Abstract WP54: Longitudinal Proteomics and Fatigue Assessment Demonstrates a Persistent Association Between Post-Stroke Fatigue and Stress Granule Related Proteins Years After Ischemic Stroke

Stroke, Volume 56, Issue Suppl_1, Page AWP54-AWP54, February 1, 2025. Introduction:Post-stroke fatigue is prevalent and significantly impacts quality of life chronically after stroke. Its underlying biological mechanisms remain largely unknown. Here we set out to understand the persistence of post-stroke fatigue and to use plasma proteomics to identify candidate mechanisms.Methods:We acquired neurocognitive assessments and blood draws from 250 stroke survivors from two sites at baseline (median 8 mo after stroke, range 5-120 mo), and 131 participants one year later. The Functional Assessment of Chronic Illness-Fatigue (FACIT) scale was used to assess fatigue, with no fatigue defined as FACIT >41, any fatigue as FACIT≤41, and severe fatigue as FACIT

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Gennaio 2025

Abstract WP16: ROLE OF EPTIFIBATIDE IN POST-THROMBECTOMY STENOSIS

Stroke, Volume 56, Issue Suppl_1, Page AWP16-AWP16, February 1, 2025. Introduction:Currently, no level A evidence exists for the optimal rescue strategy for cases at high risk for re-occlusion following endovascular thrombectomy (EVT) in acute ischemic stroke. Glycoprotein IIb/IIIa inhibitors, which inhibit platelet aggregation and adhesion, show promise as adjunctive therapy, potentially yielding favorable outcomes, especially in residual stenosis cases.Methods:In this retrospective review study, we included patients aged ≥18 who underwent EVT at a comprehensive stroke center with TICI 2b or 2c outcome (admitted between 2019 – 2024), who were noted to have high-risk residual stenosis on angiography after EVT. We defined high-risk post-EVT stenosis as any stenosis with ≥50% lumen stenosis, associated dissection, re-occlusion during thrombectomy, and severe residual luminal irregularity. We excluded patients who had a clear contraindication to Eptifibatide, received a stent, or if the luminal stenosis was related to reactive vasospasm and any cases with TICI 0, 1, or TICI 3 scores.Results:Our sample size was 60 (51.7% male, 48.3% female, mean age 63.9). Mean National Institute of Health Stroke Scale (NIHSS) on admission was 16.6; 36.7% (n=22) received eptifibatide. The rate of re-occlusion was significantly lower in patients who received eptifibatide compared to those who did not (9.1% vs. 36.8%, p=0.032). There was no difference in pre-stroke modified Rankin scale (mRS), NIHSS on admission, mortality, discharge mRS, or 90-day mRS between these two groups, nor between patients who received intravenous thrombolysis (IVT) vs. those who did not. However, among the 16 patients who received IVT, those who also received eptifibatide had significantly lower mean discharge NIHSS (5.0 vs. 13.6, p=0.028), discharge mRS (1.3 vs. 4.5, p=0.009), and 90-day mRS (1.0 vs. 4.1, p=0.038) than those who did not. Ordinal logistic regression of discharge mRS and 90-day mRS in IVT recipients with vs. without eptifibatide usage also revealed significant odds of lower mRS at both timepoints with eptifibatide (OR 7.23, p=0.011 and OR 5.2, p=0.030 respectively).Conclusions:Eptifibatide use is associated with lower re-occlusion rates in patients with residual high-risk stenosis after EVT. Among IVT recipients with post-EVT residual stenosis, eptifibatide use is associated with improved discharge mRS, discharge NIHSS, and 90-day mRS. Given our limited sample size, these findings need to be evaluated further with larger Randomized Control Trials.

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Gennaio 2025

Abstract WP78: Improving Quality of Care through the Implementation of a Dietitian-Led Enteral Access Team in the Post-Acute Stroke Population

Stroke, Volume 56, Issue Suppl_1, Page AWP78-AWP78, February 1, 2025. Introduction:Dysphagia affects approximately 30-80% of ischemic stroke patients. While most patients recover swallowing functions within a week, 10-50% may experience persistent issues for up to six months post-stroke. Early enteral access is critical for providing hydration, nutrition, and medication to these patients. Stroke patients often require specialized nutritional support through feeding tubes. At a large urban academic comprehensive stroke center, we identified an opportunity to develop a model that supports and streamlines feeding tube placement for this population to enhance care quality and improve patient outcomes.Methods:This retrospective study evaluated enteral feeding support in 43 post-acute stroke patients from October 2023 through July 31st. We compared tube placements and outcomes between nursing staff and a dietitian-led enteral access team. Nursing staff used standard NG tube procedures, while the dietitian-led team employed advanced techniques, including an electromagnetic device and bridle retention system to enhance tube stability and reduce need for replacements. We also assessed discharges to acute rehabilitation with bridled small-bore tubes who would have otherwise required PEG placement.Results:Out of 43 patients, 7 patients had NG tubes placed by nursing staff and 36 by the dietitian-led team. All 7 patients required replacement and were ultimately escalated to the dietitian-led team. The dietitian-led team achieved greater tube stability using advanced techniques and required only 1 replacement. A total of 13 patients were discharged to rehabilitation with bridled tubes.Conclusion:In conclusion, we found that a dietitian-led enteral access team can maintain high-quality care and satisfaction through advanced enteral tube placement techniques. Additionally, a subset of patients were able to defer PEG placement allowing for additional time for recovery from dysphagia. Future considerations include evaluating nurse workload reduction, decreased hospital stays, and accelerated rehabilitation placement with early, secure enteral access.

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Gennaio 2025

Abstract 156: A Mast Cell-Specific Receptor Mediates Post-Stroke Brain Inflammation Via a Dural-Brain Axis

Stroke, Volume 56, Issue Suppl_1, Page A156-A156, February 1, 2025. Background:Brain inflammation following ischemic stroke exacerbates neuronal injury. Early immune cell infiltration into the brain after ischemia is correlated with increased risk of subsequent stroke and higher three-month mortality. However, direct mechanisms that underly this immune cell recruitment remain unclear, preventing the development of successful therapeutics. Recent work has identified mast cells as early responders in stroke that incite inflammation, yet how these cells are activated remains unknown. We hypothesized that Mrgprb2, a mast cell receptor known to trigger neurogenic inflammation, initiates mast cell activity in stroke, and that inhibition of this receptor can attenuate stroke injury.Methods:We performed MCA occlusion (MCAO) on wild-type and Mrgprb2-null (Mrgprb2-/-) mice and assessed stroke volume, and behavior. We used flow cytometry and ELISA for immune cell and cytokine profiling to evaluate inflammation. Human stroke patient dura and blood was sampled to assess mast cell activity and to identify potential ligands for Mrgprb2 activation. Lastly, we used osthole, a Mrgprb2 inhibitor, as a post-MCAO treatment to determine if pharmacologic inhibition can attenuate post-stroke deficits in mice.Results:We found that Mrgprb2 is activated in meningeal mast cells after stroke, causing mast cell degranulation and release of chemokines that attract immune cells. Mrgprb2-/-mice exhibited reduced brain inflammation after stroke, leading to attenuated infarct size, and reduced mortality. Further, we show evidence that Mrgprb2-/-mice recruited fewer skull bone marrow neutrophils into the brain, suggesting a novel mechanism whereby mast cells regulate skull bone marrow recruitment. We demonstrated that the human ortholog of this receptor, MRGPRX2, is expressed in human meningeal mast cells, and that these cells are activated in stroke patients. Further, substance P, a known ligand of Mrgprb2/X2, is increased in stroke patient serum. Lastly, osthole-treated mice have reduced post-stroke brain inflammation and improved functional outcomes, confirming that pharmacologic inhibition of Mrgprb2 is a promising therapeutic strategy.Conclusions:Our study identifies Mrgprb2 as a key receptor which triggers mast cell activity in stroke and initiates brain inflammation. Mrgprb2/X2 provides a specific and druggable target to attenuate post-stroke inflammation and holds potential to meaningfully alter the clinical course for stroke patients.

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Gennaio 2025

Abstract 158: Post-Stroke Migrasome-dependent Lysosomal Quality Control Supports Microglia/macrophage Efferocytosis via TSPAN14

Stroke, Volume 56, Issue Suppl_1, Page A158-A158, February 1, 2025. Introduction:Clearing necrotic tissue from lesions by microglia/macrophage is crucial for recovery after acute ischemic stroke (AIS). Lysosomal activity is key for efferocytosis. In the chronic phase, reduced lysosomal activity impairs clearance, causing residual debris and worsening cognitive impairment. Migrasomes, formed during cellular migration, help maintain other organelles like mitochondria.Hypothesis:This study explored how migrasomes in microglia/macrophage help load damaged lysosomes for expulsion, preserving lysosomal quality and efferocytosis post-stroke.Methods:Male C57BL/6 mice including wild-type (WT) andTspan14conditional knockout (Tspan14fl/flLyz2Cre, TSPAN14 CKO) underwent transient middle cerebral artery occlusion (tMCAO). Migrasome production and TSPAN14 expression were evaluated through staining and nano flow cytometry. Neurobehavioral performance was measured by rotarod, foot fault, novel object recognition, and water maze tests up to 14 days post-stroke. In vitro, bone marrow-derived macrophages (BMDM) were cultured with blebbistatin to inhibit migrasome production. BMDM efferocytosis of dead neurons was assessed by staining and flow cytometry.Results:In cultures, 76.9% of migrasomes from BMDM engulfing dead neurons contained damaged lysosomes. Inhibiting migrasome production in BMDM impaired efferocytosis and increased damaged lysosome accumulation. TSPAN14 on the lysosomal membrane mediated lysosome sorting into migrasomes. Migrasomes from TSPAN14 CKO BMDM engulfing dead neurons had 62.3% less lysosomal content than those from WT BMDM, though their numbers were similar (P

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Gennaio 2025

Abstract WMP44: Post Acute Care at Inpatient Rehabilitation Facilities Maximizes 1-Year Home Time among Patients with Acute Ischemic Stroke: Cluster Analysis of Health System and Statewide Data

Stroke, Volume 56, Issue Suppl_1, Page AWMP44-AWMP44, February 1, 2025. Background:The post-acute journey for stroke patients is highly variable. We evaluated patient and health-system factors that contribute to the variability in 1-year home time (HT) by employing unsupervised learning (cluster analyses) among Acute Ischemic Stroke (AIS) patients.Methods:Texas statewide medical claims data on post-stroke care transitions were extracted from a CMS Qualified Entity housing data for ≥80% of the population (including 100% of Medicare Fee-for-Service). Clinical information on a matched sub-population was linked from the EMR of a 7-hospital certified stroke health system. K-means clustering was performed on 1) the statewide dataset on post-discharge care utilization, and 2) the hospital dataset which further included clinical and acute care features. The optimal number (k) of cluster centers was compared algorithmically using direct (average silhouette) and gap statistic methods. Cluster performance, with respect to distinguishing high risk patients more likely to have low HT post-discharge (i.e., total 1-year home time of

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Gennaio 2025

Abstract NS8: Enhancing Post-Stroke Care: Implementing the Transitional Care Model

Stroke, Volume 56, Issue Suppl_1, Page ANS8-ANS8, February 1, 2025. Background and Purpose:Patients discharged home after a stroke are particularly vulnerable during the immediate post-discharge period. We identified significant gaps in post-discharge care for stroke patients at our Comprehensive Stroke Center, including inconsistent follow-up timing and a high rate of missed appointments. This initiative aimed to enhance the post-discharge process to improve care quality and reduce missed follow-ups.Methods:We implemented a streamlined follow-up process for stroke patients discharged home, aligning with the Centers for Medicaid and Medicare (CMS) definition of the Transitional Care Management (TCM). A Nurse Practitioner (NP) conducted inpatient rounds, coordinated follow-up appointments before discharge, and contacted patients within 24-48 hours. Patients were seen by the outpatient stroke NP within 7 to 14 days, either in clinic or via telemedicine. This process, compliant with CMS requirements and billable under TCM, was evaluated over seven months, focusing on clinic no-show rates and reimbursement compared to standard discharge practices.Results:Patients discharged home under our TCM model had a 3% no-show rate, significantly lower than the 14% observed in those discharged without TCM. All patients discharged home with TCM had a post-discharge follow-up appointment scheduled compared to 9% of patients discharged home without TCM who had no scheduled stroke follow-up. Additionally, using the appropriate CMS codes for TCM resulted in higher reimbursement and increased revenue compared to standard follow-up billing.Conclusions:Implementing this initiative aligned our discharge process with the CMS-recognized TCM model, improved scheduling of post-discharge follow-up appointments, reduced post-discharge clinic no-show rates, and increased departmental revenue.

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Gennaio 2025

Abstract WMP37: Prevalence of LRP4 and AGRIN Antibodies in Stroke Patients with Post-Stroke Fatigue: An Observational study

Stroke, Volume 56, Issue Suppl_1, Page AWMP37-AWMP37, February 1, 2025. Introduction:Post-stroke fatigue (PSF) is a common and debilitating consequence of cerebrovascular accidents, potentially stemming from central and peripheral mechanisms. Recent studies have linked myasthenia gravis-related antibodies to PSF, though data on their role remains limited. Current treatments for PSF are often ineffective, underscoring the need for more research into its underlying causes and management.Objectives:This study investigates the presence of myasthenia gravis-related antibodies in patients with PSF after motor recovery, focusing on low-density lipoprotein receptor-related protein 4 (LRP4) and AGRIN antibodies. We aim to evaluate their clinical response to targeted therapies, excluding anti-AChR and anti-MuSK antibodies.Methods:We conducted a cross-sectional study involving patients with PSF who had undergone myasthenia antibody testing. The study cohort included individuals with fatigue following good motor recovery, who tested positive for LRP4 and AGRIN antibodies. Clinical, demographic, and imaging data were analyzed, with clinical response assessed using the Modified Rankin Scale (mRS) at follow-up.Results:Among 935 patients at the stroke unit over two years, 50 were tested for myasthenia antibodies due to PSF. Of these, 17 (34%) were positive for either anti-AGRIN (70.58%) or anti-LRP4 (64.71%) antibodies. Fatigue was reported by 82.35% of the antibody-positive patients. This group consisted of 35.29% females with a mean age of 66.7 years. Most had a history of ischemic stroke (88.23%), with 11.76% having experienced hemorrhagic stroke.All 17 patients received cholinergic medications, showing significant improvement in mRS scores. The Wilcoxon signed-rank test revealed a p-value of

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Gennaio 2025

Abstract 150: Racial and Ethnic Disparities in Post-stroke Quality of Life: A Post-Hoc Analysis of the SHINE Trial

Stroke, Volume 56, Issue Suppl_1, Page A150-A150, February 1, 2025. Background and Purpose:Stroke is a leading cause of long-term disability, often resulting in functional and cognitive impairments that significantly reduce quality of life. While racial and ethnic differences in clinical outcomes after stroke are well-documented, the impact of post-stroke disability on patient-centered outcome measures, which account for physical, emotional, and sociocultural factors, remains insufficiently understood. This study aimed to investigate racial and ethnic differences in post-stroke quality of life among participants in the SHINE trial.Methods:This is a post-hoc analysis of the Stroke Hyperglycemia Insulin Network Effort (SHINE) trial. Self-reported race, ethnicity, and the 12-item Stroke Specific Quality of Life (SSQOL) Scale at 90-day follow-up were used for correlation analyses, adjusted for age, sex, hypertension, diabetes, stroke size, recurrent stroke, and 90-day modified Rankin Scale. The SSQOL is a patient-centered outcome measure that assesses health-related quality of life specific to stroke survivors across 12 domains (Table 1).Results:A total of 907 ischemic stroke patients with hyperglycemia (mean age 65±12.8, 44.7% female, 80.9% with diabetes) were included in this study. At 90-day follow-up, no significant differences were found in overall SSQOL summary scores by race/ethnicity. However, Hispanic patients reported significantly lower scores in self-care (p < .0001) (Figure 1), vision (p = .015), and upper extremity function (p = .007), while Black patients reported lower energy (p = 0.012).Discussion:These findings indicate that Hispanic and Black stroke survivors experience lower quality of life in specific domains after adjusting for stroke severity and other potential confounders. In addition to clinical outcomes, it is crucial to understand stroke survivors’ perceptions of their quality of life which can inform more culturally competent care. Future research should validate these associations and examine the role of socio-economic factors in shaping post-stroke quality of life to promote effective and equitable care in line with the WHO 2030 Rehabilitation agenda.

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Gennaio 2025

Abstract WMP41: Evaluation of a Digital Cognitive Self-Assessment Method for Post-Stroke Cognitive Decline

Stroke, Volume 56, Issue Suppl_1, Page AWMP41-AWMP41, February 1, 2025. Introduction:Post-stroke cognitive decline (PSCD) is a common complication of strokes, and early assessment is crucial. However, outpatient cognitive assessment protocols are inconsistent, leading to missed diagnoses of PSCD. A potential solution is the XpressO application, introduced in 2023 by the creators of the Montreal Cognitive Assessment (MoCA). Because XpressO is self-paced, it can be completed by patients while waiting for an appointment and hence can assess cognition without impacting clinic workflow.Hypothesis:This study aims to investigate the feasibility of using the XpressO online self-administered cognitive assessment and compare its ability to detect PSCD with the MoCA short form (MoCA-sf) at our out-patient stroke clinic.Methods:Patients at the clinic with a history of ischemic or hemorrhagic strokes were included. We used

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Gennaio 2025

Abstract WP356: Use of MicroRNA as a Prospective Biomarker for Post-Stroke Socially Isolated Patients

Stroke, Volume 56, Issue Suppl_1, Page AWP356-AWP356, February 1, 2025. Introduction:Blood-based biomarker investigations for neurological diseases such as ischemic stroke are commonly used in clinical practice and traditionally have focused on measuring alterations in cytokine quantity and composition. An emerging area has been the use of microRNA studying the effects of gene expression after ischemic stroke. There has been extensive evidence that gene expression changes after ischemic injury, especially in gene pathways related to inflammatory response, vascular injury, and cellular degeneration. Establishing a reliable blood-based biomarker used to quantify clinical indications is necessary for emergent treatment. With a blood-based assessment that utilizes transcriptomics, healthcare providers can better understand post-stroke molecular changes more rapidly, which is crucial during this acute phase.Methods:Peripheral blood samples were collected from ischemic stroke patients (N=100) during the acute onset of disease, 24 hours after the last known well. In this study, we investigated possible differences among the stroke population based on risk factors including age, sex, race, social isolation status, and presence of cognitive impairment. For this analysis, overall social isolation status was defined by a mixed model matrix comprised of Lubben Social Network score and UCLA Loneliness score. We used whole transcriptomic sequencing to assess these variables.Results:Overall, there were 8 miRNA sequences significantly upregulated in socially isolated patients. There were no significant differences found among patients based on sex or age variability. Interestingly, we found that circulatory miR-24-3p (FDR adjusted p-value

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Gennaio 2025

Abstract WP327: Identifying Novel Determinants of Death and Readmission Post-Stroke Using Explainable Machine Learning Algorithms

Stroke, Volume 56, Issue Suppl_1, Page AWP327-AWP327, February 1, 2025. Background:Identifying new determinants of death and hospital readmission can help inform target patient populations at high risk for poor transitions of care. Explainable machine learning (XML) algorithms are valuable tools to determine novel modifiable predictors in complex datasets. The goal of this study was to identify risk factors for death and readmission within 90 days post-stroke, focusing on novel non-clinical factors, including social determinants of health (SDOH), neighborhood characteristics, and post-stroke health behaviors. To achieve this goal, we explored the results of 11 distinct XML models, to identify predictors that were common and strong across models.Methods:The study population included 1300 stroke survivors in the Transitions of Care Stroke Disparities Study (TCSD-S), a prospective cohort of patients from 10 comprehensive stroke centers who participated in the Florida Stroke Registry in 2018-2023 (mean age=63.8 (13.9), 56% male, 22% Hispanic, 23% Non-Hispanic Black,51% Non-Hispanic White; 92% ischemic stroke). 90-Day death and readmission (N=192) were obtained from patient interviews and review of medical records. Data on 65 potential risk factors were obtained from Get With The Guidelines-Stroke (demographics, clinical characteristics, medical history, acute care), as well as publicly available neighborhood characteristics (SES, race/ethnicity, business density), and patient interviews at discharge (SES, living arrangement, social support) and 30 days post-stroke (health behaviors). We used 11 distinct XML models to identify the top 12 predictors of death or readmission in each model, resulting in 38 out of 65 distinct predictors across models. Predictors were ranked based on strength of association and consistency across models using feature agreement.Results:Table 1 shows model fit statistics across all XML models with best values in bold. Out of 38 identified predictors, 20 are non-clinical variables. Table 2 shows their rank order. The identified variables reflect the importance of SDH, environmental factors, and behavioral modifications, beyond traditional clinical predictors of death/readmission.Conclusion:XML methods emphasized the importance of non-clinical factors, including SDOH, environmental factors, and behavioral modifications, in transitions of stroke care and stroke outcomes. This illustration of the ability of XML models to find novel and nonobvious predictors may increase the trust in results produced by XML.

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Gennaio 2025

Abstract WMP56: Getting To The Heart of StrokeTM: Novel American Heart Association Initiative Which Increases Identification Of Stroke Etiology And Use Of Evidence-Based Post-Stroke Evaluation By Strengthening Neurology And Cardiology Collaboration

Stroke, Volume 56, Issue Suppl_1, Page AWMP56-AWMP56, February 1, 2025. Background:Nearly one million individuals in the U.S. experience ischemic stroke annually and one-year recurrent stroke risk may exceed 10%. The American Heart Association (AHA) Get-With-The-Guidelines-Stroke® Registry (GWTG-S) suggests that more than 40% of patients with stroke are discharged with a cryptogenic or undocumented etiology which may lead to suboptimal secondary prevention. Consequently, improved neurology and cardiology collaboration and evidence-based post-stroke evaluation may help identify stroke etiology, reduce recurrences and improve outcomes.Methods:In 2022, the AHA, in collaboration with HCA Healthcare and HCA Healthcare Foundation, designed and launched Getting to the Heart Of StrokeTMin 10 HCA Healthcare advanced stroke centers (GTTHOS) to improve neurology and cardiology collaboration, evidence-based post-stroke diagnostic evaluation and assessment of social determinants of health and barriers to care. Components included a learning collaborative model, virtual performance improvement consultations, Plan-Do-Study-Acts, multidisciplinary teams and performance improvement feedback. This analysis compared GTTHOS centers to the rest of HCA Healthcare’s GWTG-S centers (Non-GTTHOS; n=112) at baseline (2022) and follow-up (2023), using custom and existing GWTG-S metrics.Results:At follow-up, GTTHOS documented higher stroke etiology rates (58.06% vs. 48.63%), lower cryptogenic stroke (31.01% vs. 34.89%) and lower undocumented stroke etiology (10.93% vs. 16.48%)(all vs. baseline; p

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Gennaio 2025

Abstract WP126: Identifying Characteristics Associated with Development of Posttraumatic Stress Disorder in Young Adult Stroke Survivors

Stroke, Volume 56, Issue Suppl_1, Page AWP126-AWP126, February 1, 2025. Introduction:Posttraumatic stress disorder (PTSD) has emerged as a mental health barrier that can be experienced by survivors of stroke. PTSD triggered by thoughts of stroke impacts a patient’s ability to optimize their health outcome and maintain compliance with secondary prevention. A young adult stroke clinic treating survivors aged 18-50 in an urban setting in Maryland implemented a standardized practice to screen all patients for PTSD. A retrospective data analysis was performed to determine prevalence of PTSD in the young stroke population and identify predictive characteristics.Methods:Clinic patients were eligible for screening if they were survivors of ischemic or hemorrhagic stroke. The PCL-5 was utilized as the validated PTSD screening tool. Patients were asked to think about their stroke as the stressful event when answering the questions on the tool. A score on the PCL-5 of ≥ 31 was considered positive for PTSD and < 31 was negative. Only the initial screening for each patient was included in the analysis. Additional data collected included demographics, medical history, mental health history, substance use at time of stroke, and mRS at the time of visit. Data collection began in September 2023. Univariate analysis was done to identify which characteristics are associated with developing symptoms of PTSD after stroke.Results:A total of 106 young stroke survivors were screened. Mean age of first stroke was 39.5 years (range 5-50), 57.5% were female (61/106), and 57.5% were black (61/106). PTSD was prevalent in young adult stroke survivors at a rate of 17% (18/106). Compared to patients without the following characteristics, there was a significant increase in the rate of developing PTSD after stroke for patients with a history of anxiety (OR 5.1, 95% [1.2-21.5]) or active smoking (OR 3.8, 95% [1.18-12.4]). The remaining characteristics did not have statistically significant associations with PTSD.Conclusion:PTSD prevalence in this age group of stroke survivors is consistent with what is reported in the literature for all stroke survivors. Preliminary analysis shows there may be predictive characteristics of young stroke survivors who develop PTSD, which can impact their recovery and secondary prevention. The first months are the most impactful in stroke recovery. Further data collection and analysis should be done in this population to look for additional characteristics associated with PTSD to identify at-risk patients early.

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Gennaio 2025

Abstract WP367: Attenuating Post-stroke Ischemia Reperfusion Injury: Establishing the Efficacy of Disodium Malonate in a Clinically Relevant Sheep Model

Stroke, Volume 56, Issue Suppl_1, Page AWP367-AWP367, February 1, 2025. Introduction:Ischemia reperfusion injury (IRI) is a paradoxical and deleterious consequence of current interventions for acute ischemic stroke (AIS). Rapid restoration of oxygen to brain tissue upon reperfusion initiates mitochondrial reverse electron transport (RET) and production of reactive oxygen species (ROS), which exacerbate cell death. A pivotal role of the citric acid cycle intermediate succinate has been identified in driving RET post-reperfusion, whereby succinate accumulated during ischemia is rapidly reoxidized following reperfusion leading to a burst of ROS. Disodium malonate (DSM), a competitive inhibitor of succinate dehydrogenase, has been shown to attenuate RET ROS production following reperfusion and reduce infarct volume in rodent models. Here, we sought to evaluate the effect of DSM on infarct evolution post-reperfusion in a clinically-relevant sheep model of AIS for enhanced clinical translation.Methods:Male Merino sheep (N=13, 24-36 months, 62±6 kgs) underwent right pterional craniotomy and middle cerebral artery occlusion (MCAo) via aneurysm clip application for 4 hrs followed by reperfusion. Animals were pre-operatively randomized into vehicle (0.9% saline, N=5), medium dose DSM (0.5 mmole/min; N=4) and high dose DSM (1.0 mmole/min; N=4). Treatment was administered via right common carotid catheter at a rate of 15 mL/min for 10 min, starting 5 min prior to reperfusion. MCAo and reperfusion were confirmed on digital subtraction angiography (DSA). One hour following reperfusion, animals underwent magnetic resonance imaging (MRI) with a follow-up MRI performed 6 hours later. Infarct volume was calculated on diffusion weighted imaging (DWI) at each time-point to assess ischemic evolution.Results:All animals displayed evidence of MCAo and successful reperfusion following aneurysm clip removal (Figure 1). Infarct volume between groups was comparable at 1 hr post reperfusion (P >0.05), however, by 6 hrs infarct expansion was attenuated in animals receiving DSM compared with vehicles (P=0.0037). This was apparent in both the medium (P=0.006) and high (P=0.011) DSM groups.Conclusions:Intraarterial DSM administration reduces infarct expansion following reperfusion in a sheep model of MCAo. Evaluation of treatment efficacy in a larger cohort of animals is essential to address stroke therapeutic and industry roundtable (STAIR) guidelines and provide evidence to progress DSM to clinical trial for the treatment of IRI in AIS.

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Gennaio 2025

Abstract WP343: Effects of Exogenous Taurine Supplementation on Post-Stroke Recovery in Aged Mice

Stroke, Volume 56, Issue Suppl_1, Page AWP343-AWP343, February 1, 2025. Background:Taurine is a sulfur-containing amino acid present in most mammalian tissues that plays a critical role in regulation of numerous physiological processes. Taurine has been recently identified as a potential neuroprotective agent due to its potent antioxidant and anti-inflammatory properties. However, its effects on stroke recovery are unexplored. Here, we investigated the effects of chronic taurine supplementation on immune cells and recovery in aged stroke mice.Hypothesis:We hypothesized that aged stroke mice treated with taurine will show enhanced recovery compared to vehicle-treated mice. We examined if this beneficial effect was independent of infarct size and was associated with changes in immune cell responses.Methods:Human plasma samples were assessed by mass spectrometry in control and stroke patients. For murine studies, aged (16-18 months) C57BL/6 WT mice were subjected to a reversible 60-MCAO. Three days after stroke, mice were randomly assigned into two groups: one received taurine (n=6M,10F) and the other received water without taurine (n=5M,11F). Behavioral tests were performed at intervals until euthanasia on post-stroke day 42. Flow Cytometry (FACS) was performed to assess for cellular changes in the blood and tissues. Finally, as gut microbiota composition is implied in immune regulation, we determined changes in the microbiota following taurine treatment by performing 16s analysis on fecal samples.Results:First, we compared plasma taurine levels in healthy controls (n=20) and acute stroke patients (n=29) obtained through unbiased metabolomics. Taurine was significantly lower in stroke patients (p

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Gennaio 2025