bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TP270: Syphilis Screening in Acute Stroke Hospital Admissions: A Retrospective Investigation at a US Comprehensive Stroke Center
Authors: Gezer Aysegul , Braza Samuel , Lewis Angela , Olalde Heena , Lang Caroline , Knosp Noah , Gudenkauf Julie
Published: January 2025

Introduction:
Syphilis is associated with increased risk of cerebrovascular disease and acute stroke; stroke may even be the initial clinical manifestation of syphilis (Images 1 and 2). In the United States, syphilis rates have been increasing at an alarming rate since 2000, and between 2018-2022 cases increased by nearly 80%. Knowing the infectious status of a patient changes acute and secondary stroke management strategies, and widespread screening is imperative toward national eradication efforts. This study aims to explore syphilis laboratory screening trends in hospitalized stroke patients, whether rates of screening have risen with increases in national cases, and which demographic factors predict screening.

Hypothesis:
We hypothesized that 1) overall screening for syphilis in acute stroke is low, especially in comparison to screening for diabetes and hyperlipidemia, 2) screening rates increase annually from 2016-2020, and 3) screening for syphilis occurs more often in younger and minority patients.

Methods:
We reviewed all stroke admissions from a US comprehensive stroke center between 2016-2020 and collected syphilis laboratory data and patient demographics. Of patients without known history of syphilis, we evaluated screening rates of syphilis and compared to that of Hemoglobin A1c (HbA1c) or Low-Density Lipoprotein (LDL) for this period with Student’s t-test. We used logistic regression to determine the relationship between screening rates of syphilis and patient age and race.

Results:
Between 2016-2020, there were 5,653 stroke admissions without established infection. The average annual screening rate of syphilis (1.19%) was significantly lower than that of HbA1c (58%; p=0.002) and LDL (69.0%; p<0.001). Annual screening rates increased from 0.44% to 2.5% between 2016-2019, but then dropped to 1.02% in 2020. Age at admission was inversely correlated with syphilis screening (p<0.001) and minority status was associated with higher syphilis screening (p<0.001).

Conclusions:
Syphilis screening rates in the acute stroke setting are low overall and have not increased over time despite continued rises in national infections in the US. Younger and racial minority patients are more likely to be screened. Future work is needed to examine if enhanced syphilis screening practices in acute stroke hospitalizations can be used to inform stroke management and improve patient outcomes.
Abstract TP278: Final infarct volume reduction may mediate EVT effects on mortality
Authors: Ballekere Anjan Nagesh , Iyyangar Ananya , Azeem Hussain , Sheth Sunil , Ebirim Emmanuel , Lee Eunyoung , Le Ngoc Mai
Published: January 2025

Background:
Recent trials of endovascular stroke therapy (EVT) have shown reduced rates of mortality compared to medical management, a finding in contrast with earlier studies. Because earlier studies had also suggested EVT-derived clinical benefits were largely not mediated by effects on final infarct volume (FIV), here we determine how FIV mediates mortality outcomes in a more modern cohort of EVT treatments.

Methods:
From our prospectively collected multi-center registry across four comprehensive stroke centers (CSC) in the Houston area, we identified patients from 2017 to 2023 with large vessel occlusion acute ischemic stroke (LVO AIS) who underwent thrombectomy. A large infarct core was defined by CTP as exceeding 70 ml or by CT ASPECTS < 6. This study conducted a mediation analysis to investigate the relationship between EVT (independent variable), 90-day mortality (outcome), and FIV (mediator). Bootstrapping was used to estimate indirect effect, adjusting for confounders, including age and sex. Separate mediation analyses were performed for severe and non-severe subgroups.

Results:
Among 616 patients with LVO AIS who underwent EVT, median NIHSS was 14 [8,20 IQR], age was 67 [57,77 IQR] and 47.2% were female. Median FIV was 20.38 [ 4.26, 60.20 IQR] and 19.2 % of patients suffered mortality. In the overall cohort, the total effect of EVT on 90-day mortality was not statistically significant (P = 0.46 unadjusted; P = 0.68 adjusted). EVT significantly influenced FIV with a P-value < 0.001, and FIV was a strong predictor of mortality with a P-value < 0.001. However, when accounting for FIV, the direct effect of EVT on mortality was not significant (P = 0.17 unadjusted; P = 0.31 adjusted). The impact of EVT on 90-day mortality was partially mediated via FIV. The indirect effect of EVT on mortality through FIV was significant (P < 0.001). Subgroup analyses indicated that in severe stroke patients (NIHSS ≥ 16), EVT did not significantly affect FIV (Path A, P = 0.21), precluding mediation analysis. In non-severe stroke patients (NIHSS < 16), EVT had a significant impact on FIV (P < 0.001), and FIV was a significant predictor of mortality (P = 0.026). In this group, 77.7% of EVT’s effect on mortality was mediated by FIV.

Conclusions:
Reductions in FIV partially mediate the effect of EVT on 90-day mortality, particularly in patients with NIHSS < 16. These findings support the results of recent clinical trials demonstrating mortality benefit with reperfusion.
Abstract TP289: The Interaction Between Brain Natriuretic Peptide and QTc Interval Prolongation on Short-Term Mortality Risk in Patients With Stroke-Heart Syndrome
Authors: Wang Yongle , Wang Lanjing , Huang Shuangfeng , Zhao Wenbo , Ji Xunming , Li Sijie
Published: January 2025

Introduction:
Cardiac complications following ischemic stroke are common. The term "stroke-heart syndrome" describes new adverse cardiac events post-stroke, with QTc prolongation being the most frequent electrocardiographic abnormality. Elevated brain natriuretic peptide (BNP) levels, indicating myocardial damage and increased cardiac load, may lead to prolonged myocardial repolarization. This study examines the interaction between BNP levels and QTc interval and their impact on the short-term prognosis of stroke-heart syndrome patients.

Methods:
The study included patients who presented to the emergency department from January 2021 to July 2022 with acute ischemic stroke complicated by stroke-heart syndrome, defined as new-onset cardiac dysfunction within three days post-stroke, including acute coronary syndrome, heart failure, and arrhythmias. All patients underwent routine laboratory tests and ECG evaluations. QTc prolongation was defined as >430 ms for males and >450 ms for females. Patients were followed for three months, with outcomes including all-cause and cardiovascular-related mortality. The optimal BNP cutoff for predicting mortality was determined using ROC curve analysis. The relationship between BNP, QTc interval, and mortality was evaluated using Cox proportional hazards regression, with further assessment of the interaction between BNP and QTc interval.

Results:
The study included 448 patients, with 14 deaths during follow-up, 9 of which were cardiovascular-related. QTc prolongation was observed in 217 patients (48.44%), who also had significantly higher BNP levels (p=0.008). High BNP was significantly associated with QTc prolongation (OR, 1.90; 95% CI, 1.20-3.01, p=0.006)(Table 1). The optimal BNP cutoff was 122.5 pg/mL. High BNP increased the risk of all-cause mortality (HR, 5.94; 95% CI, 1.22-29.03, p=0.028), while QTc prolongation increased mortality risk only in patients with high BNP (HR, 2.22; 95% CI, 0.53-9.25, p=0.273; p for interaction <0.001)(Table 2). The group with QTc prolongation and high BNP had a significantly increased mortality risk compared to the control group (HR 4.92, 95% CI 1.03-23.39, p=0.045)(Figure 1).

Conclusions:
QTc prolongation and elevated BNP levels interact to influence short-term mortality in stroke-heart syndrome patients. In patients with high BNP levels, QTc prolongation is a potential mortality risk predictor. Monitoring and treatment adjustments are recommended for such patients to reduce mortality risk.
Abstract TP294: The Impact of Chronic Kidney Disease Severity on Incident Acute Ischemic Stroke
Authors: Yq Tan Benjamin , Tan Yong Yi , Lim Sean , Toh Emma , Yeo Leonard , Sharma Vijay , Chua Yan Ting , Ngoh Clara
Published: January 2025

Introduction:
Chronic kidney disease (CKD) and ischemic stroke are both associated with significant global disease burdens and share common risk factors. Understanding the impact of CKD on stroke incidence is essential for improving patient outcomes. Traditionally, CKD severity has been graded using the estimated glomerular filtration rate (eGFR). However, the Kidney Failure Risk Equation (KFRE), which incorporates age, sex, eGFR, and the urine albumin/creatinine ratio, has emerged as a more robust tool for predicting progression to end-stage kidney disease. This study aimed to investigate if CKD severity, as assessed by these parameters is associated with incident acute ischemic stroke.

Methods:
Consecutive CKD patients receiving care within the National University Health System from March 2022 to September 2023 were included for analyses. Patients with a previous history of ischemic stroke or transient ischemic attack were excluded. CKD severity was defined by eGFR calculated with the CKD-EPI equation and as per KDIGO guidelines. The 2-year and 5-year risk of kidney failure was estimated by the 4-variable KFRE. Cox proportional hazards model was used to study the relationship between CKD stage and KFRE scores with acute ischemic stroke.

Results:
A total of 14,794 consecutive CKD patients were included, of which 155 (1.05%) experienced an acute ischemic stroke. The median age was 73 years old (IQR = 14), with 6,251 females (42.3%) and the majority being Chinese (n = 10,759; 73.5%). The median days-to-stroke was 265 days (IQR 242 days). Older age (p<0.001), ischemic heart disease (p<0.001), advanced CKD Stage 4-5 (p=0.013) and KFRE strata (p=0.0018) were associated with ischemic stroke. The risk of ischemic stroke was higher with advanced CKD stage; CKD Stage 4-5 patients were more likely to develop an acute ischemic stroke event as compared to CKD Stage 1-3b patients (HR 1.70, 95%CI: 1.14-2.53). Moreover, a 10% increase in 2-year and 5-year kidney failure risks corresponded to significantly higher risks of ischemic stroke, with hazard ratios of 1.38 (95% CI: 1.17-1.63) and 1.20 (95% CI: 1.10-1.31), respectively. These associations remained significant after adjusting for age, gender, ethnicity, comorbidities, HbA1c and lipid parameters.

Conclusion:
CKD patients at elevated risk of kidney failure also face an increased risk of suffering an acute ischemic stroke. Implementing the KFRE in CKD management could prove valuable in assessing ischemic stroke risk.
Abstract TP30: The Effect of Angiotensin II Administration Dose and Duration on The Brain CD38 Expression and Enzymatic Activity
Authors: Ewees Mohamed , Dodd Daniel , Amro Hani , Abdelhady Ali , Gallego-Perez Daniel , Zweier Jay , Hannawi Yousef
Published: January 2025

Introduction:
CD38 is an ectoenzyme that is the main determinant of NAD
+
level. We have shown that the brain CD38 expression and enzymatic activity are increased in the setting of hypertension (HTN) including spontaneously hypertensive stroke prone rat and angiotensin-II (Ang-II) induced HTN. Therefore, we aimed to characterize the effects of Ang-II administration dose and duration on the brain CD38 expression and enzymatic activity.

Methods:
Male C57BL/6J mice (10-13) weeks (wks) of age (N=10) underwent subcutaneous infusion of Ang-II for a duration of 2-wks at (100 ng/kg/min or 600 ng/kg/min) or 6-wks (N=6) at 600 ng/kg/min through osmotic pumps. Control mice (N=10) underwent matching durations of saline infusion. CD38 enzymatic activity was measured by the NAD
+
analogue conversion to the fluorescent product (ε-ADPR). CD38 expression was assessed by immunoblotting and immunofluorescence (IF). Amyloid beta (Aβ) and CD38 localization to the different brain cells were done by IF. Superoxide generation was measured using dihydroethidium (DHE).

Results:
Ang-II infusion at 600 ng/kg/min caused a slow rise in systolic blood pressure (SBP) with sustained HTN by 2 wks (Ang-II: 151±6.5 vs saline: 110±4.3 mmHg, p=0.0007) and worsening HTN by 6 wks. 100 ng/kg/min of Ang-II did not significantly raise SBP and the brain expression of CD38 at this dose primarily localized to the vessels and endothelial cells (ECs). While CD38 was significantly expressed on ECs in the brain at 2 wks of 600 ng/kg/min of Ang-II, it was also seen on astrocytes and microglia. The expression pattern remained similar at 6 wks Ang-II infusion. Total brain CD38 expression and enzymatic activity were increased at 2 wks of 600 ng/kg/min Ang-II infusion and they remained elevated at similar levels at 6 wks Ang-II infusion. A 362% increase in superoxide was seen at 2 wks of 600 ng/kg/min Ang-II compared to that in control mice and remained similarly elevated at 6 wks Ang-II infusion. Aβ was 233% higher at 2 wks of 600 ng/kg/min of Ang-II and further increased with 6 wks of Ang-II infusion to 331% of levels in control mice.

Conclusions:
Nonpressor dose of Ang-II primarily increases CD38 expression in the cerebral vessels and ECs. Higher Ang-II dose leading to HTN increases the brain CD38 expression and enzymatic activity with accompanied neuronal injury in prolonged Ang-II infusion. These results suggest CD38 as a potential target for improving HTN induced cerebrovascular dysfunction and brain health.
Abstract TP305: Prevalence and Predictors of Post-Stroke Anxiety and Depression
Authors: McNamara Katelyn , White Milo , Peyravi Reza , Zubair Adeel , Driskell Lucas , Fesharaki-Zadeh Arman , Leary Megan , Torres Lopez Victor , Kampp Michael , Shah Dipti , Forman Rachel , Falcone Guido , Sheth Kevin , Sansing Lauren , Pittenger Christopher , Sharma Richa
Published: January 2025

Introduction:
Acute ischemic stroke (AIS) may be associated with feelings of anxiety and/or depression (A/D) in subsequent months. The purpose of this study was to determine the frequency of feelings of A/D after AIS longitudinally and to identify risk factors that may predict post-stroke feelings of A/D.

Methods:
Data were collected from patients with AIS at a stroke center from 2016-2022. Patients were excluded if <18 years old, did not fill out the EQ-5D, or who were deceased or designated as comfort measures only upon hospital discharge. Patient demographics, medical history, stroke anatomic location, and pre-morbid modified Rankin score, a score of functional status, were collected during hospital admission. A/D was the outcome of interest and was collected via the self-reported EQ-5D. It is scored from 1-3, with 1 indicating no perceived problems, 2 indicating feelings of being moderately anxious or depressed, and 3 indicating feelings of being extremely anxious or depressed. Scores were dichotomized with a score of 1 representing no feelings of A/D and a score of 2 or 3 indicating any feelings of A/D. We built a multivariate logistic regression model using the collected covariates to predict the odds of feelings of A/D 3-months post-stroke.

Results:
The cohort was 1,225 patients. The prevalence of feelings of A/D was 38.7% at 3-months after stroke. Compared to those without feelings of A/D at 3-months, patients with feelings of A/D were more frequently female (56.5% vs 43.14%, p<0.0001), Hispanic (9.8% vs 5.5%, p=0.014), had NIHSS > 10 (33.7% vs 24.4%, p=0.0006), had prior stroke (22.1% vs 16.6%, p=0.025), and had a history of drug use (12.4% vs 8.2%, p=0.0486). In the adjusted multivariate model, female sex (OR 1.76, 95% CI 1.27-2.43), non-White race (OR 1.21, 95% CI 1.04-1.41), Hispanic ethnicity (OR 1.87, 95% CI 1.05-3.36), absence of atrial fibrillation (OR 1.79, 95% CI 1.08-3.03), anticoagulation use (OR 2.04, 95% CI 1.18-3.57), and statin non-use (OR 1.59, 95% CI 1.09-2.34) were significant, independent predictors of feelings of A/D at 3-months post-stroke.

Conclusions:
Over one in three patients experience feelings of A/D at 3-months after stroke. We identified predictors of feelings of A/D at 3-months post-stroke. Our findings are hypothesis-generating and require further study. Understanding the factors that may predispose patients to have feelings of A/D post-stroke may enhance screening efforts, particularly in these high-risk groups.
Abstract TP310: The Shifting Evidence for Statin Use in the Setting of Intracerebral Hemorrhage
Authors: Mellacheruvu Pranav , Vedamurthy Deepak , Odenigbo Charles , Burke Skyler , Cucchiara Brett , Soffer Dan
Published: January 2025

Introduction:
Intracerebral Hemorrhage (ICH) is associated with a high case fatality and survivors of ICH are at increased risk for ICH recurrence. Roughly 20-30% of patients with ICH take a statin at the time of ICH onset. The role of statins, whether protective or deleterious, in the setting of ICH remains unclear. The SPARCL (Stroke Prevention by Aggressive Reduction of Cholesterol Level) study amongst others, have suggested that statin use may increase risk of ICH in those with prior history ICH, due to increased erythrocyte fragility and inhibition of platelet aggregation. However subsequent observational studies refuted these findings citing statins improve endothelial function and reduce oxidative stress thus theoretically. We reviewed relevant studies discussing the relationship between statin use and risk of ICH.

Methods:
A comprehensive search strategy utilizing the key terms “statin use” and “intracerebral hemorrhage” was performed utilizing four electronic databases: Cochrane, Embase, Google Scholar, PubMed. The search was conducted by two authors (PM and CO). Following the search, articles citing a correlation between statin use and risk of intracerebral hemorrhage were included. Below is a table citing selected studies from our review (Table 1).

Discussion:
There continues to be mixed evidence regarding statin use and risk of ICH. Current clinical guidelines do not provide a formal recommendation on statin use restriction in those with prior ICH. However, contrary to the SPARCL study, newer studies have suggested there is neither a statistically nor clinically significant relationship between LDL-C and ICH incidence. Our review also uncovered that one’s genetic signature may play a mediating role in this relationship as evidenced namely by the Honolulu Heart study, which analyzed a relatively monogenic study population. This implies a more nuanced relationship and we posit the burgeoning use of polygenic risk scoring may provide more utility here as well. Ultimately consideration of statin therapy should be determined by weighing one’s atherogenicity versus propensity to develop ICH. An optimal LDL-C goal has yet to be determined however many studies suggest targeting between 70-160 mg/dL is optimal. Additional studies should assess the role of other lipid lowering agents in the setting of ICH such as bempedoic acid and PCSK9 inhibitors, as well as discern optimal ranges for newer Apo-B and Lp(a) lipid biomarkers.
Abstract TP326: Increased Prevalence of Device-Detected AF in ESUS Compared to Non-ESUS Stroke
Authors: Chang Jason , Shu Liqi , Goldstein Eric , Khan Farhan , Kala Narendra , Stretz Christoph , Burton Tina , Perelstein Elizabeth , Furie Karen , Yaghi Shadi
Published: January 2025

Background:
In patients with ischemic stroke who receive insertable cardiac monitors, the CRYSTAL-AF and STROKE-AF randomized trials showed similar (~12%) AF detection rates at one year among patients with cryptogenic stroke and stroke from large vessel disease and small vessel disease, respectively. This finding may suggest that AF detected on an insertable cardiac monitor in cryptogenic stroke is often not pathogenic. In this study, we aim to compare AF detection rates on ZIOPATCH in ESUS vs. non-cardioembolic ischemic stroke.

Methods:
From a comprehensive stroke center registry, we identified patients with a diagnosis of ischemic stroke who underwent a ZIOPATCH to look for AF. The primary predictor was stroke subtype (ESUS vs. non-cardioembolic). Non-cardioembolic stroke was defined as stroke from large artery atherosclerosis, small vessel disease, or other known mechanism. ESUS was defined using the ESUS consensus criteria. The study outcome was AF detected on ZIOPATCH. We compared baseline characteristics and risk factors between patients with vs. without AF detected. Univariate and multivariate regression models were used to determine odds ratios (OR).

Results:
We identified 478 patients who had a ZIOPATCH placed; 410 had the ZIOPATCH completed (217 ESUS, 71 small vessel disease, 100 large vessel disease, and 22 had another defined mechanism). The mean age was 69 years and 51% were men. The mean duration of ZIOPATCH monitoring was 12 days and 17 (4.1%) had AF. Patients with AF were more likely to be older (82 years vs. 68 years, p<0.001), female (88% vs. 48%, p<0.001), and have ESUS (88% vs. 52%, p = 0.013). In adjusted models, ESUS patients were more likely to have AF detected on ZIOPATCH (adjusted OR 3.70, 95% CI 1.01-13.5, p = 0.048). Notably, only 29% of patients with ESUS and negative ZIOPATCH underwent and insertable cardiac monitor.

Conclusions:
There is increased prevenance of AF on ZIOPATCH in patients with ESUS compared to non-cardioembolic stroke. This suggests that AF detected after the stroke on ZIOPATCH may present a pathogenic entity.
Abstract TP55: Analysis of Factors and Paths Influencing the Health Information Seeking Behavior of Stroke Patients
Authors: Chen Lu , He Manlan , Hu Yufan
Published: January 2025

Background and purpose:
Good health behaviors can effectively reduce the incidence and recurrence rate of stroke. Improving the health information seeking behavior of chronic disease patients, which can effectively improve their health behavior and self-management level. This study aims to explore the role of digital health literacy and information self-efficacy on health information seeking behavior, and attempt to provide theoretical basis for improving health information seeking behavior and enhancing patients’ self-management level from a new perspective.

Methods:
From June to December 2022, 239 stroke patients in a hospital in Nanjing were selected by convenience sampling method. According to the Planned Risk Information seek Model (PRISM), general information questionnaire, health information seeking behavior scale, ehealth literacy scale and information self-efficacy scale were used to investigate. T test and F test were used to determine the health information seeking behavior scores of stroke patients with different characteristics. A structural equation model was constructed according to Harman single factor method and Pearson correlation analysis, and the model was verified by Bootstrap method.

Results:
The total score of the 239 patients’ health information seeking behavior was (133.86+15.30), and the patients’ health information seeking behavior was significantly positively correlated with digital health literacy and information self-efficacy (
r
1
=0.638,
r
2
=0.672; All
P
<0.01). Digital health literacy could directly and positively predict information self-efficacy and health information seeking behavior (
β
1
=0.910,
β
2
=0.549; All
P
<0.01 ). Digital health literacy could also indirectly predict health information seeking behavior by using information self-efficacy as a mediating variable (
β
=0.449,
P
<0.01).

Conclusions:
The current situation of health information seeking behavior of stroke patients is poor, and information self-efficacy plays a mediating role between patients' electronic health literacy and health information seeking behavior. Medical staff can take corresponding measures to strengthen stroke patents' digital health education and improve their positive belief in obtaining health information, so as encourage them to form a good health information seeking behavior and improve the health level of patients.
Abstract TP9: Hemorrhagic Transformation in Acute Ischemic Stroke and Diabetes: Is it Different between Alteplase and Tenecteplase?
Authors: Hegde Sheetal , Hernandez Roberto , Salter Amber , Ray Bappaditya
Published: January 2025

Introduction:
Tenecteplase (TNK) is now an accepted alternative to Alteplase (ALT) for intravenous thrombolysis (IVT) in acute ischemic stroke (AIS). Hemorrhagic transformation (HT), a complication of IVT, is more frequent in acute hyperglycemia and diabetes (DM) and is associated with poor clinical outcomes. We previously reported better clinical outcomes in DM patients treated with TNK. In this study we explored if HT is associated with the observed less favorable outcomes in ALT-treated DM patients.

Methods:
In this 4-year retrospective cohort of AIS patients from 2 comprehensive stroke centers, DM was defined by known history, antidiabetic medication use, and admission glycated hemoglobin ≥6.5%. Time to IVT was grouped as ultra-early (0-90 min), early (91-180 min), and late (181-270 min). Peripheral blood indices, neutrophil to lymphocyte ratio (NLR), and systemic immune inflammation index (SII) were used to assess acute immune response at admission and 24 hours. Non-parametric tests compared intergroup differences with statistical significance at p-value <0.05.

Results:
Three hundred and twelve patients (ALT, n=165 [DM, n=63; non-DM, n=102]; TNK, n=147 [DM, n=48; non-DM, n=99]) were included. The distribution was similar across groups of time to IVT between ALT and TNK (ultra-early [ALT, n=30%; TNK, n=36%]; early [ALT, n=51%; TNK, n=48%]; late [ALT, n=20%; TNK, n=17%], p=0.5). Baseline characteristics were similar between DM and non-DM within IVT groups. Rise in NLR at 24 hours was higher in non-DM ALT-treated patients compared to DM (109 [21, 262] vs. 45 [-14, 217], p=0.039), though other inflammatory markers were similar. HT was lower in non-DM compared to DM (17% vs. 33%, p=0.013) ALT-treated patients, though similar among TNK-treated patients. There were no differences in inflammatory markers or rates of HT in ultra-early or late periods. In the early period, non-DM TNK-treated patients experienced a higher rise in NLR (163 [60, 492] vs. 25 [-8, 168], p=0.015) and SII (134 [56, 447] vs. 28 [-8, 128], p=0.019) at 24 hours compared to DM, though HT rates were similar. In the early ALT cohort, DM experienced higher HT (33% vs. 12%, p=0.021).

Conclusions:
There was a higher rate of HT in ALT-treated DM patients compared to non-DM when administered at 91-180 min. This difference was not seen in ultra-early or late ALT administration or with TNK. Larger studies will need to validate these findings and clarify the role of early inflammation in mediating HT.
Abstract WMP102: Ischemic and hemorrhagic risks of patients with cortical superficial siderosis on antithrombotic therapy
Authors: Inutsuka Ryoko , Miwa Kaori , Koga Masatoshi , Yakushiji Yusuke , Tanaka Kanta , Yoshimura Sohei , Sasaki Makoto , Kudo Kohsuke , Shiozawa Masayuki , ide toshihiro , Okada Yasushi , Hasegawa Yasuhiro , Terasaki Tadashi , Ihara Masafumi , Hirano Teruyuki , Toyoda Kazunori
Published: January 2025

Objectives:
Cortical superficial siderosis (cSS) has been implicated as a putative hemorrhagic MRI finding of cerebral small vessel disease (SVD) related to cerebral amyloid angiopathy. Few reports have examined the association between cSS and antithrombotic-related clinical events. The aim of this study is to investigate the association of cSS with the risk of hemorrhagic or ischemic events in patients receiving antithrombotic agents.

Methods:
This is a prospective, multicenter, observational study that enrolled patients with cerebrovascular or cardiovascular diseases who were taking oral antithrombotic agents from 52 hospitals across Japan between 2016 and 2019. The MRI scans were centrally evaluated for SVD, including white matter hyperintensities (WMH), cerebral microbleeds (CMBs), lacunes, basal ganglia-enlarged perivascular spaces (BGPVS), cortical superficial siderosis (cSS), using a visual scale. The outcomes included subsequent ischemic events (ischemic vascular events [IVE], ischemic stroke [IS]), hemorrhagic events (major bleeding [MB], intracranial hemorrhage [ICH], non-major bleeding[nMB]), and mortality. We calculated incidence rates (IR) per 1,000 patient-years of each event and the IR ratio (IRR).

Results:
Of 5037 patients (mean age 71.2 ± 11.2 years, 67% men), cSS was detected in 105 (2.0%) patients. The cSS group was older and had a higher proportion of males, atrial fibrillation, histories of intracerebral hemorrhage or subarachnoid hemorrhage and a higher frequency of strictly lobar CMBs, WMH, and lacunes compared to the non-cSS group. During a median 2 [IQR1.8–2.03] years, 278 IVE, 197 IS, 93 MB, 55 ICH, 147 nMB, and 217 deaths were observed. In the cSS group, IVE and IS were numerically less frequent (IVE: IR 20.95 vs 29.13; IS: 15.64 vs 20.34, per 1000 patient-years), while MB and mortality (MB: IR 9.61 vs 5.15; mortality: IR 35.82 vs 21.87) were numerically more frequent, compared to the non-cSS group, but the IRR of each event did not significantly differ between the 2 groups. In the cSS group on warfarin (n=12), there was a trend towards numerically higher rates of MB (IR 80.36 vs 18.54), ICH (IR 80.36 vs 15.84), and mortality (IR 142.95 vs 39.61, per 1000 patient-years) compared to the non-cSS group.

Conclusion:
Individuals with cSS receiving antithrombotic agents exhibited a higher trend for mortality and major bleeding.
Abstract WMP104: Impact of Labor Activism on Historic Geospatial Stroke Mortality in Richmond, Virginia
Authors: Caudill Craig , Meier Helen , Wing Jeffrey
Published: January 2025

Introduction:
Post-Civil War, Richmond emerged as a major center for tobacco cultivation and manufacturing, driven by its exploitation of Black labor. Laborers were often employed in physically demanding positions in unventilated and smoke-filled environments, coupled with forced residence in undesirable neighborhoods due to historic redlining. In response, Black laborers organized strikes leading to lower working hours, increased wages, and improved workplace safety. We investigated whether these changes in social determinants of health (SDOH) may have contributed to the reduction in stroke mortality among Black workers in Richmond in the 20
th
century.

Methods:
Data was sourced from the Richmond Cemetery Collaboratory (RCC), which digitized Black Death Records in Richmond, Virginia. Death records were ICD-10 coded by ChatGPT. A total of 1,815 death records (1907-1979), were georeferenced based on their proximity to tobacco factories. We conducted hotspot analysis across the study period to assess stroke mortality across time and space. The age distribution of stroke deaths within the period was compared to the 1940 Vital Statistics, which documented stroke mortality for all non-white races.

Results:
Stroke mortality in RCC data significantly declined following the period of labor activism between 1937 and 1941. Hot spot analysis revealed a geospatial shift in stroke mortality in Richmond, moving from the east side in the early 1900s to the south side in the mid-1900s (Figure 1A). The stroke mortality rate within a 1 km radius of tobacco manufacturing plants was 109.46 per 100,000. The observed K value indicated high levels of stroke death clustering within the sample, likely due to historic redlining (Figure 1B). Additionally, stroke mortality was more common among individuals <45, compared to the 1940 statistics on non-white stroke mortality in Virginia.

Conclusion:
Labor activism was a critical SDOH that played a key role in reducing stroke mortality among Black workers in Richmond's tobacco industry during the 20th century. Through strikes, Black laborers directly targeted social factors that likely contributed to stroke mortality and prevalence. The younger age at death among Richmond’s Black population, compared to statewide stroke mortality statistics, underscores the tobacco industry’s detrimental impact on stroke risk, especially for those living near manufacturing plants. The drop in stroke mortality highlights leadership's role in addressing SDOH.
Abstract WMP111: Progranulin Enhances the Engraftment of Transplanted Human induced Pluripotent Stem Cell-derived Cerebral Neurons in Cell Replacement Therapy
Authors: Yamagami Keitaro , Samata Bumpei , Doi Daisuke , Tsuchimochi Ryosuke , Kikuchi Tetsuhiro , Amimoto Naoya , Ikeda Megumi , TAKAHASHI Jun
Published: January 2025

Background:
Stroke or traumatic brain injury (TBI), due to damage to the cerebral motor cortex, often results in significant motor dysfunction and disabilities. Cell replacement therapy emerges as a prospective alternative treatment, promising to restore the impaired neural circuits and facilitate functional recovery. The current study aimed to systemically identify new factors capable of enhancing the efficacy of cell transplantation with human-induced pluripotent stem cell-derived cerebral organoids (hiPSC-COs). Earlier research demonstrated the effectiveness of delaying the transplantation procedure by 1 week and we hypothesized in this study that brain tissues 1 week after brain damage possess a more favorable environment for cell transplantation when compared to immediately after injury.

Methods and Results:
Using rodent models, we made a transcriptomic comparison to differentiate gene expression between these two temporal states in order to discern novel factors that could potentiate the therapeutic impact of cell transplantation. Ultimately, 7 candidate genes coding for secreted and extracellular proteins (apolipoprotein D, cathepsin D, cathepsin S, lysozyme 2, secreted phosphoprotein 1, granulin, and secreted protein acidic and cysteine rich) were selected through the transcriptome analysis. In controlled in vitro conditions, recombinant human progranulin (rhPGRN) bolstered the survival rate of dissociated neurons sourced from hiPSC-COs by approximately 25% under oxidative stress. Further experiments revealed that this increase in viability was attributable to a reduction in apoptosis via Akt phosphorylation. In addition, rhPGRN pretreatment before in vivo transplantation experiments augmented the number of engrafted cells about 3.3 times compared to the control group and facilitated neurite elongation along the host brain’s corticospinal tracts in rodent models. Subsequent histological assessments at 3 months post-transplantation revealed an elevated presence of graft-derived subcerebral projection neurons—crucial elements for reconstituting neural circuits—in the rhPGRN-treated group.

Conclusion:
Our data highlight the potential of PGRN as a neurotrophic factor suitable for incorporation into hiPSC-CO-based cell therapies for stroke or TBI.
Abstract WMP113: Investigating Cholesterol Dynamics in Post-Stroke Recovery through Optogenetic Neuronal Stimulation
Authors: Radit Nahin T. , Chen Hansen , Uchino Haruto , Chiang Terrance , Kim Anika , Lee Alex , Cheng Michelle , Steinberg Gary
Published: January 2025

Introduction:
Post-stroke brain stimulation is a promising neurorestorative approach, yet the molecular mechanisms driving recovery remain unclear. Our previous work demonstrated that post-stroke optogenetic stimulations of the ipsilesional primary motor cortex (iM1) promotes functional recovery. To understand the mechanisms driving post-stroke recovery, we investigated the transcriptome of iM1 in non-stimulated and stimulated mice using RNA sequencing.

Methods:
C57Bl6 male mice underwent stereotaxic surgery to express Channelrhodopsin in iM1 excitatory neurons, with optical fiber implanted in the same location. After 5-6 weeks, mice underwent transient middle cerebral artery occlusion (30 minutes). Stimulated mice received optogenetic stimulations from post-stroke days (PD) 5–14. Rotating beam test was performed at pre-stroke baseline, PD4, 7 and 14. iM1 from stimulated, non-stimulated stroke mice at PD 7&15, and sham mice were processed for RNA sequencing (n=4-5/group). Expression of cholesterol enzymes such as HMGCS1 was examined using quantitative PCR and immunohistochemistry. Cholesterol levels were visualized using filipin or BODIPY.

Results:
iM1 stimulations enhanced recovery at PD14, with longer distance traveled and faster speed on the rotating beam test (p<0.05). RNA sequencing revealed a distinct transcriptomic landscape between stimulated and non-stimulated stroke mice. In non-stimulated mice, 4526 differentially expressed genes (DEGs) were identified in iM1 at PD7, and number of DEGs dropped to 95 by PD15, compared to sham controls. In contrast, stimulated mice exhibited 1446 DEGs at PD7, which remained elevated at 1090 DEGs by PD15. Ingenuity pathway analysis highlighted downregulation of multiple cholesterol biosynthesis and metabolism pathways in iM1-stimulated mice. qPCR confirmed that iM1 stimulation reduced the expression of cholesterol enzyme HMGCS1 in iM1. Preliminary BODIPY and HMGCS1 staining data indicated noticeable cholesterol level changes in iM1 post-stroke.

Conclusions:
Our transcriptome data revealed important insights into the molecular signaling of optogenetic stimulation-induced recovery, particularly cholesterol metabolism. Ongoing studies include immunostaining of cholesterol metabolism related genes and co-staining of cholesterol levels with cell type specific markers (neurons, glia, microglia). These data suggest that reduction in cholesterol accumulation may be a key mechanism in post-stroke recovery.
Abstract WMP12: Heterogeneous Treatment Effects of Colchicine in patients with acute ischaemic stroke or transient ischaemic attack
Authors: Jin Aoming
Published: January 2025

Background:
The trial of colchicine in high risk patients with acute minor-to-moderate ischaemic stroke or transient ischaemic attack (CHANCE-3) evaluated the efficacy and safety of low dose colchicine on reducing subsequent stroke within three month. The study did not provide any evidence showing that colchicine could reduce the risk of any stroke within three months after onset, possibly due to heterogeneity of treatment effect (HTE) across patients. Better assessing HTE could identify some subpopulations with derived benefit.

Objective:
In the post-hoc analysis, we aimed to assess HTE through different approaches and explore the subgroup of patients who may benefit from colchicine.

Method:
Exploratory analysis of a multicentre, double blind, randomised, controlled trial of low dose colchicine versus placebo in patients with a minor-to-moderate ischaemic stroke or transient ischaemic attack and a high sensitivity C-reactive protein ≥2 mg/L. The primary outcome was any new stroke within three month after onset. Heterogeneity of treatment effect was assessed two ways: using a multivariable outcome prediction model, and a causal forest model. Cox proportional hazards models were used to evaluate the effect of colchicine in subgroup patients with specific characteristics.

Results:
The trial enrolled and assigned 8,343 patients to colchicine or placebo group and baseline characteristics were balanced between two groups (mean age, 65.6 years; 62.4% male). In the overall population, colchicine was not associated with an decreasing risk of stroke (HR: 0.98, 95%CI: 0.83-1.16, p =0.79). Based on causal forest models, mean corpusular volume, triglyceride, BMI, and the neutrophil count distinguished patients who differentially benefited from colchicine (interaction p =0.02). Cox proportional hazards models revealed a number needed to treat of 29.4 to prevent one stroke among participants with mean corpusular volume higher than 86.2 g/L, triglyceride higher than 1.39 mmol/L, BMI higher than 23.39 Kg/m
2
, and the neutrophil count higher than 4.35×10
9
/L (HR: 0.65, 95%CI: 0.44-0.94, p =0.02).

Conclusion:
Among patients with acute minor-to-moderate ischaemic stroke or transient ischaemic attack, the effect of colchicine on stroke within three months was heterogeneous. Approaches to assessing HTE could identify individuals who might have derived benefit, which shed light on the design and analysis of further trials.
Abstract WMP120: Circulating Mucosal-Associated Invariant T Cells Are Associated with Acute Human Ischemic Stroke and Predict Poor Outcome
Authors: Ozawa Tadashi , Chiba Asako , Hayakawa Hiroko , Miyake Sachiko , Fujimoto Shigeru , Tanaka Ryota
Published: January 2025

Introduction:
We previously demonstrated that Mucosal-associated Invariant T (MAIT) cells were involved in acute ischemic stroke by regulating neuroinflammation (JAHA 2021). This study aimed to clarify the dynamics and role of circulating peripheral MAIT cells in acute ischemic stroke patients.

Methods:
We enrolled patients with acute ischemic stroke who admitted to Jichi Medical University Hospital, classifying them into severe (NIHSS ≥10) and mild (NIHSS <10) groups and outpatients were also enrolled as control. The proportion of circulating MAIT cells, activity (CD69
+
), and cytokine production (IFN-γ
+
or IL-17
+
) were measured by flow cytometry on days 3, 10, and 17 post-stroke. Other innate-like T cells (iNKT and γδT cells) and CD4
+
and CD8
+
T cells were also analyzed for comparison. Associations between MAIT cell dynamics, function, and clinical outcomes were investigated.

Results:
A total of 30 severe stroke, 39 mild stroke, and 30 control subjects were included (Table 1). The mean ages were 77.7, 74.0, and 72.9 years, respectively. On day 3, the proportion of MAIT cells was significantly lower in the severe group, but not in the mild group, compared to control [severe, mild, and control (median): 0.10% (0.07-0.15), 0.31% (0.15-0.79), 0.31% (0.19-0.80); p <0.0001] (Figure 1A). In the severe group, the MAIT cell proportions gradually recovered by day 17. Severe stroke MAIT cells showed significantly higher CD69 positivity and IL-17 production rates from day 3 compared with the control (Figure 1B). The iNKT and γδT cell proportions showed no significant differences in both groups compared to the control. The MAIT cell proportion on day 3 was inversely correlated with the mRS at 3 months (r = -0.2524, p = 0.0425) (Figure 1C). Finally, stroke patients were categorized into four groups (Q1-Q4) based on their MAIT cell population quartile on day 3 and compared with their 3-month mRS. Multivariate analysis revealed that the Q4 group had a significantly lower probability of poor outcomes (defined as not returning to the pre-stroke mRS score at 3 months) than the Q1 group (OR 0.04, 95% CI 0.002-0.59, p = 0.0191) (Table 2).

Conclusions:
We found dynamic changes in peripheral MAIT cells in acute human ischemic stroke. An early decrease in MAIT cells and an increase in activity and cytokine production might correlate with poor outcomes. MAIT cells could play a significant role in acute cerebral infarction and are associated with unfavorable outcomes.
Abstract WMP20: Enhanced Small Extracellular Vesicle Uptake By Activated Interneurons Improves Stroke Recovery In Mice
Authors: Wang Mingjin , Liu Zhongwu , Chopp Michael , Millman Michael , Li Yanfeng , Cepparulo Pasquale , Li Chao , Kemper Amy , Zhang Li , Zhang Zheng Gang , Zhang Yi
Published: January 2025

Background:
Neuronal circuitry remodeling which compromises excitatory and inhibitory neurons is critical to improve neurological outcome after stroke. Cerebral endothelial cell (CEC) generated small extracellular vesicles (CEC-sEVs) have a therapeutic effect on stroke recovery. However, it remains challenge to use sEVs for specifically targeting individual neurons for enhancement of the circuitry after stroke. Using a chemogenetic approach, we tested the hypothesis that Designer Receptors Exclusively Activated by Designer Drugs (DREADD) activated peri-infarct cortical interneurons preferentially take up exogenous CEC-sEVs to enhance neuronal remodeling and functional recovery.

Methods:
Adeno-associated viruses (AAVs) carrying Gq-DREADD and Tomato under the control of the transcription factor distal-less homeobox (Dlx) enhancer element (AAV-hDlx-Gq, 500 nL) were injected into the cortex. The mice were then subjected to middle cerebral artery occlusion (MCAO). CEC-sEVs (1x10
11
particles, i.v.) were administered following interneuron activation by Clozapine-N-oxide (CNO, 5mg/kg, i.p). The circuitry was assayed by Golgi-Cox staining and biotinylated dextran amine labeled axons in the corticospinal tract (CST). Transmission electron microscope (TEM) was used to measure CEC-sEVs in neurons and neuronal mitochondrial (Mito) integrity.

Results:
The adjunct therapy of CEC-sEVs and CNO increased CEC-sEV uptake by peri-infarct cortical neurons and improved somatosensory functional outcome by ~70% vs CEC-sEVs or CNO alone (p<0.05, n=10/group). The adjunct therapy (p<0.05) augmented peri-infarct cortical axonal/dendritic outgrowth and CST axonal remodeling but did not reduce infarct volume. TEM analysis revealed that the neurons with uptake of CEC-sEVs (p<0.05) increased their Mito with intact cristae. Western blot showed that adjunct CEC-sEVs with CNO (p<0.05) decreased ischemia-increased Drp1 and Mff, and elevated ischemia-reduced Mito oxidative phosphorylation (OXPHOS) protein, COX5A, vs CEC-sEVs or CNO alone. Increases of Mito Drp1 and Mff impair Mito crista integrity, which reduces OXPHOS-induced ATP production.

Conclusions:
Our data demonstrate that activated cortical interneurons preferentially increased the uptake of CEC-sEVs, leading to the improvement of functional outcome after stroke. The increased CEC-sEV uptake by activated interneurons reduced ischemic neuronal Mito damage, which may contribute to enhanced neuronal circuitry remodeling.
Abstract WMP24: Heart-Brain Connection: White Matter Hyperintensity Associated with Low Heart Rate Variability
Authors: Martin Ansley , Parrish Michael , Suri Fareed , Rosamond Wayne , Wasserman Bruce , Sen Souvik
Published: January 2025

Background:
Cerebral autonomic regulation is measurable through heart rate variability (HRV). Low HRV (L-HRV) is linked to an increased risk for ischemic stroke. White Matter Hyperintensities (WMH) is a measure of cerebral small vessel disease (cSVD) which is associated with lacunar ischemic stroke. However, limited studies have investigated the link between L-HRV and WMH. This study aimed to investigate the association between L-HRV and WMH.

Methods:
The Atherosclerosis Risk in Communities (ARIC) study measured HRV using 2-minute readings in middle-aged adults at visit 4 conducted between 1996-1998 and conducted MRI scans during visit 5 between 2011-2013. Subjects on medications that influence HRV were excluded. HRV indicators were calculated using the standard deviation of normal-to-normal (SDNN), mean of RR intervals (mean RR), and root mean square of successive differences (RMSSD). cSVD was accounted for by WMH as a percent of total intracranial volume. All HRV metrics and WMH were not normally distributed, hence stratified into quartiles. An ordinal regression model was used to estimate the relationship between the lowest quartile of HRV measure and the highest quartile of WMH volume, adjusted for age, race, sex, body mass index, hypertension, and diabetes.

Results:
Spline graphs depicting the crude and adjusted odds ratio (OR) representing the association between WMH and HRV metrics (N = 1353, mean age 76 ± 5, 72% white and 59% female) shown in figures 1A through 3B. The lowest quartile of RMSSD was significantly related to the highest quartile of WMH (OR = 1.82, CI = 1.38 – 2.39). The relationship remained significant after the adjustment (OR = 1.49, CI = 1.12 – 1.97). The lowest quartile of mean RR was significant with the highest quartile of WMH (OR = 1.52, CI = 1.16 – 1.99). The association remained significant after the adjustment (OR = 1.45, CI = 1.08 - 1.94). The lowest quartile of SDNN was associated with the highest quartile of WMH (OR = 1.57, CI = 1.20 - 2.06). The association remained borderline significant after the adjustment (OR = 1.27, CI = 0.95 – 1.68).

Conclusion:
Our results suggest that L-HRV is associated with the highest quartile of WMH volume. Previously L-HRV has been suggested to associate with atrial fibrillation, a harbinger of cardioembolic stroke. Our results raise the possibility of its association with cSVD, a harbinger of lacunar stroke and vascular cognitive impairment.