Acute ischemic stroke of unkown time of onset or beyond 4h30 : when should reperfusion therapy be considered in 2022 ?

Abstract

Wake-up and late-presenting strokes are frequent and particularly challenging in terms of indications for reperfusion therapy. Intraveinous thrombolysis by Alteplase had initially been validated within 4h30 from onset, and mechanical thrombectomy within the first 6 hours.  Since 2018, several studies dedicated to strokes outside these time windows have been published. The WAKE-UP trial established the benefit of Alteplase in stroke with unknown time of unset and MRI diffusion-FLAR mismatch. In patients with perfusion mismatch, the EXTEND trial opened the way for thrombolysis beyond 4h30. DAWN and DEFUSE 3 have demonstrated the benefit of thrombectomy beyond 6h, on a clinical-MRI and perfusion mismatch basis, respectively. Several studies are currently under way to possibly further widen indications for reperfusion therapy. Questions remain about how these studies may apply in clinical daily practice. In this review, we shall present this recent littérature, the resulting guidelines, and future perspectives.