急性CO中毒后迟发性脑病的相关因素及P300的研究

目的 探讨急性一氧化碳（CO）中毒后迟发性脑病（DEACMP）的相关因素及P300对其病情判定和预后的意义。方法 对44例DEACMP患者与42例未发生迟发性脑病的急性CO中毒（ACMP）患者在C0接触时间，昏迷时间等13个方面进行比较，并行P300检测，且与DEACMP组发生CO中毒初期清醒后所测P300（DEACMP0组）及44名正常人的P300（NC组）进行比较。结果 DEACMP在CO接触时间，昏迷时间，高压氧治疗时间，年龄，合并症等方面与ACMP组比较有极显著差异（P＜0．01），在扩血管药治疗，心脑血管病及呼吸系统疾病史，吸烟，职业方面亦有显著差异（P＜0．05）。DEACMP组较DEACMP0组P300潜伏期明显延长，波幅明显下降（P＜0．01），DEACMP0组较NC组亦有类似改变。结论 长时间接触CO，长时间昏迷，高压氧治疗时间较短，扩血管药治疗时间短，年龄较大，有合并症，患心脑血管病及呼吸系统疾病，吸烟，脑力劳动与发生DEACMP相关。急性CO中毒患者的P300潜伏期越长，波幅越低，其认知功能越差，发生DEACMP的可能性越大。P300对DEACMP的发生，预后可做出较准确评价。     

急性脑梗死诱发全身炎症反应综合征致多器官功能障碍综合征的机制探讨

目的探讨急性脑梗死（ACI）后诱发SIRS及导致多器官功能障碍综合征（MODS）的发病机制。方法收集急性脑梗死患者48例，分为三组，急性单纯脑梗死组（SACI）26例；急性脑梗死致全身炎症反应综合征组（SIRS组）22例；急性脑梗死致多器官功能障碍综合征组（MODS组）13倒；应用酶联免疫吸附法（ELISA法）分别测定不同组别患者血清中TNF-α、IL-6值，与对照组（20例同期健康体检者）比较。结果（1）48例ACI致SIRS的发生率为45．83％，ACI致MODS的发生率为27．08％，ACI致SIRS时诱发MODS的发生率为59．09％。（2）ACI致MODS时均已提前发生了SIRS。（3）SACI组、SIRS组及MODS组患者血清TNF-α、IL-6含量均明显高于正常对照组（P〈0．01）；且SIRS组明显高于SACI组（P〈0．01）；MODS组明显SIRS组（P〈0．01），呈逐渐升高的趋势。（4）MODS不同积分组血清TNF-α、IL-6含量均明显高于SIRS组（P〈0．01）；且MODS组患者，严重者（积分≥9分）血清TNF-α、IL-6含量明显高于病情较轻者（积分〈9分）（P〈0．01）。（5）MODS组死亡患者血清TNF-α、IL-6含量明显高于存活者（P〈0．01）。结论（1）急性脑梗死（ACI）可以诱发全身炎症反应综合征（SIRS），并且是脑梗死致多器官功能障碍综合征（MODS）的发病基础和前提。（2）ACI首先诱发SIRS，SIRS是致MODS的主要机制，动态监测急性脑梗死患者血清TNF-α、IL-6的变化对急性脑梗死是否导致SIRS及MODS的发生有很高的预警价值。（3）急性脑梗死患者血清TNF-α、IL-6含量可作为判断急性脑梗死致SIRS、急性脑梗死致MODS病变程度、预后及转归的指标，并对及时指导临床早期治疗有着重要意义，对SIRS向MODS过度的早期诊断有非常重要的参考价值。     

白介素6在脂多糖致大鼠脑水肿中的表达

目的 探讨白介素6（IL-6）在脂多糖（LPS）致大鼠脑水肿发病过程中的表达及纳洛酮对其干预作用。方法 SD大鼠84只，对照组（NS组）28只，0．2ml生理盐水颈内动脉注射；内毒素组（LPS组）28只，颈内动脉注射LPS 200μg；纳洛酮治疗组（NAL组）28只，颈内动脉注射LPS后10min、1h、2h、6h、12h及处死前2h腹腔注射纳洛酮lmg／kg。于不同时间点测定脑组织匀浆IL-6的含量。干湿法测定脑组织含水量，甲酰胺法测定伊文思兰（EB）含量。结果 LPS组脑组织含水量和EB含量显著高于NS组（P〈0．01）。NAL组脑组织含水量和EB含量显著低于LPS组（P〈0．01），但仍较NS组高（P〈0．01）。注射LPS后4h，LPS组脑组织IL-6含量即增加，于6h达高峰，与NS组比较，差异有统计学意义（P〈0．01）。NAL组IL-6含量低于LPS组（P〈0．05或P≤O．01），但高于NS组（P〈0．01）。LPS组脑组织含水量和EB含量呈正相关（r=0．743，P〈0．01），IL-6含量与含水量呈正相关（r=0．459，P〈0．05），IL-6含量与EB含量呈正相关（r=0．568，P〈0．05）。结论IL-6参与脑水肿的发生发展，纳洛酮可以抑制IL-6的生成，减轻脑水肿。     

脑卒中后抑郁患者血清白细胞介素-2水平变化的研究

目的研究脑卒中后抑郁（poststroke depression，PSD）患者血清白细胞介素-2（interleutin-2，IL-2）水平变化，并探讨PSD患者的免疫功能变化。方法采用放射免疫法检测59例PSD患者、36例非PSD患者及43例正常人的血清LI-2水平；观察29例PSD患者抗抑郁治疗后血清IL-2水平变化。结果治疗前，PSD治疗组血清IL-2水平显著低于非PSD组（P〈0．01）和正常对照组（P〈0．01）；治疗后，PSD治疗组与PSD非治疗组相比，IL-2水平显著升高（P〈0．01），HAMD评分显著降低（P〈0．01）。PSD组治疗前、PSD治疗组治疗后和PSD非治疗组中，HAMD评分与血清IL-2水平呈显著性负相关。结论PSD患者血清IL-2水平明显降低，且与抑郁程度相关，提示PSD可能影响患者免疫功能的变化。     

亚低温对急性脑卒中患者血清IL-2、IL-6、TNF-α水平的影响和临床意义

目的 探讨亚低温对急性脑卒中患者血清IL-2、IL-6、TNF-α的影响和临床意义。方法 将36例急性脑卒中患者随机分为亚低温和常规治疗组．检测入院第1天（d1）、第3～5天（d3～5）、第14天（d14）血清IL-2、IL-6、TNF-α水平并进行对照比较。结果 两组患者d1、d3～5、d14血清IL-2、IL-6、TNF-α水平均高于正常组（P〈0．05）,亚低温组出d3-5、d14血清IL-2、IL-6、TNF-α水平低于同期常规治疗组（P〈0．05）。结论 亚低温可降低急性脑卒中患者血清IL-2、IL-6、TNF-α水平．抑制脑卒中后炎症反应．保护脑神经细胞。     

一氧化碳中毒后迟发性脑病与神经免疫的相关性研究

目的探讨一氧化碳中毒后迟发性脑病(DEACMP)与神经免疫的相关性。方法应用ELISA法测定30例DEACMP患者(DEACMP组)、27例急性一氧化碳中毒未发生迟发性脑病患者(ACOP组)及28例健康对照者(健康对照组)中血清IL-4、IL-10、IFN-γ、TGF-β1的水平并进行比较。结果 IL-4水平DEACMP组低于及健康对照组(P0.05),ACOP组低于健康对照组(P0.05);IL-10水平DEACMP组低于ACOP组(P0.05),ACOP组高于健康对照组(P0.05);IFN-γ水平DEACMP组高于ACOP组及健康对照组(均P0.05),ACOP组高于健康对照组(P0.05);TGF-β1水平DEACMP组低于ACOP组及健康对照组(均P0.05),ACOP组高于健康对照组(P0.05)。结论 DEACMP的发生与神经免疫损伤机制有关。     

分期综合治疗急性CO中毒后迟发性脑病疗效观察

目的探讨分期综合治疗急性CO中毒后迟发性脑病（DEACMP）的临床疗效。方法将68例DEACMP患者随机分为观察组（34例）和对照组（34例）。观察组采取脑病加重期和恢复期分期综合治疗，对照组施以高压氧等常规治疗。结果观察组和对照组痊愈率、显效率、有效率分别为61．76％、26．47％、11．77％和23．53％、20．59％、26．47％。观察组疗效明显高于对照组（x^2=17．95，P〈0．01）。观察组病程27～130d，平均64．73d；对照组病程66～290d，平均182．06d。结论分期综合治疗DEACMP疗效较好，病程较短，是临床较理想的治疗方法。     

急性一氧化碳中毒后迟发性脑病的预后因素分析

目的探讨影响急性一氧化碳中毒后迟发性脑病（DEACMP）预后的因素。方法回顾性分析2008年7月至2011年3月在川北医学院附属医院神经内科住院的42例DEACMP患者临床资料,根据其恢复情况将患者分为无效组（n=21）和好转组（n：21）,分别比较两组患者年龄、性别、基础疾病、中毒时间、意识丧失时间、假愈期、入院时日常生活活动量表（ADL）评分、并发症、是否在急性期接受高压氧（HBO）治疗、头颅CT是否异常、头颅MRI是否异常以及是否使用神经节苷脂（GM1）、依达拉奉、多奈哌齐治疗等可能影响DEACMP预后的因素。结果年龄、假愈期、人院时ADL评分以及并发症与DEACMP患者预后相关（P〈0．05）,其中年龄和最低ADL评分更具意义（P〈0．01）,而其余因素对DEACMP患者预后无明显影响（P〉0．05）。结论年龄较大、假愈期较短、入院时ADL评分较低以及出现并发症均提示DEACMP患者预后不良,应高度警惕。     

急性一氧化碳中毒后迟发性脑病患者血清皮质醇、促肾上腺皮质激素水平及其临床意义

目的 探讨急性一氧化碳中毒后迟发性脑病(DEACMP)患者血清皮质醇(COR)、促肾上腺皮质激素(ACTH)水平的变化及其临床意义.方法 采用酶联免疫吸附法动态检测33例DEACMP患者血清COR、ACTH的水平,并与32例急性一氧化碳(CO)中毒后未发生DEACMP患者和32例正常对照者进行比较;采用日常生活能力量表(ADL)、常识-记忆-注意测验(IMCT)、长谷川痴呆量表(HDS)动态检查DEACMP患者的病情变化.结果 DEACMP组急性期血清COR水平明显高于急性CO中毒组和正常对照组(均P＜0.05);ACTH水平明显高于急性CO中毒组(P＜0.05),与正常对照组比较无显著差异(P＞0.05).DEACMP组恢复期血清COR、ACTH水平较急性期均有不同程度的降低,但只有COR水平有显著差异(P＜0.05).DEACMP组急性期ADL、HDS、IMCT评分与恢复期比较均有显著差异(均P＜0.01).DEACMP组急性期、恢复期血清COR水平变化与HDS和ADL评分变化之间呈显著正相关(P＜0.05).结论 DEACMP患者血清COR、ACTH水平动态变化与病情变化基本一致,动态检测血清COR、ACTH水平变化可作为DEACMP病情变化和治疗效果的生物学指标之一.     

阿伐他汀对实验性自身免疫性脑脊髓炎免疫功能的影响

目的观察阿伐他汀（Atorvastatin）对EAE的治疗作用并初探其治疗机制。方法以豚鼠脑、脊髓为原料提取髓鞘碱性蛋白MBP,免疫Lewis大鼠建立EAE模型。建模后每日对大鼠神经症状进行评分,采用ELISA法检测大鼠脾细胞培养上清液中IFN-γ、IL-12和IL-4水平。结果与EAE组相比,Atorvastatin组大鼠发病时间有所延迟,症状有不同程度减轻。与正常组相比,EAE组大鼠17d、21d时,IL-4水平明显升高（P〈0．01）,13,17,21d时IFN-γ、IL-12水平均明显升高（P〈0．01）;IFN-γ、IL-12浓度与神经症状评分有较强的正相关关系（RIFN-γ=0．904,P〈0．01;RIL-12=0．885,P〈0．01）。与EAE组相比,Atorvastatin组13d、17d时IL-4水平明显升高（P〈0．01）。IFN-γ、IL-12水平在13,17,21d时均显著低于EAE组（P〈0．05）。结论Alorvastalin能改善EAE大鼠的症状,其机制可能与纠正Th1／Th2失衡有关。     

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.