创伤性脑损伤后局部脑缺血的研究进展

局部脑缺血是创伤性脑损伤后继发颅脑损伤的重要原因之一,颅脑外伤死亡的病人约90%都存在脑缺血。外伤后脑缺血将加重脑损伤,并将导致神经元和胶质细胞坏死和凋亡。外伤后局部缺血的机制及创伤半暗带范围界定尚待进一步研究,外伤缺血的病理过程较脑梗塞后的缺血更复杂。脑血流及脑氧监测、微透析技术、核磁影像及PET对于脑外伤病人缺血判定都各有优缺点,只有对脑血流及脑组织代谢行多方法监测,才能为临床提供更精确的脑缺血证据,以期改善病人预后。     

创伤后癫痫的研究进展

颅脑创伤后继发癫痫即创伤后癫痫(posttraumatic epilepsy,PTE)是颅脑创伤后最严重的并发症之一,也是症状性癫痫中最常见的一种类型.约有5%癫痫发生于颅脑创伤之后[1].PTE即颅脑创伤后反复出现的无诱发的痫性发作不同于颅脑创伤后早期出现的反复痫性发作(posttraumatic seizure,PTS).PTE是指因颅脑创伤的原因而使患者在伤后出现癫痫的反复发作,PTS是指因颅脑创伤后当时的病理生理变化而产生的临床发作,将来并不一定会发展成为PTE[2].     

创伤后脑缺血与脑血管损伤

创伤后脑缺血是创伤性脑损伤后继发颅脑损伤的重要原因之一,颅脑外伤死亡的病人约90%都存在脑缺血。创伤后脑缺血将加重脑损伤,并将导致神经元和胶质细胞坏死和凋亡。创伤后脑缺血的机制尚待进一步研究,创伤后缺血的病理过程较脑梗塞后的缺血更复杂。随着影像学的广泛应用,发现颅脑创伤后患者出现缺血表现常提示存在潜在的脑血管损伤。脑血管损伤是创伤后脑缺血发生的主要原因。     

镁离子对颅脑创伤患者的治疗作用

近几年，人们通过动物实验发现，镁离子(Mg^2 )作为内源性神经保护因子在颅脑创伤后的脑组织代谢中起着重要作用。大量实验研究证实，Mg^2 可预防及减轻颅脑创伤后的继发性脑损伤。     

纳洛酮治疗重型颅脑损伤疗效分析

近年来,国内外大量研究证明颅脑损伤后脑组织中内源性阿片肽含量异常改变参与继发性脑损伤发病过程[1].纳洛酮是一种人工合成的阿片受体拮抗剂,它能有效阻断急性颅脑损伤后内源性阿片肽含量异常增高所致的继发性脑损害[2].     

华东地区运动相关颅脑创伤的流行病学调查

在运动相关的各类损伤中,颅脑创伤的致残与死亡率最高.头颈部损伤致死占运动员所有创伤死亡的70％,占永久性致残的20％[1].在美国,运动相关的颅脑创伤最常发生于美式橄榄球,冰球和拳击等对抗性运动.所有高中橄榄球运动员中有20％每年遭受一次脑震荡,平均每年有8人因为颅脑创伤而死亡[2].本研究通过回顾性分析华东地区2004年运动相关颅脑创伤的病例,了解我国华东地区运动相关颅脑创伤的伤情及流行病学特点,报道如下.     

重型颅脑创伤多参数脑缺血指标与预后关系的研究

创伤性脑损伤是一个非常严重的社会医学问题,美国每年有约150万的颅脑外伤患者,57％的重型颅脑创伤患者预后不良,尸检发现,颅脑外伤死亡的患者约90％都存在脑缺血,脑缺血是继发性颅脑创伤的重要原因之一[1].在颅脑创伤患者中,脑缺血是继发性损伤中最常见的病理改变.本文通过62例资料分析研究脑缺血指标与预后的关系.     

颅脑创伤模型小鼠海马水通道蛋白1表达及作用

研究背景颅脑创伤后继发性脑损伤包括脑组织缺血、缺氧和脑水肿,可进一步加重原发性损伤,影响预后。作为选择性易损区,海马对缺血和水肿尤为敏感,易出现不可逆性损伤。水通道蛋白1(AQP1)与脑水肿的发生关系密切,但迄今尚无颅脑创伤后海马AQP1表达变化及其相关作用的报道。本研究采用闭合性颅脑创伤小鼠模型对海马水肿过程进行观察,以探讨AQP1在相关病理生理学过程中的作用机制。方法采用改良自由落体法建立BALB/c系小鼠闭合性颅脑创伤模型,于创伤后不同观察时间点(1、6、24和72 h)进行神经功能缺损程度评价和脑组织含水量测定,并通过TUNEL法观察海马神经元凋亡率、免疫组织化学染色和Western blotting法检测AQP1表达变化。结果成功制备闭合性颅脑创伤小鼠模型,并经神经功能评价和脑组织含水量测定证实存在重型颅脑创伤和脑水肿。TUNEL检测显示,模型组小鼠伤后6 h海马神经元凋亡率即升高[(44.26±15.18)%对(8.61±8.25)%;t=-9.676,P=0.002],至72 h达峰值水平[(61.62±26.55)%对(10.17±6.08)%;t=-5.018,P=0.015];免疫组织化学染色和Western blotting法观察,模型组小鼠创伤后各观察时间点海马AQP1表达水平均高于假手术组(P0.05),以伤后24 h表达水平最高(0.69±0.32对0.15±0.07,t=-4.335,P=0.023;0.46±0.19对0.14±0.04,t=-4.113,P=0.004)。结论颅脑创伤后小鼠海马AQP1表达上调可能参与了脑水肿和迟发性神经元凋亡等病理生理学过程,AQP1可能成为继发性脑损伤机制研究的新靶点。     

一种新型的亚低温治疗方法——血管内降温

大量基础研究和临床资料表明,重型颅脑创伤的患者进行亚低温治疗可以降低颅内压,减少脑水肿,从而增加脑灌注压,同时可以保护血脑屏障,阻断毒性代谢产物对神经细胞的损害,具有一定的脑保护作用,可以减少致残率和死亡率,因此,国内外神经外科医生开始将亚低温治疗应用于颅脑创伤患者的治疗中,并研究出了一整套简单有效、安全可靠的临床降温方法[1-7].目前国内外有条件的医院已将亚低温治疗方法列为重型颅脑创伤患者的治疗常规.     

大鼠颅脑创伤后脑红蛋白表达变化的实验研究

目的研究弥漫性颅脑创伤后大鼠脑组织中脑红蛋白的核酸与蛋白表达变化情况，初探脑红蛋白与颅脑创伤的关系。方法选择Marmarou’s自由落体打击装置复制弥漫性颅脑创伤模型，采用实时定量PCR及Westernblotting分别检测伤后不同时间（30min、1h、2h、6h、12h、24h、48h、72h、5d）脑组织中脑红蛋白核酸及蛋白水平的表达情况，并对所得数据进行统计学分析。结果在伤后30min，脑组织中脑红蛋白的核酸表达m现首个高峰，相应地其蛋白表达于伤后1h增高，于伤后2h达峰值；伤后12h，脑红蛋白的核酸表达再次升高，于伤后48h达高峰，其蛋白表达亦于伤后24h增高，至72h达峰值。结论颅脑创伤后脑组织中脑红蛋白呈“双峰”样表达。提示脑红蛋白可拮抗对神经元的创伤应激及伤后继发缺血、缺氧性损害，对创伤后脑组织具有一定的保护作用。     

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.