Abstract 1122‐000167: Hyperintense Acute Reperfusion Marker and Hemorrhagic Conversion in Stroke Patients Undergoing Mechanical Reperfusion

2021 ◽  
Vol 1 (S1) ◽  
Author(s):  
Pouria Moshayedi ◽  
Hamidreza Saber ◽  
David S Liebeskind ◽  
Jeffrey Gornbein ◽  
Bryan Yoo ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
White Matter ◽  
Clinical Outcome ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Periventricular White Matter ◽  
Vessel Occlusion ◽  
Blood Brain ◽  
Ischemic Core ◽  
Core Volume

Introduction : Endovascular thrombectomy (EVT) is a highly effective treatment to improve clinical outcome in patients with acute ischemic stroke due to large vessel occlusion (AIS‐LVO). However, blood‐brain barrier (BBB) disruption causing hemorrhagic transformation and reperfusion injury can potentially negate the beneficial effect of reperfusion. Studying determinants, frequency, and outcomes of the hyperintense acute reperfusion marker (HARM) sign, a biomarker of BBB disruption, would help to identify individual patients at increased risk, as well as developing therapies to prevent BBB breakdown. Methods : In consecutive AIS‐LVO patients with AIS‐LVO who underwent EVT followed by MRI within the next 24 hours, we evaluated frequency, determinants, and outcomes of HARM sign. Results : Among 81 patients meeting study criteria, age was 71.0 (SD 19.7), 58% female, mean NIHSS was 14.5 (SD 6.8), and time from last known well to treatment was 355 min (IQR 206.5 ‐ 664). HARM sign was observed in 64% (52/81) of patients. On multivariate logistic analysis, presence of HARM sign was independently associated with greater periventricular white matter hyperintensity, higher pre‐EVT ischemic core volume, more proximal target vessel occlusion, and achievement of successful reperfusion or better. Hemorrhagic conversion was seen in 31.8% of patients with HARM sign and 26.7% of patients without HARM sign. Multivariate analysis identified higher blood glucose, lower ASPECT, score and greater post‐EVT ischemic core volume as independent predictors of hemorrhagic conversion. HARM sign was identified to correlate with poor clinical outcome in bivariate analysis, but multivariate analysis only identified less neurological deficits, lower baseline systolic BP, lower degree of periventricular white matter hyperintensities, shorter time to device deployment and reduced post EVT ischemic core volume as independent predictors of good clinical outcome (mRS 0–2) upon discharge. Conclusions : The HARM sign indicating disruption of the blood‐brain barrier following EVT is common, present in about 6 of every 10 treated patients. Independent risk factors for HARM sign are chronic ischemic microangiopathy, greater acute ischemic core, and successful reperfusion. HARM sign presence is associated with worse functional outcome.

Abstract P71: Global Blood-Brain Barrier Disruption After Acute Stroke

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Richard Leigh ◽  
Kyle Kern ◽  
Clinton B Wright
Keyword(s):  
White Matter ◽  
Blood Brain Barrier ◽  
Multivariable Analysis ◽  
Brain Barrier ◽  
Acute Ischemia ◽  
Periventricular White Matter ◽  
Stroke Patients ◽  
Whole Brain ◽  
Deep White Matter ◽  
Blood Brain

Background: Acute ischemia is known to cause local disruption of the blood-brain barrier (BBB), but studies have also shown that BBB disruption can be detected remote from the acute lesion. We sought to test a whole brain measurement of BBB disruption. Methods: This is a retrospective analysis of a deidentified dataset of stroke patients who did not undergo thrombolysis or thrombectomy and had an MRI performed with perfusion weighted imaging (PWI) 4-24 hours after symptom onset. We used PWI source images to identify voxels that demonstrated gadolinium leakage during the acquisition. BBB disruption was defined as a >1% change in signal due to leakage compared with normal tissue. Voxels that did not demonstrate adequate bolus tracking where excluded as noise. This yielded a whole brain average of voxels demonstrating BBB disruption that was not due to noise (wbBBB). We examined age, sex, NIHSS, Fazekas score, and time from onset as predictors of wbBBB using linear regression (continuous variables) and logistic regression (binary variables). Results: The 432 patients included in the analysis had a median age of 72 and 50% were women (mean NIHSS=6). wbBBB was highly correlated with age (p<0.001); figure 1A shows the 95% confidence intervals for the linear fit between age and wbBBB. There was no significant association with sex (p=0.143), NIHSS (p=0.097), or time from onset (p=0.149). wbBBB was associated with Fazekas score of the deep white matter (p<0.001) and the periventricular white matter (p<0.001). In multivariable analysis, age (p=0.011) and deep WMH (p=0.027), but not periventricular WMH (p=0.725), were independently associated with wbBBB. Figure 1B shows a boxplot of how wbBBB increases with increasing Fazekas score in the deep white matter. Conclusions: Global BBB disruption measured in stroke patients increased with increasing age and cerebral small vessel disease. It remains to be determined if these findings represent an acute exacerbation of a chronic process.

scholarly journals Sustained Opening of the Blood-Brain Barrier with Progressive Accumulation of White Matter Hyperintensities Following Ischemic Stroke

2019 ◽  
Vol 9 (1) ◽  
pp. 16 ◽  
Author(s):  
Imama Naqvi ◽  
Emi Hitomi ◽  
Richard Leigh
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Acute Stroke ◽  
Blood Brain Barrier ◽  
White Matter Hyperintensities ◽  
Brain Barrier ◽  
Common Finding ◽  
Blood Brain ◽  
History Of ◽  
Iv Tpa

Objective: To report a patient in whom an acute ischemic stroke precipitated chronic blood-brain barrier (BBB) disruption and expansion of vascular white matter hyperintensities (WMH) into regions of normal appearing white matter (NAWM) during the following year. Background: WMH are a common finding in patients with vascular risk factors such as a history of stroke. The pathophysiology of WMH is not fully understood; however, there is growing evidence to suggest that the development of WMH may be preceded by the BBB disruption in the NAWM. Methods: We studied a patient enrolled in the National Institutes of Health Natural History of Stroke Study who was scanned with magnetic resonance imaging (MRI) after presenting to the emergency room with an acute stroke. After a treatment with IV tPA, she underwent further MRI scanning at 2 h, 24 h, 5 days, 30 days, 90 days, 6 months, and 1-year post stroke. BBB permeability images were generated from the perfusion weighted imaging (PWI) source images. MRIs from each time point were co-registered to track changes in BBB disruption and WMH over time. Results: An 84-year-old woman presented after acute onset right hemiparesis, right-sided numbness and aphasia with an initial NIHSS of 13. MRI showed diffusion restriction in the left frontal lobe and decreased blood flow on perfusion imaging. Fluid attenuated inversion recovery (FLAIR) imaging showed bilateral confluent WMH involving the deep white matter and periventricular regions. She was treated with IV tPA without complication and her NIHSS improved initially to 3 and ultimately to 0. Permeability maps identified multiple regions of chronic BBB disruption remote from the acute stroke, predominantly spanning the junction of WMH and NAWM. The severity of BBB disruption was greatest at 24 h after the stroke but persisted on subsequent MRI scans. Progression of WMH into NAWM over the year of observation was detected bilaterally but was most dramatic in the regions adjacent to the initial stroke. Conclusions: WMH-associated BBB disruption may be exacerbated by an acute stroke, even in the contralateral hemisphere, and can persist for months after the initial event. Transformation of NAWM to WMH may be evident in areas of BBB disruption within a year after the stroke. Further studies are needed to investigate the relationship between chronic BBB disruption and progressive WMH in patients with a history of cerebrovascular disease and the potential for acute stroke to trigger or exacerbate the process leading to the development of WMH.

scholarly journals Combined Perfusion and Permeability Imaging Reveals Different Pathophysiologic Tissue Responses After Successful Thrombectomy

2021 ◽  
Author(s):  
Arne Potreck ◽  
Matthias A. Mutke ◽  
Charlotte S. Weyland ◽  
Johannes A. R. Pfaff ◽  
Peter A. Ringleb ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Blood Brain Barrier ◽  
Hemorrhagic Transformation ◽  
Brain Barrier ◽  
Dynamic Susceptibility ◽  
Blood Brain Barrier Disruption ◽  
Flow Maps ◽  
Blood Brain ◽  
Patients At Risk ◽  
Brain Barrier Disruption

AbstractDespite successful recanalization of large-vessel occlusions in acute ischemic stroke, individual patients profit to a varying degree. Dynamic susceptibility-weighted perfusion and dynamic T1-weighted contrast-enhanced blood-brain barrier permeability imaging may help to determine secondary stroke injury and predict clinical outcome. We prospectively performed perfusion and permeability imaging in 38 patients within 24 h after successful mechanical thrombectomy of an occlusion of the middle cerebral artery M1 segment. Perfusion alterations were evaluated on cerebral blood flow maps, blood-brain barrier disruption (BBBD) visually and quantitatively on ktrans maps and hemorrhagic transformation on susceptibility-weighted images. Visual BBBD within the DWI lesion corresponded to a median ktrans elevation (IQR) of 0.77 (0.41–1.4) min−1 and was found in all 7 cases of hypoperfusion (100%), in 10 of 16 cases of hyperperfusion (63%), and in only three of 13 cases with unaffected perfusion (23%). BBBD was significantly associated with hemorrhagic transformation (p < 0.001). While BBBD alone was not a predictor of clinical outcome at 3 months (positive predictive value (PPV) = 0.8 [0.56–0.94]), hypoperfusion occurred more often in patients with unfavorable clinical outcome (PPV = 0.43 [0.10–0.82]) compared to hyperperfusion (PPV = 0.93 [0.68–1.0]) or unaffected perfusion (PPV = 1.0 [0.75–1.0]). We show that combined perfusion and permeability imaging reveals distinct infarct signatures after recanalization, indicating the severity of prior ischemic damage. It assists in predicting clinical outcome and may identify patients at risk of stroke progression.

scholarly journals Blood-brain barrier breakdown in non-enhancing multiple sclerosis lesions detected by 7-Tesla MP2RAGE ΔT1 mapping

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0249973
Author(s):  
Seongjin Choi ◽  
Margaret Spini ◽  
Jun Hua ◽  
Daniel M. Harrison
Keyword(s):  
Multiple Sclerosis ◽  
Relaxation Time ◽  
White Matter ◽  
Blood Brain Barrier ◽  
White Matter Lesions ◽  
Brain Barrier ◽  
7 Tesla ◽  
T1 Relaxation Time ◽  
T1 Relaxation ◽  
Blood Brain

Although the blood-brain barrier (BBB) is altered in most multiple sclerosis (MS) lesions, gadolinium enhancement is seen only in acute lesions. In this study, we aimed to investigate gadolinium-induced changes in T1 relaxation time in MS lesions on 7-tesla (7T) MRI as a means to quantify BBB breakdown in non-enhancing MS lesions. Forty-seven participants with MS underwent 7T MRI of the brain with a magnitude-prepared rapid acquisition of 2 gradient echoes (MP2RAGE) sequence before and after contrast. Subtraction of pre- and post-contrast T1 maps was used to measure T1 relaxation time change (ΔT1) from gadolinium. ΔT1 values were interrogated in enhancing white matter lesions (ELs), non-enhancing white matter lesions (NELs), and normal appearing white matter (NAWM) and metrics were compared to clinical data. ΔT1 was measurable in NELs (median: -0.139 (-0.304, 0.174) seconds; p < 0.001) and was negligible in NAWM (median: -0.001 (-0.036, 0.155) seconds; p = 0.516). Median ΔT1 in NELs correlated with disability as measured by Expanded Disability Status Scale (EDSS) (rho = -0.331, p = 0.026). Multiple measures of NEL ΔT1 variability also correlated with EDSS. NEL ΔT1 values were greater and more variable in patients with progressive forms of MS and greater in those not on MS treatment. Measurement of the changes in T1 relaxation time caused by contrast on 7T MP2RAGE reveals clinically relevant evidence of BBB breakdown in NELs in MS. This data suggests that NEL ΔT1 should be evaluated further as a biomarker for disease severity and treatment effect in MS.

Adverse effects of erenumab on cerebral proliferative angiopathy: A case report

Cephalalgia ◽  
2020 ◽  
pp. 033310242095048
Author(s):  
Laura L Lehman ◽  
Rebecca Bruccoleri ◽  
Amy Danehy ◽  
Julie Swanson ◽  
Christine Mrakotsky ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
White Matter ◽  
Magnetic Resonance ◽  
Blood Brain Barrier ◽  
Vascular Malformations ◽  
Hippocampal Sclerosis ◽  
White Matter Injury ◽  
Brain Barrier ◽  
Resonance Imaging ◽  
Blood Brain

Background Cerebral proliferative angiopathy is a vascular malformation associated with compromised blood-brain barrier and with migraine-like headache. Treating blood-brain barrier-compromised patients with erenumab, an anti-calcitonin gene-related peptide receptor monoclonal antibody, may be risky. Case We describe a case of a 22-year-old chronic migraine patient with cerebral proliferative angiopathy who presented to our hospital in status epilepticus 2 d after his first dose of erenumab. Serial magnetic resonance imaging (MRI) studies demonstrated progressive areas of diffusion restriction including the brain tissue adjacent to the cerebral proliferative angiopathy, bilateral white matter and hippocampi. His 6-month post-presentation magnetic resonance imaging was notable for white matter injury, encephalomalacia surrounding cerebral proliferative angiopathy and bilateral hippocampal sclerosis. He remains clinically affected with residual symptoms, including refractory epilepsy and cognitive deficits. Conclusion The evidence presented in this case supports further investigation into potential deleterious side effects of erenumab in patients with compromised blood-brain barrier, such as individuals with intracranial vascular malformations.

scholarly journals A PET study in healthy subjects of brain exposure of 11C-labelled osimertinib – A drug intended for treatment of brain metastases in non-small cell lung cancer

2019 ◽  
Vol 40 (4) ◽  
pp. 799-807 ◽  
Author(s):  
Andrea Varrone ◽  
Katarina Varnäs ◽  
Aurelija Jucaite ◽  
Zsolt Cselényi ◽  
Peter Johnström ◽  
...  
Keyword(s):  
White Matter ◽  
Brain Metastases ◽  
Blood Brain Barrier ◽  
Healthy Subjects ◽  
Standardized Uptake Value ◽  
Brain Barrier ◽  
Pharmacokinetic Parameters ◽  
Blood Brain ◽  
Brain Exposure ◽  
The Brain

Osimertinib is a tyrosine kinase inhibitor (TKI) of the mutated epidermal growth factor receptor (EGFRm) with observed efficacy in patients with brain metastases. Brain exposure and drug distribution in tumor regions are important criteria for evaluation and confirmation of CNS efficacy. The aim of this PET study was therefore to determine brain distribution and exposure of 11C-labelled osimertinib administered intravenously in subjects with an intact blood–brain barrier. Eight male healthy subjects (age 52 ± 8 years) underwent one PET measurement with 11C-osimertinib. The pharmacokinetic parameters Cmax (brain) (standardized uptake value), Tmax (brain) and AUC0–90 min brain/blood ratio were calculated. The outcome measure for 11C-osimertinib brain exposure was the total distribution volume ( VT). 11C-osimertinib distributed rapidly to the brain, with higher uptake in grey than in white matter. Mean Cmax, Tmax and AUC0–90 min brain/blood ratio were 1.5 (range 1–1.8), 13 min (range 5–30 min), and 3.8 (range 3.3–4.1). Whole brain and white matter VT were 14 mL×cm−3 (range 11–18) and 7 mL×cm−3 (range 5–12). This study in healthy volunteers shows that 11C-osimertinib penetrates the intact blood–brain barrier. The approach used further illustrates the role of molecular imaging in facilitating the development of novel drugs for the treatment of malignancies affecting the brain.

The effects of blood–brain barrier disruption on glial cell function in multiple sclerosis

2009 ◽  
Vol 37 (1) ◽  
pp. 329-331 ◽  
Author(s):  
Stephen McQuaid ◽  
Paula Cunnea ◽  
Jill McMahon ◽  
Una Fitzgerald
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Blood Brain Barrier ◽  
Cell Function ◽  
Brain Barrier ◽  
Blood Brain Barrier Disruption ◽  
Normal Appearing White Matter ◽  
Blood Brain ◽  
Capillary Endothelial Cells ◽  
Brain Barrier Disruption

Dysfunction of the BBB (blood–brain barrier) is a major hallmark of MS (multiple sclerosis). Studies in our laboratories over the last decade have shown that increased BBB permeability is associated with decreased expression of TJ (tight junction) proteins in brain capillary endothelial cells. Results have revealed that TJ abnormalities were most common in active lesions (42% of vessels affected), but were also present in inactive lesions (23%) and in MS normal-appearing white matter (13%). Importantly, TJ abnormality was also positively associated with leakage of the serum protein fibrinogen which has recently been shown to be an activator of microglia. TJ abnormality and the resultant vascular permeability in both lesional and non-lesional white matter may impair tissue homoeostasis, which may have effects on disease progression, repair mechanisms and drug delivery.

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