Piracetam in acute stroke: a systematic review

We studied whether the administration of piracetam in acute, presumed ischemic stroke affects case fatality and functional outcome. The Cochrane Stroke Group strategy was used to evaluate all randomized controlled trials of patients with presumed ischemic stroke examined within 48 h; death and (when available) functional outcome were used as end points. Three studies were included; the most recent one contributed more than 97% of the data. There were 501 patients treated with piracetam and 501 controls. Piracetam was associated with a nonsignificant 31% increase in the odds of death (95% CI –5% to 81%). This result was due almost completely to the effect of the larger trial, which, however, reported that the difference in case fatality rate between piracetam and control disappeared after correcting for the imbalance in stroke severity between the two groups. Data on functional outcome were available only for the largest study, and no difference was reported. Data obtained from the manufacturer suggested a nonsignificant trend (–10%) towards reduction in dependency with piracetam (CI –33% to 20%); the proportions of patients dead or dependent in the two groups were the same. Relevant adverse effects were not reported. The evidence from this review does not support routine administration of piracetam in patients with acute ischemic stroke; however, since a possible beneficial effect cannot completely be ruled out, further controlled trials are warranted. Received: 31 August 1999/Received in revised form: 3 November 1999/Accepted: 25 November 1999     

Inflammatory system gene polymorphism and the risk of stroke: a case-control study in an Indian population

Sequence variations in genes involved in inflammation system are known to contribute to the risk of cardiovascular diseases (CVD) including stroke. In this study, we performed a genetic association study on the single nucleotide polymorphisms (SNPs) present in the genes CD14 (-159 C/T), TNFalpha (-308 G/A), IL-1alpha (-889 C/T), IL-6 (-174 G/C), PSMA6 (-8 C/G), and PDE4D (SNP83 T/C, respectively) in order to discern their possible role in the susceptibility to stroke in a North Indian population. These SNPs were previously found to be associated with CVD through their contribution to inflammation. A case-control design was used to examine 176 stroke patients (112 ischemic and 64 hemorrhagic stroke patients) and 212 unrelated healthy control individuals. After adjustment for the confounding risk factors, the IL-1alpha -889 T allele carriers (TT+CT) were found to be strongly associated with both forms of stroke (OR=2.56; 95% CI=1.53-4.29; P=0.0004). The CC genotype of PDE4D was found to be associated only with ischemic stroke (OR=2.02; 95% CI=1.08-3.76; P=0.03). None of the variants tested for the CD14, TNFalpha, IL-6, and PSMA6 genes found to confer risk for stroke in the study population. In conclusion, the -889 C/T and SNP83 T/C SNPs of the IL-1alpha and PDE4D genes, respectively, appear to be genetic risk factors for stroke in our study population.     

急性缺血性卒中血管内治疗新技术探讨

卒中包括脑梗死和脑出血,其现已成为中国城市人群死亡原因的第二位,农村人群死亡原因的第一位.据报道,全国约有600万～700万卒中幸存者,每年新发卒中人数约250万～300万,死亡人数约150万.卒中幸存者中有3/4的存在不同程度的神经功能丧失,重残者超过40％.缺血性脑梗死即缺血性卒中,包括动脉血栓形成性脑梗死、脑栓塞、腔隙性梗死和分水岭梗死等.血栓形成、栓子脱落、血管壁斑块形成及血管狭窄等是导致急性缺血性卒中的常见病因.由于缺血性卒中发病原因复杂,导致了血管内治疗技术的多样性和高难度.     

Interleukin-18 promoter polymorphisms and risk of ischemic stroke

Ischemic stroke (IS) is a major cause of morbidity and mortality around the world. Interleukin-18 (IL-18) plays an important role in the pathogenesis of IS and IL-18 promoter polymorphisms have been shown to be associated with levels of expression of IL-18. We investigated the association of two functional polymorphisms in IL-18 promoter, −607C/A (rs1946518) and −137G/C (rs187238), with the risk of ischemic stroke in a Han Chinese population of 423 patients and 384 healthy controls matched for sex and age. The results revealed that the −607C allele was associated with an increased risk of IS with an odds ratios (OR) of 1.358 (P = 0.002, power = 100%) and the presence of the −137G allele was correlated with increased the risk of IS in the subtype of patients with large artery atherosclerosis (LAA) (OR = 1.583, P = 0.02, power = 94%). Patients with the −607C/−137G haplotype also had significantly increased risk of IS compared to controls (OR = 1.341, P = 0.005, power = 100%). Our findings suggest that these functional polymorphisms in the IL-18 promoter are involved in development of IS in the Han Chinese population.     

Tumor necrosis factor alpha serum levels and inflammatory response in acute ischemic stroke patients

Abstract. Experimental evidence indicates that tumor necrosis factor alpha (TNF-) is involved in brain damage following ischemic injury. The present study was designed to monitor serum TNF- levels in acute stroke patients and to correlate TNF- levels with lesion size, neurological impairment and vascular risk factors. In 41 patients with ischemic stroke, serum TNF- levels were serially measured by a solid enzyme amplified sensitivity immunoassay (EASIA) in the first 10 days after stroke onset. Serum fibrinogen and Creactive protein (CRP), white blood cell (WBC) and neutrophil counts were determined on the same days to monitor acute phase response changes. Lesion size was calculated on computed tomograms by a computer-assisted procedure. Neurological impairment was evaluated on the Canadian Neurological Scale. Forty age-matched subjects were used as controls. Compared to baseline, TNF- levels significantly increased during the study (p=0.0001), peaking on day 7. Peak TNF- levels did not correlate with neurological impairment or lesion size. Multivariate analysis showed that sex, age, vascular risk factors and infectious complications did not influence TNF- levels. Fibrinogen, CRP, WBC and neutrophil concentrations increased, indicating an acute phase response occurred after stroke. In conclusion, serum TNF- levels showed an early and prolonged increase after stroke onset, unrelated to lesion size, neurological impairment, age, sex, vascular risk factors or infectious complications. Serum increase of TNF- may be explained as part of the acute phase response occurring in stroke patients.     

Translating research into practice: Lessons from trials of thrombolysis in acute stroke

There exist individual, institutional and national barriers to change, none more so than when introducing new therapies into medical practice especially those that involve organizational change. This paper, presented as an address to the joint meeting of the Association of British Neurologists and the Indian Academy of Neurology in October 2007, explores these barriers in the context of the instruction of thrombolytic therapy for patients with acute ischaemic stroke and suggests how they might be overcome using evidence from relevant clinical trials and observational studies.     

核心蛋白多糖与缺血性卒中的研究现状

缺血性卒中（IS）是临床常见的脑血管疾病,其发病率、病死率和致残率一直居高不下,严重威胁到人类的健康和生命,其发病机制、治疗策略已成为目前研究的焦点。核心蛋白聚糖（DCN）是一种细胞外基质成份,大量研究发现DCN可以起到抗炎、抑制肿瘤生长、抗脏器纤维化等作用,近年来已成为肿瘤、心脑血管疾病研究的热点之一。本文着重从IS的早期和晚期两个方面阐述DCN通过抗MMPs家族、上调内皮细胞p21和p27（周期素依赖性蛋白激酶抑制剂）表达及调节血管内皮生长因子（VEGF）表达等机制进而发挥抗炎、稳定粥样硬化斑块、调节细胞凋亡、促进血管生成的脑保护作用。     

临床护理对2型糖尿病患者并缺血性脑卒中的影响

目的探讨针对性临床护理对2型糖尿病患者并缺血性脑卒中的影响。方法选择2012-01—2014-01我院收治的2型糖尿病并缺血性脑卒中者110例,将其随机分为研究组与对照组,每组各55例,对照组给予常规护理,研究组给予针对性临床护理干预,对比2组疗效。结果 2组患者治疗前空腹血糖、餐后2h血糖、收缩压和舒张压均高于正常值,且组间比较差异无统计学意义(P0.05),治疗后2组患者空腹血糖、餐后2h血糖、收缩压和舒张压均显著降低,且研究组上述指标显著低于对照组(P0.05)。研究组经过相应治疗及针对性临床护理干预后,总有效率为96.36%,明显高于对照组的81.82%(P0.05)。研究组Harris分值及Barthel分值均高于对照组(P0.05)。结论 2型糖尿病并缺血性脑卒中者给予针对性的临床护理干预,可以有效提高患者的肌体功能,加强日常生活能力,改善临床症状,适于临床推广。     

Carotid webs and ischemic stroke: Experiences in a comprehensive stroke center

Background and purpose

Carotid webs are intraluminal filling defects at the carotid bulb which are considered rare, though possibly underappreciated entities with recent studies demonstrating a likely casual association with ischemic stroke. The purpose of the study is to describe our recent experience with clinical and imaging manifestations of carotid webs.

CX37基因I1297D多态性与缺血性脑卒中及临床分型的关系探讨

目的探讨连接蛋白37(connexins37,CX37)基因I1297D多态性位点与缺血性脑卒中及其亚型的关系。方法采用限制性片段长度多态性分析技术,检测缺血性脑卒中组232例(根据诊断分为动脉粥样硬化性血栓性脑梗死组115例,脑栓塞组31例,腔隙性脑梗死组86例)和健康对照组235例CX37基因I1297D多态的分布。结果 CX37基因I1297D多态性,缺血性脑卒中组和对照组中均以II基因型和I等位基因为主。基因型(II型I、D型、DD型)I、和D等位基因分布频率在缺血性脑卒中组分别为46.56%、39.22%、14.22%、66.16%和33.84%,对照组分别为47.66%、43.40%、8.94%、69.36%和30.64%,2组比较差异无统计学意义(P>0.05),且其基因型、等位基因分布频率在缺血性脑卒中各亚型之间与对照组比较,差异无统计学意义(P>0.05)。结论 CX37基因I1297D的多态性与缺血性脑卒中易感性无关。     

糖尿病与进展性缺血性脑卒中相关性研究

目的 探讨糖尿病与进展性缺血性脑卒中的相关性.方法 我院神经内科2006-05～2009-05收治的缺血性脑卒中患者130例为研究对象,其中伴糖尿病患者64例为糖尿病组,非糖尿病患者66例为非糖尿病组,比较2组发展为进展性缺血性脑卒中的差异.结果 糖尿病组64例中诊断为进展性卒中41例,占64.1%;非糖尿病组66例诊...     

弥散加权和灌注加权在缺血性中风的应用

目的　观察缺血性中风早期病灶的部位及程度,评价病灶的微循环状态。方法　ＤＷＩ和ＰＷＩ是一 种新的磁共振成像技术,ＤＷＩ通过测定水分子的布朗运动而获得;ＰＷＩ通过静脉团注造影剂而得到。结果　ＤＷＩ 能明确早期急性缺血性病灶的部位,ＰＷＩ证实病灶区微循环不良的范围。结论　有助于对缺血性中风患者治疗方 法的选择,并提供了一种高度敏感的评价治疗效果的方法。     

手针与电针对于缺血性脑卒中偏瘫患者的治疗效果

目的 比较手针与电针对于缺血性脑卒中偏瘫患者的治疗效果。方法 选取本院针灸科收治的200例缺血性脑卒中偏瘫患者作为研究对象,按照治疗方法分为手针组与电针组,各100例; 在药物治疗的基础上手针组患者给予手针治疗,电针组患者给予电针治疗; 比较手针组与电针组在治疗中各项观察指标的变化,评估其疗效和安全性。结果 治疗结束后手针组与电针组NIHSS评分均下降,Fugl-Meyer运动评分均升高,Barthel指数均升高,但电针组更加显著(P<0.05); 电针组疗效优于手针组(P<0.05),均未发生不良事件。结论 手针和电针对于缺血性脑卒中偏瘫患者均具有一定康复效应,但电针疗效更加显著。     

Skating to where the puck is going to be: a plan for clinical trials and translation research in mood disorders.

As part of the National Institute of Mental Health Strategic Plan for Mood Disorders Research effort, the Clinical Trials and Translation Workgroup was asked to define priorities for clinical trials in mood disorders and for research on how best to translate the results of such research to clinical practice settings.Through two face-to-face meetings and a series of conference calls, we established priorities based on the literature to date and what was known about research currently in progress in this area.We defined five areas of priority that cut across developmental stages, while noting that research on adult mood disorders was at a more advanced stage in each of these areas than research on child or geriatric disorders. The five areas of priority are: 1) maximizing the effectiveness and cost-effectiveness of initial (acute) treatments for mood disorders already known to be efficacious in selected populations and settings when they are applied across all populations and care settings; 2) learning what further treatments or services are most likely to reduce symptoms and improve functioning when the first treatment is delivered well, but the mood disorder does not remit or show adequate improvement; 3) learning what treatments or services are most cost-effective in preventing recurrence or relapse and maintaining optimal functioning after a patient's mood disorder has remitted or responded maximally to treatment; 4) developing and validating clinical, psychosocial, biological, or other markers that predict: a) which treatments are most effective, b) course of illness, c) risk of adverse events/tolerability and acceptability for individual patients or well-defined subgroups of patients; 5) developing clinical trial designs and methods that result in lower research costs and greater generalizability earlier in the treatment development and testing process. A rationale for the importance of each of these priorities is provided.     

Lutein enhances survival and reduces neuronal damage in a mouse model of ischemic stroke

Introduction

Stroke is one of the leading causes of death worldwide. Protective agents that could diminish the injuries induced by cerebral ischemia/reperfusion (I/R) are crucial to alleviate the detrimental outcome of stroke. The aim of this study is to investigate the protective roles of lutein in cerebral I/R injury.

Methods

Two-hour cerebral ischemia was induced by unilateral middle cerebral artery occlusion (MCAo) in mice. Either lutein (0.2 mg/kg) or vehicle was given to mice intraperitoneally 1 h after MCAo and 1 h after reperfusion. Neurological deficits were evaluated at 22 h after reperfusion while survival rate was assessed daily until 7 days after reperfusion. Brains were cut into 2 mm-thick coronal slices and stained with 2% 2,3,5-triphenyltetrazolium chloride to determine the infarct size after MCAo. Paraffin-embedded brain sections were prepared for TUNEL assay and immunohistochemistry. Protein lysate was collected for Western blotting experiments.

Results

Higher survival rate, better neurological scores, smaller infarct area and smaller infarct volume were noted in the lutein-treated group. Immunohistochemistry data showed a decrease of immunoreactivity of nitrotyrosine, poly(ADP-ribose) and NFκB in the lutein-treated brains. Western blotting data showed decreased levels of Cox-2, pERK, and pIκB, but increased levels of Bcl-2, heat shock protein 70 and pAkt in the lutein-treated brains.

Conclusions

Post-treatment of lutein protected the brain from I/R injury, probably by its anti-apoptotic, anti-oxidative and anti-inflammatory properties. These suggest that lutein could diminish the deleterious outcomes of cerebral I/R and may be used as a potential treatment for stroke patients.     

Glucagon-like peptide-1 receptor agonists as neuroprotective agents for ischemic stroke: a systematic scoping review

Stroke mortality and morbidity is expected to rise. Despite considerable recent advances within acute ischemic stroke treatment, scope remains for development of widely applicable neuroprotective agents. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), originally licensed for the management of Type 2 Diabetes Mellitus, have demonstrated pre-clinical neuroprotective efficacy in a range of neurodegenerative conditions. This systematic scoping review reports the pre-clinical basis of GLP-1RAs as neuroprotective agents in acute ischemic stroke and their translation into clinical trials. We included 35 pre-clinical studies, 11 retrospective database studies, 7 cardiovascular outcome trials and 4 prospective clinical studies. Pre-clinical neuroprotection was demonstrated in normoglycemic models when administration was delayed by up to 24 h following stroke induction. Outcomes included reduced infarct volume, apoptosis, oxidative stress and inflammation alongside increased neurogenesis, angiogenesis and cerebral blood flow. Improved neurological function and a trend towards increased survival were also reported. Cardiovascular outcomes trials reported a significant reduction in stroke incidence with semaglutide and dulaglutide. Retrospective database studies show a trend towards neuroprotection. Prospective interventional clinical trials are on-going, but initial indicators of safety and tolerability are favourable. Ultimately, we propose that repurposing GLP-1RAs is potentially advantageous but appropriately designed trials are needed to determine clinical efficacy and cost-effectiveness.     

发病前他汀治疗与rt-pA静脉溶栓后血浆MMP-9水平及预后的相关性研究

目的探讨发病前他汀治疗对rt-PA静脉溶栓的急性缺血性卒中患者血浆金属基质蛋白酶-9(MMP-9)水平及预后的影响。方法采用前瞻性队列研究纳入2011年1月-2015年5月南京市第一医院神经内科首次急性缺血性脑卒中,并行rt-PA静脉溶栓患者258例。他汀组64例:溶栓前曾使用他汀药物;对照组194例:溶栓前未使用过他汀药物。采用ELISA法测量其中193例患者(47例他汀组及146例对照组)溶栓前及溶栓后6 h、12 h、24 h、72 h血浆MMP-9水平,观察静脉溶栓前、后MMP-9水平变化。比较所有两组患者7 d与90 dmRS评分及症状性颅内出血发生率。结果两组患者的MMP-9水平均于静脉r-t PA溶栓后上升,24 h后达到最高值。他汀组与对照组的溶栓前及溶栓后6 h血浆MMP-9无统计学差异,治疗组在12 h、24 h及72 h(P0.001)的MMP-9水平均低于对照组。他汀组与对照组在溶栓7 d、90 d后mRS评分(0~2分)及发生sICH无统计学差异。Mann-Whitney U检验提示两组间7 d与90 d mRS评分分布无统计学差异。结论溶栓前接受他汀类药物治疗对急性缺血性卒中患者溶栓后的MMP-9上升有明显的抑制作用,但与对照组相比静脉溶栓患者的预后未显示有统计学差异。     

Force and aspiration on catheters utilized in the ADAPT technique in acute ischemic stroke: A bench top analysis

IntroductionGiven the high morbidity and mortality of stroke, there remains a demand for techniques that provide rapid and safe intervention while improving time to recanalization. The direct aspiration first pass technique (ADAPT) uses force and aspiration for clot removal without the aid of separators or retrievers. In this study, we compare the force and aspiration qualities of commercially available catheters.MethodsFour different catheters with varying inner diameters were set up in a bench top model to test catheter tip pressure and flow rate. Catheter tip pressure was measured by attaching the catheter to a vacuum pressure gauge and an aspiration pump. The flow rate was calculated by measuring the volume of room temperature water aspirated through each catheter over a given time.ResultsThe Microvention Sofia catheter generated the greatest tip force (21.32 g), and the Stryker AXS Catalyst 6 catheter generated the smallest tip force (15.88 g). The Penumbra ACE 068 catheter and Medtronic ARC catheter measured 20.87 g and 16.78 g respectively. The ACE 068 had highest rate of aspiration at 289 mL/min, and the Catalyst 6 catheter had the lowest rate at 214. The Microvention Sofia catheter had the second highest rate while the ARC had the third highest rate, measuring 285 mL/min and 256 mL/min, respectively.ConclusionsWhen using the ADAPT technique, knowledge of the tip force and catheter flow rate of newer catheters with larger distal inner diameters may guide selection of aspiration catheters. While this study demonstrates differences in tip force and flow rate of different commercially available catheters, clinical translation will require further testing and evaluation.     

Glioblastoma multiforme presenting with ischemic stroke: case report and review of the literature

A 58-year-old woman presented with acute onset of global aphasia. Imaging studies revealed a left frontotemporal enhancing tumor and ischemic stroke in the territory of the middle cerebral artery. The patient was operated on, and the diagnosis of glioblastoma multiforme was confirmed. At the time of surgery, several branches of the left middle cerebral artery were found embedded in the tumor. One branch, which was infiltrated by tumor and completely occluded, was resected to achieve complete resection. Postoperatively, the stroke area within the middle cerebral artery territory increased, together with worsening of the patient's clinical status, thus requiring urgent decompressive craniectomy. Thereafter, the patient gradually improved, and received radiation therapy and chemotherapy with no recurrence after 24 months of follow-up. To our knowledge, glioblastomas presenting with ischemic stroke are rare, and such patients should be considered to be at high surgical risk.     

Toward cell replacement therapy: promises and caveats

Studies in animal models have suggested a role for stem cells in repair and regeneration of the nervous system. Human equivalents of stem and precursor cells have been isolated and their efficacy is being evaluated in rodent and primate models. Difficulties exist in translating results of these preclinical models to therapy in humans. Evolutionary differences among rodents, primates, and humans; fundamental differences in the anatomy and physiology; differences in immune responses in xenotransplant models; the paucity of good transplant models of chronic disease; and allelic variability in the cells themselves make any study evaluating the efficacy of cells in transplant models difficult to interpret. As no better alternatives to testing in animals exist, we suggest that at this early stage a considered step-by-step approach to testing and comparison of different transplant strategies in isolation will prepare us better for clinical trials than simple evaluation of functional outcomes in various models of disease. We emphasize that we do not recommend delaying or abandoning clinical trials; rather, we suggest that one anticipate failures and design experiments and data collection such that we learn from these failures to ensure future success in as rapid a time frame as possible.