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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>
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.
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>
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.
Impact of Reperfusion after 3 Hours of Symptom Onset on Tissue Fate in Acute Cerebral Ischemia
Bang, Oh Young,Liebeskind, David S.,Buck, Brian H.,Yoon, Sa Rah,Alger, Jeffry R.,Ovbiagele, Bruce,Saver, Jeffrey L. Wiley (Blackwell Publishing) 2009 Journal of neuroimaging Vol.19 No.4
<P>BACKGROUND: Reperfusion of penumbral tissue is a promising strategy for treatment of acute cerebral ischemia more than 3 hours from symptom onset. However, there has been only sparse direct evidence that reperfusion after 3 hours prevents infarct growth. METHODS: We analyzed clinical and serial magnetic resonance imaging (MRI) data on patients who received endovascular recanalization therapy 3-12 hours after last known well time. Multimodal MRIs were acquired pretreatment, early (1-20 hours), and late (2-7 days) after treatment. Degree of recanalization was assessed on end of procedure catheter angiogram, degree of reperfusion on early posttreatment perfusion MRI, and infarct growth by analysis of diffusion lesion volumes on pretreatment and late MRIs. RESULTS: Twenty-seven (12 men, 15 women) underwent endovascular recanalization procedures at 6.0 +/- 2.1 hours (range, 3.0-11.5 hours) after last known well time. Immediate posttreatment perfusion lesion (Tmax > or =4 seconds) volume correlated strongly with infarct growth (r= .951, P < .001), exceeding the correlations of vessel recanalization score (r=-.198, P= .446) and pretreatment diffusion-perfusion mismatch volume (r= .518, P= .033). Without reperfusion, enlargement of DWI lesion volume was observed in all patients, and extent of enlargement depended on volume of immediate posttreatment perfusion defects. CONCLUSION: Our data indicate that posttreatment reperfusion is the major determinant of threatened tissue outcome, and suggest reperfusion even after 3 hours of symptom onset can alter tissue fate over a wide range of mismatch volumes.</P>
Pouria Moshayedi,David S. Liebeskind,Ashutosh Jadhav,Reza Jahan,Maarten Lansberg,Latisha Sharma,Raul G. Nogueira,Jeffrey L. Saver 대한뇌졸중학회 2020 Journal of stroke Vol.22 No.3
Background and Purpose Speedy decision-making is important for optimal outcomes from endovascular thrombectomy (EVT) for acute ischemic stroke (AIS). Figural decision aids facilitate rapid review of treatment benefits and harms, but have not yet been developed for late-presenting patients selected for EVT based on multimodal computed tomography or magnetic resonance imaging. Methods For combined pooled study-level randomized trial (DAWN and DEFUSE 3) data, as well as each trial singly, 100 person-icon arrays (Kuiper-Marshall personographs) were generated showing beneficial and adverse effects of EVT for patients with AIS and large vessel occlusion using automated (algorithmic) and expert-guided joint outcome table specification. Results Among imaging-selected patients 6 to 24 hours from last known well, for the full 7-category modified Rankin Scale (mRS), EVT had number needed to treat to benefit 1.9 (interquartile range [IQR], 1.9 to 2.1) and number needed to harm 40.0 (IQR, 29.2 to 58.3). Visual displays of treatment effects among 100 patients showed that, with EVT: 52 patients have better disability outcome, including 32 more achieving functional independence (mRS 0 to 2); three patients have worse disability outcome, including one more experiencing severe disability or death (mRS 5 to 6), mediated by symptomatic intracranial hemorrhage and infarct in new territory. Similar features were present in person-icon figures based on a 6-level mRS (levels 5 and 6 combined) rather than 7-level mRS, and based on the DAWN trial alone and DEFUSE 3 trial alone. Conclusions Personograph visual decision aids are now available to rapidly educate patients, family, and healthcare providers regarding benefits and risks of EVT for late-presenting, imaging-selected AIS patients.