Blood-brain barrier integrity of stroke patients presenting in an extended time window

Abstract

Background: 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. Methods: We 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. Results: Of 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. Conclusions: Estimating BBB integrity may help to expand the treatment window for stroke patients by identifying those individuals for whom thrombolytic therapy can be considered.

The Relationship Between Penumbral Tissue and Blood-Brain Barrier Disruption in Acute Stroke Patients Presenting in an Extended Time Window

“…However, when treating time-to-MRI as a continuous variable and dichotomizing by the presence of a TP, later presentation was associated with decreased likelihood of a TP (OR 0.99, CI 0.997:0.999, p = 0.12). Comparing time-to-MRI with MPD > 20 did not find an association ( p = 0.138) which is in agreement with our previously published findings ( 7 ).…”

“…The details of this population have been described in a previous publication ( 7 ). Briefly, it includes patients presenting to two stroke centers over a 5 year period who were evaluated and underwent MRI with diffusion weighted imaging (DWI) and perfusion weighted imaging (PWI) within 24 h of being last seen normal.…”

“…Details of the MRI protocol have been published previously ( 7 ). Ischemic lesions were identified on PWI using a TTP threshold of 4 s delay relative to the contralateral hemisphere.…”

“…The mean permeability derangement (MPD), which is a measure of BBB disruption, was calculated from the source images of the PWI scan in the same manner previously described ( 7 ). PWI is generated using a dynamic susceptibility contrast (DSC) image sequence.…”

Pathophysiology of Blood–Brain Barrier Permeability Throughout the Different Stages of Ischemic Stroke and Its Implication on Hemorrhagic Transformation and Recovery

“…So far, we are unable to withhold patients from reperfusion therapies based on BBB status evaluated from these imaging techniques, but imaging of the BBB in the early hours of stroke is a promising strategy to improve patient safety. Also promising is the usage of these imaging modalities in the selection of patients that may benefit from an extended time window of intravenous thrombolysis ( 176 ) and in the early detection of patients that may develop severe stroke complications such as HT, which would be key in the specific guided treatment of AIS patients avoiding, therefore, poorer prognosis and adverse clinical developments ( 154 ).…”