Abstract 59: Extending the Time for Thombolysis in Emergency Neurological Deficits (EXTEND) - High Prevalence of Intracranial Vessel Occlusion in Wake-up-stroke Patients

Abstract

Background: EXTEND is an investigator-initiated, randomised, double-blind and placebo-controlled Phase III trial of intravenous alteplase vs placebo in patients with ischemic stroke 4.5-9 hours from stroke onset or wake-up-stroke (WUS). The prevalence of intra-cranial vessel occlusion in WUS patients remains to be determined and can guide the development of optimal therapy for this unique group of stroke patients. Objective: To study the prevalence and characteristics of intra-cranial vessel occlusion in this WUS cohort. Methods: Ischemic stroke patients within 4.5-9 hours from stroke onset or with WUS (time of WUS onset defined as the midpoint between time to sleep and awakening with the stroke symptoms) are eligible for enrollment. Criteria for entry into the trial include perfusion-diffusion mismatch using a perfusion threshold of Tmax>6sec and a perfusion:diffusion lesion volume ratio of >1.2. Diffusion lesion volume must be <70mL based on assessment by automated RAPID software. Intra-cranial vessel occlusion was assessed on MR or CT angiogram performed at randomisation and 24 later. Two expert readers assessed these images independently. Results: 97 patients had images with adequate quality, including 63 (65%) in the WUS group with median age of 77.0 yrs (IQR 67.0, 81.0) and NIHSS of 14.0 (9.0, 19.0). 62 of 63 patients (98%) had vessel occlusion with 44.4% involving M1 of the middle cerebral artery, 17.5% M2, 4.8% M3, 25.4% both internal carotid artery (ICA) and M1, 4.8% ICA alone and 3.1% the posterior cerebral artery. The median ischemic core volume was 15.0 ml (6.5, 31.5), Tmax>6 volume 88.5ml (58.0, 122.0), mismatch volume 65.5ml (42.8, 92.0), and ratio of 4.8 (2.5, 8.7). 19 patients (30%) demonstrated recanalization on follow-up imaging. Conclusion: In WUS patients there is a very high rate of intracranial vessel occlusion with relatively large volumes of salvageable penumbral tissue. Intravenous thrombolytic therapy followed by thrombectomy in selected cases may be an appropriate therapeutic option with safety and efficacy remaining to be established in randomized controlled trials.