难治性癫(癎)的早期判断

难治性癫痫（intractable epilepsy，IE）是指经系统正规地应用2种以上抗癫痫药物（AEDs）治疗，且药物在体内达到有效浓度，并至少观察2年，发作仍然得不到有效控制。据统计30％癫痫患者经药物治疗后难以得到有效的控制，最终发展为IE。这些患者长期承受着由癫痫发作可能引起的各种并发症的巨大风险和长期无效AEDs治疗带来不必要的药物不良反应和经济损失。     

抗癫痫药物与骨折风险

癫痫是神经系统的一种常见疾病,药物治疗是癫痫治疗的首选方法。由于癫痫病程长,患者常常需要长期服药甚至终身服药,药物长期服用的安全性是必须考虑的。有研究显示癫痫患者的骨折风险是普通人群的2~6倍,长期服用抗癫痫药物(AEDs)是导致骨折风险增加的独立危险因素。不同类型的AEDs对不同年龄阶段人群的骨代谢有不同的影响,应根据不同年龄选择合适的药物。如何预防骨折是癫痫专科医生应该关心的问题,应注意监测相关指标,防止骨折的发生。     

抗癫痫药物对骨骼健康影响的研究进展

癫痫是最常见的神经系统疾病之一,目前控制癫痫发作以抗癫痫药物(AEDs)为主,国内外大量研究表明长期应用抗癫痫药物会影响骨骼健康。本文从传统AEDs和新型AEDs对骨代谢相关血清学标志物、骨密度的影响、可能机制及AEDs使用者骨骼健康的监测、预防等方面进行综述。     

抗癫痫药物与骨强度降低相关性的研究

正癫痫患者骨折的风险是正常人的2～6倍~([1]),此类患者出现的骨质流失和骨折发生率增加还存在许多未解决的问题。过去两年发表的论文关注了抗癫痫药物(antiepileptic drugs,AEDs)对骨骼系统的影响,以及癫痫患者骨质疏松和骨折的风险。这些危险因素包括长期使用AEDs、多药联合以及女性性别等。本文综述AEDs诱导骨质减少的发病机制,并建立癫痫人群骨质疏松症的管理和预防指南~([1-11])。1.流行病学癫痫是一种常见的慢性神经系统疾病,通常需要长期使用AEDs治疗。许多研究报道AEDs治疗与代谢性骨病相关,是骨折的主要医源性危险因素,癫痫患者骨折的风险是正常     

维生素B6相关性癫痫进展

目前癫痫治疗仍以药物为主,近年来临床使用的10 余种新一代抗癫痫药物( antiepileptic drugs,AEDs)依然以控制癫痫发作症状为主,癫痫的整体治疗状况并未明显改善,仍有20％ ～30％的患者无法由AEDs完全控制发作,称为药物难治性癫痫(drug resistant epilepsy,DREP)[1]...     

维生素B6相关性癫痫进展

目前癫痫治疗仍以药物为主,近年来临床使用的10余种新一代抗癫痫药物(antiepileptic drugs,AEDs)依然以控制癫痫发作症状为主,癫痫的整体治疗状况并未明显改善,仍有20％ ～ 30％的患者无法由AEDs完全控制发作,称为药物难治性癫痫(drug resistant epilepsy,DREP)[1]....     

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。     

抗癫药物对内分泌系统及妊娠的影响

疾病状态的药物干预是内科治疗的重要方法之一,药物疗效和安全性在疾病治疗中具有同等重要的作用。对于癫痫这一慢性脑疾病而言,由于患者需要接受长期的药物治疗,故其安全性显得尤为重要。自Isoj(a|¨)rvi报告丙戊酸(VPA)可引起女性癫痫患者生殖内分泌系统功能失调后,有关抗癫痫药物(AEDs)对内分泌系统的影响即成为癫痫药物治疗研究的焦点。     

生酮饮食治疗癫痫的神经保护作用

近年来抗癫痫药物(AEDs)得到很大的发展和深入研究,但AEDs治疗通常面临着很多显著的副作用,仍有很多类型的癫痫无法控制.19世纪90年代以来,生酮饮食(ketogenic diet,KD)已成为有效治疗癫痫的方法之一,尤其是在难控制的癫痫和减少药物副作用方面。研究表明,对于儿童难治性癫痫的治疗,KD比AEDs更为有效.KD是一种营养均衡的以脂肪为主的饮食,已被FDA认证并列为控制儿童顽固性癫痫的医疗食品.本文就KD用于治疗癫痫的神经保护作用进行综述.     

儿童急性淋巴细胞白血病合并癫痫发作的研究

急性淋巴细胞白血病(Acute lymphoblastic leukemia,ALL)是儿童白血病最常见的类型,在急性治疗期间癫痫发作并不少见。据报道,在8%～13%的ALL患者中可见癫痫发作,多发生在化疗诱导和中枢神经系统巩固的急性治疗阶段,诱导缓解的前6周内,化疗药物的不良反应可增加癫痫发作风险。大多数癫痫是急性症状性,对早期治疗阶段首次发作的ALL患者的评估应从颅脑成像开始,除非代谢原因立即显现出来,否则,所有癫痫发作的患者都应进行颅脑核磁共振(MRI)检查,仅有少数患者需长期使用抗癫痫药物(AEDs)治疗,AEDs的选择应考虑到与化疗或支持药物的潜在相互作用,癫痫发作后可导致神经系统后遗症,需早期诊断、早期治疗。现就ALL合并癫痫发作的特点作一综述。     

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.     

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.     

Hepatic Considerations in the Use of Antiepileptic Drugs

Summary: Virtually all of the major antiepileptic drugs (AEDs) can cause hepatotoxicity, although fatal hepatic reactions are rare. The mechanisms, incidences, and risk profiles for such reactions differ from drug to drug. With carbamazepine and phenytoin, hepatotoxicity may be due to drug hypersensitivity. Although the profiles of patients at risk have not been well-defined for these two antiepileptic drugs, it would appear from reports in the literature that older adolescents and adults are at higher risk than children of developing serious or fatal hepatotoxicity. Once hepatotoxicity develops, mortality rates are 10–38% with phenytoin and 25% for carbamazepine. The risk profile for valproate fatal hepatotoxicity has been more clearly defined. Those at primary risk of fatal hepatic dysfunction are children under the age of 2 years who are receiving multiple anticonvulsants and also have significant medical problems in addition to severe epilepsy. The risk is considerably lower for patients over the age of 2 years on valproate monotherapy. In contrast to the risk profile with other AEDs, adults receiving valproate as monotherapy have the lowest risk of hepatotoxicity. Fatal hepatic dysfunction coincident with valproate may be the result of aberrant drug metabolism. Concomitant use of AEDs that induce microsomal P450 enzymes (e.g., phenytoin and phenobarbital) may enhance the production of a toxic metabolite, and hence the greater risk of hepatotoxicity with polypharmacy.     

Vascular Malformations and Epilepsy: Clinical Considerations and Basic Mechanisms

Summary: Vascular malformations (VMs) are associated with epilepsy. The natural history of the various VMs, clinical presentation, and tendency to provoke epilepsy determine treatment strategies. Investigations have probed the mechanisms of epileptogenesis associated with these lesions. Electrophysiologic changes are associated with epileptogenic cortex adjacent to VMs. Putative pathophysiologic mechanisms of epileptogenesis include neuronal cell loss, glial proliferation and abnormal glial physiology, altered neurotransmitter levels, free radical formation, and aberrant second messenger physiology.     

Neonatal Seizures: Problems in Diagnosis and Classification

Summary: The clinical identification of neonatal seizures is critical for the recognition of brain dysfunction; however, diagnosis is often difficult because of the poorly organized and varied nature of these behaviors. Current classification systems are limited in their ability to communicate motor, autonomic, and electroencephalo-graphic features of seizures precisely and to provide a basis for uniform effective diagnosis, therapy, and determination of prognosis. Recent investigations of neonates, utilizing bedside electroencephalographic/polygraphic/ video monitoring techniques, have provided the basis for improved diagnosis and classification of seizures in the newborn. These studies have demonstrated that not all clinical phenomena currently considered to be seizures require electrocortical epileptiform activity for their initiation or elaboration. In addition, the specific clinical character of the phenomena considered to be seizures, the clinical state of the infant, and the character of the EEG indicate the probable pathophysiological mechanisms involved and suggest probable etiologies, prognosis, and therapy. Similarities between animal models that demonstrate reflex physiology and neonates with motor automatisms and tonic posturing suggest that these clinical behaviors may not be epileptic in origin but, rather, primitive movements of progression and posture mediated by brainstem mechanisms. Although not all clinical behaviors currently considered to be neonatal seizures may have similar pathophysiological mechanisms, they are clinically significant because they all indicate brain dysfunction.     

Valproate Monotherapy in the Management of Generalized and Partial Seizures

Summary: For decades, therapeutic tradition has promoted the concept of polypharmacy in the management of epilepsy. In recent years, however, studies have shown that, for most patients, monotherapy can provide comparable or better seizure control than administration of multiple anticonvulsants, while diminishing the potential for adverse reactions, drug interactions, and poor compliance. Valproate is an important monotherapeutic agent that is highly effective in the control of idiopathic primary and secondarily generalized epilepsies, and partial seizures that do not generalize. Comparative studies have found that valproate is at least as effective as phenytoin and carbamazepine in the treatment of generalized and partial seizures. Given the similar efficacy, other factors such as pharmacokinetics and side effects may therefore determine anticonvulsant selection for monotherapy.     

Carbamazepine Efficacy and Utilization in Children

Summary: Carbamazepine is effective for preventing partial and generalized tonic-clonic seizures in children. Although absence epilepsies are more common in children than adults, an estimated 80% of children with epilepsy have seizure types or epilepsies that are potentially responsive to carbamazepine. The differential diagnosis of ictal staring is an especially important issue in children because absence and atypical absence seizures are more prevalent in children than adults. Age-related pharmacokinetic differences and drug interactions are major considerations in children. On average, children have higher clearance rates of carbamazepine, shorter half-lives, and higher ratios of carbamazepine-10, 11-epoxide to carbamazepine than adults. In addition, children with severe epilepsy are more likely to require multiple-drug therapy, which can lead to complex drug interactions. When carbamazepine is administered along with valproate, drug protein binding interactions can cause intermittent side effects.     

Un nouveau cadre conceptuel de travail pour la psychiatrie

In an attempt to place psychiatric thinking and the training of future psychiatrists more centrally into the context of modern biology, the author outlines the beginnings of a new intellectual framework for psychiatry that derives from current biological thinking about the relationship of mind to brain. The purpose of this framework is twofold. First, it is designed to emphasize that the professional requirements for future psychiatrists will demand a greater knowledge of the structure and functioning of the brain than is currently available in most training programs. Second, it is designed to illustrate that the unique domain which psychiatry occupies within academic medicine, the analysis of the interaction between social and biological determinants of behavior, can best be studied by also having a full understanding of the biological components of behavior.