Project description:Intracranial hemorrhage is one of the most feared complications following brain infarct. Ischemic tissues have a natural tendency to bleed. Moreover, the first recanalization trials using intravenous thrombolysis have shown an increase in mild to severe intracranial hemorrhage. Symptomatic intracerebral hemorrhage is strongly associated with poor outcomes and is an important factor in recanalization decisions. Stroke physicians have to weigh the potential benefit of recanalization therapies, first, with different risks of intracranial hemorrhage described in randomized controlled trials, and second with numerous risk markers that have been found to be associated with intracranial hemorrhage in retrospective series. These decisions have become quite complex with different intravenous thrombolytics and mechanical thrombectomy. This review aims to outline some elements of the pathophysiological mechanisms and classifications, describe most of the risk factors identified for each reperfusion therapy, and finally suggest future research directions that could help physicians dealing with these complications.
Project description: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.
Project description:Following the success of recent endovascular trials, endovascular therapy has emerged as an exciting addition to the arsenal of clinical management of patients with acute ischemic stroke (AIS). In this paper, we present an extensive overview of intravenous and endovascular reperfusion strategies, recent advances in AIS neurointervention, limitations of various treatment paradigms, and provide insights on imaging-guided reperfusion therapies. A roadmap for imaging guided reperfusion treatment workflow in AIS is also proposed. Both systemic thrombolysis and endovascular treatment have been incorporated into the standard of care in stroke therapy. Further research on advanced imaging-based approaches to select appropriate patients, may widen the time-window for patient selection and would contribute immensely to early thrombolytic strategies, better recanalization rates, and improved clinical outcomes.
Project description:Background: Thrombolysis, with or without thrombectomy, for acute ischaemic stroke is associated with an increased risk of intracranial bleeding. We assessed whether treatment with glyceryl trinitrate (GTN), a nitric oxide donor, may influence the associated bleeding risk. Methods: We searched for completed randomized controlled trials of GTN vs. no GTN in acute ischaemic stroke with data on reperfusion treatments (thrombolysis and/or thrombectomy). The primary efficacy outcome was functional status as assessed by the modified Rankin Scale (mRS) at day 90; the primary safety outcome was intracranial bleeding. Secondary safety outcomes included symptomatic intracranial hemorrhage and haemorrhagic transformation of infarction. Individual patient data were pooled and meta-analysis performed using ordinal or binary logistic regression with adjustment for trial and prognostic variables both overall and in those randomized within 6 h of symptom onset. Results: Three trials met the eligibility criteria. Of 715 patients with ischaemic stroke who underwent thrombolysis (709, >99%) or thrombectomy (24, 3.4%), 357 (49.9%) received GTN and 358 (50.1%) received no GTN. Overall, there was no difference in the distribution of the mRS at day 90 between GTN vs. no GTN (OR 0.94, 95% CI 0.72-1.23; p = 0.65); similarly, there was no difference in intracranial hemorrhage rates between treatment groups (OR 0.90, 95% CI 0.43-1.89; p = 0.77). In those randomized to GTN vs. no GTN within 6 h of symptom onset, there were numerically fewer bleeding events, but these analyses did not reach statistical significance. Conclusions: In ischaemic stroke patients treated predominantly with thrombolysis, transdermal GTN was safe, but did not influence functional outcome at 90 days.
Project description:We investigated the relationship between the mean blood pressure (BP) at 24-72 h and the clinical outcomes after acute ischemic stroke (AIS) in patients treated with reperfusion therapy. The primary outcome was measured using the modified Rankin Scale (mRS) at 3 months after AIS, and was based on the mean systolic BP at 24-72 h post-AIS. Favorable outcome was defined as mRS scores of 0-2. A total of 1,540 patients treated with reperfusion therapy were enrolled in the study. Favorable outcomes occurred more frequently in patients with BP ≤ 130/80 mmHg, and the risks of symptomatic intracranial hemorrhage and early neurological deterioration were lower in this optimal BP group. Multivariable analysis showed a significant association between mean BP ≤ 130/80 mmHg at 24-72 h and favorable outcomes at 3 months after AIS (odds ratio 2.95, 95% confidence interval 2.32-3.77, p < 0.001). Prespecified subgroup analyses showed that BP ≤ 130/80 mmHg had a more significant impact on clinical outcome in patients with recanalization than in those without recanalization. These data indicate that a mean BP of ≤ 130/80 mmHg at 24-72 h post-AIS is independently associated with favorable outcomes in patients treated with reperfusion therapy, particularly in those with recanalization.
Project description:Background and purposeControversy exists about the role of perfusion imaging in patient selection for endovascular reperfusion therapy in acute ischemic stroke. We hypothesized that perfusion imaging versus noncontrast CT- based selection would be associated with improved functional outcomes at 3 months.Materials and methodsWe reviewed consecutive patients with anterior circulation strokes treated with endovascular reperfusion therapy within 8 hours and with baseline NIHSS score of ≥8. Baseline clinical data, selection mode (perfusion versus NCCT), angiographic data, complications, and modified Rankin Scale score at 3 months were collected. Using multivariable logistic regression, we assessed whether the mode of selection for endovascular reperfusion therapy (perfusion-based versus NCCT-based) was independently associated with good outcome.ResultsTwo-hundred fourteen patients (mean age, 67.2 years; median NIHSS score, 18; MCA occlusion 74% and ICA occlusion 26%) were included. Perfusion imaging was used in 76 (35.5%) patients (39 CT and 37 MR imaging). Perfusion imaging-selected patients were more likely to have good outcomes compared with NCCT-selected patients (55.3 versus 33.3%, P = .002); perfusion selection by CT was associated with similar outcomes as that by MR imaging (CTP, 56.; MR perfusion, 54.1%; P = .836). In multivariable analysis, CT or MR perfusion imaging selection remained strongly associated with good outcome (adjusted OR, 2.34; 95% CI, 1.22-4.47), independent of baseline severity and reperfusion.ConclusionsIn this multicenter study, patients with acute ischemic stroke who underwent perfusion imaging were more than 2-fold more likely to have good outcomes following endovascular reperfusion therapy. Randomized studies should compare perfusion imaging with NCCT imaging for patient selection for endovascular reperfusion therapy.
Project description:BackgroundThe interplay between collateral status and stroke aetiology may be crucial in the evaluation and management of acute ischemic stroke (AIS). Our understanding of this relationship and its level of association remains sub-optimal. This study sought to examine the association of pre-intervention collateral status with stroke aetiology, specifically large artery atherosclerosis (LAA) and cardio-embolism (CE), in AIS patients receiving reperfusion therapy, by performing a meta-analysis.MethodsRelevant search terms were explored on Medline/PubMed, Embase and Cochrane databases. Studies were included using the following inclusion criteria: (a) patients aged 18 or above; (b) AIS patients; (c) patients receiving reperfusion therapy; (d) total cohort size of >20, and (e) qualitative or quantitative assessment of pre-intervention collateral status on imaging using a grading scale. Random-effects meta-analysis was performed to investigate the association of aetiology with pre-intervention collateral status, and forest plots of risk ratio (RR) were generated.ResultsA meta-analysis was conducted on seven studies, with a cumulative cohort of 1235 patients, to assess the association of pre-intervention collateral status with stroke aetiology. Patients with LAA were associated significantly with an increased rate of good collaterals (RR 1.24; 95% CI 1.04-1.50; p = 0.020, z = 2.33). Contrarily, CE aetiology was associated significantly with a decreased rate of good collaterals (RR 0.83; 95% CI 0.71-0.98; p = 0.027, z = -2.213).ConclusionsThis study demonstrates that, in AIS patients receiving reperfusion therapy, LAA and CE aetiologies are associated significantly with collateral status.
Project description:BackgroundThere are limited data on the safety of intravenous recombinant tissue plasminogen activator (rtPA) for treating acute ischemic stroke in patients with gastrointestinal malignancy or recent gastrointestinal bleeding within 21?days of their index stroke.AimsTo evaluate clinical outcomes in patients treated with rtPA for acute ischemic stroke who had gastrointestinal malignancy or recent gastrointestinal bleeding.MethodsWe identified patients who were treated with rtPA for acute ischemic stroke between 2/2009 and 12/2015 from the Get With The Guidelines-Stroke linked to Medicare claims data. Gastrointestinal malignancy and recent gastrointestinal bleeding were defined as any gastrointestinal malignancy hospitalisation within one?year prior to acute ischemic stroke and gastrointestinal bleeding hospitalisation within 21?days prior to acute ischemic stroke, respectively. Outcomes of interest included in-hospital mortality and bleeding complications.ResultsAmong 40,396 patients aged 65?years or older treated with rtPA for acute ischemic stroke from 1522 sites (mean age [SD] 81.0 [8.1] years; 41.9% women), 136 (0.3%) had gastrointestinal malignancy (n?=?96) or recent gastrointestinal bleeding (n?=?43). Patients with gastrointestinal malignancy or bleeding had more severe stroke than those without (median NIHSS [interquartile range]: 14.0 [8.0-19.0] vs. 11.0 [6.0-18.0]). The rates of in-hospital mortality and life-threatening systemic haemorrhage were not significantly different between those with and without gastrointestinal malignancy or bleeding (mortality: 10.3% vs. 9.0%, adjusted odds ratio [aOR] 1.01, 95%CI 0.58-1.75; bleeding: 2.3% vs. 1.2%, aOR 1.72, 95%CI 0.58-5.11).ConclusionsIn this observational cohort, we did not find increased risk of in-hospital mortality and bleeding in rtPA-treated patients with gastrointestinal malignancy or recent gastrointestinal bleeding.
Project description: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.