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Patterns and Predictors of Blood-Brain Barrier Permeability Derangements in Acute Ischemic Stroke
Bang, Oh Young,Saver, Jeffrey L.,Alger, Jeffry R.,Shah, Samir H.,Buck, Brian H.,Starkman, Sidney,Ovbiagele, Bruce,Liebeskind, David S. Ovid Technologies Wolters Kluwer -American Heart A 2009 Stroke Vol.40 No.2
<P>BACKGROUND AND PURPOSE: MRI permeability imaging is a promising approach to identify patients with acute ischemic stroke with an increased propensity for hemorrhagic transformation (HT). Permeability imaging provides direct visualization of blood-brain barrier derangements in ischemic fields. METHODS: We retrospectively analyzed clinical and MRI data on patients with acute cerebral ischemia within the middle cerebral artery territory to identify the frequency, patterns, and predictors of permeability derangements and their association with HT types. RESULTS: A total of 179 permeability scans was obtained in 127 patients (59 men; mean age, 66.8 years). Among 179 image sets (82 pre-/no treatment and 97 posttreatment), permeability derangements were present in 29 images, frequently at the basal ganglia (n=23) and rarely at the juxta-cortical area (n=6). After adjusting for covariates, diastolic pressure (OR, 1.12, per 1-mm Hg increase; 95% CI, 1.02 to 1.22) and s-glucose (OR, 1.04, per 1-mg/dL increase; 95% CI, 1.01 to 1.07) were independently associated with pretreatment permeability derangements, whereas low-density lipoprotein cholesterol (OR, 0.97, per 1-mg/dL increase; 95% CI, 0.94 to 0.99), malignant MRI profile (OR, 24.84; 95% CI, 1.50 to 412.93), and time from onset to recanalization therapy (OR, 1.47, per 1-hour increase; 95% CI, 1.10 to 1.96) were independently associated with permeability derangements after recanalization therapy. Types of HT varied among the patients with permeability derangements (no HT, 4; hemorrhagic infarct type, 12; and parenchymal hematoma, 13) and transient derangements (without subsequent HT) and normalization of derangements (in the presence of HT) on permeability images was observed in several cases. CONCLUSIONS: Permeability derangements, a dynamic process associated with ischemic stroke pathophysiology and recanalization therapy, vary in pattern and evolution toward HT. Several prognostic and therapeutic predictors for HT are independently associated with pre- and posttreatment permeability derangements.</P>
Bang, Oh Young,Saver, Jeffrey L.,Kim, Suk Jae,Kim, Gyeong-Moon,Chung, Chin-Sang,Ovbiagele, Bruce,Lee, Kwang Ho,Liebeskind, David S. Ovid Technologies Wolters Kluwer -American Heart A 2011 Stroke Vol.42 No.8
<P>Collaterals sustain the ischemic penumbra to limit growth of the infarct core before revascularization, yet the impact of baseline collateral flow on hemorrhagic transformation (HT) after endovascular therapy remains unknown.</P>
Determinants of the distribution and severity of hypoperfusion in patients with ischemic stroke
Bang, O. Y.,Saver, J. L.,Alger, J. R.,Starkman, S.,Ovbiagele, B.,Liebeskind, D. S. Ovid Technologies (Wolters Kluwer) - American Acad 2008 Clinical Neurophysiology Vol.71 No.22
<P>BACKGROUND: In acute cerebral ischemia, two variables characterize the extent of hypoperfusion: the volume of hypoperfused tissue and the intensity of hypoperfusion within these regions. We evaluated the determinants of the intensity of hypoperfusion within oligemic regions among patients who were eligible for recanalization therapy for acute ischemic stroke. METHODS: We analyzed data, including pretreatment diffusion-weighted imaging (DWI) and perfusion-weighted imaging, on 119 patients with acute middle cerebral artery infarctions. The intensity of hypoperfusion within oligemic regions was characterized by the hypoperfusion intensity ratio (HIR), defined as the volume of tissue with severe hypoperfusion (Tmax > or = 8 seconds) divided by the volume of tissue with any hypoperfusion (Tmax > or = 2 seconds). Based on the DWI data, we divided the patients into four stroke phenotypes: large cortical, small (< 1 cm diameter) cortical, border-zone, and deep pattern. RESULTS: The mean (SD) volume of severe hypoperfusion was 54.6 (52.5) mL, and that of any hypoperfusion was 140.8 (81.3) mL. The HIR ranged widely, from 0.002 to 0.974, with a median of 0.35 (interquartile range 0.13-0.60). The volume of any hypoperfusion did not predict the intensity of hypoperfusion within the affected region (r = 0.10, p = 0.284). Angiographic collateral flow grade was associated with HIRs (p value for trend = 0.019) and differed among DWI lesion patterns. In multivariate analysis, diastolic pressure on admission (odds ratio 0.959, 95% CI 0.922-0.998) and DWI pattern of deep infarcts (odds ratio 18.004 compared with large cortical pattern, 95% CI 1.855-173.807) were independently associated with a low HIR. CONCLUSIONS: The intensity of hypoperfusion within an oligemic field is largely independent of the size of the oligemia region. Predictors of lesser intensity of hypoperfusion are lower diastolic blood pressure and presence of a deep diffusion-weighted imaging lesion pattern.</P>
김경준,정상욱,류위선,Jeffrey L. Saver,김종성,권순억 대한신경과학회 2021 Journal of Clinical Neurology Vol.17 No.1
Background and Purpose We aimed to determine the relationships of 33 biomarkers of inflammation, oxidation, and adipokines with the risk of progression of symptomatic intracranial atherosclerotic stenosis (ICAS). Methods Fifty-two of 409 patients who participated in the TOSS-2 (Trial of Cilostazol in Symptomatic Intracranial Stenosis-2) showed progression of symptomatic ICAS in magnetic resonance angiography at 7 months after an index stroke. We randomly selected 20 patients with progression as well as 40 age- and sex-matched control patients. We serially collected blood samples at baseline, 1 month, and 7 months after an index stroke. Multiplex analysis of biomarkers was then performed. Results Demographic features and risk factors such as hypertension, diabetes, and smoking history were comparable between the two groups. Univariate analyses revealed that the levels of platelet-derived growth factor (PDGF)-AA [median (interquartile range)=1.64 (0.76–4.57) vs. 0.77 (0.51–1.71) ng/mL], PDGF-AB/BB [10.31 (2.60–25.90) vs. 2.35 (0.74–6.70) ng/mL], and myeloperoxidase [10.5 (7.5–22.3) vs. 7.8 (5.5–12.2) ng/mL] at 7 months were higher in the progression group. In the multivariate analysis using logistic regression, the PDGF AB/BB level at 7 months was independently associated with the progression of ICAS (p=0.02). Conclusions The PDGF-AB/BB level is associated with the progression of ICAS, and so may play a significant role in the progression of human ICAS.
Chia-Yu Hsu,Shao-Wen Chiu,Keun-Sik Hong,Jeffrey L. Saver,Yi-Ling Wu,Jiann-Der Lee,Meng Lee,Bruce Ovbiagele 대한뇌졸중학회 2018 Journal of stroke Vol.20 No.1
Background and Purpose Additional folic acid (FA) treatment appears to have a neutral effect on reducing vascular risk in countries that mandate FA fortification of food (e.g., USA and Canada). However, it is uncertain whether FA therapy reduces stroke risk in countries without FA food fortification. The purpose of this study was to comprehensively evaluate the efficacy of FA therapy on stroke prevention in countries without FA food fortification. Methods PubMed, EMBASE, and clinicaltrials.gov from January 1966 to August 2016 were searched to identify relevant studies. Relative risk (RR) with 95% confidence interval (CI) was used as a measure of the association between FA supplementation and risk of stroke, after pooling data across trials in a random-effects model. Results The search identified 13 randomized controlled trials (RCTs) involving treatment with FA that had enrolled 65,812 participants, all of which stroke was reported as an outcome measure. After all 13 RCTs were pooled, FA therapy versus control was associated with a lower risk of any future stroke (RR, 0.85; 95% CI, 0.77 to 0.95). FA alone or combination of FA and minimal cyanocobalamin (≤0.05 mg/day) was associated with a lower risk of future stroke (RR, 0.75; 95% CI, 0.66 to 0.86) whereas combination of FA and cyanocobalamin (≥0.4 mg/day) was not associated with a lower risk of future stroke (RR, 0.95; 95% CI, 0.86 to 1.05). Conclusions FA supplement reduced stroke in countries without mandatory FA food fortification. The benefit was found mostly in patients receiving FA alone or combination of FA and minimal cyanocobalamin.