胶质母细胞瘤的预后影响因素分析

目的探讨与胶质母细胞瘤(GBM)生存预后相关的影响因素。方法回顾性分析61例GBM病人的临床资料,统计分析性别、年龄、病变部位、病程时间、术前Karnofsky评分(KPS)、肿瘤残余体积、同步放化疗、MGMT表达、Ki-67表达、对疾病认知情况对病人生存期的影响。结果 61例病人生存时间为2~42个月,中位数为10个月,1、2、5年生存率分别为26.2%、9.2%、0。术前KPS评分≥70分、完成同步放化疗及Ⅳ级认知程度病人生存期较长,差异有统计学意义(P0.05)。术前KPS评分、是否同步放化疗、病人对疾病的认知程度是影响GBM病人预后的独立因素。结论手术是治疗GBM不可缺少的手段,术前KPS评分、是否完成同步放化疗及病人对病情的认知程度可影响生存期,认知程度转化、心理辅导的必要性及对生存期的影响有待进一步研究。     

多模态精准手术在老年胶质母细胞瘤治疗中的应用价值

目的 探讨老年胶质母细胞瘤(GBM)患者以手术为主的综合治疗的生存情况和预后相关因素,以及多模态精准手术在老年GBM治疗中的应用价值。方法 回顾性分析河南省人民医院神经外科2013年1月—2018年9月手术治疗的102例老年GBM患者的临床资料。以性别、年龄等17个可能影响因素作为观察指标,通过Kaplan-Meier单因素分析法和Cox回归模型分析筛选出影响老年GBM患者手术治疗预后的因素。根据患者的手术方式分为多模态精准手术组和常规手术组,比较两组患者的手术肿瘤切除程度、术后Karnofsky功能状态(KPS)评分及住院时间。结果 本组患者至术后末次随访的中位总生存时间(overau survival,OS)为11. 71个月。单因素分析结果显示:年龄、术前癫痫、KPS评分、肿瘤大小、多模态精准手术、手术切除程度、放化疗及同步放化疗是影响老年GBM患者生存期的因素。多因素Cox回归模型分析显示:患者的年龄(P 0. 001)、术前KPS评分(P=0. 002)、肿瘤切除程度(P 0. 001)、放化疗(P 0. 001)、同步放化疗(P=0. 046)均为影响预后的独立因素。多模态精准手术组的全切率(73. 7%)及术后KSP评分(73. 7%)均显著高于常规手术组(37. 3%和45. 8%);并且比常规手术组明显缩短了住院时间(P 0. 05)。MGMT甲基化的患者中,替莫唑胺单药化疗组与同步放化疗组的中位OS比较,差异无统计学意义(P0. 05)。结论 术前KPS评分60分的老年GBM患者接受最大范围的手术切除肿瘤,并术后行短程低频放疗及替莫唑胺化疗等综合治疗,可获得较长的生存期。多模态精准手术可显著提高老年GBM患者的肿瘤切除程度,改善其术后生活质量,缩短住院时间。对于MGMT甲基化的老年GBM患者术后应尽早使用替莫唑胺化疗。     

以癫痫为首发症状的胶质母细胞瘤预后影响因素分析

目的分析以癫痫为首发症状的胶质母细胞瘤预后的影响因素。方法回顾性分析239例幕上胶质母细胞瘤患者的临床资料。调查收集患者的年龄、性别、首发症状、肿瘤部位、手术切除程度、抗癫痫药物使用,以及术后放化疗,IDH值和总生存期。癫痫患者按抗癫痫药物使用种类分为丙戊酸钠组和其他药物组。结果本组患者中,以癫痫为首发症状者94例,无癫痫发作表现者145例。肿瘤位于额叶76例、顶叶47例、颞叶58例及枕叶58例;全切、次全切和部分切除患者分别为66例、93例和80例。132例患者术后接受完整的放化疗方案,107例患者未能接受完整的放化疗。癫痫组与非癫痫组患者在性别、肿瘤部位、手术切除程度和术后放化疗方面的差异均无统计学意义;而两组患者年龄、IDH突变的差异有统计学意义(均P0.001)。癫痫组患者的中位生存期为19.93(13.51~26.35)个月,非癫痫组患者中位生存期为12.00(9.32~14.68)个月,差异有统计学意义(P0.001)。在癫痫患者中,丙戊酸钠组与其他药物组患者的中位生存期的差异无统计学意义(P=0.865)。结论胶质母细胞瘤患者中以癫痫为首发症状者的预后较好;丙戊酸钠对胶质母细胞瘤的预后无明显改善作用。     

影响胶质母细胞瘤切除术后的预后因素分析

目的 探讨影响胶质母细胞瘤切除术后的预后因素.方法 对山东省三家医院1999-2004年经手术治疗且随访资料完整的205例胶质母细胞瘤进行回顾性研究,Kaplan-Meier单因素分析筛选预后相关因素,并通过Cox回归模型对筛选出的相关因素进行多因素分析.结果 患者中位生存期为12.0个月,术后6、12、18、24个月的积累生存率分别为82%、52%、27%、17%.多因素分析显示年龄、肿瘤部位、术前KPS评分、手术切除程度、术后放疗、化疗是影响预后的主要因素.结论 经多因素分析证实肿瘤的切除程度、术后放疗和化疗均能显著影响胶质母细胞瘤的预后,其中放疗是最具统计学意义的治疗方式.     

胼胝体胶质瘤的预后影响因素(附60例分析)

目的 分析与胼胝体胶质瘤患者预后相关的临床因素.方法 回顾性分析第二军医大学长征医院神经外科自1995年1月至2007年12月收治、接受手术和行术后放、化疗的60例胼胝体胶质瘤患者的临床资料,随访其生存状况,分析性别、年龄、肿瘤部位、术前机能状况标准(KPS)评分、术前有无癫痫、肿瘤病理级别、肿瘤大小、影像学强化、手术切除程度对胼胝体胶质瘤患者生存预后的影响.结果 Kaplan-Meier法单因素分析显示年龄小、KPS评分高和胶质瘤病理级别低患者无进展生存时间(PFS)及总生存时间(OS)均较长,胶质瘤部位不同患者OS不同,相比差异均有统计学意义(P<0.05);Cox多元回归分析显示年龄、肿瘤病理级别为胼胝体胶质瘤患者PFS的影响因素,而年龄、病理级别、手术切除程度是OS的影响因素.结论 患者年龄较小、肿瘤病理级别低及切除程度高是胼胝体胶质瘤患者预后的保护因素,采取积极正确的治疗策略可使患者的预后得到改善.     

影响人脑胶质瘤的预后因素

目的研究影响人脑胶质瘤预后的因素,为临床治疗提供理论依据。方法收集自2000年1月至2000年6月在南方医科珠江医院神经外科手术治疗的89例原发性星形细胞肿瘤病人的资料。生存分析单因素使用KaplanMeier法计算生存率并采用对数秩(Logrank)检验;多因素分析使用Cox比例风险模型,采用逐步回归分析。结果单因素分析结果显示年龄、术前机能状况(KPS)评分、术前癫痫、组织学分级、术后放疗等因素与患者预后有关(P<0.01);多因素分析示患者的年龄、术前KPS评分、组织学分级均为独立的预后因素,而术前癫痫、术后放疗则未显示出与预后有关。性别、肿瘤部位、肿瘤范围、手术治疗方式等因素两种分析均未发现与预后有关。结论患者年龄、术前KPS评分、组织学分级对预后影响较大;而术前癫痫史、术后放疗对判断预后价值有限;患者的性别、肿瘤部位和范围、手术治疗方式与预后无关。     

荧光素钠“黄荧光”染色技术引导胶质母细胞瘤手术的研究

目的研究荧光素钠(FLS)“黄荧光”染色引导手术切除胶质母细胞瘤(GBM)的作用,及其与临床因素的关系。方法回顾分析24例胶质母细胞瘤患者的临床资料,并对汉族与少数民族患者的临床资料进行比较。患者术中静脉注射荧光素钠染色,分别在肿瘤黄染边界及黄染边界外0.5 cm范围内的无黄染区域多点取材行病理检查,观察肿瘤细胞浸润程度,以确定肿瘤边界并引导手术切除肿瘤。对比术前、术后MRI增强扫描的肿瘤体积确定肿瘤切除程度。以术前、术后1周、术后1个月KPS评分评判患者的疗效。采用Spearman秩相关对肿瘤切除程度、瘤周无黄染区病理改变与临床因素的相关性进行分析。结果汉族与少数民族患者各临床资料比较,差异均无统计学意义。本组患者中,肿瘤黄染边界组织病理检查示,19例患者为胶质母细胞瘤,3例患者为胶质细胞增生,2例患者为间变星形细胞瘤;瘤周无黄染区组织病理检查示,22例患者为胶质细胞增生,2例患者为弥漫星形细胞瘤。肿瘤全切除者16例,次全切除者8例(肿瘤均涉及脑功能区、基底节区和脑室)。术后1个月与术前的KPS评分对比,好转17例,无变化3例,加重4例。肿瘤切除程度与肿瘤部位涉及基底节区核团和脑室呈负相关(r=-0.84,P<0.05);瘤周无黄染区组织病理改变与1P19Q呈负相关(r=-0.44,P<0.05)。结论荧光素钠“黄荧光”染色技术可在术中实时有效引导胶质母细胞瘤切除,提高切除率,改善患者预后;肿瘤切除程度与肿瘤部位,瘤周无黄染区病理改变与1P19Q相关。     

影响恶性胶质瘤生存预后的临床因素分析

目的 探讨与大脑半球恶性胶质瘤生存预后相关的临床因素. 方法 选择中山大学附属第一医院神经外科自2004年1月至2009年12月收治的194例恶性胶质瘤患者,其中间变性星形细胞瘤120例,胶质母细胞瘤74例,随访其生存状况,Kaplan-Meier生存分析与Cox多元同归分析患者无进展生存时间与总生存时间的影响因素. 结果 间变性星形细胞瘤和胶质母细胞瘤患者的无进展生存时间分别为18、10个月,总生存时间分别为21、12个月;Kaplan-Meier生存分析法显示年轻、KPS评分高、肿瘤无强化、术前有抽搐症状及间变性星形细胞瘤患者无进展生存时间及总生存时间均较长,差异有统计学意义(P＜0.05); Cox多元回归分析显示患者年龄、KPS评分、有无抽搐、病理分级是无进展生存时间、总生存时间的影响因素,年轻、KPS评分较高、有抽搐症状、间变性星形细胞瘤患者无进展生存时间与总生存时间较长. 结论 年龄较小、高KPS评分、间变性星形细胞瘤及术前有抽搐症状被提示是恶性胶质瘤患者获得较长生存期的保护因素,而性别、肿瘤部位、大小和手术切除程度对预后无影响,肿瘤强化与预后的关系有待进一步研究证实.     

手术切除程度对胶质母细胞瘤预后预测因素的影响

目的探讨肿瘤切除程度对胶质母细胞瘤生存预后预测因素的影响。方法回顾性分析135例接受肿瘤最大程度切除及术后辅助性放化疗的胶质母细胞瘤病人的临床资料,分析肿瘤切除程度对经典预后因素临床预测价值的影响。结果肿瘤全切除57例,近全切除78例。全切除和近全切除两组生存期存在显著性差异(20.8个月:13.8个月,P=0.003),单因素分析显示预后相关因素还有年龄(P=0.001)、术前KPS评分(P=0.001)、异柠檬酸脱氢酶1(IDH1)状态(P=0.005)和O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)启动子状态(P=0.017)。进一步亚组分析发现,在肿瘤全切除背景下MGMT的预后相关性没有统计学意义(P=0.464),年龄的预后价值也下降(P=0.046);COX多因素回归分析显示总生存期的独立预测因素仅有KPS(相对危险度:0.365,P=0.011)和IDH1(相对危险度:0.436,P=0.044)。结论肿瘤切除程度影响预后预测因素的临床价值,在评估预后相关因素时应充分考虑到手术切除质量的影响。     

复发性多发胶质母细胞瘤的预后分析

目的 探讨复发性多发胶质母细胞瘤（GBM）预后的影响因素。方法 2005年1月至2012年12月手术切除并获得完整随访的复发性GBM 106例,其中单发78例,多发28例（多发组）;根据患者年龄、性别、肿瘤部位、手术切除程度、术后是否放化疗、术前KPS评分从单发GBM中选取与多发GBM相匹配的病例28例作为对照（单发组）;多发组根据肿瘤切除程度进一步分为全切组和部分切除组。结果 本组复发性多发GBM占26.4%。多发组中位生存期（4.5个月）明显短于单发组（8.5个月;P <0.05）。多发患者中,全切组中位生存期（7.9个月）明显长于部分切除组（3.7个月;P <0.05）。结论 复发性多发GBM预后较单发患者差;肿瘤切除程度越高,患者预后也越好,建议术中在保证重要功能的基础上尽量多切除肿瘤。     

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.