丙戊酸和托吡酯对癫痫患儿游离肉毒碱的影响

目的探讨丙戊酸（VPA）和托吡酯（TPM）对癫痫患儿游离肉毒碱的影响。方法35例癫痫患儿，年龄6～8岁，男20例，女15例，其中12例予VPA单药治疗，11例予TPM单药治疗，12例予VPA及TPM联合治疗6～8个月。15例健康儿童作为正常对照组。测定血浆游离肉毒碱的浓度。结果VPA组血浆游离肉毒碱的浓度明显低于对照组及TPM组，VPA-plus-TPM组与VPA组比较差异无显著性，TPM组与对照组比较差异无显著性。结论VPA可降低癫痫患儿血浆游离肉毒碱水平，而TPM对血浆游离肉毒碱无明显影响。     

丙戊酸治疗成人癫(癎)致血浆肉毒碱下降

目的观察丙戊酸(valproic acid,VPA)治疗成人癫患者后患者血浆游离肉毒碱改变规律,并探讨导致其改变的相关因素。方法VPA治疗组为41例成人癫患者,其中接受VPA单药治疗者33例,联合其他抗癫药物治疗者8例,30例非VPA治疗的成人癫患者作为癫对照组,包括其他抗癫药物治疗的患者14例,和未进行药物治疗的患者16例。33名同龄健康者作为正常对照,用酶循环法测定血浆游离肉毒碱浓度,3组间进行比较。结果VPA治疗组血浆游离肉毒碱浓度(31.43±11.75μmol/L)明显低于正常对照组(43.25±12.57μmol/L)和非VPA治疗的癫对照组(40.71±12.83μmol/L,P均<0.05)。血浆游离肉毒碱浓度与VPA剂量、VPA疗程、其他抗癫药物、年龄、性别、血ALT、AST无相关性。结论VPA治疗成人癫可能导致血浆游离肉毒碱水平下降,其下降程度和VPA无剂量和疗程依赖性,也不受患者的生理状态以及其他抗癫药物的影响。     

托吡酯添加治疗转换为单药治疗癫疒间56例疗效观察

目的观察添加托吡酯(TPM)治疗有效的癫癎患者转换为TPM单药治疗的疗效.方法对56例添加TPM治疗有效并持续6个月以上的患者,逐渐减、停合用的抗癫癎药,转换为TPM单药治疗.结果转换成功32例(57.1%),完全控制13例,显效15例,有效4例,恶化4例,中途退出20例;不良反应减少14例次(35.8%).结论添加TPM治疗有效且稳定的非难治性癫癎患者大多数可成功转换为TPM单药治疗,而难治性癫癎患者转换为TPM单药治疗的成功率较低.     

苯巴比妥对癫(癎)患者血浆型PAF-AH酶活力的影响

目的检测苯巴比妥癫癎患者血浆型血小板活化因子乙酰水解酶(PAF-AH)活性,了解苯巴比妥抗癫癎治疗对免疫功能的影响。方法采用ELISA法测定16例单药PB抗癫癎治疗未发作EP患者,14例单药PB抗癫癎治疗发作患者及16例健康对照组的血浆型PAF-AH活性。结果癫癎未发作组、癫癎发作组和健康对照组血浆型PAF-AH活性分别为(15.91±1.59)、(17.66±1.46)(、15.52±1.18)nmol/(min.μl),发作组血浆型PAF-AH活性高于健康对照组(P<0.01),未发作组与对照组无显著差异(P>0.05)。结论单药苯巴比妥抗癫癎治疗EP患者发作后血浆型PAF-AH活性升高,可能是机体的一种自我保护措施。     

托吡酯对儿童骨代谢的影响

目的研究托吡酯(TPM)对癫患儿骨代谢的影响。方法正常对照组30例,诊断明确的癫患儿30例,于治疗前、TPM单药治疗3个月、6个月后,分别测定血清Ⅰ型前胶原羧基末端前肽(PICP)和Ⅰ型胶原氨基末端交联肽(NTX)浓度。结果 (1)TPM组治疗前的血清PICP浓度和血清NTX浓度与正常对照组无明显差异。(2)治疗6个月后,TPM组的血清PICP浓度低于正常对照组(P<0.01)。(3)TPM组治疗6月后的血清PICP浓度低于治疗前、治疗3月后(P<0.05),治疗前后的血清NTX浓度无统计学意义(P>0.05)。结论提示应用TPM治疗癫可抑制骨形成,对于长期服用TPM的癫患儿需要补充维生素D、钙剂。     

奥卡西平和托吡酯单药治疗癫(癎)的临床观察

目的 比较奥卡西平(OXC)、托吡酯(TPM)单药治疗癫(癎)的疗效和安全性.方法 癫(癎)门诊病人78例,随机分为OXC组和TPM组,单药治疗,观察24周.结果 TPM组38例,有效率76.3%、显效率63.1%,控制率(无发作)44.7%.OXC组40例,有效率75%、显效率62.5%,控制率(无发作)45%.经统计学处理两组疗效没有显著性差异(P=0.89＞0.05).TPM组有效剂量中位值为100 mg/d,OXC组为600 mg/d.TPM组不良反应8例,OXC组6例,两组不良反应发生率没有显著性差异(P=0.49＞0.05).TPM组不良反应常见胃纳差、记忆力减退、头部不适、嗜睡,其中2例分别因为手足麻木及胃纳差、体重减轻而退出.OXC组不良反应常见乏力、头昏、头疼、嗜睡、恶心、皮疹等,没有因为不良反应而退出.结论 TPM和OXC单药治疗癫(癎)疗效明显,不良反应轻,耐受性好,安全性高.二者疗效、不良反应没有显著性差异.     

托吡酯单药治疗初诊成人癫(癎)的临床研究

托吡酯(Topiramate,TPM,商品名妥泰,Topamax)是一种新型抗癫(癎)药物,于1995年开始在临床应用.国内关于TPM作为添加治疗难治性癫(癎)的报道较多,未见TPM单药治疗新诊断成人癫(癎)的报道,我院癫(癎)中心于2008-12-2010-12采用TPM单药治疗新诊断成人癫(癎)患者10例,对其进行了开放性自身对照临床研究,观察和评价其临床有效性和安全性.     

托吡酯单药治疗小儿癫癎45例疗效观察

目的 托吡酯(TPM)单药治疗儿科癫癎的疗效及安全性。方法 45例患儿入组,TPM目标维持剂量为2.5mg/(kg·d)。基础期1个月,记录癫癎发作次数;加药期2-3个月;稳定期3个月,坚持服用维持剂量,记录发作次数及不良反应。结果 45例患儿癫癎总有效率为82.2％,其中显效71.1％,无效17.7％,治疗各种类型癫癎有效率均>75％,不良反应率58％。多数短暂而轻微。结论 TPM单治小儿癫癎疗效明显,且较安全。     

托吡酯及丙戊酸钠对癫痫患儿血清六种常微量元素的影响

目的观察托吡酯及丙戊酸钠对癫痫患儿血清六种常微量元素的影响。方法选取80例癫痫患儿,40例予托吡酯(TPM)单药治疗,40例予丙戊酸钠(VPA)单药治疗,选取40例健康儿童作正常对照。所有儿童于治疗前及治疗6个月后行锌、铁、铜、钙、镁及铅检测。结果癫痫患儿治疗前血清钙、铁及锌分别为(1.45±0.40)mmol/L、(7.25±2.16)mmol/L、(69.88±10.99)μmol/L,明显低于对照组[分别为(1.66±0.45)mmol/L、(8.26±2.65)mmol/L、(78.24±12.44)μmol/L],差异有统计学意义(P0.05),铜、镁及铅含量与对照组比较,差异无统计学意义(P0.05)。VPA组与TPM组治疗前铜、锌、镁、钙、铁及铅含量比较,差异无统计学意义(P0.05)。2组治疗后各种元素含量比较,差异无统计学意义(P0.05)。癫痫患儿治疗前后各种元素含量比较,差异无统计学意义(P0.05)。结论癫痫患儿血清锌、钙及铁含量降低。VPA及TPM治疗对癫痫患儿血清锌、铁、铜、钙、镁、铅含量无明显影响。     

抗癫癎药物与大鼠海马CA1区胶质细胞TUNEL阳性表达关系的研究

目的:探讨抗癫癎药物对大鼠海马胶质细胞凋亡的影响。方法:35只60天龄SD大鼠随机分为生理盐水组(NS)、戊四氮(PTZ)组、卡马西平组(CBZ)、丙戊酸钠组(VPA)、苯妥英钠组(PHT)、托吡酯组(TPM)、拉莫三嗪组(LTG)7组,起始体重(200±20)g,戊四氮点燃其中6组制作癫癎模型,再给与抗癫癎药物治疗3周,应用TUNEL法观察大鼠海马胶质细胞的阳性表达率。结果:CA1区胶质细胞TUNEL阳性表达:NS组阳性率4.195%,PTZ组阳性率6.536%,CBZ组阳性率4.321%,VPA组阳性率5.587%,4组之间TUNEL阳性表达率差异无显著性(χ2=1.158,P>0.05);PHT组阳性率24.460%,TPM组阳性率21.605%,LTG组阳性率18.902%,三组之间TUNEL阳性表达率差异无显著性(χ2=1.378,P>0.05)。NS组、PTZ组、CBZ组、VPA组与PHT组、TPM组、LTG组之间TUNEL阳性表达率差异有显著性(χ2=70.227,P<0.005)。结论:大鼠癫癎模型经PTH、TPM、LTG治疗后,海马CA1区存在TUNEL阳性胶质细胞。     

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.