bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TP439: Statin Treatment and Prevalent Cerebral Microbleeds: A Systematic Review and Meta-Analysis
Authors: Katsanos Aristeidis H , Lioutas Vasileios-Arsenios , Charidimou Andreas , Catanese Luciana , Ng Kelvin K , Perera Kanjana , de Sa Boasquevisque Danielle , Romero Jose Rafael , Tsivgoulis Georgios , Smith Eric E , Sharma Mukul , Selim Magdy H , Shoamanesh Ashkan ,   International META-MICROBLEEDS Initiative
Published: June 2021

Introduction:
Statins have been reported to increase the risk of intracererbral hemorrhage, however their effects on cerebral microbleeds (CMBs) formation is not well understood. We systematically reviewed previously published studies to pool adjusted and unadjusted estimates of the association between prevalent CMBs and current statin use.

Methods:
We performed a systematic search in MEDLINE and SCOPUS databases on July 28
th
, 2019 to identify all cohorts from randomized clinical trials or observational studies reporting CMB prevalence and statin use. We extracted cross-sectional data on CMBs presence, as provided by each study, in association to the history of current statin use. Associations are reported as odds ratios (ORs) with corresponding 95% confidence intervals (95%CI). Random effects model was used to calculate the pooled estimates.

Results:
We included 7 studies (n=3671 participants): unselected general population [n=1965], ischemic stroke [n=770], hemorrhagic stroke [n=252], hypertension [n=605] or neuroimaging based studies [n=72]. Statin use was not associated with CMBs presence in either unadjusted (OR=1.15, 95%CI: 0.76-1.74) or adjusted analyses (OR=1.01, 95%CI: 0.62-1.64). Statin use was more strongly related to lobar CMB presence (OR=2.01, 95%CI: 1.48-2.72) in unadjusted analysis. The effect size of this association was consistent, but no longer statistically significant in adjusted analysis that was confined to two eligible studies (OR=2.26, 95%CI: 0.86-5.91). Except for the analysis on the unadjusted probability of CMBs presence, considerable heterogeneity was present in all other analyses (I
2
>60%).

Conclusion:
Our findings suggest that statin treatment is not associated with CMBs overall, but may increase the risk of lobar CMB formation. This hypothesis deserves further investigation within magnetic resonance imaging ancillary studies of randomized trials.
Abstract TP452: Long Term Opioid Use in Patients With Aneurysmal Subarachnoid Hemorrhage
Authors: Azher Idrees , Anderson Matthew , Dakay Katarina , Mac Grory Brian , Moody Scott , Kaushal Ashutosh , Reznick Michael , Thompson Bradford B , Wendell Linda C , Rao Shyam , Potter Nicholas S , Mahmoud Leana N , Cutting Shawna , Yaghi Shadi , Furie Karen L , Mahta Ali
Published: June 2021

Background:
Headache and neck pain are common in patients with aneurysmal subarachnoid hemorrhage (aSAH) throughout their course. Because pain is often a sequela, these patients are at risk for opioid dependence. Long term opioid use has not been well studied in this population.

Methods:
We analyzed a cohort of consecutive patients who were admitted with diagnosis of aSAH to an academic referral center from 2015 to 2018. We excluded patients who died during hospitalization or were discharged to hospice or were previously taking any opioids. The following variables were collected: demographics, any opioid use during hospitalization, short-term low-dose steroid use (mostly for headache management but some cases for immediate post craniotomy for aneurysm clipping), opioid prescription at the time of discharge and 3-month or longer opioid use verified by pharmacy and any follow up out patient records.

Results:
Of 200 patients with aSAH, 144 patients (72%) met our inclusion criteria. Mean age was 58 years (SD 14.8); Ninety-four patients (65%) were women; All patients received opioids at some point during hospitalization but 66% (96/144) were discharged with opioid prescription. Of these, 31% (30/96) continued to use opioids at ≥3 months. The overall rate of chronic opioid use was 20% (30/144). The rate of opioid prescription at discharge was 72% (52/72) in patients who received short course steroids and 61% (44/72) in patients who did not receive steroids. (p=0.21; OR 2.6, 95% CI 0.82-3.3). Steroids did not prevent long term opioid use. (p=0.30; OR 0.6, 95% CI 0.26-1.3)

Conclusion:
Opioids are regularly used as the main treatment option for pain control in patients with aSAH. A noteworthy number of patients continue to use opioids beyond their initial hospitalization. Steroid use does not prevent long term opioid use in these patients. Non-opioid pain control strategies should be explored in the future.
Abstract TP453: The Effect of Case Volume and Comprehensive Stroke Centre Capabilities on Patient Outcomes of Clipping and Coiling for Subarachnoid Haemorrhage
Authors: Kurogi Ryota , Kada Akiko , Ogasawara Kuniaki , Kitazono Takanari , Shiokawa Yoshiaki , Miyachi Shigeru , Tominaga Teiji , Onozuka Daisuke , Nishimura Ataru , Arimura Koichi , Kurogi Ai , Ren Nice , Hagihara Akihito , Nishimura Kunihiro , Iihara Koji
Published: June 2021

Objectives:
To examine whether hospital case volume and comprehensive stroke centre(CSC) capabilities affect patient outcomes of clipping and coiling for subarachnoid haemorrhage (SAH).

Methods:
We conducted a nationwide retrospective cohort study. Using the J-ASPECT Diagnosis Procedure Combination database, we identified 27,490 SAH patients who underwent clipping or coiling in 621 institutions between 2010 and 2015. The CSC capabilities of each hospital were assessed using a validated scoring system (CSC score: 1-25 points). We classified the hospitals into quartiles based on CSC score and case volume of clipping or coiling for SAH.

Results:
In clipped patients, a high case volume (
>
14 cases / year) was significantly associated with reduced in-hospital mortality (Q1 as control, Q4 odds ratios (ORs) 0.71 [95% confidence interval 0.55 - 0.90]) but not poor outcome. In coiled patients, a high case volume (
>
9 cases / year) was associated with reduced in-hospital mortality (Q4 0.69 [0.53 - 0.90]) and poor outcomes (Q3 (
>
5 cases / year) 0.75 [0.59 - 0.96], Q4 0.65 [0.51 - 0.82]). A high CSC score (
>
19 points) was significantly associated with reduced in-hospital mortality of clipped (0.68 [0.54 - 0.86]) but not coiled patients. There was no association between CSC capabilities and poor outcomes.

Conclusions:
The effect of case volume and CSC capabilities on in-hospital mortality and short-term functional outcomes in SAH patients was different between clipping and coiling. In the modern endovascular era, better outcomes of clipping may be achieved in facilities with high CSC capabilities.
Abstract TP454: Immunological Responses in Patients With Vasospasm After Aneurysmal Subarachnoid Hemorrhage: A Pilot Study
Authors: Roa Jorge A , Sarkar Deepon , Zanaty Mario , Hasan David , Samaniego Edgar , Ortega Sterlng B
Published: June 2021

Introduction:
Cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI) are frequently observed after aneurysmal subarachnoid hemorrhage (aSAH) and contribute to neurocognitive decline and worse outcomes. We hypothesize that aSAH initiates a cascade of neuroinflammatory events which contributes to the development of DCI.

Methods:
Patients who presented with aSAH requiring external ventricular drainage (EVD) for concomitant hydrocephalus were prospectively enrolled. Cerebrospinal fluid (CSF) samples were collected at different time-points relative to index aSAH injury: acute (days 0-1); pre-vasospasm (days 2-5); vasospasm peak (days 6-9) and post-vasospasm (days 10+). Presence and severity of CVS were assessed using CTA/CTP scans and clinical exam. VEGF and MMP9 (immune affectors) protein levels in the CSF were quantified using ELISA. Mobilization of the immune system was characterized by quantification of innate and adaptive immune cells in the CSF using flow cytometry. Production of inflammatory effector proteins was evaluated using intracellular cytokine staining.

Results:
Of 13 patients analyzed, 6 (46.2%) experienced CVS. Levels of VEGF and MMP9 were consistently higher in aSAH patients who developed CVS, with the highest difference occurring at the acute phase. Similarly, cellularity analysis revealed elevated counts of monocytes (CD11b
+
) in the CSF during the acute phase, with progressive decline at later phases. Microglia (CD45
dim
CD11b
+
) cells were found to be significantly increased at the post-vasospasm phase. A higher percentage of IFN-γ production cytotoxic T helper cells were found at the acute phase, while the later time points revealed an elevated leveled of CD45RA
-
CD27
+
cytotoxic T cells.

Conclusion:
Our preliminary data shows an active production of proteins with known immunological functions, mobilization of innate cells, production of inflammatory mediators by adaptive immune cells and altered differentiation status. Our overall goal is to determine if there are potential targets of immunomodulatory therapies which can be used to prevent or treat vasospasms and its related deleterious outcomes.
Abstract TP457: Intraventricular and Intravenous Milrinone for Cerebral Vasospasm in Aneurysmal Subarachnoid Hemorrhage
Authors: Purohit Meghan , Mullaguri Naresh , Ahrens Christine , Newey Christopher , Dhimant Dani , George Pravin
Published: June 2021

Introduction:
Cerebral vasospasm (CVS) is a complication of aneurysmal subarachnoid hemorrhage (aSAH). Intraventricular milrinone (IVtM) and intravenous milrinone (IVM) have been studied for treatment of CVS. We aimed to determine the effect of milrinone therapy on clinical and transcranial Doppler (TCD) measures of CVS.

Methods:
We performed a retrospective analysis of patients with aSAH treated with IVtM at a single tertiary center between 2016 and 2018. Patients were treated with IVtM if they had symptomatic CVS or TCD suggestive of critical CVS that persisted despite blood pressure augmentation or endovascular therapies. Nimodipine was given as standard of care. A subset of patients were also treated with IVM, which was dosed in a standard fashion based on Montreal Neurological Institute protocol. We collected demographic data, TCD mean flow velocity and pulsatility index, angiographic data, as well as utilization and frequency of IVtM and IVM.

Results:
Twenty-eight patients in our cohort had modified Fisher grade 4 (57%) or grade 3 (25%) and median Hunt-Hess score of 3 (IQR 2, 4). Twenty-one of 28 patients were treated with IVtM+IVM. Seven (25%) who received IVtM alone had no significant improvement in TCD velocities or reduction in symptomatic CVS (p=0.611). Patients received between 1 and 30 doses of IVtM. There was no significant improvement with time or with number of IVtM doses IVtM. There was also no significant improvement in TCD velocities of CVS patients nor reduction in symptomatic CVS with IVtM+IVM (p=0.69). The number of IVtM doses correlated with an increased discharge mRS (p=0.05). There were no direct complications due to IVtM or IVM.

Conclusion:
Neither IVtM+IVM nor IVtM alone appear to be effective treatment of CVS in aSAH. Our data represent one of the first case series reporting IVtM and IVtM+IVM utilization for the treatment of CVS.
Abstract TP460: Regulatory T-Cells and CD4+ T Helper Cell Subsets Are Differentially Regulated and Express Distinct Activation States After Aneurysmal Subarachnoid Hemorrhage (SAH) and During Post-SAH Complications
Authors: Chaudhry Shafqat R , Muhammad Sajjad
Published: June 2021

Background:
Aneurysmal subarachnoid hemorrhage (SAH) is associated with high morbidity and mortality. Devastating post-SAH complications after aneurysm treatment lead to poor clinical outcome. Current research suggests critical role of inflammation during early and delayed brain injury phases over which these complications arise. T helper cells can polarize to multiple functionally unique subsets. Here, we investigate different CD4+ T cell subsets during these brain injury phases after SAH and their dynamics during post-SAH complications.

Methods:
Anticoagulated peripheral venous blood was obtained from 15 SAH patients on days 1 and 7, and once from healthy controls. After erythrocyte lysis and single cell wash, 1 million cells were stained with different anti-human mouse monoclonal antibodies and were acquired on BD LSR Fortessa. Lymphocytes were gated based on low side scatter and high CD45 expression. Different CD3+CD4+ T cell subsets were characterized by differential cell surface expression of CXCR3 and CCR6 into Th1, Th2, Th17, whereas Tregs by CD25
hi
and CD127
lo
. SAH patients were dichotomized based on presence or absence of different post-SAH complications (hydrocephalus, seizures, CVS, cerebral ischemia) to assess association of T cell subsets with these complications.

Results:
Total CD4+ T cells were significantly increased after SAH. Interestingly, Th2 cells were significantly decreased and Th17 cells increased on day 7 compared to day 1 after SAH. However, regulatory T-cells were significantly increased on both assessment days compared to controls. The analysis of activation states was done by CD38 and HLA-DR expression. Th1 and Treg cells were significantly increased on day 1 in SAH patients who developed seizures and CVS, respectively. HLA-DR
+
CD38
+
Th2 cells significantly increased on day 1 in SAH patients who developed hydrocephalus, whereas HLA-DR
-
CD38
-
Th1 cells significantly increased on day 1 in patients with infections. HLA-DR
-
CD38
-
Treg cells were significantly reduced on day 1 and day 7 in patients developing
cerebral ischemia
.

Conclusion:
CD4+ T cell subsets and Treg cells display dynamic patterns after SAH, and show a distinct pattern of polarization and activation states in specific post-SAH complications.
Abstract TP465: Autonomic Dysfunction and Potentially Related Brain Regions in Cerebral Small Vessel Disease
Authors: Miaoyi Zhang , Huan Yu , Ding Ding , Weijun Tang , Fu Jianhui
Published: June 2021

Objects:
To observe the fluctuations of nocturnal oxygen saturation, heart rate and blood pressure and whether there are autonomic dysfunction related brain regions in cerebral small vessel disease (CSVD).

Methods:
Consecutive patients with arteriosclerotic CSVD and community-dwelling elders without CSVD between 50 and 80 years old were enrolled. The parameters of oxygen saturation fluctuations and heart rate variability(HRV) were synchronously collected by polysomnography(PSG). 24-hour ambulatory blood pressure monitoring were also performed to assess the circadian rhythm and blood pressure variability(BPV). The differences in the above parameters were analyzed using appropriate statistical methods. Additionally, the voxel based morphometry (VBM) analysis was used to determine whether there were autonomic dysfunction associated structural alterations in CSVD.

Results:
1. 51 patients were included in CSVD group and 37 in control group. After adjustment for gender, age, hypertension, stroke, BMI and apnea-hypopnea index(AHI), CSVD was independently associated to oxygen desaturation index (P=0.039).After adjusting age, gender, hypertension, stroke, AHI, and periodic limb movement index during sleep, significant difference of the standard deviation of normal-to-normal intervals(SDNN) during sleep period existed (P=0.030).The ratio of patients with reverse dipping patterns was higher in CSVD group after correcting age, gender, stroke, use of antihypertensive drugs, AHI and BP levels at the same periods. But no statistical differences in all BPV parameters were determined between two groups. 2. 19 CSVD patients and 16 community elders were finally included for VBM analysis. After adjustment for age, gender and AHI, grey matter atrophy in certain brain regions were more significant in CSVD group, especially in the right inferior orbitofrontal gyrus, superior medial frontal gyrus, insula, medial cingulate and bilateral medial temporal gyrus.

Conclusion:
CSVD patients have autonomic dysfunction which may be related with grey matter atrophy in part of autonomic network associated brain regions.
Abstract TP468: Differential Effect of Ischemia and Thrombin Mediated Toxicity on Neurovascular Unit
Authors: Rajput Padmesh S , Kothari Shweta , Lyden Patrick
Published: June 2021

Objectives:
Brain is a complex structure during ischemia along with neurons; components of vascular unit astrocytes, pericytes and endothelial cells play a major role in hypoxic and blood brain barrier leakage mediated injury. Thrombin acts via protease activated receptor-1 (PAR-1) and leads to neuronal survival or death, PAR-1 knockout cells survive ischemia. We hypothesize that different elements of the Brain vascular unit play different roles in responding to injury. The present study aimed to establish a correlation between astrocytes, pericytes and endothelial cells vulnerability via OGD model of ischemia and Thrombin mediated toxicity.

Methods:
Using highly reproducible oxygen glucose deprivation (OGD) model Primary cultured cells were exposed to OGD for various durations and Thombin doses to determine the optimum time point for 80 % cell death or cell viability measured using LDH release assay MTT assay. LD50 dose of OGD and Thrombin was used to determine the effect of various drugs mediating PAR-1 receptor pathway

Results:
The viability assay using MTT showed that the three elements of vascular unit respond differentially to longer durations of ischemia, with pericytes being the most vulnerable, followed by endothelial cells, followed by astrocytes. Our thrombin dose effect shows that Pericytes and endothelial respond to thrombin similarly whereas, astrocytes on lower concentration proliferate, but don’t survive the higher concentrations.

Conclusion:
An exciting, novel finding in our data is that different elements of the vascular unit—astrocytes, pericytes and endothelial cells—all exhibit effect of ischemia and reperfusion at different time scales. Up until recently, studies of neuroprotection addressed the brain as a homogenous unit, with the tacit assumption that all elements responded similarly. Our data on astrocytes, endothelial cells and pericytes—allows more focused investigation.
Abstract TP469: Impact of Multiparity on Retinal Vascular Structure in Middle-Aged Mice
Authors: Thompson Rachael , Shao Qingmei , Warrington Junie P
Published: June 2021

Objective:
Parity is associated with protection from cardiovascular disease mortality. In a pre-clinical study, multiparous mice had smaller stroke-induced infarcts, pointing to a neuro-protective role. We therefore investigated whether multi-parity induced protective structural changes in the retinal vasculature.

Methods:
Age-matched virgin (n=6) and multiparous (n=11, retired breeder with 4±1 litters) Smooth Muscle Actin-Green Fluorescent Protein (SMA-GFP) mice (8.0-8.75 months old) were included. Eyes were extracted, fixed, and cryoprotected in 30% sucrose before retinal dissection. Retinal flat mounts were imaged and analyzed using NIS-Elements software.

Results:
Multiparous mice had an increase in body mass (46.3±2.3g vs. 33.5±1.8g; p=0.002), heart weight (189.3±9.2mg vs. 130.8± 8.5; p=0.001), and right (222.1±10.2 vs. 165± 6.3mg; p=0.002) and left kidney (198.7±8.0mg vs. 156.2±4.1mg; p=0.002) weight compared to virgin mice. There was no difference in brain weights (471.1±5.6mg vs. 470±1.9mg; p=0.890) between groups. Virgin mice had 4±0.2 primary retinal arterioles compared to multiparous mice with 5±0.4; p=0.039. Arterioles in multiparous mice were wider than virgins (26.4±2.3 vs. 21.0±1.1μm; p=0.046). There was no difference in the number of venules (4±0.2 vs. 4±0.2; p=0.813) or venous diameter (41.3±2.3 vs. 35.4±2.1; p=0.110); however, venous pericyte density (number per area of venule) decreased in multiparous mice and was negatively associated with the time since last litter (Pearson r= -0.53; p=0.047).

Conclusions:
Our results show that pregnancy experience induces increased arteriole density and caliber and decreased venous coverage by pericytes. Our data support the hypothesis that venular coverage by pericytes decreases postpartum and may have functional consequences at the blood-brain barrier. Thus, ongoing studies assess whether the retinal vascular changes have functional consequences or are mirrored in the brain.
Abstract TP471: Oxygen-Glucose Deprivation and Denser Extracellular Matrix Cause Cerebral Capillary Endothelial Cells to Lose Elasticity
Authors: Mack Alexis , Maniskas Michael , Reynolds Caroline , Urayama Akihiko
Published: June 2021

Objective:
Cerebral ischemia affects the mechano-response of vasculature and the remodeling of extracellular matrix (ECM) components. The present study investigates how oxygen-glucose deprivation (OGD) affects the brain endothelial cell (BEC) stiffness. We further aim to study whether ECM components affect the cellular stiffness in normal and energy deprived conditions.

Methods:
Primary human BECs received a 16h OGD followed by the reperfusion with normal culture media. Young’s Modulus (YM) and topography in the BEC surface were determined by atomic force microscopy (AFM). To test the effect of ECM composition on the BEC stiffness, various concentrations (5-500 uM) of collagen type IV were used for culture dish coating. BECs on the coating beds underwent 16h OGD and served for YM measurements. Per dish, 10-20 single BECs were measured.

Results:
BECs under OGD conditions became significantly stiffer (2.1-fold, *P<0.05) than the normoxic control, and the increased stiffness sustained even after the reperfusion for 24h, indicating energy deprivation is a primary factor for the increased stiffness under acute stress conditions. AFM topography confirmed that OGD induced rough and filamentous plasma membrane surface in BECs, suggesting a cytoskeletal change was induced by OGD.

BECs grown on a 10x denser collagen type IV (500 uM) layer showed a significant increase (2.3-fold, ***P<0.001) in cellular stiffness, compared with the conventional concentration of 50 uM, suggesting that denser extracellular matrix makes BEC stiffer. Also, in BECs cultured on a denser ECM layer, OGD response was absent in terms of cellular stiffness.

Conclusion:
The present study found that OGD increased BEC stiffness. In addition, increasing the density of the ECM alone was enough to generate stiffer BECs. These mechanical properties of BECs may be a physical factor mediating endothelial responses after stroke.
Abstract TP475: Effect of Udenafil, a Phosphodiesterase-5 Inhibitor, on Angiogenesis in a Cav-1 Deficient Moyamoya Disease Model
Authors: Kim Hyung Jun , Bang Oh Young , Baek In-Young , Kim Jae-Hwan , Kim Ye Sel , Lee Mee So , Kim Ingyeong , Kim Gyeong-Moon
Published: June 2021

Background:
Although pathogenic mechanisms of moyamoya disease remain unknown, recent studies suggest that it is a caveolae disease. This study evaluated the effect of udenafil, a phosphodiesterase-5 inhibitor, on vessel maturation in
in vitro
and
in vivo
moyamoya disease models.

Methods:
Angiogenesis and vessel maturation were assessed in
in vitro
models, caveolin-1 (Cav-1) knockdown human umbilical vessel endothelial cells (HUVECs) and coronary artery smooth muscle cells (CASMCs), and in
in vivo
model of bilateral internal carotid artery occlusion (bICAo). Udenafil was administered (1,3,10 and 30 μM) in cell culture conditions, and functional studies (migration and tube formation assay) were performed and vessel maturation factors and cyclic guanosine monophosphate (cGMP) accumulation were measured. Udenafil (3 and 10 mg/kg) was orally administered once daily for 4 weeks in bICAo rat model, and histological analysis for angiogenesis and vessel maturation was performed.

Results:
Udenafil increased vessel formation in both Cav-1 knockdown HUVEC and bICAo models without increased migration/proliferation of HUVECs and CASMCs. Udenafil increased CD31+ vessel density and NG2/Col4+ mural cell density in bICAo models. Cav-1 knockdown inhibited accumulation of cGMP, and udenafil treatment restored cGMP levels in Cav-1 knockdown HUVEC models. Vessel maturation factors (angiopoietin-1 and platelet-derived growth factor receptor-β) and angiogenic factors (endothelial nitric oxide synthase) were increased after treatment with udenafil
in vitro
.

Conclusion:
Our results indicate that udenafil reversed cellular levels of cGMP related to Cav-1 deficiency and induced angiogenesis and vessel maturation. Further studies are warranted to confirm the therapeutic effects of this strategy in moyamoya disease.
Abstract TP478: Mechanisms of Brain Endothelial Erythrophagocytosis: Insights Into the Pathogenesis of Cerebral Microbleeds
Authors: Sun Jiahong , Vyas Prema , Mann Samar , Yarlagadda Sriyansh , Fisher Mark J , Sumbria Rachita K
Published: June 2021

Background:
Cerebral microbleeds, MRI signatures of cerebral microhemorrhage, are thought to arise from brain microvessel disruption. Our prior work suggests an alternate origin for some microbleeds, emphasizing brain endothelial erythrophagocytosis (BEE) producing microhemorrhage-like lesions (“pseudo-microbleeds”) in absence of vascular disruption (Frontiers Cell Neurosci 9-18; PMID: 30237761). We demonstrated an erythrophagocytic phenotype of brain microvascular endothelium for oxidatively-stressed red blood cells (RBC), and migration of iron-rich hemoglobin across the brain endothelium. However, cellular mechanisms underlying BEE and hemoglobin passage across brain endothelium are not defined. Herein we investigated a) role of oxidative stress and RBC phosphatidylserine (PS) exposure in BEE and b) intracellular endosomal trafficking of RBC within brain endothelial cells.

Methods:
Murine brain endothelial cells (bEnd.3 cells) were incubated with 2x10
6
mouse RBC treated with 3mM tert-butylhydroperoxide (t-BHP, an oxidative stressor) or sterile PBS (control) for 48h at 37°C, in the presence of 7.5 μg annexin V to cloak PS, or vitamin C (15μM-1500μM) to reduce reactive oxygen species (ROS). BEE was evaluated by hematoxylin & eosin stain and diaminofluorene assay for hemoglobin. RBC ROS levels, PS exposure, and cell viability were measured. bEnd.3 cells were immunostained to visualize RBC in early and late endosomes, the latter being the presumed site of RBC degradation post-erythrophagocytosis.

Results:
tBHP induced both ROS production and PS exposure in RBC. There was a 9-fold increase (p<0.001) in BEE of t-BHP-RBC compared with control. Vitamin C reduced RBC ROS levels (70%, p<0.001) and PS exposure (27%, p<0.001), while annexin V blocked RBC PS exposure (65%, p<0.001). BEE was significantly attenuated by annexin V (63%, p<0.001) and vitamin C (39%, p<0.001). No change in bEnd.3 viability was observed and t-BHP-RBC localized to both early and late endosomes.

Conclusions:
These data demonstrate the importance of RBC PS exposure in BEE, and describe the intracellular trafficking of RBC in brain endothelial cells. These findings provide insights into the development of microhemorrhage-like lesions and cerebral microbleeds.
Abstract TP479: Early Effect of Human Immunodeficiency Virus on Cerebral Blood Flow and Autoregulation
Authors: Sen Souvik , An Hongyu , Powers William J
Published: June 2021

Introduction:
Human immunodeficiency virus (HIV)-infected individuals are at high risk for ischemic stroke. We measured cerebral blood flow (CBF), oxygen extraction fraction (OEF), and autoregulation in HIV infected subjects and controls.

Methods:
In treatment-naive HIV infected subjects and age-, gender-, and race-matched controls, OEF was measured by using MRI T2*-weighted echo-planar imaging sequences and CBF was measured by MRI pulsed arterial spin labeling (PASL) approach. Static cerebral autoregulation was determined by measuring changes in CBF and OEF, in response to ≈10% reductions in MAP induced by using IV Nicardipine infusion. All images were acquired using a Siemens 3T MR scanner (Treo, Siemens Medical Systems Inc). Cerebral autoregulation was measured globally and regionally in gray matter (GM), white matter (WM) and subcortical GM. Autoregulatory Index (AI) was computed using the equation AI = %CBF change/% MAP change supplemented by CBF associated OEF changes. Nominal p-values are uncorrected for multiple comparisons.

Results:
Forty-one treatment naive HIV-infected subjects and 47 age-, gender-, race-matched controls participated. HIV-infected subjects had higher CBF in cortical GM compared to the controls (76.8± 12 mL/100 g/min versus 71.6 ± 11 mL/100 g/min; p= 0.04), but not in white matter (30.9± 8 mL/100 g/min versus 30.0 ± 8 mL/100 g/min; p = 0.60) or subcortical GM (62.8± 13 mL/100 g/min versus 61.3 ± 13 mL/100 g/min; p = 0.57). Whole brain (WB), GM, WM, and subcortical GM, OEF were similar between the groups (p > .05). The median AI were similar between cases and controls in WB (0.40 vs 0.18, p=0.86), GM (0.10 vs. 0.16, p=0.87), WM (0.80 vs. 0.87, p=0.31), and subcortical GM (1.65 vs. 1.77, p=0.26). A 12-month follow-up (N=30) in HIV-subjects on antiretroviral therapy did not produce a significant change in CBF or OEF in the WB, GM, WM, or subcortical GM (Paired sample t test p>0.05). Similarly, no changes were noted on the AI (Wilcoxon Match Rank test p>0.05).

Conclusions:
AI was similar between HIV cases and control and remained so after 12-months of antiretroviral therapy. We found no evidence of a defect in autoregulation to explain the high-risk of ischemic stroke documented in other studies.
Abstract TP485: Aortic Stiffness Detrimental Effect in Brain Blood Flow Autoregulation
Authors: Gutierrez Jose , Khasiyev Farid , Brickman Adam M , Manly Jennifer L , Marshall Randolph S , Mayeux Richard P
Published: June 2021

Background:
Cerebral hemodynamic dysfunction is associated with brain small artery disease and poorer cognition. With aging, systemic arteries stiffen, magnifying the spread of pulsatility to distal organs. The brain is especially susceptible to pulsatility due to low impedance to flow. Increased pulsatility causes abnormal brain arteriolar remodeling in animal models. Therefore, we hypothesize that measures of aortic stiffness relate to poorer cerebral autoregulation, an in-vivo measure of arteriolar function.

Methods:
We recruited participants in the Washington Heights-Inwood Community Aging Project for this study. For autoregulation, both middle cerebral arteries were insonated at a depth of 50-58 mm. End-tidal CO2 (EtCO2) was measured continuously with a facemask. After ten minutes of baseline recording, a mixture of air enriched with 5% CO2 was administered through the facemask for 2 minutes. Cerebrovascular reactivity was calculated as % change in mean CBFV (mCBFV) per 1 mm increase in mean EtCO2 during CO2 inhalation. We averaged the right and left CO2 reactivity percentage. For aortic stiffness, we acquired carotid-femoral pulse wave velocity (cfPWV) with non-invasive oscillometry using the Vicorder system (Skidmore Medical Limited, Bristol, UK). We used generalized linear model to obtain beta estimates of the association between CO2 reactivity and cfPWV.

Results:
We included 158 participants (mean age 77±6.4 years, 67% women, 40% non-Hispanic black, 38% non-Hispanic white, and 20% Hispanic). Hypertension was present in 54% of the participants. cfPWV was associated with poorer CO2 reactivity (B=-0.038, P=0.047), independent of age, sex, ethnicity, and hypertension. Brachial pulse pressure (B=0.007, P=0.38) and mean arterial pressure (B=-0.017, P=0.21) were not associated with CO2 reactivity, and adding brachial pulse pressure and mean arterial pressure to the adjusted model did not change the association between cfPWV and poorer CO2 reactivity.

Conclusions:
Aortic stiffness is associated with poorer CO2 reactivity independent of traditional measures of hypertension, a marker of cerebral autoregulation and arteriolar health. Poorer CO2 reactivity may mediate the reported effects of aortic stiffness on brain outcomes.
Abstract TP49: Acute Intracranial Stenting With Mechanical Thrombectomy Shows No Difference in Discharge Outcomes Compared With Mechanical Thrombectomy Alone
Authors: Hassan Ameer E , Ringheanu Victor M , Tekle Wondwossen G , Preston Laurie , Qureshi Adnan I
Published: June 2021

Background:
Mechanical thrombectomy (MT) is a proven method of treating patients with acute ischemic stroke (AIS) from a large vessel occlusion. However, there has been controversy regarding the safety and efficacy of incorporating acute intracranial stenting in addition to standard MT especially after the WEAVE trial results which showed a significant increase in stroke and hemorrhage in patients receiving wingspan stenting within 7 days of index ischemic event. We compared the outcomes of all AIS patients treated with acute intracranial stenting + MT versus MT alone.

Methods:
Through the utilization of a prospectively collected endovascular database at a comprehensive stroke center between 2012-2019, variables such as demographics, co-morbid conditions, symptomatic intracerebral hemorrhage (ICH), mortality rate at discharge, and good/poor outcomes in regard to modified thrombolysis in cerebral infarction score (TICI) and modified Rankin Scale at discharge (mRS dc) were examined. The outcomes between patients receiving acute intracranial stenting + MT and patients that underwent MT alone were compared.

Results:
There were a total of 439 AIS patients who met criteria for the study (average age 70.38 ± 13.46 years; 45.6% were women). Analysis of 36 patients from the acute stenting + MT group (average age 66.72 ± 13.17 years; 30.6% were women), and 403 patients from the MT Alone group (average age 70.71 ± 13.45 years; 46.9% were women); see Table 1 for baseline characteristics and outcomes. Three patients (8.3%) in the acute stenting + MT group experienced ICH versus forty-four patients (10.9%) in the MT alone group (P=0.631); no significant increases were noted in length of stay (9.08 days vs 9.84 days; P=0.620) or good mRS scores at dc (P=0.636).

Conclusion:
Acute intracranial stenting in addition to MT was not associated with an increase in ICH rates, overall length of stay, or poor outcome upon discharge of patients. Prospective studies are recommended.
Abstract TP493: Herpes Zoster Vaccine Live And Risk For Stroke Among Medicare Beneficiaries: Population Based Matched Cohort Study
Authors: YANG Quanhe , Chang Anping , Tong Xin , Merritt Robert
Published: June 2021

Introduction:
Herpes zoster (HZ) is associated with increased risk of stroke, and Zoster Vaccine Live (ZVL) reduces risk of HZ. No study examined the association between ZVL and risk for stroke. The present study examined this association among US older population.

Methods:
We included 1,382,051 Medicare fee-for-service beneficiaries age ≥66 years without a history of stroke and who received ZVL during 2008-2014, and 1,382,051 matched controls (using a comprehensive list of matching variables) without ZVL followed from ZVL receipt to December 31 2016. We used Cox proportional hazard models to examine the association between ZVL and composite fatal/non-fatal incident stroke outcomes.

Results:
During a median of 3.9 years follow-up (interquartile range 2.7-5.4), we documented 42,267 stroke events including 33,510 acute ischemic strokes (AIS) and 4,318 hemorrhagic strokes among beneficiaries who received ZVL over 5,890,113 person years. The corresponding numbers for controls were 48,139, 39,334, and 4,713 during 5,693,943 person years. Crude incidence comparing beneficiaries with and without ZVL were 7.18 vs. 8.45 per 1000 person years for all stroke, 5.40 vs. 6.53 for AIS, and 0.73 vs. 0.82 for hemorrhagic stroke (p<0.001 for difference). Adjusted hazard ratios comparing beneficiaries with ZVL to controls were 0.84 (95% CI 0.83-0.85), 0.82 (0.81-0.83), and 0.88 (0.84-0.91) for all stroke, AIS and hemorrhagic stroke respectively. The association between ZVL and risk for stroke appeared to be stronger among beneficiaries 66-79 years compared to those ≥80 years of age (p=0.020 for interaction), but largely consistent across sex, and racial groups.

Conclusion:
Among Medicare beneficiaries, receipt of ZVL was associated with lower incidence of stroke. Further study is needed to confirm our findings.
Abstract TP5: Optimizing First Pass TICI 3: FAST (Flow Arrest Aspiration Stentriever Technique)
Authors: Parra-Farinas Carmen , Diestro Jose Danilo , Almusalam Noora , Phillips Rebecca , Alqabbani Abdullah , Qazi Emmad , Bharatha Aditya
Published: June 2021

Introduction:
Timely restoration of cerebral blood flow using mechanical thrombectomy for acute ischemic stroke is constantly evolving. We evaluated the impact of combining distal access catheter with proximal balloon guiding catheter and stentriever technique for mechanical thrombectomy in acute ischemic stroke patients.

Methods:
In accordance with our institutional review board approval, we retrospectively analyzed all the patients who underwent mechanical thrombectomy with stentriever between May 2011 and June 2019. The patients were divided by the techniques adopted, the combined technique: proximal balloon guiding catheter, distal access catheter and stentriever and the conventional approach: proximal balloon guiding catheter and stentriever. Analysis and outcome parameters: complete recanalization (TICI ≥2b), procedural time, early independent functional outcome (mRS ≤2 at discharge).

Results:
Among the 267 patients included, in 58.8% the combined technique was performed. Mean age at treatment was 68.4±13.3, 55.4% male. There were no statistically significant differences in baseline characteristics between the treatment groups. Median NIHSS score was 16 (6-34) on arrival. The overall complete recanalization rate was 68.5%. The combined technique group achieved higher complete recanalization rate; TICI ≥2b: 75.6% vs. 66.3% (p=0.001). In addition, the distal access catheter group achieved lower non-reperfusion rate; TICI=0: 15.4% vs. 26.5% (p=0.001). No significant differences were observed in first-pass successful reperfusion rate: 70.5% vs. 64.2% (p=0.333). The distal aspiration approach was not associated with longer procedural time: 67.4±28.4 min vs. 31.8±74.9 min (p=0.467). There were no significant differences regarding procedural complications: 8.3% vs. 7.3% (p=0.763); SICH: 8.5% vs. 12.2% (p=0.333). There were no significant differences in clinical outcomes; early functional independence rate: 45.0% vs. 54.3% (p=0.256), mortality rate: 12.8% vs. 15.2% (p=0.256).

Conclusions:
The combined techniquefor mechanical thrombectomy is associated with higher complete recanalization rate. The use of aspiration system does not seem to increase the procedural time or influence in complications development.
Abstract TP54: Visual Aids for Patient, Family, and Physician Decision Making About Late Imaging-Guided Endovascular Thrombectomy for Acute Ischemic Stroke
Authors: Moshayedi Pouria , Liebeskind David , Jadhav Ashutosh , Jahan Reza , Lansberg Maarten , Sharma Latisha , Nogueira Raul , Saver Jeffrey
Published: June 2021

Background:
Speedy decision-making is helpful for optimal outcomes from endovascular thrombectomy (EVT) for acute ischemic stroke (AIS). Visual displays may facilitate rapid review of relevant outcomes with different courses of action, but have not yet been developed for late-presenting patients selected for EVT based on multimodal CT or MR imaging.

Methods:
From pooled, study-level randomized trial (DAWN and DEFUSE 3) data, 100 person-icon arrays (Kuiper-Marshall personographs) were generated showing beneficial and adverse effects of endovascular thrombectomy for patients with acute cerebral ischemia and large vessel occlusion using (1) automated (algorithmic) and (2) expert-guided joint outcome table specification.

Results:
Among imaging-selected patients 6-24 hours from last known well, for the full 7-category modified Rankin Scale (mRS), endovascular thrombectomy had number needed to treat to benefit 1.9 (IQR 1.9-2.1) and number needed to harm 40.0 (29.2-58.3). 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 0-2); 3 patients have worse disability outcome, including 1 more experiencing severe disability or death (mRS 5-6), mediated by symptomatic intracranial hemorrhage and infarct in new territory. The person-icon figure integrated these outcomes, and early side-effects, in a single display (Figure). 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 giving special emphasis to normal or near-normal outcome (mRS 0-1) rather than functional independence (mR 0-2).

Conclusion:
Personograph visual decision aids are now available to rapidly educate patients, family, and healthcare providers on the benefits and risks of late, imaging-guided endovascular thrombectomy therapies for acute ischemic stroke.
Abstract TP57: Tenzing™ 7 Delivery Catheter: A Novel Delivery Assist Catheter Significantly Facilitates Catheter Delivery in an Anatomically Challenging Stroke Model
Authors: Frölich Andreas M , English Joey , Jansen Olav , Möhlenbruch Markus , Szikora István , Wodarg Fritz , Fiehler Jens , Otto Kim , Chou Tony , Buhk Jan-Hendrik
Published: June 2021

Background:
In large vessel occlusion stroke, intracranial navigation of large-bore aspiration catheters can be impeded by vessel curvature and ophthalmic artery origin. Novel conically-shaped delivery assist devices are designed to facilitate delivery. We assessed aspiration catheter deliverability in several patient-specific in vitro models.

Methods:
In a flow model replicating vascular access from the femoral to the middle cerebral artery, two different commercially available aspiration catheters were repeatedly advanced through a commercial 0.088” sheath from the carotid bifurcation to the middle cerebral artery by five neurointerventionalists under fluoroscopy. Three craniocervical access scenarios were manufactured based on challenging patient anatomy. Catheter deliverability was assessed with standard microwire/microcatheter combinations (MC) and the Tenzing™ 7 catheter (T7). Procedural characteristics were recorded, and operators rated carotid artery deflection, guide catheter pushback and difficulty passing the ophthalmic artery origin on a 5-point scale (1=none, 5=most severe).

Results:
Among 117 delivery attempts, the target vessel was reached significantly more often with T7 (96%) than with MC (66%, p<0.001). Successful delivery was faster with T7 (33s, 95%CI:30-35s) than with MC (69s, 95%CI:55-83s, p<0.001) and there was less need to cross the occlusion site with T7 (12%) than with MC (53%, p<0.001). Operators assigned superior ratings to T7 than to MC regarding carotid artery deflection (2, IQR1-3 vs. 3, IQR2-4, p=0.014), guide catheter pushback (2, IQR1-3,5 vs. 3, IQR3-4, p=0.005) and ophthalmic artery origin passage (2, IQR1-2 vs. 4, IQR3-5, p<0.001).

Conclusion:
Compared to microcatheter & microwire combinations, the T7 delivery assist catheter significantly facilitates aspiration catheter delivery to the target vessel in vitro.
Abstract TP71: Delayed Lesion on Diffusion-Weighted Image is Not Uncommon in Elderly and Severe Stroke-Suspected Patients
Authors: Kida Hiroyuki , Sakai Kenichiro , Takatsu Hiroki , Sato Takeo , Komatsu Teppei , Umehara Tadashi , Omoto Shusaku , Murakami Hidetomo , Mitsumura Hidetaka , Iguchi Yasuyuki
Published: June 2021

Introduction:
No lesion on admission DWI but delayed appearance in the follow-up DWI are not uncommon in acute stroke. Our aim is to investigate clinical features of patients with delayed-high intensity area (DHIA) on follow-up DWI.

Methods:
We enrolled 1) TIA patients and 2) clinically suspected stroke patients sustaining a neurological deficit over 24 hours without ischemic lesion on initial DWI. Follow-up DWI was performed in 7 days after admission. We divided into two groups as follows; DHIA group and no hyper-intense lesion on initial and second DWI (NHIA group). Univariate and multivariate logistic regression analysis were conducted on backgrounds, clinical courses including time from onset to MRI, symptom duration, and favorable outcome (mRS 0-1) in 3 months in both groups.

Results:
One hundred seventy-two cases were identified (male 68%, median age 66 yo, median NIHSS score 1, delayed-HIA group; 48 patients) between October 2012 and March 2019. DHIA group was older (72 yo vs 64 yo, p<0.001), higher NIHSS score on admission (1 vs 0, p=0.001), elevated serum BNP (42.5 pg/dL vs 15.6 pg/dL, p<0.001), D-Dimer (0.8 μg/mL vs 0.6 μg/mL, p=0.023). Then, favorable outcome was frequently observed in NHIA group (72% vs 88%, p=0.019). Time from onset to initial DWI of DHIA group was similar with those of NHIA group (130 min vs 148 min, p=0.142). Age and NIHSS score on admission were independent factors for DHIA (Age: OR 1.03, 95%CI 1.01-1.06, p=0.021, NIHSS on admission: OR 1.21, 95%CI 1.04-1.40, p=0.011).

Conclusion:
Follow-up DWI may play an important role of outcome biomarker in TIA and initially suspected stroke. Repeated MRI should be performed for elder and severe neurological deficits.
Abstract TP82: Factors Associated With Good Collateral Flow in Acute Stroke Patients With Large Vessel Occlusion
Authors: Seners Pierre , Roca Pauline , Legrand Laurence , Turc Guillaume , Oppenheim Catherine , Baron Jean Claude
Published: June 2021

Introduction:
Retrograde collateral flow is critical to maintain tissue perfusion despite large vessel occlusion. However, the premorbid factors associated with good collateral flow remain unclear, with substantial discrepancies in the literature.

Methods:
Patients from the registries of 6 French stroke centres with the following criteria were included: (1) acute stroke with isolated M1 occlusion (
i.e
, without tandem occlusion) referred for thrombectomy between May 2015 and March 2017; and (2) baseline brain MRI, including diffusion weighted imaging, MR-angiography and dynamic susceptibility-contrast perfusion-weighted imaging (PWI). A collateral flow map derived from PWI source data was automatically generated, replicating Kim et al’s previously validated method (Ann. Neurol., 2014). Collateral flow was dichotomized into good and poor. The association between good collateral flow and baseline clinical, biological and radiological variables was studied.

Results:
One hundred and sixteen patients were included, of which 66 (57%) had good collaterals. As expected, the latter patients had lower admission NIHSS (median: 15
vs
. 18, P=0.005) and lower baseline DWI lesion volume (median: 7ml
vs
. 32ml, P<0.001) than patient with poor collaterals. Onset-to-imaging delay and M1 occlusion site (proximal
vs
. distal) were similar in both groups (123min
vs
. 118min, P=0.75; 70%
vs.
68%, P=0.85, respectively). There was no significant (P>0.05) difference in gender, age, history of hypertension or diabetes, current smoking, baseline blood glucose and use of statins or antiplatelets between the good and poor collaterals groups.

Conclusions:
Despite the expected association between PWI-derived collateral flow and baseline clinical and radiological stroke severity in our sample of acute M1 occlusions, there was no association with premorbid factors previously found associated in some -but not all- studies. Our findings suggest that collateral flow is predominantly explained by genetic factors.