癫痫病人棘波灶的电镜改变

报告２５例癫痫患者在进行手术治疗时，皮层脑电监测下，取棘波最明显最多的大脑皮质层电镜观察，同时对８例病人的胼胝体也做电镜观察，结果发现超微结构下的神经细胞，突触与神经毡，星形胶质细胞，毛细血管及髓鞘均有不同程度的病理变化，突触前轴突末梢及突触后树突均发生不同程度的水肿，尤以突触后树突水肿明显并伴有突触前轴突末梢突触小泡的聚集增多，这些同癫痫的发生有密切关系，在癫痫发病和脑电棘波形成中具有重要意义，     

癫痫病人棘波灶的电镜改变

报告２５例癫痫患者在进行手术治疗时，皮层脑电监测下，取棘波最明显最多的大脑皮层做电镜观察，同时对８例病人的胼胝体也做电镜观察。结果发现超微结构下的神经细胞，突触与神经毡，星形胶质细胞，毛细血管及髓鞘均有不同程度的病理变化，突触前轴突末梢及突触后树突均发生不同程度的水肿，尤以突触后树突水肿明显并伴有突触前轴突末梢突触小泡的聚集增多。这些同癫痫的发生有密切关系，在癫痫发病和脑电棘波形成中具有重要意义，本文对这些改变进行分析讨论。     

颞叶癫痫脑电图分析及病灶超微结构观察

目的 研究影像学检查无异常的颞叶癫痫患者,电生理异常与皮层棘波灶及海马超微病变的关系.方法 选择经CT或MRI检查未见异常的颞叶癫痫患者7例,术前做脑电图或24h视频脑电监测,术中在脑电监测下取颞叶大脑皮质棘波灶和海马组织,做电镜观察.结果 7例患者电生理检查均可见典型痫样放电.颞叶皮质痫灶和海马可见不同程度的神经元固缩,胶质细胞变性,胶质增生,突触数量及突触结构改变,血脑屏障破坏等改变.结论 影像学无异常的颞叶癫痫患者颞叶皮层痫灶和海马超微结构病理变化明显,特别是突触的变化,是导致癫痫患者脑电生理机能异常及癫痫反复自发性发作的形态学基础.     

癫痫患者棘波灶的电镜观察

本文总结２４例癫痫患者在行手术治疗过程中分别在有棘波和无棘波的部位取材进行电镜检查，以探讨癫痫的发病机制。皮层组织取自额叶１２例，颞叶９例，枕叶３例，结果观察到癫痫患者的皮层无论有无棘波，超微结构下的神经细胞、突触与神经毡，星形胶质细胞及毛细血管均有不同程度的病理变化。其变化的特点是水肿，有棘波的部位最严重，尤其是突触前末梢，并有突触小泡减少，这些与癫痫的发生有密切关系，是棘波产生的形态学基础。     

顽固性颞叶癫(癎)海马超微结构的体视学分析

目的对顽固性颞叶癫痫病人的海马癫痫灶组织和癫痫灶周围正常组织的超微结构进行形态定量观察，以探讨颞叶癫痫的发生机制．方法对45例病人在深部电极监测下手术切除海马．电镜观察癫痫灶组织和癫痫灶周围正常组织中锥体细胞和突触结构的形态学变化：采用体视学分析颞叶癫痫灶组织和癫痫灶周围正常组织锥体细胞线粒体体积密度（Vv）、面积密度（Sv）、数密度（Nv）、比表面积（δ）、平均体积（V）：测量突触间隙的宽度。结果癫痫灶组织锥体细胞线粒体较癫痫灶周围正常组织明显肿胀，且嵴断裂．数量减少，平均截面积增大：线粒体的Vv、V较癫痫灶周围正常组织大，Sv、Nv、8较癫痫灶周围正常组织小。癫痫灶组织中锥体细胞的轴突和树突内线粒体较癫痫灶周围正常组织的锥体细胞肿胀明显；轴棘、轴树突触间隙宽度变窄。结论海马锥体细胞超微结构的改变和细胞线粒体功能变化与顽固性颞叶癫痫的发生关系密切。     

癫痫灶的超微结构观察及与癫痫发生机制的关系探讨

目的 观察癫痫患者痫灶的超微结构变化，以探讨癫痫的发生机制。方法 对12例顽固性癫痫患者进行皮质电图监测下手术切除痫灶，电镜下观察痫灶皮质。结果 痫灶有明显的病理变化，包括神经细胞数量减少、神经细胞水肿变性、核浓缩、异染色质边集，线粒体水肿、崩解、嵴排列紊乱，神经突触水肿，小血管或毛细血管扭曲、堵塞或内皮细胞水肿，基底膜增厚或分层，星形胶质细胞突起水肿。结论癫痫的发生均有一定的病理形态学基础，除了神经细胞、突触、星形胶质细胞的变化外，血脑屏障的改变与癫痫的发生及预后天系密切。     

癫痫发作的基本机理:神经生理和神经生化病因学

神经胶质细胞增生为癫痫发生灶中病变的一个特点,此外还有神经细胞减少以至消失,局部脑循环障碍,显著的树突结构异常。树突的形态改变主要为树突棘消失,树突分支减少产生扭曲和不规则的肿胀。树突棘消失的结果,使突触传入减少导致去神经型过敏(denervation type of Supersensitivity)产生重复放电。神经元全面减少,剩留的神经元为中型到小型的,它们比大的神经元更容易放电。神经胶质细胞增生是癫痫发生灶发展过程中主要现象之一,对说明癫痫发作具有重要意义。     

70例颞叶癫痫的病理与临床研究

对７０例颞叶癫痫切除病灶作了病理学观察。其中肿瘤６例，血管畸形１３例．疤痕７例，外伤等脑损伤５例。蛛网膜囊肿及囊虫病各１例。以上同时伴有海马硬化者２３例；仅有海马硬化者３７例，其中７例有局部脑组织结构不良，４例有神经细胞增生灶，２例白质内灰质异位。表现为神经细胞变性脱失和胶质增生的海马硬化，主要波及齿状回、Ａｍｍｏｒｉｓ角和下托。还讨论病理诊断和鉴别诊断、病因病灶和致癫灶的确立。原发病变与继发病变的区分。     

颞叶癫痫海马、杏仁核及皮层病灶的超微结构观察

对１９例临床确认为颞叶癫痫而行海马杏仁核及皮层病灶切除术棘波灶的标本进行了电镜观察，发现在病变神经元周围，有髓神经纤维髓板松解、融合，轴突出芽；无髓神经纤维内微丝、微管排列紊乱，缠绕成团，见团样小体结构；突触中圆形突触小泡增多或耗竭。扁平状突触小泡相对较少；神经毡及毛细血管旁可见许多颗粒性电子致密物沉着，经Ｘ射线显微分析排除无机离子，考虑这些沉着物仍为机体的有机成份。半定量观察结果显示三个部位超微病理变化具有相似性。本课题的观察提示神经纤维及突触的病变可能是痫性活动的直接形态依据，而这种具有病变神经纤维及突触的神经元在痫性活动中则可能起着“起搏细胞”的作用，痫性活动的产生与兴奋性及抑制性递质的平衡失调有关。     

颅脑CT表现为小型低密度病灶的顽固性癫痫病理所见及手术治疗

目的：探讨颅脑CT表现为小型低密度灶的顽固性癫痫临床表现、病理所见及手术治疗。方法：回顾性研究自1992年以来24例临床资料。结果：术中皮层电图均可监测出尖波或棘波。病灶病理多样，占多数的是小胶质瘤、胶质细胞增生、炎症或囊性病变、小型脑血管畸形及寄生虫。痫灶主要病理变化为神经元变性、坏死，不同程度丧失，树突棘脱失；噬节及胶质细胞增生；脱髓鞘；小血管增生。结论：颅内小型低密度灶并非罕见病变，是顽固性癫痫的一个重要的CT影像学表现。对此类患要采取积极手术治疗，既要注重病灶切除，更要注重痫灶切除。     

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.     

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 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.     

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.     

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.     

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.