脑星形细胞瘤瘤周水肿区活检组织病理及超微结构研究

目的 探讨星形细胞瘤瘤周脑水肿区的病理及发生水肿可能机制。方法 对15例星形细胞瘤瘤周水肿的宽度进行分级,共分三级：一级0-20mm、二级21-40mm、三级〉41mm。并对其立体定向多靶点活检组织进行光镜及电镜检查。结果 在星形细胞瘤瘤周水肿区内,发现有浸润的肿瘤细胞,肿瘤细胞形态与瘤体区标本的肿瘤细胞形态一致。随着肿瘤恶性度及瘤周水肿程度的增加,肿瘤细胞浸润的范围就更广。瘤体和瘤周水肿区毛细血管的分布和结构变化影响着瘤周水肿区的形态,瘤体毛细血管的明显异常,出现于大范围瘤周水肿区的病例。结论 脑星形细胞瘤瘤周水肿区是肿瘤浸润的范围,伴有脑水肿。瘤体及瘤周水肿区毛细血管超微结构均有不同程度的改变。     

脑胶质瘤血脑屏障超微结构及其CT对照研究

应用透射电镜对18例星形细胞瘤、2例少树突细胞瘤、2例髓母细胞瘤及其水肿带,正常脑组织的血脑屏障超微结构进行比较分析,并与颅脑CT影像对照研究。结果表明,瘤体、瘤周水肿区的血脑屏障有不同程度异常改变,表现为内皮细胞肿胀,紧密联接变长变宽,基膜厚薄不均,质膜局部缺损。病灶区CT平扫显示低密度,增强扫描呈不同程度增强,与对照观察血脑屏障的变化呈正相关,结果揭示瘤周水种区的CT强化影像观察是化疗时判定血脑屏障开放的简便方法。     

脑胶质瘤血脑屏障超微结构及其CT对照研究

应用透射电镜对22例脑胶质瘤及其水肿带、正常脑组织的血脑屏障(BBB)超微结构进行观察,与病人颅脑CT图象作对照研究。结果表明,瘤体及其瘤周水肿带的BBB均有不同程度的异常改变,表现为毛细血管内皮细胞肿胀,紧密联接变宽,基膜厚薄不均,质膜局部缺损。病灶区CT平扫显示低密度,增强扫描呈不同程度增强,对照观察,BBB变化越异常,这一CT特征越明显。     

脑肿瘤周围水肿范围影响因素的CT研究

本文研究了37例脑瘤CT片上所示水肿剖面和水肿的不同原因.其中8例多形性胶质母细胞瘤,13例转移瘤、8例脑膜瘤、7例星形细胞瘤(II～Ⅲ级),2例为脑脓肿.按肿瘤周围脑水肿半径分为0～20mm、21～40mm和>40mm三组.均行普通及增强CT扫描.按两个方向测量:(1)从肿瘤边缘向白质的半卵圆中心,(2)从肿瘤边缘向脑室.测量两半球对应部位的CT值,取其差代表移入水肿区水分的近似值.根据以往文献,水肿局部CT值和局部组织水含量有显著的线性关系.因此可借水肿区CT值的降低行人体脑水肿量的测量.研究发现:水肿长度<20mm多为环形水肿;20mm以上则多为不规则形且常有指状突起.瘤周区水含量和水肿长度有关.两者的关系在半对数坐     

脑胶质瘤瘤周CT低密度区的病理和超微结构研究

为阐明脑胶质瘤瘤周CT低密度区（CT－PTLDA）本质及其与预后的关系，本研究对20例胶质瘤瘤周CT低密度区的宽度进行分级，并以光镜观察其病理特征；结合CT平扫及增强扫描的影像，取代表性的14例肿瘤瘤体、水肿区和正常脑组织进行电镜观察比较。结果显示：（1）CT－PTLDA内可见瘤细胞浸润；（2）电镜下可见瘤体及瘤周毛细血管内皮细胞呈不同程度肿胀，紧密连接扩张、扭曲，基膜完整但厚薄不均，胶质膜局部缺损。CT－PTLDA越宽其血脑屏障改变也越严重；（3）CT－PTLDA宽度与预后密切相关，CT－PTLDA越宽预后越差。以上结果提示脑胶质瘤CT－PTLDA是瘤细胞浸润扩散的实际范围及伴有脑水肿的表现，对CT－PTLDA宽度进行分级有助于对预后的判断。笔者建议在胶质瘤手术中应尽可能切除非功能区组织的水肿带，以免留下肿瘤复发根源。     

星形细胞瘤生物学行为特征及机理探讨

目的:阐明星形细胞瘤生物学行为特征及形成机理.方法:①根据CT影像学对52例星形细胞癌瘤周水肿厚度进行分级:一级:<20mm;二级:20～40mm;三级:>40mm.②电镜对照观察6例瘤体、水肿区和正常脑组织的血脑屏障超微结构.③光镜观察3例瘤体及水肿组织的连续切片.④免疫组化方法检测52例星形细胞瘤、18例瘤周水肿组织、11例胶质增生的p53、CerbB-2/neu、PCNA表达.结果:①水肿级别与瘤体及水肿区的血脑屏障改变程度呈正相关;瘤体及水肿组织连续切片可见瘤体各部位分化不一致;水肿区可见瘤细胞浸润,水肿越明显,浸润越明显,水肿不明显者,未见瘤细胞浸润.②星形细胞瘤p53、CerbB-2/neu、PCNA异常表达率分别为46.2%(24/52)、38.5%(20/52)和77%(40/52);瘤周水肿组织分别为:44.4%(8/18)、0和72.2%(13/18).与正常组织对比P值分别为:0.0169、0.044和<0.001;0.0251、1和0.003.其表达率与病理级别、分化程度、水肿分级有关.病理Ⅲ、Ⅳ级阳性率80%(16/20)、40%(8/20)、100%(20/20);Ⅱ级:33.3%(8/24)、50%(12/24)、83.3%(20/24);Ⅰ级阳性率均为0,Ⅰ与Ⅱ比P值为:0.1522、0.0302、0;Ⅰ与Ⅲ、Ⅳ比P值为:0.0002、0.0628、0;Ⅱ与Ⅲ、Ⅳ比P值为:0.0199、0.5071、0.1651.水肿一级者阳性率:0、0、14.2%(1/7).二级:31.6%(6/19)、31.6%(     

脑膜瘤血管内皮细胞超微结构改变与瘤周脑水肿

目的研究不同程度水肿的脑膜瘤组织血管内皮细胞（ＥＮ）通透性改变的差异。方法对２１个脑膜瘤组织标本，３个水肿脑组织标本的ＥＮ超微结构进行观察和形态计量学分析，并以３个正常脑组织标本为对照。结果水肿组织和肿瘤组织的ＥＮ超微结构发生明显改变，其程度与瘤周水肿程度相关。其中，基板厚度随水肿程度加重而显著增加，裂隙指数也随水肿程度加重渐增大，重度水肿组显著高于无／轻度水肿组及中度水肿组，而胞饮小泡数量及窗孔的出现则以中度水肿组改变最显著。结论不同程度水肿的脑膜瘤ＥＮ超微结构改变程度不同，不同程度的细胞间连接开放可能是不同程度瘤周脑水肿形成的最重要原因。     

星形细胞瘤生物学行为特征及机理探讨

目的：阐明星形细胞瘤生物学行为特征及形成机理。方法：①根据CT影像学对52例星形细胞瘤瘤周水肿厚度进行分级：一级：<20mm；二级：20～40mm；三级：>40mm。②电镜对照观察6例瘤体、水肿区和正常脑组织的血脑屏障超微结构。③光镜观察3例瘸体及水肿组织的连续切片。④免疫组化方法检测52例星形细胞瘤、18例瘤周水肿组织、11例腔质增生的p53、CerbB-2/neu、PCNA表达，结果：①水肿级别与瘤体及水肿区的血脑屏障改变程度呈正相关；瘤体及水肿组织连续切片可见瘤体各8部位分化不一致；水肿区可见瘤细胞最润，水肿越明显．浸润越明显．水肿不明显，未见瘤细胞浸润。②星形细胞瘤p53、CerbB-2／neu、PCNA异常表达率分别为46．2%（24／52)、38．5％(20/52)和77％（40/52)；瘤周水肿组织分别为：44．4％（8/18)、0和72．2％(13/18)。与正常组织对比P值分别为：00169、0．044和<0．001；00251、1和0．003。其表达率与病理级别、分化程度、水肿分级有关。病理Ⅲ、Ⅳ级阳性率80％(16/20)、40％(8／20)、100％(20/20)；Ⅱ级：33.3％(8/24)、50％(12/24)、83.3％(20/24)；Ⅰ级阳性率均为0，Ⅰ与Ⅱ比P值为：0.1522、0．0302、0；Ⅰ与Ⅲ、Ⅳ比P值为：0．0002、0.0628、0；Ⅱ与Ⅲ、Ⅳ比P值为：0．0199、0．5071、0．1651。水肿一级阳性率：0、0、14．2％（1/7)。二级：31.6％(6/19)、31.6％(6/19)、68．4％(13/19)：三级：69.2％(18／26）、53．8％(14／26)、100％(26/26)，一级与二级比P值为：0.1456、0．1456、0.0261；一级与三级比：0.0015、0.026、0；二级与三级比：0．001239、0.1376、0．0084。FCNA表达与CerbB-2/neu表达无一致性．P>005，③11例胶质增生有1例显示p53表达，CerbB-2／neu、PCNA无表达，随访3年，病变复发。术后病理诊断星形细胞瘤Ⅱ级，同时CerbB-2，neu表达，PCNA高指数，瘤周出现水肿。结论；①水肿的产生与p53、CerblB-2/neu、PCNA异常表达引起瘤体、瘤周血脑屏障改变有关，而肿瘤侵袭与水肿有关。水肿区是瘤细胞侵袭扩散实际范围．其增生的胶质细胞也具有恶性表型。②p53、CerbB-2／neu、PCNA异常表达与肿瘤发生发展有关，可作为肿瘤恶性程度及预后指标，p53主要影响肿瘤的分化。p53对预测早期癌症有帮助。③肿瘤起动基因可能来自分化调节基因，而肿瘤的异常分化又可能引发其它相关的异常表达，构成肿瘤发生发展的多击中过程，作在此基础上，提出肿瘤生物学行为所遵守的可能法则。     

组织蛋白酶D在星形细胞瘤中心区、周缘区和水肿区的表达情况

目的 探讨组织蛋白酶D(CathD)在人脑星形细胞瘤瘤体中心区、周缘区和瘤周水肿区的表达情况及临床意义.方法 选择核磁共振检查未见肿瘤坏死或囊变且瘤体区与水肿区有明显分界的41例星形细胞瘤患者,分为复发组13例、未复发组28例.术中对照磁共振FLAIR序列留取瘤体中心区、周缘区和水肿区后行CathD免疫组化染色,对其在不同区域表达水平进行分析.结果 CathD在正常脑组织无或弱表达,其在瘤体中心区、瘤周水肿区和周缘区呈阳性表达,且周缘区[(10.780±1.557)分]高于中心区[(2.610±0.945)分],差异有统计学意义(P<0.05).在瘤体周缘区复发组CathD表达[(11.539±1.127)分]强于未复发组[(10.429±1.620)分],差异有统计学意义(P<0.05),而在瘤体中心区复发组与未复发组CathD表达差异无统计学意义(P>0.05).结论 周缘区和水肿区CathD明显表达提示瘤周水肿区可能是瘤细胞易于发生浸润的区域:中心区CathD相对低表达说明该区细胞外基质已被降解殆尽,是肿瘤侵袭较早发生的区域;周缘区和水肿区CathD表达情况可作为一种判断肿瘤复发的指标.     

不典型星形细胞瘤的CT诊断

目的 研究不典型星形细胞瘤的CT征象。方法 回顾分析13例CT首次误诊，手术病理证实的星形细胞瘤的术前CT图像与临床表现。结果 ①13例星形细胞瘤，9例年龄＞50岁，11例部位在大脑半球。②星形细胞瘤表现为低密度或带回状高密度灶；形态为楔形或圆形；无强化或带回状强化；瘤周水肿。结论 定期追踪CT复查，应用多项指标综合分析，能够提高CT诊断不典型星形细胞瘤的准确率。     

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.