Intra-arterial thrombolysis in acute ischaemic stroke

Several thrombolytic agents for the treatment of acute ischaemic stroke have been examined; however, to date, only the i.v. administration of recombinant tissue plasminogen activator is licensed in Australia. Although no trials directly comparing intra-arterial and i.v. delivery of thrombolytics exist, intra-arterial thrombolysis has several potential advantages, including angiographic assessment of the thrombus and the site of occlusion and collateral circulation, improved recanalization, and delivery of higher local concentrations of thrombolytic agents and extending the therapeutic time window for treatment. We conducted a retrospective audit of our experience with the use of intra-arterial urokinase to treat acute ischaemic stroke at an Australian tertiary-care hospital between June 1993 and June 2003. We examined time from stroke onset to assessment, computerized tomography scan, cerebral angiography and thrombolysis, anatomical classification of intra-arterial thrombus, rates of symptomatic intracerebral haemorrhage, and clinical outcome at 3 months. We believe that in carefully selected individuals in appropriate centres of expertise, intra-arterial thrombolytic therapy holds great promise.     

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.     

Acute stroke therapy: A review

This review summarizes the modern early diagnosis and acute phase treatment of acute stroke. The guidelines for treatment of acute ischemic stroke underwent major changes in 2015 and endovascular therapy (catheter-based mechanical thrombectomy with a stent retriever) became the class IA indication for patients presenting within less than 6 h from symptom onset who have proven occlusion of large intracerebral artery in anterior circulation. Acute stroke care organization should enable to perform effective revascularization therapy as soon as possible after the initial brain imaging whenever this examination provides indication for the procedure.     

Efficacy and safety of mechanical thrombectomy for cardioembolic stroke: A protocol for systematic review and meta-analysis

Background:Several randomized clinical trials have demonstrated the safety and efficiency of mechanical thrombectomy in the management of acute ischaemic stroke caused by larger vessel occlusion. According to the trial of Org 10172 in Acute Stroke Treatment (TOAST) classification, acute ischaemic stroke can be divided into cardioembolic stroke and non-cardioembolic stroke. Previous studies have shown that mechanical thrombectomy in cardioembolic stroke with intracranial large artery occlusion has a poor prognosis. The reason may be that the old emboli are hard, making it difficult to remove. However, recent evidence shows that mechanical thrombectomy is also effective and safe in patients with cardioembolic stroke. Therefore, the aim of this study is to evaluate the efficacy and safety of mechanical thrombectomy for cardioembolic stroke.Methods:The electronic database, including PubMed, Cochrane Library, EMBASE, the China National Knowledge Infrastructure (CNKI), China Biology Medicine disc (CBM), VIP database, and Wan-fang database, were thoroughly retrieved from inception to December 1, 2021, without language restrictions. All randomized controlled trials that evaluated the efficacy and safety of mechanical thrombectomy in the treatment of cardioembolic stroke will be included. Primary outcomes will include vascular recanalization rate and score scale. Two authors will independently scan the articles searched, extract the data from articles included, and assess the risk of bias by Cochrane tool of risk of bias. Disagreements will be resolved by discussion among authors. All analysis will be performed based on the Cochrane Handbook for Systematic Reviews of Interventions. Dichotomous variables will be reported as risk ratio or odds ratio with 95% confidence intervals and continuous variables will be summarized as mean difference or standard mean difference with 95% confidence intervals.Results:This review will be to assess the efficacy and safety of mechanical thrombectomy for cardioembolic stroke.Conclusions:The results of our findings may be helpful for clinicians and health professionals to re-examine the clinical decision-making in the treatment of cardioembolic stroke, promising way for treatment of patients with cardioembolic stroke.Systematic review registration number:INPLASY2020120035     

Stroke intervention: catheter-based therapy for acute ischemic stroke

The majority (>80%) of the three-quarters of a million strokes that will occur in the United States this year are ischemic in nature. The treatment of acute ischemic stroke is very similar to acute myocardial infarction, which requires timely reperfusion therapy for optimal results. The majority of patients with acute ischemic stroke do not receive any form of reperfusion therapy, unlike patients with acute myocardial infarction. Improving outcomes for acute stroke will require patient education to encourage early presentation, an aggressive expansion of qualified hospitals, and willing providers and early imaging strategies to match patients with their best options for reperfusion therapy to minimize complications.     

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。     

Acute stroke intervention for acute embolic procedural strokes performed by cardiologists

Acute ischemic stroke is a feared complication during cardiovascular procedures associated with high morbidity and mortality if not immediately recognized and treated. We conducted a review of cases at our center where patients experienced an acute, procedure-related ischemic stroke and underwent immediate endovascular stroke treatment by the interventional cardiologists trained in acute endovascular stroke intervention. Baseline demographics, procedural and follow-up data were collected. Three patients were identified in whom the percutaneous procedure (peripheral arterial intervention, transapical NeoChord [NeoChord Inc, Minnesota, USA] implantation and transcatheter aortic valve implantation, respectively) was complicated by an acute embolic ischemic stroke. In all cases, cerebral vessel re-canalization was technically successful with thrombolysis in cerebral infarction (TICI) IIB/III flow. Follow-up computed tomography scans showed no infarct demarcation, oedema or intracranial hemorrhage. One patient survived with no neurological symptoms at 6-month follow-up whereas the two other patients died of unrelated intensive care complications and decompensated heart failure. We conclude that endovascular stroke treatment during cardiovascular interventions can be performed by interventional cardiologists with appropriate training. It offers the unique opportunity to treat cerebral embolization in a time-efficient manner, potentially improving morbidity and mortality of affected patients.     

Periprocedural antithrombotic medication in acute ischemic stroke treated by catheter-based thrombectomy. A review

This review summarized limited information known about periprocedural antithrombotic therapy before, during and immediately after percutaneous catheter-based thrombectomy for acute ischemic stroke. Very few data on this topic were published so far. In general, rtPA should be used upfront whenever clinically clearly indicated (0–3 h from stroke onset, absence of contraindications) irrespective of subsequent mechanical thrombectomy. If mechanical treatment follows after thrombolysis, neither anticoagulation, nor antiplatelet agents should be used in the acute phase. No data exist about the periprocedural use of anticoagulation or antiplatelet therapy in patients who cannot receive fibrinolysis and undergo direct mechanical thrombectomy alone. Most centers use no or very low dose heparin and a single dose of aspirin.     

The age factor influencing long-term physical functionality in stroke patients undergoing intra-arterial thrombectomy treatment

The treatment of acute ischemic stroke is heavily time-dependent, and even though, with the most efficient treatment, the long-term functional outcome is still highly variable. In this current study, the authors selected acute ischemic stroke patients who were qualified for intravenous thrombolysis with recombinant tissue plasminogen activator and followed by intra-arterial thrombectomy. With primary outcome defined by the functional level in a 1-year follow-up, we hypothesize that patients with older age are at a disadvantage in post-stroke recovery. However, an age-threshold should be determined to help clinicians in selection of patients to undergo such therapy. This is a retrospective chart review study that include 92 stroke patients in Changhua Christian hospital with a total of 68 evaluation indexes recorded. The current study utilized the forward stepwise regression model whose Adj-R² and P value in search of important variables for outcome prediction. The chngpt package in R indicated the threshold point of the age factor directing the better future functionality of the stroke patients. Datasets revealed the threshold of the age set at 79 the most appropriate. Admission Barthel Index, Age, ipsilateral internal carotid artery resistance index (ICA RI), ipsilateral vertebral artery (VA) PI, contralateral middle cerebral artery (MCA) stenosis, contralateral external carotid artery (ECA) RI, and in-hospital pneumonia are the significant predicting variables. The higher the age, in-hospital pneumonia, contralateral MCA stenosis, ipsilateral ICA RI and ipsilateral VA PI, the less likely patient to recover from functional deficits as the result of acute ischemic stroke; the higher the value of contralateral ECA RI and admission Barthel Index, the better chance to full functional recovery at 1-year follow up. Parameters of pre-intervention datasets could provide important information to aid first-line clinicians in decision making. Especially, in patients whose age is above 79 receives diminish return in the benefit to undergo such intervention and should be considered seriously by both the patients and the physicians.     

动静脉联合溶栓治疗急性缺血性卒中的临床研究

目的探讨动静脉联合溶栓治疗急性缺血性卒中的临床疗效及安全性。方法将65例发病在6h内的急性缺血性卒中患者随机分为两组:超选择性动脉溶栓 静脉溶栓组(联合组)共35例;超选择性动脉溶栓组(动脉组),30例。动脉组用微导管超选择病变动脉,尿激酶用量50万~150万U。联合组先静脉滴注尿激酶0.5万~1.0万U/kg,再动脉给尿激酶,总量不超过150万U。术前及术后6h、24h、7d、30d、90d采用欧洲卒中量表(ESS)评价神经功能缺损情况。结果治疗24h、30d后ESS评分联合组为83±24、88±26;动脉组为77±29、81±24。治疗后总再通率:联合组为42.8%,动脉组为33.3%,两组比较差异有显著性(P<0.05)。结论起病6h内,动静脉联合溶栓与动脉溶栓治疗相比,总再通率增加。     

A decision analysis of thrombolytic therapy compared with standard therapy in acute ischaemic stroke

OBJECTIVES: Experts draw different conclusions on whether thrombolysis can be recommended or not for acute ischaemic stroke. A major problem is weighing the improvement in functional ability against the risk of increased mortality. We wanted to examine this uncertainty regarding thrombolysis using a systematic approach and with a strong emphasis on the patient's point of view. METHODS: We performed a decision analysis where the base case focused on an average stroke patient. We used published probabilities for different functional outcomes after standard supportive care and after adding tissue plasminogen activator (tPA), and we tried to estimate corresponding long-term survival. We interviewed 158 subjects with the standard gamble method to elicit their preference values (utility) for these outcomes. RESULTS: When using the baseline data for an average stroke patient, thrombolysis with tPA was the better choice, with 48 extra quality-adjusted living days; tPA was also superior in 117 individual decision analyses, giving from 10 to 173 extra days. However, sensitivity analysis showed that these results were highly susceptible to changes in utility for major disability, probability of early death, and long-term survival after thrombolysis. To increase the gain as well as the margin of safety regarding the treatment choice, thrombolysis should be restricted to patients who assign low utility values < 0.6-0.7 to major poststroke disability (death = 0.0, good health = 1.0). CONCLUSION: Evaluated by decision analysis, thrombolysis with tPA is on average superior to standard therapy for the few patients fulfilling the strict medical inclusion criteria. Individual incorporation of the patient's point of view narrows the indication even further.     

Nationwide temporal trend analysis of reperfusion therapy utilization and mortality in acute ischemic stroke patients in Japan

This study aimed to elucidate nationwide trends in reperfusion therapy utilization and subsequent 30-day mortality in acute ischemic stroke patients in Japan. The analysis focused on intravenous recombinant tissue plasminogen activator (IV rt-PA) and endovascular thrombectomy (EVT).Using health insurance claims data, we calculated the age- and sex-adjusted monthly number of acute ischemic stroke patients who received IV rt-PA and/or EVT in Japan from April 2010 to March 2016, and investigated the 30-day all-cause mortality rates after undergoing these therapies. Through an interrupted time-series analysis, we examined the

• (1)trends prior to extension of the IV rt-PA therapeutic time window from 3 hours to 4.5 hours in September 2012,
• (2)changes that occurred immediately after the extension, and
• (3)differences in trends between the pre- and post-extension periods.

During the study period, 69,920 patients with acute ischemic stroke (mean age ± standard deviation: 74.9 ± 12.0 years; 41.4% women) received IV rt-PA and/or EVT. The age- and sex-adjusted number of patients receiving IV rt-PA monotherapy increased immediately after the time window extension (<rk-italic > P < .001), but did not change during the pre- (P = .90) and post-extension (P = .58) periods. In contrast, the number of patients receiving EVT with or without IV rt-PA continuously increased during the pre-extension period (P < .001), and further increased during the post-extension period (P <.001); however, this number decreased immediately after the extension (P < .001). There were no significant changes in 30-day all-cause mortality during the pre- (P = .40) and post-extension (P = .64) periods, as well as immediately after the extension (P = .53).The extension of the IV rt-PA therapeutic time window and progressively widespread use of EVT in Japan have increased the number of acute ischemic stroke patients eligible for reperfusion therapy. These trends were not accompanied by a higher risk of post-reperfusion mortality.     

Blood biomarkers in cardioembolic stroke

One promising field in neurovascular diseases investigation is the use of biomarkers to guide stroke etiology diagnosis and classification. Since treatment differs among etiologic subtypes and nowadays many patients receive a diagnosis of undetermined stroke, biomarkers might become an important additional diagnostic tool. In this review we update current knowledge about biomarkers related with cardioembolic stroke etiology (such as BNP and D-dimer proteins, or PITX2 and ZFHX3 genes), that in the future, might allow rapidly guiding other diagnostic tests and accelerating the onset of an optimal secondary prevention.     

急性脑梗死超早期的r-tPA溶栓治疗

目的　探讨重组组织型纤溶酶原激活物 (r- t PA)溶栓治疗发病 6h内脑梗死的疗效及并发症。方法　共收集本院 2 0 0 1～ 2 0 0 3年 43例溶栓治疗的急性脑梗死病例 ,其中 32例经静脉溶栓 ,1 1例经动脉溶栓。分别对两组病例进行溶栓前后的 NIHSS,ESS及 ADL量表评分 ,根据 3个月时的随访记录判断溶栓疗效 (分为治愈、显效、有效、无效 )。结果　静脉溶栓组和动脉溶栓组的总有效率分别为 79.3%、90 .9% ;治愈率分别为2 7.6%、45.5% ,溶栓后脑出血率分别为 1 0 .3%、1 8.2 % ,但由于动脉组例数较少 ,两组疗效差异无统计学意义。结论　 6 h内溶栓治疗是安全有效的 ,低 NIHSS的患者有较好转归。     

急性缺血性卒中患者尿激酶动脉溶栓治疗的临床观察

目的:评价尿激酶选择性动脉溶栓治疗急性脑梗死的疗效和安全性.方法:38例急性脑梗死患者在发病后6 h内进行尿激酶选择性动脉溶栓治疗,术后即刻和24 h分别行头颅CT检查了解有无颅内出血.采用Barthel指数(BI)和美国国立卫生研究院卒中量表(NIHSS)评分对患者6个月时的生活状态和功能转归进行评价.结果:38例患者中,21例完全再通,8例部分再通,3例发生有症状颅内出血,1例死亡.术后90 d时,22例功能转归良好(BI≥90分),11例较好(50分≤BI＜90分),4例较差(BI＜50分);术后6个月时,24例功能转归良好,9例较好,4例较差.术后14 d时的NIHSS评分显著优于术前水平(12.68±7.43对15.38±4.32,P＜0.01).结论:尿激酶动脉溶栓能使闭塞血管再通,改善患者急性期临床症状和远期预后.     

Reperfusion Therapies for Acute Ischemic Stroke: An Update

Acute ischemic stroke is a major cause of morbidity and mortality in developed countries. Intravenous thrombolysis with tissue plasminogen activator (tPA) within 4.5 hours of symptoms onset significantly improves clinical outcomes in patients with acute ischemic stroke. This narrow window for treatment leads to a small proportion of eligible patients to be treated. Intravenous or intra-arterial trials, combined intravenous/intra-arterial trials, and newer devices to mechanically remove the clot from intracranial arteries have been investigated or are currently being explored to increase patient eligibility and to improve arterial recanalization and clinical outcome. New retrievable stent-based devices offer higher revascularization rates with shorter time to recanalization and are now generally preferred to first generation thrombectomy devices such as Merci Retriever or Penumbra System. These devices have been shown to be effective for opening up occluded vessels in the brain but its efficacy for improving outcomes in patients with acute stroke has not yet been demonstrated in a randomized clinical trial. We summarize the results of the major systemic thrombolytic trials and the latest trials employing different endovascular approaches to ischemic stroke.     

Combined pharmacomechanical thrombectomy for acute inferior vena cava filter thrombosis

Inferior vena cava (IVC) filter thrombosis has been reported to occur in up to 30% of cases and is associated with significant morbidity. The optimal treatment of IVC thrombosis has not been established to date. We report a case of IVC filter thrombosis with associated vena caval obstruction successfully treated with catheter-directed thrombolysis and adjunctive mechanical thrombectomy.     

急性缺血性卒中的动脉内溶栓治疗

近年来,多中心研究证实动脉内溶栓是治疗急性脑梗死的有效方法。文章对动脉内溶栓治疗的时间窗、治疗前评价、病例和药物选择等研究现状做了综述。