生酮饮食治疗儿童难治性癫痫

生酮饮食(ketogenic diet KD)是一种通过高脂肪饮食来治疗儿童癫痫的方法.其治疗癫痫的厣史山来已久.早在上世纪初期,有人发现饥饿可以有效的控制癫痫发作.     

CYP基因多态性与抗癫痫药物代谢相关性的研究进展

癫痫( epilepsy,EP)是一种常见的神经系统疾患,已成为重要的公共卫生问题[1].目前癫痫治疗仍以抗癫痫药物(antiepileptic drugs,AEDs)控制发作为主,通过规范的诊疗,大多数患者可以控制发作.但在癫痫的临床治疗过程中,作者发现AEDs的代谢存在较大的个体差异,即使患者发作类型相同,应用相同剂量的同种AEDs治疗,其血药浓度与疗效也相差甚远,有的患者用到最大耐受剂量时,仍不能控制发作,而有的患者应用常规剂量,就会出现严重的药物副作用.单核苷酸多态性(single nucleotide polymorphism,SNPs)是指同一物种不同个体基因组DNA等位基因序列存在差别的现象.诸多研究表明[2-5]:细胞色素P450( cytochrome P450,CYP)基因SNPs是影响多种AEDs代谢的重要因素,特别是CYP2C9与CYP2C19基因突变后会引起多种AEDs血药浓度升高,如苯妥英( phenytoin,PHT)、苯巴比妥(phenobarbital,PB)、丙戊酸(valproic acid,VPA)等,说明CYP基因SNPs影响多种AEDs的代谢,是导致AEDs个体代谢差异的重要原因.基于不同个体的特定基因型选择合适的药物剂量,以求达到临床个体化治疗的目的.本文将从与AEDs代谢相关的CYP基因SNPs及其对AEDs代谢的影响等几个方面做一综述.     

生酮饮食联合抗癫痫药物对难治性癫痫的疗效评价

目的评价生酮饮食(KD)联合抗癫痫药物对难治性癫痫的疗效。方法对77例难治性癫痫患者在原有药物不变的基础上添加KD治疗3个月。观察癫痫临床发作频率的改变,判断疗效。比较有效组和无效组患者的临床资料,分析影响KD疗效的因素。结果在KD治疗后,完全控制16例(20.8%),显著有效14例(18.2%),有效12例(15.6%),无效35例(45.5%);KD添加治疗的总有效率为54.5%,保留率为76.6%。KD添加治疗无效组合用药物种类、智能障碍比例及睡眠障碍比例均明显高于有效组;而痉挛发作比例则明显低于有效组(均P0.05)。结论 KD联合抗癫痫药物治疗难治性癫痫总体有效,尤其是痉挛发作类;对伴有智能障碍、睡眠障碍及合用药物种类偏多者疗效欠佳。     

生酮饮食对儿童难治性癫痫疗效与安全性的Meta分析

目的 系统评价生酮饮食(KD)治疗儿童难治性癫痫的有效率和不良反应。方法 检索PubMed、Cochrane Library、中国知网、万方数据库、维普中文科技期刊数据库，检索时限自建库至2021年6月30日，纳入KD治疗儿童癫痫的随机对照研究文献。采用Review Manager 5.4软件对符合纳入标准的临床研究进行Meta分析。结果 最终纳入14篇随机对照研究，包含1 080例病例。KD组癫痫控制发作有效率显著高于对照组(RR=2.13,95%CI:1.46～3.11,P<0.05)。经典KD组与改良Atkins生酮饮食(MAD)组的癫痫控制有效率(RR=1.21,95%CI:0.95～1.53,P=0.12)及不良反应率(RR=1.11,95%CI:0.81～1.53,P=0.52)差异无统计学意义。结论 KD可提高难治性癫痫患儿的治疗有效率，是难治性癫痫的重要手段之一，经典KD和MAD的疗效和不良反应相当。     

电压门控钠离子通道与药物抗性癫痫

癫痫患者中约三分之一无法以现有抗癫痫药物(anti-epilep-tic drugs,AEDs)有效控制发作,称为药物抗性癫痫(drug-resist-ance epilepsy,DRE).药物抗性癫痫的主要形成机制之一是AEDs的作用靶点发生结构或功能改变,AEDs无法结合预定靶点抑制神经元过度放电,无法控制癫痫发作.电压门控性钠离子通道(voltage-gated sodium channel,VGSC)主要在可兴奋性细胞中表达,其结构和功能异常可引起神经元的膜兴奋性改变,参与癫痫的发病机制.     

迷走神经刺激术治疗儿童难治性癫痫的研究进展

癫痫是一种严重威胁人类身心健康的慢性功能性神经疾病,是几个世纪以来困扰医学界的难题之一。药物难治性癫痫以反复癫痫发作为主要特征,通常规范使用2种及以上抗癫痫药物(AEDs)症状难以控制,伴有认知功能损害的疾病。迷走神经刺激术(Vagus nerve stimulation,VNS)是一种无需开颅、通过神经调控治疗难治性癫痫的方法,在不损害重要神经功能的前提下,通过手术的方式阻断癫痫发作时电流传导通路,从而减少或者控制癫痫发作,可以降低因痫性放电继发脑损害,进而减少抗癫痫药物使用产生的副作用。自1997年美国食品药品监督局批准VNS上市应用于治疗癫痫以来,其适应证已经从成人逐步扩展到了儿童。儿童作为癫痫患者的特殊群体,处于生长发育关键期,有效、及时的调控干预可以为患儿中枢神经系统发育创造时机,为难治性癫痫患者治疗提供新思路。文章探讨了VNS的年龄适应证以及在不同年龄段儿童中的应用,并对VNS在改善儿童认知行为,儿童遗传性癫痫、发育性和癫痫性脑病、儿童结构性病因相关性癫痫治疗的有效性,VNS使用的安全性和不良反应等方面作一综述。     

癫痫患者高动脉粥样硬化风险形成机制探讨

癫痫是一种常见的神经系统疾病,目前控制癫痫发作的主要方法为药物治疗,大多数患者需要长期服用抗癫痫药物(anti-epileptic drugs,AEDs),但是长期AEDs治疗会导致各种不良反应.     

生酮饮食治疗对人体各系统影响

正癫痫是儿科系统常见病,据中国卫生部及抗癫痫协会统计数据显示,0~14岁儿童癫痫发病率为151/10万,患病率为3.45‰,经过各种抗癫痫药物治疗,虽70%~80%患儿可治愈,仍有20%~30%患儿发作得不到控制,成为难治性癫痫,需要寻求其他治疗手段~[1]。生酮饮食(KD)用于难治性癫痫治疗在国外已有90余年历史,通过让癫痫患者进食脂肪/(蛋白质+碳水化合物)重量比为4∶1的饮食来控制癫痫发作(饮     

癫痫患者更换抗癫痫药物后的预后分析:一项配对的前瞻性研究

一系列单队列研究已对癫痫患者更换抗癫痫药物(AEDs)预后进行了分析。研究以对照研究方式第一次探究了这个问题,针对服用所有类型的AEDs的控制不佳和癫痫无发作的癫痫患者,通过配对前瞻性研究方法对这些结果作进一步补充研究回顾9个月内所有的门诊患者以确定单药治疗局灶性癫痫患者。并将更换AEDs的患者作为病例组,维持原来单药治疗方案作为对照组。分别针对发作现状(前6个月内是否有癫痫发作)、目前AEDs和控制不佳的AEDs数量对病例组和对照组进行配对,并在6个月后评估结果。病例组中癫痫无发作患者(n=12)在6个月随访期间癫痫发作复发率为16.7%,对照组为2.8%(n=36,P=0.11)。病例组中控制不佳癫痫患者(n=27)在6个月随访期癫痫发作缓解率为37%,对照组为55.6%(n=27,P=0.18)。控制不佳癫痫患者中治疗失败的药物在2种或2种以上的患者更不容易在6个月内达到病情缓解(P=0.057)。AEDs的药理机制和改变AEDs剂量均对癫痫预后无影响。研究进一步对癫痫无发作患者进行评估,更换药物的患者比维持原药物治疗患者癫痫发作的复发风险高14%。与维持原来药物方案相比,更换AEDs对控制不佳癫痫患者来说并不可能更易获得缓解,说明癫痫缓解是疾病的自发性改变,而非药物作用。     

癫痫与微小RNA和生酮饮食的研究进展

微小RNA（microRNA ,miRNA）与癫痫的发生发展过程有重要关系,可通过调控其靶基因参与信号传导通路,发挥着类似于癌基因或抑癌基因的作用,目前已发现多种miRNA与癫痫关系密切。生酮饮食（keto‐genic diet ,KD）是一种用来治疗儿童癫痫的方法,其有效性和安全性已经得到全世界的公认,目前认为KD治疗癫痫的可能机制有KD影响脑组织的能量代谢和神经递质以及KD具有抗氧化和抗凋亡作用。全面研究KD治疗癫痫的miRNA调控机制将可能对研发新型抗癫痫药物提供理论依据。     

Diagnostic Difficulties and Treatment Implications

Summary: Differentiation between types of epileptic seizures has been aided in recent years by the introduction of intensive neurodiagnostic techniques and the development of increasingly detailed classification systems. Paradoxically, these developments have not simplified the task of matching the appropriate antiepileptic drug to a particular seizure type. It is reasonable to assume that anticonvulsant drugs will have different effects on different types of seizures, but faulty, circular reasoning can enter the picture if one also assumes that responses of seizures to different drugs signify different seizure types. There are several examples of differential diagnoses that can fall prey to this problem, including the diagnosis between partial seizures with secondary generalization and generalized tonic-clonic seizures, and the diagnosis between complex partial seizures and absence seizures with automatisms, among others. Considerations of etiology in future classification systems can further complicate the problem: should one then choose an anticonvulsant drug on the basis of individual seizure type or on the basis of the type of epilepsy? Ramifications of this issue extend even to the drug approval process. Official sanction is not given for use of a drug for a seizure type not included in the original efficacy studies, even if later scientific evidence shows that seizure type to be related to a type that is included. New trials must be undertaken. These problems arise from how we choose to classify seizures.     

Cognitive Dysfunction Associated with Antiepileptic Drug Therapy

Summary: Epilepsy is frequently associated with cognitive dysfunction. However, the reasons for this correlation are unclear. Possible influential factors include patient age; duration, frequency, etiology, and type of seizures; hereditary factors; psychosocial issues; and antiepileptic drug (AED) therapy. Whereas many of these factors are beyond the physician's control, AED therapy is one element that can be addressed in treatment decisions by recognizing the potential cognitive effects of particular AEDs. For example, phenobarbital impairs memory and concentration; phenytoin affects attention, problem solving ability, and performance of visuomotor tasks. In contrast, carbamazepine may affect concentration, while valproate would appear to have minimal effects on cognition. Moreover, cognitive effects of AEDs are amplified with coadministration of multiple anticonvulsants (polytherapy). A review of studies on the cognitive effects of monotherapy with AEDs, as opposed to those of polytherapy, provides evidence that drug-related cognitive dysfunction can be reversed if patients are switched to a simpler therapeutic regimen. Future research should be directed toward developing reliable measures for assessing and monitoring cognition, and understanding the particular cognitive side effects of each AED. Physicians also need to revise their opinions about which side effects are "tolerable" for epileptic patients.     

Carbamazepine Efficacy in Adults With Partial and Generalized Tonic-Clonic Seizures

Summary: Carbamazepine and phenytoin are drugs of choice in initial monotherapy for adult partial and secondarily generalized tonic-clonic seizures. These designations reflect the results of the Veterans Administration Epilepsy Cooperative Study Group of 1985. An earlier comparative study of carbamazepine and phenytoin by Ramsay and associates found both drugs equally effective in controlling new-onset seizures. Among the advantages of carbamazepine is that it causes relatively few cognitive and dysmorphic side effects. Its disadvantages are its unavailability in parenteral formulation and its metabolic autoinduction. The latter must be compensated for by planned dosage increases to maintain therapeutic plasma steady-state levels during the first 2 or 3 months of treatment. Carbamazepine is judged a drug of choice in the treatment of these secondarily generalized tonic-clonic seizures, and the drug of choice in children, adolescents, and women susceptible to the dysmorphic side effects associated with other anticonvulsant agents.     

Etiologic and Preventive Aspects of Epilepsy in the Child–Bridging the Gap Between Laboratory and Clinic

Summary: Four broad categories of basic phenomena are pertinent to developing ways to prevent epilepsy. These include mechanisms of epileptogenesis, ictal initiation and temporary entrainment by the seizure discharge of normally functioning brain, seizure propagation, and control mechanisms that function both to restrain the cascade of epileptic events culminating in a seizure and to arrest the epileptic event and restore the interictal state. In newborns and children, hypoxia-ischemia is a major factor leading to epileptogenesis, and several schemes are proposed to classify, quantify, and prevent hypoxic-ischemic encephalopathy. Control mechanisms must be better understood in order to develop prophylactic recommendations for epilepsy, and an experimental model of "kindling antagonism" may increase our understanding of these. Programs of prevention of seizures in children will evolve only if basic researchers and clinicians work productively together to develop an adequate understanding of factors important in epileptogenesis and antiepileptogenic control mechanisms.     

Epilepsy and anomalies of neuronal migration: MRI and clinical aspects

Neuronal migration disorders are the result of disturbed brain development. In such disorders, neurons are abnormally located. In diagnosing these conditions, magnetic resonance imaging is superior to any other imaging technique. This enables us to improve our knowledge of the clinical correlates of neuronal migration. With reference to migrational disorder, a retrospective study of all 303 patients with epileptic seizures referred for magnetic resonance imaging during a 3-year period was performed, 13 patients (aged 12-41, mean age 27) were identified. They represent 4.3% of the entire study group. Of the patients with known epilepsy, 6.7% and of the mentally retarded, 13.7% had migrational disorders. Four patients had schizencephaly as the dominant finding, one was classified as hemimegalencephaly, 2 had isolated heterotopias, and 6 had localized pachy- and/or poly-microgyria. The clinical pictures are complex. Ectopias of grey matter are recognised foci of epilepsy, but from an epileptological and a clinical viewpoint little attention has been given to these disorders. The present study shows that malmigration is not rare in epilepsy patients, especially not in the mentally retarded.     

Predisposing and Causative Factors in Childhood Epilepsy

Summary: We review information from large studies of defined populations, examining the role of known factors and especially of prenatal and perinatal factors in contributing to nonfebrile seizure disorders of early childhood. We depend especially, but not exclusively, on the recently completed analyses from the Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke, the NCPP. About 4% of children in the NCPP who had at least one non-febrile nonsymptomatic seizure by the age of 7 years had a previous seizure during acute neurologic illness, such as meningitis or during the acute illness after trauma. Many such seizures should potentially be preventable. Of children with seizures, 10% had had a neonatal seizure and 13% had had a febrile seizure. Among the hundreds of prenatal and perinatal factors explored as predictors of childhood seizure disorders, the principal predictors identified were congenital malformations of the fetus, cerebral and noncerebral; family history of certain neurologic disorders; and neonatal seizures. In agreement with the British National Child Development Study, labor and delivery factors in the NCPP appeared to contribute very little to childhood seizure disorders. Maldevelopment, rather than damage at birth to an initially intact nervous system, appeared to be the more common mechanism. Most seizure disorders of early childhood remained unexplained by the large set of prenatal and perinatal characteristics examined.     

Classification of methods in transcranial Electrical Stimulation (tES) and evolving strategy from historical approaches to contemporary innovations

Transcranial Electrical Stimulation (tES) encompasses all methods of non-invasive current application to the brain used in research and clinical practice. We present the first comprehensive and technical review, explaining the evolution of tES in both terminology and dosage over the past 100 years of research to present day. Current transcranial Pulsed Current Stimulation (tPCS) approaches such as Cranial Electrotherapy Stimulation (CES) descended from Electrosleep (ES) through Cranial Electro-stimulation Therapy (CET), Transcerebral Electrotherapy (TCET), and NeuroElectric Therapy (NET) while others like Transcutaneous Cranial Electrical Stimulation (TCES) descended from Electroanesthesia (EA) through Limoge, and Interferential Stimulation. Prior to a contemporary resurgence in interest, variations of transcranial Direct Current Stimulation were explored intermittently, including Polarizing current, Galvanic Vestibular Stimulation (GVS), and Transcranial Micropolarization. The development of these approaches alongside Electroconvulsive Therapy (ECT) and pharmacological developments are considered. Both the roots and unique features of contemporary approaches such as transcranial Alternating Current Stimulation (tACS) and transcranial Random Noise Stimulation (tRNS) are discussed. Trends and incremental developments in electrode montage and waveform spanning decades are presented leading to the present day. Commercial devices, seminal conferences, and regulatory decisions are noted. We conclude with six rules on how increasing medical and technological sophistication may now be leveraged for broader success and adoption of tES.     

Anticonvulsant Drugs and Cognitive Function: A Review of the Literature

Summary: Alterations of cognitive function are separate from disturbances of behavior seen in association with epilepsy. The nature of the cognitive disability may to a certain extent depend on the seizure type. Partial seizures, mainly derived from a temporal lobe focus, impair memory tasks, while generalized seizures seem to have more effect on attentional abilities. A number of studies, reviewed in this paper, suggest that anticonvulsant drugs further impair cognitive function. Maximal impairments are seen in patients receiving polytherapy: rationalization of polytherapy improves cognitive abilities. Studies in children and adults have allowed differentiation of the effects of various commonly used antiepileptic agents. Maximal cognitive deficits are seen with. phenytoin, while phenobarbital and sodium valproate induce moderate disturbances, and carbamazepine seems relatively free from such toxicity. Further research is needed on the interrelationship between types of seizure disorders, types of anticonvulsant medications, and cognitive function.     

Treatment Considerations in Anticonvulsant Monotherapy

Summary: The long-standing practice of polypharmacy in treating epilepsy is giving way to use of monotherapy. Monotherapy can improve seizure control as well as reduce the risk of serious idiosyncratic reactions, dose-related side effects, and complex drug interactions. Monotherapy also offers improved compliance and cost-effectiveness. The basis of monotherapy is accurate diagnosis and assessment of the patient's seizure type(s), followed by selection of a single appropriate anticonvulsant drug. Many patients currently treated with multiple anticonvulsants can be successfully converted to monotherapy with a carefully monitored program in which troublesome and redundant drugs are gradually withdrawn from the therapeutic regimen.     

Effects of NMD A- and AMPA-Receptor Antagonists on Different Forms of Epileptiform Activity in Rat Temporal Cortex Slices

Summary: Lowering extracellular magnesium induces different patterns of epileptiform activity in rat hippocampus and entorhinal cortex. Short recurrent epileptiform discharges in the hippocampus are stable over time, whereas seizurelike events (SLEs) in the entorhinal cortex, the subiculum, and the neighboring neocortex develop into late recurrent discharges which are not blocked by clinically employed antiepileptic drugs. We tested the sensitivity of the different epileptiform discharge patterns to. /V-methyl-D-aspartate (NMDA)- and non-NMDA-receptor antagonists. As NMDA-receptor antagonist we used dextrorphan, ket-amine, and 2-aminophosphonovalerate (2APV); as α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)-receptor antagonist we employed the quinoxaline derivative glutamate 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). The findings show that the different patterns of epileptiform activity, including the late recurrent discharges, are sensitive to all NMDA-receptor antagonists. However, when dextrorphan was employed to suppress seizure-like events, later recurrent discharges did not develop during the remaining time course of the experiment. CNQX reversibly suppressed recurrent discharges in the hippocampus and SLEs in the entorhinal cortex. However, late recurrent discharges become insensitive to CNQX, even at a high concentration of 60 μM m. This finding suggests a prominent role for NMDA receptors in the generation of late recurrent discharges.