胶质瘤MGMT基因启动子甲基化研究及应用进展

O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)是一种DNA修复酶,MGMT基因启动子CpG岛甲基化是近年研究较多的胶质瘤相关分子标志,既是评价胶质瘤对烷化剂是否敏感的重要分子标志,也是胶质瘤患者预后评价及复发与假性进展鉴别的重要参考指标。尤其是老年恶性胶质瘤患者,MGMT基因启动子CpG岛甲基化是指导其分子分型和制定个性化治疗方案的重要参考依据。本文对MGMT蛋白功能,以及MGMT基因启动子CpG岛甲基化在指导胶质瘤治疗、判断预后及鉴别复发与假性进展中的应用进行概述。     

MGMT、Caspase-3蛋白在胶质瘤中的表达及预后分析

目的探讨MGMT、Caspase-3蛋白表达水平与胶质瘤患者生存预后的关系。方法运用免疫组织化学方法检测75例不同病理级别胶质瘤组织和10例正常脑组织MGMT、Caspase-3表达情况,分析两者与胶质瘤患者临床病理特征及预后的相关性。结果 MGMT、Caspase-3在胶质瘤中的表达均高于正常脑组织,差异有统计学意义。MGMT、Caspase-3表达水平与患者的年龄、性别、术前KPS评分、病理级别无关联。两者表达情况与恶性胶质瘤患者的生存期关系用KaplanMeier生存曲线表示,结果表明MGMT表达水平与患者预后呈负相关(P0.05),Caspase-3表达水平与患者预后无相关性(P0.05)。MGMT和Caspase-3两者表达呈负相关(r=-0.230,P=0.047)。结论 MGMT表达与胶质瘤预后有关,可作为胶质瘤预后的生物学指标之一,Caspase-3表达与胶质瘤预后无关,但与MGMT有关联。     

显微手术与传统手术治疗脑胶质瘤的疗效对比研究

脑胶质瘤占颅内肿瘤的 33 3%～ 5 8 9% [1] ,肿瘤可发生于中枢神经系统任何部位。除少数星型细胞瘤、毛细胞型细胞瘤可视为良性 ,预后较好外 ,多数病人预后较差 ,平均存活 3～ 5年[2 ] 。目前脑胶质瘤治疗首选手术切除 ,肿瘤切除越彻底 ,病人预后越好。但传统手术很难准确识别肿瘤边界 ,不利于肿瘤全切及保护重要功能结构 ,影响了病人预后。本文收集我院1992年 7月 - 1998年 8月手术治疗脑胶质瘤 97例 ,其中显微手术 32例 ,传统手术 6 5例 ,现报告如下。临床资料及方法一般资料　本组 97例患者 ,男 6 6例 ,女 31例 ,年龄 10～ 6 9岁 ,平均 3…     

荧光引导切除术治疗胶质瘤的临床研究及进展

胶质瘤是最常见的颅内肿瘤,在国内其发病率占颅内肿瘤的35.26%～60.96%,平均44.69%[1]。虽然针对胶质瘤的外科手术及辅助治疗技术发展迅速,但患者预后仍然不佳。研究提示,胶质瘤切除程度与患者预后关系十分密切[2]。然而,其向周围正常组织浸润的生长模式,使肿瘤全切变得十分     

贝伐单抗治疗复发性恶性胶质瘤的临床研究进展

恶性胶质瘤是最常见的恶性原发性颅内肿瘤,尽管目前手术联合放疗及替莫唑胺辅助化疗的标准治疗方案使得患者预后得到一定改善,但仍不容乐观,以胶质母细胞瘤(glioblastoma,GBM)为例,患者在接受手术+放疗+化疗的标准治疗后,中位生存期仅为12～15个月[1]。而对于治疗后肿瘤复发的患者,目前尚无更加有效的治疗方法,其中位生存期小于6个月[2]。此外,恶性胶质瘤患者往往同时存在由肿瘤导致的脑水肿所引起的神经功能障碍,作为减轻胶质瘤患者脑水肿的重要药物,皮质类固醇激素存在许多副作用,对患者生存质量造成一定影响。     

荧光素钠术中荧光辅助显微手术切除脑胶质瘤的研究进展

胶质瘤是颅内最常见的原发性恶性肿瘤[1],以手术治疗为主,但预后较差,高级别胶质瘤(high-grade glioma,HGG)即使采用手术联合术后放化疗及免疫分子靶向治疗等综合治疗,5年生存率仍低于9.8％.肿瘤切除程度为预测无进展生存期(progression-free survival,PFS)、总生存期(ove...     

胶质瘤相关循环生物标志物的研究进展

正胶质瘤是中枢神经系统(central nervous system,CNS)最常见的原发性肿瘤。胶质瘤的诊断、分型、分级、治疗及预后等研究一直是神经外科领域的热点。在胶质瘤患者分级、高危人群的确定以及治疗效果的监测中的生物标记研究,已经成为病理学临床试验的重要组成部分[1]。从手术切除的肿瘤组织或活检获取的肿瘤组织中确定遗传或免疫组织化学标志物具有重要临床意义,但肿瘤组织的重复采样     

经Ommaya囊局部治疗脑胶质瘤的研究进展

脑胶质瘤是颅内最常见的恶性肿瘤,约占颅内肿瘤的44.69% ,其中恶性胶质瘤约占70% [1],呈浸润性生长,手术无法彻底切除.尽管术后辅以联合放、化疗,但预后仍不理想,胶质母细胞瘤(GBM)患者中位生存期为1 年左右,间变性星形细胞瘤(AA)为3 年左右[1-2],且容易复发,因此探索行之有效的治疗方法一直是医学领域的重大课题之一.     

微流控技术在脑胶质瘤治疗方面的基础研究进展

脑胶质瘤是中枢神经系统最常见的恶性肿瘤,其治疗以手术切除为主,但患者总体预后较差。微流控技术在脑胶质瘤治疗方面提供了研究方向,具有临床应用的可行性。该文对微流控技术在脑胶质瘤治疗方面包括脑胶质瘤药物筛选、外泌体及肿瘤微环境的基础研究新进展进行综述。[国际神经病学神经外科学杂志, 2023, 50(5):69-73]     

脑胶质瘤手术的预后分析

颅内肿瘤中脑胶质瘤最常见，发病率占原发性颅内肿瘤的37.8％～57.37％［1］。脑胶质瘤呈浸润性生长，且无根治手段，术后复发率高，严重影响患者的生活质量。脑胶质瘤的综合治疗是影响预后的重要因素，但手术切除是脑胶质瘤综合治疗策略中最为关键的一步，决定了胶质瘤手术的预后。我科于2008‐11—2013‐11采用显微外科手术切除胶质瘤42例，术后恢复良好，现报告如下。     

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.