Post‐stroke blood–brain barrier disruption predicts poor outcome in patients enrolled in the ACTION study

Abstract

Background and Purpose A prior study found a link between post‐stroke blood–brain barrier disruption and functional outcomes. The current study aimed to replicate this finding in a cohort of patients recruited in the context of a randomized clinical trial. Methods The ACTION trial was a study of natalizumab in acute stroke patients. Patients with MRI‐perfusion weighted imaging (PWI) were included in this post‐hoc analysis. Blood‐brain permeability images (BBPI) were calculated from the PWI source images. Mean BBPI values from the 24 h time point were compared with modified Rankin scores (mRS) at 5, 30, and 90‐day assessments using linear regression. Good functional outcome (mRS< = 1) was compared with mean BBPI using logistic regression. Results One hundred and nineteen patients were included in the analysis (median age = 74, 43% female). Higher mean BBPI was associated with worse mRS at 5 days (p = 0.002; r2 = 0.078) and 30 days (p = 0.036; r2 = 0.039) but did not reach statistical significance at 90 days (p = 0.30; r2 = 0.010). When removing high‐value outliers, all outcome measures showed a stronger relationship with mean BBPI. Logistic regression found that with every 1% increase in mean BBPI measured 24 h after the stroke, the likelihood of achieving a good functional outcome at 90 days is decreased by half (OR = 0.53; CI = 0.30:0.95; p = 0.032). Conclusions With sufficient image quality, elevated BBPI measured in the days after an ischemic event is predictive of worse functional outcome and may serve as a biomarker for post‐stroke inflammation.

The role of peripheral inflammatory insults in Alzheimer’s disease: a review and research roadmap

“…Efforts to identify and understand the pathways through which peripheral inflammation may exert effects on the aging human brain have been hampered due to a limited capacity to assess peripheral-central immune crosstalk and the integrity of conduits, such as the BBB, through which this crosstalk occurs. Currently, there are several tools available for the measurement of BBB permeability in humans, including dynamic contrast enhanced (DCE) MR imaging and blood–brain permeability imaging (BBPI), both of which quantify leakage of gadolinium contrast into the tissue parenchyma [ 158 , 159 ]. Using DCE, BBB breakdown adjacent to the hippocampus has been demonstrated in individuals at risk for AD [ 160 ].…”

Seizures and epilepsy in patients with ischaemic stroke

“…Using MRI techniques, the occurrence of BBB disruption in acute ischaemic stroke has been increasingly investigated, particularly with regard to associated demographic and clinical factors, the impact of reperfusion therapies, and the prognostic relevance of BBB dysfunction for predicting haemorrhagic transformation and clinical outcomes after stroke [101]. For the assessment of BBB disruption in the setting of acute stroke, perfusionweighted imaging (PWI) is a particularly useful technique that can easily be incorporated into a standardised stroke imaging protocol and has been widely used [102][103][104][105]. The PWI approach that has traditionally been applied to the investigation of pathological changes in BBB permeability is dynamic contrast-enhanced imaging (DCE, often referred to as permeability imaging) and considers differences in the pre-and post-contrast T1-weighted images [102].…”

“…However, patients exhibiting a cerebral perfusion deficit, such as in acute stroke, require an arrival time correction for DSC-based permeability imaging to control for altered blood flow effects before calculating the permeability signal [103,105]. Both the DCE-PWI and delay-corrected DSC-PWI techniques to assess BBB permeability have successfully been applied successfully to investigate pre-and post-treatment BBB leakage in previous studies, which demonstrated associations between BBB disruption and haemorrhagic transformation, parenchymal haemorrhage, and unfavourable clinical outcomes [102,104,105,107,108] (Fig. 4).…”

The evolution of blood–brain barrier permeability changes after stroke and its implications on clinical outcome: A systematic review and meta-analysis

“…Eleven of the primarily excluded studies (1637 patients and 1687 evaluations) did not present separate contralateral/ipsilateral BBBp values but reported quantitative BBBp as a relative-to-normal. [17][18][19][20][21][22][23][24][25][26][27] These studies represent relevant information to our research and were included in a comprehensive review (Supplementary Table 2).…”