Reperfusion Therapies in Acute Ischemic Stroke Beyond the Conventional Time Window: A Narrative Review

Stroke is the second most common cause of death worldwide, with 50% of survivors experiencing long-term disability. For more than two decades, treatment with intravenous thrombolysis (IVT) and mechanical endovascular thrombectomy (MET), the only approved stroke reperfusion therapies, was restricted to patients within the 4.5-6 hour time window, respectively. Therefore, patients who presented with acute ischemic stroke (AIS) beyond the conventional time window were excluded from reperfusion treatment. This narrative review aims to review the scientific literature on the possibilities of reperfusion therapies for patients who present with an unknown time of stroke onset, and those with stroke onset beyond the conventional 4.5-6 hour time window. Beyond the conventional time window, the eligibility of patients for IVT or MET, the two main therapeutic procedures, is decided based on the concept of penumbral imaging. Penumbral imaging identifies patients with hypoperfused but viable brain tissue, who could benefit from reperfusion. On the other hand, clock-based DWI-fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) can detect stroke that has occurred within 4.5 hours in patients with an unknown time of onset, including patients who awaken with stroke. The introduction of penumbral imaging and MRI-based tissue clocking as imaging biomarkers for stroke has revolutionized stroke therapy, potentially allowing for personalized treatment of eligible stroke patients.