颞叶孤立性胶质母细胞瘤的手术治疗分析

目的 探讨颞叶孤立性胶质母细胞瘤的手术方法及疗效。方法 回顾性分析2016年7月至2020年5月手术治疗的38例颞叶孤立性胶质母细胞瘤的临床资料。接受肿瘤全切除+前颞叶切除术（ALT）治疗14例（ALT组）,行常规颞叶肿瘤全切除术治疗24例（常规组）。术后随访6~28个月,中位数15个月;术后3、12个月采用KPS评分评估神经功能状态,其中KPS评分≥70分为预后良好;根据RANO标准评估肿瘤进展,国际抗癫痫联盟分级1级定义为癫痫完全控制;记录总生存期（OS）和无进展生存期（PFS）。结果 ALT组术后脑室开放率（100%,14/14）明显高于常规组（33.3%,8/24;P<0.001）。ALT组与常规组术后1年癫痫完全控制率（64.3% vs. 66.7%）、术后肿瘤进展率（78.5% vs. 70.8%）、术后3个月预后良好率（92.9% vs. 66.7%）均无统计学差异（P>0.05）。ALT组术后1年预后良好率（78.6%,11/14）明显高于常规组（41.7%,10/24;P<0.05）。ALT组中位PFS和中位OS较常规组均明显延长（P<0.05）。多因素Cox比例回归风险模型分析显示,ALT是延长PFS（OR=7.3;95% CI 1.105~47.422;P=0.037）和OS（OR=7.8;95% CI 1.117~55.183;P=0.041）的独立预测因子。结论 对于颞叶孤立性胶质母细胞瘤,在全切除肿瘤基础上,进行ALT,可明显改善病人预后。     

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.     

间变性脑膜瘤病人预后的影响因素

目的 探讨间变性脑膜瘤生存预后的影响因素。方法 回顾性分析2012年6月~2019年1月手术治疗的50例间变性脑膜瘤的临床资料。采用多因素Cox比例回归风险模型分析无进展生存期（PFS）和总生存期（OS）的影响因素。结果 34例出现肿瘤进展,PFS为3~64个月,中位PFS为18个月;22例死亡,OS为5~65个月。多因素Cox比例回归风险模型分析显示,年龄≥60岁、术前KPS评分低是间变性脑膜瘤PFS较短的独立危险因素（P<0.05）,肿瘤全切除和术后放疗是间变性脑膜瘤PFS较长是有利因素（P<0.05）。本文纳入的因素与OS均无明显关系（P>0.05）。结论 间变性脑膜瘤术后容易复发,PFS和OS较短。年龄大是间变性脑膜瘤PFS较短的危险因素,术前KPS高、肿瘤全切除和术后放疗是PFS较长的有利因素     

幕上大脑半球高级别星形细胞瘤预后的影响因素分析

目的探讨与幕上大脑半球高级别星形细胞瘤生存预后相关的临床因素。方法回顾接受手术与术后辅助性放疗及化疗的97例高级别星形细胞瘤的临床资料,其中间变性星形细胞瘤(AA)60例,胶质母细胞瘤(GB)37例。随访其生存状况,用Kaplan-Meier单因素生存分析与COX多元回归分析作统计学处理。结果间变性星形细胞瘤和胶质母细胞瘤的无进展生存时间(PFS)分别为18和10个月,两者总生存时间(OS)分别为21和12个月;年龄“≤40岁”与“>40岁”者PFS各为18和10个月,OS各为21和13个月;治疗前“KPS≥80”与“<80”PFS各为15和10个月,OS为18和12个月;术前有抽搐症状与否的PFS各为21和11个月,OS为24和14个月;术前MR检查肿瘤强化与否的PFS各为11和18个月,OS为14和21个月。单因素分析显示,上述各因素与病人PFS和OS相关(P<0.05)。性别、肿瘤直径、肿瘤部位、肿瘤切除程度与病人PFS、OS关系无统计学意义(P>0.05)。COX回归分析显示年龄大小、肿瘤级别的高低、治疗前KPS评分、术前有无抽搐症状是影响预后的显著因素。结论年龄较小、高KPS评分、低病理级别及术前有抽搐症状被提示是高级别星形细胞瘤患者获得较长生存期的保护因素,而性别、肿瘤部位、肿瘤大小和手术切除程度对预后影响无统计学意义。肿瘤强化与预后的关系有待进一步研究证实。     

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。     

影响胶质母细胞瘤患者预后的多因素分析

目的 探讨影响胶质母细胞瘤患者预后的临床因素.方法 回顾2008年1月至2013年1月于南方医科大学南方医院行显微手术治疗的198例原发胶质母细胞瘤患者的临床资料,对性别、年龄、起病至就诊时间、术前有无癫痫发作、术前KPS评分、肿瘤部位、肿瘤直径、肿瘤是否发生囊变、手术切除程度、术后是否行同步放化疗、术后是否存在颅内感染共11项因素进行生存分析.结果 单因素分析结果示术前有无癫痫发作、肿瘤部位、术前KPS评分、手术切除程度、术后是否同步放化疗、术后是否存在颅内感染对胶质母细胞瘤患者的预后有影响(P＜0.05);多因素分析结果示手术切除程度、肿瘤部位、术前KPS评分、术后是否同步放化疗、术后是否颅内感染具有统计学意义(P＜0.05).结论 手术切除程度、肿瘤部位、术前KPS评分、术后同步放化疗是影响胶质母细胞瘤患者的主要预后因素,其中手术切除程度是最重要的预后因素;而术后颅内感染的患者生存时间延长,可能与感染诱导的肿瘤免疫有关.     

髓母细胞瘤的治疗与预后分析

目的探讨儿童及成人髓母细胞瘤患者的治疗及预后情况。方法回顾性研究80例经病理证实的髓母细胞瘤，对其成人与儿童患者的生存情况与肿瘤切除程度、脑脊液分流情况、放疗方式对其预后的影响作多因素分析比较。结果61例（76％）获得6个月至14年随访。5年生存率与10年生存率分别为50．8％和27．9％。成人患者5年生存率较儿童高（P＜0．05），而10年生存率两组相近。肿瘤全切或次全切除生存率高于大部分切除（P＜0．05）。全脑加脊髓放疗可改善患者近期生存率（P＜0．05）。3例患儿生存超过Collins危险期。结论手术与术后常规放疗是治疗髓母细胞瘤的关键。全切除或次全切除肿瘤、全脑加脊髓放疗可明显提高生存率。少数患者有可能获得长期生存。     

CREPT在人脑胶质母细胞瘤组织中的表达及其与病人预后的关系

目的 探讨人脑胶质母细胞瘤（GBM）组织肿瘤高表达细胞周期相关蛋白（CREPT）的表达水平及其与病人预后的关系。方法 收集2010年1月至2011年1月手术切除的GBM组织104例和2018年1~12月颅脑损伤内减压术中切除的正常脑组织40例,采用免疫组织化学染色法检测CREPT的表达,根据染色情况将GBM分为高表达组和低表达组。GBM病人术后随访截止时间为2019年4月,记录总生存期（OS）和无进展生存期（PFS）。采用多因素Cox比例回归风险模型分析GBM病人生存预后的影响因素。用Kaplan-Meier法绘制生存曲线,采用Log-rank检验。结果 GBM组织CREPT高表达率（73.08%,76/104）明显高于正常脑组织（10.00%,4/40;P<0.05）。多因素Cox比例回归风险模型分析结果显示CREPT高表达是GBM病人OS和PFS较短的独立影响因素（P<0.05）。低表达组OS和PFS均明显高于高表达组（P<0.05）。结论 人脑GBM组织CREPT呈高表达,与病人不良生存预后和肿瘤进展有关。     

异柠檬酸脱氢酶-1突变与胶质瘤化疗疗效关系的初步研究

目的回顾性研究人脑胶质瘤患者46例中异柠檬酸脱氢酶-1(IDH1)R132H变异与其化疗疗效的关系。方法采用建立的MGB双荧光探针实时荧光定量聚合酶链式反应(PCR)方法检测患者IDH1基因R132H突变,同时根据临床随访获得患者化疗预后情况,比较IDH1基因132位点突变与野生型患者化疗预后及生存分析。结果单因素分析IDH1基因突变的继发性胶质母细胞瘤(sGBM)患者化疗后有更长的无进展生存期(PFS)和总体生存期(OS)(P0.001),患者年龄小于50岁,行为状态评分(KPS)大于80均有较长的PFS和OS;多因素分析(COX回归分析)中,IDH1基因突变与PFS和OS呈显著正相关(P0.001);TMZ化疗显示IDH1基因突变中有效组患者为47.2%,IDH1基因野生型中有效组患者为10.0%,两组间差异具有统计学意义(P0.001)。生存分析显示替莫唑胺(TMZ)化疗患者IDH1基因突变有更长的PFS。结论本实验结果分析显示IDH1基因R132H突变是s GBM患者TMZ化疗疗效的敏感指标之一,为后续s GBM治疗提供新的参考选择。     

48例原发性胶质母细胞瘤的治疗经验

目的探讨胶质母细胞瘤手术加放疗、化疗综合治疗的疗效。方法 2007～2009年收治胶质母细胞瘤患者48例,均采用显微手术切除肿瘤;术后行全脑分割剂量放疗,部分患者采用立体定向放疗;同时联合化疗,方案是静脉滴注替尼泊甙60mg/(m2·d)+司莫司汀100mg/d,或口服替莫唑胺75mg(/m2·d)。结果肿瘤全切除43例,次全切除5例;术后无新增神经功能损伤33例,出现新的失语症状11例,新的肢体偏瘫症状10例。患者1年生存率为56.25%,肿瘤复发时间平均6.8个月。结论全切除肿瘤+术后早期行放疗+个性化化疗可延长胶质母细胞瘤患者生存期。     

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.