bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 3476: Factors Affecting The Incidence of Spontaneous Intracerebral Hemorrhage in a Multiracial Community in Northern California.
Authors: Guisado Raul , Catalli Linda , de la Cuesta Karen
Published: July 2021

INTRODUCTION:
Santa Clara County, California is a multi-racial community with a large Asian and Hispanic representation (30.6% Asian, 31.8% White and 31.9% Hispanics). The annual incidence of non-traumatic intracerebral hemorrhage (ICH) in our population is higher than the national average (29.2% vs. 13%) and the proportion of Asian patients with ICH is higher than expected (46.5% vs. 30.6% ). The reasons for the higher incidence of ICH in Asian populations are not known. We conducted a retrospective review of all cases of ICH in two Primary Stroke Centers in Santa Clara County, California to test the hypothesis that certain co-morbidities may explain the higher incidence of ICH in our community.

METHODS:
All cases of ICH admitted to two PSCs were abstracted from the Get With The Guidelines database. Data abstracted included racial and ethnic distribution (White, African American, Asian, Pacific Islander, Native American and Hispanic), age, sex, and selected co-morbidities (diabetes mellitus, hypertension and warfarin use.

FINDINGS:
There were a total of 260 patients. The total number of Pacific Islanders (4), Native Americans (1) and African Americans (13) was too small for further analysis and was not included. The age and sex distribution was similar between White, Asian and Hispanic patients but White women were significantly older (p = 0.018) than males. The rate of warfarin use was similar in all three groups. There was a higher incidence of hypertension and diabetes mellitus in Asian and Hispanics compared to White subjects (
Table
). Asian and Hispanic patients with hypertension and/or diabetes mellitus were at higher risk for ICH compared to White (
Table
).

CONCLUSION:
In our population, the incidence of ICH is disproportionately high in Asian subjects compared to Whites and Hispanics. This increase is only partially explained by higher incidence of hypertension and diabetes mellitus in Asians. Other factors, not included in the available databases, may include the geographic origin of Asian and Hispanic subjects (East vs. South Asian, North, Central or South American) and a generational effect on co-morbidities. Future epidemiological studies should include geographic and generational, as well as racial and ethnic data.
Abstract 3513: Randomized Trial of Outpatient Cardiac Monitoring After Cryptogenic Stroke
Authors: Kamel Hooman , Navi Babak B , Elijovich Lucas , Josephson S. Andrew , Yee Alan H , Johnston S. Claiborne , Smith Wade S
Published: July 2021

Background:
Diagnosis of atrial fibrillation (AF) as a cause of stroke or TIA is important because it identifies patients who may benefit from anticoagulation. Observational studies indicate that outpatient cardiac monitoring detects previously undiagnosed AF in 5-20% of patients with stroke, but these studies may overestimate the rate of AF if selection bias prompts analysis and publication. It is also unknown whether the yield of cardiac monitoring is higher than that of routine clinical follow-up.

Methods:
In a pilot trial, we randomly assigned consecutive patients with cryptogenic ischemic stroke or high-risk TIA (ABCD
2
score ≥ 4) to wear a Cardionet mobile cardiac outpatient telemetry monitor for 21 days after discharge, or to not wear a monitor. We excluded patients with a known history of AF, AF detected by inpatient cardiac telemetry (at least 24 hours required), a definite small-vessel etiology, a source found by vascular imaging or echocardiography, an obvious culpable systemic illness such as endocarditis, or inability to provide written, informed consent. All patients received routine clinical follow-up from their primary care physician and neurologist. We contacted patients and their physicians 3 months after discharge and used validated questionnaires to inquire about clinical diagnoses of AF and recurrent stroke or TIA.

Results:
The target enrollment of 40 patients was completed over 18 months. The mean age was 67 years (± 13), 23 (58%) were men, and 32 (80%) had at least one vascular risk factor; the baseline characteristics of our cohort were broadly similar to those in prior observational studies of cardiac monitoring after stroke. Our prespecified feasibility criteria were met, with full follow-up on 38 patients (95%) and successful completion of monitoring in 15 of the 20 patients (75%) randomized to monitoring. Overall, patients wore monitors for 64% of the assigned days. No patient in either study arm received a diagnosis of AF. Cardiac monitoring revealed AF in zero patients (0%, 95% CI 0-17%), brief episodes (< 10 seconds) of atrial tachycardia in two patients (10%, 95% CI 1-32%) and nonsustained ventricular tachycardia in two patients (10%, 95% CI 1-32%). There were no recurrent strokes; recurrent TIAs occurred in two patients assigned to the control group.

Conclusions:
The results of our pilot trial indicate that randomizing patients to outpatient cardiac monitoring after stroke is feasible. However, rates of AF detection were lower than expected, which may be due to publication bias in prior observational studies or selection of lower risk patients in our trial. Furthermore, 25% of patients assigned to undergo monitoring were not compliant. These results suggest that an adequately powered randomized trial of cardiac monitoring after stroke may require large numbers of participants.
Abstract 3536: Expanding Telestroke Partnerships: Building A Quality Assessment And Improvement Program To Support A Stroke System Of Care
Authors: Schlegel Sherene , Likosky William , Cress Tam , Gabelein Chad , Czartoski Todd , Gregg Mary , Stroming Scott , Moseley Randal , Kasnic Tracey , Vixie Marcy , Dyet Tom , Budden Jane , Kremer John , Stewart Kerry , Kennedy Scott , Wall Lorraine , Neff Stacie , Thompson Betsi , Weidemann Michael , McCoy Anita , Rookstool Robert , Allen Tami , Pate Lois , Merrill Kimberly
Published: July 2021

Throughout the U.S., many hospitals lack infrastructure and resources to provide acute stroke care rescue therapy. In a Washington state review (2008), it was determined that of hospitals which admit stroke patients only 50.7% had a neurologist available and 18.3% had a stroke team. Telestroke, although an efficient and cost effective way to bring neurological expertise to patients, has not been traditionally implemented to address other components of a system of care, such as transfer decisions and inpatient care requirements. A partnership (philanthropically supported) was created with the goal of supporting the expansion of traditional telestroke relationships commensurate with system of stroke care requirements. This consortium was created in Washington state amongst a tertiary stroke center and four centers who receive Telestroke services. This expanded relationship built upon basic telemedicine technology and training infrastructure and added in clinical training for inpatient unit staff, and development and implementation of a collaborative dashboard with quality metrics benchmarked against Joint Commission Primary Stroke Centers. Implementation strategies comprised partnering agreements, deployment of teams responsible for IT, training, and administrative tasks. Quality was addressed during monthly meetings and quarterly workshops. Comprehensive training programs were administered and tailored to meet specific needs assessment of each site with additional training offered via live streaming and archived series designed to address systems of stroke care. Communities, organizations and patients have benefited by the creation of a system which promotes local provision of care and the early development of a system of stroke care. Outcomes have included assured access to specialists when needed, improved patient selection for thrombolysis with some sites witnessing an increase in the number of patients who were appropriately treated with rtPA. In addition to rtPA usage and availability, patients have benefited from access to tertiary services such as advanced imaging, care consultations with vascular neurologists, and interventional services. All organizations have benefited from the collaboration resulting in local implementation of shared best practices. The program has been useful as a model for the establishment of Stroke Systems of Care in Washington. This implementation program may be a model for developing patient centered stroke systems of care recognizing that care needs extend beyond the IV thrombolytic process.
Abstract 3579: Prevalence And Distribution Of Asymptomatic Cervicocephalic Atherosclerosis In A Caucasian Population: Risk Factors And Biomarkers
Authors: Lopez-Cancio Elena , Dorado Laura , Millan Monica , Reverte Silvia , Galan Amparo , Alzamora Maite , Davalos Antoni , Arenillas Juan F
Published: July 2021

Objective:
To study clinical and biological factors associated with the different cervicocephalic location of atherosclerosis in Caucasian stroke-free individuals.

Methods:
Carotid and intracranial atherosclerosis were assessed in the same lab by ECO-Doppler in a random sample population of 933 Caucasian subjects older than 50, with a moderate-high vascular risk and without history of stroke (64% males, mean age 66 years). Hypertension, dyslipemia, diabetes and smoking habit were defined based on clinical history and/or current medications. The following inflammatory and endothelial dysfunction biomarkers were determined at baseline and considered as continuous variables for the analyses: C-reactive protein (CRP), plasminogen activator inhibitor (PAI-1), resistin and asymmetric dimethylarginine (ADMA).

Results:
Subjects were classified according to the cervicocephalic location of atherosclerotic lesions: 449 (48.1%) had no lesions (reference group), 404 (43.3%) had isolated carotid extracranial lesions (EC), 57 (6.1%) had isolated intracranial lesions (IC) and 23 (2.5%) had combined extra-intracranial lesions (C). After multinomial regression analyses, factors independently associated with each location of atherosclerosis compared to the reference group were: with EC, age (OR 1.06[1.04-1.09]p<0.001), male sex (OR 1.8[1.3-2.5]p=0.001), hypertension (OR 1.5[1.1-2]p=0.001), smoking (OR 1.7[1.2-2.4]p=0.004) and ADMA levels (1.7[1.05-2.9]p=0.03); with IC, age (OR 1.07[1.03-1.12]p<0.001), diabetes (OR 3.5[1.7-7.3]p=0.001) and ADMA levels (OR 3.2[1.3-8.1]p=0.01); with C, age (OR 1.2[1.05-1.2]p<0.001), male sex (OR 4.8[1.4-15.9]p<0.001), diabetes (OR 6.4[2.1-19.4]p=0.001), hypertension (OR 7.1[1.5-32.9]p=0.01) and resistin levels (OR 1.1[1.008-1.26]p=0.03).

Conclusions:
Our findings show distinct clinical and biological signatures of the cervico-cephalic location of subclinical atherosclerosis.
Abstract 3602: Inhibition of Soluble Epoxide Hydrolase Improves Neuronal Survival after Cardiac Arrest and Alters Microglial Activation towards a Neuroprotective Phenotype
Authors: Wang Jianming , Fujiyoshi Tetsuhiro , Kosaka Yasuharu , Herson Paco S , Koerner Ines P
Published: July 2021

Introduction:
Ischemia/reperfusion during cardiac arrest and cardiopulmonary resuscitation (CA/CPR) causes significant neuronal death and leads to long-term functional deficits. While neuronal death in the hippocampus is one likely cause of memory loss after CA/CPR, the local inflammatory milieu present after CA/CPR also contributes to functional deficit. However, the signaling pathways involved in the inflammatory response are poorly understood. Microglia, the brain resident immune cells, are activated in response to different types of brain injury. We hypothesized that CA/CPR activates microglia, which then contribute to subsequent neuronal loss and functional deficit. We tested whether pharmacologic inhibition of the pro-inflammatory enzyme soluble epoxide hydrolase (sEH) alters microglial activation and neuronal death in a mouse model of CA/CPR.

Methods:
Male adult C57Bl/6 mice underwent 8 minutes of CA followed by CPR. The sEH inhibitor 4-phenylchalcone oxide (4-PCO; 5 mg/kg ip) was administered at 5 minutes and 24 hours after CA/CPR. Microglial activation was assessed histologically by immunostaining for the activation marker Mac-2 at 24 and 72 hours after CA/CPR. Surviving CA1 hippocampal neurons were counted at 72 hours after CA/CPR. Hippocampal expression of inflammatory cytokines was measured by quantitative RT-PCR.

Results:
Phenotypically activated microglia expressing Mac-2 appeared in the hippocampus as early as 24 hours after CA/CPR, before significant neuronal death was present. Concurrently, expression of the pro-inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-1β increased. In animals treated with 4-PCO, hippocampal expression of the anti-inflammatory cytokine IL-10 was significantly increased (2-fold vs. vehicle), while expression of pro-inflammatory TNF- α and IL-1 β was unchanged. Subsequent death of CA1 neurons at 72 hours after CA/CPR was significantly reduced in animals treated with 4-PCO (34+/-3.7% 4-PCO vs. 52+/-7.1% vehicle), whereas the number of Mac-2 positive microglia was unchanged.

Conclusions:
Microglia are activated and produce pro-inflammatory cytokines early after CA/CPR. Inhibition of sEH induces hippocampal expression of anti-inflammatory and neuroprotective IL-10 and reduces subsequent neuronal death after CA/CPR, without altering the number of phenotypically activated Mac-2 positive microglia or expression of pro-inflammatory cytokines in the hippocampus. This suggests that sEH inhibition may alter gene expression in activated microglia after brain ischemia, thus protecting neurons and maintaining function. IL-10 induction by sEH inhibition is a promising therapeutic approach after ischemic brain injury from CA/CPR.
Abstract 3616: A Novel Model of Large Vessel Ischemic Stroke in New Zealand White Rabbits: Microcatheter Occlusion of the Posterior Cerebral Artery
Authors: English Joey , Hetts Steven , El-Ali Alex , Kolli Pallav , Do Loi , Wilson Mark , Saeed Maythem
Published: July 2021

Introduction:
The rabbit small clot embolic model for large vessel occlusion (LVO) is well established, yet remains with limitations. Blind introduction of autologous thrombus often fails to occlude the target vessel, and when successful, the precise timing of occlusion and revascularization are difficult to control. Studies of cellular biology and neuroimaging of acute reversible cerebral ischemia (i.e., penumbral tissue) would benefit from a rabbit model in which LVO can be reliably induced and easily confirmed, where the time of occlusion and revascularization can be precisely controlled.

Hypothesis:
We hypothesized that microcatheterization of the posterior cerebral artery (PCA) in New Zealand white rabbits (NZWRs) would result in LVO, with time of revascularization controlled by microcatheter removal. We hypothesized that transient LVO would produce ischemia in subcortical structures supplied by the PCA (e.g., hippocampus), sparing the cortex, with longer duration LVO leading to irreversible cortical ischemia.

Methods:
Transfemoral 1.5F microcatheterization of the PCA was performed in anesthetized NZWRs using fluoroscopic guidance. LVO was maintained for 30 minutes (n=2), 60 minutes (n=2), 180 minutes (n=2) and 210 minutes (n=1), followed by microcatheter removal and reperfusion. Neuroimaging was obtained 3 hours later with MRI (3T DWI, FLAIR, gradient and perfusion sequences) and CT (64 slice noncontrast and perfusion imaging). Post-mortem histologic analysis of infarct was assessed using triphenyltetrazolium choloride (TTC) stain. Matched DWI and TTC sections were analyzed using ImageJ software.

Results:
Percent infarct of matched DWI and TTC sections was strongly correlated (r2 = 0.86). Transient LVO of 30-60 minutes resulted in infarction of the ipsilateral hippocampus and thalamus, sparing the cortex, while more prolonged LVO (180-210 minutes) led to cortical infarction as well.

Conclusions:
Image-guided microcatheter induction of LVO in NZW rabbits can reliably produce time-dependent infarction of cortical and subcortical structures, and thus may be a useful model for the study of penumbral cortical tissue.
Abstract 3663: Characterization of Cerebrovascular Parameters using MRI in Endothelial Nitric Oxide Synthase Knockout Mice
Authors: Suh Ji-Yeon , Huang Shunning , Atochin Dmitriy N , Kim Jeong Kon , Shim WH , Kwon Seon-Joo , Kim Young Ro
Published: July 2021

Endothelial-derived nitric oxide (NO) is important for properly regulating vascular tone and maintaining blood pressure. Mice lacking endothelial NO synthase (eNOS), i.e. loss of endothelial NO production, have systemic hypertension and develop larger cerebral infarction upon cerebral ischemia. Given that constitutively produced NO is necessary for a normal endothelial function, we posit that cerebrovascular characters in eNOS KO mice brain may differ in structure and physiology. In this study, we aim to establish MRI-derived vascular parameters such as cerebral blood volume (CBV), water exchange index (WEI), and vessel size index (VSI) using two different MRI intravascular contrast agents (Gd-PGC (Protected graft copolymer bearing covalently linked Gd- DTPA residues) and SPION (superparamagnetic iron oxide nanoparticle)). We also investigated whether perivascular aquaporine (AQP) proteins, which play a central role in the pathophysiology of many diseases, are differently expressed in eNOS KO mice. Flip angle dependence of the MRI signal intensity on transvascular water exchange rate was used to quantify CBV and WEI before and after intravenous administration of Gd-PGC using wild type mice (C57BL/6, n=8) and eNOS KO mice (n=5). 2D T2 and T2* maps were also acquired before and after SPION administration for measurements of cerebral VSI. As results, eNOS KO mice have lower VSI than that that in wild type mice (
Fig. A
). The CBV of eNOS KO mice is not significantly different from that of wild type mice (
Fig. B
). Furthermore, baseline WEI significantly increased in the eNOS KO mice, indicating higher BBB water permeability. However, both AQP1 and AQP4 were less expressed in eNOS KO mice than those in wild type mice (
Fig. D
). These suggest that the loss of eNOS contribute to the decrease of the vessel diameter and increase of water permeability under a baseline physiological condition. However, expression of AQP proteins forming vascular water channels is not involved with the observed water exchange rate increase across the BBB in eNOS KO mice. The study warrants future investigations to elucidate the relationship between NO synthase and the BBB integrity and its involvement with ischemic damage.
Abstract 3686: Stroke, TIA, Amaurosis Fugax, or No Symptoms as Predictors of Outcomes in the Carotid Revascularization Endarterectomy versus Stenting Trial
Authors: O'Mara Charles S , Hakaim Albert G , Spetzler Robert F , Bulas Robert , Nazzal Munier , Longbottom Mary E , Voeks Jenifer H , Brott Thomas G
Published: July 2021

Background
In previous carotid revascularization trials, stroke as a qualifying symptom has had the greatest importance as a predictor of subsequent outcomes. However, the importance of stroke, TIA, amaurosis fugax, and asymptomatic status has not been analyzed together and comparatively as predictors of outcome for carotid stenosis in a randomized clinical trial (RCT).

Methods
Qualifying events were analyzed for the 1321 symptomatic patients in the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) and were modeled as predictors of the primary outcome (stroke, myocardial infarction, and death during a 30-day peri-procedural period, or ipsilateral stroke over the follow-up period out to 4 years); the potential predictive value was also tested for the outcome of stroke and death. The model included other potential predictors such as age, sex, and treatment.

Results
The distribution of pre-randomization qualifying events among symptomatic patients in CREST was 572 strokes, 550 TIA, and 199 amaurosis fugax. Relative to symptomatic patients qualifying for the study with stroke, the risk of subsequent primary endpoint was 15% lower for those qualifying with TIA (HR=0.85; 95% CI = 0.57 - 1.28), 36% lower for those qualifying with amaurosis fugax (HR=0.64; 95% CI = 0.3 - 1.23), and 48% lower for asymptomatic patients (HR=0.52; 95% CI = 0.35 - 0.76). The risk of stroke or death was 11% lower for TIA (HR=0.89; 95% CI = 0.57 - 1.40), 18% lower for amaurosis fugax (HR=0.82; 95% CI = 0.42 - 1.60), and 57% lower for asymptomatic patients (HR=0.43; 95% CI = 0.28 - 0.67) when compared to symptomatic patients qualifying with stroke. The risk for patients with stroke or TIA did not differ significantly, and the risk for asymptomatic patients and patients with amaurosis fugax did not differ significantly.

Conclusion
Outcomes in patients with carotid disease were predicted in descending order by stroke, TIA, amaurosis fugax, and asymptomatic status in a large RCT. Asymptomatic status and amaurosis fugax have a comparatively benign prognosis. Better understanding of these predictors may help in determining who will benefit from carotid revascularization and how quickly they may benefit given the perioperative risks.
Abstract 3710: Nasal Continuous Positive Airway Pressure Therapy In Acute Stroke: Results Of A Feasibility Study
Authors: Minnerup Jens , Wersching Heike , Ringelstein E. Bernd , Dziewas Rainer
Published: July 2021

Introduction:
Sleep related breathing disorder (SRBD) is a frequent complication in the early phase after stroke. SRBD is associated with poor outcome. Continuous positive airway pressure (CPAP) was shown to be feasible and to improve outcome when applied in the chronic phase after stroke. We hypothesized that CPAP therapy initiation in the first night after stroke is feasible.

Methods:
In this open-label, parallel group study with blind assessment of outcomes 50 patients were randomly assigned to the CPAP or the control group. Intervention patients received CPAP therapy for three nights. Patients of the CPAP group with an apnea-hypopnea index (AHI)>10/hour as measured by polysomnography (PSG) at night four were treated with CPAP for additional four nights. The primary end point was feasibility defined by reduction in AHI with CPAP treatment, CPAP adherence and nursing workload within the first three nights. The secondary end point was NIHSS score improvement on day eight.

Results:
Under CPAP treatment the AHI was significantly reduced (P=0.0001). Nursing work load was similar between the CPAP (n=25) and the control group (n=25) (P=0.741). Ten patients (40.0 %) had excellent CPAP use, 14 patients (56.0 %) had some use, and 1 patient (4.0 %) had no use. We found a trend towards greater NIHSS score improvement in the CPAP group (P=0.092) and a significantly greater NIHSS score improvement in patients with excellent CPAP use (P = 0.022) when compared to the control group.

Conclusions:
This is the first randomized trial that investigated the feasibility of CPAP therapy in acute stroke patients. Compliance was moderate without increasing the nursing workload. CPAP significantly reduced the AHI and might thereby improve clinical outcome after stroke. Our findings warrant further investigation in a larger trial.
Abstract 3769: Barriers to Obtaining Informed Consent in Acute Stroke Clinical Trials
Authors: Masuca Sacha R , Das Devsmita S , Delano Deji , Irani Malcom , Pandurengan Renga , Barreto Andrew D , Ifejika-Jones Nneka , Misra Vivek , Bursaw Andrew , Peng Hui , Rahbar Mohammad H , Savitz Sean I , Grotta James , Gonzales Nicole R
Published: July 2021

Background
Identification of barriers to enrollment in acute stroke clinical trials may identify ways to improve enrollment and expedite completion of clinical research trials. In this exploratory analysis we sought to evaluate the differences in presenting characteristics between patients who are able to provide informed consent (IC) compared with those who were enrolled by the legal authorized representative (LAR).

Methods
From our single center, prospectively collected registry, we identified consecutive patients with acute ischemic stroke (AIS) who presented to our emergency department and were enrolled into acute (<8hrs from symptom onset) prospective clinical treatment trials. Data collected included arrival time, thrombolysis time, IC time, source of IC (LAR or patient), aphasia or neglect and method of arrival. For analysis, the patients who were consented by a LAR were compared with patients who provided their own IC.

Results
From 2003 - 2011, we identified 124 patients who met inclusion criteria. There were no differences in age, sex, presentation or door to needle times (Table 1). Patients who were able to provide IC presented with less severe stroke (p<0.0001). Aphasia and neglect were significantly more common when a LAR provided IC (p<0.0001). LAR consent required a significantly longer amount of time (90 vs. 71 min., p=0.04).

Conclusions
In our single center study, we found that patients with milder stroke are able to provide IC and the presence of aphasia or neglect can hinder enrollment in the absence of a LAR. In addition, when patients are able to provide IC, they do so almost on average 20 minutes faster than the LAR. Additional evaluation is necessary to determine the reasons for delay. Since good outcomes with investigational therapies for AIS treatment are likely to be time dependent, further efforts should target improvement of the IC process to minimize delay in clinical trial enrollment.
Abstract 3772: High Precision and Accuracy of B-flow Ultrasound Morphometry of Internal Carotid Artery Stenosis: Improved Non-invasive Stenosis Grading
Authors: Macharzina Roland R , Böhme Tanja , Fan Nian , Rastan Aljosha , Witzel Charlotte , Vach Werner , Weber Johannes , Moske-Eick Olaf , Beschorner Uli , Búrgelin Karlheinz , von Sússkind-Schwendi Julius , Neumann Franz-Josef , Zeller Thomas
Published: July 2021

Background:
Evaluation of various imaging modalities for grading internal carotid artery (ICA) stenosis can be performed by comparison of minimal lumen diameters (MLD) as well as percent ICA-stenosis calculated with a healthy distal reference segment (NASCET method). The new B-Flow (BF) ultrasound (US) imaging method displays stenosis in a similar fashion as reference methods like catheter angiography (A) and multi-slice CT-angiography (MS CTA).

Aim:
to evaluate the accuracy of MSCTA by using multiplanar reformation (MPR) for measuring ICA stenosis compared with of A as well as accuracy and precision of BF-US compared with MSCTA at corresponding projections and locations.

Methods and patients:
CTA of ICA were compared with A in 37 low to high grade ICA stenoses of patients screened by doppler US velocity criteria. CTA were compared with US in 80 ICA stenoses of 63 patients in a similar fashion at identical projections. Diameters of stenosed ICA were rendered coaxial on CTA. A was made with AXIOM (Siemens, Germany), MSCTA with SOMATOM (Siemens, Germany); Ultrasound Logic 9 with 6-8 Mhz linear scanner, GE, USA. All readings were by two independent observers for each technique. Quantitative A was done with MEDIS software (Netherlands), Bland-Altman analysis and statistics with SPSS (Germany). Identical planes were confirmed by overlay technique.

Results:
MLD was slightly overestimated by CTA compared with angiography with mean differences (±SD) of 0.093 ± 0.25 mm for longitudinal sections. Pearson correlation coefficient (PCC) was 0.95. NASCET stenosis grade showed no bias between CTA and A (-0,5%±6.23% SD) and resulted in a PCC 0.93 for MPR's compared with A. MLD was slightly underestimated by parasaggital section (PSS) BF-US (0.031mm ± 0.23mm SD) compared with CTA, PCC = 0.96. NASCET ICA-stenoses were slightly underestimated by CTA, with mean differences of 1,16% ± 6,04% (SD), PCC was 0.92. In this cohort, discrimination of binary 50% NASCET stenosis with PSS BF-US had a 87%sensitivity, 86% specifity and an accuracy of 86%; discrimination of binary 70% NASCET stenosis with PSS BF-US had a sensitivity of 92%, specifity of 90% and an accuracy of 90%.

Conclusion:
diagnostic performance of CTA proved to be excellent compared with angiography and PSS 2D BF-US was highly accurate, when using corresponding projections. 2D BF-US may be a valuable additional tool for screening and confirmation of CAS for therapeutic stratification.
Abstract 3878: The Role of Routine Carotid Artery Duplex in Patients Referred for Coronary Artery Bypass Grafting
Authors: Moraca Robert J , Wanamaker Kelly , Nitzberg Diana , Bailey Stephen H , Benckart Daniel , McGregor Walter , Maher Thomas , Magovern George
Published: July 2021

Introduction
In the past decade, there has been an increase in the amount of patients with medical co-morbidities referred for coronary artery bypass surgery (CABG). Cerebrovascular accident (CVA) after CABG is a devastating and multi-factorial problem. Carotid artery disease in patients undergoing cardiopulmonary bypass procedures may increase the risk of significant neurological complication. We review the results of carotid screening, management and outcome of carotid disease in patients referred for CABG.

Methods
Between 2008 through 2010, 673 patients were referred for isolated coronary artery bypass surgery at a single institution. Patients were identified through a systematic review of The Department of Cardiothoracic Surgery Society of Thoracic Surgery Outcomes Database. A retrospective analysis of prospectively collected demographic, clinical data and outcomes were preformed. All patients with screening preoperative carotid duplex were reviewed. We defined the degree of carotid disease as: none to mild stenosis (<50%), moderate stenosis (50-69%), severe stenosis (70-99%).

Results
559 (83%) patients underwent screening preoperative carotid ultrasonography prior to surgery. Patient demographics and clinical variable are listed in
Table 1
. Severity of carotid disease on preoperative imaging was none/mild (68%), unilateral moderate disease (17%), bilateral moderate (7%) and severe (8%). 12 (2.1 %) of patients underwent a preoperative carotid endarterectomy and subsequent CABG, with no peri-operative cardiac events or CVAs. Only 4 (0.7%) patients in the entire series had a peri-operative CVA.

Conclusions
Routine use of carotid ultrasound in patients referred for CABG with aggressive management may reduce the incidence of peri-operative CVA.
Abstract 3977: Neuroprotective Effects of Echogenic Liposomes-Mediated Xenon Delivery in a Rat Embolic Stroke Model Combined With Tissue Plasminogen Activator Thrombolysis
Authors: Peng Tao , Britton George L , Aronowski Jaroslaw , Cattano Davide , Klegerman Melvin E , Laing Susan T , McPherson David D , Huang Shao-Ling
Published: July 2021

BACKGROUND:
Ischemic stroke is the second most common cause of death worldwide and a major cause of disability. Intravenous (iv) tissue plasminogen activator (tPA) in combination with the neuroprotective gas, xenon (Xe), is a promising strategy for ischemic stroke treatment. However, Xe delivery by inhalation may reduce oxygen uptake and tPA activity. We have developed novel Xe-containing echogenic liposomes (Xe-ELIP). In this study, we investigated the therapeutic effect of Xe-ELIP in a rat embolic stroke model.

METHODS:
Xe-ELIP was prepared by the pressurized-freeze method. Thrombotic strokes were induced in male Sprague-Dawley rats (n=16) by injecting a 13mm long blood clot into the middle cerebral artery (MCA). In the treatment group, tPA (10mg/kg) was infused intravenously at 2 hours after the onset occlusion. Xe-ELIP was administrated into the common carotid artery just before iv tPA. Continuous wave ultrasound (1 MHz, 50% duty cycle, 0.5 W/cm
2
) was applied to trigger Xe release from ELIP during the 5 min of Xe-ELIP administration. Behavioral tests (limb placement, grid walking and beam walking) were conducted three days after the thrombotic stroke. Two mm-thick coronal brain sections were cut and stained with TTC to determine infarct size.

RESULTS:
The thrombotic stroke control group without any treatment exhibited the largest damage and infarct size (17±5% of the whole brain); tPA treatment reduced the damage and the infarct size to 5.2±0.4% of (p=0.025
vs
stroke). tPA treatment in combination with Xe-ELIP further reduced the infarct size to 1.5±0.4% (p=0.05
vs
tPA group) (
Fig
1a, 1b). Behavioral deficit correlated with the infarct volume reduction. Regional blood flow velocity monitored by a laser Doppler flow meter was the same in both tPA and tPA+Xe-ELIP treatment groups.

CONCLUSIONS:
This study has demonstrated a significant neuroprotective effect of ELIP-encapsulated xenon released by application of 1 MHz ultrasound. Xe-ELIP can be used in combination with tPA without affecting tPA thrombolytic activity.
Abstract 3983: Decreased Brain Swelling, Stroke- and Blood-Brain Barrier-lesion Volumes after Combination Treatment with Simvastatin and Tissue Plasminogen Activator in a Rat model of Embolic Stroke
Authors: Nagaraja Tavarekere N , Bezerra Francisco J , Karki Kishor , Ewing James R , Fenstermacher Joseph D , Knight Robert A
Published: July 2021

Background and Purpose -
Cytotoxic and vasogenic edema in acute stroke may lead to brain swelling. Acute treatment with tissue plasminogen activator (TPA) can increase blood-brain barrier (BBB) damage and vasogenic edema. Using a rat embolic stroke model, this study investigated the efficacy of simvastatin in combination with TPA to reduce brain swelling.

Methods -
One middle cerebral artery in young adult male Wistar rats (300 g) was embolized with a day-old fibrin-rich blood clot. The rats were divided randomly into 6 groups (N=6-8 per set): 1) Control; 2) Simvastatin (20 mg/kg; subcutaneous) at 30 min and at 24 h post-ictus; 3) TPA (10 mg/kg; intravenous) at 2 h post-ictus; 4) TPA at 3 h post-ictus; 5) Simvastatin plus TPA at 2 h; and 6) Simvastatin plus TPA at 3 h. They were injected with [
14
C]α-aminoisobutyric acid and the brains processed for Nissl histology and quantitative autoradiography (QAR) at 48 h. Brain hemispheric and stroke lesion volumes from Nissl-stained brain sections and BBB lesion volumes from QAR images were measured using an image analysis system. Data were expressed as mean ± standard deviation of the ratios to the contralateral hemisphere volumes. They were analyzed by Student’s t-tests and significance inferred at
P
<0.05 (*).

Results -
Compared to controls, simvastatin and TPA treatments alone, combination treatment at both 2 and 3 h post-ictus was effective in reducing brain swelling, stroke- and BBB-lesion volumes (
Figure
). Treatment at 2 h post-ictus seemed to be more effective than at 3 h.

Conclusions -
These data suggest that simvastatin in combination with TPA may attenuate brain swelling in acute stroke and, thus, may be a viable adjuvant agent with TPA. Edema fluid formation and consequent brain swelling influnce the disease outcome and, moreover, can even be fatal. Therefore, efficacy and mechanisms of action of simvastatin in controlling them in stroke and other acute brain trauma deserve further investigation.
Abstract 4017: Safety of Intra-Arterial Bolus and Intravenous Infusion of Eptifibatide as an Adjunct to Intravenous Alteplase in Acute Ischemic Stroke: A Prospective Registry
Authors: Kirmani Jawad F , Moussavi Mohammad , Ahmed Younus , Channapragada Theja , Carlowicz Cecilia , Botros David , Gizzi Martin , Ibrahim Mohammad
Published: July 2021

Background and Purpose:
Eptifibatide, a competitive platelet glycoprotein IIb-IIIa receptor inhibitor with high selectivity for platelet glycoprotein IIb-IIIa receptors and a short half-life, has been shown to reduce the risk of ischemic events associated with coronary interventions. However, its role in conjunction with full dose intravenous alteplase in neurointerventional procedures needs to be determined. We report the results of an open-label prospective registry to evaluate the safety (in terms of avoiding hemorrhagic complications) and effectiveness (in terms of recannalization rates and clinical improvement) of administering eptifibatide.

Method:
Patients data was prospectively maintained at a University-affiliated community hospital from January 2010 to June 2011. Consecutive patients with moderate to severe stroke who received intravenous Alteplase and failed to improve were studied. Femoral artery access was established and site of cerebral occlusion crossed with microcatheter. Each patient was administered 135 mcg/kg intraarterial bolus followed by intravenous eptifibatide infusion (0.5-microg/kg/min) for 20 hours. The outcome analysis was done to look at recannalization rates, clinical improvement within 24 hours and mRS at discharge. The primary safety end point was symptomatic intracranial or major extra-cranial bleeding.

Result:
Sixteen patients (Mean Age 72.7, Range 30-93, Male-5(31.25%), Female-11(68.75%)) underwent treatment with this strategy. Recannalization was achieved in 93.75%(n=16)(Complete Recannalization in 43.75%, Partial Recannalization in 50%). There was immediate clinical improvement in 68.75% and good outcomes in 31.25%. One symptomatic and one asymptomatic intracerebral hemorrhage occurred during the follow-up period. Minor femoral site bleeding without requiring transfusion occurred in one patient.

Conclusions:
In conclusion, eptifibatide administered as an adjunct to thrombectomy for bridging after intravenous Alteplase appears to be safe and promotes recannalization in patients with acute ischemic stroke. Further studies are required to analyze eptifibatide efficacy after intravenous alteplase and its role in neurointerventional procedures.
Abstract 4020: The Novel TrkB Agonist, 7,8-Dihydroxyflavone Enhances Stem Cell Mobilization After Stroke.
Authors: Mocco J , Afzal Aqeela , Thomas Nagheme , Warraich Zuha , Kleim Jeffery
Published: July 2021

Background:
Increasing levels of circulating Hematopoietic Stem Cells (HSC)/Hematopoietic Progenitor Cells (HPC), bone marrow derived mononuclear cells that promote repair in areas of injury, have been demonstrated to correlate with improved neurological function following stroke, suggesting a potentially critical role for HSC/HPC’s in limiting stroke injury and/or facilitating stroke recovery. Flavonoids, found in plants and fruit, exert anti-oxidative effects. Recent studies have demonstrated that 7,8 Dihydroxyflavone (DHF) is a potent TrkB agonist mimicking Brain Derived Neurotropic Factor, thus making it a powerful potential tool for treating neurological disorders. Stromal Derived Growth Factor 1-Alpha (SDF1-A) along with its receptor CXCR4 is a potent chemo attractant released by areas of injury. SDF1-A has been shown to mobilize HSC/HPC from the bone marrow to the blood and lead to ‘homing’ of the cells to an area of injury. We investigated the effect of DHF on HSC/HPC function following cerebral ischemia.

Methods:
Ischemic damage was induced in adult male Long Evans hooded rats (350-400g) with a peri-MCA injection of the vasoconstriction peptide ET-1. The rats were sacrificed at 24 hours post surgery and their bone marrow and blood HSC/HPC enriched using nanoparticles tagged with LIN negative and CD90 markers.

Results:
Stroked animals showed an increase in bone marrow production of HSC/HPC versus control animals (31.9±7 versus 2±0.5, p<0.05). The mobilization of the HSC/HPC from the bone marrow to the blood was also significantly higher in the stroked animals versus control animals (43±19 versus 3.6±0.3, p<0.05). Following stroke, DHF pre-treated HSC/HPC’s demonstrated significantly improved migration along an SDF-1 gradient compared to controls (129±1.0 versus 108±1.15, p<0.05), despite the fact that DHF alone provided no independent migratory stimulus.

Conclusions:
The results suggest that DHF may be a viable compound to facilitate HSC/HPC migration post-stroke.
Abstract 46: Initial Experience with Bedside Monitoring of Stroke and Cerebral Perfusion using Time Domain Near-infrared Spectroscopy (TD-NIRS): Feasibility and Future Directions
Authors: Rosenthal Eric S , Selb Juliette , Schwamm Lee H , Iftimia Nicusor
Published: July 2021

Background:
Near-infrared Spectroscopy (NIRS) may provide continuous, multiregional parenchymal bedside perfusion monitoring without the risks of patient transport, contrast, or radiation. Time-domain NIRS (TD-NIRS) uses pulsed light attenuation at multiple wavelengths (600-950 nm) to discretely quantify oxyhemoglobin and deoxyhemoglobin and determine total hemoglobin, oxygen saturation (OS) and cerebral blood volume (BV) in the region between each light source and detector. This study aimed to assess the feasibility of employing a novel TD-NIRS technology to assess absolute levels of cerebral BV and OS with broad spatial coverage in order to detect regions of ischemia.

Methods:
Ischemic stroke (IS) and subarachnoid hemorrhage (SAH) patients underwent TD-NIRS measurements. IS patients were fitted with a rectangular probe over the region of ischemia (2 rows of 4 sources between 3 rows of 5 detectors), using CT as a guide (external acoustic meatus as reference). SAH patients were fitted with a linear “anterior crown” probe with light sources and detectors arranged alternating in a single row (7 sources, 6 detectors). Clearance above the frontal sinus was guided by CT imaging (nasion as reference). 1.8 cm separated all source-detector pairs. Time-correlated single photon-counting photomultiplier tubes detected photons to measure absorption of pulsed light emitted at 3 wavelengths (690, 805, and 835 nm). Maximal OS (OSmax) and BV (BVmax) were calculated for the entire region measured by the probe to enable multiple comparisons.

Results:
In IS patients, ischemic regions (n=4) had an OSmax of 65.8 SD 13.1; contralateral normal tissue had an OSmax of 85.3 SD 27.1 (paired t-test; p 0.14). Ischemic regions had a BVmax of 76.25 SD 24.17 compared with 104.0 SD 42.5 in contralateral normal tissue (p 0.18). Regional inspection showed good visual correlation with infarcts (
Figure
). Of SAH patients with serial measures (n=2), one developed heparin-induced thrombocytopenia and bilateral infarcts, coincident with decreased BVmax on the right (72, day 1; 48, day 12) and left (153, day 1; 56, day 12); OS did not change.

Conclusion:
We were able to calculate multiregional BV and OS for patients with cerebral ischemia. Despite small sample size, we demonstrated a trend between contralateral (ischemic stroke) and historical (subarachnoid hemorrhage) controls. Leakage of light and absorption by hair produced artifacts that will require improvement in future applications. This system requires validation and further ergonomic refinement but has potential to enable continuous multiregional parenchymal monitoring.
Abstract 47: Use Of Intra-arterial Infusion of Calcium-Channel Blockers Through An Indwelling Microcatheter: One Institution's Experience
Authors: Volk Jerome M , Culicchia Frank , Dawson Robert
Published: July 2021

INTRODUCTION:
Vasospasm following aneurysmal subarachnoid hemorrhage is a very extensively studied source of morbidity and mortality. Numerous treatment regiments have been investigated and published. A recently published article discussed the use of prolonged infusion of verapamil through an indwelling catheter as an effective treatment for medically refractory severe vasospasm. The goal of our study is to report our institution's experience with this method of treatment.

METHODS & MATERIALS:
All patients with medically refractory vasospasm from July 2009 through August 2011 were included in the study. A retrospective review of data was compiled. In particular, age, sex, aneurysm location, aneurysm treatment, intra-arterial treatment fo vasospasm, dosages and times of medication infusion, and presence of new ischemia or progression of ischemia on CT scan were investigated.

RESULTS:
A total of 13 treatments were administered. Nicardipine was used in two treatments, and verapamil was used in the remaining eleven treatments. The doses of nicardipine were 10mg and 49 mg, and were infused over 20 min and 75 min respectively. The doses of verapamil ranged from 41 mg to 200 mg. One patient was treated with both nicardipine and verapamil at one treatment session. The infusion times ranged from 25 min to 22 hr. Between 1 and 3 vessels were treated per patient resulting in a total of 19 vessels treated. The number of treatments per patient ranged from one to two. Review of pre- and post-treatment CT scans revealed worsening of ischemic changes in 9 of the 13 treatments, while the remaining 4 treatments showed no change or progression of ischemic changes on imaging. One patient had a conversion to a hemorrhagic infarct from an inschemic infarct after a treatment.

CONCLUSIONS:
Upon reviewing our data we have come to the conclusion that prolonged infusion of calcium channel blockers is not an effective treatment for medically refractory severe vasospasm. After 13 treatments we have decided to not continue with this treatment. Therefore, we believe that angioplasty is still the gold standard for treatment of medically refractory vasospasm.
Abstract 74: Degree of Clot-related Susceptibility Artifact is an Independent Risk Factor for Parenchymal Hematoma Following Mechanical Thrombectomy
Authors: Franceschi Ana M , Chaudhry Zeshan A , Yoo Albert J , Kamalian Shervin , Hirsch Joshua A , Schwamm Lee H , Lev Michael H
Published: July 2021

Purpose:
We observed that in several cases of embolectomy treated acute stroke patients complicated by parenchymal hematoma (PH), there was marked susceptibility change (“blooming artifact”) on admission gradient echo MRI sequences surrounding the occlusive thrombus. We sought to determine if this imaging feature was associated with hemorrhagic risk.

Methods:
We identified 91 consecutive embolectomy treated patients who had admission susceptibility weighted MRI sequences (51 MPGR, 26 perfusion GRE, and 14 low B) and follow-up imaging. PH was defined as PH1 or PH2 per ECASS criteria. A “susceptibilty ratio score” (SRS) was determined by dividing the maximum width of the blooming artifact of the involved vessel (n=69 proximal MCA, 13 ICA/MCA, and 10 terminal ICA) by that of the corresponding segment of the contralateral uninvolved vessel. Patients were stratified according to SRS <2 (Group 1), 2-4 (Group 2), or >4 (Group 3). Univariate and multivariate analyses were performed to test the association between SRS scores and PH on post-treatment follow-up imaging.

Results:
Mean age was 67.3 ± 17.7, and median NIHSS score was 17 (IQR 14-20). The mean SRS was 2.5 ± 1.3. Using ECASS criteria, no hemorrhages were seen in 46 (50.5%); HI1 in 26 (28.6%); HI2 in 10 (11.0%); PH1 in 4 (4.4%); and PH2 in 5 (5.5%). The PH rate was 0% (0/22) for Group 1, 9.6% (5/52) for Group 2, and 24% (4/17) for Group 3 (p=0.04, two-tailed Fishers Exact Test). Adjusting for age, NIHSS score, TICI reperfusion, and IV tPA pre-treatment, ordinal SRS was an independent predictor of parenchymal hematoma (O.R. 4.13, 95%C.I.:1.2-13.8; p=0.02). There was an interaction between ordinal SRS and IV tPA (multivariate p=0.02 for interaction term), such that IV tPA prior to embolectomy resulted in a higher rate of PH in the SRS >4 group (33.3% vs 12.5%).

Conclusion:
An easy to calculate “susceptibility ratio score” appears to be associated with development of PH in acute stroke patients treated with mechanical thrombectomy, with low risk (SRS<2, 0% PH incidence) and high risk (SRS>4, 24% PH incidence) groups. For the high risk group, PH was more likely in those with IV tPA pre-treatment. We speculate that this imaging sign may be a biomarker for occlusive thrombus burden and/or the degree of baseline vessel wall injury surrounding the occlusive clot. Replication of this novel observation in independent cohorts is needed.

Figure 1
A.

Sample measurement for calculation of SRS from MPGR image.

Figure 1
B.

CT scan post mechanical thrombectomy demonstrates acute development of PH2 superior to the region of maximal susceptibility.