Hyperacute ischemic stroke care-Current treatment and future directions

Abstract

A decade on from the first positive thrombectomy trials, hyperacute therapies for ischemic stroke continue to rapidly advance. Effective treatments remain limited to reperfusion, although several cytoprotective approaches continue to be investigated. Intravenous fibrinolytics are now demonstrated to be beneficial up to 24 h in patients selected using perfusion imaging, but their role in patients with non-disabling symptoms appears very limited. Tenecteplase is superior to alteplase in meta-analysis of the latest trials, and adjuvant thrombolytics are an area of active investigation. Endovascular thrombectomy is beneficial in a wide range of anterior and posterior circulation large vessel occlusions up to 24 h after onset with the more distal occlusions, mild presentations, and >24 h window being the main frontiers to be tested in ongoing trials. Imaging parameters are prognostic but appear not to modify the relative treatment benefit of thrombectomy versus standard medical care. Therefore, deciding who not to treat with thrombectomy is a key clinical challenge that requires careful but rapid integration of clinical, imaging, and patient preference considerations. Systems of care to accelerate delivery of these highly effective therapies will maximize benefits for the greatest number of patients with stroke.

Keywords: Pre-hospital triage; basilar artery occlusion; endovascular thrombectomy; mild stroke; reperfusion; thrombolytic.

Figure 1.

Meta-analysis of trials comparing tenecteplase 0.25 mg/kg versus alteplase 0–4.5 h after stroke onset for the outcome of modified Rankin Scale 0–1 (no disability) at 90 days.

Figure 2.

Perfusion imaging assists in finding the site of occlusion on computed tomography (CT) angiography in a patient with distal vessel occlusion and indicates the spatial location and extent of tissue at risk: (a) coronal and (b) sagittal maximum intensity projections of CT angiogram (arrows = distal left middle cerebral artery occlusion); (c) time to maximum (Tmax) map demonstrating the critically hypoperfused region.

Figure 3.

(a) Automated CT perfusion processing suggests perfusion mismatch: Ischemic Core 13 mL, Tmax > 6 s 39 mL = mismatch volume 26 mL, mismatch ratio 3.0. However, (b) unequivocal non-contrast CT hypodensity extends beyond the current perfusion lesion and cerebral blood flow within residual parietal hypoperfusion is no longer below the 30% threshold for ischemic core, despite clear CT hypodensity in that region. Manually outlined CT hypodensity volume was 105 mL. Partial reperfusion and collateral improvement increase in prevalence as time passes and can create a false appearance of perfusion mismatch. Hence, CT perfusion needs to be interpreted in conjunction with non-contrast CT. This patient does not have a true perfusion mismatch and would not have met eligibility for the EXTEND trial of thrombolytic >4.5 h.