bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 57: Proteomic markers in large core ischemic stroke and pharmaco-therapeutic possibilities
Authors: Aboul-Nour Hassan , Frank Jacqueline , Miller Lauren , Stowe Ann , Trout Amanda , Pahwa Shivani , Al-Kawaz Mais , Dornbos David , Fraser Justin
Published: January 2025

Background:
Acute ischemic stroke is a leading cause of death and disability in the U.S. Mechanical thrombectomy (MT) has transformed care for patients with small or moderate core infarcts and recently expanded to include those with large infarcts, demonstrating both functional and survival benefits. Despite this, many patients undergoing MT still experience significant disability or death. The discovery of novel adjuvant pharmacotherapies is increasingly critical as MT indications broaden. This study aimed to identify proteomic expression patterns in large core infarct patients undergoing MT to inform potential pharmacological intervention targets.

Methods:
The Blood And Clot Thrombectomy Registry And Collaboration (BACTRAC) tissue registry was reviewed for anterior circulation MT patients treated between June 2017-December 2023. Patients with an initial Alberta Stroke Program Early CT Score (ASPECTS)
>
6 were compared to those with ASPECTS < 6. The primary outcome was the development of malignant cerebral edema (MCE), defined as edema with any degree of midline shift secondary to a completed infarct in the intracranial internal carotid or middle cerebral artery territories.

Results:
One hundred and thirty patients were eligible for out study of which 15 (11.5%) had ASPECTS <6. Patients with ASPECTS <6 were younger (60.5 vs 67.5 years, p=0.04) and more likely to have history of myocardial infarction (27% vs 4%, p=0.01), higher NIHSS on admission (26 vs 17, p<0.0001) and discharge (25 vs 7, p<0.0001) when compared to patients with ASPECTS
>
6. Other baseline demographics were comparable. Ten patients (66.6%) with ASPECTS<6 developed MCE versus 11 patients (9.5%) with ASPECTS
>
6 (p<0.0001). In MCE patients those with ASPECTS<6 had significantly higher expression of FGF 21, DPP4 and NT-3 (p=0.02, 0.04 and 0.04, respectively) and lower expression of IGFBP6 and TWEAK (P=0.006 and 0.03, respectively).

Conclusion:
Patients with large core infarcts (ASPECTS <6) undergoing MT are at a significantly higher risk of developing malignant cerebral edema. The differential expression of proteomic markers such as FGF 21, DPP4, NT-3, IGFBP6, and TWEAK in these patients suggests potential targets for pharmacological intervention. These findings highlight the need for further research into neuroprotective strategies to improve outcomes in this high-risk population.
Abstract 58: Tenecteplase Beyond 4.5 Hours in Acute Ischemic Stroke: A Systematic Review and Meta-analysis of Clinical Trials
Authors: Aladawi Mohammad , Abuawwad Mohammad , Taha Mohammad , kozaa yasmeena , Alrubasy Warda , Hamad Abdullah , Alhnidi Fatema , Elfil Mohamed , Najdawi Zaid , Hataway Felicia , Bakradze Ekaterina , Lyerly Michael
Published: January 2025

Background:
Acute ischemic stroke (AIS) is a leading cause of disability worldwide. While intravenous thrombolysis is recommended within 4.5 hours of symptom onset, many patients present beyond this window. Tenecteplase (TNK) has shown to be non-inferior to tissue plasminogen activator (tPA) in early treatment window. However, its efficacy and safety in the extended 4.5 to 24-hour window remain unclear.

Methods:
We conducted a systematic review and meta-analysis of published clinical trials investigating TNK administration in AIS patients between 4.5 to 24 hours of symptom onset. PubMed, Cochrane Library, Google Scholar, and ClinicalTrials.gov were searched from inception through June 23rd, 2024. Inclusion criteria were: (1) clinical trials, (2) published in English, (3) full-text available, and (4) TNK administration in AIS or transient ischemic attack patients within 4.5-24 hours of onset. Primary outcomes assessed were functional independence at 90 days (defined as a modified Rankin Scale [mRS] score of 0-2) and ordinal shift in the mRS. Safety outcomes included symptomatic intracranial hemorrhage (sICH). Random-effects models were used to calculate pooled odds ratios (OR) with 95% confidence intervals (CI).

Results:
Five clinical trials met inclusion criteria with a total of 1,197 patients (599 TNK, 598 best medical therapy). Mean age was 71 years, with 61.7% males and a median baseline NIHSS of 10. Studies varied in imaging selection criteria, using either MRI DWI/FLAIR mismatch or CTP imaging with different perfusion cut-off values. Additionally, the proportion of patients receiving EVT post-randomization varied among studies. TNK treatment was associated with increased functional independence at 90 days (OR 1.33, 95% CI 1.04-1.70, p=0.02), but no significant difference in overall mRS (standardized mean difference: 0.01, 95% CI -0.37 to 0.39, p=0.969). A trend towards increased sICH with TNK was observed, though not statistically significant (OR 2.16, 95% CI 0.96-5.05, p=0.06).

Conclusion:
This meta-analysis suggests that TNK might be safe and effective for AIS patients in the 4.5 to 24-hour time window, potentially offering improved functional outcomes without significant increase in sICH. Future research should focus on conducting large, multicenter randomized controlled trials with refined patient selection criteria and standardized imaging protocols, to more precisely access the risk-benefit profile of TNK in extended time window.
Abstract 60: Implementing Screening for Post-Stroke Cognitive Impairment in an Outpatient Stroke Clinic: A Step Beyond Subjective Cognitive Complaints
Authors: Uttarkar Ruta , Jones Erica
Published: January 2025

Introduction:
Over 70% of patients experience post-stroke cognitive impairment (PSCI), which can lead to functional decline. Outpatient stroke clinics often lack a consistent and validated cognitive assessment protocol for follow-ups. This increases the risk of missed diagnosis of PSCI, which is often determined based on the subjective assessment of cognitive functioning by patients or caregivers. Our goal was to assess the practice of unstructured PSCI screening at our stroke clinic and test if a cognitive screening protocol would improve PSCI detection in follow-up patients.

Methods:
We led a quality improvement project to identify root causes of the problem and plan interventions for introducing a feasible cognitive screening protocol. We performed a baseline chart review on 79 stroke patients seen at the clinic to assess documentation of discussion of cognitive symptoms during visits. We developed a pre-screening survey to assess educational level, post-stroke rehabilitation participation, and vascular risk factors. We enrolled 30 follow-up patients with either an ischemic or hemorrhagic stroke. An examiner conducted a short-form MoCA (MoCA-sf) test and a CLCE-24 questionnaire for subjective cognitive complaints (SCC) on each patient. We collected data from the electronic record on discharge mRS and NIHSS scores and measured time spent on screening to assess feasibility.

Results:
In baseline chart review, 65% of 79 patients did not have any discussion of cognitive symptoms documented during their visit before our intervention. In our initial screening results, 53% of patients screened positive for cognitive impairment (<=12 MoCA-sf score). There was a moderately negative correlation between MoCA-sf scores and a history of hypertension (-0.48, p 0.007) and hyperlipidemia (-0.38, p 0.044). There was no statistically significant correlation between subjective cognitive complaints (CLCE-24 score) and MoCA-sf scores (-0.09, p 0.626) and only a weak correlation between MoCA-sf and discharge NIHSS (-0.26, p 0.251) and mRS scores (-0.29, p 0.207). The screening took 13 minutes on average to complete.

Conclusion:
Relying on patient-initiated discussion, subjective cognitive complaints, or discharge functional status may lead to missed diagnosis of PSCI. The high prevalence of PSCI in follow-up patients confirms the need for an objective screening protocol like MoCA-sf in stroke clinics for diagnosing PSCI early, especially in patients with hypertension and hyperlipidemia.
Abstract 61: (PFO-ACCESS): Augmenting Communications for medical care or Closure in the Evaluation of Stroke patients with cardiac Shunts
Authors: Pirahanchi Yasaman , Shifflett Ben , Mahmud Ehtisham , Brennan Stefanie , Meyer Dawn , Mortin Melissa , Hailey Lovella , Ravi Vikas , Carrion Penagos Julian , Bowers Jeffrey , Bavarsad Shahripour Reza , Agrawal Kunal , Hemmen Thomas , Meyer Brett
Published: January 2025

Introduction:
Patent Foramen Ovale (PFO) contributes to a quarter of Embolic strokes of Undetermined Source (ESUS). Although benefit of PFO closure in selected patients has been demonstrated, our workflow resulted in a low rate of PFO evaluation for closure. The aim of the PFO-ACCESS program (which included implementation of the Viz.ai PFO-specific communications module) was to determine any change in PFO management due to improved communication between stroke and interventional cardiology (IC) teams.

Methods:
In this Quality Improvement (QI) project, we compared pre-PFO ACCESS (12/22-11/23) to post- periods (11/23-6/24) for PFO referrals. The Viz.ai PFO module was deployed to the stroke team and IC team members. No other workflow changes were introduced. Key performance indicators (KPIs) included referral frequency, PFO closure rates, and referral- related time intervals. Statistical comparisons utilized Mann-Whitney U tests.

Results:
The post-implementation period noted a 492% PFO referral increase (11,65(annualized);p<0.0001). PFO closure number totals showed a 186% increase pre- vs. post- (6,17(annualized);p=0.02), with PFO closure of percentage of total referred cases not increasing (54.55%,26.32%;p=0.08). Time comparisons showed a non-significant decrease in median “referral sent to referral viewed” (10:37hrs, 1:08hrs; p=0.73), “referral sent to referral accepted” (10:37hrs, 1:03hrs; p=0.67) time interval, and “referral sent to closure” time interval (102 days, 97 days; p=0.55).

Conclusions:
The PFO-ACCESS program with Viz.ai PFO module use resulted in a 492% increase in PFO referrals and a 186% increase in closures due to enhanced communication and efficiency in managing PFO related stroke cases. Though increased number of referrals and closures were observed, the PFO closure percentage of total referred cases did not increase indicating selective case management. The higher number of PFO closures shows that more patients are appropriate for PFO closure consideration. Future efforts should focus on expanding outpatient use and increasing provider education to optimize PFO management.
Abstract 65: Stroke Location on Imaging in Patients with a Stroke Hospitalization after an Emergency Department Visit for Dizziness.
Authors: Monjazeb Sanaz , Sangha Navi , Kerber Kevin , Cline Trevor , Scott Lisa , Burke James , Meurer William , Jancis Molly , Baecker Aileen , Nguyen Huong , Manthena Prasanth , park stacy
Published: January 2025

Introduction:
Dizziness is a common reason patients visit the emergency department (ED). Stroke-dizziness diagnosed in the ED is typically due to cerebellar or brainstem lesions which might only have subtle signs of central vestibular dysfunction. Stroke after the ED visit is infrequent but could have been missed at the index visit. In attempts to reduce missed stroke, efforts have focused on implementing the use of vestibular evaluations. However, lacking are details about the strokes in the follow-up period. Imaging details might inform the likelihood that the strokes could have been identified with a vestibular evaluation or were directly related to the index dizziness visit.

Methods:
We conducted a retrospective cohort study from January 2016 to December 2020 across 13 EDs within a large integrated healthcare system in Southern California. We identified all adults with a stroke hospitalization (primary discharge diagnosis of I60-I64) in the 30 days following discharge home from the ED after a primary dizziness visit, excluding those with DNR/hospice status, trauma, or index stroke diagnosis. We abstracted stroke characteristics from the available imaging studies and reports.

Results:
From a total of 77,315 index ED dizziness visits discharged home, we identified 92 (0.12%) patients with stroke hospitalization in the subsequent 30 days. Median age was 59 years (IQR,44-71) and 62% were female. The imaging studies identified an infarct in 69 (75%), hemorrhage in 17(18%), and no lesion in 5(5%) (imaging results not available in 1). In the 91 patients with available imaging results, stroke lesions were present in the anterior fossa in 55% (50 of 91) and the posterior fossa in 41% (37 of 91; 23 cerebellar, 14 brainstem). In 69 patients with imaging results available for measurement, the maximal lesion diameter was a median of 2.1 cm (IQR,0.9-4.0) [anterior fossa: 2.3 cm (IQR, 1.1-4.0); posterior fossa: 2.1 cm (IQR, 0.9-4.0)].

Conclusions:
We found that most strokes diagnosed after ED dizziness visits were due to small lesions in the anterior fossa. These findings suggest that a large proportion of subsequent strokes are unlikely to be identified on vestibular evaluations and/or may not be directly related to the previously dizziness visit.
Abstract 68: Association of Hypoperfusion Intensity Ratio, Cerebral Blood Volume Index, and the CRISP2 Collateral Score with Good Outcome for Patients Transferred for Thrombectomy
Authors: Asimos Andrew , Yang Hongmei , Strong Dale , Teli Katelynn , Clemente Jonathan , DeFilipp Gary , Bernard Joe , Stetler William , Parish Jonathan , Hines Andrew , Rhoten Jeremy , Karamchandani Rahul
Published: January 2025

Background:
For patients with an intra-cranial ICA, M1 or M2 vessel occlusion (ACLVO) initially presenting to non-thrombectomy centers, a CT Perfusion collateral score derived from the CRISP2 study cohort based on the HIR and CBVI obtained at the non-thrombectomy center, has been associated with fast infarct growth and functional outcome, but further validation is needed.

Methods:
We conducted a retrospective study from our stroke network of patients with an ACLVO who underwent CTP scanning (Rapid Software, iSchemaView, Inc., ver 5.5) at a non-thrombectomy center and were subsequently transferred for consideration of thrombectomy. We evaluated the association of three measures of collateral status (HIR, CBVI and the CRISP2 score as depicted in figure1) to 90-day mRS.

Results:
From December 2016 to March 2024, a total of 438 patients with a diagnostic quality CTP, a median age of 70 years (IQR 59-80) and a baseline NIH Stroke Scale score of 15 (IQR 9-20) were included, of whom 92% underwent thrombectomy, with a median CTP to arterial puncture time of 109 minutes (IQR 94-129). Among all patients, HIR (both numerical and dichotomized at both <0.5 or <0.4) was not associated with good functional outcome (90-day mRS 0-2) nor a significant shift toward good functional outcome. The CRISP2 collateral score was associated with a significant shift, but not with good functional outcome. CBVI (both numerical and dichotomized at 0.7), predicted both good functional outcome and a shift toward good functional outcome (see univariate results table). After adjusting for covariates, CRISP2 lost significance in predicting 90-day mRS, while CBVI remained significantly associated with outcome (see multivariate results table). Similar results were seen when limiting the study population to patients achieving recanalization (n=385), defined as a post-thrombectomy TICI score of ≥2B.

Conclusion:
Our study of a large cohort of ACLVO patients transferred for thrombectomy did not find a significant association of HIR and the CRISP2 collateral score with good functional outcome, but did for CBVI. Among CTP measures of collateral status, CBVI alone may play an important role in stroke prognostication and management for ACLVO patients initially presenting to non-thrombectomy centers. Additionally, a favorable CBVI may help identify ACLVO patients to target for future cytoprotective trials when interfacility transfer is required for thrombectomy.
Abstract 71: Relationship Between Timing of Carotid Artery Stent Placement and One Month Rate of Stroke and or Death: Analysis of The National Vascular Quality Initiative
Authors: Suri Fareed , Khan Mohammed Sulaiman , Tolba Hatem , Gomez Camilo , Qureshi Adnan
Published: January 2025

Background:
The ideal timing of carotid artery stenting (CAS) in symptomatic internal carotid artery (ICA) stenosis is partly determined by the risk of stroke and/or death associated with timing of the procedure. We evaluated the risk of stroke and/or death within 30 days of CAS, considering various time intervals from the last ipsilateral cerebral/retinal ischemic event, using real-world data.

Methods:
We analyzed the data for symptomatic patients with ICA stenosis who underwent CAS as part of the national Vascular Quality Initiative (VQI). We divided the time interval between ipsilateral cerebral/retinal ischemic events and CAS into 0-1 days, 2-7 days, 8-14 days, 15-30 days, and 31-180 days. We performed logistic regression analysis to identify the effect of time interval strata between ipsilateral cerebral/retinal ischemic event and CAS on the combined endpoint of any stroke or death within 30 days after adjusting for adjusting for age, gender, severity of stenosis strata, ipsilateral cerebral/retinal ischemic event type, pre-operative use of aspirin, and pre-operative use of antiplatelets other than aspirin.

Results:
The cohort consisted of 5431 patients, of which 308 patients underwent CAS 0-1 days, 1680 patients 2-7 days, 804 patients 8-14 days, 725 patients 15-30 days, and 1914 patients 31-180 days after the ipsilateral cerebral/retinal ischemic event. The proportion of patients who developed any stroke or death within 30 days was greatest in the shorter time interval group (3.2% for Days 0-1) and lowest in the longer interval group (1.7% for Days 31-180). The risk of any stroke or death within 30 days was significantly higher for those undergoing CAS within 0-1 days (odds ratio [OR] 1.99, 95% confidence interval [CI] 1.01-3.79) compared to those undergoing CAS 31-180 days after the ischemic event. The odds ratio was non significantly different for patients who underwent CAS 2-7 days (OR 1.36, 95% CI 0.87-2.16), 8-14 days (OR 1.47, 95% CI 0.85-2.51), and 15-30 days (OR 1.25, 95% CI 0.67-2.24) after ipsilateral cerebral/retinal ischemic event.

Conclusion:
Our results highlight the increased risk of stroke and/or death when CAS is performed within the first 2 days after ipsilateral cerebral/retinal ischemic event. Identifying the ideal relationship between timing of CAS after the non-disabling ischemic event and the combined risk of stroke or death within 30 days will allow appropriate triage of symptomatic ICA stenosis patient.
Abstract 78: Evaluation of AneuScreen
TM
, a Blood-Based Gene Expression Diagnostic for Intracranial Aneurysm
Authors: Tutino Vincent , Poppenberg Kerry , Santo Briana , Lai Rosalind , Burkhardt Jan-Karl , Mokin Maxim , Samaniego Edgar , Levy Elad , Siddiqui Adnan
Published: January 2025

Introduction:
Intracranial aneurysm (IA), a cerebrovascular disease affecting 3-5% of US population, leads to subarachnoid hemorrage. A non-invasive diagnostic to identify those with an IA could facilitate more widespread screening and better disease management.

Objective:
We have designed a PCR-based diagnostic assay for IA, AneuScreen
TM
, that is comprised of a previously-published 50-gene panel. This project aimed to further develop the assay’s predictive model in a large cohort and its predictive power in independent cases.

Methods:
Before testing, the assay underwent rigorous standardization to test signal strength, dynamic range and linearity, and variation across replicates. Blood from consenting individuals with/without IA (angiogram confirmed) were collected under IRB approval from University at Buffalo, University of Pennsylvania, and University of South Florida. One mL of blood was collected into DxTerity RNA-stabilizing blood tube. After running each sample on the assay and standardizing data, gene expression levels of all 50 genes (as well as gene ratios and patient data) were used for support vector machine (SVM) model development in 85% of the data. Top 50 features selected by statistical filtering and ranking were used in nested loops to maximize training performance. Optimal model was validated in remaining 15% of samples.

Results:
We enrolled 497 individuals (276 had IAs). In training, 12 features were most important. The final SVM model performed well in testing set without showing evidence of overfitting, achieving an AUC of 0.74. In independent validation set, the model reached an AUC of 0.80 (Fig. 1A and B).

Conclusion:
SVM model developed using expression data from AneuScreen
TM
in a large cohort of individuals with and without IA was able to predict IA cases with an AUC of 0.80. This demonstrates the potential of using circulating blood to screen for IA presence. Additional testing is required to finetune model and improve accuracy.
Abstract 79: A cerebrovascular longitudinal atlas: different rates of morphological change in aneurysm patients associated with hypertension and diabetes
Authors: Chien Aichi , Salamon Noriko , VINUELA FERNANDO , Szeder Viktor , Colby Geoffrey , Jahan Reza , Boyle Noel , Villablanca Juan , Duckwiler Gary
Published: January 2025

Introduction:
During imaging follow-up of unruptured intracranial aneurysms (IA), changes in cerebrovascular (CV) anatomy are commonly found. While the focus is on the IA site, clinical images capture evidence of vascular remodeling and longitudinal change in the Circle of Willis. This study hypothesizes an association between IA and broader CV changes. This study developed a CV longitudinal atlas (CV shape vs. age) to determine a shared trajectory of CV morphological change in IA patients and identified clinical risk factors associated with IA which affected this trajectory.

Methods:
A total of 405 longitudinal standard clinical magnetic resonance angiography (MRA) image studies were included in the study. On the average there were 3.68 ± 1.34 MRA studies for each IA patient, with follow-up time ranging from 2.5 to 14 years. The Deformetrica was used to analyze the shape changes in the DICOM images. Specifically, a machine learning diffeomorphic analysis of arterial shape with age was performed. A hybrid geodesic regression/Bayesian atlas 4D longitudinal atlas model that inferred the average trajectory of arterial change from patients with overlapping ages of follow-up was created. Parameters mapping individual IA patients to the average trajectory were then analyzed based on patient characteristics.

Results:
The general longitudinal atlas trajectory consisted of longer cerebral arteries as patient age increased. The Kruskal-Wallis test associated several factors related to IA patient medical histories with this pattern of change. Specifically, diabetes mellitus (p=0.016) and no previous subarachnoid hemorrhage (p=0.023) were associated with a faster median rate of CV change (1.5-fold and 2.7-fold, respectively). Hypertension (p=0.0004), atherosclerosis (p=0.001), and ICA IA (p=0.013) were associated with CV morphology more advanced along the CV-age trajectory.

Conclusion:
We developed the first longitudinal atlas model of CV morphological change over time. We used this new technique to investigate the association of IA location and related risk factors with the trajectory of CV change. We identified characteristics that affected the speed and degree of CV change in individual patients. Risk factors like diabetes and hypertension impact a variety of vascular diseases, and our findings indicate IA patients with these factors may have broad CV change and may benefit from review of the Circle of Willis, in addition to the IA site during MRA follow-up.
Abstract 81: New Insights into the Hemodynamic Environment Inducing Cerebral Aneurysm Growth: the NHO CFD ABO Study
Authors: Fukuda Shunichi , Shimogonya Yuji , Watanabe Aoi , Yonemoto Naohiro , Fukuda Miyuki , Yasoda Akihiro
Published: January 2025

Background:
Cerebral aneurysm rupture has a poor prognosis, and a growing aneurysm is prone to rupture. Although hemodynamics is thought to play an important role in aneurysm growth, it is not well understood what hemodynamic environments are involved. We therefore conducted the NHO CFD ABO Study, a prospective observational study to clarify the aneurysm growth risk associated with hemodynamics.

Methods:
Computational fluid dynamics analysis was performed using the unique arterial geometry and flow velocities of the enrolled patients. Hemodynamic metrics were compared by multivariate analysis between aneurysms that grew more than 1 mm and those that did not during the 3-year observation period, using known growth risks as confounding factors.

Results:
A total of 481 patients were enrolled, and 26 growth aneurysms and 176 non-growth aneurysms met the criteria. For aneurysms <4 mm in size, the time-averaged wall shear stress (WSS) and time-averaged WSS gradient were significantly higher in growth aneurysms for the whole aneurysm, neck, body and parent artery, and transverse WSS was significantly higher on the neck and parent artery. In aneurysms ≥4 mm, the normalized transverse WSS, which represents the degree of multi-directional WSS disturbance, was significantly higher in growth aneurysms for the whole aneurysm and the aneurysm dome. Aneurysms <4 mm were more likely to show whole-aneurysm growth, while aneurysms ≥4 mm were often enlarged at the dome.

Conclusions:
These results suggest that there exist two distinct hemodynamic mechanisms for cerebral aneurysm growth depending on size. Aneurysms <4 mm may grow near the aneurysm neck in environments with high magnitudes and multi-directional disturbances of WSS, similar to the environments present at aneurysm development, while aneurysms ≥4 mm may grow in the dome in environments having enhanced multi-directional WSS disturbance. The present evidence may help resolve two conflicting hemodynamic theories of rupture; the "high stress rupture theory" may apply to rupture of aneurysms <4 mm, and the "low stress rupture theory" to rupture of aneurysms ≥4 mm since aneurysm growth is considered a precursor to rupture. Since growing aneurysms, even if not particularly large, are prone to rupture, it would be useful to consider indications for surgical treatment with reference to the hemodynamic predictors of growth obtained in this study.
Abstract 84: Impact of DOAC plasma levels on Hematoma Expansion in DOAC-associated intracerebral hemorrhage
Authors: Schoene Daniela , Tiebel Oliver , Siepmann Timo , Puetz Volker , Barlinn Kristian
Published: January 2025

Background:
Direct oral anticoagulants (DOAC) are associated with an increased risk of

hematoma expansion (HE) in spontaneous intracerebral hemorrhage (ICH). However, the

critical DOAC level influencing this risk remains unclear. This study investigates the impact of DOAC levels on the risk of HE in patients with DOAC-associated ICH.

Methods:
We conducted a retrospective analysis of patients with DOAC-associated ICH who had DOAC-calibrated anti-Xa or -IIa activity levels measured upon admission. Patients were categorized based on a clinically established cutoff for subtherapeutic DOAC levels (<30 ng/ml). Hematoma expansion was defined as a ≥35% increase in hematoma volume between admission and 24-72 hour follow-up CT scans, with symptomatic HE defined as a concurrent ≥4-point increase in the National Institutes of Health Stroke Scale (NIHSS). Multivariable logistic regression models were used to assess the association between DOAC levels and HE, adjusting for baseline ICH volume, onset-to-imaging time, systolic blood pressure, and the use of reversal agents.

Results:
Among 2147 ICH patients admitted between January 2012 and November 2023, 88 had DOAC-associated ICH with available DOAC levels (apixaban, n=36; rivaroxaban, n=30; edoxaban, n=17; dabigatran, n=4). No significant differences were observed in baseline (24.3±27.5 vs. 19.5±16.6 ml; p=0.6) or follow-up ICH volumes (30.6±36.4 vs. 36.4±14.6 ml; p=0.6) between patients with high versus low DOAC levels. Rates of HE (15.4% vs. 22.2%; p=0.6) and symptomatic HE (7.7% vs. 11.1%; p=0.5) were also similar across groups. DOAC levels below the cutoff did not predict HE (adjusted OR 0.7, 95% CI 0.1-4.5; p=0.7). These findings remained consistent when applying a <50 ng/ml DOAC cutoff and in the subgroup of patients not receiving reversal therapy.

Conclusions:
Our study suggests that DOAC levels, as defined by the current cutoffs, do not significantly predict hematoma expansion in patients with DOAC-associated ICH. Further research in multicenter cohorts is necessary to better delineate the relationship between specific DOAC levels and the risk of HE.
Abstract 88: Prophylactic Antiseizure Medication is Associated With Lower Seizure Rates and Worse Health Related Quality of Life
Authors: Banker Margaret , Silva Pinheiro do Nascimento Juliana , Shownkeen Harish , Chang Tiffany , Goldenberger Fernando , Faine Brett , Cella David , Schuele Stephan , Luo Yuan , Tipton Elizabeth , Naidech Andrew
Published: January 2025

Background and Objectives:
Early seizures are a common (10-25%) complication in the first week after acute intracerebral hemorrhage (ICH). However, prophylactic antiseizure medications have not been found to improve outcomes. We tested the hypothesis that prophylactic antiseizure medication would be associated with early seizures in patients at high risk for seizures after acute ICH and outcomes at follow-up.

Methods:
We analyzed prospectively identified consecutive patients with lobar ICH at five sites in the US. We defined high risk for seizures as lobar location of the hematoma, and explored the addition of younger age, larger hematoma volume, and sex as a biological variable. We prospectively recorded the use of antiseizure medications as prophylactic or therapeutic, and identified the occurrence of early seizures clinically or on electroencephalography. At three months, we measured functional outcomes with the modified Rankin Scale and HRQoL in the domains of mobility, cognitive function, and satisfaction with social roles in T Scores (normal 50 +/- 10).

Results:
There were 300 patients with lobar ICH. The mean age was 70 +/- 14 years, and 158 (53%) were female. Overall, 43 (14.3%) patients had an acute seizure. In patients who did not receive antiseizure prophylaxis, 34 of 157 (21.6%) had a seizure. Prophylactic antiseizure medication was associated with a reduced incidence of early seizures (OR 0.25, 95% CI 0.11 - 0.54, P = 0.0005). At three months, T Score of Cognitive Function HRQoL were 11.8 (95%CI 5.6 - 18, P=0.0003) points lower in patients who received prophylactic antiseizure medication, with similar results after stratification by early seizure. In multivariable models, prophylactic antiseizure medication was associated with reduced cognitive function HRQoL (P=0.0004) after correction for age, hematoma volume, seizure, and sex. Results for T Scores of satisfaction with social roles and activities HRQoL were similar to cognitive function HRQoL. T Scores of mobility HRQoL and the Rankin Scale were not different.

Discussion:
In patients with lobar ICH, prophylactic antiseizure medication was associated with a reduced likelihood of an early seizure and reduced HRQoL in multiple domains. Precise patient selection could reduce the incidence of early seizures and minimize effects on HRQoL.

Note:
This abstract is to be considered for the Robert G. Siekert New Investigator Award (Member ID: 100001645980).
Abstract 9: Bridging thrombolysis prior to thrombectomy does not modify the association between Direct-to-angiography vs Repeat Imaging approaches and functional outcomes after EVT in transferred patients
Authors: Shafiq Ameena , Pujara Deep , Goyal Nitin , Chen Michael , Grotta James , Blackburn Spiros , Requena Manuel , Kamal Haris , Abraham Michael , Elijovich Lucas , Dannenbaum Mark , Mir Osman , Tekle Wondwossen , Maali Laith , Narangoli Adeeb , Yaghmoor Bassam , Al-Shaibi Faisal , Saidi Yazid , Al Mostaneer Alhassin , Albedaiwi Mohammed , Montgomery Kelly , Sundararajan Sophia , Opaskar Amanda , Xiong Wei , DeGeorgia Michael , Duncan Kelsey , Ray Abhishek , Hu Yin , Sunshine Jeffrey , Alenzi Bader , Abdulrazzak Mohammad , Hoit Daniel , Martin-Schild Sheryl , Song Sarah , sitton clark , Tsivgoulis Georgios , Arthur Adam , Sila Cathy , Bambakidis Nicholas , Hassan Ameer , Ribo Marc , Sarraj Amrou
Published: January 2025

Introduction:
For patients transferred for EVT considerations, direct-to-angio approach is shown to reduce time to procedure and improve clinical outcomes. We aimed to assess if IV thrombolytics status prior to transfer modifies the association between direct-to-angio approach and improved clinical outcomes in transferred patients who received EVT.

Methods:
In a secondary analysis of a retrospective cohort of transferred EVT patients from 6 centers across US and Europe, patients were stratified based on IV thrombolytic status. Association of direct-to-angio approach vs repeated imaging approach with functional outcomes was assessed among patients with and without IV thrombolytics using appropriate regression models adjusted for age, stroke severity, time to procedure, occlusion location, serum glucose and successful reperfusion status. Heterogeneity of association was evaluated using multiplicative interaction.

Results:
Of 1135 patients with documented IV thrombolysis status, 612 (54%) received IVT – with younger age (IVT - 68 (57-78)y, no IVT - 70 (60-79)y, p=0.032) and higher CT ASPECTS (IVT: 8 (7-10) vs no IVT: 8 (7-9), p=0.038), but similar NIHSS (IVT: 17 (13-21) vs no IVT: 17 (12-21), p=0.91). Estimates of association favored direct-to-angio approach among both no IVT (acOR: 2.06, 95% CI: 1.38 to 3.08, p-value<0.001) and IVT (acOR: 1.33, 95% CI: 0.95 to 1.86, p-value: 0.099), without significant heterogeneity (p-interaction: 0.17). Similar findings were also observed for functional independence (IVT - aOR: 1.64, 95% CI: 1.08 to 2.49, p-value: 0.021; no IVT: aOR: 2.12, 95% CI: 1.25 to 3.58, p-value: 0.005; p-interaction: 0.57) and independent ambulation (IVT: aOR: 1.45, 95% CI: 0.93 to 2.26, p-value: 0.097; No IVT: aOR: 2.92, 95% CI: 1.68 to 5.06, p-value<0.001; p-interaction: 0.10) – Table 1.

Interpretation:
From a retrospective cohort of transferred patients who received EVT, use of IV thrombolytics at baseline did not modify the association between DTA vs RI approach and functional outcomes at 90-day follow-up, suggesting the feasibility of DTA approach regardless of baseline IVT status.
Abstract 91: Lipid Accumulation in Leukocytes Post-Stroke: A Contributor to Impaired Immune Function?
Authors: Do Trang , Couture Lucy , Guzman Gary , Delevati Colpo Gabriela , Khan Romeesa , West Bryce , Devlin Patrick , Cahuiche Ana , Denis Anna , Roh Solji , Venna Venugopal , McCullough Louise , Ritzel Rodney
Published: January 2025

The acute phase of ischemic stroke triggers a complex cascade of cellular responses in the brain and the immune system. Previous studies show that ischemic stroke induces microglial lipid accumulation from 3d to 7d after stroke, linked to pro-inflammatory activation. However, little is known about cellular lipid alterations in peripheral immunity acutely after stroke. We hypothesized that acute ischemic stroke would increase neutral lipid content (lipid droplets) in peripheral myeloid cells and promote immunosuppression phenotypes.

To assess neutral lipid levels during the first week of stroke, we used the BODIPY493/503 dye probe and performed flow cytometry on human PBMCs of healthy volunteers (N=31), and ischemic stroke patients at 3d (N=43) and 7d (N=52). In time course experiments on C57BL/6 mice (1d, 3d and 7d post-MCAO), the same technique was performed using Staph A pHrodo bioparticles, BODIPY, LipiM and Bodipy-cholesterol probes to explore changes in neutral lipid level, lipid uptake, and phagocytic activity of leukocytes. We collected white adipose tissue (WAT)-conditioned PBS from sham and 1d post-MCAO mice to stimulate naive spleen cells and examine whether factors released from WAT alter lipid content and phagocytosis.

In human PBMCs, we found a significant increase in neutral lipids across innate and adaptive cells for up to 7d post-stroke (p<0.01). Consistently, we observed similar results in mice after MCAO (p<0.01). Peripheral monocytes exhibited higher uptake C12 fatty acids and cholesterol and had persistently decreased phagocytic ability up to day 7 post-MCAO (p < 0.05). The impairment in bacterial engulfment was more severe in BODIPY-Hi versus BODIPY-Lo monocytes at both day 1 and day 3 after MCAO, suggesting that higher lipid loads are associated with greater impairment in bacterial phagocytosis (p<0.05). Secretory factors from WAT juice profoundly affected splenic cells of naive mice. We observed an increasing trend in monocyte lipid levels (p = 0.07) after stimulation with stroke (versus sham) WAT-derived supernatant. Immune functions were also impacted, as evidenced by reduced CD68 and MHCII expression, and decreased phagocytosis in dendritic cells.

To conclude, our study provides evidence for lipid accumulation in circulating leukocytes after stroke in humans and mice, which was shown to impair phagocytic engulfment of bacteria. Our findings suggest a novel mechanism of post-stroke immune suppression implicating the brain-fat axis.
Abstract 92: Blocking the VCAM1-VLA4 axis prevents cognitive decline in a mouse model of infarct-induced neurodegeneration
Authors: Zera Kristy , Bradshaw Karen , Zhu Li , Hahn Oliver , Foltz Aulden , Peterson Todd , Yousef Hanadie , Lee Davis , Mayne Elizabeth , Wyss-Coray Tony , Buckwalter Marion
Published: January 2025

Introduction:
Infarct-induced neurodegeneration occurs chronically after stroke and can be prevented by inhibiting B cell influx to the brain. Vascular cell adhesion molecule 1 (VCAM1) facilitates immune cell diapedesis by binding very late antigen 4 (VLA4), and VCAM1 plasma levels are elevated after stroke in people and mice. We hypothesized that chronic treatment with anti-VCAM1 or anti-VLA4 would reduce lymphocyte trafficking and prevent cognitive decline.

Methods:
Adult (3 month old) and middle-aged (10 month old) C57BL/6J male&female mice (N=9-10/group) underwent permanent middle cerebral artery occlusion and were dosed with anti-VCAM1, anti-VLA4 or control IgG every 3 days beginning 4 days after stroke. Sham mice received IgG only. Barnes maze and novel object were performed at -1, 1 and 6 weeks, and single-cell RNA sequencing was performed on immune and endothelial cells at 10 weeks. We quantified pericyte (CD13) vascular (CD31) coverage and extravascular fibrinogen leakage with immunostaining.

Results:
Blocking either VCAM1 or VLA4 reduced B cells 67% or 55%, respectively, compared to IgG treated stroked mice three weeks after stroke. Stroked mice treated with IgG developed a cognitive deficit in both Barnes maze and novel object by 6 weeks, while both anti-VCAM1 and anti-VLA4 treated mice performed comparably to sham animals in the Barnes maze (p=0.398; p=0.972, respectively). Similarly, sham IgG (p<0.0001), stroke anti-VCAM1 (p<0.0001) and VLA4 (p=0.0059) could all perform the novel object task. Single-cell sequencing of immune and brain endothelial cells demonstrated that most transcriptional changes occur in endothelial cells and not immune cells. Anti-VCAM1 and anti-VLA4 both increase expression of BBB maintenance genes (
cdh5, cldn5, ocln, pecam1, lama2
) and decrease inflammatory genes
CD74
and
IL1r1
. Blocking either VCAM1 or VLA4 increased pericyte vascular coverage by 67% (p=0.0113) and 65% (p=0.0215), respectively. Finally, extravascular fibrinogen leakage was also reduced 18% by anti-VCAM1 (p=0.031) and 15% by anti-VLA4 (p=0.0493).

Conclusion:
Blocking either VCAM1 or VLA4 prevents infarct-induced neurodegeneration in middle-aged mice. BBB restoration via increased pericyte coverage and decreased immune cell trafficking into the brain likely both contribute to these therapeutic effects. Together, these findings establish the VCAM1-VLA4 axis as a promising target to restore BBB integrity and prevent infarct-induced neurodegeneration.
Abstract 93: Increased IFN-γ Levels in African American Women Following Ischemic Stroke: A Study of Ethnic Disparities in Plasma Biomarkers
Authors: Sumani Destiny , Dongarwar Deepa , El Hamamy Ahmad , Delevati Colpo Gabriela , Couture Lucy , Li Jun
Published: January 2025

Background:
Stroke outcomes vary with ethnicity, with immune response markers like interferon-gamma (IFN-γ) playing a significant role in stroke pathophysiology. IFN-γ, a proinflammatory cytokine produced by T cells and natural killer (NK) cells, regulates immune responses by activating macrophages and promoting inflammation. Baseline IFN-γ levels in healthy African Americans are similar to Whites. Ethnic variations in IFN-
γ
have been noted in diseases like Rheumatoid arthritis and Hepatitis C. Given the worse stroke outcomes experienced by African Americans, we hypothesized that IFN-γ levels may vary with sex and ethnicity post stroke.

Methods:
Plasma samples were collected from stroke patients admitted to Memorial Hermann Hospital, Houston by UTHealth biobank within 24 hours of admission and analyzed for IFN-γ levels using ELISA. Patients were stratified by sex and ethnicity (Black, Hispanic, White), and statistical analysis was performed using ANOVA, with post-hoc pairwise comparisons. Multilinear regression analysis was conducted to examine the adjusted associations.

Results:
The mean age of patients was 63.6 years, 35% were women, 88% had hypertension, 47% had diabetes mellitus, and 53% had hyperlipidemia. In men, no significant differences in plasma IFN-γ levels were observed across ethnic groups. However, in women (n=21), IFN-γ levels varied significantly by ethnicity, p=0.04. African American women had the highest IFN-γ levels, 4.0±1.7 pg/mL, followed by Hispanic 2.6±1.6 pg/mL, and White women 1.5±0.8 pg/mL. Pairwise comparisons showed a significant difference between African American and White women (p=0.04), but no difference between Hispanic and White women, p=0.62. This association held true when adjusted for other co-morbidities in the multilinear model.

Conclusions:
The higher IFN-γ levels observed in African American women likely reflects an exaggerated proinflammatory response to stroke in women. This heightened response may contribute to worse stroke outcomes in this population. The absence of such differences in men suggests a potential sex-specific inflammatory response to stroke. Understanding the up and downstream pathways of IFN-γ in African American women after ischemic stroke can help elucidate the mechanisms behind disparities in stroke and explore potential sex and ethnicity specific therapeutic interventions targeting inflammation.
Abstract 96: Integrated Genomic and Proteomic Profiling Support Cathepsin-B as a Drug Repurposing Target in Cerebral Small Vessel Disease
Authors: Rivier Cyprien , Huo Shufan , Clocchiatti-Tuozzo Santiago , Renedo Daniela , Sharma Richa , Payabvash Sam , Sansing Lauren , RANGARAJU Srikant , Sheth Kevin , Falcone Guido
Published: January 2025

Background:
White Matter Hyperintensities (WMH) are a radiographic manifestation of cerebral small vessel disease (CSVD), representing myelin and axonal loss. Currently, no drugs specifically target or reduce the burden of WMH. Integrating genomic and proteomic data may identify proteins as potential targets to slow WMH progression. Particularly promising are proteins that serve as pathway-level hubs through which polygenic effects converge.

Methods:
We analyzed data from 53,014 participants enrolled in the UK Biobank. The analytical pipeline involved (Figure 1): 1) linear regression analyses between a polygenic risk score of WMH (from 27 independent variants) and normalized levels of 2,923 proteins ascertained at baseline, adjusting for age, sex, and genetic principal components; 2) evaluation of proteins selected in step 1 for association with WMH volume, ascertained through dedicated research MRIs; 3) mediation analyses to confirm that proteins with significant and directionally concordant associations with both the polygenic score and WMH are indeed mediators of the polygenic score-WMH relationship; 4) Mendelian Randomization using cis-protein quantitative trait loci as instruments to evaluate the causality between selected proteins and WMH and other clinical manifestation of CSVD. Each step was adjusted for multiple testing using Bonferroni correction.

Results:
Our analyses identified two proteins (Cathepsin B and ECHDC3) that met all the criteria to mediate the polygenic effect of CSVD on WMH. However, only one of these, Cathepsin B, was confirmed by Mendelian Randomization (Beta: -0.092, SE: 0.003, P<0.001). Mendelian Randomization also confirmed the association between Cathepsin B and the risk of intracerebral hemorrhage, small vessel stroke, perivascular spaces volumes, and alterations in white matter microstructure (Figure 2).

Conclusions:
Our combined genetic and proteomic approach successfully identified Cathepsin B as a protein linked to WMH and other CSVD phenotypes. Cathepsin B, a lysosomal protease, is well-known for its involvement in programmed cell death, including hypoxia/ischemia-induced neuronal death, a key pathophysiological process leading to WMH (Figure 3). Compounds targeting Cathepsin B have shown promising results in reducing neuronal death and neurotoxicity in Alzheimer’s disease models, where WMH often precedes disease onset. This finding provides a basis for repurposing Cathepsin B-targeting compounds to stabilize WMH burden.