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     

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。     

抗癫痫药物的致癫痫作用

近年来越来越多的文献报道抗癫痫药(AEDs)可导致癫痫恶化,甚至诱发出现新的癫痫类型[1,2]。与癫痫自然病程的恶化不同,AEDs致癫痫恶化常出现于用药后不久,或在药物加量期,药物减量或换药后症状缓解或消失。有关AEDs致痫作用的内在机制目前尚不明确。现主要对AEDs导致不同     

癫痫患者初次用药时机的选择

药物治疗目前仍是治疗癫痫的主要手段,治疗前发作次数越多,患者预后越差,而抗癫痫药物(AEDs)可对50%～90%新诊断癫痫患者的复发起到预防作用[1],因而对于多次或频繁发作的癫痫患者一直主张积极治疗.由于AEDs的普遍应用,使我们对癫痫的自然病程并不十分了解.流行病资料显示,近30%癫痫患者可不经治疗达到自发缓解[2],考虑到AEDs可产生不同程度的不良反应,故对于初次非诱发性痫样发作、早期发作稀少或可能自发缓解的某些癫痫患者,如何处理尚无定论.目前有关癫痫患者初次用药时机的研究较少,结果也不尽相同,国内更缺乏相应的研究.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

Dextromethorphan: Cellular Effects Reducing Neuronal Hyperactivity

Summary: Dextromethorphan is a dextrorotary morphinan without affinity for opioid receptors, commonly used as an antitussive medication. During the past 5 years, interest in the compound and its demethylated derivative, dextrorphan, has been revived because additional neuroprotective and an-tiepileptic properties were found in in vitro studies, animal experiments, and a few clinical cases. Both morphinans are able to inhibit N -methyl-D-aspartate (NMDA) receptor channels and voltage-operated calcium and sodium channels with different potencies. The inhibition of the NMDA receptor is believed to be the predominant mechanism of action responsible for the anticonvulsant and neuroprotective properties of the compounds.