脑动静脉畸形伽玛刀治疗后的组织病理研究(附5例报道)

目的研究脑动静脉畸形(CAVM)经伽玛刀治疗后的组织病理变化。方法对5例CAVM伽玛刀治疗后的病理标本进行HE染色,并用α-SMA、PCNA、OPN及VEGF等抗体进行免疫组化研究。结果伽玛刀治疗后CAVM血管病理变化包括内膜增厚,管壁增厚、玻璃样变,管腔狭窄至消失等。玻璃样变的管壁或闭塞的管腔可见管腔的再通。OPN、PCNA在表现为早期放射反应的动脉管壁中有强表达;1例标本见内皮细胞PCNA及VEGF阳性染色的网状毛细血管样血管。结论放射治疗后CAVM血管中层的VSMC增生,部分转变为合成表型。VSMC的迁移、增殖和变性是伽玛刀治疗后CAVM进行性血管病理变化的关键因素。     

骨桥蛋白在人脑动静脉畸形的表达及意义

目的研究骨桥蛋白(OPN)在脑动静脉畸形(CAVM)的血管组织及其在放射、栓塞治疗后血管病理变化中的表达。方法采用免疫组化方法检测42例CAVM病理标本及对照组10例内减压手术所获脑组织血管中OPN的表达。结果26例无术前治疗史的畸形血管组织中22例有OPN的表达,主要见于CAVM的静脉部分,在粥样硬化样病变的动脉处也有表达。对照组脑组织的血管中未见OPN的表达;有伽玛刀治疗史的5例中,2例在早、中期放射反应的动脉中可见OPN的明显表达;在经历栓塞治疗的11例中,7例在新生内膜组织或异物巨细胞中有强阳性表达。结论人CAVM血管组织中多有OPN的表达,这可能是其适应于适应血流动力学状态而具有的血管重塑的表现,并可能在放射及栓塞治疗后的血管重塑中发挥重要作用。     

中枢神经系统海绵状血管畸形的免疫组化染色研究

目的 应用免疫组化染色观察不同类型中枢神经系统海绵状血管畸形的内皮细胞标记物、血管生成和增殖活性,探讨病变出血的分子基础. 方法 以自2004年4月至2008年8月南方医院神经外科经显微手术切除的97例中枢神经系统轴内海绵状血管畸形的病理标本为观察对象,根据患者MRI表现分类及其与术中病理形态的比较将所有患者分为出血组(47例)和非出血组50例；另设正常对照组20例,标本来自颅脑外伤患者切除的脑组织.将3组病理标本进行CD34、α-平滑肌肌动蛋白(α-SMA)及血管内皮生长因子(VEGF)免疫组化染色并比较. 结果 海绵状血管畸形内皮层中,CD34呈不同程度的表达,有明显的不连续性；管腔小的病变血管中.CD34染色层较厚；而在管腔大的病变血管中,CD34染色层却较薄,且常不连续.α-SMA表现为阴性或弱阳性(-)～(++).弥散地分布于内皮下层.VEGF有较明显的表达(-)～(++),主要弥散地位于内皮层、内皮下层以及病变血管之间的纤维结缔组织中.正常对照组、出血组与非出血组之间CD34、α-SMA及VEGF免疫组化染色经Kruskal-Wallis H检验示差异均有统计学意义(P＜0.05).所有标本Ki-67染色均呈阴性. 结论 血管结构上缺乏平滑肌可能是部分海绵状血管畸形容易出血的原因之一；VEGF弥散性的表达增多,可能与出血诱导的非特异上调有关；Ki-67染色呈阴性表明至少在标本取得时不存在增殖状态.     

骨髓基质细胞源内皮样细胞对微血管新生的影响

目的研究骨髓基质细胞(BMSCs)源内皮样细胞移植对大鼠局灶性脑损伤血管生成的影响,探讨BMSCs源内皮样细胞移植修复大鼠脑损伤的机制。方法制备大鼠局灶性脑损伤动物模型,进行BMSCs源内皮样细胞移植,通过ELISA、免疫组织化学、电镜等观察局部血管内皮细胞生长因子(VEGF)、内皮细胞及微循环的变化。结果 BMSCs源内皮样细胞移植后,局部VEGF水平升高、凝血因子FⅧ染色阳性细胞数增加,染色加深;局部微血管内膜较光滑,细胞核形态较规则,基底膜较完整,微血管管腔受压缓解。结论 BMSCs源内皮样细胞移植促进损伤区周围内皮细胞增殖和新生血管形成,损伤区局部微循环得以改善。     

VEGF在人脑胶质瘤中的表达与肿瘤增殖及肿瘤血管生成的关系

目的研究血管内皮细胞生长因子(vascular endothelial growth factor,VEGF)在人脑胶质瘤中的表达与肿瘤增殖及血管生成的关系。方法应用免疫组化技术和形态定量分析法,检测98例手术切除脑胶质瘤中VEGF表达、PCNA标记指数(PCNA LI)、微血管密度(Microvessel density,MVD)表达。结果(1)肿瘤细胞及血管内皮细胞均可以表达VEGF,阳性颗粒分布于肿瘤胞浆中;(2)高级别肿瘤PCNA、LI、MVD显著高于低级别肿瘤(P<0.05);VEGF表达阳性肿瘤的PCNA、LI、MVD显著高于VEGF表达阴性肿瘤(P<0.05);(3)在星形细胞肿瘤中,随着MVD的增大,VEGF在肿瘤血管内皮的染色率逐渐增加,与肿瘤的MVD存在正相关关系(r值为0.44,P<0.01)。结论脑胶质瘤的VEGF表达与MVD呈正相关关系,VEGF在肿瘤细胞增殖及血管再生过程中起重要作用。     

脊髓血管畸形血管内皮生长因子在脑脊液的表达

目的探讨脊髓血管畸形是否存在血管内皮生长因子(VEGF)表达,及其表达与临床特征之间是否存在相关性。方法在手术中留取56例脊髓血管畸形的脑脊液标本,其中动静脉畸形(SCAVM)23例,硬脊膜动静脉瘘(SDAVF)19例,海绵状血管瘤(CM)14例;以我院12例蛛网膜下腔阻滞病人脑脊液作为对照组,分别通过酶联免疫吸附方法(ELISA)测定脊髓血管畸形脑脊液中VEGF含量。结果SCAVM脑脊液中VEGF浓度为(277±66)pg/ml、SDAVF为(318±54)pg/ml、CM为(146±32)pg/ml均高于正常对照组(123±27)pg/ml。术前栓塞和出血均可导致脑脊液VEGF升高。结论VEGF与脊髓血管畸形的发生、发展存在一定关系,出血和栓塞均可影响VEGF的表达。     

脑膜瘤血管内皮生长因子与肿瘤增殖活性及瘤周脑水肿关系的研究

目的研究血管内皮生长因子(VEGF)在脑膜瘤中的表达及其与脑膜瘤增殖活性、微血管密度及瘤周脑水肿的关系.方法应用免疫组化方法检测36例脑膜瘤组织中VEGF、增殖细胞核抗原(PCNA)、第Ⅷ因子的表达,测定其阳性细胞数;瘤周脑水肿通过术前颅脑MRI/CT来评估.结果脑膜瘤VEGF表达率为72%(26/36),5例可疑表达;PCNA、Ⅷ因子全部表达.VEGF表达与瘤周脑水肿和微血管密度有显著正相关关系,其r分别为0.878和0.631;VEGF表达与PCNA表达没有相关性,其r为0.087.PCNA标记指数＜25%者占97%(35/36)).结论VEGF存在于脑膜瘤组织中,在瘤周脑水肿和微血管形成方面起着重要的作用.脑膜瘤属于低增殖活性的良性肿瘤.     

脑动静脉畸形原癌基因c-myc表达与内皮细胞增殖活性研究

目的 探讨脑动静脉畸形(cAVM)中原癌基因c-myc表达及其与血管内皮细胞增殖活性的关系。方法 采用免疫组化方法检测47例cAVM中c-myc和增殖细胞核抗原(PCNA)的表达情况。结果 cAVM血管内皮细胞可见c-myc和PCNA免疫阳性染色,其中PCNA表达随病灶扩大而递增,与正常对照组及组间比较差异有显著性(P<0.05);c-myc和PCNA表达呈正相关关系(r=0.827,P<0.05)。结论 cAVM血管内皮细胞具有较高的增殖活性,可能与原癌基因c-myc表达有重要关系。     

体外培养人脑动静脉畸形血管内皮细胞中VEGF表达增加

目的探讨体外培养的人脑动静脉畸形血管内皮细胞和正常脑血管内皮细胞中血管内皮细胞生长因子(VEGF)表达水平的差异。方法采用组织块贴壁法对人脑动静脉畸形血管内皮细胞进行培养和形态学观察;免疫组化检测CD31和vWF抗原验证内皮细胞;采用RT-PCR和Western blot技术检测脑动静脉畸形血管内皮细胞VEGF mRNA和蛋白表达,并与和正常脑血管内皮细胞进行比较。结果体外培养的内皮细胞CD31和vWF染色阳性率达95%以上。人脑动静脉畸形血管内皮细胞中VEGF mRNA和蛋白表达均显著升高(P0.05)。结论体外培养的人脑动静脉畸形内皮细胞中VEGF的高表达,提示血管生成在脑动静脉畸形的发病机制中起重要作用。     

人脑胶质瘤中血管内皮生长因子表达与胶质瘤微血管数及肿瘤增殖活性关系的研究

目的　研究血管内皮生长因子 (VEGF)表达与胶质瘤微血管数、肿瘤增殖活性及其与胶质瘤恶性程度的相关性。方法　应用免疫组化方法检测 5 0例胶质瘤、8例正常脑组织中VEGF、血小板内皮细胞粘附分子 (CD3 1)和增殖细胞核抗原 (PCNA)的表达 ,测定其阳性细胞数和阳性血管数。结果　胶质瘤中均有VEGF、CD3 1及PCNA表达。其表达水平与肿瘤恶性程度呈显著正相关 ,其r分别为 0 .745 ,0 .765及 0 .685。结论　VEGF、CD3 1和PCNA在胶质瘤中的高表达是胶质瘤恶性表型之一 ,可作为病理诊断的补充。     

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.