bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TP226: Impact Of Apolipoprotein A-i In The Attenuation Of Stroke And Stroke Symptoms
Authors: Kindy Mark S
Published: February 2023

Apolipoprotein AI is the major protein component of high-density lipoprotein (HDL) particles in plasma. Inflammatory cytokines such as TNF and IL-1β repress the production of ApoA-I from hepatocytes and increase the expression of serum amyloid A (SAA), which becomes the major protein component of HDL in this context. Consequently, lipid-poor ApoA-I is rapidly catabolized in the liver and the kidney. These findings could be meaningful if ApoA-I, in addition to its proimmune features, had anti-inflammatory potential. In this way, removal of ApoA-I could intensify the inflammatory response, resulting in a more robust effect. Recent studies have suggested that serum apolipoprotein A1 maybe a predictor and prognostic biomarker in acute ischemic stroke in humans. To understand the impact of ApoA-I in stroke, we have begun to analyze the role of ApoA-I in mouse models of stroke. Mice with reduced or deficient in ApoA-I and subjected to ischemia and reperfusion injury or permanent ischemia, had increased inflammatory responses, larger infarct volumes, and poorer outcomes than wildtype mice. Mice transgenic for the human ApoA-I gene showed a level of protection not seen in the wildtype mice when given an ischemic injury. Administration of AAV human ApoA-I increased HDL levels in deficient mice and provided protection against ischemic injury. Additionally, drugs to enhance ApoA-I expression showed protection against strokes in the mouse models. These studies, along with subsequent investigations will provide a better understanding and potential therapeutic approaches in the field of stroke.
Abstract TP231: Low Hemoglobin Causes Cerebral Hypoxia Resulting In Changes In Blood-brain Barrier Function In Mice
Authors: Cottarelli Azzurra , Kumar Aditya , Mao Eric , Hod Eldad , Roh David
Published: February 2023

Introduction:
Low hemoglobin is associated with stroke and poor cerebrovascular outcomes. It is unclear whether hemoglobin concentrations directly impact cerebrovascular health. Thus, we sought to investigate the role of hemoglobin concentration on cerebral hypoxia and blood brain barrier (BBB) function in murine models of anemia.

Hypothesis:
Low hemoglobin will cause relevant cerebral hypoxic changes and impair BBB function.

Methods:
Two different models of anemia and their respective controls were generated from 30 8-week-old, female C57/BL6 mice. The separate cohorts generated included: 1) an acute anemia model cohort via anti-TER119 injection (red blood cell hemolysis) compared to IgG control injected mice; 2) chronic anemia model cohort via iron-deficient chow compared to iron replete diet control. Hemoglobin concentrations were assessed using modified Drabkin assays. Mice were euthanized by intracardiac perfusion with saline and fixative and the brain was dissected and processed for histological analysis of vascular permeability (IgG), microglia number and activation (Iba1 and CD68), response to hypoxia (HIF1α) and endothelial markers of BBB function (GLUT1). Statistical analyses were performed using two-tailed Student's t-tests.

Results:
Hemoglobin concentrations were lower in our separate anemia model mice compared to their respective controls (acute anemia: 5.5 ± 4.02 vs 13.1 ± 1.69, p=0.007; chronic anemia: 7.9 ± 1.05 vs 11.9 ± 2.31, p=0.0006). Postmortem histological analyses revealed stronger microglial activation (p<0.005) and higher microglial expression of hypoxia-response protein HIF1α (p<0.05) in both acute and chronic anemia models compared to their respective controls. Additionally, anemic mice had increased vascular permeability to serum IgG and decreased expression of the endothelial-specific glucose transporter GLUT1 (p<0.05).

Conclusions:
Anemic mice appear to display stronger microglial activation, greater HIF1α expression, and BBB dysfunction compared to non-anemic mice. Future studies will be needed to further clarify cellular and molecular mechanisms driving relationships between anemia, hypoxia, BBB dysfunction and clinical outcomes in cerebrovascular disease.
Abstract TP235: Temporal Change Of Brain Mitochondrial Function In A Rodent Model Of Subarachnoid Hemorrhage
Authors: Bömers Jesper P , Karlsson Michael , Mathiesen Tiit I , Edvinsson Lars , Haanes Kristian Agmund
Published: February 2023

Introduction:
Subarachnoid hemorrhage (SAH) is a devastating disease. A third of the patients die and a large percentage of the survivors require support in daily living and suffers from reduced quality of life. As part of clinical practice for these patients, a cerebral microdialysis catheter may be placed to monitor cerebral metabolic function. Using this monitoring technique, the patients often demonstrate an increase in the lactate-pyruvate ratio, despite adequate supply of glucose and oxygen, which may be an indirect marker of mitochondrial dysfunction. We wanted to identify a possible mitochondrial dysfunction in a rat SAH model at different time points by directly measuring mitochondrial function in brain tissue
ex vivo
.

Method:
The pre-chiasmatic single injection model of SAH was used. Oroboros Oxygraph high resolution respirometry was used to evaluate the electron transport chain of the mitochondria. We also analyzed ROS generation simultaneously at the same time points using the Oroboros LED2 module. We measured tissue from the cortex and the hippocampus.

Results:
45 rats at four different timepoints, 6-, 24-, 48- and 96 hours after surgery, were included. We identified a significant reduction in respiration through complexes I and II of the electron transport chain in hippocampal tissue at 96 hours after SAH compared to sham. The respiration of cortical tissue at the same time point was reduced compared to sham but did not reach significance. No differences were identified at other time points and no differences in ROS generation were identified.

Conclusion:
We conclude that the SAH model can be used as a suitable model to identify mitochondrial dysfunction and that the respiratory capacity of the electron transport chain is reduced in the hippocampus at 96 h post insult in this rat model of SAH.
Abstract TP239: The Cylinder Project: Pre- And Post-stroke Assessment
Authors: Rojas Valerie , Armshaw Jared , Becker April M
Published: February 2023

In rodent research, the cylinder test is frequently used to assess for hemiparesis following various forms of motor cortical damage, such as stroke. The cylinder test utilizes rodents’ natural tendency to engage in exploratory behaviors including rearing. When a rodent rears, their paws frequently come into contact with walls of the cylinder. In healthy rodents, paw contacts are relatively equal across forepaws; however after a stroke, rodents are generally more reliant on their forelimb paw that is contralateral to their affected brain hemisphere. The cylinder test is often an effective assessment for hemiparesis, but it does have limitations such as extensive research coding time, rodents’ habituation to the environment, and insensitivity to mild stroke. Therefore, we developed a technologically-infused cylinder assessment that uses a touchscreen and camera to capture the data, which is then analyzed with an AI image algorithm. We believe that using an automated system for the cylinder assessment will produce results at a more efficient rate and provide potential new measures of rearing behavior that may be more sensitive to stroke. The validation of this project fits into the greater scheme of the Neuroplasticity and Repertoire Recovery Lab to improve functional motor recovery after a stroke.
Abstract TP241: Therapeutic Effects Of Magnet-induced Stem Cells Using Ferrimagnetic Iron Oxide Nanoparticles In Ischemic Stroke Model
Authors: Kim Chi Kyung , Kim Han Jun , Han Jung Hoon , Oh Kyungmi
Published: February 2023

Background:
The efficiency of targeted delivery of stem cells via transplantation by intravenous injection is limited because of rapid clearance. Thus, more effective, newer methods are required. We hypothesized that combining the use of ferrimagnetic iron oxide nanoparticles (FION) labeling and magnetic fields could enhance the targeted delivery of stem cells after ischemic stroke.

Methods:
In a typical synthesis of FION nanocubes, iron(III) acetylacetonate was added to a mixture of oleic acid, 4-biphenylcarboxylic acid, and benzyl ether. Therapeutic effects of neural stem cells (NSC) using the magnetic nanoparticles in the cerebral ischemic stroke. Transient middle cerebral artery occlusion (MCAO) was induced in SD-rats. Iron oxide nanoparticle-labeled NSCs were injected into the tail vein. Magnetic resonance tracking and confirming labeled stem cells with Prussian blue staining. Polypeptides derived from receptors for advanced glycation end products and pharmaceutical composition for preventing and treating cerebrovascular disease comprise the same.

Results:
In the F3-VEGF NSC cell, FION uptake was shown as immunofluorescence. After overexpression of VEGF in F3 cells, it was confirmed by Western blotting. The measurements of cytotoxicity in FION's NSC showed toxicity over 80g but 40g was treated for 7 days and was not toxic. Six hours after MCAO induction, 4x10
6
NSCs were injected, and a magnet hat so that the stem cells implanted in the pathogen could move well. After one day, a behavioral test was conducted every week for up to 35 days. After MCAO induction, the group transplanted with FION-NSCs significantly improved in the behavioral test on Day 35 compared to the control group. In order to measure the distribution of FION in tissue, MRI was performed showing penetrating into the lesions of the white circles. As a result of ICP-MS, the magnet-applioed group was concentrated with FION 7 times more compared with the FION-only group. The distribution in brain tissue was observed through FION's Fluorescence images.

Conclusions:
Our study suggests that this use of a magnetic field may be useful for improving the efficacy of targeted migration of stem cells in stem-based cell therapy in ischemic brain injury.
Abstract TP31: Achieving Compliance With A Nurse Driven Stroke Timer Initiative
Authors: Pozo Jessilyn , Cruz Nina A , Belnap Starlie , De Los Rios La Rosa Felipe
Published: February 2023

Background:
The concept “time is brain” has guided the international stroke community since the early nineties. The use of a visual countdown has been shown to improve turnaround times during acute stroke management; however, use of these devices is not a standard of practice and therefore not used consistently in most hospitals. Furthermore, compliance with a stroke timer initiative can be hampered by logistical and emotional responses to the timer concept.

Purpose:
The purpose of this project is to improve compliance with a stroke countdown timer during stroke alerts for potential acute ischemic stroke reperfusion treatments (thrombolysis and/or neuroendovascular intervention) candidates at our Joint Commission CSC.

Methodology:
A pre- and post-intervention design method was used by implementing measures to improve timer adherence. These included changing the timer storage location and modification to the nurse stroke alert documentation to capture timer utilization. Stoke nurse education about these changes and the 100% compliance expectation was provided. The countdown timer was set to 25-min from arrival for IV thrombolysis, then reset to 35 minutes for puncture access for mechanical thrombectomy. To minimize stress on the stroke response team, there were no alarms or push buttons necessary, other than the one needed to set the countdown timer upon patient arrival.

Results:
During the study period, the median DTN, DTP, DTD were 21, 69, and 81 minutes respectively. After post-intervention implementation, the stroke clock was utilized in 92% (n=58) of the stroke alerts, a 50 percent increase from initial utilization (42%, n=31). There was no statistical significance found in any of the treatment times (H[2]=0.280, p=.869 [DTN]; H[2]=2.238, p=.327 [DTP]; H[2]=1.973, p=0.373 [DTD]) despite a median decrease of 15 minutes on DTP and DTD with improved compliance.

Conclusions:
Great compliance with a nurse driven stroke countdown timer initiative can be achieved with simple workflow changes however it did not result in improved treatment performance metrics. Our analysis was limited by a small sample size. We are planning on a larger analysis using data from our multicenter stroke network.
Abstract TP34: Positive Covid-19 Cases Requiring Neurology Consultation: Retrospective Review Of Cases
Authors: Bush Kelly
Published: February 2023

Background and Purpose:
Descriptive study to review 200 patients presenting with Covid-19 and neurology consultation.

Methods:
Retrospective review of 200 patients with Covid-19 requiring neurologic consultation from April 2020 to February 2021. Characteristics reviewed included age, sex, BMI, past medical history, presenting symptoms, labs, imaging, symptomatic vs asymptomatic Covid-19, acute stroke, stroke intervention, and death status. Labs reviewed were on the day of neurologic consultation.

Results:
All 200 patients were laboratory confirmed Covid-19 positive. Consultation indication included stroke symptoms (36%), encephalopathy (32%), abnormal movements / seizure (9.5%), myopathy (5.5%), headache (4.5%), and other (11.5%). The mean age of the patient was 67.2 ± 16.6, and 85 (47.5%) were female. 88 (44%) of the patients were obese, 123 (61.5%) were diabetic, and 118 (59%) had dyslipidemia, while 40% reported history of neuropathy. CRP was elevated in 47.9%, d-dimer elevated in 41.9%. 29.5% of patients complained of dizziness and 34% headache. 65% had acute upper respiratory symptoms, 68% acute encephalopathy, and 53% impaired consciousness. 29% (59) had finding of acute ischemic stroke on imaging. 46% (27) of the acute stroke patients were deceased. 17% of the acute strokes that met criteria underwent acute intervention with IV-tPA (8.6%) and thrombectomy (8.6%).

Conclusions:
In conclusion, there is a high mortality rate with acute stroke in the setting of Covid-19 and neurology consultation. Additionally, increased rates of co-morbidities such as obesity, diabetes, and dyslipidemia are noted, interesting 40% had a history of neuropathy. Further review of these characteristics in comparison to death status in patients with Covid-19 and neurology consultation is recommended and will follow.
Abstract TP38: Gender Disparities In Ischemic Stroke Thrombolytic Treatment In Nebraska Hospitals
Authors: Malina Beth L , Jones Olivia N , Bobenhouse James A , Thorell William E , Gregath Trevor , Stout Pamela , Palmer Pamela , Poudel Remy , Dunn Patty , Orr Chastity , Beldin Hanne , Gonzalez Castellon Marco A
Published: February 2023

Introduction:
Mission: Lifeline Stroke Nebraska was a 4-year program to enhance stroke systems of care in Nebraska. With 68% of hospitals in Nebraska participating in GWTG-Stroke, analysis of stroke treatment data can be accomplished on disparities across the state.

Methods:
De-identified data was accessed through AHA GWTG-Stroke registry to assess stroke outcomes of patients at 49 participating NE hospitals in 2020. Data were analyzed based on AHA specified Mission: Lifeline reporting, achievement, and pre-hospital measures. The purpose of analysis was to describe patient characteristics and determine differences in IV thrombolytic treatment and mean patient NIH stroke score (NIHSS) upon admission. Percentages and counts were reported for categorical variables. The mean, standard deviation (SD) and median were reported for continuous variables. The Kruskal-Wallis rank sum, Wilcoxon sign rank, T-tests, chi-square and one-way ANOVA tests were used, where appropriate, to assess differences in stroke outcomes by age, gender, and race/ethnicity.

Results:
Of the 3,952 patient encounters registered in GWTG-Stroke from 01/01/2020 to 12/31/20, 2670 (67.5 %) were patients 18+ at time of admission with clinical diagnosis of ischemic stroke. Statistically significant differences in age, NIHSS at admission, and treatment with thrombolytics by gender were observed. Compared to males, females were older (72.7 vs. 68.1 years), had a lower mean NIHSS at admission (5.8 vs. 6.0), and a smaller proportion of females received thrombolytic treatment (42% vs. 58%).

Conclusions:
Overall, females were less likely to receive IV thrombolytic treatment compared to males. Women in the study were older with lower NIHSS than males. Results from this analysis align with those from the study “The Impact of Sex and Gender on Stroke” (Rexrode, et al.,2022) indicating that females may present different signs of a stroke than males. Our data showed the NIHSS scores to be lower for females possibly leading to lower frequency of treatment. As a part of the Mission: Lifeline initiative, this information was shared with hospitals and providers across the state. These results led to public awareness and education targeted to women, including a local podcast and social media.
Abstract TP56: Us Comprehensive Stroke Center Utilization Of FAST And BEFAST Mnemonics For Public Education
Authors: Hogge Christopher , Goldstein Larry B , Aroor Sushanth
Published: February 2023

Introduction:
Symptom recognition and timely access to treatment are critical components of acute stroke care systems. Two mnemonics widely used in public educational campaigns for recognizing stroke symptoms include FAST (Face-Arm-Speech-Time) and BEFAST (Balance-Eyes-Face-Arm Speech-Time). The FAST mnemonic, endorsed by the AHA/ASA can miss up to 14% of strokes. BEFAST includes common posterior circulation stroke symptoms and has been implemented by several Comprehensive Stroke Centers (CSCs).

Methods:
We sought to analyze the pattern of public educational materials available on the websites of US CSCs. The Joint Commission (JC) quality check website compiles a list containing the names and locations of the country’s 217 JC-certified CSCs, which was downloaded in August, 2022. Each CSC’s website was searched for educational material containing FAST and BEFAST mnemonics for stroke symptom recognition.

Results:
The FAST mnemonic was listed by 35% of CSCs, the BEFAST by 58%, with 7% listing no specific mnemonic. The highest portion of CSCs using BEFAST was in western (65%) and southeastern (63%) states. The highest percentage of CSCs with no listed mnemonic were in the northeastern (14%) and southeastern (13%) states.

Conclusions:
Consistency is critical in shaping public health education related to stroke symptoms recognition. Our study suggests further effort is needed to unify the public messaging on stroke recognition.
Abstract TP69: Prediction Performance Of Socio-economic And Clinical Factors Of Prolonged Acute Ischemic Stroke Hospitalization
Authors: Aldridge Chad M , Southerland Andrew M , De Havenon Adam H
Published: February 2023

Introduction:
Patients with acute ischemic stroke (IS) experience varying length of stay (LOS), which is a key hospital outcome linked with resource allocation and cost. We investigated predictive performance of socio-economic and clinical factors of prolonged LOS in the National Inpatient Sample (NIS) data set.

Methods:
We performed a retrospective analysis on the NIS data set containing patients with an IS diagnosis (I63*) from years 2016 to 2019. We investigated differences between patients with a LOS 14 ≥ vs < 14 days. We utilized a LASSO regression to select predictors of LOS 14 ≥ vs < 14 prior to a ROC analysis. We included: age, sex, race/ethnicity, hypertension, Diabetes II, Atrial fibrillation, congestive heart failure, NIHSS categories, insurance payer, income, teaching hospital and bed size, thrombolytic therapy, mechanical thrombectomy (MT), intubation, tracheostomy, and percutaneous endoscopic gastrostomy (PEG) tube.

Results:
The cohort (n=137,370; 51% male) had a mean (SD) age of 68.39(± 14.01) years and admitted NIHSS of 6.32 (± 6.81). All differences between LOS 14 ≥ vs < 14 were significant (p ≤ 0.021). Groups were similar in age (66.31 ± 13.91 vs 69.50 ± 13.99), but differed in metrics of stroke severity including NIHSS > 15 (41.61% vs 10.55%), MT (21.04% vs 6.40%), intubation (23.4% vs 1.60%), tracheostomy (11.54% vs 0.11%), and PEG tube (34.06% vs 1.89%). They were more likely to have Medicaid (19.74% vs 8.78%) and identify as Black (27.86% vs 16.93%). LASSO regression identified 13 predictive variables (Pseudo-R2 0.264) with an ROC AUC of 0.84 discriminating between LOS ≥ 14 vs $lt 14 (
Figure)
.

Conclusion:
Independent of stroke severity and procedure, Medicaid insurance and identifying as black were significant predictors of prolonged acute stroke hospitalization. Although the ROC curve was highly accurate in identifying prolonged LOS, the LASSO only accounted for 26% of the variance. Further research into novel predictors of LOS is warranted.
Abstract TP70: Association Between Race And Length Of Stay Among Stroke Patients: The National U.S. Emergency Departments Dataset
Authors: Patel Karan , Taneja Kamil , Wolfe Jared , Campellone Joseph V , Farooqui Mudassir , Ortega-Gutierrez Santiago , Siegler James E
Published: February 2023

Background:
There remain ongoing racial and ethnic disparities in care and outcomes among stroke patients treated in the US. However, length of stay (LOS) and inpatient costs warrant further evaluation.

Methods:
The 2019 Nationwide Emergency Department Sample (NEDS), which includes data from roughly 20% of US emergency departments, was queried for patients with cerebral infarction. Multivariable logistic regression was used to estimate the odds of prolonged length of hospital stay (>75th percentile) and inpatient costs among various race/ethnic groups, including income and payor status, age, modified Charlson Comorbidity Index (mCCI), vascular risk factors, and treatment with thrombolysis and thrombectomy.

Results:
Of 617,946 estimated patients with acute ischemic stroke, 398,661 (65.5%) were > 65y, and 386,096 (63.5%) were Medicare beneficiaries. Lower income and Medicaid or self-pay status were more commonly observed in Black and Hispanic versus White patients (p<0.001). In multivariable regression, Black patients were more likely to have a prolonged LOS (Odds Ratio 1.41, 95% confidence interval 1.28-1.55) compared to Whites. Prolonged LOS was inversely related to income, but there was no significant interaction between race and income bracket (p>0.05). Prolonged LOS was also associated with Medicaid (versus Medicare), higher mCCI, thrombolysis, and thrombectomy (p<0.05). Race was not independently associated with higher inpatient costs.

Conclusions:
These results build on prior population-based studies that indicate ongoing disparities in stroke care based on differences in socioeconomic status and race, but no difference in inpatient cost.
Abstract TP74: Reducing Complications From Gastrostomy Tube Insertion In Stroke Patients - Quality Improvement Project At An Academic Tertiary Hospital
Authors: Hwang Mu Ji , Sosa Crystal , Goldstein Eric D , Stretz Christoph , Paolucci Gino , Kala Narendra , DeMoranville Colleen R , Perelstein Elizabeth , Harmon Melissa , Burton Tina M , Mandel Daniel , Furie Karen L , Yaghi Shadi
Published: February 2023

Introduction:
Percutaneous gastrostomy tubes are frequently required for patients with strokes due to dysphagia, malnutrition, and intestinal dysmotility. Though generally well tolerated, delayed detection of complications following percutaneous gastrostomy tube insertion (including dislodgement, infection and bleeding) can lead to increased morbidity and mortality.

Methods:
At a single academic tertiary hospital, a standardized protocol was instituted (September 2021) to enhance early detection and prevention of feeding tube complications on the neurology service, consisting predominantly of stroke patients. The protocol comprised of: 1) consistent documentation of feeding tube insertion by proceduralists, 2) universal abdominal binder application, 3) nursing driven delirium screening, 4) post procedural nursing assessment for high-risk feeding tube site changes, and 5) an escalation algorithm to address early complications. We compared rates of complications pre- (July 2020 - August 2021, 13 months) and post- (September 2021 - June 2022, 10 months) protocol implementation.

Results:
A total of 103 gastrostomy tube insertions were reviewed (64 pre and 39 post protocol implementation). Overall complication rates decreased from 12.5% (N = 8 of 64; 3 dislodgements, 3 infections, 2 insertion site bleeding) to 2.5% (N = 1 of 39; 1 dislodgment) following the intervention. Mortality from complications decreased from 1.6% to 0%.

Conclusion:
Complication rates of percutaneous gastrostomy tube placement may be reduced through implementation of standardized protocols on inpatient stroke patients. Further studies are warranted to assess its long-term effects and viability in other specialty services.
Abstract TP91: Automated Cerebral Hemorrhage Volume Calculation And Stability Detection Using RAPID Software
Authors: Sreekrishnan Anirudh , Venkatasubramanian Chitra , Heit Jeremy J
Published: February 2023

Introduction:
The measurement of intraparenchymal hemorrhage (IPH) volume is important for management, particularly in evaluating expansion on subsequent imaging. However manual volumetric analysis is time-consuming, especially in busy hospital settings. We aimed to use automated RAPID hyperdensity software to accurately measure IPH volume across repeated imaging.

Methods:
We identified primary IPH cases, without evidence of IVH, SDH, or SAH, from two randomized ICH trials where enrollment was not based on IPH volume. Scans were excluded if (1) there was CT acquisition artifact, (2) measured IPH volume was < 0.4ml, or (3) patient underwent a neurosurgical procedure. Repeat imaging, conducted within 12h, was included in a secondary stability analysis. Manual IPH measurements were conducted by one neuroimaging expert using MIPAV software and compared to the performance of the RAPID hyperdensity module.

Results:
149 scans were included with median IPH volume manually measured at 13.3ml (IQR 3.2-27.5) compared to RAPID detection of 18.0ml (IQR 5.1-36.8). The two modalities were highly correlated (Figure 1, r = 0.948, p < 0.001) with a median absolute difference of 3.4ml (IQR 0.2-9.4) and standard error of 0.655. Repeat imaging was available in 65 patients, with a median absolute difference of 0ml (IQR: -2.6-1.5) compared to RAPID detection at 0.1ml (IQR: -2.3-2.7). These absolute differences were also highly correlated (r = 0.878, p < 0.001), with the ability of RAPID to detect a 5ml IPH expansion with a Sensitivity of 98.1% and Specificity 72.7%. Processing time for the software was < 3 minutes.

Conclusion:
In our pilot data, the RAPID hyperdensity module has high reliability in its ability to quickly automatically detect IPH volume and high sensitivity to detect expansion on subsequent imaging.
Abstract WMP101: Plasma Proteomic Determinants Of White Matter Hyperintensities And Covert Brain Infarction In The Cardiovascular Health Study
Authors: Sharma Malveeka , Longstreth W T , Kalani Rizwan , Psaty Bruce , Elkind Mitchell , Floyd James S , Heckbert Susan R , Buckwalter Marion S , Gomez Gabriela , Walker Keenan , Bartz Traci , Austin Thomas , Bis Joshua , Brody Jennifer , Tirschwell David L , Tracy Russell P , Gerszten Robert E , Fohner Alison
Published: February 2023

Background:
Identification of novel biomarkers of cerebral small vessel disease is critical to elucidate pathophysiology and guide therapeutic development for prevention. We evaluated plasma proteomic associations of clinically asymptomatic, covert brain infarction (cBI) and white matter hyperintensity (WMH) burden on cranial magnetic resonance imaging (MRI) in the population-based Cardiovascular Health Study (CHS).

Methods:
Eligible CHS participants underwent one or two cranial MRI scans (~5 years apart) and aptamer-based SOMAScan platform measurement of up to 7288 plasma proteins concurrent with the initial MRI. cBI was defined by MRI signal characteristics and size ≥ 3 mm, and WMH burden was graded (WMG) 0 (least) to 9 (most severe). The relationship between 1-standard deviation increase in each log
2
-normalized plasma protein fluorescence was modeled separately with incident cBI and WMG worsening (≥1 grade increase) using multivariable relative risk regression, adjusting for demographics, estimated glomerular filtration rate (eGFR), and stroke risk factors. In secondary analyses, multivariable linear regression evaluated the cross-sectional relationship between each plasma protein with number of cBI and WMG on initial MRI. Bonferroni correction, based on the number of principal components that explained 99% of the protein fluorescence variance in CHS participants, accounted for multiple comparisons (p<2.1x10
-5
(0.05/2377)).

Results:
For eligible participants (n=2615), mean age was 74.4 ± 4.9 years, 61.7% were women, and 16.4% were Black. After adjustment for demographics, eGFR, and stroke risk factors, multiple circulating proteins were associated with cBI and WMG (Table).

Conclusion:
Multiple plasma proteins - implicated in systemic inflammation, fatty acid metabolism, neuronal adhesion/migration, and cellular cytoskeletal integrity/remodeling - were independently associated with cBI and WMG in a cohort of older adults.
Abstract WMP102: Diabetes-Related Polygenic Risk Is Associated With Poor Glycemic Control And Higher Risk Of Acute Cardiovascular Events In Stroke Survivors
Authors: Demarais Zachariah , Conlon Carolyn , Huo Shufan , Rivier Cyprien , Renedo Daniela , Sheth Kevin N , Falcone Guido J
Published: February 2023

Introduction:
Though uncontrolled diabetes leads to recurrent cardiovascular events in stroke survivors, many don’t achieve appropriate glycemic control. We hypothesize an adverse polygenic risk profile leads to worse glycemic control and higher risk of recurrent cardiovascular events in stroke survivors.

Methods:
We conducted a population genetic study using data of stroke survivors enrolled in the UK Biobank and the Vitamin Intervention for Stroke Prevention (VISP) trial. In both studies, we modeled polygenic risk to diabetes through a polygenic risk score that included 462 single nucleotide polymorphisms known to associate with type 2 diabetes mellitus. Participants were stratified as low, intermediate, or high polygenic risk according to percentile values of this score (<20
th
, 20-80
th
and >80
th
percentile). We used multivariable linear, logistic, and Cox regression models to test for association between polygenic risk to diabetes and 1) hemoglobin A1c (HbA1c), 2) risk of treatment-resistant diabetes (HbA1c ≥7 despite pharmacological therapy), and 3) composite risk of recurrent stroke or coronary artery disease (CAD).

Results:
In 5,670 stroke survivors enrolled in the UK Biobank (mean age 61, 41% females), a higher polygenic risk to diabetes was associated with higher HbA1c in both participants with and without diabetes, and with higher risk of treatment-resistant diabetes (all p<0.05, see Table). In 1,750 stroke survivors (mean age 68, 35% female 34) enrolled in VISP, a higher polygenic risk to diabetes was associated with higher composite risk of recurrent stroke or CAD (p<0.05, see Table).

Conclusions:
Among stroke survivors, a higher polygenic risk to diabetes is associated with worse glycemic control and higher risk of recurrent acute vascular events. Further research is needed to evaluate the portability of these results to non-white individuals and identify specific medications that may be more effective in patients with adverse genomic profiles.
Abstract WMP114: Changes In Gut Microbiome Precede Cognitive Impairment In A Mouse Model Of Vascular Cognitive Impairment And Dementia
Authors: Venna Venugopal Reddy , Maniskas Michael E , Quaicoe Victoria , Petrosino Joseph , McCullough Louise D
Published: February 2023

Introduction:
Vascular cognitive impairment (VCI) is the second most common cause of clinical dementia after Alzheimer’s disease. VCI results from injury to the cerebral blood vessels. Cerebral perfusion is diminished in elderly individuals and additional reduction of cerebral blood flow increases the risk of developing VCI. These findings have been successfully modeled in mice with bilateral common carotid artery stenosis (BCAS). Age is associated with gut dysbiosis and transplantation of aged microbiome leads to cognitive decline in young animals. However, there are large gaps in our understanding of the molecular mechanisms induced by chronic hypoperfusion contributes to impaired cognitive function.

Methods:
C57Bl6 aged (~18m) male mice were subjected to a sham or a BCAS surgery using 0.18mm titanium coils placed on both common carotid arteries. Mice were followed for 90d after surgery to assess both gut microbial content and behavioral changes. 16S ribosomal RNA (rRNA) sequencing analysis was performed on fecal samples collected from aged baseline, sham and BCAS animals at 7 and 28 days. Cognition was assessed using Y-maze. Tissues were collected at the time of euthanasia for metabolomics and histological analysis.

Results:
BCAS resulted in significant reduction of cerebral blood flow, measured using laser speckle (p<0.05; n=4/grp; t test). 16s rRNA analysis revealed BCAS led to a remarkable shift in bacterial diversity as early as day 7 in aged male mice, measured by using unweighted UniFrac analysis. These differences remained significant (p<0.05; n=4/grp) in BCAS compared to sham mice on day 28. In depth analysis revealed significant changes at the genus level between both groups. Interestingly, BCAS mice did not show significant difference in Y-maze at day 14, but significant cognitive impairment was found at day 90 compared to sham mice (n=8-9/grp).

Conclusions:
We found that chronic cerebral hypoperfusion is associated with significant changes in gut microbiome and cognitive impairment in aged mice. Importantly, shifts in the microbiome preceded cognitive decline. These findings suggest that targeting these detrimental changes in the gut microbiome might be a novel therapeutic strategy to delay or prevent progression of VCI.
Abstract WMP119: Novel Therapeutic Potential Of Intestinal Stem Cell Transplants For Ameliorating The Long Term Effects Of Cerebrovascular Stroke
Authors: Mani Kathiresh Kumar , El-Hakim Yumna , Sohrabji Farida , Branyan Taylor , Samiya Nadia T
Published: February 2023

Background:
Stroke is a leading cause of disability and dementia with limited treatment options. Evidence suggests that stroke rapidly dysregulates the intestinal epithelium, causing a ‘leaky gut’ and elevated blood levels of inflammatory cytokines.

Hypothesis:
In view of the emerging evidence of the gut-brain connection, we tested whether early repair of the gut after ischemic stroke would prevent stroke-induced cognitive impairment.

Methods:
Adult and middle-aged Sprague-Dawley female and male rats were used for this study and assigned to the following groups: Control (sham), stroke with sham transplant (vehicle), or stroke with IESC transplantation. Rats were subjected to stereotaxic middle cerebral artery occlusion (MCAo) using Endothelin-1 (vasoconstrictor). Primary IESCs were isolated from young female and male rats to prepare organoid cultures. Dispersed organoid cells were labeled with PKH67 and injected iv 4h/24h/48h to middle aged hosts after stroke. Behavioral assessments were performed before stroke and 4 weeks after stroke. This included tests for depressive-like behaviors(Burrowing test and the Social Interaction test). Cognitive performance (Novel object Recognition test and Barnes maze test), which assess declarative and visuospatial memory respectively.

Results:
Vehicle-treated MCAo animals displayed depressive-like behaviors compared to their pre-stroke performance. In contrast, stroke animals that received IESC transplants showed were no different from their pre-stroke performance and no different from sham (no-stroke animals). A similar pattern was seen in tests of cognition. MCAo+vehicle animals showed poor ability to discriminate the novel object and displayed impaired learning and recall on the Barnes maze. In both tests, MCAo animals + IESC transplants animals were not impaired and had similar performance to the Sham (no stroke) group. MCAo caused a persistent elevation of the gut metabolite LPS and the inflammatory cytokine IL-17A, which was abated by IESC treatment.

Conclusion:
Overall, these data show that an intestinal stem cell population derived from a healthy young animal transferred to an older host after stroke can significantly improve long term behavior stroke outcomes.
Abstract WMP26: Acute Left Superior Temporal Damage Results In Phonological Errors In Word Comprehension
Authors: Chu Brian , Satoskar Sanika , Hillis Argye E
Published: February 2023

Right hemisphere deactivation by right carotid injection of sodium amytal (Wada testing) in chronic epilepsy results in few phonological errors in word comprehension. Based on this finding, recent models of language processing indicate that speech sound and spoken word processing is bilateral, so that unilateral stroke should not affect distinguishing phonologically similar words (e.g. boat/note) for word comprehension. We tested the alternative hypothesis that acute left hemisphere stroke in superior temporal gyrus (STG) results in phonological errors in a word-picture verification task, which would support the proposal that the right hemisphere does not support speech sound processing and word comprehension before recovery through reorganization of structure/function relationships.

Methods:
A series of 218 participants were tested with a word-picture verification test with targets and phonologically similar words and had brain MRI within 4 days of stroke onset. We evaluated associations between any damage to left STG and phonological errors using chi square, and the correlation between degree of damage to STG and number of errors using Spearman Rho.

Results:
We found a very strong association between infarct in left STG and the production of phonological errors in word comprehension (chi squared= 31.2; p <0.00001). Furthermore, the number of phonological errors was strongly correlated with the degree of infarct in left STG (rho=0.49; p<0.00001). Results indicate that left STG, when acutely damaged, often results in phonological errors in word comprehension. These results indicate that the paucity of such errors in comprehension in studies of chronic left hemisphere stroke or Wada testing is a result of reorganization following chronic left temporal dysfunction. Patients with acute left STG stroke should be tested with sensitive tests for word comprehension deficits, including phonologically similar words, before giving verbal direction on exam or obtaining informed consent for procedures.
Abstract WMP31: Lifetime Stress, Acute Stress, And Long-term Outcomes After Stroke: A Longitudinal Study
Authors: Holman Alison , Cramer Steven C ,   STRONG Study Team
Published: February 2023

Background:
Stroke is a sudden-onset, unexpected life event over which individuals have little control. These features can make the experience of having a stroke extremely stressful, which may potentiate its debilitating effects. We previously identified short-term associations among lifetime stress/trauma exposure (LSE), post-stroke acute stress (AS), Modified Rankin Scale (mRS) and Fugl-Meyer at 90 days post-stroke. However, their association with long-term stroke-related disability remains unknown.

Hypothesis:
Higher lifetime trauma and AS symptoms will be associated with poorer long-term disability 1-year post stroke.

Method:
Multi-site national study of patients admitted for a new stroke. Assessments included Acute Stress Disorder Interview 2-10 days post-stroke, LSE 90 days post-stroke, and Stroke Impact Scale (SIS), modified Rankin Scale (mRS), & Telephone Montreal Cognitive Assessment (tMOCA) at 1-year post-stroke. Structural Equation Modeling examined relationships among LSE, AS, and outcomes, controlling for admission NIHSS score and demographics.
Results:
Among key predictors and covariates (demographics, acute NIHSS), AS immediately post-stroke was the strongest direct correlate of poorer mRS scores and SIS scores at 1-year (
p
s < .001), and the second strongest direct correlate of tMOCA scores at 1-year; higher d90 LSE was directly associated with poorer SIS (
p
< .001), and indirectly associated with poorer mRS, SIS, & tMOCA scores at 1-year (all
p
s < .001) through its association with high AS (
p
< .001) at admission.

Conclusion:
Lifetime stress and stress symptoms in the acute stroke setting are both associated with disability and cognitive impairment 12 months post-stroke; their assessment may be useful to facilitate early identification of high-risk patients and development of interventions that help improve functional and cognitive outcomes after stroke.
Abstract WMP41: Changes In Stroke Mortality Among Black And White Persons Before And During Covid-19 Pandemic, United States 2015-2021
Authors: Yang Quanhe , Tong Xin , Merritt Robert K
Published: February 2023

Introduction:
Although stroke death rates declined since 1950s, age-adjusted rates remained higher among non-Hispanic Black (NHB) than among non-Hispanic White (NHW) persons. No study has examined changes in disparities of stroke mortality among NHB and NHW before and during the COVID-19 pandemic.

Methods:
We calculated age-adjusted (US 2000 population) stroke death rates per 100,000 people among NHB and NHW ages ≥35 years from 2015-2021 using CDC WONDER. We compared NHB and NHW stroke death rates from 2015-2019 (before pandemic) to 2020-2021 (during pandemic) with respect to changes in rates, rate ratios (RR) and difference-in-difference in rates.

Results:
Trends and disparities of overall stroke death rates before the pandemic remained consistent between NHB (100.9 to 101.6 per 100,000 people) and NHW (69.1 to 70.6 per 100,000 people), with an average difference in rates of 31.3/100,000 and RR of 1.45. During the pandemic, stroke death rates increased but with different magnitudes among NHB (110.0 and 113.4 per 100,000) and NHW (72.0 and 73.1 per 100,000). Between pre-pandemic and pandemic periods, the absolute difference in rates increased 25% from 31.3 (95% confidence interval 30.8-31.7) to 39.1 (38.3-39.8) per 100,000 and the relative difference measured by RR increased from 1.45 (1.44-1.46) to 1.54 (1.53-1.55) (p<0.001). The difference-in-difference in rates and RR comparing before to during pandemic were 7.8 per 100,000 and 1.06, respectively, indicating widened disparities in stroke death rates (p<0.001) (Figure). During the pandemic (2020-2021), estimated excess stroke deaths was 4,030 among NHB (9.9% more than expected deaths) and 11,790 among NHW (5.3% more than expected deaths).

Conclusion:
Disparities in stroke death rates between NHB and NHW widened during the COVID-19 pandemic in the United States. Identifying factors associated with the widened disparities and providing the targeted interventions may be necessary to reduce the disparities.
Abstract WMP44: Feasibility Of Monitoring Door-in-door-out Across A Fourteen Hospital Telemedicine Supported Stroke System Of Care
Authors: Rho Howard J , Cheng Pamela , Sangha Navdeep S
Published: February 2023

Background:
Door-In-Door-Out (DIDO) times are crucial to help improve outcomes for patients presenting to Primary Stroke Centers (PSCs) needing urgent endovascular therapy. However, DIDO is often a difficult measure to track and improve due to relatively low volumes at a single stroke program. Healthcare networks hold a significant advantage through standardization of processes which then allow for aggregate data collection.

Methods:
We designed a system that went live 1/2021 using PowerBI™ and Microsoft Suite™ products to monitor DIDO across 13 PSCs. Data queries from existing centralized stroke data were modeled together with internal transport team data into one report resulting in an interactive chart used to track DIDO and its related performance measures including: door to transfer center contact time (DTCC), door to ambulance arrival time (DAA), ambulance arrival to ambulance departure Time (AAAD) and reasons for delayed transfer. Data was analyzed using Wilcoxon Rank Sum test.

Results:
Metrics were assessed pre (1/1/2021-3/31/2021) and post (4/1/2021-12/31/2021) implementation of a dashboard guided process improvement. There were 32 transfers pre vs. 86 post-implementation. Median DIDO improved: (Pre: 120 min {IQR:82-146} vs. post: 86 min {IQR: 62-108} p=0.004). Other sub-metrics of DIDO all improved: Median DTCC (Pre: 55 min {IQR:32-76} vs. post: 38 min {IQR: 22-53} p=0.032); median DAA (Pre: 89 min {IQR:68-126} vs. post: 67 min {IQR: 43-84} p=0.041). There was a trend to improvement for the median AAAD: (Pre: 24 min {IQR:12-36} vs. post: 19 min {IQR: 10-24} p=0.054).

Conclusion:
Relatively low volume but high-risk events like DIDO transfers can be improved by leveraging the use of modern data display and analysis software solutions that process the collective data aggregate generated from standardized workflows across a health care network.
Abstract WMP46: Impact Of Poverty On Stroke Incidence And Recurrence: A Population-based Study
Authors: Becker Christopher J , Kissela Brett , Sucharew Heidi , Alwell Kathleen , Robinson David , Woo Daniel , De Los Rios La Rosa Felipe , Mackey Jason , Ferioli Simona , Mistry Eva , Demel Stacie L , Haverbusch Mary , Coleman Elisheva R , Jasne Adam , Slavin Sabreena , Walsh Kyle B , Star Michael , MARTINI SHARYL , Flaherty Matthew L , Kleindorfer Dawn O
Published: February 2023

Background:
Poorer socioeconomic status (SES) is associated with higher stroke incidence. Less is known about SES and stroke recurrence. We sought to obtain updated estimates of stroke incidence stratified by aggregate measures of SES, and to explore the association between SES and stroke recurrence.

Methods:
The Greater Cincinnati/Northern Kentucky region includes a population of 1.3 million, representative of the US population in terms of sociodemographics and percent black race. We ascertained all hospitalized strokes in the region in 2015 by screening ICD-9 codes 430-437 and ICD-10 codes I60-69, G45-46. Recurrent strokes were ascertained from 1/1/2015-12/31/2018. Patients’ home addresses were geocoded using DeGAUSS. Population estimates were obtained from the US Census Bureau using the 2015 5-year American Community Survey. Aggregate SES was estimated by percentage below poverty in each census tract. Regional incidence and recurrence rates were adjusted for age, sex, and race and calculated both with and without SES adjustment using Poisson regression models.

Results:
Stroke incidence and recurrence rates stratified by SES are shown in the Table. Poorer SES was associated with greater stroke incidence (p<0.01) and recurrence (p<0.01) across races. The relative risk (95% CI) for first-ever stroke among black compared with nonblack individuals was 2.06 (1.79-2.38) before adjusting for SES, and 1.79 (1.54-2.08) after adjusting for SES. The relative risk (95% CI) for recurrent stroke among black compared with nonblack individuals was 2.54 (1.91-3.37) before adjusting for SES, and 2.00 (1.47-2.74) after adjusting for SES. There was no race by SES interaction.

Conclusions:
Poorer SES was associated with increased risk for both incident and recurrent stroke across races. Of the excess risk for stroke incidence among black individuals, 25.5% was accounted for by SES, while 35.1% of the excess risk for recurrence was accounted for by SES.