丘脑底核脑深部电刺激术联合药物治疗帕金森病有效性和安全性的Meta分析

目的评价丘脑底核脑深部电刺激术联合药物治疗帕金森病的有效性和安全性。方法以subthalamic nucleus、deep brain stimulation、DBS、STN、Parkinson disease、random等英文检索词,计算机检索1980年1月1日-2016年10月1日美国国立医学图书馆生物医学信息检索系统、荷兰医学文摘、Cochrane图书馆等数据库收录的关于丘脑底核脑深部电刺激术联合药物治疗帕金森病的随机对照临床试验,采用Jadad量表、Cochrane系统评价手册和Rev Man 5.2统计软件进行文献质量评价和Meta分析。结果共获得3245篇文献,经剔除重复和不符合纳入标准者,最终纳入6项高质量(Jadad评分≥4分)临床试验共958例帕金森病患者。Meta分析显示:与单纯药物治疗相比,丘脑底核脑深部电刺激术联合药物治疗可以显著降低帕金森病患者服药(SMD=-0.570,95%CI:-0.710~-0.430;P=0.000)和未服药(SMD=-1.170,95%CI:-1.500~-0.850;P=0.000)状态下统一帕金森病评价量表第三部分(UPDRSⅢ)评分,以及UPDRSⅠ评分(SMD=-0.150,95%CI:-0.290~-0.010;P=0.030)和39项帕金森病调查表评分(SMD=-0.510,95%CI:-0.660~-0.370;P=0.000);但增加严重不良事件(RD=0.140,95%CI:0.090~0.190;P=0.000)和构音障碍不良事件(RD=0.070,95%CI:0.010~0.120;P=0.020)发生率,而减少运动障碍不良事件发生率(RR=0.450,95%CI:0.330~0.620;P=0.000)。结论丘脑底核脑深部电刺激术联合药物治疗能够显著改善帕金森病患者运动功能、精神状态和生活质量,但术后发生严重不良事件和构音障碍不良事件的风险增加,应引起临床医师的重视。     

中国人群ApoE基因多态性与迟发性阿尔茨海默病关系的Meta分析

目的探讨中国人群载脂蛋白E(Apo E)基因多态性与迟发性阿尔茨海默病的关系。方法以载脂蛋白E基因(Apo E)、迟发性阿尔茨海默病(late onset Alzheimer's disease)、基因多态性(polymorphism)、China和Chinese等中英文词组,检索美国国立医学图书馆生物医学信息检索系统、荷兰医学文摘、EBSCO-CINAHL、Cochrane图书馆,以及中国生物医学文献数据库、中国知网中国知识基础设施工程、万方数据库等近20年发表的关于中国人群Apo E基因多态性与迟发性阿尔茨海默病关系的病例对照研究,采用Newcastle-Ottawa量表(NOS)进行文献质量评价,Rev Man 5.0统计软件进行Meta分析。结果共获得249篇文献,经剔除重复和不符合纳入标准者并补充相关文献,最终纳入13篇高质量临床研究(NOS评分≥5分),共3372例受试者(迟发性阿尔茨海默病患者1360例、对照者2012例)。Meta分析显示:携带Apo Eε4等位基因者发生迟发性阿尔茨海默病的风险高于携带Apo Eε3等位基因者(OR=3.710,95%CI:2.960~4.640;P=0.000);表现为Apo Eε3/ε4(OR=3.160,95%CI:2.390~4.180;P=0.000)、Apo Eε2/ε4(OR=3.410,95%CI:2.160~5.380;P=0.000)和Apo Eε4/ε4(OR=16.400,95%CI:8.200~32.810;P=0.000)基因型者发生迟发性阿尔茨海默病的风险高于Apo Eε3/ε3基因型者。结论携带Apo Eε4等位基因,以及Apo Eε3/ε4、Apo Eε2/ε4和Apo Eε4/ε4基因型是中国人群发生迟发性阿尔茨海默病的危险因素。     

他汀类药物与帕金森病关系的Meta分析

目的系统评价他汀类药物应用与帕金森病发病风险之间的关系。方法计算机检索MEDLINE、Pubmed、EMbase、the Cochrane Library、CNKI、VIP、万方数据库,并辅以人工检索,查找他汀与帕金森病相关性的病例对照研究及队列研究。评价纳入研究方法学质量后,采用Stata14.0软件进行Meta分析。结果共纳入11项研究,其中帕金森病患者2 101例。Meta分析结果显示他汀组帕金森病发病率低于对照组,差异有统计学意义(OR=0.81,95%CI:0.71~0.92,P=0.002)。结论他汀类药物应用可降低帕金森病发病风险,但上述结论需更多高水平队列研究及随机对照研究进一步验证。     

中国人群帕金森病危险因素及保护性因素的Meta分析

目的探讨中国人群帕金森病(PD)的危险因素及保护性因素。方法检索MEDLINE、EMbase等外文数据库及中国期刊全文数据库、维普中文科技期刊全文数据库、中国万方数据库等中文数据库,纳入国内PD危险因素及保护性因素的病例对照研究,采用Newcastle-Ottawa量表(NOS)对入选文献进行质量评价,并用Review Manager 5.2软件对各影响因素进行Meta分析。结果共有18篇文献纳入分析,纳入病例1663例,对照2630例。Meta分析结果显示,中国人群PD的危险因素有PD阳性家族史(OR=5.31,95%CI:3.16~8.92,P0.00001)、重大精神创伤或抑郁史(OR=4.35,95%CI:2.76~6.84,P0.00001)、头外伤史(OR=3.70,95%CI:2.36~5.81,P0.00001)、从事脑力劳动(OR=2.08,95%CI:1.33~3.24,P=0.001)和杀虫剂、化肥等毒物接触史(OR=2.03,95%CI:1.48~2.79,P0.0001)。保护性因素有饮茶(OR=0.39,95%CI:0.23~0.67,P0.00001),吸烟(OR=0.58,95%CI:0.49~0.68,P0.00001),饮酒(OR=0.71,95%CI:0.56~0.90,P=0.005)。结论中国人群PD的危险因素有PD阳性家族史、重大精神创伤或抑郁史、头外伤史、从事脑力劳动和杀虫剂、化肥等毒物接触史,保护性因素有饮茶、吸烟、饮酒。     

重组组织型纤溶酶原激活物治疗合并大脑中动脉高密度征的急性缺血性卒中有效性和安全性的系统评价

目的系统评价合并大脑中动脉高密度征(HMCAS)的急性缺血性卒中患者重组组织型纤溶酶原激活物(rt-PA)静脉溶栓治疗的有效性和安全性。方法以hyperdense middle cerebral arterysign/HMCAS/hyperdense artery sign/hyperdense cerebral artery sign、ischemic stroke/cerebral infarction/brain infraction/cerebral embolism、thrombolysis/thrombolytic therapy/rt-PA/recombinant tissue plasminogenactivator,以及大脑中动脉高密度征/致密动脉征/大脑中动脉致密征/脑动脉高密度征、缺血性脑卒中/缺血性卒中/脑梗死/脑梗塞/脑栓塞、溶栓治疗/rt-PA/重组组织型纤溶酶原激活剂等中英文词组为检索词,计算机检索1994年1月-2014年12月美国国立医学图书馆生物医学信息检索系统、荷兰医学文摘、Cochrane临床对照试验中心注册库,以及中国生物医学文献数据库等收录的关于rt-PA静脉溶栓治疗合并HMCAS的急性缺血性卒中随机或非随机对照临床试验;分别采用Newcastle-Ottawa量表和Rev Man5.2统计软件行文献质量评价和Meta分析。结果经剔除重复和不符合纳入标准者,166篇英文文献中最终纳入8项非随机对照临床试验共11 373例患者[2455例合并HMCAS(rt-PA静脉溶栓治疗2316例、安慰剂治疗139例)、8918例未合并HMCAS]。Meta分析显示:rt-PA静脉溶栓组患者不良预后风险低于安慰剂组(OR=0.360,95%CI:0.150~0.850;P=0.020),但症状性颅内出血发生率组间差异无统计学意义(OR=1.640,95%CI:0.380~7.040;P=0.500);合并HMCAS患者rt-PA静脉溶栓治疗不良预后风险高于未合并者(OR=2.830,95%CI:2.550~3.150;P=0.000),但症状性颅内出血发生率组间差异无统计学意义(OR=1.090,95%CI:0.500~2.410;P=0.820)。结论尽管rt-PA静脉溶栓治疗合并HMCAS的急性缺血性卒中患者安全、有效,但发病3个月时易出现不良预后,而发生症状性颅内出血风险较低。     

DJ-1基因多态性与帕金森病易感性的Meta分析

目的评价DJ-1基因多态性与帕金森病(PD)易感性的关系。方法检索知网、万方、Web of Science、Pub Med、EMBASE和Cochrane数据库,检索时间为2001年01月01日至2017年01月01日。确定文献纳入排除标准,并采用Newcastle-Ottawa Scale(NOS)进行质量评估,提取高质量文献的有用部分,使用stata12.0软件进行统计分析。结果共纳入12篇文献,收集到2895组病例和2817组对照,Meta分析结果显示,在帕金森病患者中,DJ-1基因g.168_185del缺失突变(OR=1.26,95%CI:1.06~1.50,P0.05)和c.G293A点突变(OR=2.74,95%CI:1.22~6.16,P0.05)均为PD的危险因素。在g.168_185del与PD相关性研究的亚组分析中,发现非中国人群g.168_185del多态性也是PD的危险因素(OR=1.41,95%CI:1.14~1.73,P0.05),但在中国人群中未发现其相关性(OR=0.98,95%CI:0.72~1.34,P0.05)。c.G293A与PD相关性病例对照研究中均为非中国人群,故未进行亚组分析。结论DJ-1基因g.168_185 del缺失突变和c.G293A点突变是PD的易感因素,但本Meta分析未发现DJ-1基因g.168_185 del缺失突变和c.G293A点突变与中国人群PD具有相关性。     

重复经颅磁刺激治疗帕金森病临床效果Meta分析

目的评价重复经颅磁刺激治疗帕金森病的临床效果。方法以经颅磁刺激(transcranial magnetic stimulation or TMS)、帕金森病(Parkinson's disease or PD)、随机对照试验(randomized controlled trial)为中英文检索词分别检索美国国立医学图书馆、荷兰医学文摘、Ovid MEDLINE、维普中文科技期刊数据库、万方数据库、中国知识基础设施工程等国内外知名数据库1999-2013年发表的有关经颅磁刺激治疗帕金森病的文献,最终共计纳入16篇,中文4篇、英文12篇,根据高频(1 Hz)和低频(≤1 Hz)磁刺激分别进行Meta分析。结果 16篇文献共纳入455例帕金森病患者,试验组(经颅磁刺激组)236例、对照组219例。经高频和低频磁刺激治疗后,两组患者统一帕金森病评价量表(UPDRS)总评分差异具有统计学意义(WMD=.5.010,95%CI:.7.370~.2.650,P=0.000;WMD=.6.140,95%CI:.8.750~.3.530,P=0.000)。经高频磁刺激治疗后,两组患者UPDRSⅢ评分(WMD=.4.380,95%CI:.8.260~.0.500;P=0.003),日常生活活动能力量表评分(WMD=.3.740,95%CI:.4.660~.2.820;P=0.000)差异有统计学意义,而简易智能状态检查量表评分差异无统计学意义(WMD=0.260,95%CI:.0.660~1.180;P=0.580)。经低频磁刺激治疗后,两组患者UPDRSⅢ评分差异无统计学意义(WMD=.2.160,95%CI:.5.010~0.690;P=0.370)。结论重复经颅磁刺激可以改善帕金森病患者部分临床症状,提高生活质量,但未发现其对精神症状有效。     

强化控制血压治疗脑出血有效性和安全性的Meta分析

目的评价强化控制血压治疗脑出血的有效性和安全性。方法以intracerebralhemorrhage、ICH、blood pressure、intensive、acute等英文检索词,计算机检索1980年1月1日-2015年9月30日美国国立医学图书馆生物医学信息检索系统、荷兰医学文摘、Cochrane图书馆等数据库收录的关于强化控制血压治疗脑出血的随机对照临床试验,采用Jadad量表和Rev Man 5.3统计软件进行文献质量评价和Meta分析。结果共获得3322篇文献,经剔除重复和不符合纳入标准者,最终纳入4项较高质量(Jadad评分≥4分)的临床试验共3360例脑出血病例。Meta分析显示:强化控制血压早期并不能减少发病24 h内血肿体积增加1/3的病例数(RR=0.910,95%CI:0.750~1.090;P=0.310),亦不增加治疗90 d时改良Rankin量表评分≤2分的病例数(RR=1.070,95%CI:0.990~1.150;P=0.090)和美国国立卫生研究院卒中量表评分(RR=0.950,95%CI:0.800~1.120;P=0.530)以及循环系统不良事件(RR=0.910,95%CI:0.610~1.370;P=0.660)和严重低血压(RR=0.840,95%CI:0.370~1.940;P=0.690)发生率。结论强化控制血压治疗脑出血并不能在短期内减少血肿增加,但有可能改善患者远期预后,降低病残率和病死率;不增加神经系统损害症状,以及循环系统不良事件和严重低血压发生率。     

亚甲基四氢叶酸还原酶基因C677T多态性与先兆型偏头痛相关性的Meta分析

目的探讨亚甲基四氢叶酸还原酶(MTHFR)基因C677T多态性与先兆型偏头痛(MA)的相关性。方法检索1994年1月~2013年3月MEDLINE、EBSCO、EMBASE数据库及PubMed,以及中国医院知识仓库中文期刊全文库、中国生物医学文献数据库、维普、万方等中文数据库中关于MTHFR基因C677T多态性与MA相关性的文献,按纳入、排除标准选择文献,并采用RevMan 5软件进行Meta分析。结果共纳入18项病例对照研究,其中MA患者4276例,对照者27979例。各研究间具有很强的异质性(P0.05,I2=72%),采用随机效应模型分析。Meta分析显示,MTHFR基因TT基因型发生MA的风险明显高于CT+CC基因型(OR=1.33,95%CI:1.02~1.75,P0.01)。剔除不符合H-W遗传平衡定律的3篇文献后,总的分析结果依然稳定(OR=1.39,95%CI:1.02~1.88,P0.01)。在MA人群中所做种族分层分析结果显示,在地中海人种TT基因型增加了MA的发病风险,而在其他高加索人(包括北欧人种和印度雅利安人种)、芬兰人、土耳其人及日本人的研究并未显示出这种相关性。结论 MTHFR基因C677T多态性与MA相关,其TT基因型个体MA发病的风险增加。这在不同种族间存在一定差别。     

脑卒中后疲劳危险因素的Meta分析

目的通过循证医学方法分析脑卒中后疲劳相关危险因素。方法分别以post-stroke fatigue、PSF、factor、prevalence、risk factor等英文词汇作为检索词,检索美国国立医学图书馆生物医学信息检索系统(PubMed)、荷兰医学文摘(EMBASE/SCOPUS)、英国Cochrane图书馆等数据库中关于脑卒中后疲劳危险因素的随机对照试验、病例对照研究、队列研究和回顾性病例系列研究结果;采用Jadad量表和Stata 12.0统计软件进行文献质量评价和Meta分析。结果共获得6986篇文献,经剔除重复和不符合纳入标准者,最终获得23项临床研究计9135例脑卒中后疲劳患者。分析显示,脑卒中前疲劳(OR=4.790,95%CI:0.790～29.160;P=0.000)、抑郁(OR=3.530,95%CI:2.580～4.850;P=0.000)、焦虑(OR=1.200,95%CI:1.070～1.350;P=0.041)是脑卒中后疲劳的危险因素。结论脑卒中前疲劳、抑郁、焦虑是脑卒中后疲劳的危险因素,临床医师应重视相关危险因素,早期预防并治疗,提高脑卒中患者的生活质量。     

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.