帕金森病猴苍白球神经元的电生理特性

目的 探讨帕金森病(Parkimon disease,PD)猴模型苍白球(globus pallidus,GP)神经元的电生理特性,为研究帕金森病的病理生理过程提供动物实验依据.方法 应用颈内动脉注射1-甲基4-苯基-1,2,3,6-四氧吡啶(1-methyl-4-phenyl-1,2,3,6-tetrahydropyri-dine,MPTP)建立PD猴模型.在立体定向仪引导下记录造模前后猴病理及正常生理状态下GP神经元的放电活动,并对其放电模式进行分析.结果 电生理记录显示外侧苍白球神经元(29个)放电频率在生理状态下为(4.39±2.10)Hz,在病理状态下(34个)为(9.69±4.99)Hz(P<0.05);内侧苍白球神经元放电频率在生理状态下(25个)为(2.69±1.57)Hz,在病理状态下(31个)为(17.50±4.94)Hz(P<0.01);在记录到内侧苍白球神经元单一放电时,进行长时间观察并给予APO(0.2 mg/kg)肌注,可见神经元放电频率和振幅明显减低.结论 PD猴模型GP神经元较生理状态下放电频率明显增加,其放电模式也有明显变化,簇状放电模式比例增大.     

帕金森病大鼠苍白球神经元簇发放电及峰峰间期序列的研究

目的 观察帕金森病大鼠模型苍白球神经元的电活动.方法 30只大鼠注射6-羟基多巴胺(6-hydroxydopamine, 6-OHDA)建立PD模型,并通过跑步机测试、注射阿朴吗啡诱发旋转和免疫组化检测黑质对模型进行评价;10只大鼠注射含0.2%抗坏血酸的人工脑脊液建立对照组.在立体定向仪引导下记录大鼠在PD病理及正常生理状态下GP神经元的自发放电活动.结果 模型组大鼠中有13只行为学及病理学检测结果符合PD模型标准.电生理记录显示对照组大鼠GP神经元放电频率为(6.04±2.12)Hz,模型组大鼠GP神经元放电频率为(21.10±3.21)Hz(P=0.001).模型组GP神经元簇发放电模式的比例术后4周为59%,术后8周为61%,而对照组GP神经元簇发放电模式的比例在术后4周和8周均为11%.模型组大鼠神经元放电的峰峰间期散点图在100ms以下有一分布密集条带.结论 PD模型大鼠GP神经元较生理状态下放电频率明显增加,簇状放电模式比例增大,ISI序列发生明显变化.     

帕金森病大鼠苍白球神经元放电模式的分析

目的 探讨帕金森病(Parkinson's disease,PD)大鼠苍白球(globus pallidus,GP)神经元的放电模式,为研究帕金森病的病理生理过程提供实验依据.方法 大鼠30只,应用6-羟基多巴胺(6-hydroxydopamine,6-OHDA)建立PD大鼠模型(模型组),多种方法对模型进行评价.在立体定向仪引导下记录PD模型组及正常生理状态下大鼠(对照组,10只)GP神经元放电活动,并对其放电模式进行分析.结果 模型组大鼠中有13只行为学及病理学检测结果符合PD模型标准.电生理记录显示对照组大鼠GP神经元放电频率为6±2Hz,模型组大鼠GP神经元放电频率为21±3Hz,模型组大鼠的放电频率显著高于对照组(P＜0.05).对照组共记录到四种形式的放电模式,模型组记录到三种.对照组GP神经元簇发放电模式的比例为11%,而模型组GP神经元簇发放电模式的比例术后四周为59%,术后八周为61%,两者比较具有统计学意义(P＜0.05).结论 PD模型大鼠GP神经元较生理状态下放电频率明显增加,其放电模式也有明显变化,簇状放电模式比例增大.这可能在帕金森病的病理生理变化中具有重要作用.     

帕金森病患者僵直迟缓症状神经元电活动特点研究

目的探讨帕金森病(PD)患者僵直迟缓症状的神经元电活动特点。方法 25例僵直迟缓为主征的PD患者接受立体定向丘脑底核(STN)脑深部电极植入术(DBS)。术中通过微电极记录技术采集神经元电活动。应用单细胞分析方法,峰间隔分析方法分析神经元放电的频率和形式,应用功率谱分析方法分析神经元放电周期节律。结果分析了180个信号稳定的神经元,平均放电频率为(40.6±22.3)Hz;有35.6%(n=64)神经元有周期节律性放电,放电周期节律在β节律内。结论β节律的神经元周期节律性电活动可能和PD僵直迟缓症状的病理生理改变有关。     

帕金森病患者丘脑底核的微电极定位技术

目的　研究帕金森病(PD)患者丘脑底核(STN)及其邻近结构神经元电活动的特点,指导手术靶点的准确定位。方法　30例PD患者在行STN电极埋植(8例)或毁损术(22例)时,应用微电极和EMG记录技术,采集STN及其邻近结构的细胞外电活动和肢体的EMG活动。分析其电活动的特点。结果　在31个记录针道中,共记录到388个STN神经元,其中14%呈紧张性放电,28%呈规律性簇状放电,58%呈不规则或簇状放电。放电频率20～50Hz,平均42.2±11.6Hz。确认震颤细胞,节律为3.8～6Hz,与肢体震颤密切相关(r=0.63,P<0.01)。多数(82%)震颤细胞位于STN中上部分。黑质神经元呈均匀的紧张性放电,放电频率72.5±17.9Hz。结论　STN及其邻近结构存在特征性的电活动,微电极记录技术为STN手术的精确定位提供了可靠的技术保证。     

帕金森性震颤和与震颤相关的电活动

目的对PD患者行STN和GPi切开术术中应用微电极记录技术采集神经元的电活动,术后分析其与震颤的关系和特点,为手术选择最佳的毁损位置提供客观的电生理指标.方法40个PD患者,其中21例PD患者接受了立体定向GPi切开术和19例PD患者接受立体定向STN切开术.病人要求清醒合作且处于“关”状态.术中应用微电极和肌电(EMG)记录技术,采集GPi和STN神经元和手术对侧肢体震颤的生物电活动.术后应用分析软件甄别单细胞及其电活动特点,分析其与震颤症状的关系,并进行相关性检验.结果在21个针道共记录到184 GPi个神经元单位,其簇状放电的节律与肢体震颤的节律高度一致(4～6Hz),R2=0.78(P＜0.01).在20个针道共记录到161个STN神经元单位,其放电频率在42～88Hz之间.STN的簇状放电的节律与肢体震颤的节律一致(4～6Hz),R2=0.64(P＜0.01).毁损这些震颤细胞导致震颤症状的消失.结论震颤型PD患者的GPi和STN存在与肢体震颤节律一致的震颤细胞,且震颤和震颤细胞有着内在的关系.对于指导手术毁损的部位和范围提供了可靠的依据.     

神经性厌食症大鼠伏隔核神经元电活动及峰峰间期序列的分析

目的观察神经性厌食症大鼠模型伏隔核神经元的电活动并分析其峰峰间期。方法通过微阵列电极记录大鼠在神经性厌食症病理及正常生理状态下伏隔核神经元的自发放电活动。结果电生理记录显示模型组大鼠NAc神经元平均放电频率为6.89±2.67Hz,对照组大鼠NAc神经元平均放电频率为3.22±1.23Hz。(P=0.001)。模型组大鼠伏隔核神经元放电的峰峰间期散点图在200ms以下有密集分布。模型组伏隔核神经元放电峰峰间期直方图呈逐渐衰减的正偏态分布,对照组伏隔核神经元放电峰峰间期直方图呈对称分布。结论神经性厌食症模型大鼠伏隔核神经元较生理状态下放电频率明显增加,峰峰间期序列发生明显变化。     

高频电刺激丘脑底核对偏侧帕金森病猴模型苍白球内侧部神经元放电的影响

目的 探讨深部电刺激丘脑底核(STN)治疗帕金森病(PD)的可能作用机制. 方法 通过在模型猴单侧大脑注入1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)制备偏侧PD模型,随后在立体定向技术下参照猴脑立体定向图谱,将记录的玻璃微电极和刺激电极分别插入苍白球内侧部(Gpi)和STN内,通过单细胞胞外记录法记录并分析神经元刺激前和刺激时的放电改变情况. 结果 PD猴未注药侧GPi神经元自发放电较规则,放电频率为(44.38±13.66)锋电位/s;注药侧GPi神经元放电频率为(50.57±15.53)锋电位/s,较未注药侧稍快但差异无统计学意义(P＞0.05).刺激过程中GPi神经元存在4种反应:部分抑制、完全抑制、兴奋和无变化,多数神经元表现为受到抑制,注药侧更为明显,平均抑制率为56.29％±29.66％,高于未注药侧的36.03％±35.25％,差异有统计学意义(P＜0.05). 结论 深部电刺激术治疗PD的作用机制为通过高频刺激对STN神经元异常兴奋性的调控,改变相关的联系核团如GPi或黑质网状部(SNr)的异常功能状态,最终使基底节运动环路正常控制功能重新恢复,进而改善PD症状.     

神经性厌食症大鼠伏隔核神经元局部场电位分析

目的观察神经性厌食症大鼠模型伏隔核神经元的电活动并分析其局部场电位。方法实验动物分为运动诱发的厌食症(activity-based anorexia,ABA)大鼠模型组及对照组(各12只)。ABA模型的建立基础是模型大鼠不受限制的滚轮运动以及限制饮食(1h/d),通过这种限制饮食及过度活动,造成明显的体重下降,从而模拟AN的行为学特征。通过微阵列电极记录大鼠在神经性厌食症病理及正常生理状态下伏隔核神经元的局部场电位。结果电生理记录显示模型组大鼠NAc神经元平均放电频率为(6.89±2.67)Hz,对照组为(3.22±1.23)Hz。模型组大鼠伏隔核神经元放电的峰峰间期散点图在200ms以下有密集分布。模型组伏隔核神经元放电峰峰间期直方图呈逐渐衰减的正偏态分布,对照组伏隔核神经元放电峰峰间期直方图呈对称分布;回归映射分析结果显示病理状态下数据明显较生理状态下集中。功率谱密度分析显示模型组在10~20Hz范围内出现了能量高值成分。结论神经性厌食症模型大鼠伏隔核神经元较生理状态下放电频率明显增加,峰峰间期序列发生明显变化,局部场电位模式发生变化。     

运动障碍病的神经电生理基础

目的探讨运动障碍病的细胞学病理生理基础,提高手术治疗的有效率和安全性.方法回顾过去3年的工作,1200例运动障碍病患者接受了微电极导向的立体定向神经外科手术.包括帕金森性病(PD)、原发性震颤(ET)、扭转痉挛和痉挛性斜颈等.手术的靶点包括苍白球腹后部(PVP),丘脑底核(STN)和丘脑腹外侧核(VL).术中应用微电极和肌电(EMG)记录技术,采集GPi,STN和VL神经元和肢体肌电活动.术后应用分析软件甄别单细胞及其电活动特点,分析其与临床症状的关系,并进行相关性检验.结果PD性震颤在GPi,STN、VL获得相关神经元簇放电频率是不一致,可指导临床.原发性震颤在丘脑腹中间核(Vim)获取的放电频率,也有临床指导意义.扭转痉挛和痉挛性斜颈扭转痉挛和痉挛性斜颈患者的神经元簇放电无明显规则可寻.结论识别和确定GPi、STN和VL细胞电活动特点及其分布,对于指导立体定向手术的功能定位,提高运动障碍病手术治疗的疗效和降低手术并发症具有重要的意义.     

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.