bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WP221: Rnaseq Reveals An Angiogenic Signature Of Leptomeningeal Collaterals In Pig Brain.
Authors: WU TING , Janssen Christopher , Doan Andrea , Ahn John , Horscroft Margaret , Smith Michelle , Harmon Elisabeth , Andersohn Alexander , Kim Gab , Marrelli Sean P
Published: February 2023

Introduction:
The leptomeningeal collaterals (LMCs) are specialized brain surface arterioles that interconnect the distalmost arterioles (DMAs) of the major cerebral arteries. In normal conditions, flow in LMCs is negligible. However, during ischemic stroke, the LMCs provide a vital route for rescue blood flow from neighboring vessel territories, thereby lessening ischemic injury and improving outcome. With sustained flow, the LMCs rapidly remodel to further increase perfusion capacity. The LMCs differ in function and molecular composition compared to DMAs, however, a comprehensive transcriptional signature of these two vessel types is not available. Therefore, we developed methods to identify and isolate LMCs and DMAs from pig brain for subsequent unbiased RNAseq analysis.

Methods:
Duroc pigs were used to due to their larger vascular anatomy and gyrencephalic brains. We first mapped the cerebral vasculature and location of LMCs using blue dye infusion (surface vessel tracing) and BaSO4 microparticle infusion (3D microCT imaging). Having established location of LMCs, we infused an RNAlater/blue ink solution to facilitate vessel visualization and RNA stabilization during dissection. Harvested LMCs and DMAs were pooled by type and processed for RNAseq and analysis by R.

Results:
RNAseq analysis of LMCs and DMAs revealed 349 differentially expressed genes (DEGs) (adjusted p value < 0.05, fold change > 0.5), of which 241 were upregulated and 108 were down regulated in LMCs. Gene ontology (GO) analysis showed upregulation of biological processes including “vasculature development”, “sprouting angiogenesis”, “angiogenesis”, and “regulation of smooth muscle cell proliferation” in the LMC group. Angiogenesis related genes (
Cldn5
,
Kdr
,
Vegfc
, and
Vwf
) were markedly upregulated in LMCs compared to DMAs (1.75 to 2.75 fold). In contrast, “extracellular matrix organization” and “positive regulation of smooth muscle cell migration” were among the most downregulated biological processes in LMCs.

Conclusions:
Our unbiased RNAseq approach revealed numerous DEGs between LMCs and DMAs. Interestingly, GO analysis revealed a proangiogenic signature in LMCs, which may shed new light on how they are able to rapidly remodel following ischemic stroke.
Abstract WP224: Pharmacological Clearance Of Senescent Cells Prevents Intracranial Aneurysm Rupture
Authors: Ishiguro Taichi , Ai Jinglu , Sato Hiroki , Lawton Michael , Eguchi Satoru , Hashimoto Tomoki
Published: February 2023

Background:
Clinical studies consistently show a strong association between aging and increased risk of intracranial aneurysmal rupture. Aging causes the accumulation of senescent cells that promote chronic inflammation through the senescence-associated secretory phenotype. Since inflammation is emerging as a vital component of the pathophysiology of intracranial aneurysms, the accumulation of senescent cells in the aneurysm wall may play a critical role in the rupture of intracranial aneurysm. We hypothesized that the pharmacological clearance of senescent cells reduces the risk of aneurysmal rupture. We tested this hypothesis using a well-established mouse model with a senescent cell-clearing senolytic drug, ABT263.

Methods:
We used male C57BL/6J mice and induced intracranial aneurysms by combining an elastase injection and hypertension. We treated mice with either ABT263 (50 mg/kg/day, oral gavage) or a vehicle from one day before aneurysm induction and continued for three weeks. The development of aneurysmal rupture was used as the primary endpoint. We also assessed the effects of ABT263 or vehicle on mRNA expression levels of senescent cell markers (p16 and p21) in cerebral arteries.

Results:
The pharmacological clearance of senescent cells with ABT263 significantly decreased the rupture rate in mice (P<0.05, Figure A). Furthermore, ABT263 treatment significantly reduced the mRNA expression of p16 and p21 in cerebral arteries (P<0.05, Figure B and C).

Conclusion:
We demonstrated that pharmacological clearance of senescent cells decreased intracranial aneurysmal rupture. The reduction of rupture rate was associated with the reduction of senescence markers. These findings suggest a link between cellular senescence and aneurysmal rupture. Cellular senescence may be responsible for the age-dependent increase in aneurysm rupture. Senolytic drugs may serve as a novel therapy for preventing aneurysm rupture.
Abstract WP229: Hub Genes Drive Specific Gene Expression Changes Seen In Intracerebral Hemorrhage And Ischemic Stroke.
Authors: Carmona-Mora Paulina , Knepp Bodie , Rodriguez Fernando , Jickling Glen C , Zhan Xinhua , Hakoupian Marisa , Hull Heather , Amini Hajar , Sharp Frank R , Ander Bradley P , Stamova Boryana
Published: February 2023

Gene expression changes in peripheral leukocytes display distinctive profiles after intracerebral hemorrhage (ICH) and ischemic stroke (IS), differentiating both conditions at the molecular level. The breadth of data produced by high-throughput transcriptomic analyses can identify groups of genes and main gene expression drivers that have meaningful functional associations with the disease. This can help prioritize the investigation of key genes for diagnosis and treatment. Thus, we performed whole transcriptome analyses on ICH and IS samples and constructed gene networks from a genome-wide perspective. RNA-seq was performed on peripheral blood (WB) and isolated monocytes (MON) and neutrophils (NEU) (n=6 ICH, n=33 IS and n=9 vascular risk factors control (VRFC) subjects). Gene expression results were used to construct separate co-expression networks for all datasets analyzed (ICH + VRFCs, and IS + VRFCs, for MON, NEU and WB) using Weighted Gene Co-expression Network Analysis. Modules of genes significantly associated with ICH in the ICH + VRFCs network, and with IS in the IS + VRFCs network, were identified. The most highly interconnected genes in each of these modules were identified, representing hub genes that are potential master regulators. Functional annotation of the modules and hubs were done using gene ontology. From the significantly associated modules for ICH and IS in all sample types analyzed, there was little overlap in genes between diagnoses (≤2% in MON, ≤21 % in NEU and ≤16% in WB), and no overlap of ICH or IS hub genes from MON and NEU. In WB, ≤2% of the hubs were common to ICH and IS. It is plausible that these potential master regulators drive diagnosis-specific gene expression profiles. ICH hubs were associated with RNA splicing and mRNA processing (MON), cell adhesion (NEU) and NF-κβ signaling (WB). IS hubs were associated with cell migration (MON), T cell chemotaxis (NEU) and transcription factor activity (WB). In addition, most hubs in IS MON were noncoding RNA. The gene networks and their respective hub genes provide novel cell-specific pathophysiological insights and could represent potential key pharmacological targets and biomarkers.
Abstract WP231: Timecourse Characterization Of Neuronal Activation In The Contralesional Cortex After Stroke
Authors: Chiang Terrance , Ito Masaki , Harvey Sean , Cheng Michelle Y , Steinberg Gary
Published: February 2023

Introduction:
Functional neuroimaging studies have reported increased activation in the contralesional cortex in both experimental and clinical settings of stroke. However, the dynamics of activation and neuronal subtypes involved is unclear. In this study we performed a time course analysis of neuronal activation and its subtypes in the contralesional cortex during post-stroke recovery using neuronal activity marker and cell type-specific markers.

Methods:
C57BL6 male mice (11-13 weeks old) underwent transient middle cerebral artery occlusion (MCAO, 30 minutes). Infarct was visualized by T2-weighted MRI and/or histology. Time course study used brains collected at PD1, 3, 7, 15, 21 and 28 and were processed for immunostaining using activity-dependent marker Early growth response 1 (Egr1). Egr1 positive cells were quantitatively assessed in the primary motor cortex (M1), pre-motor cortex (M2), and somatosensory cortex (SS) regions in the contralesional hemispheres. Cell type markers for NeuN (mature neurons), CaMKII and SATB2 (excitatory neurons), Parvalbumin (GABAergic neurons) and GFAP (astrocytes) were co-stained with Egr1 to identify its cell type specificity.

Results:
In the contralesional cortex, Egr1 predominantly co-localized with NeuN, indicating mature neurons. After stroke, contralesional cortical activity of Egr1 is detected at PD1-3 and peaks at PD7-15. Activity of Egr1 in contralesional cortex persisted at PD21-28 but begins to decrease in some regions. In-depth analysis of specific regions indicate that these changes occurred at contralesional M1, M2 and SS. Cell type co-localization analysis showed that Egr1 expressing cells are mostly colocalized with excitatory markers SATB2 and CaMKII but not inhibitory neuronal marker Parvalbumin, suggesting activated neurons in these contralesional cortical regions are mostly excitatory.

Conclusion:
Our results show that Egr1 expression is increased in excitatory neurons in the contralesional cortex after stroke, particularly in somatosensory and primary motor cortex. These data reveal dynamic changes of excitatory neuronal activity in the contralesional cortex post-stroke and highlight its involvement in post-stroke recovery.
Abstract WP232: Endothelial Knockout Of Piezo1 Results In Reduced Cerebral Blood Flow, Brain Gliosis, And Functional Changes In Gait.
Authors: WU TING , Doan Andrea , Do Trang , Ahn John , Harmon Elisabeth , Andersohn Alexander , Kim Gab S , Marrelli Sean P
Published: February 2023

Introduction:
Piezo1 is a calcium-permeable mechanosensitive ion channel that is opened by membrane stretch or increased shear force. In peripheral vasculature, activation of endothelial Piezo1 promotes vasodilation. Whether endothelial Piezo1 regulates cerebral blood flow and the consequences of endothelial cell (EC) Piezo1 loss-of-function in the brain are unknown. The present study was designed to test the overall hypothesis that loss of EC Piezo1 results in reduced cerebral blood flow and subsequent brain pathology consistent with chronic hypoperfusion.

Methods:
EC specific Piezo1 knockout mice were generated by crossing Piezo1 fl/fl mice with inducible EC-specific Cre mice (Cdh5(Pac)CreERT2). Tamoxifen (75 mg/kg) was administrated to generate EC Piezo1 KO or as control in Piezo1 “floxed only” mice. At 1 month after tamoxifen injection, three cohorts were evaluated: (cohort 1) measure CBF by MRI ASL, (cohort 2) gait analysis (Digigait) and subsequent immunofluorescence (IF), (cohort 3) scRNAseq analysis. Gait analysis was chosen as a behavioral measure sensitive to white matter injury.

Results:
EC Piezo1 KO resulted in >8% reduction in resting CBF in striatum (n=5; p<0.05, females). Gait analysis showed significant change in stride time, stride length, and cadence (n = 9-10 males, 6-9 females; p< 0.01). IF showed gliosis in the corpus callosum of EC Piezo1 KO mice, in the form of astrogliosis (Gfap) in males and microgliosis (Iba1) in females (n=5-7 in each group; p<0.05). From scRNAseq of EC Piezo1 KO and control brains (males), GO analysis from all clusters revealed GO terms including: inflammatory response, synapse pruning, gliogenesis, learning or memory, and locomotory behavior. GO analysis from EC clusters revealed GO terms including: gliogenesis, myelination, and vascular morphogenesis. Among the most highly upregulated genes in the EC cluster, were
Ctss
and
C1q
family genes. In choroid plexus cluster, EC Piezo1 KO showed increased expression of Hif1a target genes.

Conclusions:
We conclude that EC Piezo1 loss-of-function promotes hypoperfusion sufficient to induce induction of inflammatory signaling and hypoxia-dependent transcription. White matter injury was evident as gliosis in the corpus callosum and by alterations in gait.
Abstract WP235: Hyperglycemia In The Days After Stroke Exacerbates Brain Injury By Increasing Microglial Superoxide Production
Authors: Won Seok Joon , Mocanu Ebony , Davis Jacqueline , Swanson Raymond A
Published: February 2023

It has been recognized for decades that elevated blood glucose (hyperglycemia) during ischemia/reperfusion greatly exacerbates injury; however, little is known about the effect of hyperglycemia that begins later, over the hours to days after ischemia. This often occurs after stroke as part of a systemic stress response, even in non-diabetic patients, but neither clinical evidence nor prior basic science studies provide guidance on how post-stroke hyperglycemia should be managed. Here we investigated this issue using a mouse photothrombotic model of permanent ischemia. Normoglycemia or hyperglycemia (blood glucose of 300-400 mg/dL; 15-20 mM) was maintained between 17 - 48 hours after ischemia onset. Post-stroke hyperglycemia was found to increase the final infarct volume, increase hemorrhage formation, and exacerbate motor dysfunction. Hyperglycemia also increased superoxide formation in peri-lesional microglia/macrophages. Importantly, hyperglycemia did not have these deleterious effects in p47
phox-/-
mice, which cannot form an active superoxide-producing NADPH oxidase-2 complex, or in wild-type mice treated with a peptide inhibitor of NADPH oxidase-2 (gp91-TAT peptide). These results suggest that hyperglycemia occurring many hours after ischemia can increase oxidative stress in peri-infarct tissues by fueling NADPH oxidase activity in reactive microglia/macrophages, and by this mechanism may contribute to worsened outcome.
Abstract WP236: Tet3 Overexpression Improves Functional Recovery In Male And Female Mice Following Focal Ischemia
Authors: Probelsky Samantha M , Gaillard Alexis B , Jeong Soomin , Davis Charles K , Arruri Vijay , Vemuganti Raghu , Morris-Blanco Kahlilia C
Published: February 2023

Epigenetic mechanisms have been shown to play a major role in the progression of stroke pathophysiology. The ten eleven translocases (TETs) are enzymes involved in generating DNA hydroxymethylcytosine (5hmC), a brain enriched epigenetic modification that is associated with transcriptional activation and neuroprotection. We have previously shown that the TET3 isoform may be involved in promoting endogenous neuroprotective pathways following brain injury. In the current study, we investigated the role of TET3 activity after stroke by examining functional recovery, neuroprotection, and sex-specific differences after TET3 modulation. Adult C57BL6/J mice were subjected to transient middle cerebral artery occlusion (MCAO) to induce focal cerebral ischemia. Dot blotting analysis revealed robust induction of 5hmC levels from 1 hour to 24 hours of reperfusion in the mouse cortex. Intracerebral injection of a neuronal-specific TET3 adenovirus further enhanced TET activity and 5hmC levels in both male and female mice. Overexpression of TET3 led to decreased infarct volume and edema and improved neurological scores at 24 hours of reperfusion. Furthermore, both male and female mice subjected to a battery of motor function assessments from 3 days to 14 days of reperfusion displayed enhanced motor function recovery with increased TET3. These results indicate that TET3-mediated epigenetic regulation may hold therapeutic potential following cerebral ischemia.
Abstract WP24: Promotion Of Stroke Education For The Nation
Authors: Okongo Casey , Brown Harold E , Elkins Kelley , Sumner Jessica , Zielke Shelly , Bellamy Lisa M
Published: February 2023

Introduction:
Stroke education is an ever-present need and there is a shortage of stroke expertise across the nation. The advent of technology has changed the methods by which education is provided. One network in a midwestern state saw this need and had a vision to meet the need by providing stroke education every month. The network began providing this education every month in person in 2012. The vision grew, and this education began to be disseminated through social media platforms in a virtual format in 2019. The goal was to reach as many individuals as possible with valuable education regarding the stroke standards of care to improve the quality of care given to stroke patients.

Methods:
The virtual stroke education that was initially offered was only promoted internally. In April of 2020, the network started to promote the presentation of these virtual offerings via social media sites, such as Facebook and LinkedIn, as well as through stroke message boards and other community connections. In the beginning, the education that was being offered was accredited for RN, MD, and EMS. In 2021, continuing education credits accreditation was obtained for other disciplines including PT/OT, SLP, RRT, and RX to promote better inclusivity.

Results:
In the initial period of January 2019 to April 2020, the educational offerings had a total of 357 participants from 6 states. From April 2020 to April 2021, the attendance grew to a total of 972 participants in 14 states. The participation grew again in the 2021-2022 time period to a total of 1040 participants in 20 states. The educational offerings have grown 191% over the time from 2019 to April 2022. While not everyone chose to claim credit for the education provided, during this time frame 1770 continuing credit hours were claimed. These virtual sessions have now reached 26 of the states in the US.

Conclusions:
The promotional efforts that were employed for the education being offered every month, along with the incorporation of multiple disciplines in the accreditation of this education, has improved the overall participation. This increase in engagement in stroke education is supporting the goal of educating individuals on stroke standards of care and strengthening the stroke systems across the nation.
Abstract WP244: Localization And Expression Of Transporters For Cationic Drugs At The Blood-brain Barrier: Relevance To The Pharmacotherapy Of Ischemic Stroke
Authors: Stanton Joshua , Williams Erica I , Betterton Robert , Lochhead Jeffrey , Davis Thomas , Ronaldson Patrick
Published: February 2023

Purpose:
Cationic drugs have often been considered for stroke treatment but their utility is dependent upondelivery across the blood-brain barrier (BBB). This process can involve transporters for cationic substratessuch as organic cation transporters 1 and 2 (Oct1 and Oct2) as well as the multidrug and toxin extruder 1(Mate1). The goal of this study was to show that the Oct/Mate system at the BBB represents an endogenoustransporter mechanism that can be exploited for efficient brain delivery of cationic drugs relevant to stroketherapy.

Methods:
Male Sprague-Dawley rats (200-250 g) were subjected to middle cerebral artery occlusion (MCAO;90 minutes) followed by reperfusion. Sham-operated rats were used as controls. Memantine (5 mg/kg, i.v.), arepresentative cationic neuroprotective drug, was injected 2 h following intraluminal suture removal in thepresence and absence of cimetidine (15 mg/kg, i.v.), an inhibitor of cation transporters. Localization andprotein expression of Oct1, Oct2, and Mate1 were evaluated by confocal microscopy and western blottingrespectively. Progression of cerebral infarction volume was determined via TTC-stained brain slices.Neurological and motor outcomes during the acute (1 day) and subacute (3-7 days) recovery period post-stroke were assessed using functional neuroscores (i.e., based upon the modified Rankin Scale) and rotorodanalysis.

Results:
Localization and protein expression of Oct1, Oct2, and Mate1 were confirmed in cerebralmicrovessels isolated from Sprague-Dawley rats subjected to MCAO and in Sham controls. Memantinereduced progression of cerebral infarction, reduced neurological scores, and improved rotorod performanceduring the acute and subacute recovery periods following MCAO. Pharmacological effectiveness of memantinewas decreased in the presence of cimetidine.

Conclusions:
Our data show that memantine cannot exert beneficial effects during acute and subacute post-stroke recovery without functional expression of endogenous transporters for organic cations (i.e., Oct1, Oct2,and Mate1) at the BBB. This work is highly translational and emphasizes the critical need to evaluate BBBtransport mechanisms during preclinical development of drugs for ischemic stroke treatment.
Abstract WP245: Casein Kinase 2 Preconditions White Matter Against Ischemic Injury
Authors: Nguyen Hung , Baltan Selva
Published: February 2023

White matter injury (WMI) causes debilitating neurological impairments observed in stroke patients. Ischemic preconditioning (IPC) has been investigated as a protective mechanism against stroke in experimental studies. However, mechanisms of IPC have been mainly studied in gray matter and in vivo rodent models of IPC are not clinically relevant. There is a need to develop clinically-applicable pharmacologically preconditioning approaches that protect the brain against ischemia. Casein kinase 2 (CK2) is upregulated during WMI. Consequently, we have previously reported that application of CX-4945, a CK2 selective inhibitor, protects axon function in young and aged in ex vivo WM stroke model. However, whether CX-4945 preconditioning exerts similar axon function protection and alleviates behavior deficits in ex vivo and in vivo of WMI models remains to be investigated. We hypothesize that pharmacologically preconditioning with CX-4945 protects young and old WM against ischemic injury and alleviates behavioral deficits. Mouse optic nerves (MONs), a pure white matter tract, were used to measure axon function in an ex vivo stroke model. Compound action potentials (CAPs) were evoked and recorded from control and treated MONs. CX-4945 preconditioning did not alter axon function at baseline but protected axon function during recovery against oxygen-glucose deprivation. Behavioral deficits were assessed using cylinder tests and pasta eating tests. At baseline, mice preferentially used both paws; while injured mice showed a biased use of contralateral paw over bilateral paw. Additionally injured mice spent longer time eating pasta and with higher frequency of drops indicating the loss of paw dexterity. Mice were administered orally either CX-4945 (75mg/kg) or vehicle twice/day for 5 days before undergoing WMI. Treated mice showed improved bilateral paw use, and maintained paw dexterity. This behavioral protective effects of CK2 inhibition correlated with survival of oligodendrocyte, preservation of axonal integrity and axonal mitochondrial dynamics. We demonstrated that WM preconditioning with CX-4945 protects axon function, WM integrity, and alleviates behavior deficits in young and age mice.
Abstract WP247: Amylin, A Diabetes-associated Amyloid-forming Peptide, Accumulates In Thrombi And On Red Blood Cells - A New Biomarker For Stroke?
Authors: Leibold Noah , Kotiya Deepak , Sheikhi Lila , Dornbos David L , Pahwa Shivani S , Trout Amanda L , Frank Jacqueline A , Pennypacker Keith R , Goldstein Larry B , Despa Florin , Fraser Justin F
Published: February 2023

Emergent large vessel occlusions result in severe ischemic stroke without appropriate treatment with thrombolysis and/or mechanical thrombectomy. Type-2 diabetes mellitus (T2DM) is a major risk factor in stroke, with 25% of ischemic attacks occurring in individuals with T2DM. T2DM diagnosis is also associated with poorer functional outcomes, prolonged hospitalizations, and increased risk of recurrent stroke. Amylin, a peptide co-secreted with insulin in pancreatic β-cells, is hypersecreted in T2DM and readily forms neurotoxic oligomers which deposit in brain parenchyma. Due to amylin’s role in T2DM and T2DM’s relationship to stroke, we anticipated an increased level of amylin would be deposited on red blood cells (RBCs) of stroke patients when compared to non-stroke patients. Additionally, we anticipated an increased level of amylin immunoreactivity (AIR) in clot lysates when compared to RBC lysates and plasma. Blood samples and thrombi (
n
=47) were collected from patients undergoing mechanical thrombectomies for stroke while blood samples (
n
=21) were collected from patients with non-stroke neurological conditions. Samples were lysed and assayed for total protein concentration and intensity of AIR. Amylin uptake coefficients (AUCs) demonstrating the proportionality of amylin deposited on RBCs compared to total circulating amylin were calculated. After normalizing to total protein concentration, analysis revealed a significantly increased level of AIR in stroke clots when compared to stroke and non-stroke plasma and RBC lysates (p<0.001 for each). Additionally, a significant increase (p<0.0073) in AUC was found in stroke versus non-stroke. In summary, amylin accumulates in thrombi and deposits on RBCs of stroke patients. Further research into amylin’s potential role in thrombus formation is justified. Future studies are also needed to determine if stroke severity is associated with amylin level in thrombi and if T2DM exacerbates amylin-stroke pathology.
Abstract WP27: Beyond The Call: EMS Feedback And Education Improving Stroke Care
Authors: Steiner Nili E , Stokes Sean , Jack Caroline , Figueroa Sonia , Paletz Laurie B
Published: February 2023

Background and Purpose:
Emergency Medical Services (EMS) providers are an integral part of the chain of acute stroke care, stroke patient survival and improving patient outcomes. It is imperative that EMS providers have tools to make accurate critical, time-sensitive decisions. This information impacts care patients receive in the Emergency Department (ED). This collaborative quality improvement project was created to provide feedback to paramedics with the goal of continued rapid, high-quality care for stroke patients in the ED. The purpose of this project is to determine if improved assessment, documentation and information gathering in the prehospital setting decreases door-to-thrombolytic times (DTN).

Methods:
Collaboration with the Beverly Hills Fire Department (BHFD) educators was initiated in July of 2021. We created a feedback form which included EMS documentation elements for the paramedics to obtain. These forms were completed by BHFD educators and our team. We performed ED chart reviews to extract data correlating items such as last known well time (LKWT), witness contact information and other pertinent data. We then provided a summary of the patient’s hospital course. Forms were returned to BHFD educators who distributed them to the paramedics for feedback purposes. Data was collected and analyzed for 12 data points over three quarters (Q3 and Q4 of 2021 and Q1 of 2022).

Results:
Data points analyzed showed sustained improvement. Three data elements demonstrated significant improvement: documentation of LKWT (67% Q3 2021, 89% Q4 2021, 100% Q1 2022), witness contact information collected (11% Q3 2021, 46% Q4, 83% Q1 2022) and over triage reduction (80% Q3 2021, 53% Q4 2021, 50% Q1 2022). Retrospective chart review revealed that patients delivered to our ED by BHFD treated with thrombolytics during Q3 and Q4 202 and Q1 2022 had a median DTN time of 32.6 minutes. This is outstanding and well within the national stroke DTN benchmark.

Conclusion:
We found that feedback to the paramedics improves documentation and assessment skills. Having information we need upon the patient’s arrival to the ED expedites and improves the quality of care we provide to our patients. We will continue to track this data with hopes of including other EMS providers in our network.
Abstract WP29: Investigating Needs, Concerns, And Quality Of Life In Working Age Informal Caregivers Of Stroke Survivors
Authors: Rose Dixie R , Newman Susan D , Mueller Martina , Magwood Gayenell S , Lutz Barbara J
Published: February 2023

Informal caregivers are an essential component of stroke survivor care, yet they are at risk for poorer outcomes due to their own unmet needs, feelings of isolation and abandonment, and lack of personal resources. While a substantial body of research literature on stroke caregiving exists, there is a notable research gap related to the specific needs of working age (18-64) stroke caregivers. The purpose of this study was to characterize unmet needs and concerns, caregiver self-efficacy, social support, and quality of life of working age caregivers of stroke survivors. A cross-sectional descriptive design was used. Participants (N=103) included family or friends that provided unpaid care for a stroke survivor outside of healthcare institutions recruited through national organizations, local support groups, and Facebook ads. Participants completed an online survey comprised of questions exploring sociodemographic characteristics, stroke survivor functional independence, perceived social support, and caregiver needs and concerns, strain, self-efficacy, and quality of life. Descriptive statistics and linear regression analysis were performed using the IBM Statistical Program for Social Sciences (SPSS) v28 software package. In individual regression models, stroke survivor functional independence, caregiver self-efficacy, perceived social support, race, gender, relationship with the stroke survivor, transportation, and responsibilities outside of the caregiving role were predictive of caregiver quality of life. In multiple regression models, stroke survivor functional independence, caregiver self-efficacy, race and gender were statistically significant predictors of caregiver quality of life. In conclusion, this study adds to the current literature by exploring unmet needs and concerns of working age caregivers of stroke survivors and relationships between caregiver quality of life and sociodemographic characteristics, stroke survivor functional independence, perceived social support, and caregiver needs and concerns, strain, and self-efficacy. A greater understanding of these needs can inform intervention designs to meet the unique needs of a diverse population of informal caregivers of stroke survivors.
Abstract WP3: The Use Of Monitored Anesthesia Care In Place Of Nurse Administered Conscious Sedation Does Not Result In Delays To Emergent Thrombectomy.
Authors: Velasco Cesar , Padmanaban Varun , Richardson Alicia M , Cekovich Erin , Reichwein Raymond K , Church Ephraim W , Wilkinson David , Simon Scott , Cockroft Kevin M
Published: February 2023

Introduction:
There has been considerable emphasis on the use of monitored anesthesia care (MAC) versus general anesthesia for emergent mechanical thrombectomy (EMT). However, due to concerns over potential delays many centers do not involve anesthesia services but instead rely on nurse administered conscious sedation (NACS). Since our center switched from NACS to MAC in 2020, we decided to investigate the impact of this switch on our thrombectomy procedures.

Methods:
Using a prospectively maintained Comprehensive Stroke Center quality improvement database, we reviewed our hospital EMT cases from June 2018 to April 2020 (pre-anesthesia involvement, NACS only) and May 2020 to March 2022 (post-anesthesia involvement). Main inclusion criteria were evidence of a proximal LVO and emergent transport for EMT. Variables reviewed included, time to arterial access from neurointerventional suite arrival, time to first pass, and time to TICI 2b/3. Median outcomes were compared using Mann-Whitney U test.

Results:
From June 2018 through April 2020 there were a total of 146 LVO cases that received EVT, compared to a total of 209 LVO cases receiving EVT from May 2020 to March 2022. The median time to arterial access from arrival in the neurointerventional suite was significantly longer before anesthesia involvement (June 2018 to April 2020, 16 minutes) compared to the period after anesthesia involvement (May 2020 to March 2022, 10 minutes) (p < 0.0001). There was no significant difference in median time to first pass between the pre-anesthesia (25 minutes) versus post-anesthesia (26 minutes) time frame (p = 0.43). Median time to TICI 2b/3 was faster post-anesthesia (35 minutes) versus pre-anesthesia (40 minutes) involvement (p = 0.19).

Conclusion:
Our data suggests faster arterial access for EMT and no significant increase in time to first pass or final recanalization after starting to use anesthesia services. The reasons for this are likely multifactorial but may include the offloading of operator responsibilities for managing sedation, blood pressure, and airway security in these often critically ill LVO stroke patients.
Abstract WP31: Driving Down Door To Needle Time: ED Stroke Leadership's Commitment To Continuous Improvement
Authors: Burton Mary ,   ED Stroke Leadership Team
Published: February 2023

Background:
In March 2019, our 126 bed community hospital received Primary Stroke Center Certification. The Emergency Department (ED) Stroke Leadership Team was tasked with the responsibility of identifying opportunities for process improvement and implementing changes within the ED.

Purpose:
The purpose of this poster is to illustrate the ED Stroke Leadership Team’s commitment to continuous improvement ultimately reducing EMS Door to Needle time.

Method:
Data was obtained through retrospective case review of patients who arrived via EMS and received IV thrombolysis for acute ischemic stroke in the ED, between April 2019 and June 2022. Process improvement data was reviewed monthly and interventions were implemented at various intervals using the Plan-Do-Check-Act (PDCA) method. Some early interventions included but were not limited to: EMS pre-notification, a broadcasted stroke alert for all ED staff including pharmacy and CT, and the creation of an EMS direct to CT process. January 2022, the ED Stroke Leadership Team began their 4
th
cycle of the PDCA. In addition to changing the IV thrombolytic from alteplase to tenecteplase, the team took the opportunity to make additional changes to the process and provided education of the stroke protocols and measures to the staff.

Results:
The ED began receiving stroke patients via EMS in April 2019. At the end of 2019 a total of 13 stroke patients arrived via EMS with 5 patients receiving IV thrombolytic therapy with a median Door to Needle baseline of 51 minutes. In 2020 & 2021 EMS stroke pre-notifications increased to 30 and 72 patients respectively but the IV thrombolytic was given to a two year combined total of 9 patients with a median Door to Needle time of 41 minutes. January 2022 we began to see a rise in the volume of stroke patients. As of June 2022, EMS delivered 53 patients in which 9 received IV tenecteplase with a median Door to Needle time of 28 minutes. These incremental process improvements represent a 45% decrease in EMS Door to Needle over the last 3 years.

Conclusions:
In conclusion, the ED Stroke Leadership Team’s commitment to continuous improvement has been the driving factor in the reduction of the EMS Door to Needle time.
Abstract WP32: Addressing Disparate Clinical Stroke Resources With A Telestroke Taskforce
Authors: Bluma Dot , Bowser John , Abelt Susan , Bennett Nicole L , Landreman Hollie
Published: February 2023

Introduction:
Telestroke can enhance the timeliness and overall quality of stroke care for rural populations geographically separated from higher level stroke centers. To help hospitals utilize this resource, the Wisconsin (WI) Coverdell Stroke Program (Coverdell) and American Heart Association® (AHA) partnered with 15 hospital systems for a Telestroke Taskforce (TF) which met monthly June 2021-February 2022.

Methods:
A TF Charter and Framework guided the work. Framework items included: decision to call, telestroke consult, treatment and transfer decision, feedback, and patent satisfaction. Challenges, successes, WI consensus criteria, WI document development, Get With The Guidelines® (GWTG), resource needs and availability were addressed for these items. A manual and two videos were developed. The first video is a four clinician panel across four hospital systems sharing perspectives on telestroke implementation. Second, a demonstration video of conducting the National Institutes of Health Stroke Scale (NIHSS) via telestroke was produced to assist those unfamiliar with the process. The WI Telestroke Toolkit, which includes the charter, framework and established resources, will be published to the Coverdell website in Fall 2022.

Results:
Five measures were assessed quarterly Q1 2021-Q1 2022 among WI hospitals entering into GWTG® • Proportion of stroke patients w/ telestroke consult - 16.9ppt
increase
• Thrombolytic administration rate - 0.2ppt
increase
• Mechanical endovascular rate - 0.6ppt
increase
• Median time to consult - 2 minute
reduction
• Door-in-door-out times - 1 minute
reduction

Conclusions:
Measure improvement, given the timeframe, is likely due to an increased focus on telestroke associated with the TF. As the Toolkit is shared and utilized by hospitals, we are hopeful for continued improvement. The Toolkit will be updated annually. Future considerations are to formally evaluate TS recipient satisfaction.
Abstract WP35: Neighborhood Effects On Knowledge Of Stroke Risk Factors And Stroke Warning Signs
Authors: Nobel Lisa , Rasnick Erika , Ding Lili , Robinson David , Ayala Felipe , Kissela Brett M , Kleindorfer Dawn O
Published: February 2023

Background:
Low socio-economic status has been associated with worse stroke outcomes and longer arrival times to the ED.

Objective:
To determine whether stroke knowledge is different by neighborhood and if neighborhood socio-economic status (NSES) predicts knowledge of stroke risk factors (RF) or stroke warning signs (WS).

Methods:
A survey was done in the Greater Cincinnati Northern Kentucky Region in 2016 where participants were targeted to match those of ischemic stroke patients within the same population. The participants were asked open-ended questions regarding stroke WS and RFs. Participants also provided their zip codes. NSES was determined based on zip code and census data. NSES was determined using a previously validated index and divided into quartiles. We used regression to determine the association between NSES and only being able to name 0-1 RF or WS.

Results:
There were 1902 participants in the surveys with non-missing geographic data who lived in 96 different zip codes. Participants were 66.8±16.4 years old, 56.2% were female, 24.4% were black and 36.0% had less than a HS education. About 20% of participants were unable to name one stroke risk factor or one warning sign. There was substantial heterogeneity of stroke knowledge by zip code (Figure 1). There was no significant association between NSES and knowledge of stroke WS. After adjustment for age, sex, and race, participants who lived in neighborhoods in the lowest quartile of NSES were more likely to be only able to name 0-1 RFs when compared to all other neighborhoods (Lowest Quartile of NSES OR 1.45 (95% CI 1.06-1.98)).

Conclusion:
We identified geographic disparities of stroke knowledge in a well-defined population, emphasizing the need for targeting public health interventions towards areas most in need. NSES accounted for some of the disparities in stroke RF knowledge, but not stroke WS knowledge.

1
Abstract WP38: Variation In Performance On Stroke Care Delivery Measures Among Us Community Emergency Departments
Authors: Zachrison Kori S , Rothenberg Craig , Adeoye Opeolu M , Feeser V. Ramana , Ganti Latha , Goldstein Joshua N , Jauch Edward C , Lo Bruce , Madsen Tracy , Corral Mitra , Decker-Palmer Marquita , Mendez-Hernandez Cindy , Finch Melissa , Goyal Pawan , Venkatesh Arjun
Published: February 2023

Introduction:
Many stroke patients initially present to non-stroke center hospitals. However, the delivery of Emergency Department (ED)-based acute stroke care at smaller, non-academic (i.e., community) EDs is less well-described than for larger, academic hospitals.

Hypothesis:
There is wide variation in community EDs’ performance on acute stroke care delivery measures.

Methods:
This is a retrospective analysis of a cohort of stroke patients from EDs participating in the Emergency Quality Network (E-QUAL) stroke collaborative, a national stroke quality improvement project targeted to community EDs. Sites used ICD10 codes to identify ischemic stroke patients and submitted data using a web-based submission portal. EDs with data from at least 20 patients were included. For each site, we calculated median door-to-imaging (DTI), door-to-needle (DTN), and door-in-door-out (DIDO) times among transferred patients and ED length of stay (LOS) among admitted patients. We also determined the proportions of eligible patients arriving with 3.5 hours of last known well who received thrombolysis within 4.5 hours, of patients with documentation of severity assessment performance and of dysphagia screening. We used descriptive statistics to illustrate variation.

Results:
Of the 54 participating EDs, data were available for 45, and 28 included ≥ 20 patients. Of included EDs, median annual ED volume was 34,648 (IQR 21,250-47,120) and 40% were rural. Performance varied on DTI, DIDO among transferred patients, and LOS among admitted patients (Table). Performance was more consistent on documentation of severity assessment and dysphagia screening.

Conclusions:
Performance on stroke care delivery measures varied between these community EDs and data in the literature from larger hospitals that typically participate in national registries. Future efforts to improve emergency stroke care delivery should consider unique factors impacting care at smaller, community EDs.
Abstract WP40: Development Of The System For National Statistics Of Stroke And Acute Myocardial Infarction Using Claims-based Algorithms In Korea
Authors: Kim Tae Jung , Oh Hyun-kyung , Lee Hak Seung , Kim Seong-eun , Park Jinju , Kim Jun Y , Lee Jiyoon , Song Jieun , Hong Jin-Hyuk , Seo Soon-young , Ahn Eunmi , Lee Seon Kui , Lee Joongyub , Chung Joong-Wha , Kim Hyeon Chang , Shin Dong-ho , Lee Hae-Young , Kim Bum Joon , Seo Woo-Keun , Park Jong-moo , Lee Soo Joo J , Jung Keun-hwa , Kwon Sun U , Hong Yun-Chul , Kim Hyo S , Kang Hyun-Jae , LEE JUNEYOUNG , BAE Hee-joon
Published: February 2023

Background:
The epidemiology of stroke and acute myocardial infarction (AMI) in Korea is limited by inaccurate methods for estimating incidence. Therefore, this study aimed to build the system for national statistics of stroke and AMI in Korea using claims-based identification algorithms.

Methods:
We identified stroke and AMI using the claims-based algorithms based on the 2018 National Health Insurance Service (NHIS) data. The identification algorithms were validated using investigation of medical records of the sampled cases including the patient groups and the control groups based on a 2-stage stratified sampling method. The sampled cases were divided into 6 strata according to regions (capital and non-capital) and types of centers (tertiary hospitals, general hospitals, and hospitals). Based on the medical records results, we calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), and weighted PPV and weighted NPV were calculated by applying strata-specific sampling rates. The incidence rate of stroke and AMI is the number of new cases of stroke and AMI, including recurrent events, which was calculated by applying the algorithms using weighted PPV and NPV to the claims data.

Results:
In total, 2,200 cases (1,086 cases in stroke [578 patients and 508 controls] and 1,114 cases in AMI [520 patients and 594 controls]) were sampled after applying algorithms for review of hospital records. In hospital record reviews, the stroke algorithm had 95.2% sensitivity, 99.6% specificity, 89.3% PPV, and 99.8% NPV, and AMI algorithms showed 97.7% sensitivity, 99.9% specificity, 90.0% PPV, and 99.9% NPV. We identified 94,994 stroke and 33,834 AMI cases including recurrent events using validated identification algorithms in 2018. The age- and sex-standardized incidence rate of stroke was 175.7 cases per 100,000 person-years and the incidence rate of AMI was 49.3 cases per 100,000 person-years in 2018.

Conclusion:
We developed the national statistical system to estimate the incidence of stroke and AMI using validated claims-based algorithms in Korea. By using this system, we expect that it will be possible to conduct nationwide epidemiological research and improve acute cardiovascular care in Korea.
Abstract WP41: Should They Stay Or Should They Go? The Impact Of AI-based Care Coordination On Stroke Patient Transfers Across A Hospital Network
Authors: Love Christopher J , Bonner James
Published: February 2023

Introduction:
A key decision facing non-thrombectomy capable hospitals is whether to transfer a suspected large vessel occlusion (LVO) patient to a thrombectomy-capable stroke center (TSC). We report our experience with a commercially available AI-based care coordination platform (Viz.ai) designed to detect and alert LVOs on imaging (CTA) and improve communication among spoke and hub providers.

Methods:
All patients presenting across our community hospital network (consisting of two primary stroke centers, one stroke-ready hospital, and two freestanding emergency departments) with the diagnosis of acute stroke were included. We investigated the effect of the Viz.ai software platform on the number of stroke patients transferred out of our health system to the TSC and CTA utilization by comparing transfer patterns in a cohort of patients before (pre-Viz, 12/2018 - 10/2020) and after (post-Viz, 10/2020 - 08/2022) implementation.

Results:
A total of 1778 pre-Viz and 1779 post-Viz patients were compared. The post-Viz transfers significantly decreased by 33% (158 post-Viz vs 236 pre-Viz, p<0.0001) and the post-Viz patients receiving a CTA within our system increased by 64% (1167 post-Viz vs 710 pre-Viz, p<0.0001). The proportion of patients receiving a thrombolytic (tPA or TNK) who were cared for at the spokes was significantly higher post-Viz (74% vs 63%, p=0.02). The baseline clinical characteristics and study outcomes are summarized in the Table.

Conclusions:
In a consecutive cohort of stroke patients across a system of community hospitals that are not thrombectomy-capable, the implementation of the Viz.ai software platform was associated with reduced transfers to the thrombectomy center and an increased use of in-house CTA for LVO screening. There was an increase in the proportion of patients treated with intravenous thrombolysis who did not undergo transfer and received care locally suggesting improved identification of patients who benefit from transfer.