Abstract
BackgroundCurrent guidelines limit thrombolytic treatment of stroke to those patients who present within 4.5 h to minimize the risk of hemorrhagic complications. Risk of hemorrhage increases with increasing blood-brain barrier (BBB) disruption. This study aimed to determine, in a cohort of patients presenting outside of an IV-tPA treatment window, whether disruption of the BBB is time dependent, and what proportion of patients could be safely treated.MethodsWe analyzed untreated stroke patients, seen between 2011 and 2015, who had MRI studies in the time window of 4 to 24 h from symptoms onset. Permeability of the BBB was measured within the ischemic tissue using an application of dynamic susceptibility contrast imaging. Patients were dichotomized into two groups based on a 20% threshold of BBB disruption and compared using logistic regression.ResultsOf the 222 patients included in the final analysis, over half, 129 (58%), had preserved BBB integrity below the 20% threshold. There was no relationship between time imaged after symptom onset and the amount of BBB disruption (p = 0.138) across the population; BBB disruption varied widely.ConclusionsEstimating BBB integrity may help to expand the treatment window for stroke patients by identifying those individuals for whom thrombolytic therapy can be considered.
Highlights
Current guidelines limit thrombolytic treatment of stroke to those patients who present within 4.5 h to minimize the risk of hemorrhagic complications
Of the 3469 patients with stroke or TIA seen by our stroke service during the study period, 893 presented with a known time of last seen normal (LSN) that was in the 4–24-h window, of whom 612 had an Magnetic resonance imaging (MRI)
We found that patients with larger perfusion deficits had less blood-brain barrier (BBB) disruption despite there being no significant difference in the size of the strokes on diffusion weighted imaging (DWI)
Summary
Current guidelines limit thrombolytic treatment of stroke to those patients who present within 4.5 h to minimize the risk of hemorrhagic complications. Risk of hemorrhage increases with increasing blood-brain barrier (BBB) disruption. This study aimed to determine, in a cohort of patients presenting outside of an IV-tPA treatment window, whether disruption of the BBB is time dependent, and what proportion of patients could be safely treated. Presenting to the hospital beyond this time window is the main reason an AIS patient is not treated with IV-tPA [4]. There is a dose dependency between the severity of BBB disruption within the ischemic lesion and the severity of the HT in patients treated with IVtPA [9] or endovascular therapy [10], a relationship that has been confirmed using multiple BBB-imaging approaches [11, 12]. Imaging of the BBB has not previously been used for prospective selection of patients in clinical trials of thrombolysis in the extended time window (beyond 4.5 h)
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