bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TP242: Risk of symptomatic intracranial hemorrhage after mechanical thrombectomy in randomized clinical trials: A systematic review and meta-analysis
Authors: Reda Abdullah , Ghozy Sherief , Gajjar Aryan , Kallmes David F , Rabinstein Alejandro
Published: January 2025

Background:
Symptomatic intracranial hemorrhage (sICH) is the most dreaded complication after reperfusion therapy for acute ischemic stroke. We performed a meta-analysis of randomized controlled trials to estimate and compare risks of sICH after mechanical thrombectomy (MT) depending on the location of the large vessel occlusion, concomitant use of intravenous thrombolysis, timing of treatment, and core size.

Methods:
Randomized controlled trials were included following a comprehensive search strategy on different databases from inception to March 1, 2024. Random-effect models in a meta-analysis were employed to get the pooled risk ratios (RRs) and their corresponding 95% confidence intervals (95% CI) for sICH with MT, compared to other reperfusion treatment regimens, including best medical treatment and intravenous thrombolysis (IVT).

Results:
MT in the anterior circulation was associated with a significantly higher risk of sICH as compared with no-MT (RR: 1.46; 95%CI: 1.03-2.07; P = 0.037). Risk of sICH was comparable between the MT and MT+IVT groups (RR: 0.77; 95%CI: 0.57-1.03; P = 0.079). There was no difference in sICH risk with MT as compared with no-MT within 6 hours of last known well (RR: 1.14; 95%CI: 0.78-1.66; P = 0.485) and beyond that time (RR: 1.29; 95%CI: 0.80-2.08; P = 0.252); the risk of sICH was also comparable between MT conducted within 6 hours of last known well and MT conducted beyond that time (P = 0.512). The sICH risk for MT in the posterior circulation (RR: 7.48; 95%CI: 2.27-24.61) was significantly higher than for MT in the anterior circulation (RR: 1.18; 95%CI: 0.90-1.56) (P = 0.003). MT was also associated with a significantly higher sICH risk than no-MT among patients with large-core strokes (RR: 1.71; 95%CI: 1.09-2.66, P = 0.018).

Conclusion:
When evaluating cumulative evidence from randomized controlled trials, the risk of sICH is increased after MT compared with patients not treated with MT. Yet, the difference is largely driven by the greater risk of sICH in patients treated with MT for posterior circulation occlusions and, to a lesser degree, large core strokes. Concomitant use of intravenous thrombolysis and the use of MT in the extended therapeutic window do not raise the risk of sICH.
Abstract TP244: Coil Embolization or Clipping for Elderly Patients with Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis
Authors: Rossi Yohanna , Bolner Gabriel , Costa Dall'Acqua Jonathan , Dolovitsch de Oliveira Fabiana , Vincenzi Zacaria Lucas , Denicol Taís Luise
Published: January 2025

Introduction:
Although older patients with subarachnoid hemorrhage (SAH) are often preferentially treated with coiling, in practice, there are insufficient data to support a clear benefit of coiling in this population. We aimed to do a meta-analysis comparing clipping with coil embolization for treatment of SAH in elderly people.

Methods:
We systematically searched Pubmed, Embase and Cochrane databases for studies that compared clipping with coiling for treatment of patients ≥ 60 years old with SAH. Our main endpoint was a compound unfavorable outcome that included Modified Rankin Score (mRS) >2, Glasgow Outcome Scale (GOS) < 4, death or dependency. Other endpoints were an unfavorable outcome in the GOS, mortality and a favorable outcome in the mRS separately. Heterogeneity was assessed with I
2
statistics.

Results:
We included 25 studies, two randomized, with a total of 49,540 patients, of whom 19,263 (38.8%) were treated with coil embolization. In pooled analysis, there was no statistical difference in the compound unfavorable outcome (RR 1.06; 95%CI 0.79-1.01; p = 0.15; I
2
=56%), GOS (RR 0.88; 95%CI 0.68- 1.14; p = 0.02; I
2
= 55%) and mRS (RR 0.97; 95%CI 0.88- 1.08; p = 0.61; I
2
= 20%). However, all-cause mortality was more common in patients treated with coiling (RR 1.14; 95%CI 1.01- 1.28; p = 0.03; I
2
= 35%). In randomized studies, although not significant, the point estimate seems to favor coiling whereas in observational studies it happened to clipping.

Conclusions:
The results of our meta-analysis suggest that clipping is a better treatment for SAH in elderly patients regarding all-cause mortality. Otherwise, the endpoints GOS, mRS and compound unfavorable outcome didn't show significant difference between the groups.
Abstract TP250: Comparative Utility of CT and MRI in Initial Imaging for Mechanical Thrombectomy in Patients with Large Vessel Occlusion
Authors: Ueda Toshihiro , TAKEUCHI MASATAKA , MORIMOTO MASAFUMI , Yamamoto Ryoo , Tsuboi Yoshifumi , SHOGO KAKU , Ito Hidemichi , Onodera Hidetaka , Tatsuno Kentaro , Usuki Noriko , Takaishi Satoshi , Murata Hidetoshi , Yamano Yoshihisa
Published: January 2025

Background:
Computed tomography (CT) is globally recognized as the standard initial imaging modality for mechanical thrombectomy (MT) in large vessel occlusion (LVO). However, in Japan, many institutions prefer magnetic resonance imaging (MRI). This study aimed to evaluate and compare clinical outcomes between patients who underwent MT based on whether CT or MRI was used as the initial imaging modality, as documented in the K-NET registry.

Methods:
The K-NET registry is a prospective collection of MT cases for LVO, involving 40 Japanese institutions. Data from 3,182 cases registered between 2018 and 2021 were analyzed. These cases were categorized into three groups: MRI alone (MRI group, n=1,265), CT alone (CT group, n=830), and both modalities (Combined group, n=1,087). The primary outcome measured was the proportion of patients achieving a modified Rankin Scale (mRS) score of 0-2 at 90 days post-procedure. Secondary outcomes included onset-to-door time (OTD), door-to-image time (DTI), door-to-puncture time (DTP), puncture-to-recanalization time (PTR), and the incidence of intracranial hemorrhage (ICH), symptomatic ICH, and mortality.

Results:
The median ages were 77 years for the MRI group, and 79 years for both the CT and Combined groups. Initial NIHSS scores were lower in the MRI group (median 17) compared to the CT (19) and Combined (18) groups. The MRI group exhibited a significantly longer OTD (71 mins) than the CT (57 mins) and Combined (60 mins) groups. Conversely, DTI was similar across groups (14, 10, and 17 mins, respectively), while DTP was notably shorter in the MRI group (52 mins) compared to the CT (62 mins) and Combined (97 mins) groups. The MRI group also demonstrated a shorter PTR (37 mins) relative to the CT (53 mins) and Combined (56 mins) groups. While the MRI group had a higher overall incidence of ICH (21%), symptomatic ICH rates did not differ significantly across groups. The proportion of patients achieving an mRS score of 0-2 at 90 days was significantly greater in the MRI group (43%) compared to the CT and Combined groups (both 39%).

Conclusions:
Patients in the MRI group were significantly younger and presented with lower NIHSS scores compared to those in the CT and Combined groups. Despite a longer OTD, the MRI group experienced shorter DTP and PTR, ultimately achieving better clinical outcomes at 90 days. However, the differences in baseline characteristics across the groups necessitate careful interpretation of these findings.
Abstract TP266: Vascular disease risk and increased adherence to remote blood pressure monitoring. Data from the Skills-Based Educational strategies for Reduction of Vascular Events in Orange County, Ca (SERVE OC) Trial
Authors: Kurzman Alissa , Albala Bruce , Ding Xueting , Valenti Emma , Gutierrez Desiree , Chavez Aryanna , Wing Jeffrey , Draughter Darnisha , Cardenas Cassandra , Huynh Julie , Porron Joceline , Boden Bernadette
Published: January 2025

Background:
Stroke is the 5
th
leading cause of death in the U.S. contributing to ≥$56 billion in annual healthcare costs. Effective blood pressure (BP) management is crucial for reducing stroke and CVD risk, yet controlled hypertension remains suboptimal especially among minority populations. Technological advancements such as remote blood pressure monitoring (RPBM) devices are promising tools to enhance BP management and reduce risk of primary and secondary stroke/CVD. This study aims to examine the association between RBPM adherence and vascular disease risk plus other demographic factors in Latino and Vietnamese individuals living in Southern California.

Methods:
Baseline data from the Skills Based Education strategies for Reduction of Vascular Events in Orange County (SERVE OC) RCT were used (Grant: P50MD017366). The SERVE OC intervention compares the efficacy of a community health worker led, family-based health management approach focused on skill-building, risk perception, and goal setting versus self-management in reducing BP and enhancing AHA Life’s Essential 8 scores. All households with adult participants ≥18 years were trained and given a RBPM device with instructions to take their BP remotely at least 1x/week. ANOVA and t-tests were conducted to assess the association between RBPM adherence and vascular risk, demographic factors and intervention exposure.

Results:
Among the 322 randomized adults in the study, 151 adults had 2+ RBPM readings indicating at least one RBPM reading was taken at home in addition to the in-clinic baseline training session, a primary factor for inclusion (Figure 1). Of the 151 adults included (Table 1), the average age was 48.9 (SD=15.8); 63.8% were female, 76.2% identified as Latino and 81.2% had access to healthcare. Risk factors included history of hypertension (37.1%), heart disease (5.6%), stroke (2.1%), and diabetes (29.1%). 44.1% of adults had elevated risk (44.1%) and 7.0% were high risk. Vascular risk (VR) levels and having high VR were significantly associated with higher adherence to RBPM (Mean % of weeks: Low VR: 15.53 weeks; Elevated VR: 15.90 weeks High VR: 29.59 weeks).

Conclusion:
Our findings suggest that RBPM in at-risk adults may be a feasible and important prevention strategy for stroke and CVD prevention. Further research is needed to better understand barriers and facilitators of using RBPM devices, especially among minority populations who are at higher risk for vascular disease.
Abstract TP267: Effects of Exposure to Chemical Components of Fine Particulate Matter on Ischemic Stroke: A Case-Crossover Study
Authors: Matsuo Ryu , Michikawa Takehiro , Yoshino Ayako , Takami Akinori , Ago Tetsuro , Kitazono Takanari , Kamouchi Masahiro
Published: January 2025

Introduction:
We previously reported that acute exposure to fine particulate matter (PM
2.5
) within one day before the onset (lag days 0-1) is linked to ischemic stroke events. This study aimed to examine the association between specific components of PM
2.5
and the occurrence of ischemic stroke.

Methods:
Toral of 5,872 patients with acute ischemic stroke enrolled in a multicenter, hospital-based stroke registry in Fukuoka, Japan. All patients were previously independent and were hospitalized within 24 hours of stroke onset between November 2013 and September 2019. We collected data on daily mean concentrations of PM
2.5
and its specific chemical components that were measured aerosol speciation analyzers (ACSA, Kimoto Electric Co., Ltd) within Fukuoka city —including optical black carbon, water-soluble organic compounds, nitrate ion, and sulfate ion. The time of symptom onset was confirmed, and the association between these specific PM
2.5
components and ischemic stroke occurrence was analyzed using a time-stratified case-crossover design and a conditional logistic regression model.

Results and Conclusions:
Ambient PM
2.5
at lag days 0 to 1 was not associated with the subsequent occurrence of ischemic stroke (percent increase for ischemic stroke per 10 μg/m
3
PM
2.5
[95% confidence interval]: 2.7 [-2.7 to 8.3]), after adjusting for ambient temperature, humidity, influenza epidemics, and PM
2.5
at lag days 2 to 3 and lag days 4 to 6. No significant association was found between the specific chemical components of PM
2.5
and ischemic stroke occurrence, either in a single-component model (percent increase for ischemic stroke [95% confidence interval]: optical black carbon, -7.3 [-24.7 to 14.2]; water-soluble organic carbon, -2.6 [-13.6 to 9.8]; nitrate ion, -3.6 [-9.5 to 2.7]; sulfate ion, -0.3 [-3.0 to 2.5]) or in a multicomponent model (percent increase for ischemic stroke [95% confidence interval]: optical black carbon, 0.6 [-23.7 to 32.6]; water-soluble organic carbon, 5.1 [-14.8 to 29.7]; nitrate ion, -6.5 [-16.3 to 4.4]; sulfate ion, 5.1 [-3.1 to 4.0]). These results were consistent across different age groups, sexes, and ischemic stroke etiologies.

In conclusions, these findings suggest that short-term exposure to specific chemical components of PM
2.5
within 1 day before onset is not associated with the subsequent occurrence of ischemic stroke. Further studies are warranted to clarify the effects of PM
2.5
on ischemic stroke occurrence.
Abstract TP282: Hypertension Control in Individuals with Previous Stroke: data from ELSI-Brazil study
Authors: Trombin Marques Marina , M. R. Pinho Pedro J , Sadala Reges Danyelle , Rocha Eva
Published: January 2025

Introduction:
Cerebrovascular diseases are the second leading cause of death and the third cause of disability worldwide. The main risk factor is hypertension, and blood pressure (BP) control is crucial in the primary and secondary prevention of stroke. We studied the prevalence of stroke and hypertension control in a representative cohort of the Brazilian population over 50 years and the factors related to uncontrolled hypertension in individuals with previous stroke.

Methods:
We performed a retrospective analysis of the ELSI-Brazil study, a nationally representative sample of adults aged 50 and over, including 9412 individuals. Individuals self-reported previous medical history of stroke (including TIA, ischemic and hemorrhagic stroke), hypertension, medication intake, and other vascular risk factors. The BP was measured three times with a 2-minute interval under adequate conditions. The 2020 AHA Guideline was used to define hypertension and target BP. Statistical analysis was performed using STATA/SE 17.0 software. A logistic regression analysis was performed to study the variables associated with uncontrolled hypertension in individuals with previous stroke.

Results:
From the total sample, 536 (5.3%) reported previous stroke, 255 (51.4%) were male, with mean age of 68.3 (SD 10.6). The systolic BP was higher among individuals with previous stroke (p=0.003). Uncontrolled BP was observed in 60.9% of individuals with previous stroke. High blood pressure levels were detected in 13.2% of individuals with previous stroke who did not report a prior diagnosis of hypertension. In the logistic regression model, younger age and lower education levels were related to uncontrolled hypertension in individuals with previous stroke. Undiagnosed hypertension was associated with higher education, not having a medical appointment in the last year, and not having private health insurance.

Conclusion:
More than half of individuals with a previous stroke have uncontrolled hypertension, which is associated with lower education and younger age in the Brazilian elderly population. Undiagnosed hypertension is related to not having a medical appointment in the past year and the absence of private health insurance. Understanding the factors associated with uncontrolled hypertension is a crucial component of public health policies to decrease stroke recurrence in developing countries.
Abstract TP291: COVID-19 Infection is Associated with Stroke Subtype, Severity, and Outcomes in Patients with Acute Ischemic Stroke
Authors: Belits Anna , Salottolo Kristin , Wang Frank , Higgins Katie , Kim Diana , Rankine Ian , Pirahanchi Yasaman , Bar-Or David , Burrell Christian
Published: January 2025

Introduction:
In patients with severe COVID-19 infection there is an increased risk of cerebrovascular events, including acute ischemic stroke (AIS). In patients who present with COVID-19 infection and AIS, certain stroke subtypes have been reported with greater frequency. The objective of this study was to determine differences in patient demographics and stroke sub-type by COVID status at a US comprehensive stroke center.

Methods:
We retrospectively evaluated adults (≥18) with AIS admitted during the first year of the COVID pandemic (3/1/2020 – 3/1/2021). Demographics (age, sex, race, comorbidities with ≥5% incidence), stroke subtype (TOAST classification), severity (NIHSS), management (intravenous and intraarterial therapy [IVT and IAT]), and outcomes (in-hospital mortality and discharge modified Rankin scale [mRS]) were compared for patients who were COVID+ vs COVID– using Pearson chi-square tests.

Results:
Among 1,086 AIS patients, 475 (44%) were evaluated for COVID-19 infection during their inpatient stay. Most patients (94%) had PCR testing. Thirty-five (7%) patients were COVID+ and 441 (93%) were COVID–. There were significant differences in study covariates by COVID status, table 1. COVID+ patients had a greater proportion of cryptogenic strokes (62% vs. 32%, p<0.001), were more likely to report previous COVID infection (19% vs. 2%, p<0.001), were more likely to receive IVT (41% vs. 24%, p=0.03), and were less likely to be non-Hispanic white (53% vs. 71%, p=0.02) compared to COVID– patients. In-hospital mortality was significantly greater in COVID+ versus COVID– patients (12% vs. 4%, p=0.03); however, discharge mRS was not significantly different (p=0.08). When comparing symptomatic (n=10) and asymptomatic (n=24) COVID+ patients, symptomatic patients were more likely to present with severe stroke (NIHSS ≥21: 41% vs. 0%, p=0.03) and worse mRS (independent [0-2]: 17% vs. 60%, p=0.04); there were no other demographic or clinical differences by symptomatology.

Discussion:
In the setting of a widespread pandemic such as COVID-19, stroke etiology, severity, and clinical outcomes can differ significantly based on COVID status. These data suggest that patients with AIS and COVID were more likely to have cryptogenic stroke, higher mortality, and, in the case of symptomatic COVID, worse stroke severity and neurologic disability at discharge.
Abstract TP303: Identifying Risk factors for Major Adverse Cardiovascular Events (MACE) in Patients with Migraine: A Logistic Regression Analysis of Demographics, Comorbidities, and Brain Imaging Findings
Authors: Dumkrieger Gina , Dumitrascu Oana , Tariq Amara , Banerjee Imon , Schwedt Todd , Chong Catherine
Published: January 2025

Background:
Prior studies indicate a relationship between migraine and MACE. Here we assess whether brain white matter hyperintensities (WMH), which are a common imaging finding in patient with migraine, contribute to the risk of MACE above demographics and common risk factors for MACE.

Methods:
60,454 patients, ages 18-89, with a ICD-9 or ICD-10 migraine diagnosis code in 2010 or later were identified from the Mayo Clinic electronic health record. Only patients who were seen for migraine in the Neurology Department were included. Patients with a migraine diagnosis who did not have MACE were included only if they had at least two visits at Mayo Clinic during five years. Only patients with sex and race information were included. The final cohort included 577 migraine patients with and 598 migraine patients without MACE. Presence of WMH was determined from radiology notes. Individuals without a brain MRI were assumed not to have WMH. A logistic regression model that included sex, race, known lifetime MACE risk factors (atrial fibrillation, diabetes, hypertension, hyperlipidemia, tobacco use) and WMH as independent variables to predict MACE outcome was fit.

Results:
Significant factors that increased the risk of MACE in individuals with migraine included being Black or African American (adjusted OR: 2.9, 95% CI: 1.24-6.82, p = 0.014), presence of atrial fibrillation (adj. OR: 1.63, 95% CI: 1.23-2.17, p < 0.001), diabetes (adj. OR: 1.34, 95% CI: 1.02-1.75, p = 0.036), hypertension (adj. OR: 1.9, 95% CI: 1.39-2.6, p < 0.001), tobacco use (adj. OR: 1.66, 95% CI: 1.29-2.14, p < 0.001), and the presence of WMH (adj. OR: 1.43, 95% CI: 1.1-1.87, p = 0.008). Hyperlipidemia showed a marginal association (adj. OR: 1.34, 95% CI: 0.99-1.81, p = 0.061), while other variables such as sex and other racial/ethnic groups did not significantly alter the risk of MACE outcome.

Discussion:
Results indicate that African American race and presence of WMH in addition to common comorbidities independently increase the risk of MACE outcome.
Abstract TP304: Racial Disparities and Trends in Stroke-Related Mortality Among Infective Endocarditis Patients Aged 65 and Older in the United States and Texas: Insights from the CDC WONDER Database
Authors: Naz Sidra , Lohana Sameer , Hazique Mohammad , Wajid Zarghoona , Naz Hira
Published: January 2025

Introduction:
Stroke is a common complication of infective endocarditis (IE), affecting 16–25% of cases, and can be the initial or sole manifestation of the condition. This study aims to analyze annual mortality trends and demographic factors related to stroke in IE patients in the U.S. and Texas from 1999 to 2020, to guide public health initiatives and enhance prevention strategies.

Methods:
The data was analyzed from the CDC's WONDER database from 1999 to 2020, focusing on stroke and IE-related mortality (ICD-10 Code I64.0 “Stroke”&Code I33.0 “IE”) in adults aged ≥65 years, annual percent changes (APCs) in age-adjusted mortality rates (AAMRs) with 95% confidence intervals across various demographic (sex, race/ethnicity, age) subgroups was calculated.

Results:
The AAMR for stroke-related mortality in IE cases reduced in the US from an adjusted rate (AR) 448.7 in 1999 to 171.6 in 2018 (APC: -8.09%; 95% CI: -9.00% to -6.81%) and then it increased to 183.5 in 2020 (APC: 3.07%; 95% CI: 1.22% to 4.69%). In Texas, AAMR for stroke-associated IE-related mortality overall decreased from AR 485.7 in 1999 to 176.2 in 2020 (APC: -5.23%; 95% CI: -5.50% to -4.96%). Males had higher consistently higher AAMRs than females (196.4 vs. 172). The AAMR in the US men decreased from 468.6 in 1999 to 176.7 in 2018(APC: -7.55%; 95% CI: -8.51% to -6.21%), then it increased to 196.4 in 2020(APC: 4.99%; 95% CI: 2.93% to 6.81%). The AAMR in the US women decreased from 431.5 in 1999 to 165.6 in 2018(APC: -8.25%; 95% CI: -9.15% to -6.97%) after which it increased to 172 in 2020(APC: 1.48%; 95% CI: -0.31% to 3.06 %). The non-Hispanic (NH) Black or African American (AA) has the greatest AAMR (278.7), followed by the NH White with an AAMR (179) and the NH American Indian or Alaska Native population with an AAMR (165.4). The low-risk populations were the Hispanic or Latino (143.6) and the NH Asian or Pacific Islander (135.2). AAMR also varied by region (overall AAMR: Midwest: 200.8; South: 193.9; Northeast: 166.2; West: 162.8) and non-metropolitan areas had higher AAMR (non-core areas: 233.4; micropolitan areas: 224.5) than metropolitan areas (large fringe metro areas: 170.5; large central metropolitan areas:160.4).

Conclusions:
The stroke-related mortality in infective endocarditis cases has overall risen in the United States than in Texas over the past two decades, specifically men and (NH) Black or AA, (NH) White and (NH) American Indian or Alaska Native are at high risk.
Abstract TP308: The Impact of the Family and Lay Others on Care-Seeking During Stroke
Authors: Berner Marisa , Bediako Nana , Usmanov George , Dhongade Vrushali , Rothfeld-Wehrwein Zach , Johnson Ian , Peasley Emma , Lalwani Dheeraj , Champagne Alison , Sheth Kevin , Dhand Amar
Published: January 2025

Introduction:
The social environment plays an essential role in a patient’s arrival time to the hospital when experiencing medical emergencies. For stroke events an understanding of these socio-ecological factors may provide insight on eligibility for time-based interventions. This study aimed to assess the relationship between the first person made aware during a stroke and the impact on a patient’s hospital arrival timeliness.

Methods:
Time is Brain is a multi-center observational study assessing the role of social network mechanisms involved in delays to the hospital. As part of this study, we enrolled patients who had an acute stroke syndrome within the past seven days and received hospital care at either Mass General Brigham or Yale New Haven Hospital. We collected data on the social circumstances and the decision-making during the acute stroke in the community. We asked participants: 1. Did you tell anyone about your symptoms? 2. If yes, who did you tell about these symptoms? 3. Did anyone other than yourself notice symptoms? 4. If yes, who noticed your symptoms? We combined the responses for these questions into the first person aware of symptoms. The categories for people first aware were family members, spouse, co-worker/friend/stranger, and no one made aware. Here, we describe the median last known well to hospital arrival time and the median symptom onset to hospital arrival for each of these categories.

Results:
In 181 patients, we found that 72 (39.6%) individuals identified a spouse, 51 (28.2%) identified a family member, 33 (18.2%) identified a co-worker, friend, or stranger, and 25 (13.8%) did identified no one. Patients who reached out to friends, co-workers, or strangers had a median last known well to hospital arrival time of 180 minutes and a median symptom onset to hospital arrival time of 92 minutes. In contrast, arrival times were longest for those who contacted family with a median last known well to hospital arrival time of 615 minutes and median symptom onset to hospital arrival time of 120 minutes.

Conclusion:
The decision to seek care during stroke usually includes family or lay others. This preliminary analysis suggests that who is involved may influence the time to arrival to the hospital and ultimately improve individual stroke recovery. When considering how to improve arrival times, this multi-person decision-making process should be a factor in intervention development.
Abstract TP319: Areas of Persistent Longitudinal Lending Discrimination are Associated with Stroke Prevalence
Authors: Wing Jeffrey , Meier Helen , Rajczyk Jenna
Published: January 2025

Introduction:
Residential segregation influences individual health outcomes across the life course. Historic and modern racist lending practices, a form of structural racism, have contributed to residential segregation. Using historic and contemporary measures, we investigated whether longitudinal lending discrimination was associated with stroke prevalence in the U.S.

Methods:
We used a historic redlining index which linked Home Owners’ Loan Corporation (HOLC) maps to 2010 census tract boundaries to measure the degree of redlining (ranging from best [1] to hazardous [4]). Historic redlining data was combined with current lending discrimination (Home Mortgage Disclosures Act) to assess perceived area lending risk over time. Historic redlining index was dichotomized at the 25
th
percentile, and paired with modern lending discrimination measure to create a 4-level categorical measure of lending trajectory: (1) persistent discrimination- high levels of redlining¤t discrimination; (2) growing investment- high levels of redlining&no current discrimination; (3) declining investment- low levels of redlining¤t discrimination; and (4) no discrimination- low levels of redlining&no current discrimination. Census tract stroke prevalence was estimated using 2021 CDC PLACES data. ANOVA was used to measure the differences between categories of longitudinal lending discrimination.

Results:
Total of 68172 census tracts had stroke prevalence estimates; of those 10351 were HOLC graded. Nearly half (47%) of graded census tracts had persistent discrimination and tracts with persistent discrimination were younger, less non-Hispanic white, and had higher proportions of diabetes, obesity and hypertension (Table). Stroke prevalence was 1.59% (95% CI:1.50-1.69) higher in tracts with persistent discrimination compared to tracts with no discrimination. Stroke prevalence was also higher in tracts with declining investment (1.40%; 95% CI: 1.18-1.63%) however, tracts that had growing investment had only slightly higher stroke prevalence (0.27%; 95% CI: 0.18-0.37%) compared to tracts with no discrimination. Visual geospatial correlation is shown between stroke and persistent discrimination in New York City (Figure).

Conclusions:
Areas with persistent lending discrimination for the last 80-90 years are associated with higher stroke prevalence. The influence of the historical and modern social environment in which one resides influences the burden of stroke in a community.
Abstract TP325: Incidence and Cardiometabolic Risk Factors For Strokes in The Cameron County Hispanic Cohort
Authors: Musfee Fadi , North Kari , Fisher-hoch Susan , McCormick Joseph B , Savitz Sean
Published: January 2025

Introduction:
The Cameron County Hispanic Cohort (CCHC) represents a random sample of the Hispanic community residing in Cameron County, Texas. Participants were invited, regardless of their medical history, to participate every five years and went through extensive interviews and laboratory workout. This is the first report on the incidence of stroke in this cohort and provides a comprehensive examination for the associations between strokes and several cardiometabolic indicators.

Methods:
We conducted a case-cohort analysis to measure the associations between incident stroke and several cardiometabolic risk factors in the CCHC. Strokes were self-reported and we exclude subjects who reported strokes at their first visit as well as those who did not report on their stroke status. Chi square and Student t-test were used to test for univariate associations of several cardiometabolic indicators with incident strokes. We ran logistic regression models to estimate the associations of several cardiometabolic indicators with incident strokes after adjusting for age, diabetes, and hypertension. We used multiple imputation to estimate missing values for variables with more than 25% missingness. All analyses were conducted in R software (version 4.4.2)

Results:
The cumulative incidence for strokes was 0.02 (87 out of 4692 subjects). Those who presented with incident strokes were older (mean(sd): 61.4 (13.9) vs. 45.3 (15.9)), more likely to be diabetic (44 (50.6%) vs. 759 (16.5%)), and hypertensive (58 (66.7%) vs. 1194 (25.9%)), have higher inflammatory profile (e.g., C-Reactive Protein) (11.0 (26.3)vs. 7.92 (14.8)), thicker carotid intima (0.796 (0.250) vs. 0.681 (0.179)), lower left ventricular ejection fraction (60.8 (8.69) vs. 63.9 (4.89)), and higher left ventricular mass (159 (45.7) vs. 141 (36.9)) when compared to those without strokes at baseline. Adjusted logistic regression models comparing those with strokes to those without strokes at baseline showed that Low Density Lipoprotein (OR: 0.99, 95%CI: 0.98 - 0.99) and metabolic syndrome (OR: 0.53, 95%CI: 0.33-0.84) to be significantly associated (p <0.05) with incident stroke.

Conclusion:
This is the first analysis for incident strokes in this population which consists mostly (about 82%) of young (<65-year-old) Mexican Americans. Our longitudinal study design provided robust results; however, the small sample size may have limited our ability to detect important signals in our multivariate logistic models.
Abstract TP331: Building Stroke Awareness: A Nationwide Rollout of the FAST Heroes Program in Czech Schools
Authors: Svobodova Veronika , Prazakova Lucie , Bedrichova Zuzana , Marsalkova Hana , Mikulik Robert
Published: January 2025

Introduction:
FAST Heroes is an international awareness campaign. Its mission is to teach 1 million children worldwide to recognize a stroke and respond correctly. The campaign has been developed and sponsored by ANGELS Initiative and is implemented in 38 countries. The education of the pupils takes five lessons in five weeks. Each country follows its own implementation plan. Here, we present the implementation practice of the Czech Republic.

Methodology:
The campaign was conducted in 10 of the 14 regions in the Czech Republic. Schools with primary grades and kindergartens were selected from public school databases and all of them were directly contacted using low and middle intensity recruitment strategy. A low-intensity recruitment used communication with emails or letters with no follow up. Middle intensity recruitment used not only emails or letters but also follow-up with emails or letter, organizing events for children, engagement of regional hospital and/or EMS. The cost of low and middle intensity recruitment strategy was 6 USD and 18 USD per school respectively.

Results:
From April 2023 to June 2024, 5,573 schools and kindergartens were contacted via email or letter and 488 schools had registered for the program (36% kindergartens and 64% primary schools), covering 518 classes and 10,888 pupils. Four regions used low intensity recruitment while six regions used middle intensity recruitment strategy. Low intensity strategy recruited from 2% to 9% of all schools while middle intensity strategy recruited 10%, 11%, 14%, and 17% of all schools in the region, respectively. The best recruitment (10-17%) was achieved if regional authority, such as governor, hospital or EMS communicated the campaign to schools.

Conclusion:
Pupils in more than 10% of all schools were educated about stroke using relatively low-cost recruitment strategy. Most likely, it is however not realistic to recruit schools without at least moderate funding. It is beneficial to involve regional hospitals, EMS, or regional government to increase school recruitment in health awareness program.
Abstract TP349: Deleted NLRP3 inflammasome improves functional outcome and improves cerebral blood flow in an experimental model of Vascular Cognitive Impairment and Dementia
Authors: Khan Mohammad B. , Siddiqui Shahneela , Kamat Pradip , Nisar Mohammad , Dua Ashraar , Murudkar Tej , Gill Hunarmeet , Santiago Urbauer Ana , Arbab Ali , Hess David
Published: January 2025

Background:
Inflammation, a key player in both acute and chronic cerebral ischemia, is activated in brain tissues by bilateral carotid stenosis (BCAS)- induced chronic cerebral hypoperfusion. Our study aimed to investigate whether the deletion of the NLRP3inflammasome could abolish the deleterious effects of BCAS-induced chronic hypoperfusion in an experimental model of VCID.

Methods:
Microcoil-induced BCAS was used to induce chronic hypoperfusion. Middle-young (8-10 mice per group,4-5 months old, male) NLRP3WT and NLRP3KO were randomly assigned to BCAS-induced chronic hypoperfusion for four weeks. Cerebral blood flow was measured by laser speckle contrast imaging (LCSI) and CBF-ASL perfusion by MRI, and novel object recognition (NOR) and wire-hanging tests were also measured. Biochemical and histopathological staining was also assessed on the brain tissues.

Results:
At four weeks, there was a significant increase in CBF by LSCI and CBF-ASL perfusion by MRI in NLRP3KO mice compared to NLRP3WT groups. More importantly, the cognitive and motor function, as measured by NOR and wire-hanging tests, showed a remarkable improvement in NLRP3KO mice compared to WT.

Conclusions:
The findings suggest that deletion of NLRP3 inflammasome not only mitigates the cognitive impairment and motor effects of chronic hypoperfusion but also significantly improves cerebral blood flow. This indicates that targeting the NLRP3 inflammasome may be a new therapeutic approach against VCID.
Abstract TP363: Cognitive Consequences of IL-6 Trans-Signaling Inhibition in Aged Mice: A Comparative Study of Males and Females
Authors: Chauhan Anjali , Nguyen Dustin , Hall Cassie
Published: January 2025

Introduction:
IL-6 is a pro-inflammatory cytokine typically low in healthy young individuals but elevated after stroke, correlating with worse outcomes. IL-6 binds to soluble IL-6 receptors, which then interact with the glycoprotein gp130, initiating pro-inflammatory trans-signaling. In young mice, gp130Fc administration showed dose-dependent benefits. To test this in older individuals, gp130Fc (0.5 mg/kg, intraperitoneally) was given to aged mice 4 hours after middle cerebral artery occlusion. This dose caused 80% mortality in aged males within 72 hours, while all females survived. A lower dose (0.25 mg/kg) improved survival to 70% in aged males. Aged females had higher baseline plasma IL-6, which may explain their higher dose tolerance. Aging is associated with cognitive decline, leading us to hypothesize that inhibiting IL-6 trans-signaling could improve cognitive function in older animals.

Methods:
Aged (18-19 months) C57BL/6 male and female mice were used to assess cognitive deficits following gp130Fc treatment. The mice received either saline or gp130Fc at doses of 0.25 mg/kg (for males) and 0.5 mg/kg (for females) via intraperitoneal injection a week before behavioral testing and at day 14. Cognitive function was evaluated using several tests: Y-Maze on day 7, Novel Object Recognition Test (NORT) on day 14, and Object Location (OL) on day 21. From days 22-26, mice underwent training on the Barnes Maze, with testing on day 27. Mice were euthanized on day 28.

Results:
Older animals exhibited similar deficits in short-term memory as assessed on the Y maze, NORT, and OL task regardless of sex, but aged females showed worse long-term memory retention compared to age-matched males, as assessed by the Barnes Maze. Female mice took longer to escape and made more incorrect entries (P<0.05) than males. Inhibition of peripheral IL-6 trans-signaling worsened (P<0.05) long-term memory retention in aged males compared to vehicle-treated animals, whereas gp130Fc treatment improved long-term memory retention in aged females.

Conclusion:
This study demonstrates that aged female mice exhibit more pronounced cognitive impairments than their male counterparts. Inhibition of IL-6 trans-signaling with gp130Fc ameliorates cognitive deficits in aged females but exacerbates cognitive decline in aged males.
Abstract TP368: Targeted Lipid Nanoparticles to Modulate Blood-Brain Barrier Transcytosis in Acute Ischemic Stroke
Authors: Nong Jia , Marcos-Contreras Oscar , Muzykantov Vladimir
Published: January 2025

Ischemic stroke affects more than 600,000 Americans annually. Thrombectomy, where occluded arteries are cannulated for mechanical clot removal, can restore blood flow and improve survival, but still leaves 1/3 of patients functionally dependent, largely due to secondary ischemia-reperfusion injury. Brain edema in the acute phase of ischemia-reperfusion primarily associates with early-stage neurovascular damage and plays a major role in poor outcomes of stroke. Early on after ischemia/reperfusion, edema is mediated by increased transcytosis in the blood brain barrier (BBB) endothelium. Suppression of transcytosis has not yet been tested as a treatment for stroke. Major facilitator superfamily domain containing 2a (Mfsd2a) is a transporter protein that regulates caveolar transcytosis and is downregulated in ischemic stroke. We have previously demonstrated that 1) lipid nanoparticles loaded with mRNA (mRNA/LNP) enable rapid and robust protein expression; 2) vascular cell adhesion molecule (VCAM) targeting selectively delivers nanoparticles to stroke-affected BBB endothelium; 3) mRNA/LNP targeted to VCAM enabled protein expression in BBB endothelium. Therefore, we hypothesize that using LNPs containing Mfsd2a mRNA and targeted to vascular cell adhesion molecule (VCAM) can modulate Mfsd2a expression in inflamed BBB and improve outcome in ischemic stroke. In this work, we screened 10 LNP formulations and identified the optimized formulation on bEND.3 brain endothelial cells for Mfsd2a expression. The induction of Mfsd2a expression significantly enhanced Cav-1 expression and reduced the number of apical caveolae-formations by electron microscopy. Next, we used the acute ischemic stroke animal model (transient middle cerebral artery occlusion for 45 minutes) to assess the therapeutic outcome of VCAM-targeted LNP loaded with Mfsd2a mRNA. Right after reperfusion, we intravenously injected LNP and two additional dose every 24 hours (8ug RNA per dose). On day 3, we assessed brain edema by measuring the extravasation of radiolabeled albumin into the brain parenchyma. The percent of the extravasated albumin was significantly reduced after LNP treatment. In addition, using transmission electron microscopy, we observed less number of caveolae in the treated mice, compared to vehicle control. In conclusion, we have showed that VCAM targeted LNPs are able to deliver Mfsd2a mRNA to the inflamed brain vasculature and reduce brain edema by suppression of transcytosis.
Abstract TP377: A Biomarker Based on Aneurysm Wall Enhancement and Blood Gene Expression to Identify Symptomatic Intracranial Aneurysms
Authors: Veeturi Sricharan , Poppenberg Kerry , Jaikumar Vinay , Pinter Nandor , Levy Elad , Siddiqui Adnan , Tutino Vincent
Published: January 2025

Introduction:
Intracranial aneurysms (IAs) are weak outpouchings on cerebral vessels that can rupture, causing subarachnoid hemorrhage. Timely and accurate risk stratification of IAs is paramount.

Objective:
Aneurysm wall enhancement (AWE) is a potential imaging biomarker for risk stratification. We propose to combine this with whole blood RNA sequencing to improve IA risk stratification.

Methods:
We retrospectively collected images and blood of patients who had undergone vessel wall imaging. We performed RNA sequencing and radiomics analysis on the IA sacs on pre- and post-contrast T1 MRI scans. Using univariate analysis, we selected significantly different radiomic features (RFs). We removed all collinear features, and pooled radiomic and expression features. We classified each IA as symptomatic or asymptomatic based on symptoms at presentation. We then built separate machine learning models: one based solely on the radiomics features and another with combined features. We performed principal component analysis (PCA) and a leave-one-out (LOO) cross validation to quantify models’ performances.

Results:
Our final cohort consisted of 7 patients. We found 34 significantly different RFs between symptomatic and asymptomatic IAs. The final feature set consisted of 9 RFs and 6 genes. PCA of whole dataset using the RFs alone reflected variances of 38% and 29% on the best principal components. We trained a random forest model using LOO cross validation and observed an accuracy of 57.1% (33.3% sensitivity, 75% specificity). With the addition of the gene expression features, we found the PCA explained variance to be 41% and 26%. The LOO accuracy improved to 85.7% (66.6% sensitivity, 100% specificity).

Conclusion:
In this study, we demonstrated that radiomics from the aneurysm wall alone have a low predictive value in identifying symptomatic IAs. However, adding gene expression levels improves the predictive value. Future work will be aimed at adding more cases.
Abstract TP384: The secretome of intestinal epithelial stem cells attenuates acute and chronic stroke impairment
Authors: Mani Kathiresh Kumar , Pickle Kaylin , Miller Kate , Duque Mitchell , Obhrai Akruti , Wertz Anna , Sohrabji Farida
Published: January 2025

Background:
We showed that intestinal epithelial stem cells (IESCs) obtained from healthy young donor rats and transplanted to aging animals after stroke reduced infarct volume and sensorimotor impairment in the acute phase and mitigated cognitive impairment in the chronic phase. In most cases, stem cell transplants do not engraft or differentiate
in vivo
and their beneficial effects are proposed to occur through their secretions. Here we tested the hypothesis that IESC conditioned media (CM) would be similarly effective in improving acute and chronic stroke outcomes.

Methods:
IESCs from young animals were cultured as organoids using our published protocol (PMID:36328163). Conditioned media was collected from these cultures and tested for treatment efficacy in middle-aged male and female rats assigned to the following groups: Control (sham), stroke+vehicle injection, or stroke+ IESC-CM treatment. Two treatment regimens were performed for IESC-CM treatments: 4h/24h/48h or 4h/12h/36h/48h after stroke. Stroke was induced by middle cerebral artery occlusion (MCAo) via Endothelin-1 (vasoconstrictor) followed by intraperitoneal injection (ip) of IESC-CM. Infarct volume and sensorimotor function were assessed on 4d post stroke and at 30 days post stroke, animals were tested on the Social Interaction test (depressive-like behavior) and, Novel object Recognition test and Barnes maze test respectively (cognitive assessment). Serum levels of the gut permeability markers and cytokines level were measured at both time points.

Results:
IP treatment with IESC-CM significantly improved acute stroke outcomes and reduced gut permeability in middle-aged females. In chronic phase, vehicle-treated MCAo animals showed depressive-like behaviors compared to their pre-stroke behavior. In contrast, stroke animals that received IESCs-CM were no different from their pre stroke performance and were similar sham (no-stroke) animals. When assessing cognition, the MCAo+ vehicle animals showed poor discrimination abilities and impaired learning and retrieval memory. MCAo+IESCs-CM animals showed some improvement in episodic memory and spatial learning and retrieval with the 3 dose treatment, and significant improvement in both tests with the 4 dose treatment.

Conclusion:
These data indicate that the secretome of IESCs is sufficient to promote stroke recovery and suggests a strategy to increase the translational potential of this therapy.