Mechanical thrombectomy (MT) has become the cornerstone of acute ischemic stroke management in patients with large vessel occlusion (LVO). The aim of this guideline document is to assist physicians ...in their clinical decisions with regard to MT.
These guidelines were developed based on the standard operating procedure of the European Stroke Organisation, and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. An interdisciplinary working group identified 15 relevant questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and wrote evidence based recommendations. Expert opinion was provided if not enough evidence was available to provide recommendations based on the GRADE approach.
We found high quality evidence to recommend MT plus best medical management (BMM, including intravenous thrombolysis whenever indicated) to improve functional outcome in patients with LVO related acute ischemic stroke within 6 hours after symptom onset. We found moderate quality of evidence to recommend MT plus BMM in the 6-24 hour time window in patients meeting the eligibility criteria of published randomized trials. These guidelines further detail aspects of prehospital management, patient selection based on clinical and imaging characteristics, and treatment modalities.
MT is the standard of care in patients with LVO related acute stroke. Appropriate patient selection and timely reperfusion are crucial. Further randomized trials are needed to inform clinical decision making with regard to the mothership and drip-and-ship approaches, anesthaesia modalities during MT, and to determine whether MT is beneficial in patients with low stroke severity or large infarct volume.
Background
Mechanical thrombectomy (MT) has become the cornerstone of acute ischaemic stroke management in patients with large vessel occlusion (LVO). The aim of this guideline document is to assist ...physicians in their clinical decisions with regard to MT.
Methods
These Guidelines were developed based on the standard operating procedure of the European Stroke Organisation and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. An interdisciplinary working group identified 15 relevant questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and wrote evidence based recommendations. Expert opinion was provided if not enough evidence was available to provide recommendations based on the GRADE approach.
Results
We found high quality evidence to recommend MT plus best medical management (BMM, including intravenous thrombolysis whenever indicated) to improve functional outcome in patients with LVO-related acute ischaemic stroke within 6 hours after symptom onset. We found moderate quality of evidence to recommend MT plus BMM in the 6-24h time window in patients meeting the eligibility criteria of published randomized trials. These guidelines further detail aspects of prehospital management, patient selection based on clinical and imaging characteristics, and treatment modalities.
Conclusions
MT is the standard of care in patients with LVO-related acute stroke. Appropriate patient selection and timely reperfusion are crucial. Further randomized trials are needed to inform clinical decision making with regard to the mothership and drip-and-ship approaches, anesthaesia modalities during MT, and to determine whether MT is beneficial in patients with low stroke severity or large infarct volume.
Reperfusion therapies are the mainstay of acute ischemic stroke (AIS) treatments and overall improve functional outcome. Among the established complications of intravenous (IV) tissue-type ...plasminogen activator (tPA), intracranial hemorrhage (ICH) is by far the most feared and has been extensively described by seminal works over the last two decades. Indeed, IV tPA is associated with increased odds of any ICH and symptomatic ICH responsible for increased mortality rate during the first week after an AIS. Despite these results, IV tPA has been found beneficial in several pioneering randomized trials and improves functional outcome at 3 months. Endovascular therapy (EVT) combined with IV tPA for AIS patients consecutive to an anterior circulation large-vessel occlusion does not increase ICH occurrence. Of note, EVT following IV tPA leads to significantly higher rates of early reperfusion than with IV tPA alone, with no difference in ICH, which challenges the paradigm of reperfusion as a major prognostic factor for ICH complications. However, several blood biomarkers (glycemia, platelet and neutrophil count), clinical factors (age, AIS severity, blood pressure management, diabetes mellitus), and neuroradiological factors (cerebral microbleeds, infarct size) have been identified as risk factors for ICH after reperfusion therapy. In the years to come, the ultimate goal will be to further improve either reperfusion rates and functional outcome, while reducing hemorrhagic complications. To this end, various approaches being investigated are discussed in this review, such as blood-pressure control after reperfusion or the use of new antiplatelet agents as an adjunct to IV tPA and exhibit reduced hemorrhagic potential during the early phase of AIS.
Neutrophil Extracellular Traps (NETs) are DNA extracellular networks decorated with histones and granular proteins produced by activated neutrophils. NETs have been identified as major triggers and ...structural factors of thrombosis. A recent study designated extracellular DNA threads from NETs as a potential therapeutic target for improving tissue-type plasminogen activator (tPA)-induced thrombolysis in acute coronary syndrome. The aim of this study was to assess the presence of NETs in thrombi retrieved during endovascular therapy in patients with acute ischemic stroke (AIS) and their impact on tPA-induced thrombolysis.
We analyzed thrombi from 108 AIS patients treated with endovascular therapy. Thrombi were characterized by hematoxylin/eosin staining, immunostaining, and ex vivo enzymatic assay. Additionally, we assessed ex vivo the impact of deoxyribonuclease 1 (DNAse 1) on thrombolysis of AIS thrombi.
Histological analysis revealed that NETs contributed to the composition of all AIS thrombi especially in their outer layers. Quantitative measurement of thrombus NETs content was not associated with clinical outcome or AIS pathogenesis but correlated significantly with endovascular therapy procedure length and device number of passes. Ex vivo, recombinant DNAse 1 accelerated tPA-induced thrombolysis, whereas DNAse 1 alone was ineffective.
This study suggests that thrombus NETs content may be responsible for reperfusion resistance, including mechanical or pharmacological approaches with intravenous tPA, irrespectively of their etiology. The efficacy of a strategy involving an administration of DNAse 1 in addition to tPA should be explored in the setting of AIS.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT02907736.
Modern endovascular thrombectomy (MET), using stent retrievers or large-bore distal aspiration catheters in stroke patients with acute basilar artery occlusion (BAO), is routinely performed to date. ...However, more than 35% of BAO patients treated with MET die within 90 days despite high recanalization rates. The purpose of this study is to investigate the parameters associated with 90-day mortality in patients with BAO after MET.
We analyzed 117 consecutive BAO patients included in the Endovascular Treatment in Ischemic Stroke prospective clinical registry of consecutive acute ischemic stroke patients treated with MET (60 patients 51.3% treated with a stent retriever as first-line technique) between March 2010 and April 2017. Successful recanalization was defined as modified thrombolysis In cerebral infarction scores 2b-3 at the end of MET, and mortality was defined as modified Rankin Scale 6 at 90 days. Associations of baseline characteristics (patient and treatment characteristics) and intermediate outcomes (recanalization, complications) with 90-day mortality were investigated in univariate and multivariate analyses.
Overall successful recanalization rate was 79.5, and 41.9% (95% CI 32.8-51.0%) of patients died within 90 days after MET. Patients with successful recanalization had a lower mortality rate (32.9 vs. 74.4%; p < 0.001). Failure of successful recanalization was an independent predictor of mortality (OR 5.1; 95% CI 1.34-19.33). In multivariate analysis, age ≥60 years (OR 6.37; 95% CI 1.74-23.31), admission National Institute of Health Stroke Scale (NIHSS) ≥13 (OR 4.62; 95% CI 1.42-15.03), lower posterior circulation-Alberta Stroke Program Early CT Score (pc-ASPECTS; OR 1.71; 95% CI 1.19-2.44), use of antithrombotic medication prior to stroke onset (OR 3.38; 95% CI 1.03-11.08), absence of intravenous thrombolysis (OR 3.36; 95% CI 1.12-10.03), and angioplasty/stenting of the basilar artery (OR 4.71; 95% CI 1.34-16.54) were independent predictors for mortality after MET.
Failure of successful recanalization was a strong predictor for mortality. In the setting of recanalization, age, admission NIHSS, pc-ASPECTS, absence of intravenous thrombolysis, and angioplasty/stenting of the basilar artery were also independent predictors for mortality after MET of BAO patients.
Endovascular therapy is increasingly used after the administration of intravenous tissue plasminogen activator (t-PA) for patients with moderate-to-severe acute ischemic stroke, but whether a ...combined approach is more effective than intravenous t-PA alone is uncertain.
We randomly assigned eligible patients who had received intravenous t-PA within 3 hours after symptom onset to receive additional endovascular therapy or intravenous t-PA alone, in a 2:1 ratio. The primary outcome measure was a modified Rankin scale score of 2 or less (indicating functional independence) at 90 days (scores range from 0 to 6, with higher scores indicating greater disability).
The study was stopped early because of futility after 656 participants had undergone randomization (434 patients to endovascular therapy and 222 to intravenous t-PA alone). The proportion of participants with a modified Rankin score of 2 or less at 90 days did not differ significantly according to treatment (40.8% with endovascular therapy and 38.7% with intravenous t-PA; absolute adjusted difference, 1.5 percentage points; 95% confidence interval CI, -6.1 to 9.1, with adjustment for the National Institutes of Health Stroke Scale NIHSS score 8-19, indicating moderately severe stroke, or ≥20, indicating severe stroke), nor were there significant differences for the predefined subgroups of patients with an NIHSS score of 20 or higher (6.8 percentage points; 95% CI, -4.4 to 18.1) and those with a score of 19 or lower (-1.0 percentage point; 95% CI, -10.8 to 8.8). Findings in the endovascular-therapy and intravenous t-PA groups were similar for mortality at 90 days (19.1% and 21.6%, respectively; P=0.52) and the proportion of patients with symptomatic intracerebral hemorrhage within 30 hours after initiation of t-PA (6.2% and 5.9%, respectively; P=0.83).
The trial showed similar safety outcomes and no significant difference in functional independence with endovascular therapy after intravenous t-PA, as compared with intravenous t-PA alone. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT00359424.).
Downstream microvascular thrombosis (DMT) is known to be a contributing factor to incomplete reperfusion in acute ischemic stroke. The aim of this study was to determine the timing of DMT with ...intravital imaging and to test the hypothesis that intravenous alteplase infusion could reduce DMT in a transient middle cerebral artery occlusion (MCAO) rat stroke model.
Rats were subjected to 60-minute transient MCAO. Alteplase (10 mg/kg) was administered 30 minutes after the beginning of MCAO. Real-time intravital fluorescence microscopy through a dura-sparing craniotomy was used to visualize circulating blood cells and fibrinogen. Cerebral microvessel patency was quantitatively evaluated by fluorescein isothiocyanate-dextran perfusion.
Immediately after MCAO, platelet and leukocyte accumulation were observed mostly in the venous compartment. Within 30 minutes after MCAO, microthrombi and parietal fibrin deposits were detected in postcapillary microvessels. Alteplase treatment significantly (P=0.006) reduced infarct volume and increased the percentage of perfused vessels during MCAO (P=0.02) compared with saline. Plasma levels of fibrinogen from alteplase-treated rats showed a rapid and profound hypofibrinogenemia. In vitro platelet aggregation demonstrated that alteplase reduced platelet aggregation (P=0.0001) and facilitated platelet disaggregation (P=0.001). These effects were reversible in the presence of exogenous fibrinogen.
Our data demonstrate that DMT is an early phenomenon initiated before recanalization. We further show that alteplase-dependent maintenance of downstream perfusion during MCAO improves acute ischemic stroke outcome through a fibrinogen-dependent platelet aggregation reduction. Our results indicate that early targeting of DMT represents a therapeutic strategy to improve the benefit of large artery recanalization in acute ischemic stroke.
In The Lancet Neurology, Noor Samuels and colleagues2 report the findings of a post-hoc analysis of pooled individual patient data from seven randomised controlled trials comparing standard treatment ...versus endovascular therapy in patients with ischaemic stroke, to assess the effect of admission systolic blood pressure (SBP) on functional outcome. Of note, a spontaneous drop in SBP after successful endovascular therapy is a consistent predictor of neurological recovery.9 A one-size-fits-all approach for blood pressure management (ie, one SBP target for all patients with ischaemic stroke and large vessel occlusion) seems not to be the best option to improve functional outcome. For the time being, and until better evidence becomes available, guidelines recommend to avoid blood pressure drops and to target blood pressure levels below 180/105 mm Hg in patients with acute ischaemic stroke and large vessel occlusion undergoing endovascular therapy.10 I declare no competing interests.
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