提高急性缺血性卒中静脉溶栓有效性和安全性的研究进展

重组组织型纤溶酶原激活剂(recombinant tissue plasminogen activator alteplase,rt-PA)是目前急性缺血性卒中时间窗内静脉溶栓最有效的治疗药物,然而,静脉溶栓也伴随着出血转化、症状性颅内出血风险的增加,导致患者预后不良,甚至死亡。因此,研究静脉溶栓治疗及预后的影响因素,提高静脉溶栓治疗的有效性及安全性,对急性缺血性卒中患者的预后有着重大意义。     

阿替普酶静脉溶栓治疗急性缺血性卒中临床分析

目的探讨不同剂量重组组织型纤溶酶原激活剂(reconstructive tissue plasminogen activator,rt-PA,阿替普酶)静脉治疗合并房颤的急性缺血性卒中的安全性与疗效。方法选择2017-01-2019-11在河南科技大学第一附属医院神经内科接受rt-PA静脉溶栓治疗的70例合并心房颤动的急性缺血性脑卒中患者为实验组,选择同时期未给予rt-PA静脉溶栓治疗的38例合并心房颤动的急性缺血性脑卒中患者为对照组。将实验组患者随机分为低剂量组(0.6 mg/kg,A组)与标准剂量组(0.9 mg/kg,B组)。记录实验组溶栓前和溶栓后7 d NIHSS评分,记录对照组入院时和入院7 d NIHSS评分,记录3组患者7 d内的颅内出血发生情况和90 d病死率,采用改良Rankin量表(mRS)对各组患者90 d预后进行分析。结果低剂量组和标准剂量组患者溶栓后7 d较溶栓前NIHSS评分改善率均较对照组增高,差异有统计学意义(P0.05)。rt-PA静脉治疗后,低剂量组颅内出血发生率和90 d病死率均低于标准剂量组,但组间比较无显著性差异(P0.05);低剂量组与标准剂量组90 d预后良好率比较差异无统计学意义(P0.05)。结论对于合并心房颤动的急性缺血性脑卒中患者,低剂量rt-PA与标准剂量rt-PA在功能恢复方面相比无显著性差异,但具有潜在较低的脑出血率及病死率。     

rt-PA静脉溶栓治疗高龄急性缺血性脑卒中的研究进展

静脉溶栓治疗是急性缺血性脑卒中超早期治疗的首选方法,重组组织型纤溶酶原激活剂(rt-PA)是目前临床上广泛应用的静脉溶栓药物。既往静脉溶栓将80岁以上高龄患者排除在外,现年龄因素不再是应用排除标准。现对高龄缺血性脑卒中患者应用rt-PA静脉溶栓治疗有效性、时间窗、剂量、颅内出血并发症等相关研究进行综述,以对高龄患者应用rt-PA静脉溶栓治疗提供临床参考依据。     

多学科团队协作模式在MRI指导下脑卒中静脉溶栓诊疗中的应用

目的探讨多学科团队协助模式在脑卒中静脉溶栓诊疗中的应用,为急性脑梗死的诊疗提供参考。方法选取2017年1～12月行rt-PA静脉溶栓治疗的113例急性缺血性脑卒中患者为对照组,另选取流程改进后(2018年1～12月)行rt-PA静脉溶栓治疗的120例急性缺血性脑卒中患者为观察组,分析就诊至完善影像学检查时间、就诊至溶栓开始时间(DNT)时间、静脉溶栓治疗前后美国国立卫生研究院卒中量表(NIHSS)评分、改良Rankin量表(mRS)评分、Barthel指数变化、有无出血并发症等影响因素。结果观察组CT至完成头颅MRI时间、MR至静脉溶栓时间、DNT时间均较对照组缩短(P 0. 05);两组溶栓后24 h NIHSS评分改善差异无统计学意义(P 0. 05),观察组溶栓后7、30和90 d NIHSS评分、mRS评分、Barthel指数改善均优于对照组(P 0. 05);静脉溶栓过程中牙龈出血及症状性颅内出血两组比较差异无统计学意义(P 0. 05)。结论多学科团队协助模式可有效缩短急性缺血性脑卒中患者的就诊时间、检查时间及DNT时间,促进患者的神经功能恢复。     

CT灌注成像在急性缺血性脑卒中rt-PA溶栓中的指导意义

目的 探讨CT灌注成像(CTP)在rt-PA静脉溶栓治疗急性缺血性脑卒中的价值.方法 25例急性缺血性脑卒中(发病时间<3h)患者行CTP检查组15例:见缺血半晴带应用rt-PA静脉溶栓组(见IP)10例,无缺血半暗带常规治疗组(无IP)5例.未行CTP检查应用rt-PA静脉溶栓组(对照组)10例.评价CTP指导下见IP组、无IP组和对照组患者疗效和预后.结果 见IP组rt-PA静脉溶栓后各时间段NIHSS评分与治疗前相比均有明显改善(P<0.001),而对照组NIHSS评分于24h、7d均无明显变化,直到30d后明显改善(P<0.01),而两组相比于24h后见IP组NIHSS评分明显低于对照组(P<0.05).见IP组未出现颅内出血及死亡病例,且Barthel指数明显高于对照组.对照组颅内出血率44%,死亡率11%.无IP组常规抗栓治疗NIHSS评分于24h、7d均无明显变化,30d后明显改善(P<0.01),与对照组相比无明显差异(P>0.05).结论 急性缺血性脑卒中在发病3h内,经CTP检查见IP者应用rt-PA溶栓安全、效果可靠;无IP者不予溶栓治疗而给予常规抗栓治疗,即能避免盲目溶栓所带来的出血及死亡风险,还能取得较好的远期疗效.     

急性缺血性脑卒中rt-PA静脉溶栓后出血性转化的特殊类型

目的溶栓后出血性转化(hemorrhagic transformation,HT)是重组组织型纤维蛋白溶酶原激活剂(rt-PA)治疗急性缺血性脑卒中的一个重要安全指标。HT有不同的亚型,而不同亚型的预后也不尽相同。我们对急性缺血性脑卒中患者rt-PA静脉溶栓后出现的特殊型HT进行分析。方法对发病3zh内的98例缺血性卒中患者用rt-PA(剂量0．6 mg/kg,最大剂量5 0 mg)进行静脉溶栓治疗,溶栓前后行头颅CT、MRI或数字减影血管造影(DSA)检查判断是否有HT,并判定这种HT与责任病灶的关系。结果溶栓后经CT或MRI检查发现4种特殊的远端HT类型,1例发生蛛网膜下腔出血(SAH),1例梗死部位的对侧出现明显占位效应的脑实质出血,1例出现梗死灶对侧的侧脑室出血,1例出现梗死部位对侧的腔隙性出血。这4例患者所引起的4类HT在临床上均为无症状,预后好。结论对急性缺血性脑卒中的溶栓治疗要坚持动态观和平衡观,对症状性出血性转化的诊断要慎重,充分考虑HT的分型和程度,从而正确判断HT对预后的影响。     

阿替普酶静脉溶栓治疗急性后循环缺血性卒中患者的预后相关因素分析

目的探讨分析影响阿替普酶静脉溶栓治疗急性后循环缺血性卒中患者的预后的相关因素。方法选取发病0~4.5 h急性后循环缺血性卒中患者,分为阿替普酶静脉溶栓组和非静脉溶栓组,记录患者的一般人口学资料及基本资料、美国国立卫生研究院卒中量表(National Institutes of Health Stroke Scale,NIHSS)评分,溶栓组记录发病至溶栓时间及溶栓后24 h NIHSS评分下降。结局指标采用90 d改良Rankin量表(modified Rankin Scale,m RS)评分、症状性颅内出血(symptomatic intracranial hemorrhage,SICH)及患者死亡率,应用Logistic回归模型分析卒中患者90 d不良结局的相关因素。结果急性后循环缺血性卒中患者共116例,其中成功给予阿替普酶静脉溶栓治疗的患者84例,非静脉溶栓32例。静脉溶栓组3个月预后良好53例(63.1%),预后不良31例(36.9%),其中发生出血转化6例(7.1%),症状性颅内出血3例(3.5%),死亡3例(3.5%)。非静脉溶栓组3个月预后良好12例(37.5%),预后不良20例(62.5%),其中发生出血转化5例(15.6%),症状性颅内出血3例(9.3%),死亡3例(9.3%)。静脉溶栓组经多因素Logistic回归分析显示,年龄、发病至溶栓时间、基线NIHSS评分、高血压与90 d不良预后相关(P0.05)。静脉溶栓组和非静脉溶栓组相比,静脉溶栓组有更好的临床预后及更低的死亡率,两组在症状性颅内出血发病率方面并无明显差异。结论对于急性后循环缺血性卒中患者,尽早实施静脉溶栓对改善近期预后有一定临床意义。     

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。     

炎症反应与急性缺血性脑卒中静脉溶栓后出血转化的研究进展

急性缺血性脑卒中是卒中最常见的形式之一，目前其主要的治疗方式是再灌注治疗，包 括静脉溶栓治疗和血管内治疗。急性缺血性卒中发病时间 6 h 内给予静脉溶栓可改善预后，然而静脉溶 栓同时也存在出血转化的风险，可能对患者早期神经功能改善和远期预后产生不利影响。目前的研究 认为，炎症反应主要参与急性缺血性脑卒中患者静脉溶栓后出血转化的生理病理机制。现对炎症反应 与静脉溶栓后出血转化的相关性风险预测因素进行综述，旨在为溶栓后出血转化的早期识别和预防提 供依据。     

脑白质T2高信号与缺血性卒中静脉溶栓后出血转化及神经功能的关系

目的 明确脑白质高信号(WMHs)的严重程度与急性缺血性卒中患者静脉重组组织型纤溶酶原激活剂(rt-PA)溶栓后的出血转化以及3个月后神经功能结局之间的关系.方法 连续收集就诊于我科并接受静脉rt-PA溶栓治疗的急性缺血性卒中患者144例,分析其临床资料,利用改良Schelten量表评定脑白质高信号严重程度,出血转化根据欧洲协作性急性卒中研究Ⅲ(ECASSⅢ)标准评定,改良Rankin评分≥2分定义为神经功能结局不利.结果 144例接受静脉rt-PA溶栓治疗的患者年龄为(66.6±12.6)岁,女性46例(31.9％),发病至溶栓时间为(241.9 ±88.4) min,溶栓前NIHSS为(12.31±5.98)分,脑白质高信号评分为(7.81±4.93)分.共28例(19.4％)影像学表现为溶栓后出血转化,其中18例(12.5％)为出血性梗死(HI)型,10例(6.9％)为脑实质出血(PH)型.经多元Logistic回归分析提示,WMHs严重程度不增加HI型风险(OR=1.017,95％ CI0.919 ～1.126,P =0.744),对PH型风险亦无增加(OR=1.025,95％CI0.895 ～1.175,P=0.716).二元Logistic回归分析提示,脑白质高信号严重程度是神经功能结局不利的独立危险因素(OR=1.135,95％ CI1.036 ～1.244,P=0.007).结论 严重WMHs不增加急性缺血性卒中静脉rt-PA溶栓后的出血转化风险,但与卒中后不利神经功能结局有关.     

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.     

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.     

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.     

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.