Abstract

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.

Highlights

  • To date, reperfusion therapies represent the mainstay of acute ischemic stroke (AIS) treatments [1, 2]

  • In European Cooperative Acute Stroke Study (ECASS) 3, symptomatic ICH (sICH) occurred in 5.3% and 2.2% of the type plasminogen activator (tPA) and placebo groups, respectively, according to the ECASS 2 definition (OR = 2.43, 95% confidence interval (CI) = 1.11–5.35, p = 0.02), 1.9 and 0.2% according to the SITS-MOST definition (OR = 7.84, 0.98–63, p = 0.02), and 7.9 and 3.5% according to the Neurological Disorders and Stroke (NINDS) definition (OR = 2.38, 1.25– 4.52, p = 0.006) [3]

  • - Symptomatic intracerebral hemorrhage: parenchymal hematoma type 2 (PH2) within 36 h after treatment combined with an increase of ≥4 in National Institutes of Health Stroke Scale (NIHSS) score from baseline sICH according to the SITS-MOST and ECASS 2 definitions: - PH-2 on follow-up imaging and neurologic deterioration of ≥4 in NIHSS score. - Any type of intracerebral hemorrhage on posttreatment imaging with an increase of ≥4 in NIHSS score sICH assessed at 27 ± 6 h and defined as any PH1, PH2, remote intracranial hemorrhage (ICH), SAH, IVH associated with ≥4 points worsening in NIHSS score within 24 h sICH at 24 h: visible intracranial bleeding on computed tomography (CT) or magnetic resonance imaging (MRI) plus an increase of ≥4 in NIHSS score

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Summary

INTRODUCTION

Reperfusion therapies represent the mainstay of acute ischemic stroke (AIS) treatments [1, 2]. Reperfusion can be performed pharmacologically by the use of intravenous recombinant human tissue-type plasminogen activator (IV tPA; alteplase, Boehringer Ingelheim, Germany) within the first 4.5 h after stroke onset [3], and since 2015, by endovascular therapy (EVT) in case of an anterior circulation large-vessel occlusion (LVO) [4]. These different treatments have been found effective in reducing 3 month neurological disability. After examining the different clinical, radiological, and biological baseline characteristics associated with increased ICH occurrence, we review possible modifiable factors and future therapeutic approaches

Background
Results
CONCLUDING REMARKS
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