Management of Acute Ischemic Stroke

The treatment of acute ischemic stroke includes both intravenous (IV) thrombolysis and mechanical thrombectomy. Important advances regarding both treatment modalities have occurred recently that all physicians who see patients at risk for or who have had a stroke should be aware of. This review will focus on recent clinical trials of IV thrombolysis both positive and negative. Additionally, the results of a large number of early and late time window thrombectomy trials will be presented that demonstrate the remarkable efficacy of this treatment for appropriately selected patients.     

Acute Stroke Intervention

Ischemic strokes will make up most (>80%) of the three-quarters of a million strokes that will occur in Americans this year. Reperfusion therapy is the fundamental strategy for the treatment of acute ischemic stroke. Reperfusion therapy may be accomplished noninvasively (intravenous thrombolysis) or invasively with catheter-based treatments (intra-arterial thrombolysis, thrombectomy, or angioplasty). Currently, a large majority of patients with acute ischemic stroke do not receive any form of reperfusion therapy owing to their delayed presentation (>3 hours) and lack of skilled man power for on-demand endovascular treatment. Paradoxically, improved success rates for reperfusion have been reported with the newer thrombectomy catheters, called “stentreivers.” An option for broadening access for patients who need endovascular therapy would be to use interventional cardiologists with carotid stent experience who can help to provide 24×7×365 coverage.     

伴心房颤动的急性缺血性卒中的治疗

心房颤动是缺血性卒中的一种重要病因.研究表明,与无心房颤动者相比,伴有心房颤动的卒中患者会出现更严重的神经功能缺损和更高的病死率.此外,心房颤动还是静脉溶栓后血管未能再通的独立危险因素,与转归不良相关.机械取栓治疗为伴有心房颤动的急性缺血性卒中患者提供了新的治疗方案.文章就合并心房颤动的急性缺血性卒中患者的静脉溶栓和机械取栓治疗进行了综述.     

机械取栓装置在缺血性卒中患者治疗中的应用

目前,在发病4．5h内进行静脉溶栓仍然是治疗急性缺血性卒中患者的最有效方法。对于不符合静脉溶栓治疗标准、静脉溶栓后症状无明显改善甚至恶化的患者,血管内介入治疗是一种安全的替代治疗方法。经动脉机械取栓装置能实现迅速和完全的血管再通,为急性缺血性卒中患者提供了更多的治疗选择。文章对近年来机械取栓装置相关的技术演变和临床试验进行了综述。     

静脉溶栓桥接治疗急性缺血性卒中

静脉溶栓是治疗急性缺血性卒中的首选方法,但在大血管闭塞性卒中患者中的血管再通率较低.以血管内机械血栓切除术为代表的血管内治疗能有效使缺血性卒中患者闭塞血管再通和改善转归.文章对静脉溶栓桥接治疗的现状和发展方向进行了综述.     

Treatment of acute stroke: an update

Stroke is the second leading cause of global mortality after coronary heart disease, and a major cause of neurological disability. About 17 million strokes occur worldwide each year. Patients with stroke often require long‐term rehabilitation following the acute phase, with ongoing support from the community and nursing home care. Thus, stroke is a devastating disease and a major economic burden on society. In this overview, we discuss current strategies for specific treatment of stroke in the acute phase, focusing on intravenous thrombolysis and mechanical thrombectomy. We will consider two important issues related to intravenous thrombolysis treatments: (i) how to shorten the delay between stroke onset and treatment and (ii) how to reduce the risk of symptomatic intracerebral haemorrhage. Intravenous thrombolysis has been approved treatment for acute ischaemic stroke in most countries for more than 10 years, with rapid development towards new treatment strategies during that time. Mechanical thrombectomy using a new generation of endovascular tools, stent retrievers, is found to improve functional outcome in combination with pharmacological thrombolysis when indicated. There is an urgent need to increase public awareness of how to recognize a stroke and seek immediate attention from the healthcare system, as well as shorten delays in prehospital and within‐hospital settings.     

No space left for intravenous thrombolysis in acute stroke: PROS

Five recently published RCTs (MR CLEAN, EXTEND-IA, SWIFT PRIME, REVASCAT and ESCAPE) employing mechanical thrombectomy with modern stent retriever devices clearly demonstrated the superiority of endovascular treatment compared to thrombolysis alone, which is now considered standard first-line therapy for selected patients with acute severe ischemic stroke and large vessel in the anterior circulation. RCT results led to recommendations outlined in “Mechanical thrombectomy in acute ischemic stroke by ESO-Karolinska Stroke Update 2014/2015, supported by ESO, ESMINT, ESNR and EAN”. Moreover, endovascular procedures in the 5 RCTs to date were performed at high-volume referral centers with, in some trials, rigid requirements for the interventionalist to participate, which may have contributed substantially to the excellent results, supporting the concept of centralization of intra-arterial thrombolysis resources and expertise. Therefore, patients with suspected large-artery occlusion and deemed candidates for thrombectomy, should be treated at a Comprehensive Stroke Centre with 24/7 endovascular treatment services. There seems to be limited space left for intravenous thrombolysis alone in acute stroke patients with large-vessel occlusions as thrombectomy plus thrombolysis continues to be reported as being superior with regard to outcome.     

Fibrinolytic therapy in acute stroke

Acute ischemic stroke is a major cause of morbidity and mortality in Europe, North America, and Asia. Its treatment has completely changed over the past decade with different interventional approaches, such as intravenous trials, intra-arterial trials, combined intravenous/intra-arterial trials, and newer devices to mechanically remove the clot from intracranial arteries. Intravenous thrombolysis with tissue plaminogen activator (tPA) within 4.5 hours of symptoms onset significantly improved clinical outcomes in patients with acute ischemic stroke. Pharmacological intra-arterial thrombolysis has been shown effective until 6 hours after middle cerebral artery occlusion and offers a higher rate of recanalization compared with intravenous thrombolysis, whereas combined intravenous/ intra-arterial thrombolysis seems to be as safe as isolated intravenous thrombolysis. The more recent advances in reperfusion therapies have been done in mechanical embolus disruption or removal. Merci Retriever and Penumbra System have been approved for clot removal in brain arteries, but not as a therapeutic modality for acute ischemic stroke since it is no clear whether mechanical thrombectomy improves clinical outcome in acute stroke. However, mechanical devices are being used in clinical practice for patients who are ineligible for tPA or who have failed to respond to intravenous tPA. We summarize the results of the major thrombolytic trials and the latest neurointerventional approaches to ischemic stroke.     

急性缺血性卒中再灌注治疗后血管再闭塞

急性缺血性卒中是最常见的卒中类型,在发病4.5 h内进行静脉溶栓仍是目前最有效的治疗方法.其他再灌注治疗,如血管内血栓切除术也显示出其安全性和有效性.然而,部分接受再灌注治疗的患者会出现血管再闭塞,且与转归不良相关.文章对再灌注后血管再闭塞的发生机制和可能防治措施进行了综述.     

动脉溶栓和动静脉联合溶栓及机械取栓治疗急性脑梗死的比较研究

目的评价动脉溶栓、动静脉联合溶栓和单纯机械取栓治疗急性脑梗死的疗效及安全性。方法选择急性脑梗死颅内血管狭窄或闭塞患者61例,根据不同溶栓方法分动脉溶栓组25例,动静脉联合溶栓组(联合溶栓组)17例,单纯机械取栓组(机械取栓组)19例。分别对治疗前后患者的美国国立卫生研究院卒中量表(NIHSS)评分、治疗的有效性、近期与远期疗效进行分析。结果与治疗前比较,动脉溶栓组、联合溶栓组治疗后2周NIHSS评分明显降低(P<0.05,P<0.01),机械取栓组治疗后3d、2周NIHSS评分明显降低(P<0.05,P<0.01)。动脉溶栓组残余狭窄率≤30%发生率、急性血管再闭塞率和病死率分别为16.0%、52.0%和12.0%,联合溶栓组分别为11.8%、52.9%和0,机械取栓组分别为47.4%、0和10.5%。3组残余狭窄率≤30%发生率、急性血管再闭塞率比较,差异有统计学意义(P<0.05,P<0.01)。结论不论采用动脉溶栓、动静脉联合溶栓还是机械取栓方法,均可使患者神经功能改善,对近期临床预后的改善有相近效果。采用机械取栓方法对神经功能改善时间较早、溶栓效果、安全性及远期临床预后较好。     

Acute myocardial infarction and acute stroke: What are the differences? Focus on reperfusion therapy

This review compares acute myocardial infarction and acute stroke— their similarities and differences. The focus is given on reperfusion therapy: pharmacologic, mechanical or combined. The key trials and metaanalyses are described.The published data on iv. thrombolysis show, that even among a subgroup of patients treated within 90 min from stroke onset the trend to lower mortality is not significant and in all other subgroups (i.e. treated after >90 min) there is a trend towards increased mortality with thrombolytic treatment.The data on combined therapy demonstrate, that there is no benefit from facilitated intervention (iv. thrombolysis followed by ia. thrombolysis ± catheter intervention) over iv. thrombolysis alone in acute stroke. This is very similar to the situation in acute myocardial infarction 25 years ago (intracoronary thrombolysis was not superior to intravenous thrombolysis) or more recently (facilitated PCI was not shown to be superior in several trials).The latest generation of stent retrievers is able to recanalize >70% of occluded intracranial arteries—approximately twice more compared to thrombolysis. However, it is not yet known whether this translates to better clinical outcomes. The sufficient data on clinical outcomes after primary catheter-based thrombectomy (without thrombolysis) are still missing and trials comparing iv. thrombolysis versus primary catheter-based thrombectomy are urgently needed.The future trials in acute stroke may follow the way paved by acute myocardial infarction trials. If such trials would demonstrate superiority of catheter-based thrombectomy, we can face in future similar revolution in acute stroke treatment as we have been facing in acute MI treatment in the past years.     

DRAGON评分对颅内大血管闭塞致急性缺血性卒中静脉溶栓桥接机械取栓临床结局的预测作用

目的评估前循环颅内大血管闭塞致急性缺血性卒中患者入院时DRAGON[dense cerebral artery,mRS(改良Rankin量表),age,glucose level,onset to treatment time,NIHSS(美国国立卫生研究院卒中量表)]评分对静脉溶栓桥接机械取栓术后患者临床结局的预测作用。方法回顾性连续纳入2015年1—12月急性缺血性卒中血管内治疗试验(EAST)中接受机械取栓及静脉溶栓桥接机械取栓治疗的急性缺血性卒中患者149例,为发病至治疗时间≤6 h,于术前经CT血管成像和(或)MR血管成像和(或)DSA证实。根据治疗后90 d mRS评分,将149例患者分为预后良好(mRS评分0~2分)组和预后不良(mRS评分3~6分)组。收集并比较两组患者的人口学资料、脑血管病危险因素(高血压病、糖尿病、心房颤动等)、入院时NIHSS评分、发病时间、卒中前mRS评分、影像学特征、实验室检查、DRAGON评分、治疗方式的差异。对静脉溶栓桥接机械取栓不同预后者上述指标进行比较,并采用受试者工作特征(ROC)曲线确定DRAGON预测静脉溶栓桥接机械取栓患者预后的最佳截断值。结果(1)预后良好组患者基线NIHSS评分低于预后不良组[14(11,18)分比18(14,21)分],男性比例高于预后不良组[71.1%(59/83)比50.0%(33/66)],组间差异均有统计学意义(均P<0.01);两组年龄、高血压病、糖尿病、心房颤动、高脂血症、卒中史、高密度征、早期脑梗死征象的差异均无统计学意义(均P>0.05)。(2)预后良好组血糖水平及基线DARGON评分均低于预后不良组,组间差异均有统计学意义[(6.5±1.5)mmol/L比(8.2±3.3)mmol/L,(4.4±1.3)分比(5.2±1.4)分;均P<0.01];两组发病至治疗时间、发病至再通时间、血肌酐、白细胞计数、卒中前mRS 0~1分比例及静脉溶栓桥接机械取栓比例的差异均无统计学意义(均P>0.05)。(3)静脉溶栓桥接机械取栓术后预后良好者基线NIHSS评分、发病至治疗时间、发病至成功再通时间、血糖水平、基线DARGON评分均低于预后不良者,二者差异均有统计学意义[14(10,16)分比19(16,24)分,168(126,134)min比239(210,295)min,199(183,285)min比275(260,345)min,(6.4±1.2)mmol/L比(9.0±2.4)mmol/L,(4.3±1.5)分比(6.1±1.2)分;均P<0.05];二者间其余基线和临床资料的差异均无统计学意义(均P>0.05)。(4)基线DRAGON评分预测静脉溶栓桥接机械取栓术后90 d预后的ROC曲线下面积为0.830,最佳截断值为6分,其敏感度为63.6%,特异度为91.7%。结论入院时DRAGON评分可能对前循环大血管闭塞致急性缺血性卒中患者接受静脉溶栓桥接机械取栓后的预后具有一定的预测作用。     

Treatment of Acute Ischemic Stroke With Clot Retrieval Devices

OPINION STATEMENT: Mechanical clot retrieval is increasingly used for flow-restoration and thrombectomy in acute embolic stroke. Emerging as a treatment option in addition to intravenous or intra-arterial thrombolysis, it is currently being further developed and investigated as a potential first-line and stand-alone treatment. The ability to rapidly restore flow and effectively retrieve clots from large intracranial arteries is reflected by angiographic data and preliminary clinical results. This article reviews the principles and technical aspects of this new technique, its emergence from the spectrum of intravenous and endovascular stroke treatment, and summarizes the first clinical results for acute ischemic anterior and posterior circulation stroke. Clot retrieval devices are a very promising option for treatment of acute ischemic stroke in the setting of large vessel occlusion. However, there currently exists a reported discrepancy between excellent recanalization rates and less satisfactory clinical outcomes. This problem urgently needs to be addressed in a prospective randomized fashion and improvements of treatment be recognized and implemented before clot retrieval can be considered an established form of acute stroke treatment.     

急性缺血性卒中机械取栓治疗的现状

在出现不可逆性神经细胞损伤之前迅速安全地再通血管、恢复血流以挽救缺血半暗带组织,是急性缺血性卒中（acute ischemic stroke, AIS ）的主要治疗目标。目前,在AIS早期开通血管的方法主要是静脉溶栓,但由于其治疗时间窗短、血管再通率低、出血并发症发生率高等原因,效果常不令人满意。近年来,随着机械取栓装置的研发及介入技术的发展,使得AIS的治疗时间窗显著延长,血管开通率显著提高,临床转归显著改善,机械取栓治疗已显示出良好的应用前景。     

前循环卒中血管内血栓切除术治疗：随机对照试验的汇总分析

目的：评价前循环卒中患者血管内血栓切除术治疗的有效性和安全性。方法检索PubMed、EMBASE、Cochrane、Clinical Trials 数据库和相关补充资料,纳入在前循环卒中患者中比较静脉溶栓治疗与血管内血栓切除术治疗的随机临床对照试验,进行偏倚风险评价,提取研究基本特征和90 d时转归良好(定义为改良 Rankin 量表评分0~2分)、死亡以及有症状颅内出血(symptomatic intracranial hemorrhage, sICH)等数据,应用 Review Manager 5．3软件进行统计学分析。结果共纳入10项研究,其中血管内治疗组共1557例患者,静脉溶栓治疗组共1359例患者。纳入研究的质量整体较高,产生偏倚的风险较低。血管内治疗组转归良好率显著高于静脉溶栓对照组[优势比(odds ratio, OR)2．15,95%可信区间(confidence interval, CI)1．34~3．46;P <0．01],90 d死亡风险与静脉溶栓治疗组无显性差异(OR 0．86,95% CI 0．69~1．06;P =0．16),但 sICH 风险增高存在临界性统计学意义(OR 1．35,95% CI 1．00~1．84;P =0．05)。结论前循环卒中患者行血管内血栓切除术治疗的有效性显著优于静脉溶栓治疗,但在安全性方面仍需进一步评价。     

The administration of rtPA before mechanical thrombectomy in acute ischemic stroke patients is associated with a significant reduction of the retrieved clot area but it does not influence revascularization outcome

Journal of Thrombosis and Thrombolysis - Both intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) are evidence-based treatments for acute ischemic stroke (AIS) in selected cases....     

Management of acute ischaemic stroke in patients with dementia

An estimated 10% of stroke patients have an underlying dementia. As a consequence, health professionals often face the challenge of managing patients with dementia presenting with an acute stroke. Patients with dementia are less likely to receive thrombolysis (0.56–10% vs. 1–16% thrombolysis rates in the general population), be admitted to a stroke unit or receive some types of care. Anticoagulation for secondary stroke prevention is sometimes withheld, despite dementia not being listed as an exclusion criterion in current guidelines. Studies in this population are scarce, and results have been contradictory. Three observational studies have examined intravenous thrombolysis for treatment of acute ischaemic stroke in patients with dementia. In the two largest matched case–control studies, there were no significant differences between patients with and without dementia in the risks of intracerebral haemorrhage or mortality. The risk of intracerebral haemorrhage ranged between 14% and 19% for patients with dementia. Studies of other interventions for stroke are lacking for this population. Patients with dementia are less likely to be discharged home compared with controls (19% vs. 41%) and more likely to be disabled (64% vs. 59%) or die during hospitalization (22% vs. 11%). The aim of this review was to summarize current knowledge about the management of ischaemic stroke in patients with pre‐existing dementia, including organizational aspects of stroke care, intravenous thrombolysis, access to stroke unit care and use of supportive treatment. Evidence to support anticoagulation for secondary prevention of stroke in patients with atrial fibrillation and antiplatelet therapy in nonembolic stroke will be discussed, as well as rehabilitation and how these factors influence patient outcomes. Finally, ethical issues, knowledge gaps and pathways for future research will be considered.     

Innovative Strategies in the Management of Acute Stroke

Opinion statement Advances in acute stroke therapy are rapidly changing our approach to the management of patients with ischemic stroke. Intravenous tissue plasminogen activator was the first treatment demonstrated in a randomized controlled trial to improve outcome if given within the first 3 hours of stroke onset. Subsequent trials failed to extend the time window for intravenous therapy beyond 3 hours. Intraarterial thrombolysis provides an alternative approach, with several advantages over intravenous therapy. The major drawback is the additional time needed for the interventional procedure, and the equipment and personnel requirements. New strategies aimed at reducing the total time from stroke onset to recanalization of occluded arteries include a combined intravenous/intra-arterial delivery of thrombolysis and mechanical devices. For the millions of stroke survivors, investigations are now underway into the possibility of improvement of function through neuronal transplantation.     

Innovative strategies in the management of acute stroke

Advances in acute stroke therapy are rapidly changing our approach to management of patients with ischemic stroke. Intravenous tissue-plasminogen activator (tPA) was the first treatment demonstrated in a randomized controlled trial to improve outcome if given within the first 3 hours of stroke onset. Subsequent trials failed to extend the time window for intravenous therapy beyond 3 hours. Intra-arterial thrombolysis provides an alternative approach, with several advantages over intravenous therapy. The major drawback is the additional time needed for the interventional procedure, and the equipment and personnel requirements. New strategies aimed at reducing the total time from stroke onset to recanalization of occluded arteries include a combined intravenous/ intra-arterial delivery of thrombolysis and mechanical devices. For the millions of stroke survivors, investigations are now underway into the possibility of improvement of function through neuronal transplantation.     

Catheter‐based therapy for acute ischemic stroke: A national unmet need

Early reperfusion therapy for acute stroke, similar to acute myocardial infarction, has the best opportunity to reduce morbidity and mortality. Treatment options include intravenous (IV) thrombolysis therapy and/or catheter‐based therapy (CBT). Catheter‐based therapies include local intra‐arterial thrombolysis, mechanical thrombectomy, and angioplasty techniques. Intravenous thrombolysis is limited to the first three hours after symptom onset, which excludes many patients with disabling stroke deficits. Catheter‐based therapy is effective up to seven hours after onset, but availability is limited by the lack of neurointerventionalists available around the clock to provide this care. To increase the number of providers for acute stroke reperfusion therapy, we have formed a multidisciplinary team to take advantage of cardiologists' carotid stent placement experience to provide continuous coverage for emergency reperfusion therapy. We present two cases of acute stroke treated with CBT by interventional cardiologists. © 2008 Wiley‐Liss, Inc.