bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WMP107: Outcomes in Mixed Location Intracerebral Hemorrhage and Microbleeds
Authors: Tsai Hsin-Hsi , Chen Szu-Ju , Pasi Marco , Tsai Li-Kai , Chen Ya-Fang , Tang Sung-Chun , Yen Ruoh-Fang , Jeng Jiann-Shing
Published: June 2021

Objective:
Patients with mixed location intracerebral hemorrhages/microbleeds (Mixed-ICH) have predominantly hypertensive vasculopathy rather than cerebral amyloid angiopathy (CAA), but the long-term outcomes in Mixed-ICH is unknown. In this study, we aimed to determine whether Mixed-ICH is a risk factor for vascular unfavorable outcome compared to CAA-ICH or strictly deep hypertensive intracerebral hemorrhage/microbleeds (HTN-ICH).

Methods:
305 consecutive ICH patients were included. Clinical data, neuroimaging markers and follow-up outcomes (recurrent ICH, ischemic stroke and vascular death) were compared between Mixed-ICH (n=151), CAA-ICH (n=33) and HTN-ICH (n=121). The association between follow-up events and neuroimaging markers were explored using multivariable Cox regression models.

Results:
Mixed-ICH patients were older (65.9±12.4 vs 58.1±13.2, p<0.001) than HTN-ICH, but younger than CAA-ICH patients (73.8 ± 13.9, p=0.001). The survival curves of follow-up outcomes were shown in the Figure. Compared to CAA-ICH, Mixed-ICH has similar incidence of vascular event (all P>0.05). Compared to HTN-ICH, Mixed-ICH is associated with higher ICH recurrence (hazard ratio [HR]=3.0 [1.2-7.7], p=0.021), more ischemic stroke (HR=8.2 [1.0-65.8], p=0.048), and vascular composite outcome (HR=3.5 [1.5-8.2], p=0.003) after adjustment for age and sex. In patients of Mixed-ICH, the presence of cortical superficial siderosis (cSS) is associated the development of ICH recurrence (p=0.048), ischemic stroke (p=0.009), and vascular composite outcome (p=0.008). The association between cSS and vascular composite outcome remains significant after further adjustment for microbleed number, lacune and WMH volume (p=0.019).

Conclusions:
Mixed-ICH harbors higher risk of unfavorable vascular outcome than HTN-ICH. Presence of cSS in Mixed-ICH independently predicts vascular event, suggesting the contribution of detrimental effect due to coexisting CAA.
Abstract WMP109: Implementation of a Clinical Score for Predicting Atrial Fibrillation in Cryptogenic Stroke
Authors: Zurru Maria , Lopez Armaretti Marianela , Balian Natalia , Luzzi Ariel , Brescacin Laura , Alonzo Claudia
Published: June 2021

Background:
The HAVOC score was developed to predict the risk of atrial fibrillation (AF) in patients with embolic events of undetermined origin. The purpose of this study was to evaluate the utility of the HAVOC score to predict AF in patients with cryptogenic stroke, included in a secondary prevention program (PROTEGE-ACV).

Methods:
patients with cryptogenic stroke were included. HAVOC score (one point each for peripheral vascular disease and obesity with body mass index >30, two points each for hypertension, age > 75, valvular heart disease, and coronary artery disease, 4 points for congestive heart failure) was calculated for all patients. AF was tracked by serial cardiac holter during the first 3 years of follow-up.

Results:
from December 2006 to December 2018, 836 patients with cryptogenic stroke were included. Mean age was 75 ± 13 years and 54% were women. The AF was detected in 14% of patients in the first year, 30% in the second year and 35% in the third year. When patients without AF (n: 544) and patients with AF (N: 292) were compared, a higher prevalence of women (59% vs. 50%, P0.01) and heart failure (37% vs. 20%, P0.001) were observed in patients with AF. The HAVOC score was significantly higher among patients with AF [median 4 with interquartile range (IQR) 2-5] than those without AF [median 2.0 (IQR 0-3)], p = 0.01. In the follow-up, all patients with a baseline HAVOC score greater than 4 developed AF.

Conclusions:
The HAVOC score is a simple tool based on clinical data, that can be useful for determining a high-risk AF population among patients with cryptogenic stroke.
Abstract WMP114: Safety and Efficacy of Prasugrel in Elderly/Low Bodyweight Japanese Patients With Ischemic Stroke: Randomized PRASTRO-II
Authors: Kitagawa Kazuo , Toyoda Kazunori , Kitazono Kazunori , Nishikawa Masakatsu , Nanto Shinsuke , Ikeda Yasuo , Abe Kenji , Ogawa Akira
Published: June 2021

Background and Purpose:
The safety of prasugrel in elderly and/or low body weight Japanese subjects who have a relatively high bleeding risk with antiplatelet therapy remains unknown. We aimed to investigate the safety and efficacy of long-term prasugrel monotherapy for stroke prevention compared with clopidogrel in elderly and/or low body weight Japanese patients with non-cardioembolic stroke.

Methods:
In this randomized, double-blind, comparative, phase III study, elderly (age ≥75 years) and/or low body weight (≤50 kg) Japanese patients with a previous history of non-cardioembolic stroke were assigned to a prasugrel 3.75 mg group (PRA3.75), a prasugrel 2.5 mg group (PRA2.5), or a clopidogrel 50 mg group (CLO50) and followed up for 48 weeks. The primary safety endpoint was the combined incidence of primary safety events, defined as life-threatening, major, and other clinically relevant bleeding. The efficacy endpoint was a composite of ischemic stroke, myocardial infarction, and death from other vascular causes.

Results:
A total of 654 subjects (age 76.4±7.3 years; body weight 55.6±9.3 kg; women 43.9%) were enrolled. The combined incidence of primary safety events was 4.2%, 1.9%, and 3.6% in the PRA3.75, PRA2.5, and CLO50 groups, respectively. The incidences of bleeding leading to treatment discontinuation were 2.3%, 0.9%, and 2.2% in the PRA3.75, PRA2.5, and CLO50 groups, respectively, while the incidence of ischemic stroke, myocardial infarction, and death from other vascular causes was numerically lower but non-significant in patients treated with prasugrel than in patients treated with clopidogrel [0.0% (0/216), 3.3% (7/215), and 3.6% (8/223)].

Conclusions:
Elderly and/or low body weight Japanese patients with previous non-cardioembolic stroke who received prasugrel 3.75 mg showed similar results in terms of primary safety endpoint and a numerically lower incidence of ischemic stroke, myocardial infarction, and death from other vascular causes compared with those who received clopidogrel 50 mg.
Abstract WMP116: Thromboembolism in Atrial Fibrillation: Relationship to Leukocyte Gene Expression
Authors: Jickling Glen C , Kamtchum Joseph , Sykes Gina , Batool Yusra , Boryana Stamova , Ander Bradley P , Sharp Frank
Published: June 2021

Background:
Atrial fibrillation (AF) is an important cause of stroke, for which anticoagulation provides substantial benefit. However, not all patients with AF will have a stroke. There remains uncertainty regarding factors that promote thromboembolism and stroke in patients with AF. In this study we examined differences in blood cell gene expression unique to AF in acute stroke to better understand factors important to atrial fibrillation thromboembolism in human stroke.

Methods:
Gene expression in blood was compared in acute stroke patients with AF to non-AF stroke and to controls without stroke. Blood was collected in PAXgene tubes, and leukocyte/platelet gene expression was measured by Affymetrix microarray. Differentially expressed genes were identified using ANOVA adjusted for age, sex and batch.

Results:
In the 184 patients studied, 40 were acute strokes with AF, 143 had non-AF acute stroke, and 116 were non-stroke controls. There were 43 genes unique to AF in patients with stroke, and 69 genes associated AF that were shared between AF stroke and controls (FDR<0.05, fold change>|1.5|). Functional analysis indicate acute stroke AF genes are associated with changes in the hematological system including blood cell rheology and leukocyte activation. In contrast non-stroke AF genes are associated cardiac hypertrophy and blood vessel injury.

Conclusions:
AF has differences in blood cell gene expression in acute stroke that may relate to risk of thromboembolism. Acute stroke patients with AF display changes in blood cell rheology and leukocyte activation; whereas non-stroke AF patients have changes in cardiac hypertrophy and vascular injury. These differences are important to understanding blood cell contribution to thrombus formation and stroke risk in patients with AF. Further study is required to assess the relationship of these gene changes to stroke risk and response to anticoagulation in patients with AF.
Abstract WMP12: Benefits of Thrombectomy Among Patients Who Did Not Achieve Functional Independence in DEFUSE 3
Authors: Sarraj Amrou , Lansberg Maarten , Marks Michael P , Mlynash Michael , Heit Jeremy J , Savitz Sean I , Albers Gregory W
Published: June 2021

Background:
While endovascular thrombectomy (EVT) patients may not achieve functional independence, they may avoid devastating outcomes as in profound disability/death.

Methods:
DEFUSE 3 patients who did not achieve mRS 0-2 were assessed for a shift towards reductions in severe (mRS 4-6) and profound (mRS 5-6) disability, mortality, length of stay (LOS) and increased rates of home/rehabilitation discharges.

Results:
126 of the 182 randomized in DEFUSE 3 did not achieve mRS 0-2 (EVT 51, MM 75). Baseline characteristics were similar. EVT was associated with a higher mRS 3 rate (28% vs 18%) and lower rates of severe (72% vs 82%) and profound disability (39% vs. 50%), EVT vs MM respectively, with a trend for a shift towards less disability aOR=1.6 (95%CI=0.9-3.2, P=0.138), figure 1. Mortality rates were numerically lower with EVT (25% vs 31, p=0.528). EVT patients had a trend for shorter LOS (8.6 (6.5-13.7) vs 9.3 (7.1-16.3) days, p=0.156) and increased rates of home/rehabilitation discharges 51% vs. 40%, p=0.224. Older age correlated independently with severe disability aOR=1.04 per year/age, (95%CI=1.01-1.07, p=0.023) as did more severe strokes, aOR per NIHSS point=1.07, 95%CI=0.99-1.15, P=0.096). Larger final infarct volumes had a trend towards severe disability in EVT aOR=1.005, 95%CI=0.996-1.013, p=0.257, but not in MM aOR=1.0 (95% CI 0.993-1.007, p=0.966). Lack of reperfusion (>90% Tmax>6 reduction) had a strong trend for severe disability in MM (83% in non-reperfusers vs. 50% for reperfusers), p=0.056, but not in EVT: 77% vs. 63%, p=0.484.

Conclusion:
In patients who did not achieve functional independence, EVT resulted in reduced rates of severe and profound disability, decreased length of stay and increased home and rehabilitation discharges. Older patients, more severe strokes and those who did not achieve reperfusion were more likely to have severe disability especially if not treated with EVT. EVT may result in avoiding severe disability in elderly patients.
Abstract WMP3: Exosomes Derived From Stroke Activated Platelets Impair Cerebral Endothelial Permeability
Authors: Li Chao , Wang Chunyang , Zhang Li , Michael Chopp , Zhang Zheng Gang
Published: June 2021

Introduction:
Stroke activated platelets damage the blood brain barrier (BBB). Mechanisms underlying this process remain to be investigated. The present study tested a hypothesis that exosomes, nano size extracellular vesicles, derived from stroke-activated platelets promote BBB leakage.

Methods:
Platelets were harvested from blood samples collected from non-stroke adult and aged male rats and from respective rats subjected to 4h of middle cerebral artery occlusion (MCAO) (n=6/group). Exosomes were then isolated from the platelets by means of differential ultracentrifugation. Primary cerebral endothelial cells harvested from healthy adult rats were treated with platelet exosomes. Endothelial permeability and trans-endothelial electrical resistance (TEER) were assayed. Western blot analysis was performed to measure pro-coagulation and tight junction proteins.

Results:
Platelet exosomes (P-Exos) had an average size from 70 to 82 nm among adult and aged rats and these exosomes contained platelet exosomes markers: CD41, CD63, CD9 and Alix. P-Exos derived from non-ischemic adult and aged rats exhibited TEER at 154±18 and 159 ±16 Ω.cm
2
, respectively, and did not increase FITC-dextran leakage. However, P-Exos from ischemic adult rats significantly (p<0.05) decreased TEER (118 ±11 vs 154±18Ω.cm
2
in non-ischemia) and increased FITC-dextran leakage by 178%. P-Exos from aged ischemic rats further significantly decreased TEER (98 ±9 Ω.cm
2
) and augmented dextran leakage to 216%. Western blot analysis of endothelial cells showed that P-Exos from ischemic adult rats significantly increased pro-inflammation proteins, ICAM-1, TNF-a and NFkB p65 and decreased tight junction proteins, ZO-1 and occludin, whereas P-Exos from ischemic aged rats further significantly increased and decreased pro-inflammation proteins and junction proteins.

Conclusion:
These data provide new insights into how stroke activated platelets mediate BBB disruption and promote endothelial proinflammatory protein expression via their released exosomes and how aging further negatively impacts cerebral endothelial cells.
Abstract WMP30: Updates on the Paradigm Shift to Endovascular Modalities for Treatment of Ruptured and Unruptured Cerebral Aneurysms: National Inpatient Sample 2007-2016
Authors: Wang Alice S , Campos Jessica K , Colby Geoffrey P , Coon Alexander L , Lin Li-Mei
Published: June 2021

Introduction:
The neuroendovascular space continues to evolve with innovative devices. In 2011, the Food and Drug Administration (FDA) approval of the Pipeline Embolization Device (PED) has led to adoption of flow diversion technique as the newest endovascular approach for cerebral aneurysm treatments.

Methods:
United States 2007-2016 National Inpatient Sample data was used to identify unruptured (UA) and ruptured aneurysms (RA) treated with open surgery and/or endovascular therapy. Trends in treatment patterns were analyzed.

Results:
A total of 39,282 hospital discharges were identified (UA: surgical n=7,847 vs. endovascular n=12,797; RA: surgical n=8,108 vs. endovascular n=10,530). For UA, similar mean numbers of cases were treated surgically & endovascularly up to 2011 (847.4 ± 107.7 vs. 1,120.4 ± 254.1, respectively, p=0.2118). From 2012, more UA were treated endovascularly than surgically (1,439.0 ± 419.2 vs. 722.0 ± 43.4, respectively, p=0.0007). Post 2011, the Northeast (NE), the Midwest (MW), and the South (S) performed significantly more endovascular therapies (NE: 153.8 ± 17.8 surgical vs. 290.0 ± 94.2 endovascular, p=0.0286; MW: 184.6 ± 15.1 surgical vs. 318.4 ± 81.6 endovascular, p=0.0331; S: 234.2 ± 7.2 surgical vs. 587.8 ± 152.5 endovascular, p<0.0001). For RA, similar mean numbers of cases were treated surgically & endovascularly up to 2011 (949.4 ± 52.8 vs. 1,054.4 ± 219.6, respectively, p=0.8481). From 2012, more RA were treated endovascularly than surgically (1,051.6 ± 330.2 vs. 672.2 ± 61.4, respectively, p=0.0183). The South treated significantly more RA endovascularly than surgically (418.8 ± 129.1 vs. 242.2 ± 10.9, respectively, p=0.0004).

Conclusions:
Treatment paradigm for cerebral aneurysms continues to shift towards endovascular options. The introduction of flow diversion technology in late 2011 may have contributed to the rise in endovascular treatments since then. The South displayed the greatest use of endovascular approaches.
Abstract WMP36: Wall Shear Stress Disturbances May Be Key Requirements for Cerebral Aneurysm Growth: Computational Flow Dynamic Analysis of 15 Cases in NHO CFD ABO Study
Authors: Fukuda Shunichi , Shimogonya Yuji
Published: June 2021

Introduction:
In 2013, we conducted a multi-institutional prospective observational study in order to identify hemodynamic environments involved in the rupture and growth of unruptured cerebral aneurysms by computational fluid dynamic (CFD) analysis (National Hospital Organization CFD ABO Study: UMIN000013584). There were 461 cases registered and observed for 3 years on the condition that 3DCTA and carotid echocardiography were performed every year. The observation period ended at the end of March this year. There were 32 cases that enlarged, and 209 cases that did not enlarge or rupture after 3 years of observation period. Here, 15 growing cases and 15 non-growing cases were hemodynamically evaluated.

Methods:
Pulsatile blood flow was simulated using ANSYS-CFX, based on the Navier-Stokes equations for incompressible fluid. Multivariate regression analysis was performed to find differences between growing and non-growing aneurysms in wall shear stress (WSS) magnitude-based metrics (WSS, WSSG, NWSS, NWSSG) and WSS disturbance-based metrics (OSI as a metric for unidirectional WSS disturbance, NtransWSS as a metric for multi-directional WSS disturbance)on the CFD modelling after adjustment for age, sex, hypertension, smoking history, and aneurysm size and location.

Results and Conclusions:
In the growing and non-growing aneurysms, the average age was 71.8 ± 12.6 and 66.3 ± 11.1 years, the maximum diameter 5.48 ± 2.64 and 5.47 ± 1.85 mm, female 10 and 6 cases, HT 10 and 10, smoking 6 and 11, respectively. Both OSI (p=0.0215) and NtransWSS (p=0.0428) were significantly higher in growing aneurysms compared to non-growing ones, whereas there were no significant differences in WSS magnitude-based metrics(figure). The data suggested that WSS disturbances may be closely associated with the growth of cerebral aneurysms.
Abstract WMP39: Protein Phosphatase 1 Regulatory Subunit 12C Contributes to Atrial Myosin Light Chain Dephosphorylation in Atrial Fibrillation
Authors: Perike Srikanth , Alsina Katherina M , Sridhar Arvind , Darbar Dawood , Wehrens Xander , McCauley Mark D
Published: June 2021

Background:
Atrial fibrillation (AF) increases stroke risk five-fold. Atrial hypocontractility from atrial myosin light chain (MLC2a) dephosphorylation contributes to stroke risk in AF. Recent proteomic data has shown increased protein phosphatase 1 subunit 12C (PPP1R12C) targeting to MLC2a in AF. However, it is unclear whether PPP1R12C causes MLC2a dephosphorylation in AF.

Objective:
Determine whether increased PPP1R12C expression causes MLC2a dephosphorylation and increases AF risk.

Methods:
Western blots and co-IPs were performed to evaluate the relationship among PPP1R12C, PP1c and MLC2a in human atrial tissues (AF vs SR). Mice with either a knockout (KO) or lentiviral (LV) cardiac overexpression of PPP1R12C were evaluated with invasive EP studies for AF inducibility vs WT controls.

Results:
In human AF, PPP1R12C was increased 4-fold (
P
<0.005, n=6) with an 88% reduction in S-19-MLC2a phosphorylation (
P
<0.05, n=4). PPP1R12C-PP1c and PPP1R12C-MLC2a binding was increased 2-fold in AF (
P
<0.05, n=6). AF burden in LV-12C mice increased nearly tenfold vs. KO and WT mice (
P
<0.05, n=6).

Conclusion:
In human AF, increased PPP1R12C expression is associated with reduced P-MLC2a through enhanced binding with the PP1c catalytic subunit. This dephosphorylation is a likely contributor to atrial hypocontractility and stroke risk in AF. Additionally, increased PPP1R12C expression in mice increases AF risk. Future studies will examine the effects of increased PPP1R12C expression upon atrial contractile function in mice.
Abstract WMP44: Differential Middle Cerebral Artery Plaque Characteristics in Patients With Transient Ischemic Attack and Ischemic Stroke: A High-Resolution MR Vessel Wall Imaging Study
Authors: Xiao Jiayu , Padrick Matthew , Yang Qi , Jiang Tao , Xia Shuang , Wu Fang , Guo Yu , Li Debiao , Schlick Konrad , Song Shlee , Fan Zhaoyang
Published: June 2021

Introduction:
Intracranial atherosclerotic disease (ICAD) correlates highly with transient ischemic attack (TIA) and acute ischemic stroke (AIS). Magnetic Resonance (MR) vessel wall imaging (VWI) is an emerging non-invasive imaging modality for directly assessing ICAD lesions.

Methods:
We retrospectively analyzed MR-VWI from 42 TIA patients and 45 AIS patients with ICAD. All patients fulfilled the following criteria: (1) stenosis >30% of a middle cerebral artery (MCA), (2) symptoms contralateral to stenotic MCA, (3) no coexisting stenosis at other major vessels; (4) lack of compelling evidence to other etiologies of stroke/TIA. Vascular lesions were analyzed with MR-VWI with respect to the stenosis degree, vessel wall irregularity, plaque burden (PB), remodeling index (RI), plaque-wall contrast ratio (CR) and plaque enhancement grade (EG).

Results:
EG (OR 3.88, 95%CI 1.42-10.57, P=0.006) was a risk factor for AIS while PB (OR 0.65, 95%CI 0.27-1.54, P=0.008) was a risk factor for TIA. In patients with 30-70% degree stenosis, CR (OR 5.38, 95%CI 1.39-20.75, P=0.008) was a risk factor for stroke, while PB (OR 0.4, 95%CI 0.1-1.65, P=0.006) remained a risk factor for TIA.

Conclusions:
In our study, PB appeared as a risk factor for TIA but not for AIS. This suggests that unstable plaque accounting for AIS may have a wide range of PB. We further found that CR and EG are more associated with AIS than TIA. Lesions with high CR and strong enhancement may be more prone to producing the permanent ischemic injury. Further study is needed to elucidate the role of MR-VWI in differential diagnosis and management of TIA and AIS.
Abstract WMP46: Frequency of High-Risk Features and Stroke Risk in Asymptomatic Carotid Atherosclerosis: Systematic Review and Meta-Analysis
Authors: Kamtchum Tatuene Joseph , Wilman Alan , Saqqur Maher , Sykes Gina , Shuaib Ashfaq , Jickling Glen C
Published: June 2021

Background:
The recommended treatment of asymptomatic carotid atherosclerosis is best medical therapy since the 1% annual risk of stroke is lower than the risk of stroke from revascularization. Specific imaging features may identify patients at increased risk of stroke and optimize the risk-benefit ratio of carotid surgery. To assess the relevance and feasibility of such approach, we aimed to summarize available data on the frequency of high-risk features and the related risk of stroke in patients with asymptomatic carotid atherosclerosis.

Methods:
A search of Pubmed and Ovid-Embase identified prospective studies reporting findings of carotid plaque imaging and incidence of stroke in patients with asymptomatic carotid atherosclerosis. Prevalence of high-risk features and incidence of ipsilateral ischemic events were pooled using random-effect meta-analysis.

Results:
Thirty-five studies enrolling 5808 participants with asymptomatic carotid atherosclerosis of various grades were included. The pooled prevalence (95% CI) of high-risk features on plaque imaging was 28.8 (18.8 - 38.7). The prevalence of neovascularization was 53.5% (45.2 - 61.8), echolucency 40.0% (30.8 - 49.6), lipid-rich necrotic core 35.7% (24.1 - 48.1), thin or ruptured fibrous cap 27.5% (14.2 - 43.3), silent brain infarcts 27.0% (15.3 - 40.5), impaired cerebrovascular reserve 25.9% (10.3 - 45.5), intraplaque hemorrhage 19.2% (13.9 - 25.1), microembolic signals 14.4% (8.9 - 20.8), and ulceration 13.5% (1.3 - 34.0). In 15 cohort studies enrolling 4215 participants, the mean duration of follow-up was 3.5 years (2.0 - 4.6). The pooled incidence of ipsilateral ischemic events was 2.7 per 100 person-years (1.6 - 4.0). This incidence was higher in patients with a high-risk feature (4.9%, 2.3 - 8.2) than in those without (0.9%, 0.2 - 1.8) with an odds ratio of 4.6 (2.3 - 9.3).

Conclusion:
High-risk features on imaging are frequent in asymptomatic carotid atherosclerosis and associated with a fourfold increase in the annual risk of ipsilateral ischemic events. A risk-oriented selection of patients with asymptomatic carotid atherosclerosis prior to randomization in revascularization trials appears relevant and may be a strategy to prevent stroke in asymptomatic carotid atherosclerosis.
Abstract WMP5: CT Perfusion Profiles of Infarct Growth in Large Vessel Occlusion Acute Stroke Patients Sensitive to Decreases in Blood Pressure
Authors: Ortega-Gutierrez Santiago , Dai Biyue , Dandapat Sudeepta , Holcombe Andrea , Zevallos Cynthia , Lopez Cardenas Gloria Viviana , Ansari Sameer , Quispe Orozco Darko , Nguyen Cindy Khanh , Silverman Andrew , Kodali Sreeja , Strander Sumita , Kimmel Alexandra , Peshwe Krithika
Published: June 2021

The growth of a final infarct volume largely depends on cerebral perfusion after a large vessel occlusion (LVO) stroke. Decreases of blood pressure (BP) before recanalization are associated with larger infarct and worse functional outcome. It is uncertain whether an intervention to elevate BP improves outcome, particularly if susceptibility to the BP beneficial effect varies by individual factors such as the collateral vessel status. We aim to define the association of BP, infarct growth and perfusion patterns of potential vulnerable patients. We retrospectively studied patients with anterior LVOs who underwent mechanical thrombectomy (MT) at two comprehensive stroke centers. Only patients with TICI score ≥2b and admission CTP and 24 hours MRI were included. Infarct growth was calculated as 620 ADC volume subtracted from CBF <30% in the ischemic hemisphere using the Automatic Rapid Software. Hypoperfusion intensity ratio (HIR) was calculated as the ratio of the Tmax >10s volume to the Tmax >6s volume with a lower value indicating a more favorable ratio. Intra-procedural BP was continuously monitored using a non-invasive cuff or intraarterial catheter. Systolic BP (SBP) and mean arterial pressure (MAP) were averaged at various time points throughout MT. We analyzed 199 patients from 317 MT. A quantile regression with quantile τ = 0.25, 0.5 and 0.75 was fitted to study how Infarct Growth Rate (IGR) is affected by BP change. At 0.25 and 0.5 quantiles, one unit change in MAP did not lead to a significant change for IGR. At the 0.75 quantile (quartile 3), one unit change in MAP resulted in 0.79 unit change in IGR (95% CI: -0.11, 1.69; p= 0.09). Hence, we identified patients whose IGR is above the 0.75 quantile as the vulnerable subgroup. The vulnerable subgroup had significant larger median volumes of Tmax in all sequences when compared to the non-vulnerable subgroup: Tmax10 (67.8cc vs 40.0cc, p= 0.004), Tmax8 (92.9cc vs 62.0cc, p= 0.003), Tmax6 (134cc vs 98.7cc, p =0.003), Tmax4 (228.6cc vs 184.3cc, p= 0.016). The median HIR was also significantly higher (0.4 vs 0.3, p= 0.026) in the BP vulnerable population. Admission perfusion patterns of collaterals evaluated may help to identify the most vulnerable population to increase their infarct growth when facing decrease in BP.
Abstract WMP52: Age, Sex and Regional Differences in Recent Stroke Incidence Trends Among Young Adults
Authors: Kim Youngran , Lee Songmi , Meeks Jennifer , Bambhroliya Arvind B , Karuse Trudy , Sheth Sunil , Vahidy Farhaan S
Published: June 2021

Background:
In the US, one third of strokes occur among younger adults (< 65 years). While stroke incidence among elderly has declined, trends in younger adults by age, sex and region are unknown. We report recent trends in stroke incidence among commercially-insured young adults aged 20 - 64.

Methods:
Stroke incidence was estimated using 2011 - 2017 IBM MarketScan® Commercial Database stratified by age (20 - 34, 35 - 44, 45 - 54, 55 - 64), sex, and US Census region and was extrapolated to the US population using census data. Stroke cases were identified based on a primary diagnosis of either ischemic stroke (IS) or intracerebral hemorrhage (ICH) or subarachnoid hemorrhage (SAH) using validated ICD-9 / 10 codes. We report incidence rates (IR) per 100,000 person-years, 95% confidence intervals and proportional change in IR between 2011 and 2017.

Results:
We identified 115,276 stroke admissions resulting in 172 million person-years. The overall stroke IR increased by 7% from 60.0 to 64.2 per 100,000 person-years between 2011 and 2017. The increase was greater among males as compared to females (9.8% vs 3.3%) and across both sexes the largest increase was observed for age category of 35 - 44 years (Table 1). Age-specific IR increased in all age categories except 20 - 34. Across US regions, the South showed the highest IR increase (10.0%) (Figure 1). IR for IS and ICH increased while a decrease in SAH IR was observed. The IR for IS was higher for males vs females (12.7% vs 5.4%), whereas it was higher for females vs males for ICH (14.5% vs 3.6%).

Conclusions:
Our analyses indicate an overall increase in stroke incidence for commercially-insured younger adults during a contemporary time period. Males between the ages of 35 - 44 have experienced the greatest increase in stroke incidence. Furthermore, the Southern US continues to experience highest increases in stroke incidence and there are gender differences in IR for stroke subtypes. Targeted strategies for stroke prevention may be warranted.
Abstract WMP53: Traditional Vascular Risk Factors Account for Different Proportions of Ischemic Stroke Within Different Gender and Race Groups
Authors: Aradine Elizabeth M , Hou Yan , Ryan Kathleen A , Mehndiratta Prachi , Phipps Michael S , Chaturvedi Seemant , Cronin Carolyn A , Wozniak Marcella A , Merino Jose G , Dutta Tara M , Cole John W , Kittner Steven J
Published: June 2021

Introduction:
Few studies have compared the proportion of ischemic strokes attributable to traditional vascular risk factors (population-attributable risk percent or PAR%) between genders and races. The PAR% is a function of the population prevalence and strength of association of a risk factor.

Methods:
A population-based case-control study of ischemic stroke in young adults ages 18-49 in the Baltimore-Washington region was used to study the prevalence, odds ratios, and PAR% of hypertension, diabetes, and smoking among blacks and whites. Logistic regression was used to calculate age-adjusted odds ratios. All analyses were stratified by gender.

Results:
There were 1044 cases and 1099 controls. Of the cases, 47% were black, 54% were women. Roughly a quarter to a third of all strokes in women were attributable to smoking. Due to the higher prevalence of hypertension and a higher odds ratio for hypertension in black men (OR 3.9, 95% CI 2.6-5.9) compared to white men (OR 1.8, 95% CI 1.3-2.6), there was a much higher PAR% for hypertension among black men than white men. See Table 1 for prevalence and Table 2 for PAR% stratified by gender and race.

Conclusion:
Traditional vascular risk factors have the potential to explain a high proportion of ischemic stroke in young adults. The high proportion of strokes in women attributable to smoking underscores the need for targeted smoking cessation interventions in this population. Diabetes and, especially, hypertension are important contributors to the excess population burden of ischemic stroke among blacks. These findings support the value of early screening and treatment for hypertension in young blacks.
Abstract WMP67: Changes in Left Atrial Strain Are Associated With Embolic Appearing Ischemic Stroke
Authors: Johansen Michelle C , Doria De Vasconcellos Henrique , Gottesman Rebecca
Published: June 2021

Background:
Accruing evidence suggests that changes in cardiac structure and function, irrespective of tachyarrhythmia, are responsible for thrombus formation. Although transthoracic echocardiogram (TTE) is frequently used for cardiovascular evaluation in ischemic stroke patients (IS), many cardiac features that could clarify stroke subtype are poorly characterized without optimal evaluation of the left atrium (LA). 2D speckle tracking echocardiography (STE) allows an accurate, reproducible, and detailed assessment of the LA cycle.

Methods:
IS with clinically indicated TTE provided consent. LA STE was quantified using a post processing wall motion tracking software per standard definitions. Strain/strain rate (Sr) curves for the 3 components of the LA cycle: 1) Reservoir (Global longitudinal Sr (Srmax)) 2) Conductive (Early LA Sr (Sre)) and 3) Contractile (Late LA Sr (Sra)) were evaluated. The association of embolic-appearing stroke (cardioembolic or cryptogenic; ES) with LA STE features (independent variables) was tested using logistic regression (OR (95%CI)) adjusted for covariates.

Results:
Participants (N=136) were 53-70yo, 57% female and 59% black. Incremental increases in Sra (worse LA contraction) were associated with >2 times greater odds of ES (2.47 (1.29-4.72)) and improvement in Smax (LA reservoir) was associated with decreased odds of ES when adjusting for demographics (0.98 (0.96-0.99)), but not in a fully adjusted model. Improvement in the corresponding emptying fractions was significantly associated with decreased odds of ES (aEF 0.93 (0.98-0.97) tEF 0.96 ( 0.93-0.99)).

Conclusions:
In this study the odds of ES was higher in those with worse LA contraction and decreased with improvement in LA reservoir with corresponding decreased odds of ES with improvement in emptying fractions. LA STE is an underutilized technology and may represent a promising tool for characterization of LA performance in patients with otherwise unexplained ES.
Abstract WMP72: Is Arrival Blood Pressure Indicative of Stroke Type to Optimize Premixing TPA? An Analysis of Two National Institute of Neurological Disorders and Stroke Trials
Authors: Salottolo Kristin , Wyborny Ann , McCarthy Kathryn , Bartt Russell , Bar-Or David
Published: June 2021

Introduction:
Most patients with acute neurological events present hypertensive. It is unknown whether blood pressure (BP) can aid in differentiating stroke type: acute ischemic stroke (AIS) or primary intracerebral hemorrhage (PICH). If BP is indicative, management could be expedited before confirmatory neuroimaging, such as pre-mixing IV tPA and lowering elevated blood pressure. The study objectives are a) to determine whether arrival BP can differentiate stroke type and b) to determine an optimal BP cut-off to aid in pre-mixing tPA.

Methods:
Our study population was selected from two NINDS clinical trials that did not use blood pressure as a selection criterion: ALIAS 1 trial (AIS, n=434) and ERICH trial (PICH, n=3,000). Multivariate logistic regression and t-tests were used to analyze the first recorded BP (systolic: SBP; diastolic: DBP) for patients with AIS vs. PICH. Receiver operator characteristic (ROC) curves were used to determine an optimal BP cutoff for ruling out PICH and pre-mixing tPA (specificity) and conversely for correctly identifying AIS (sensitivity).

Results:
Compared to AIS, patients with PICH had significantly higher mean SBP (186 vs. 158, p<0.001) and DBP (103 vs. 84, p<0.001), figure 1. After adjustment for age, gender, race/ethnicity, and history of hypertension, there was 23% increased odds of PICH for each 10-unit increase in SBP (p<0.001) and 35% increased odds of PICH for each 10-unit increase in DBP (p<0.001). The AUROC was 0.70, with 95% specificity for ruling out ICH (5% tPA wastage) using cutoffs of SBP <127 and DBP <80. Conversely, 95% sensitivity for identifying AIS resulted in cutoffs of SBP <211 and DBP <130, corresponding to 5% of AIS patients with a delay in tPA for not pre-mixing.

Conclusion:
Although our study demonstrated arrival blood pressure was significantly associated with stroke type, the significant overlap and moderate AUROC suggest BP is not indicative and sufficiently dichotomous to delay pre-mixing tPA.
Abstract WMP78: The Efficacy of Angiotensin II Peptide Vaccination Against White Matter Lesions of Vascular Dementia in Rats
Authors: Wakayama Kouji , Shimamura Munehisa , Nakagami Hironori , Morishita Ryuichi
Published: June 2021

Background & Purposes:
There had been no attempt to show the efficacy of therapeutic vaccination in vascular dementia. A rat model of vascular dementia was prepared by bilateral common carotid artery ligation (2VO). The purpose of this study is to investigate whether pre-exposure Angiotensin II (Ang II) peptide vaccination exhibits the protective effects against white matter lesions (WML) in 2VO rats.

Methods:
After subcutaneous injection of Ang II peptide vaccine (10μg/200μl) or saline (200μl) to Wistar rats (male) at the time point of 6, 8 and 10 week-old, 2VO or sham surgery was performed at 12 week-old. Cognitive function was evaluated after 14 days of 2VO using the novel object recognition (NOR) test. Anti-Ang II antibody (Ab) level was quantified using ELISA. Histological examinations of WML and demyelination in the corpus callosum (CC) were evaluated using immunohistochemistry (IHC), 5-bromodeoxyuridine (BrdU) assay and Klüver-Barrera staining. Western blot analyses of VCAM-1, FGF2, phospho-CREB and CREB using proteins extracted from CC were performed to investigate the mechanism of restoration of WML by Ang II vaccination.

Results:
Histological examinations presented that exacerbation of WML and demyelination observed in saline treated (S) rats was ameliorated in Ang II vaccinated (V) rats. The results of NOR test indicated that cognitive dysfunction observed in S rats was improved in V rats at 14 days after 2VO. Expression of VCAM-1 in CC of S rats was significantly reduced in V rats at 7 days after 2VO. BrdU assay exhibited that vaccination accelerated the differentiation of oligodendrocyte progenitor cells (OPCs) in WML from 14 days to 28 days of 2VO. Western blot presented that both CREB phosphorylation and FGF2 expression in CC were increased in V rats compared with S rats at 14 days after 2VO. Double IHC showed that FGF2 expressing cells were mostly endothelial cells and astrocytes in WML.

Conclusions:
Ang II vaccination restored WML as well as cognitive function in 2VO rats. Our findings suggested that Ang II vaccination ameliorated cerebrovascular endothelial dysfunction which could accelerate the OPCs differentiation through increased expression of FGF2 in endothelial cells or astrocytes in 2VO rats.
Abstract WMP8: Use, Characteristics, and Outcomes of Endovascular Thrombectomy in Acute Ischemic Stroke Patients Beyond 6 Hours of Stroke Onset in US Clinical Practice
Authors: Schwamm Lee H , Xu Haolin , Matsouaka Roland , Shah Shreyansh , Zachrison Kori , Smith Eric , Xian Ying , Fonarow Gregg , Saver Jeffrey
Published: June 2021

Introduction:
Two recent RCTs have shown benefit of endovascular thrombectomy (EVT) in acute ischemic stroke (AIS) 6-24 h from last known well (LKW) using imaging-guided patient selection, however little is known about outcomes in contemporary non-trial settings. We assessed the frequency and outcomes of EVT beyond 6 h in the US national GWTG-Stroke clinical registry.

Methods:
We analyzed all AIS hospitalizations between 1/1/09 - 10/1/18 at fully participating GWTG-Stroke sites to identify 53,702 patients at 697 sites treated with EVT (± IV tPA) who had valid LKW, symptom discovery (SxD) and treatment times recorded. Hospital characteristics were analyzed at the 470 sites that treated
>
10 patients during the study. Table 1 shows significant covariates (standardized differences >10%) and adjusted outcomes based on logistic regression models.

Results:
Treatment >6 h from LKW occurred in 33% of all EVT cases (median 4.7 h, IQR 3.3-7 h), and all were treated <6 h from SxD. The proportion of EVT cases treated >6 h from LKW varied widely across sites (median 30%, IQR 24-38%) and increased sharply in 2018 (Fig). Compared to
<
6 h, patients treated >6 h differed in age, AF, arrival mode/time, stroke severity and use of anticoagulation, and presented to higher EVT volume centers. Late window EVT patients had less favorable adjusted outcomes at discharge for mortality, ambulation and disposition to home or IRF compared to <6 h patients (Table).

Conclusions:
EVT is frequently performed >6h, accounting for one-third of cases nationally. As adjusted functional outcomes at discharge are worse in these patients, further research is required to ensure optimal EVT outcomes in clinical practice settings
Abstract WMP81: FGF21 Reduces Post-Stroke Blood Brain Barrier Damage in Diabetic db/db Male Mice
Authors: Jiang Yinghua , Liu Ning , Wang Xiaoying
Published: June 2021

Background and Purpose:
Our previous studies demonstrated that recombinant human Fibroblast growth factor 21 (rFGF21), an endocrine member of the FGF family is potently beneficial for improving long-term neurological outcomes of type 2 diabetes (T2D) stroke mice. Here we tested hypothesis that rFGF21 protects against post-stroke BBB damage by PPARγ activation of cerebral micovascular endothelium.

Methods:
T2D db/db mice and their non-diabetic counterparts db/+ mice were subjected to focal stroke of dMCAO. Four experimental groups: 1) db/+ stroke, 2) db/db stroke, 3) db/db stroke+rFGF21, and 4) db/db stroke+rFGF21+GW9662. rFGF21 (1.5mg/kg, i.p.) was injected at 6 hours after stroke and PPARγ inhibitor GW9662 (4mg/kg, i.p.) was injected 30 min prior to rFGF21 treatment. At 24 hours post-stroke, we collected peri-infarct nuclear fraction for PPARγ-DNA binding activity assay using EMSA, microvascular isolation for RT-PCR analyzing mRNA levels of proteins constituting BBB junctional complex (occluding, clauding-5, VE-cadherin and ZO-1) and PPARγ targeted downstream genes (CD36 and FABP4) as indicators of PPARγ activity in microvasculature. BBB permeability was assessed by measuring 3kDa FITC-dextran or Evans blue extravasations at 48 hour post-stroke.

Results:
Ischemic stroke induced a significant decrease of PPARγ-DNA binding activity and mRNA levels of BBB junctional proteins in peri-infarct area, and a significant increase of BBB permeability in diabetic db/db stroke mice compared to db/+ stroke mice. Changes of mRNA levels of CD36 and FABP4 in brain microvascular isolation were consistent with changes of PPARγ-DNA binding activity. rFGF21 administration significantly increased PPARγ-DNA binding activity, elevated mRNA levels of BBB junctional complex proteins and ameliorated BBB leakage. However, pre-treatment of GW9662 partially abolished the post-stroke BBB protective effects of rFGF21.

Conclusions:
rFGF21 has strong protective effects in acute BBB leakage after stroke, and the underlying mechanisms is partially via increase in PPARγ-DNA binding activity and mRNA expression of BBB junctional complex proteins. Together with our previous investigations, rFGF21 might be a promising candidate for treating diabetic stroke.
Abstract WMP87: A Quality Improvement Program’s Impact on Stroke Readmission Rates
Authors: Farooq Muhammad U , Thomas Kathie
Published: June 2021

Background/Objectives:
The Centers for Medicare and Medicaid Services (CMS), as part of its Hospital Inpatient Quality Reporting Program, examines risk-standardized 30-day hospital readmissions for ischemic stroke patients. Preventable post-stroke readmissions are not well understood. The objective of this study is to review Michigan hospitals post-stroke readmission rates in relation to the use of Get With The Guidelines (GWTG)-Stroke, an in-hospital quality improvement program.

Methods:
A retrospective review was conducted of stroke discharges and readmission rates from 135 Michigan hospitals using GWTG-Stroke and CMS 2018 calendar year data. Data was analyzed looking at use of GWTG, hospital award level, and target stroke award level.

Results:
Hospitals participating in GWTG had an average risk-standardized readmission rate of 12.1% compared to 12.9% for non-participating hospitals. Hospitals using GWTG a minimum of four years had a 11.8% readmission rate, which was a 1.1% reduction in readmission rates compared to hospitals not using GWTG. This was significant at a p-value of 0.01. GWTG award winning hospitals had an average readmission rate of 11.8% compared to a 12.8% readmission rate for non-award winning hospitals. Hospitals with a GWTG Target Stroke award had an average readmission rate of 11.8% compared to a readmission rate of 12.8% for non-Target Stroke award winning hospitals.

Conclusions:
GWTG hospitals had on average a 1% reduction in risk-standardized readmission rates, with award winning hospitals seeing an even greater reduction. Translated into cost savings, this means that a hospital that saw 350 stroke patients annually with a 1% reduction in readmissions would save $70,000 considering an average cost of a stroke readmission is around $20,000 and does not include additional cost-savings due to CMS penalties. Larger studies using a higher number of hospitals participating in quality programs is recommended.
Abstract WMP88: Shorter Door-to-Needle Times of Intravenous Alteplase Improve “Efficiency” of Care and Moderately Affect “Quality” of Care: Study Based on a Large Comprehensive Stroke Center
Authors: Rajan Suja S , Wise Jessica N , Decker-palmer Marquita , Dao Thanh , Salem Cynthia , Savitz Sean I
Published: June 2021

Introduction:
The American Heart Association (AHA) recently raised the bar on timely treatment of acute ischemic stroke (AIS) with intravenous (IV) alteplase, by recommending door-to-needle times of 30 minutes or less for 50% or more of the AIS patients. Our study looks at the effectiveness of this new standard, by examining the effect of varying door-to-needle times on efficiency and quality of care, and clinical outcomes.

Methods:
Our study examined 762 AIS patients treated with IV alteplase in a large academic health system from 2015-2018, and compared their outcomes after treatment within 30, 45 and 60 minutes of arrival. The outcomes compared were: 1)
Efficiency of care outcome
- Length of stay (LOS); 2)
Quality of care outcomes
- Inpatient mortality and Disability at discharge; 3)
Clinical outcomes
- Discharge and 90-day modified Rankin Scale (mRS), and Post-alteplase (24 hr) NIH Stroke Scale (NIHSS). Adjusted logistic and linear regression analyses were used, after controlling for baseline patient socio-demographic and clinical characteristics.

Results:
Based on the adjusted regression analyses (Table 1), being treated within 30 minutes of arrival reduced the average LOS by 1.3 days (p-value: 0.02), but did not affect the quality of care outcomes. Similarly, being treated within 45 minutes of arrival reduced LOS by 0.9 days (p-value: 0.04). Being treated within 60 minutes of arrival did not affect LOS, but reduced the odds of inpatient mortality by 68% (p-value: 0.00), and disability at discharge by 29% (p-value: 0.08). Being treated within 30 minutes of arrival was associated with better mRS and NIHSS scores as compared with being treated within 45 or 60 minutes.

Conclusion:
Quicker IV alteplase treatment significantly improved efficiency of care and clinical outcomes. Quality of care outcomes did not improve beyond the 60 minute door-to-needle threshold. This study provides evidence supporting AHA’s new recommendation of 30 minutes or less door-to-needle time.
Abstract WMP90: Marital Status and Post-Stroke Outcomes
Authors: Dong Liming , Brown Devin , Case Erin , Morgenstern Lewis , Lisabeth Lynda
Published: June 2021

Introduction:
Although the impacts of marital status on health have long been recognized, little is known about its role in stroke outcomes. The study examined the association of marital status with neuropsychiatric, cognitive, functional, and quality of life outcomes at 90 days post-stroke in a population-based sample.

Methods:
Data were obtained from the Brain Attack Surveillance in Corpus Christi (BASIC) project (2009-2016). Post-stroke outcomes included neurological status assessed by the National Institutes of Health Stroke Scale, cognitive function assessed by the Modified Mini-Mental State Examination, functioning assessed by an activities of daily living (ADL)/instrumental activities of daily living (IADL) score, depression assessed by the 8-item Patient Health Questionnaire, and quality of life assessed by the short-form Stroke Specific Quality of Life scale. Linear or Tobit regression models were used to examine the association between marital status and stroke outcomes, accounting for attrition.

Results:
Among 1,226 ischemic or hemorrhagic cases, mean age was 67.6 (SD=12.3), half were women, and three-fifths were Mexican American; 23.0% were widowed, 20.1% were divorced/separated, and 8.4% were never married. Widowed participants were more likely to be female, aged above 75, and less educated than other groups. After adjustment for age, sex, ethnicity, education and stroke severity, compared with those married, those widowed had significantly worse cognitive function and quality of life, those never married had worse neurological and cognitive outcomes, and those divorced/separated had more depressive symptoms and poorer quality of life (Table).

Conclusions:
Being unmarried at stroke onset is associated with worse outcomes after stroke, and the outcome profiles vary by marital status. Further research should investigate potential mechanisms and develop interventions to improve outcomes of unmarried stroke survivors.