帕金森病患者丘脑腹外侧核的微电极定位技术

目的研究帕金森病患者丘脑腹外侧核(VL)神经元电活动的特点,指导手术靶点的精确定位。方法25例患者在接受立体定向丘脑手术时,应用微电极记录技术采集细胞的电活动资料,分析单细胞的电活动。结果共记录并甄别出258个神经元,44%的神经元簇状放电的节律与肢体震颤的节律高度相关(R=0.78),确认为震颤细胞,且多数位于Vim(n=75);11%的神经元放电对肢体运动有反应,确认为运动相关细胞。结论VL中的细胞电活动有明确的特点,特别是Vim存在着大量的震颤细胞,为手术靶点的定位提供了重要指征。     

微电极导向立体定向手术治疗原发性震颤

目的：探讨丘脑腹外则Vim核中与震颤症状相关的神经细胞电活动的规律,总结丘脑毁损术治疗原性震颤（ET）的临床效果和安全性。方法：对42例ET患者行单侧微电极导向的丘脑毁损术。采用FAHN的临床震颤评分法对其中11例患者术前及术后进行定量评估和分析。结果：Vim核中神经细胞的簇状电活动节律与肢体震颤的节律有肯定的一致性,毁损这些与震颤症状相关的神经细胞后,所有ET患者手术对侧肢体的震颤完全消失;震颤的整体改善率52％,特殊动作和功能改善54％,功能残疾改善率77％,长期随访疗效稳定,其中40例患者的震颤症状密切相关,毁损这些细胞能完全永久性地消除震颤症状。     

内苍白球震颤细胞的电活动与帕金森性震颤

目的 探讨帕金森病（PD）特征性震颤与内苍白球（GPi）神经元电活动的关系，指导手术靶点的精确定位。方法 10例PD患者接受了立体定向苍白球腹后部毁损术，术中应用微电极和肌电（EMG）记录技术，采集GPi神经元和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GPi共记录到了112个神经元，有57个（51％）震颤细胞，且主要分布在视束上方4－6mm，其簇状放电的节律与肢体震颤的节律高度一致（4－6Hz），R^2＝0.71（P＜0.01）。毁损震颤细胞导致震颤症状的消失。结论 震颤型PD患者的GPi存在电活动与肢体震颤节律一致的震颤细胞，该细胞的发现和定位，对于指导手术毁损的部位和范围具有重要意义。     

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.     

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。     

特发性震颤的微电极导向射频治疗

目的探讨丘脑Vim核中神经细胞的电活动与特发性震颤（ET）的关系,总结Vim核射频毁损（切开）术治疗ET的可行性、并发症及疗效。方法对72例ET行CT定位微电极导向Vim核射频,并进行FAHN评分。结果Vim核中存在与肢体震颤节律一致的细胞电活动,毁损这些细胞后震颤立即消失,有效率100％。整体评分改善率60．2％;震颤程度和部位改善率53．1％;特殊动作和功能改善率51．6％;功能残疾改善率76．2％。暂时性并发症19例,3—36个月随访疗效稳定。结论丘脑Vim核中存在与ET密切相关的细胞,射频毁损Vim核是治疗ET安全有效措施。     

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.     

帕金森病外科治疗的有关问题

帕金森病(Parkinson'sdisease,PD)患病率综合世界各国资料在10～405/10万人之间,我国的PD患病率为81/10万,发病和患病率随年龄增长而增加。由于影像学和计算机技术的进步,使外科治疗PD取得了较大进展。毁损术曾经是PD治疗的最主要方法,随着脑深部电刺激术(DBS)的出现,有逐渐被后者取代的趋势。目前PD常用的毁损靶点主要是丘脑腹中间核(Vim)和苍白球内侧部(Gpi)。其中Vim对震颤的控制效果最为理想,对肢体僵直仅有轻度改善,对其他症状无效;双侧Vim毁损会引起认知功能障碍等严重并发症,已被摒弃。苍白球毁损术(PVP)对症状的改善比较全…     

帕金森病患者丘脑腹外侧核团神经元的电活动特点

目的：探讨丘脑腹外侧核（VL）神经元电活动与帕金森性震颤的关系。方法：应用微电极记录和肌电记录技术。对19例帕金森性震颤患者实施立体定向Vim切开术的同时,对Vim的神经元电信号和对侧肢体肌电活动进行记录。电信号的采集和放大器用四通道微电极放大器系统及PolyView软件,采样频率为7.5kHz。电极阻抗在0.1至0.5MΩ,数据分析包括：神经元放电频率,幅度,放电间期,神经元和肌电活动的相关性。结果：在19个针道记录到189个神经元簇,其中簇辨电活动与肢体姿势性震颤一致的有78个,占41%,这78个VL神经元放电活动与肢体震颤（4-6Hz)的相关系数为R^2=0.68。单细胞分析表明78个震颤细胞群放电频率在6-16Hz,平均放电频率8Hz(n=78)。另外101VL神经元族（59%）紧张型放电在6-35Hz之间,其中19个Vim神经元（19）与运动刺激相关,而16个Vc神经元（16%）与触觉相关,结论：VL核团作为皮层-丘脑-基底节环路的重要中继站,接受来自基底节的输入,参与了原发性帕金森震颤的发生发展。     

分期双侧丘脑及苍白球毁损治疗帕金森病的手术策略及疗效分析

目的 总结分期双侧丘脑及苍白球核团毁损治疗原发性帕金森病(PD)的疗效,探讨其有效性及安全性. 方法 安徽医科大学附属省立医院神经外科自1998年2月至2008年5月对已行一侧核团毁损术的19例患者施行微电极导向立体定向对侧丘脑及苍白球核团毁损治疗,其中16例患者一期行丘脑腹中间核(Vim核)毁损,二期行对侧苍白球内侧部(Gpi核)毁损,同时加做Vim核小灶毁损.3例患者一期行Gpi核毁损,二期行对侧Gpi核毁损及Vim核小灶毁损.采用PD国际统一评分量表(UPDRS)对患者术前、术后1周“开”、“关”两种状态进行评分,分析术后症状改善情况及并发症的发生. 结果 所有患者的整体病情和典型症状(震颤、僵直、行动迟缓)均得到明显改善,二期Gpi核毁损术对缓解僵直明显,加做Vim核小灶毁损,震颤缓解满意.2例患者术后出现构音困难,其中1例伴吞咽困难.3个月后症状缓解. 结论 对双侧症状均较严重的PD患者,只要严格掌握适应征,选择合适的靶点,严格控制毁损灶大小,分期双侧丘脑及苍白球核团毁损治疗是一种安全有效的方法.     

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.     

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.     

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.     

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.     

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.     

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.