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During the last decade, significant progress has been made in understanding thrombus composition and organization in the setting of acute ischemic stroke (AIS). In particular, thrombus organization is now described as highly heterogeneous but with 2 preserved characteristics: the presence of (1) two distinct main types of areas in the core—red blood cell (RBC)-rich and platelet-rich areas in variable proportions in each thrombus—and (2) an external shell surrounding the core composed exclusively of platelet-rich areas. In contrast to RBC-rich areas, platelet-rich areas are highly complex and are mainly responsible for the thrombolysis resistance of these thrombi for the following reasons: the presence of platelet-derived fibrinolysis inhibitors in large amounts, modifications of the fibrin network structure resistant to the tissue plasminogen activator (tPA)-induced fibrinolysis, and the presence of non-fibrin extracellular components, such as von Willebrand factor (vWF) multimers and neutrophil extracellular traps. From these studies, new therapeutic avenues are in development to increase the fibrinolytic efficacy of intravenous (IV) tPA-based therapy or to target non-fibrin thrombus components, such as platelet aggregates, vWF multimers, or the extracellular DNA network.

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.

Background and Purpose: Optimal blood pressure (BP) targets after endovascular therapy (EVT) for acute ischemic stroke (AIS) still need to be assessed, especially according to the recanalization status. Facing the lack of randomized controlled trials addressing this question, we performed a systematic review of studies assessing the post-EVT BP impact on functional outcome and symptomatic intracranial hemorrhage (sICH).Methods: Studies published after January 1, 2012 were included in the systematic review. The PRISMA checklist and flow diagram were followed for the design and reporting of this work.Results: Five studies were included in the present analysis. Despite a significant heterogeneity among studies which precluded a meta-analysis, systolic BP (SBP) was the most frequently used parameter to describe BP. BP variability (standard deviation, successive variability) after EVT was associated with worse functional outcome, especially in studies without specific BP targets after successful EVT. Lower BP values after successful EVT were associated with lower odds of sICH. Four studies evaluated the post-EVT BP impact on recanalized patients solely, with only one specifically addressing the impact of a TICI 2B vs. 2C. Interestingly, SBP reduction was inversely associated with worse outcomes in TICI 3 patients but not in TICI 2B patients, pointing to the potential value of BP management according to the exact TICI.Conclusions: BP post-EVT seems to be associated with worse functional outcomes and sICH. However, given the important heterogeneity depicted among the included studies, no decisive conclusion can be made from this systematic review, thus underlying the urgent need of randomized controlled trials evaluating this question.

More than 40% of endovascular therapy (EVT) fail to achieve complete reperfusion of the territory of the occluded artery in patients with acute ischemic stroke (AIS). Understanding factors influencing EVT could help overcome its limitations. Our objective was to study the impact of thrombus cell composition on EVT procedures, using a simulation system for modeling thrombus-induced large vessel occlusion (LVO) in flow conditions. In an open comparative trial, we analyzed the behavior of size-standardized platelet-rich and red blood cells (RBC)-rich thrombi during simulated stent retriever-mediated EVT procedures. Sixteen simulated EVT procedures were performed (8 RBC- vs. 8 platelet-rich thrombi). Platelet-rich thrombi were associated with a higher number of stent retriever passes (p = 0.03) and a longer procedure duration (p = 0.02) compared to RBC-rich thrombi. Conversely, RBC-rich thrombi released more embolic fragments than platelet-rich thrombi (p = 0.004). Both RBC-rich and platelet-rich thrombi underwent drastic compaction after being injected into the in vitro circulation model, and histologic analyses showed that these EVT-retrieved thrombi displayed features comparable to those previously observed in thrombi from patients with AIS patients having LVO, including a marked structural dichotomy between RBC- and platelet-rich areas. Our results show that the injection of in vitro-produced thrombi in artificial cerebrovascular arterial networks is suitable for testing recanalization efficacy and the risk of embolization of EVT devices and strategies in association with thrombus cell composition.

Background and Purpose: The aim of this study was to characterize neurological complications after flow diverter (FD) treatment on a long follow-up cohort and identify predictive factors associated with these complications.Methods: This study was conducted on a monocentric cohort of patients treated for intracranial aneurysms by FD.Results: Between September 2008 and July 2018, 413 patients were treated for 514 aneurysms: 18% of the patients presented with at least one neurological complication during a median follow-up of 446 days (IQR 186–1,210). Sixty-one patients presented with ischemic complications, 13 with hemorrhagic ones and 10 with compressive processes. Among 89 neurological complications 64.5% were peri-operative (occurring within the 30 days following the procedure) and 35.5% were delayed after 1 month.Conclusions: Overall, neurological complications after FD implantation were overrepresented by cerebrovascular ischemic events occurring during the peri-operative period, but also in a delayed manner after 1 year. Long-term follow-up is relevant after aneurysm intervention using FD.

Background: High systolic blood pressure (BP) is associated with an increased risk of intracranial hemorrhage (ICH) in patients undergoing reperfusion therapy. However, there are no data from randomized trials to guide BP management after reperfusion following endovascular therapy (EVT) for patients with acute ischemic stroke (AIS) with large vessel occlusion (LVO). The objective is to evaluate if BP control with a target of 100–129 mmHg systolic BP (“tight” SBP control) can reduce ICH as compared to 130–185 mmHg (“usual” SBP control) in AIS participants after reperfusion by EVT.Methods: The BP TARGET trial is a multicenter, prospective, randomized, controlled, open-label, blinded endpoint clinical trial. AIS participants with LVO experiencing successful reperfusion are randomly assigned, in a 1:1 ratio, to have a “tight” SBP control (100–129 mmHg) or a conservative SBP control (130–185 mmHg) during the following 24–36 h. The primary outcome is the rate of ICH (either symptomatic or asymptomatic) on follow-up CT scan at 24–36 h. Secondary outcomes include the rate of the symptomatic ICH, the overall distribution of the modified Rankin Scale (mRS) at 90 days, favorable outcome (90–day mRs 0–2), infarct volume at follow-up CT scan at 24–36 h, change in National Institute of Health Stroke Scale at 24 h, and all-cause mortality at 90 days.Conclusion: This is the first randomized trial directly comparing the efficacy of different SBP targets after EVT reperfusion. This prospective trial aims to determine whether a “tight” SBP control after EVT reperfusion can reduce the risk of ICH.