bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WP399: Reduced Cost and Decreased Length of Stay Associated with Acute Ischemic Stroke Care Provided by Nurse Practitioners: A Single Primary Stroke Center Experience
Authors: Roering Leah , Peterson Michelle , Miran Muhammad Shah , Freese Melissa , Shea Kenneth , Suri M. Fareed K.
Published: June 2021

Background:
Nurse practitioner (NP) have a wider role in modern stroke centers providing quality evidence based care to patients in both in and outpatient settings for acute ischemic stroke (AIS) and transient ischemic attack (TIA) patients. We studied the outcome measures, length of stay (LOS) and cost before and after implementation of nurse practitioners as the primary medical provider in a community based stroke center.

Methods:
St Cloud hospital is acute care hospital with dedicated stroke service responsible for workup and management of all patients admitted with AIS and TIA. From March 2014-March 2015, all patients were primarily managed by stroke neurologists with or without support of NP, representing physician driven arm. From June 2015-March 2016 all non-critical patients were managed primarily by NP, representing the NP driven arm of care. For this analysis, we excluded all patients with subarachnoid hemorrhage or intracerebral hemorrhage. Using ICD codes, we abstracted LOS and hospitalization cost for all patients, and compared between two arms.

Results:
A total of 822 patients were included in physician arm and 336 in NP arm. The mean age was 72±14 years for both arms, and 54.4% were male in physician arm and 57.4% were male in NP arm. The mean total LOS for the physician arm was 3.1 ±3.3 days while 2.9±3.6 for NP arm (p=0.6). The total cost for physician arm was $11,286.70 ±$10,920.90 while the NP arm was $10,277.30± $10,142.30 (p=0.1).

Conclusion:
There is a trend towards lower cost and length of stay with implementation of NP as primary stroke provider for patients admitted with acute ischemic stroke.
Abstract WP4: Transfer Patients and Patients Presenting Directly to Endovascular Capable Centers Achieve Similar Good Outcome Rates with Endovascular Therapy
Authors: Sarraj Amrou , Veznedaroglu Erol , Budzik Ronald F , English Joey D , Baxter Blaise W , Bartolini Bruno , Liebeskind David S , Krajina Antonin , Shields Ryan D , Xiang Bin , Nogueira Raul G , Blackburn Spiros , Farrell Christine M , Savitz Sean I , McCullough Louise D , Gupta Rishi
Published: June 2021

Background:
While endovascular therapy (EVT) is effective for large vessel occlusions (LVO), most patients present to hospitals without EVT capability and are transferred for intervention, delaying treatment.

Objective:
We evaluated outcomes in LVO patients treated with thrombectomy who were transferred compared to those presenting directly to EVT facilities.

Methods:
In a large multicenter international prospective cohort study of LVO patients treated with stent retriever thrombectomy (TREVO Registry), patients were stratified by initial presentation into transferred (TNS) vs direct (DIR). 90 day mRS was the primary outcome (0-1 excellent, 0-2 good outcomes); sICH and reperfusion by mTICI were secondary outcomes. Outcomes were compared in the 2 groups (0-8 hrs onset to groin puncture (GP) then in time matched 3-8 hrs subgroups for validation). Logistic regression identified independent predictors of good outcome in TNS patients.

Results:
We identified 540 patients (230 TNS; 310 DIR) (Fig 1). TNS patients were younger and had longer onset to GP times (4.6 vs 3.1 hrs;
p
<0.001) (Table 1). DIR achieved higher excellent outcomes (50.4 vs 38.7%;
p
<0.001) (Table 2). There were no significant differences in good clinical outcomes (61 DIR vs 57.4% TNS, OR 0.90, 95% CI 0.63-1.27;
p
=0.4) (Fig 2) and no difference in the time matched 3-8 hrs subgroups (59.2% DIR vs 56.3% TNS,
p
=0.6). Fig 3 plots good outcome probabilities over time, showing similar confidence interval bands. Younger age (OR 0.95), lower NIHSS (OR 0.90), glucose level < 170 mg/dL (OR 2.4), distal clot location (M2) (OR 1.7), excellent reperfusion (mTICI≥2b) (OR 2) and time to GP <5 hrs (OR 1.6) were independent predictors of good outcome in TNS patients.

Conclusion:
While excellent outcomes were higher in directly-presenting patients, EVT-treated transfers may achieve similar good outcomes. The association between earlier EVT after transfer and better outcomes emphasizes the need to streamline the transfer process.
Abstract WP402: Ischemic Stroke Admission Factors Associated with Longer Length of Stay and Disposition to Non-home Setting
Authors: Wilson Natalie , Liang John W , Toche Tara , Tuhrim Stanley , Dhamoon Mandip S
Published: June 2021

Background:
Discharge planning is a major component of stroke care. Early prediction of hospital disposition may increase efficient delivery of health care by initiating appropriate discharge planning and shortening length of stay (LOS).

Purpose:
To identify admission factors that are associated with longer LOS and discharge to non-home setting.

Methods:
In this retrospective analysis of Get With The Guidelines-Stroke data from five stroke centers of the Mount Sinai Health System in New York City from 1/1/2010 to 12/31/2015, chi-square and logistic regression analyses were used to test for admission factors associated with discharge to non-home setting. Linear regression was used to test for factors associated with LOS. Admission NIH Stroke Scale Score (NIHSS) was analyzed as a continuous variable; other covariates included demographics, medical risk factors, and weekend admission.

Results:
Among 7829 patients, mean age was 70.6 years (SD 14.8); 47.5% were male; 36.8% were non-Hispanic white, 28.1% non-Hispanic black, 10.9% Hispanic; 75.9% had hypertension, 35.6% diabetes, 37.4% dyslipidemia, 22.5% coronary artery disease, 16.6% atrial fibrillation, and 24.8% prior stroke. Factors independently associated with reduced odds of discharge home were higher admission NIHSS, per point increase (OR 0.83; 95% CI 0.82-0.85), age (OR 0.97 per year; 0.97-0.98), non-Hispanic black race (OR 0.74; 0.64-0.86), and diabetes (OR 0.75; 0.66-0.85). Factors associated with longer LOS were higher admission NIHSS (0.32 day longer LOS per point increase, 95% CI 0.29-0.35; p<0.0001), non-Hispanic black (1.43, 0.93-1.93; p<0.0001), Hispanic (1.06, 0.39-1.73; p<0.0001), and atrial fibrillation (0.55, .004-1.09; p=0.048) but not age (p=0.26) or diabetes (p=0.15).

Conclusions:
Several admission factors (NIHSS, age, race-ethnicity, and diabetes) were associated with discharge to non-home setting. Early identification of these patients may help initiate proper discharge planning. Hispanic ethnicity and atrial fibrillation, but not age or diabetes, were associated with longer LOS. Future research is required into why Hispanic patients, compared to non-Hispanic whites, have longer LOS despite similar discharge to home rates.
Abstract WP410: From the Ground to Target Stroke Elite Plus
Authors: Cairl April L , Farmer Linda , Groody Angela , Raposo R A , Kenton Edgar J , Cummings Christopher , Zand Ramin , Holland Neil
Published: June 2021

Background:
Geisinger Wyoming Valley Medical Center (GWV), in Wilkes-Barre, Pennsylvania, serves a population of approximately 320,000 people throughout Luzerne. In 2013, the stroke program was launched in GWV secondary to community need. In less than three years we achieved the highest quality metric from the American Heart and American Stroke Association. Here we describe highlights of our intuitive strategies and achievements.

Methods:
The following strategies were employed to achieve this goal. The Stroke Program Coordinator was an emergency medical service provider and emergency department nurse manager. A stroke bay was added directly outside of the ED Computer Tomography(CT) suite, patients were immediately triaged and taken directly to CT. A nurse navigator was implemented for daily rounding to provide stroke education to patients and families and collect real-time data. The real-time data abstraction and feedback system allowed opportunity for immediate action and timely targeted education. Weekly in-services were held with the inpatient nursing staff where issues were further reviewed and education provided on an ongoing basis. Staff education has been the main priority and nursing management was closely involved. A systematic approach has been implemented for patients requiring weekend stroke education. A stroke topic was included in our monthly nursing newsletter.

Results:
In less than three years we were able to achieve Target Stroke Elite Plus, the highest recognition from the American Heart and American Stroke Association. Sixty-seven percent (95% CI: 63.5-80.5%) of our acute stroke patients had a door-to-needle time below 45 minutes. Compliance with all our core measures more than 95% (95% CI: 93.4- 96.6%), and rehabilitation, in hospital antithrombotic treatment, discharge antithrombotic more than 99% of the time.

Conclusion:
A collaborative model and multidisciplinary approach is associated with improved guideline adherence. In conclusion, this model and our strategies can be successfully applied in other community hospitals.
Abstract WP413: It’s a Draw! Nurse vs. Pharmacist Mixing tPA; Who’s Faster?
Authors: Boyer Morgan
Published: June 2021

Introduction:
As a Comprehensive Stroke Center and a hub for telestroke stroke alert process is continual effort. Collaborating with spoke Stroke Coordinators is imperative to improving overall stroke alert process. A goal of national guidelines is to achieve a door to needle for administration of intravenous tissue-type plasminogen activator (tPA) of less than 60 minutes. A point of contention in the stroke alert process is the debate between Registered Nurse mixing versus pharmacy mixing of tPA. The question remains contentious in our telestroke community hospitals and therefore was analyzed.

Methods:
The telestroke network consists of 14 community hospitals of various bed sizes and stroke volume. Seven of the spokes use an Emergency Room nurse to mix tPA and the remaining seven use their pharmacy. Using data generated over 4 years from the telemedicine provider, the door to needle was assessed and compared. In addition, door to telestroke consultant decision to administer tPA was also analyzed. The average, minimum, maximum and median time in minutes was calculated for the door to needle and door to decision time points.

Results:
The average time for door to needle when nurses mix is 83 minutes versus an average door to needle time when pharmacy mixes is 93 minutes (p = 0.0398). The median time for nursing mixing is 81 minutes and pharmacy mixing is 89 minutes. The average door to consultant decision to administer tPA when nurses mix is 19 minutes compared to an average door to consultant decision to administer tPA when pharmacy mixes is 20 minutes (p = 0.5593). The fastest door to tPA administration is a spoke with a pharmacy mixing the drug at 23 minutes.

Conclusion:
The analysis of the telestroke network door to needle and door to consultant decision did not conclusively add evidence to a benefit of either the Emergency Room nurse or a Pharmacist mixing tPA. An effective and efficient stroke alert process demands a coordinated effort by all individuals. Not one role in the process makes the target achievable. Whether the Pharmacist or the bedside nurse prepares the drug, what makes it possible to achieve the target is the collaboration and understanding of everyone’s role.
Abstract WP417: Treatment of Obstructive Sleep Apnea and the Risk of Subsequent Stroke and Cardiovascular Events
Authors: Reznik Michael E , Merkler Alexander E , Segal Alan Z , Navi Babak A , Kamel Hooman
Published: June 2021

Background:
Growing evidence suggests that obstructive sleep apnea (OSA) is associated with an increased risk of stroke and adverse cardiovascular outcomes; however, there are limited data that treating OSA with positive airway pressure (PAP) devices significantly decreases this risk. We therefore examined the association between PAP therapy and the risk of subsequent stroke and cardiovascular outcomes in patients with OSA.

Methods:
We performed a population-based cohort study using outpatient and inpatient administrative claims data from a nationally representative 5% sample of Medicare beneficiaries from 2008 through 2014. Our cohort comprised patients with OSA, whom we identified using an algorithm of an ICD-9-CM procedure code for a home or lab sleep study along with at least two subsequent diagnostic code claims for OSA. Our predictor variable was prescribed therapy with continuous PAP or bi-level PAP, defined using CPT codes. Our primary outcome was a composite of hospitalization for ischemic stroke, hemorrhagic stroke (intracerebral or subarachnoid hemorrhage), myocardial infarction, or congestive heart failure. Kaplan-Meier survival statistics were used to calculate cumulative rates, and Cox regression analysis was used to calculate hazard ratios (HR) that adjusted for age, sex, race, and established vascular risk factors.

Results:
We identified 38,987 patients with OSA, of whom 1,195 were prescribed PAP therapy. The mean age of all patients with OSA was 73.0 (±5.5) years, and 43.6% were women. Patients prescribed PAP therapy had a higher baseline burden of vascular comorbidities. The mean follow-up was 2.2 (±1.6) years. By 5 years of follow-up, the cumulative rate of our composite outcome was 30.3% (95% CI, 25.4-35.9%) in patients prescribed PAP therapy versus 31.2% (95% CI, 30.4-32.0%) in untreated patients (adjusted HR, 0.8; 95% CI, 0.7-0.9). This association was similar but not statistically significant when assessing the secondary outcome of ischemic or hemorrhagic stroke (adjusted HR, 0.7; 95% CI, 0.5-1.1).

Conclusion:
Patients with OSA who were treated with PAP were less likely to experience stroke or adverse cardiovascular events compared to those who did not receive treatment.
Abstract WP418: A Systematic Comparison of Key Features of Ischaemic Stroke Prevention Guidelines in Low- and Middle-income vs High-income Countries
Authors: Bayona Hernan O , Owolabi Mayowa , Feng Wayne , Sawers James R , Olowoyo Paul , Yaria Joseph , Akinyemi Rufus , Ovbiagele Bruce
Published: June 2021

Introduction:
Implementation of contextually appropriate, evidence-based, expert-recommended stroke prevention guideline is particularly important in Low- and Middle-Income Countries (LMICs), which bear disproportional larger burden of stroke while possessing fewer resources. Focus therefore, should be on approaches enabling healthcare systems to improve control of vascular risk factors.

Objective:
We aimed to compare important features of stroke prevention guidelines between LMICs and High Income Countries (HICs).

Methods:
We systematically searched PubMed, AJOL, SciELO, and LILACS databases for stroke prevention guidelines published between January 2005 and December 2015 by country. Primary search items included: “Stroke” and “Guidelines”. We critically appraised the articles for evidence level, issuance frequency and implementation aspects to clinical practice.

Results:
Among 45 stroke prevention guidelines published, 28 (62%) met eligibility criteria: 7 from LMICs (25%) and 21 from HICs (75%). LMIC-issued guidelines were less likely to have conflict of interest declarations (57% vs. 100%, p=0.01), involve high quality systematic reviews (57% vs. 95%, p= 0.03), had good dissemination channels (14% vs 71%, p=0.02). The patient views and preferences were the most significant stakeholder considerations in HICs (43%, p=0.04) compared with LMICs.

Conclusion:
The quality and quantity of stroke prevention guidelines in LMICs are less than those of HICs and need to be significantly improved upon.
Abstract WP419: Long-term Risk of Complications after Endovascular Closure of Patent Foramen Ovale
Authors: Merkler Alexander E , Gialdini Gino , Yaghi Shadi , Okin Peter M , Iadecola Costantino , Navi Babak , Kamel Hooman
Published: June 2021

Background:
The long-term safety of patent foramen ovale (PFO) closure following stroke or transient ischemic attack (TIA) is uncertain. We sought to evaluate the long-term risk of complications following endovascular PFO closure in a large, heterogeneous group of patients with cerebrovascular disease.

Methods:
We performed a retrospective cohort study using administrative claims data on all acute care hospitalizations from 2005-2011 in California, 2006-2013 in New York, and 2005-2013 in Florida. Using
ICD-9-CM
codes, we identified patients without other forms of congenital heart disease who underwent endovascular PFO closure within 1 year of a stroke or TIA. The primary outcome was a serious complication, defined as in prior studies as atrial fibrillation, cardiac tamponade, pneumothorax, hemothorax, a vascular access complication, or death. Kaplan-Meier survival analysis was used to calculate the cumulative rate of complications. In a secondary analysis, we included other serious complications described in previous randomized trials of PFO closure after stroke: venous thromboembolism, ventricular arrhythmia, infective endocarditis, and sepsis.

Results:
We identified 1,887 patients who underwent PFO closure after stroke or TIA, among whom the mean age at the time of closure was 54.2 (±14.3) years. By 7 years, the cumulative rate of any complication or death was 18.3% (95% confidence interval [CI], 15.9-21.0%). The mortality rate was 3.4% (95% CI, 2.5-4.6%). Atrial fibrillation was the most common complication, occurring in 8.3% (95% CI, 7.1-9.5%) of patients. The rate of any complication during the index hospitalization for PFO closure was 7% (95% CI, 5.8-8.1%). When venous thromboembolism, ventricular arrhythmia, infective endocarditis, and sepsis were included, the cumulative rate of any complication or death throughout follow-up was 21.4% (95% CI, 19.0-24.0%).

Conclusions:
Approximately 1 in 5 patients who undergo PFO closure after stroke or TIA experience a serious complication or death within 7 years.
Abstract WP420: Clopidogrel with Aspirin May be More Effective in Decreasing One-year Stroke Recurrence for Acute Minor Stroke with Watershed Infarcts: Subgroup Analysis of Chance
Authors: Pu Yuehua , Liu Liping , Wang Yilong , Jing Jing , Wang Anxin , Zou Xinying , Meng Xia , Wang Chunxue , Johnston S. Claiborne , Wang Yongjun
Published: June 2021

Background and Objective:
In symptomatic cerebral large artery disease, watershed infarcts may result from hemodynamic impairment or microembolism. Such patients often have a high risk of recurrence or deterioration. It is still not clear whether dual antiplatelet therapy reduce the risk of stroke recurrence. The aim of this subgroup analysis is to discuss whether dual antiplatelet therapy could decrease the one year stroke recurrence more effectively for minor stroke patients with watershed infarcts.

Methods:
Patients enrolled in Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial and have magnetic resonance (MR) imaging data were included in this study. Diffusion-weighted imaging was obtained for detection of watershed infarcts. We assessed the interaction of the treatment effects of clopidogrel plus aspirin versus aspirin alone among patients with watershed infarcts or not.

Results:
Of the 1089 patients with MR imaging data enrolled in the CHANCE trial, 831 (76.3%) patients with acute infarcts. Among patients with acute infarcts, 93 (11.19%) were watershed infarcts, 55 (59.14%) received dual antiplatelet therapy. Patients with watershed infarcts had higher rates of recurrent stroke (17.20% vs 10.70%, p=0.063) at 1 year. For patients with watershed infarcts, one-year stroke recurrence was 6 (10.91%) in clopidogrel plus aspirin group and 10 (26.32%) in placebo plus aspirin group. There was interaction between antiplatelet therapy and presence of watershed infarcts on the primary outcome of any stroke (p=0.0933). (Kaplan-Meier curves were showed in the figure).

Conclusions:
For minor stroke patients with watershed infarcts, clopidogrel with aspirin may be more effective in decreasing 1-year stroke recurrence attributed to its potential mechanism of microembolism. Studies in other populations and subsequent analysis with adequate power are warranted to further verify such findings.
Abstract WP422:
18
F-FDG PET/CT Imaging Factors for Prediction of Ischemic Stroke in Cancer Patients
Authors: Choi Kangho , Kim Ja-Hae , Lee Jin-Heui , Kim Joon-Tae , Park Man-Seok
Published: June 2021

Objective:
18
F-FDG PET/CT can acquire both anatomical and functional images in a single session. We investigated which factors of
18
F-FDG PET/CT imaging have potential as biomarkers for an increased risk of ischemic stroke in cancer patients.

Methods:
One hundred and thirty-four cancer patients were enrolled. A new infarct lesion in brain MRI within 1 year after FDG PET/CT defined future ischemic stroke. A target-to-background ratio (TBR) for each arterial segment defined arterial inflammation on PET imaging. Abdominal obesity was defined as area and proportion of visceral adipose tissue (VAT), subcutaneous adipose tissue and total adipose tissue (TAT), on a single CT slice at the umbilical level.

Results:
Thirty patients experienced the occurrence of future ischemic stroke confirmed by MRI. Patients who suffered a stroke had TBRs in carotid arteries and the abdominal aorta (
P
<0.001) that were higher than those in patients without stroke. Patients with stroke had higher VAT (
P
=0.021) and TAT (
P=
0.041) proportions than patients without stroke. Multiple logistic regression analysis showed that TBRs of the carotid arteries and abdominal aorta, VAT and TAT proportions, and metabolically active tumors were significantly associated with future ischemic stroke. The combination of PET and CT variables improved predictive power for future ischemic stroke.

Conclusion:
Our findings suggest that arterial FDG uptake and hypermetabolic malignancy on PET, and VAT proportion on CT, could be independent predictors of future ischemic stroke in patients with cancer and identify those patients who would benefit from medical treatment.
Abstract WP426: Rock2-mediated Cerebrovascular Dysfunction During Aging
Authors: De Silva Travice M , Modrick Mary , Faraci Frank M
Published: June 2021

The pathophysiological changes that occur during vascular aging fundamentally contribute to large and small vessel disease. Despite the importance of such changes for stroke and cognitive dysfunction, mechanisms that underlie vascular aging remain very poorly defined. As a result, no specific therapies exist at present. Because loss of endothelial health is a cornerstone event in the progression of vascular disease, we explored mechanisms that underlie vascular changes with aging, testing the hypothesis that Rho kinase (ROCK) plays an important role. In C57Bl/6J mice, baseline diameter of isolated parenchymal arterioles were similar in both adult (4-5 mo of age) and old mice (22±1 mo) (15±1 microns). Endothelium-dependent dilation was significantly impaired in old mice compared to adult controls, but in a pathway-specific manner. Vasodilation mediated by endothelium-dependent hyperpolarization was intact while eNOS-mediated responses were reduced by approximately 50% (P<0.05). A similar reduction in eNOS-dependent endothelial function was present in isolated basilar arteries. Inhibition of both ROCK1 and ROCK2 isoforms with Y-27632 or ROCK2 only with SLX-2119, restored endothelial function in old mice. An inhibitor of NO synthase reversed this protective effect, demonstrating that inhibition of ROCK2 restored NO-mediated signaling during aging. Because genetic background is a determinant of vascular disease, we performed similar studies using FVB/NJ mice. Like the C57Bl/6J mice, FVB/NJ mice exhibited endothelial dysfunction with aging that was reversed by inhibition of ROCK2. Thus, aging impairs endothelial function in both cerebral arteries and the smallest parenchymal arterioles via effects on select pathways. Vascular aging and the underlying mechanisms are not limited to one genetic background. These studies provide the first evidence that ROCK2 is a key contributor to cerebrovascular dysfunction with aging.
Abstract WP431: Functionally Distinct Neuronal Nitric Oxide Synthase Expressed in the Brain Microvascular Endothelial Cells Mediates Anoxic-injury to Blood-Brain Barrier
Authors: Sure Venkata N , Peterson Nicholas R , Chen Allen L , Jain Neelesh P , Unis Graham D , Baker Tyler P , Gordon Angellica O , Merdzo Ivan , Rutkai Ibolya , Busija David W , Katakam Prasad V
Published: June 2021

Objective:
Mice with genetic deletion of endothelial (eNOS; protective) and neuronal (nNOS; detrimental) nitric oxide synthase isoforms exhibit dramatically opposite consequences of ischemic brain injury. nNOS has been identified recently in endothelial cells, however, its functional significance is unclear. Our objective was to identify nNOS and characterize its functional role in primary brain microvascular endothelial cells (MECs).

Methods and Results:
MECs from humans (hMECs), rats (rMECs), and mice (mMECs) along with cultured primary rat cortical neurons were used. In addition, rat brain microvessels were freshly isolated. Transendothelial electrical resistance (TEER) measurements of monolayers of hMECs cultured in transwells were used to quantitate in vitro blood-brain barrier (BBB) integrity. Immunocytochemistry identified von Willebrand factor, eNOS, and nNOS in MECs but stained negative for glial (GFAP) and neuronal (Neu1) markers. PCR studies confirmed the expression of eNOS and nNOS mRNA in MECs and microvessels. We utilized electron spin resonance spectrometry to measure reactive oxygen species (ROS) (1-Hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine; CMH) and NO (colloid Fe(DETC)2). Inhibition of nNOS (N-ω-Propyl-L-arginine and ARL-17477) reduced ROS but increased NO levels in MECs and rat brain microvessels. In contrast, eNOS inhibitor (L-N5-(1-Iminoethyl)ornithine) increased ROS but reduced NO levels. Inhibition of nNOS in neurons, similarly increased ROS and decreased NO levels. siRNA targeting rat nNOS in rMECs was able to knockdown nNOS mRNA as well as ROS levels. BBB studies of hMECs treated with NOS inhibitors followed by oxygen-glucose deprivation (OGD) revealed that nNOS inhibition increased TEER at baseline and promoted TEER recovery following OGD. In contrast, eNOS inhibition had no effect on TEER at baseline but weakly albeit transiently helps in the post-OGD recovery of BBB function.

Conclusions:
Thus, we identified a constitutively active nNOS in MECs that is functionally distinct from the nNOS isoform expressed in neurons and eNOS. In addition, nNOS inhibition enhances the BBB integrity and affords protection against anoxic-injury induced impairment of BBB function.
Abstract WP434: Serum MicroRNA Panel as a Candidate Biomarker of Carotid Plaque Rupture and Stroke
Authors: Brug Aaron M , Smith Sullivan , Brooks Ashton J , Lightell Daniel J , Bazan Hernan A , Woods Thomas C
Published: June 2021

Introduction:
Atherosclerotic plaque vulnerability and subsequent rupture are mediated by alterations in miRNAs that promote inflammation and fibrous cap thinning, leading to an acute ischemic stroke. Release of these miRNAs from the plaque tissue into the circulation may provide a miRNA profile that serves as a biomarker panel to identify the vulnerable patient at greatest risk of plaque rupture.

Methods:
Using RNA-Seq methodology, serum microRNA content was compared between patients undergoing carotid endarterectomy (CEA) for 2 distinct clinical phenotypes: patients without previous neurological events but high-grade carotid stenosis (asymptomatic, n=5), and patients with an acute neurological event within 5 days of the CEA (urgent, n=7). Differential expression of miRNAs was performed using the R statistical software and the DESeq2 package.

Results:
A total of 695 miRNAs detected in sera on RNA-Seq, 54 were significantly different between the asymptomatic and urgent groups. 22 miRNAs were decreased and 32 were increased in the serum of urgent patient’s compared to asymptomatic patients (adjusted p-value < 0.05). Of these miRNAs, miR-21, miR-486, miR-23b, miR-27b, and let-7f were selected for validation as a biomarker panel based on a prior association with vascular disease. A pilot study (n= 6 asymptomatic and 6 urgent) measuring these miRNAs demonstrated that while miR-486 was detectable in all samples and exhibited a 9.4-fold increase (p < 0.10) in the urgent group, the other miRNAs were only detected in a fraction of the samples (33 - 75%). Furthermore, miR-486 alone did not exhibit characteristics of a good indicator of ischemic stroke. A score normalizing the expression of miR-486 to the mean expression of the detectable miRNAs from this panel, did yield a promising C-statistic (0.97 ± 0.08, p < 0.01), suggesting its potential as an indicator of an acute ischemic event.

Conclusion:
Carotid plaque rupture resulting in an acute ischemic event is associated with alterations in the profile of circulating miRNAs and these may be useful as biomarkers of ischemic stroke. Our pilot data suggest that the development of a score based on a panel of circulating miRNAs may allow for the diagnosis of patients experiencing plaque rupture and an acute ischemic stroke.
Abstract WP435: Endothelium-Specific Sox17 Deletion Ameliorates ALK1-mediated Cerebral Arteriovenous Malformation
Authors: Lee Seungjoo , Ahn Jae Sung , Park Won Hyung
Published: June 2021

Background and Purpose:
The deletion of Sox17 stabilizes endothelial junctions and decreased proliferation, vice versa. The AVM after endothelial Alk1 deletion shows uncontrolled endothelial proliferation and cytoskeletal misarrangement. The vascular phenomena by endothelial specific deletion of Sox17 and Alk1 are diametrical. Coincidentally, these two antidotal genes act via Notch signaling pathway. Therefore, we hypothesized that deletion of Sox17 in endothelial cells are sufficient to ameliorate brain AVM via Notch pathway modulation.

Methods:
Alk1
2f/2f
Sox17
2f/2f
double transgenic mice were bred with VEcad-iCreER
T2
mice that express tamoxifen-inducible cre re-combinase in EC. EC-Alk1 and Sox17 deletion was induced by intraperitoneal injection of tamoxifen (25mg/kg) with interval of 3 days. The spatiotemporal changes of blood vessel were investigated in Alk1 deletion alone and Alk1-Sox17 co-deletion mice. Vascular morphology was analyzed using real-time multiphoton microscopy and immunostaining. EC proliferation and dysplasia index were quantified. The transcripts and protein expression of target molecules of Notch pathway (Dll4, Hey1, Hey2, NIICD) were also evaluated.

Results:
The dysplastic blood vessel index of solitary Alk1
2f/2f
deletion mice was higher than Alk1
2f/2f
-Sox17
2f/2f
double transgenic mice (P<0.001). Dysplasia in Alk1
2f/2f
mice was partially rescued by Sox17 co-deletion in morphologically. In addition, target molecules of Notch pathway, Dll4, Hey1, Hey2, Jag1 was increased in Alk1-Sox17 co-deletion mice rather than solitary Alk1 deletion mice.

Conclusions:
Collectively, our findings demonstrate that the modulation of Sox17 could restrict the Alk1-induced AVM by upregulation of Notch pathway. This work establishes the Notch-Sox17 axis as a novel regulatory mechanism underlying Notch-mediated vascular stabilization in brain AVM.
Abstract WP440: Analysis of Hypoplastic Variants of the Circle of Willis in Patients with First-ever Lacunar Stroke
Authors: Katramados Angelos M , Marin Horia , Kole Maximilian , Varelas Panayiotis , Miller Daniel , Malik Shaneela , Hefzy Hebah , Modi Sumul , Schultz Lonni , Marmagkiolis Konstantinos , Tsitlakidou Despina , Affan Muhammad , Mitsias Panayiotis
Published: June 2021

Background:
Cerebral small vessel disease is related to widespread endothelial dysfunction, and suspected hypoperfusion at the level of the microcirculation. Lacunar infarcts are a major manifestation of small vessel disease, and result in significant long-term neurological morbidity and mortality. Congenital hypoplastic variants of the vessels of the Circle of Willis may result in impairment of collateral channels at the time of ischemia.

Hypothesis:
We hypothesized that lateralization of first-ever lacunar infarcts is related to relative hypoperfusion of the ipsilateral hemisphere due to asymmetric hypoplasia of the vessels of the Circle of Willis and inadequate side-to-side collateral circulation.

Methods:
We analyzed 40 consecutive patients that presented to a stroke center with a first-ever supratentorial lacunar infarct. All patients were able to undergo intracranial vascular imaging. Patients with significant large-vessel disease (even if asymptomatic) were excluded. A neuroradiologist, blinded to the laterality of the lacunar infarct, assessed for lateralized hypoplasia of the Circle of Willis (either anteriorly at the level of the A1 artery and AComA as one functional unit, or posteriorly at the level of the PCA and PComA as one functional unit). Proportions of ipsilateral and contralateral hypoplasia were compared directly, as well as with historical controls, with the chi-squared test.

Results:
Among analyzed patients, ipsilateral and contralateral anterior pathway hypoplastic variants were not significantly different from historical controls (p=0.145 and p=0.99 respectively). However, ipsilateral and contralateral posterior pathway hypoplastic variants were significantly different from historical controls (p<0.001 for both). There was no statistical difference between ipsilateral and contralateral posterior pathway hypoplasia (p=0.21).

Conclusion:
Hypoplasia of the posterior part of the Circle of Willis is significantly more common among patients with first-ever lacunar stroke, compared to historical controls. However, the asymmetry of hypoplasia does not affect the laterality of first-ever lacunar infarct. Further studies are required to explain this phenomenon.
Abstract WP441: Association Between Troponin Levels and Embolic Stroke of Undetermined Source
Authors: Merkler Alexander E , Gialdini Gino , Murthy Santosh , Okin Peter M , Iadecola Costantino , Navi Babak , Kamel Hooman
Published: June 2021

Background:
Asymptomatic elevations in serum troponin levels often occur in patients with acute ischemic stroke. We evaluated whether patients with embolic strokes of undetermined source (ESUS) have higher rates of asymptomatic elevated troponin than patients with small- or large-vessel strokes.

Methods:
The Cornell AcutE Stroke Academic Registry (CAESAR) prospectively enrolled all adults with acute stroke at Weill Cornell Medical Center from 2011 to 2014. The etiology of stroke was retrospectively ascertained by two independent neurologists, with a third resolving any disagreements. We included patients with ESUS and, as controls, those with small- or large-vessel strokes. We defined an asymptomatic troponin elevation as a value exceeding our laboratory’s upper limit (0.04 ng/mL) within 24 hours of presentation, in the absence of a clinically recognized acute myocardial infarction. We used the chi-square test to compare rates of elevated troponin in patients with ESUS versus controls. Multiple logistic regression was used to evaluate the association between ESUS and elevated troponin after adjustment for demographics, NIH Stroke Scale score, insular infarction, and vascular risk factors. In a sensitivity analysis, we excluded patients diagnosed with atrial fibrillation during ambulatory heart-rhythm monitoring.

Results:
Among 547 patients, 258 (47.3%) had ESUS and 285 (52.7%) had a small- or large-vessel stroke. Patients with ESUS were younger (mean age 65.7 vs. 69.6 years) and more often female, and had equally severe strokes, higher rates of insular infarctions, and fewer vascular risk factors. In univariate analysis, patients with ESUS more often had an elevated troponin than controls (14.7% versus 8.0%;
P
= 0.01). After adjustment for demographics, stroke severity, insular involvement, and vascular risk factors, ESUS remained associated with elevated troponin (OR, 2.44; 95%, 1.04-5.77). This result was unchanged in our sensitivity analysis.

Conclusions:
Elevations in serum troponin appear to be more common in patients with ESUS than in those with small- or large-artery strokes. Further research is required to understand the pathogenesis and significance of elevated troponin in patients with ESUS.
Abstract WP442: Diffusion Tensor Imaging of White Matter Tracts in Transient Ischemic Attack Patients
Authors: Tariq Sana , Tsang Adrian , Ursenbach Jacob , Dutta Naomi-Rose , Andersen Linda B , Longman Richard S , Frayne Richard , Barber Philip A
Published: June 2021

Introduction:
Transient ischemic attack (TIA) greatly increases the risk of developing dementia later in life. Measurement of microstructural changes in white matter (WM) using diffusion tensor imaging (DTI) tractography has potential for identifying those at greatest risk of cognitive decline. We hypothesized that patients presenting with TIA have abnormal DTI measures in major WM tracts. Our objective was to determine changes in DTI measures for fractional anisotropy (FA) and medial diffusivity (MD) in frontoparietal (Superior Longitudinal Fasciculus; SF) and medial temporal (Uncinate Fasciculus; UF) WM tracts for TIA patients and healthy controls.

Methods:
Patients presenting with symptoms of high risk TIA but free of dementia, and healthy volunteer controls were recruited acutely. Structural MRI, inclusive of DTI sequences (31 directions b1000) was performed. FA and MD values were collected in the left and right SLF and UF. Multiple linear regression was performed to determine predictors of DTI values (FA and MD), adjusted for age. Subject’s cognition was screened using Montreal Cognitive Assessment (MoCA).

Results:
Data from 60 TIA patients (mean age = 68.75 years, SD = 9.39, 45% female) and 33 healthy controls (mean age = 64.97 years, SD = 10.45, 67% female) was analyzed. Linear regression identified that TIA patients have higher FA values in left SLF, F(2, 90) = 9.210,
p
< .001, R
2
= .170); right SLF, F(2, 90) = 7.154,
p
= .001, R
2
= .137; and left UF, F(2, 90) = 3.513,
p
= .034, R
2
= .072, compared to healthy controls. No group changes in MD were observed when corrected for age. TIA patients (median score 24, (interquartile range (IQR) = 5) performed worse than healthy controls (median score = 27, IQR = 4) on the MoCA while controlling for age, F(1, 90) = 7.689,
p
< .007.

Conclusion:
TIA patients showed changes in FA of WM tracts related to language and memory function when compared to healthy controls, supporting the presence of incipient microstructural disease. Our results show that measures of microstructural changes using DTI may help identify TIA patients at a greater risk of developing cognitive impairment. Future work aims to identify deterioration of DTI measures over time and their relation to potential vascular and neurodegenerative etiologies.
Abstract WP451: Cognitive Impairment in Cardiac Disease - Neuroimaging Associations
Authors: Cannon Jane , Findlay Mark , Dani Krishna , Dawson Jesse , Dickie David A , Quinn Terence J
Published: June 2021

Introduction:
Atrial fibrillation (AF) and heart failure (HF) are associated with cognitive impairment. We used neuroimaging to describe if this association is explained by cardioembolism or other mechanisms.

Methods:
We included adults with HF (ejection fraction<45%) and AF but no stroke history. Healthy volunteer controls were matched, 1:2 ratio. Participants were assessed with Repeatable Battery for the Assessment of Neurospychological Status (RBANS), Hospital Anxiety and Depression Score (HADS) and 3-T brain MRI. Scans were graded for:infarct, enlarged perivascular spaces, microbleeds, global and regional (hippocampal) atrophy with consensus scoring by four raters using validated, ordinal assessment scales. Brain volumes were semi-automatically acquired using cluster analysis of T1-weighted and FLAIR voxel intensities and diffeomorphic atlas-based segmentation. CSF, hippocampal and white matter volumes were corrected for intracranial volume. We described univariable differences between groups and then created multivariable models where cardiac status was the dependent variable, RBANS and MRI data were the predictors.

Results:
Of 50 participants, AF-HF (n=34) had poorer RBANS (MD:16.9, SE:3.44; p<0.001). Differences were independent of education and HADS. Infarcts and ordinal markers of atrophy were significantly different between groups, SVD markers were increased in AF-HF but did not reach significance. Quantitative measures of white matter differed between groups but measures of atrophy did not.(Table) On multivariable models, no imaging feature was independently associated with cardiac status.

Discussion:
The association between cognitive impairment and cardiac disease may not be solely driven by occult cardioembolism; small vessel disease and other, neuroimaging independent, factors also interact. Differences between ordinal scales and quantitative scores suggest that future studies should use robust volumetric analyses.
Abstract WP46: Sex Differences in Therapeutic Targets in Ischemic Stroke
Authors: Dula Adrienne N , Luby Marie , King Ben , Davis Lisa A , Latour Lawrence L ,   NINDS LESION Investigators, Warach Steven J
Published: June 2021

Sex differences exist in stroke epidemiology, acute presentation, treatment, and post-stroke clinical outcome. Neuroimaging can objectively identify potential pathological therapeutic targets and is reflective clinical observations. MCA occlusion (MCAO) is measurable by angiography and the presence of penumbra by diffusion-perfusion mismatch. We present evaluation of sex differences in the Lesion Evolution in Stroke and Ischemia On Neuroimaging (LESION) Project to determine if the probability of MCAO and penumbra depend on sex.

We hypothesize imaging-based evidence is consistent with clinical observations of sex differences in severity and interactions with age and race.

Methods:
Patients included in the LESION study were diagnosed with acute ischemic cerebrovascular syndrome, had a brain MRI obtained within 24 hours from last known well and NIHSS>3 or were treated with acute intervention with a pre-treatment MRI. MR imaging included DWI, FLAIR, MRA and PWI, which were co-localized over the entire brain. Patients with M1 or M2 abnormalities were graded as MCAO. The probability of having an MCAO or measurable pathological target was qualitatively evaluated as a function of sex with adjustment for age and race.

Results:
Women were more likely than men (all p<0.05) to have a measurable of MCAO (OR [CI’s]) = (1.43 [1.08-1.89]), perfusion defect (1.42 [1.02-2.0]), or a diffusion-perfusion mismatch (1.35 [1.02-1.80]) (Table). This sex difference remained after adjusting for time from onset, NIHSS and age. Women over 70 years are most likely to have a measurable therapeutic target and white women are more likely to have a penumbral pattern than men or non-white women (p<0.05).

Conclusion:
This preliminary imaging-based evidence is encouraging that sex differences in imaging biomarkers exist in a representative sample of acute stroke patients. This study shows that sex differences exist not only in the clinical phenotype, but in presence of a biological target.
Abstract WP47: Reperfusion Following Ischemic Stroke is Associated with Reduced Brain Edema
Authors: Irvine Hannah J , Battey Thomas W , Ostwaldt Ann-Christin , Campbell Bruce C , Davis Stephen M , Donnan Geoffrey A , Sheth Kevin N , Kimberly W. Taylor
Published: June 2021

Introduction:
Revascularization is a robust therapy for acute ischemic stroke, but animal studies suggest that reperfusion edema may attenuate its beneficial effects. In stroke patients, early reperfusion consistently reduces infarct volume and improves long-term functional outcome, but there is little clinical data available regarding reperfusion edema. We sought to elucidate the relationship between reperfusion and brain edema in a patient cohort of moderate to severe stroke.

Methods:
Seventy-one patients enrolled in the Echoplanar Imaging Thrombolysis Evaluation Trial (EPITHET) with serial brain magnetic resonance imaging and perfusion-weighted imaging (PWI) were analyzed. Reperfusion percentage was calculated based on the difference in PWI lesion volume at baseline and follow-up (day 3-5). Midline shift (MLS) was measured on the day 3-5 fluid attenuated inversion recovery (FLAIR) sequence. Swelling volume and infarct growth volume were assessed using region-of-interest analysis on the baseline and follow-up DWI scans based on our prior methods.

Results:
Greater percentage of reperfusion was associated with less MLS (Spearman ρ = -0.46;
P
<0.0001) and reduced swelling volume (Spearman ρ = -0.56;
P
<0.0001). In multivariate analysis, reperfusion was an independent predictor of less MLS (
P
<0.006) and decreased swelling volume (
P
<0.0054), after adjusting for age, baseline NIHSS, admission blood glucose, baseline DWI volume, and IV tPA treatment.

Conclusions:
Reperfusion is associated with reduced brain edema as measured by MLS and swelling volume. While our data do not exclude the possibility of reperfusion edema in certain circumstances, in stroke patients, reperfusion following acute stroke is predominantly linked to less brain swelling.
Abstract WP5: The Transfer Score May Aid Decisions Whether to Transfer Patients with Large Vessel Occlusions for Endovascular Therapy
Authors: Sarraj Amrou , Veznedaroglu Erol , Budzik Ronald F , English Joey D , Baxter Blaise W , Bartolini Bruno M , Liebeskind David S , Krajina Antonin , Shields Ryan D , Xiang Bin , Nogueira Raul G , Gupta Rishi , Dannenbaum Mark , Farrell Christine M , McCullough Louise D , Savitz Sean I
Published: June 2021

Background:
While faster reperfusion with EVT leads to better outcomes in acute ischemic stroke due to large vessel occlusion (LVO), most LVO patients present to outside hospitals without EVT capability. Treating physicians are often unsure if EVT would confer benefit upon arrival to tertiary hospitals given inter-facility transfer delays.

Objective:
We evaluated independent predictors of good outcome in transferred patients treated with EVT to devise a score that may assist treating physicians to make transfer and treatment decisions.

Methods:
Transfer patients were analyzed in a multicenter international prospective cohort study of LVO patients treated with stent retriever thrombectomy (TREVO Registry) from 11/2013 to 4/2016. Independent factors correlating with good outcome after EVT were identified using univariate and multivariate analyses. We devised a score to identify patients with LVO at the referral facility who may benefit from EVT.

Results:
Of 1000 patients enrolled, 226 were anterior circulation occlusions, transferred and treated within 0-8 hrs (Table 1). Age, stroke severity, glucose level, M2 occlusion and achieving onset to groin puncture ≤ 5 hr were independent factors associated with good outcome (Table 2). Other clinical variables were analyzed, as in ASPECTS, but were not significant. A 10 point score was devised (Table 3). Patients with a score of 0-4 had 4 times the odds of good outcome compared to a score of 5-9 (aOR 4.3, 95% CI 1.9-9.9;
p
<0.001). These results were maintained after adjustment for mTICI and IV-tPA (aOR 4.0, 95% CI 1.7-9.4;
p
<0.001). Fig 1 shows good outcome rates stratified by score points. ROC curves showed better score performance (AUC= 0.8) compared to THRIVE (AUC=0.74) and HIAT (AUC=0.69) certifying good predictability.

Conclusion:
A simple transfer score may be an effective triage method to identify patients at remote facilities who may benefit from EVT upon transfer. Further validation is necessary to confirm these findings.