Document Type

Review Article


ABSTRACT Background: The efficacy and safety of intravenous recombinant tissue plasminogen activator (IV rt-PA) for the management of unknown time onset stroke (UTOS) and wake-up stroke (WUS) are in a debate. Objective:The objective of this review is to discuss the UTOS and its management with intravenous thrombolytic therapies. Data Sources: Databases searched included PubMed and Cochrane electronic databases and manual search. Study Selection and Data Extraction: 45 articles of potential relevance were selected. Results: 14 relevant papers were included. Most of studies including recent trials using Magnetic resonance imaging diffusion-weighted imaging fluid-attenuated inversion recovery (MRIDWI FLAIR) mismatch or Computed tomography perfusion (CTP) based selection showed favorable outcome modified Rankin scale (mRS) of 0 to 2 at 90 days in range of 44.6% to 53%. While Symptomatic intracranial hemorrhage (SIH) was observed in 1.3% to3.6%. Patients selected with significant ischemic penumbra using visual assessment of MRI DWI perfusion weighted images (PWI) mismatch did not showed a significant benefit in clinical outcome. OR: 1.2; 95%CI 0.63-2.27, p = 0.5. While use of RAPID software for automated penumbral image processing with median time from "last seen well" 9.9 hours showed favorable outcome in IV rt-PA group with no significant difference in in mortality.(OR, 1.44; 95% CI, 1.01 to 2.06; P=0.04). Conclusions: The penumbral mismatch in UTOS is a cogent method to recognize the patients for thrombolytic therapy without significant risk, but the appropriate neuroimaging criteria to maximize the efficacy and minimize hemorrhagic complications of thrombolytic treatment still has to be fully defined.

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