两种新药治疗初发癫痫的疗效及对复发的影响

目的比较分析两种新药左乙拉西坦和拉莫三嗪与传统药物丙戊酸对初发癫痫疗效、脑电图及复发的影响。方法随机数字法将105例初发癫痫患者分为A、B、C 3组,A组采取左乙拉西坦治疗,B组给予拉莫三嗪治疗,C组行丙戊酸治疗,均连续用药6个月,比较3组临床疗效、不良反应、治疗前后脑电图变化,同时治疗后随访1a,统计3组癫痫复发率。结果治疗总有效率方面,3组(97.14%vs 91.43%vs 85.71%)比较差异无统计学意义(P0.05)。脑电图变化方面,与同组治疗前比较,B组治疗后α波减少0.5Hz、θ波增多、δ波增多比例显著上升(P0.05),且与A组、C组治疗后比较差异有统计学意义(P0.05);与同组治疗前比较,3组治疗后脑电图常规描记、诱发描记痫样波放电率均显著降低(P0.05),但3组间比较差异无统计学意义(P0.05)。A组、B组总不良反应发生率分别为20.00%、25.71%,均显著低于C组的57.14%(P0.05)。3组随访1a癫痫复发率比较差异无统计学意义(P0.05)。结论左乙拉西坦、拉莫三嗪、丙戊酸治疗初发癫痫疗效及随访1a复发率类似,均能明显抑制脑电图痫样波放电,但左乙拉西坦、丙戊酸对脑电图背景活动无明显影响,而拉莫三嗪影响明显;同时丙戊酸治疗不良反应明显高。     

LTG与OXC单药治疗儿童部分性癫痫的疗效和安全性对比

目的对比在儿童部分性癫痫应用拉莫三嗪(LTG)与奥卡西平(OXC)单药治疗的效果及安全性。方法选取我院收治的60例儿童初诊部分性癫痫患儿,随机分为A组与B组,每组30例,分别给予LTG与OXC单药治疗,对比2组患儿治疗1a后临床疗效、对脑电背景活动的影响、脑电图间歇期痫性放电(IEA)改善情况及药疗安全性。结果 A组治疗总有效率与IEA改善总有效率分别为83.33%、66.67%,略高于B组的80.00%、60.00%,但差异均无统计学意义(P0.05);2组患儿治疗前后的脑电背景活动α波频率比较,差异均无统计学意义(P0.05),但B组治疗后的脑电背景活动θ波、δ波频率均显著升高,治疗前后对比差异有统计学意义(P0.05);2组患儿治疗期间所发生严重的不良反应均较轻微,差异无统计学意义(P0.05)。结论采用拉莫三嗪与奥卡西平治疗儿童部分性癫痫患儿,均有确切的临床疗效,可有效改善脑电图间歇期痫性放电,且药疗安全性相当,但LTG对患儿的认知功能、脑功能等影响更小。     

奥卡西平 拉莫三嗪 左乙拉西坦对癫痫患者脑电图的影响

目的探讨抗癫痫新药奥卡西平(OXC)、拉莫三嗪(LGT)、左乙拉西坦(LEV)对癫痫患者脑电图的影响。方法对单用奥卡西平、拉莫三嗪、左乙拉西坦的癫痫患儿作服药前及服药后动态脑电图比较。结果奥卡西平、拉莫三嗪、左乙拉西坦均可使癫痫患儿脑电图痫性活动减少,但拉莫三嗪、左乙拉西坦优于奥卡西平;奥卡西平组易发生背景波减慢,α活动减少,θ、δ增多,但拉莫三嗪、左乙拉西坦影响较小。结论拉莫三嗪、左乙拉西坦对脑电图不良影响较小,有利于控制痫性活动,更易达到停药标准。     

左乙拉西坦治疗部分性癫痫发作121例的临床疗效及对脑电图的影响

目的探讨左乙拉西坦(LEV)治疗部分性癫痫患者的临床疗效及其对脑电图(EEG)的影响。方法选择LEV单药治疗的121例部分性癫痫患者,进行开放性自身对照随访研究,观察LEV治疗20w后的总有效率及对EEG波形的影响。以治疗前8w基线期平均每个月癫痫发作频率为标准,与给予LEV治疗后随访每个月癫痫发作频率比较,作为疗效评价标准,治疗前后疗效和脑电背景活动参数(α波、β波、θ波、δ波)比较采用χ~2检验,以P0.05为差异有统计学意义。结果 LEV治疗癫痫患者20w后无发作41例(33.9%),显效39例(32.2%),有效21例(17.4%),无效15例(12.4%),总有效率83.5%;不良反应发生率为18.3%,均为轻度皮疹,嗜睡,头晕,食欲下降等不良反应;治疗20w时间歇期痫样放电(IEA)消失或减少50%以上者84例(69.4%)。治疗前患者α波的均值为30±9Hz,治疗后,α波的平均值为29±8Hz,治疗前后差异无统计学意义(P0.05)。脑电背景30s内θ波数治疗前为23±7个,治疗后为33±8个,差异有统计学意义(P0.05);β波治疗前均值为12.8±6.8Hz,治疗后均值为13.2±6.6Hz,治疗前后差异无统计学意义(P0.05);δ波治疗前为17±6个,治疗后为16±8个,差异无统计学意义(P0.05)。结论 LEV治疗部分性癫痫患者有较好的疗效,副反应小,且使痫样放电减少或消失,对脑电背景活动影响较小,对EEG的改善效果明显。     

拉莫三嗪治疗新诊断的成人部分性癫痫的疗效及其对脑电活动的影响

目的 探讨拉莫三嗪(LTG)对新诊断的部分性成人癫痫患者的临床疗效及其对腑电活功的影响.方法 LTG单药治疗新诊断的65例成人部分性癫痫患者,进行开放性自身对照随访研究,观察LTG治疗2、6、12m的临床疗效及对脑电活动的影响.两样本计量资料比较采用t检验,多样本比较采用Ridit分析.结果 LTG治疗2m时无发作37例(56.9％),显效11例(16.9％),有效10例(15.4％),无效7例(10.8％),总有效率89.2％;LTG治疗2、6、12m时疗效比较差异无统计学意义(F=0.67,P＞0.05).治6m时间歇期痫样放电(IEA)消失或减少50％以上者27例(41.5％),治疗12m时IEA消失或减少50％以上者29例(44.6％).治疗 6 m时,脑电背景α波个数与治疗前相比差异无统计学意义(t=1.619,P＞0.05),δ波个数与治疗前相比差异无统计学意义(t=1.809,P＞0.05),θ波数较治疗前增加(t=4.657,P＜0.05).结论 LTG单药治疗新诊断的成人部分性癫痫患者有较好的疗效,且使痫样放电减少或消失,对脑电背景活动影响较小,对脑电图的改善有肯定作用.     

额叶癫痫患者动态脑电图与过度换气脑电图放电规律探讨

目的 了解动态脑电图(AEEG)中睡眠中放电与过度换气脑电图(EEG)的放电规律.方法 评估65例额叶癫痫患者AEEG与过度换气EEG的痫性放电特点.结果 过度换气中发现痫性放电率明显低于AEEG中浅睡眠期(非快速眼动相1,2期)EEG,差异具有统计学意义(P＜0.05);而与AEEG中清醒期和深睡眠期(非快速眼动相3,4期)比较,差异无统计学意义(P＞0.05).结论 额叶癫痫患者AEEG中浅睡眠期痫性放电率明显高于过度换气EEG,对额叶癫痫患者进行睡眠AEEG检测,有助于提高痫性放电的诊断率.     

拉莫三嗪长期治疗癫痫的疗效及脑电图变化研究

目的探讨拉莫三嗪长期治疗癫痫的临床疗效及对脑电图的影响。方法随机双盲法将72例癫痫患者分为2组各36例,对照组采取常规治疗,观察组在对照组基础上加以拉莫三嗪治疗,治疗6个月观察比较2组临床疗效、不良反应及治疗前后脑电图变化情况。结果观察组治疗总有效率、脑电图总改善率均为94.4%,显著高于对照组的75.0%、69.4%,差异有统计学意义(P0.05)。观察组不良反应发生率13.9%,对照组为11.1%,差异无统计学意义(P0.05)。结论拉莫三嗪持续长期治疗癫痫疗效明确,能明显改善脑电图,不良反应少,值得临床推广。     

左乙拉西坦对癫痫患者血清胶质纤维酸性蛋白水平、脑电活动及生活质量的影响

目的探讨左乙拉西坦对新诊断部分性癫痫患者血清胶质纤维酸性蛋白(GFAP)水平及脑电活动、生活质量的影响。方法对80例新诊断成人部分性癫痫患者进行左乙拉西坦单药治疗,分别在入组时及治疗6w、12w时采用ELISA法测定血清GFAP的浓度。长程脑电图监测棘波指数。采用癫痫生活质量量表评定患者的生活质量。结果治疗6w时血清GFAP浓度和棘波指数均明显下降(P0.05),治疗12w时下降更明显(P0.01)。患者经左乙拉西坦治疗后脑电图(EEG)背景活动α波Hz、θ波数、δ波数均无明显变化(P0.05),治疗6w后和治疗12w后生活质量量表评分均明显高于入组时(P0.05)。血清GFAP含量与棘波指数呈显著正相关(P0.05),与治疗后生活质量量表总分呈显著负相关(P0.01)。结论左乙拉西坦治疗可改善癫痫患者生活质量,可能与其抑制GFAP过度表达、抑制癫痫放电而不影响脑电背景活动有关。     

抗癫痫药物对癫痫患者脑电活动的影响

癫痫是一组由大脑神经元异常放电所引起的以短暂中枢神经系统功能异常为特征的慢性脑部疾病,具有突然发生、反复发作的特点,大脑皮层神经元过度放电是各种癫痫发作的病理基础.癫痫所见的脑电图（electroencephalogram,EEG）称为癫痫脑电图,其主要内容为癫痫波,即头皮电极记录到的反映大脑神经细胞功能状态的电变化.有些抗癫痫药物在抑制痫样放电治疗癫痫的同时,对EEG背景活动也有一定的影响,并因此而引起一系列的临床副作用.本就抗癫痫药物抑制痫样放电的机理及其对EEG背景活动的影响做一综述,以期为广大临床工作提供些许帮助。     

动态脑电图在癫痫诊断中的应用价值

目的 探讨动态脑电图在癫痫诊断中的应用价值。方法记录169例临床拟诊癫痫患者的24h脑电活动,与常规脑电图检查进行对比。结果动态脑电图痢样放电率（62．72％）及总异常率（86．98％）与常规脑电图比较差异有统计学意义（P均〈0．01）。睡眠期痫样放电率明显高于清醒期。结论24h动态脑电图可提高痫样放电的检出率,对癫痫的诊断有重要应用价值。     

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.