Extended Windows in Acute Ischemic Stroke: What is the Time Limit?

Abstract

“Time is brain” has traditionally guided acute ischemic stroke (AIS) management, with intravenous thrombolysis generally restricted to 4.5 hours and mechanical thrombectomy (MT) historically limited to selected patients within 6 hours. Advances in neuroimaging and
endovascular therapy have demonstrated that tissue viability may be more important than elapsed time alone. This review examines contemporary therapeutic windows for acute cerebrovascular events and discusses how imaging-based selection has expanded
opportunities for reperfusion therapy. Tissue-based thrombolysis using diffusion-weighted imaging–fluid-attenuated inversion (DWI-FLAIR) recovery mismatch or perfusion imaging has enabled treatment of selected patients with wake-up or unknown-onset stroke and those presenting 4.5–9 hours after last known well. Emerging evidence with tenecteplase suggests potential benefit in highly selected patients with large-vessel occlusion presenting up to 24 hours. Trials have now established substantial benefit in appropriately selected patients presenting 6–24 hours after last known well. Recent trials have further expanded thrombectomy eligibility to selected patients with large ischemic cores. Treatment beyond 24 hours remains investigational. Importantly, extended windows should not encourage treatment delays. Treatment decisions increasingly incorporate infarct-core size, collateral circulation, penumbral viability,
occlusion site, clinical severity, pre-stroke functional status, and haemorrhagic risk. This paradigm is particularly relevant to resource-limited settings, where delayed presentation and interhospital transfer frequently prevent treatment within conventional windows. There is no single universal time limit for reperfusion therapy. The therapeutic window is increasingly determined by the interaction between time, tissue viability, and clinical factors, while earlier reperfusion remains preferable whenever feasible.