应用托吡酯治疗小儿难治性癫癎的临床研究

目的观察托吡酯治疗小儿难治性癫癎疗效、用药方法及副反应.方法采用开放性方法对31例小儿难治性癫癎患者进行单用或加用托吡酯治疗.观察其疗效及副反应.结果托吡酯治疗小儿难治性癫癎总有效率67.7%.38.7%患儿停止发作,对部分性发作疗效较好.其他类型发作亦有一定疗效.平均有效剂量为(4.0±1.8)mg@kg-1@d.副反应主要为体重减轻(16例,56.6%),神经系统症状,少汗或无汗,皮疹等,结论托吡酯对小儿难治性癫癎有良好疗效.     

托吡酯治疗小儿癫痫104例临床研究

目的观察托吡酯添加或单一治疗小儿癫痫,特别是对癫痫部分性发作及继发性全身性发作、Lennox-Gastaut综合征(LGS)和West综合征的疗效和不良反应.方法对癫痫部分性发作或继发性全身性发作32例、LGS47例及West综合征25例病例中已应用传统抗癫痫药物治疗,但控制不理想的病例添加托吡酯治疗,而新诊断的病例应用托吡酯单一治疗,并进行开放性自身对照研究.治疗剂量一般由0.5～1mg*kg-1*d-1开始,每周增加0.5～1mg*kg-1*d-1.部分性发作及继发性全身性发作组平均剂量为(6.2±2.2)mg*kg-1*d-1;LGS组平均剂量为(7.4±3.5)mg*kg-1*d-1;West综合征组<6个月的患儿由12.5mg/d开始,≥6个月的患儿由25mg/d开始,每2～3d增加12.5～25mg/d,平均剂量为(8.1±4.1)mg*kg-1*d-1.结果(1)托吡酯治疗小儿癫痫104例,疗程均在6个月以上,总疗效为发作减少≥50%的患者80例(76.9%),发作停止42例(40.4%);(2)添加托吡酯治疗对卡马西平和丙戊酸钠的血浓度没有明显影响;(3)不良反应嗜睡18例(17.3%),反应淡漠7例(6.7%),思维缓慢3例(2.8%),纳差25例(24.0%),类暑热症8例(7.7%),体重下降12例(11.5%).结论托吡酯治疗部分性发作及继发性全身性发作、LGS和West综合征安全、有效,不良反应轻.     

添加托吡酯治疗难治性癫痫部分性发作临床疗效的初步观察

目的 观察添加托吡酯对难治性癫痫部分性发作的临床疗效。方法 选择难治性癫痫部分性发作11例,保持原用AEDS不变,逐步递增托吡酯剂量,目标剂量200mg/日。结果 完全控制2例,显效2例,有效4例,无效3例,有效率73％（8／11）。结论 添加托吡酯对难治性癫痫部分性发作有较好疗效。     

托吡酯添加治疗难治性癫痫的临床观察

目的 观察添加托吡酯对难治性癫痫的临床效果与副作用。方法 对18例难治性癫痫患者，加用TPM后观察其发作频率并与加用前进行比较。计算总有效率，同时进行临床疗效和副作用观察。结果 病人加用托吡酯后总有效率为50%。其中显效率达22.2%(3例未再发作），副反应以胃肠道反应及神经系统症状为主，发生率为52.6%。结论 加用TPM治疗难治性癫痫安全有效。     

应用托吡酯治疗小儿难治性癫的临床研究

目的　观察托吡酯治疗小儿难治性癫(?)疗效、用药方法及副反应。方法　采用开放性方法对31例小儿难治性癫(?)患者进行单用或加用托吡酯治疗。观察其疗效及副反应。结果　托吡酯治疗小儿难治性癫(?)总有效率67.7％。38.7％患儿停止发作,对部分性发作疗效较好。其他类型发作亦有一定疗效。平均有效剂量为(4.0±1.8)mg·kg-1·d-1。副反应主要为体重减轻(16例,56.6％),神经系统症状,少汗或无汗,皮疹等,结论　托吡酯对小儿难治性癫(?)有良好疗效。     

托吡酯治疗难治性癫痫的疗效观察

目的 评价托吡酯（TMP）添加治疗难治性癫痫的疗效和其不良反应，以及对原服用AEDs血中浓度的影响。方法 采用开放性试验的方法对80例难治性癫痫进行添加托吡酯治疗，观察其疗效。结果 托吡酯作为添加治疗难治性癫痫总有效率58.6%。对单纯部分性发作有效率66.7%。复杂部分性发作25%，且完全控制率12.9%，不良反应均与CNS有关，多为一过性，但儿童的无汗，体重减轻，持续时间长，原服用AEDs血中浓度在添加托吡酯前后无明显变化。结论 托吡酯治疗难治性癫痫有效，但要注意用药量的个体化。     

托吡酯治疗难治性癫癎32例分析

目的观察托吡酯治疗难治性癫痫的疗效与安全性。方法对32例难治性癫痫患者加用托吡酯治疗进行临床观察研究。结果15例患者发作频度减少≥50％,8例患者发作频度减少到26％～49％,疗效较佳;各种类型癫痫之间发作减少差异不显著;与不同抗癫痫药物合用疗效无差异。结论托吡酯是一种有效的广谱抗癫痫药,能与常用抗癫痫药合用。     

托吡酯添加治疗儿童难治性癫痫的开放性自身对照临床研究

目的 评价托吡酯添加治疗儿童难治性癫痫的疗效及安全性。方法 应用托吡酯对44例难治性癫痫患儿进行开放性自身对照临床研究,其中单纯部分性发作患儿14例次,复杂部分性发作患儿23例次,部分性发作继发全面性发作患儿16例次。于服药后6个月评价托吡酯的疗效和安全性,以及临床疗效与药物剂量关系。结果 托吡酯治疗总有效率为58.14％(25/43例次),以发作次数减少≥50％为界,单纯部分性发作患儿治疗总有效率为57.14％(8/14例次),复杂部分性发作63.64％(14/22例次),部分性发作继发全面性发作68.75％(11/16例次)。6例Lennox-Gastaut综合征患儿中仅2例有效。托吡酯治疗后的不良反应发生率为46.51％(20/43例次),主要为厌食(37.21％)和体重下降(27.91％)。托吡酯所致不良反应较轻微,部分患儿继续接受治疗可自行缓解。结论 尽管在服用托吡酯期间须行不良反应监测,但其作为添加剂治疗儿童难治性癫痫安全有效,且对患儿血尿常规、肝肾功能均无明显影响。     

托吡酯治疗难治性癫痫32例分析

目的 观察托吡酯治疗难治性癫(痫)的疗效与安全性.方法 对32例难治性癫(痫)患者加用托吡酯治疗进行临床观察研究.结果 15例患者发作频度减少≥50%,8例患者发作频度减少到26%～49%,疗效较佳;各种类型癫(痫)之间发作减少差异不显著;与不同抗癫(痫)药物合用疗效无差异.结论 托吡酯是一种有效的广谱抗癫(痫)药,能与常用抗癫(痫)药合用.     

托吡酯添加治疗儿童难治性癫痫的开放性自身对照临床研究

目的：评价托吡酯添加治疗儿童难治性癫痫的疗效及安全性。方法：应用托吡酯对44例难治性癫痫患儿进行开放性自身对照临床研究，其中单纯部分性发作患儿14例次，复杂部分性发作患儿23例次，部分性发作继发全面性发作患儿16例次。于服药后6个月评价托吡酯的疗效和安全性，以及临床疗效与药物剂量关系。结果：托吡酯治疗总有效率为58.14%（25/43例次）。以发作次数减少≥50%为界，单纯部分性发作患儿治疗总有效率为57.14%(8/14例次），复杂部分性发作63.64%(14/22你次），部分性发作继发全面性发作68.75%(11/16例次）。6例Lennox-Gastaut综合征患儿中仅2例有效。托吡酯治疗后的不良反应发生率为46.51%(20/43例次），主要为厌食（37.21%）和体重下降（27.91%）。托吡酯所致不良反应较轻微，部分患儿继续接受治疗可行自行缓解。结论：尽管在服务托吡酯期间须行不良反应监测，但其作为添加剂治疗儿童难治性癫痫安全有效，且对患儿血尿常规、肝肾功能均无明显影响。     

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.     

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.     

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.     

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.     

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.     

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.     

Special Pharmacokinetic Considerations in Children

Summary: Pediatric patients have greater degrees of pharmacokinetic variability and unpredictability than adults. This variability results from the effects of pharmacogenetics, age and growth, prior and current comedication, and disease. Newborns with seizures have the least predictable dosage requirements, and their needs change as drug-eliminating mechanisms mature in the neonatal period. Infants have the highest relative capacities to eliminate antiepileptics of any age group and require the largest relative doses. In addition to age-related trends, children demonstrate the same drug-specific, pharmacokinetic phenomena that adults do, including nonlinear phenytoin elimination, nonlinear valproate binding, and autoinduction of carbamazepine. Intercurrent illness and drug interactions further modify the age-related pharmacokinetic patterns in children and make dosage requirements even more unpredictable. Recent studies have shown that febrile illness can affect drug elimination, sometimes decreasing drug levels by 50% or more. Intermittent treatment with benzodiazepines administered either orally or rectally can be an important adjunct and help minimize this type of problem for children with marginally controlled epilepsy. Intermittent benzodiazepines are also helpful for children who have febrile seizures and who need only occasional antiepileptic protection.