)发作可能加重偏头痛的易患倾向.     

小儿癫(癎)的远期预后

近年来,随着对癫(癎)认识的不断深入,发病机制研究的进展,诊断技术的提高,抗癫(癎)新药的发现,治疗方法的改进,血药质量浓度监测的开展,使小儿癫(癎)的预后有了很大改善.本文就小儿癫(癎)的远期预后及影响预后的因素总结如下. 一、小儿癫(癎)的远期预后 1.预后预测及缓解率目前综合各种因素对小儿癫(癎)的远期预后进行预测尚在探讨研究中.Geelhoed等[1]评价了分类树模型(classification tree models)和逐步逻辑回归产生的预测模型(stepwise logistic regression produced predictive models)在推断儿童期起病的癫(癎)患者预后的准确性,认为根据现有的临床和脑电图变量预测儿童癫(癎)的预后较困难,约1/3不正确.     

癫(癎)与孤独症共患相关综合征基因研究进展

癫(癎)与孤独症至今都尚未发现特异性的致病基因,但二者的共患率却达到约30％,提示二者可能存在共同的发病机制.癫(癎)与孤独症共患常表现在一些常见的综合征中,如Rett综合征、结节性硬化、脆性X综合征等,这些综合征的发生多与神经系统发育相关的基因突变有关,如ARX、MECP2基因,基因突变的结果往往使突触重塑发生异常,蛋白质调节失控,致大脑兴奋与抑制系统不平衡,最终患病.早期发生的癫(癎)和孤独症的发病机制是多水平的,基因突变可以造成细胞和分子水平的改变,最终造成智力和行为异常.该文研究探讨这些综合征的发病机制研究进展,有助于了解癫(癎)与孤独症共患的发病机制以及寻找治疗共患患儿的新方法.     

注意缺陷多动障碍的定量脑电图研究进展

注意缺陷多动障碍是儿童期最常见的精神疾病之一，其临床表现为注意力不集中、多动和冲动，可严重影响患者的家庭生活、个人成就及社交关系，目前对该病仍缺乏客观指标进行诊断及评估疗效。脑电图检查可无创性地记录脑电活动，反映脑功能情况。该文就近年来定量脑电图在注意缺陷多动障碍方面的研究进展作一综述。     

癫癎发作生物节律的研究进展

随着对癫癎研究的不断深入,癫癎发作的时相性越来越受到关注。癫癎发作存在生物节律,同一类型的癫癎在不同时间段、不同状态(睡眠/觉醒、昼夜更替)发作频率不同。癫癎生物节律的分子机制、内分泌机制相当复杂,目前存在多种假说。明确癫癎发作的生物节律,根据其发作节律予以预防及治疗,既可以有效控制癫癎发作,也可以减少药物不良反应。癫癎发作生物节律的研究将为癫癎治疗提供新的思路。     

Evaluation of children for epilepsy surgery

There are three main components to the evaluation of children who are candidates for epilepsy surgery: (1) confirmation of the epileptic nature of the seizures, (2) establishing the medical intractability of the child's epilepsy and (3) localization of the epileptogenic zone. Differentiating epileptic from nonepileptic events requires careful review of the history and the electroencephalogram. Electroencephalographic recording of the habitual seizures usually suffices to confirm the epileptic or nonepileptic nature of the events. Medical intractability is established by assuring that antiepileptic medications appropriate for the child's particular epilepsy syndrome have been used and have been titrated to maximum tolerance before being deemed ineffective. Confident localization of the epileptogenic zone requires that multiple findings such as behavior during the seizure, ictal and interictal EEG, and cerebral imaging studies provide data that are convergent with respect to a likely area of seizure onset.     

The clinical conundrum of neonatal seizures

There is increasing evidence that neonatal seizures have an adverse effect on neurodevelopmental progression and may predispose to cognitive, behavioural, or epileptic complications later in life. However, given the uncertainty about the efficacy and toxicity of the commonly used anticonvulsants, when and how aggressively to treat such seizures is a difficult decision.     

Pathogenesis of bronchiectasis

Non-cystic fibrosis bronchiectasis is a heterogeneous condition and its pathogenesis is still not well defined. A combination of a defect in host defense and bacterial infection allows microbial colonization of the airways resulting in chronic inflammation and lung damage. An ongoing cycle of infection and inflammation may be established. Typically, the walls of the small airway are infiltrated by inflammatory cells causing obstruction whilst mediators, such as proteases released predominantly by neutrophils, damage the large airways resulting in bronchial dilatation. Adjacent parenchyma is also involved in the inflammation. Lung function testing generally demonstrates mild to moderate airflow obstruction that progresses over time. There are a large number of different aetiologic factors associated with bronchiectasis. A variety of different microbial pathogens is involved and they change as disease progresses.     

Neonatal epilepsy and inborn errors of metabolism]

Metabolic disorders constitute an important cause of neurologic disease, including neonatal epilepsy. Epilepsy rarely dominates the clinical presentation, which is more frequently associated with other neurologic symptoms, such as hypotonia and/or vigilance disturbances. In most cases, epilepsy secondary to inherited metabolic disorders presents with polymorphic clinical and electrographic features that are difficult to classify into precise epileptic syndromes. However, specific types of seizures, such as myoclonic seizures or distinctive electroencephalographic patterns, such as suppression burst patterns, epileptic syndrome or early myoclonic encephalopathy, may suggest a specific metabolic disease. The aim of this article is to help clinicians in reviewing potential metabolic diagnoses and approaching metabolic evaluations.     

Ohtahara syndrome or early-onset West syndrome? A case with overlapping features and favorable response to vigabatrin

BackgroundThe so called “severe neonatal epilepsies with suppression-burst pattern” include early infantile epileptic encephalopathy, and early myoclonic encephalopathy. Both syndromes are characterized by pharmacoresistant seizures that appear in the first weeks (up to the third month) of life, an electroencephalographic suppression-burst pattern, and a grim prognosis. Many patients later present with other forms of epileptic encephalopathies with difficult-to-treat seizures, such as West syndrome, and those who survive usually suffer from severe neurodevelopmental troubles. We here report the case of a patient who presented at our center with features consistent with a mixed form of these epileptic encephalopathies, and favorable neurodevelopmental evolution.AimsTo draw attention on the potentially favorable effect of vigabatrin in early-onset epileptic encephalopathies.MethodsCase study.ResultsIn our patient, seizures immediately stopped upon initiation of vigabatrin treatment, and his development and neurological examination at one year are normal.ConclusionsVigabatrin should be considered as an early treatment option in early-onset epileptic encephalopathies.     

Approach to pediatric epilepsy surgery: State of the art,Part II: Approach to specific epilepsy syndromes and etiologies

The second of this 2-part review depicts the specific approach to the common causes of pediatric refractory epilepsy amenable to surgery. These include tumors, malformations due to abnormal cortical development, vascular abnormalities and certain epileptic syndromes. Seizure freedom rates are high (usually 60–80%) following tailored focal resection, lesionectomy, and hemispherectomy. However, in patients in whom the epileptogenic zone overlaps with unresectable eloquent cortex, and in certain epileptic syndromes, seizure freedom may not be achievable. In such cases, palliative procedures such as callosotomy, multiple subpial transections and vagus nerve stimulation can achieve reduction in seizure severity but rarely seizure freedom. Integration of the new imaging techniques and the concepts of neuronal plasticity, the epileptogenic lesion, the ictal onset, symptomatogenic, irritative, and epileptogenic zones is an expanding and dynamic process that will allow us, in the future, to better decide on the surgical approach of choice and its timing.     

KCNT1基因变异致早发癫痫性脑病1例报告并文献复习

目的 探讨KCNT1基因变异所致早发癫痫性脑病的临床特点、诊断及治疗.方法 回顾分析1例确诊KCNT1基因变异相关早发癫痫性脑病患儿的临床资料,并复习相关文献.结果 患儿女,2岁7个月,自新生儿期起频繁癫痫发作,以局灶阵挛性发作为主要表现,伴发育落后.脑电图示痫样放电.头颅影像学及遗传代谢筛查无明显异常.基因检测结果患...     

儿童偏头痛与癫癎相关性的研究

目的　探讨儿童偏头痛与癫的相关性及鉴别诊断。方法　对 32例偏头痛患儿 (其中 9例并临床癫发作 )进行脑电图及临床分析。结果　 32例中脑电图异常 1 8例 ,其中 1 4例为偏头痛 ,异常率为43 .75 % ,4例枕叶癫。 3例普通型头痛伴癫发作 ,脑电图 3次复查正常 ,2例复杂型偏头痛伴临床癫发作 ,脑电图均表现异常。结论　儿童偏头痛常常表现脑电图非特异性异常 ,甚至样放电 ,但以脑电图异常不能代替临床诊断。头痛性癫的诊断必须结合临床表现和脑电图检查结果综合判定 ,并与偏头痛进行鉴别。某些偏头痛可以伴癫发作 ,两者交叉重叠 ,极易混淆。对头痛性癫的诊断应慎重