Thrombolysis beyond 4.5 h in Acute Ischemic Stroke


Purpose of Review

The purpose of this article is to review the current approaches using neuroimaging techniques to expand eligibility for intravenous thrombolytic therapy in acute ischemic stroke patients with stroke of unknown symptom onset.

Recent Findings

In recent years, several randomized, placebo-controlled trials have shown neuroimaging-guided approaches to be feasible in determining eligibility for alteplase beyond 4.5 h from last known well, and efficacious for reducing disability. DWI-FLAIR mismatch on MRI is an effective tool to identify stroke lesions less than 4.5 h in onset in patients with stroke of unknown symptom onset. Additionally, an automated perfusion-based approach, assessing for a disproportionate amount of salvageable tissue, is effective in identifying patients likely to benefit from late window alteplase treatment.


In patients with stroke of unknown symptom onset, an individualized approach using neuroimaging to determine time of stroke onset or presence of salvageable brain tissue is feasible in the acute setting and associated with improved long-term outcomes.

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Fig. 1


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Drs. Etherton and Gadhia report no disclosures. Dr. Schwamm reports the following relationships relevant to research grants or companies that manufacture products for telemedicine, thrombolysis or thrombectomy: scientific consultant regarding trial design and conduct to Genentech (late window thrombolysis); user interface design and usability to LifeImage (and holds < 1% stock options in this privately held company); stroke systems of care to the Massachusetts Department of Public Health; member of a Data Safety Monitoring Board (DSMB) for Penumbra (Separator 3D NCT01584609, last payment 2016; MIND NCT03342664, CURRENT); Diffusion Pharma PHAST-TSC NCT03763929, CURRENT); National PI or member of National Steering Committee for Medtronic (Victory AF NCT01693120, last payment 2015; Stroke AF NCT02700945, CURRENT); PI, late window thrombolysis trial, NINDS (P50NS051343, MR WITNESS NCT01282242; last payment 2017 and alteplase provided free of charge to Massachusetts General Hospital as well as supplemental per-patient payments to participating sites last payment 2017); PI, StrokeNet Network NINDS (New England Regional Coordinating Center U24NS107243, CURENT); Co-I, The Impact of Telestroke on Patterns of Care and Long-Term Outcomes, NINDS (R01NS111952; CURRENT); Co-I, REACH-PC, PCORI (NCT03375489; CURRENT); Member of steering committee, Genentech (TIMELESS NCT03785678, CURRENT).

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Etherton, M.R., Gadhia, R.R. & Schwamm, L.H. Thrombolysis beyond 4.5 h in Acute Ischemic Stroke. Curr Neurol Neurosci Rep 20, 35 (2020).

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  • Ischemic stroke
  • Thrombolysis
  • Neuroimaging
  • Systems of care