bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TP27: Angiotensin-II Induced Hypertension Impairs the Brain Energy, Amino Acid and Lipid Metabolic Pathways
Authors: Ewees Mohamed , Amro Hani , Dodd Daniel , Abdelhady Ali , Gallego-Perez Daniel , Zweier Jay , Hannawi Yousef
Published: January 2025

Introduction:
Hypertension (HTN) is a leading cause of vascular cognitive impairment and blood pressure (BP) control is linked with improved brain health. Angiotensin-II (Ang-II) infusion in mice has been used to model HTN induced end-organ dysfunction including cerebrovascular dysfunction. However, Ang-II induced HTN effects on the different cerebral metabolic processes are not well studied yet.

Hypothesis:
Since Ang-II induced HTN leads to cerebrovascular oxidative stress, we hypothesized that it would significantly alter the brain metabolic pathways involving energy production, neurotransmitter synthesis, and inflammatory responses.

Methods:
10–13 week-old male C57BL/6J mice were infused with Ang-II (N=3) at 600 ng/kg/min or saline as control (N=3) via subcutaneous osmotic mini-pumps for 14 days. Liquid Chromatography-Mass Spectrometry (LC-MS) was used for non-targeted metabolomics analysis of the brain tissue at the end of treatment. The LC-MS data were analyzed using MetaboAnalyst 6 online tool for functional analysis. Differentially changed compounds with P-value < 0.05 were used for pathway enrichment analysis using metabolic pathways library from Kyoto Encyclopedia of Genes and Genomes (KEGG).

Results:
Ang II infusion caused sustained systolic BP elevation at 2 weeks (Ang-II: 144±5.6 vs saline: 108±4.2 mmHg, P=0.0009). 590 metabolic compounds were identified from the positive and negative ion modes. Enrichment analysis revealed that Ang-II induced HTN causes significant metabolic shift in the brain by altering the pathways which are involved in glycolysis/gluconeogenesis (false discovery rate (FDR)=0.004), pentose phosphate pathway (FDR=0.002), and purine metabolism (FDR=0.004). Additionally, key amino acid metabolic pathways, including alanine, aspartate and glutamate metabolism (FDR=0.003), and arginine and proline metabolism (FDR=0.002), were disrupted. Furthermore, lipid metabolism, particularly arachidonic acid metabolism (FDR=0.007), was altered, suggesting an impact on neuroinflammatory processes.

Conclusions:
Our results indicate that Ang-II induced HTN impairs the cerebral metabolism affecting crucial pathways regulating energy balance, neurotransmitter production, and cellular signaling. This study provides new avenues for mechanistic interventions targeting cerebral metabolism to develop specific therapeutics for Ang-II induced HTN aiming to improve brain health and HTN induced cerebrovascular disorders.
Abstract TP273: Characteristics and Incidence of Stroke and Bleeding in Patients with a First-Ever Transient Ischemic Attack: A US Multi-Database Observational Study
Authors: Abdelgawwad Khaled , Rodriguez Molina Daloha , Lopez Guell Kim , Dinkel-Keuthage Carina , Dursi Fernando , Dyszynski Thomasz , Hackl Melanie , Immonen Juho , Inan-Eroglu Elif , Ko Gilbert , Kurki Samu , Mulick Amy , Soriano-Gabarro Montse , Xeni Jason , Vora Pareen , Candore Gianmario , Manlik Katrin , Vizcaya David
Published: January 2025

Introduction:
Patients suffering from transient ischemic attack (TIA) are at high risk of ischemic stroke (IS). This study describes clinical characteristics and outcomes in patients with a first non-cardioembolic TIA.

Methods:
Using two US administrative claims databases (MarketScan and Optum’s de-identified Clinformatics® Data Mart Database [CDM]) converted to the Observational Medical Outcomes Partnership (OMOP) common data model, we conducted an observational, retrospective cohort study of adults with a first diagnosis of non-cardioembolic TIA between 2012 and 2022. Demographic and clinical characteristics were described at baseline, and incidence rates of IS, intracranial bleeding, and bleeding leading to hospitalization with sensitivity analyses at different time points were calculated.

Results:
Overall, 203,757 patients were included in the study, 97,481 from MarketScan, 106,276 from CDM. Mean age was 62 years in MarketScan and 72 years in CDM. Patients were mostly women (57.6% in MarketScan, 59.3% in CDM). At baseline, prevalence of comorbidities was high (hypertension 66% and 84%, hyperlipidemia 53% and 75%, coronary artery disease 18% and 31%, diabetes 25% and 38% in MarketScan and CDM, respectively). Median follow-up time was 569 days in MarketScan and 716 days in CDM. At 1 year follow-up, incidence rates per 100 person-years of IS, intracranial bleeding, and bleeding leading to hospitalization were 10.9, 0.9, and 4.2, respectively, in MarketScan and 20.2, 1.6, and 7.6 respectively, in CDM. Sensitivity analyses showed that most IS events occurred within 7 days of the index event. Additional event rates and sensitivity analyses are shown in Table 1.

Conclusion:
Results from two US claims databases show that the annual risk of IS is higher than expected following a first TIA diagnosis, especially when including the first 7 days in the ascertainment. Implementation of guideline directed antiplatelet therapies, or new antithrombotic strategies, is needed.
Abstract TP28: Digital Clock Drawing and Recall Enables Rapid Cognitive Screening in Acute Ischemic Stroke Care
Authors: Fedorov Alex , Saurman Jessica , Ro Jennifer , Ammar Abdulraheem Ahmed Jumah , Edwards Paula , Loring David , Hu Xiao , Nahab Fadi
Published: January 2025

Cognitive impairment following acute stroke significantly impacts patient outcomes and rehabilitation. Early detection is crucial, yet comprehensive assessments are often impractical in acute settings. Digital clock drawing and recall (DCR) offers a rapid 5-minute cognitive screening by assessing clock drawing and three-word recall. While previously shown effective in early Alzheimer's detection, its utility in stroke patients has been underexplored. This study investigates the feasibility and validity of DCR compared to the Montreal Cognitive Assessment (MoCA) in stroke patients.

The study involved 80 acute ischemic stroke patients who completed both DCR and MoCA during hospitalization. DCR was implemented on the Linus Health platform. DCR data included DCR scores, battery duration, demographic variables, and recorded NIH Stroke Scale scores. Cognitive impairment was defined using a MoCA threshold of ≤24. Leave-One-Out Cross-Validation and XGBoost were used for analysis. Optuna-optimized hyperparameters and model performance were evaluated via AUC, accuracy, F1-score, sensitivity, and specificity. SHAP analysis provided insights into feature importance.

The median time from stroke to cognitive screening was 3 days [1.0, 2.0]. The impaired group (MoCA ≤ 24) was older (mean 63.2 vs. 53.2 years, p = 0.271), had lower education levels (mean 13.4 vs. 15.8 years, p = 0.005), longer battery durations (median 288.0 vs. 232.0 seconds, p = 0.017), and lower DCR scores (median 1.0 vs. 3.0, p < 0.001). NIHSS scores were higher but not statistically significant (median 4.0 vs. 2.0, p = 1.). Gender, race, and ethnicity were insignificant predictors excluded from the final model.

The XGBoost model demonstrated strong predictive performance, with an AUC of 0.8114, an F1-score of 0.8916, and an accuracy of 0.9. At the threshold of 0.5656 (Youden’s J statistic), the model achieved high sensitivity 0.9841 and moderate specificity 0.5882. SHAP analysis identified DCR score, education level, and battery duration as the most important features.

DCR screening proves to be an effective, rapid cognitive screening tool in acute ischemic stroke care. It demonstrates high sensitivity in detecting subtle cognitive impairments and correlates well with MoCA scores. While further validation is needed, this tool offers a rapid and reliable method for cognitive assessment in acute settings, potentially enhancing personalized treatment approaches and improving patient outcomes in stroke care.
Abstract TP280: PREDICT-POOR_COMP: An artificial intelligence-based tool to predict poor medication compliance after stroke
Authors: Colangelo Giorgio , Cano David , Marichal Sebastian , Baladas Maria , sanchez Ester , Paredes Carolina Kina , Guirao Cristina , Silva Yolanda , Ustrell Xavier , Purroy Francesc , FREITAS JOAO , Pagola Jorge , Muchada Marian , Rodriguez-Luna David , Rodríguez Villatoro Noelia , Garcia-Tornel Garcia-Camba Alvaro , Olive-Gadea Marta , Rizzo Federica , Rodrigo Gisbert Marc , Simonetti Renato , Molina Carlos , Ribo Marc , Rubiera Marta
Published: January 2025

Background:
Risk factor control and medication adherence are critical for stroke secondary prevention, but remain a significant challenge after discharge. We’ve developed an artificial intelligence (AI)-based algorithm to predict poor compliance to prescribed medication (PoorC-med) 90 days post-hospitalization.

Methods:
Consecutive stroke patients discharged from 5 comprehensive stroke centers followed by a multimodal holistic follow-up, including a mobile app for patient communication were evaluated. PoorC-med was defined by a score >0 on the Morisky Green scale. In-hospital and early follow-up multimodal variables were evaluated; those associated with PoorC-med (p<0.05 in the univariate analysis) were used to develop 2 logistic regression models, with variables available at 7 and 30 days after discharge. The models were optimized by grid search to maximize the F2 score, with 5-fold cross-validation to predict PoorC-med at 90 days. A subsequent pool of patients following the same protocol was used for external validation.

Results:
From January 1, 2020, 3261 patients were included in the multimodal follow-up; data on treatment compliance and >90 days follow-up were available for 1946 (59.7%). Of these, patients enrolled through September 23 (1801) were used to develop the AI algorithm; from October 2023, 145 patients were included in the validation set. Three hundred fifteen (17.5%) patients in the training and 33 (22.8%) in the validation set showed PoorC-med at 90 days. Variables associated with PoorC-med are shown in Fig.1. The logistic regression models (Fig. 2) showed the following performance on the training set: Confusion Matrix: [[549 937], [27 288]], Accuracy: 0.46, AUC: 0.64, F1 Score: 0.37, Recall: 0.91, Precision: 0.24, AUC PR: 0.36, AUROC: 0.72.The validation with an independent dataset yielded: Confusion Matrix: [[52 60], [3 30]], Accuracy: 0.57, AUC: 0.69, F1 Score: 0.49, Recall: 0.91, Precision: 0.33, AUC PR: 0.52, AUROC: 0.80 (Fig. 3).

Predictions using variables available only 7 days after discharge showed: Accuracy 0.45, AUC 0.63, Recall 0.92, Precision 0.23, AUROC 0.66

Conclusion:
Our models are able to moderately predict poor medication compliance in stroke patients 90 days after discharge. Early identification of poorC-med patients may facilitate targeted interventions and improve secondary prevention. Further research is warranted to improve our performance and to translate the implementation of predictive models into clinical practice.
Abstract TP284: Post-stroke Cognitive Impairment Based Patient Selection as an Enrichment Strategy for Secondary Stroke Prevention Clinical Trial
Authors: Nadareishvili Zurab , Ciarleglio Adam
Published: January 2025

Enrichment is the prospective use of any patient characteristic to select a study population at higher risk in which detection of a drug effect is more likely than it would be in an unselected population. Patients with post-stroke cognitive impairment (PSCI) found to have higher risk of stroke recurrence in a recently completed meta-analysis. The goal of this study is to test whether PSCI based patient selection may represent enrichment strategy for secondary stroke prevention clinical trial. This is a subgroup analysis of Insulin Resistance Intervention after Stroke (IRIS) trial. In IRIS trial, patients were randomized to receive pioglitazone vs. placebo and had a baseline Modified Mini-Mental State Examination (3MS, where 3MS ≤ 88 was indicative of global PSCI. The primary endpoint of the study was recurrent stroke or MI. We estimated the hazard ratio (HR) for the effect of pioglitazone among those with global PSCI. To determine the sample size for a subsequent trial enriched by including only subjects with global PSCI, we make the following assumptions: (1) time to event follows an exponential distribution in both the pioglizone and placebo groups where the hazard rate for the placebo group is assumed to be the same as in the IRIS trial among those with global PSCI; (2) hazards for the pioglitizon and placebo groups are proportional over the course of the study; and (3) subjects are randomized to pioglitazone or placebo in equal proportions.Data on n = 3,338 patients of original cohort of n = 3,876 were analyzed, and n = 473 among them had PSCI at baseline. During 5-years of follow-up, n=246 patients experienced recurrent stroke, and n = 118 had MI. In patients with PSCI HR was 0.56 (95% CI 0.34 - 0.92) suggesting a 44% reduction in the hazard rate for secondary stroke or MI after 5 years of follow-up in the pioglitizone group compared to the placebo. If we conservatively assume that the true HR = 0.56 (closer to the null of HR = 1 than what was observed in the IRIS trial), then a total sample size of n= 967 willl proivde 90% power using a two-sided log-rank test at the 5% significance level. This conservative sample size corresponds to a 75% reduction in the sample size that was required for the IRIS Trial. PSCI screening may represent enrichment strategy for secondary stroke prevention clinical trial potentially reducing sample size by 75%. PSCI screening-based enrichment can be tested in phase 2 secondary stroke prevention trial.
Abstract TP29: Cognitive Impairment in Patients with Comorbid Carotid Stenosis and Cardiac Disease
Authors: Ibeh Chinwe , Edwards Lloyd , Huston John , Liebeskind David , Pavol Marykay , Lazar Ronald , Marshall Randolph
Published: January 2025

Background:
Previous reports have established a relationship between asymptomatic high-grade carotid artery stenosis (CAS) and impaired cognition. Different forms of cardiac disease have also been associated with cognitive impairment and dementia. The effect of concurrent high-grade CAS and cardiac disease on cognition is unknown. We hypothesize the presence of comorbid cardiac disease has a synergistic effect on cognitive impairment in patients with asymptomatic CAS.

Methods:
Patients with ≥80% internal carotid artery stenosis with no history of stroke were recruited from inpatient and outpatient practices at a single, large, comprehensive stroke center. Patients with vs without comorbid cardiac disease (coronary artery disease [CAD], CAD with history of coronary artery bypass graft [CABG] or percutaneous intervention [PCI], heart failure [HF], atrial fibrillation [AF], or valvular disease [aortic or mitral]) were identified. Cognitive assessments were performed using a battery of 14 standardized tests of attention, memory, processing speed, visual construction, language and executive function. Z-scores were generated based on age-specifc norms. Multivariable linear regression was used to compare test-specific Z-scores in patients with vs without cardiac disease controlling for age, sex, years of education and depression.

Results:
Thirty-three patients with asymptomatic CAS were identified (21 males, age 74+/-10 years, education=16+/-3 years). Twenty-six (79%) had cardiac disease. Patients with comorbid cardiac disease had significantly lower Z-scores across multiple tests of memory compared to patients without cardiac disease (Fig). After adjusting for age, sex, years of education and depression, significant differences persisted in tests of memory in patients with CAD [Hopkins Recognition Memory Test, β= -1.127 (95% CI: -2.234, -0.020), P=0.046], CABG [Hopkins Learning Trial Memory Test, β= -1.441 (95% CI: -2.532, -0.350), P=0.012], and valvular disease [Hopkins Learning Trials Memory Test, β= -1.121 (95% CI: -2.224, -0.018), P=0.047].

Conclusion:
Cardiac disease is common among patients with asymptomatic high-grade carotid stenosis and may have a synergistic effect on impairments in memory in a manner not mediated by stroke. Further work is needed to confirm these relationships and their longterm implications on vascular brain health.
Abstract TP292: Number of destinations other than home and work within a half mile of residence and outcomes in first year poststroke
Authors: Delhey Leanna , Shi Xu , Brown Devin , Morgenstern Lewis , CASE Erin , Cox Melinda , Zelner Jon , Lisabeth Lynda
Published: January 2025

Introduction:
Residing in a neighborhood with greater destinations – places where you engage with the community aside from home and work – has been associated with more favorable functioning, and quality of life, particularly among moderate-severe stroke survivors. Prior studies were limited by cross-sectional design, confounding, or defining the neighborhood by census tract.

Hypothesis:
Greater number of destinations within a 0.5-mile radius of the survivor’s residence is associated with more favorable poststroke functioning, quality of life, and depression over the first year.

Methods:
We included non-Hispanic White and Mexican American first-ever stroke (ischemic or intracerebral hemorrhage) survivors enrolled in the Brain Attack Surveillance in Corpus Christi project (2009-19), a population-based cohort in Nueces County, Texas. Our exposure is the count of destinations within a 0.5 mile around the survivor’s residence at the time of their initial admission for stroke. We considered 11 types of destinations (Figure 1). Outcomes were assessed at approximately 3, 6, and 12-months poststroke and included functioning (activities of daily living (ADL)/instrumental ADL), health-related quality of life (abbreviated Stroke-Specific Quality of Life scale), and depression (Patient Health Questionnaire-8). We applied inverse probability weighting and multiple imputation to account for attrition and missing data. We fit adjusted linear mixed models, accounted for repeated measures, and considered interactions with follow-up time and stroke severity (NIH stroke scale - mild (<5) or moderate-severe (≥5)).

Results:
We included 1,114 Mexican American and 672 Non-Hispanic White stroke survivors who completed the 3-month (N=1,321), 6-month (N=677), or 12-month interview (N=652) (Figure 2). Median age was 64 years, 55% male, and 74% with mild stroke. Stroke severity modified the association of destinations with functioning (p=0.091) and quality of life (p=0.048). Results are shown in Figure 3. No associations were observed between destinations and depression (p>0.05). Associations did not differ by follow-up time (p>0.25).

Conclusions:
Among moderate-severe stroke survivors, greater number of nearby destinations was associated with more favorable functioning and quality of life in the first year poststroke. Future research is needed to determine if specific types of destinations may support poststroke outcomes.
Abstract TP293: Association Between Aortic Arch Type and Lateralization of Subclavian Artery Stenosis: An Observational Cohort Study
Authors: Zhang Zhao , Luo Anling , Yang Yujia , Li Xuzi , Deng Yiting , He Li , Zhou Muke
Published: January 2025

Background and Objectives:
Left subclavian artery (LSA) is more prone to atherosclerosis than the right one. The study was designed to investigate whether aortic arch types (AAT) was associated with the lateralization of subclavian artery stenosis (SAS).

Methods:
In this observational prospective registry study, we reviewed the digital subtraction angiography (DSA) database from our comprehensive stroke center between 2015-2023. Patients (age ≥ 18 years) with clinically manifest atherosclerotic vessel disease or risk factors for atherosclerosis and a normal branching pattern of the aortic arch were included. AAT and degree of SAS were determined by DSA. Breslow-Day test and multinomial logistic regression models were performed to identify the association between AAT and SAS.

Results:
A total of 7,470 patients (mean [SD] age, 57.4 [14.9] years; 5,098 [68.3%] male and 2,372 [31.8%] female; 2,430 [32.5%] aged < 60 years) were included. Among the 7,470 patients, 771 (10.3%) were detected with SAS, including 518 (6.9%) on the left side, 173 (2.3%) on the right side and 80 (1.1%) on the bilateral side. Frequency of AAT Ι, ΙΙ and ΙΙΙ were 1,741 (23.3%), 5,047 (67.6%), and 682 (9.1%) respectively. LSA is more susceptible to atherosclerotic stenosis than right subclavian artery (RSA) with AAT Ι (any degree stenosis: 6.0% vs 2.4%, p < 0.001) and ΙΙ (any degree stenosis: 8.4% vs 2.9%, p < 0.001). We found no significant difference in occurrence of stenosis between LSA and RSA among patient with AAT ΙΙΙ (any degree of stenosis: 10.4% vs 9.2%, p = 0.521) (Figure1). The Breslow-Day test showed that there existed significant differences in the odd ratio (ORs) for the side of subclavian artery across each stratum of AAT (p <0.001) (Figure 2). AAT ΙΙΙ was independently associated with LSA stenosis (OR 0.65, 95% confidential interval [CI] 0.23-0.79, p = 0.027) and RSA stenosis (OR 2.01, 95% CI 1.20-3.42, p = 0.011).

Conclusions:
AAT was associated with the preferential lateralization of SAS to the left side. Considering the complex interrelationship between vascular geometry, local hemodynamics, vascular aging and atherosclerosis, the finding needs to be validated with longitudinal studies and the underlying mechanism should be further explored with hemodynamics assessments in upcoming research.
Abstract TP3: Safety of Tenecteplase in Stroke Mimic
Authors: Rowe Anthony , Wiseman Brian , Hamilton Leslie , Crowell Sarah , McCampbell Lillian , Williams Destiny
Published: January 2025

Introduction:
Thrombolysis is the gold standard of treatment for acute ischemic stroke, but it must be administered within a narrow time window. This urgency requires healthcare providers to make swift treatment decisions, even when other diagnoses might explain stroke-like symptoms. While treatment with alteplase has been shown to be safe in stroke mimics, the safety of tenecteplase (TNK) in stroke mimics remains unknown. Therefore, our objective was to evaluate the safety of TNK in patients with stroke-like symptoms with and without a confirmed stroke diagnosis.

Methods:
This was a retrospective cohort study comparing those with acute ischemic stroke (AIS), defined as an ischemic stroke diagnosis on discharge, and those with a stroke mimic, those without an ischemic stroke diagnosis on discharge. Consecutive patients admitted between June 1, 2020, and June 30, 2023, were screened for inclusion in the study. Those patients less than 18 years old, without neuroimaging within 24 hours of TNK administration, who received TNK for an indication other than acute ischemic stroke, and who received mechanical thrombectomy were excluded from the trial. The primary outcome was symptomatic intracranial hemorrhage as defined by the ECAS III criteria. Secondary outcomes included major systemic hemorrhage, minor systemic hemorrhage, asymptomatic intracranial hemorrhage, length of stay, angioedema, and discharge disposition.

Results:
A total of 250 patients were included in the study. Of those 174 were in the AIS group and 76 in the stroke mimic group. Those in the AIS group were older (69 [13.8] vs. 62.3 [16.1]; p=0.0008), but otherwise were similar with regards to baseline demographics. There was no statistical difference in symptomatic intracranial hemorrhage when comparing the AIS and mimic groups (5 [2.9%] vs. 0 [0%]; p=0.3267); however, there was a statistically higher proportion of patients who experienced an asymptomatic intracranial hemorrhage in the AIS group (15 [8.6%] vs. 0 (0%); p=0.0067). In addition, those in the AIS group had a longer median length of stay as compared to the mimic group (3 days [2 days, 6 days] vs. 2 days [2 days, 4 days]; p=0.0018). There were no statistical differences in major systemic hemorrhage, minor systemic hemorrhage, angioedema, or discharge disposition.

Conclusion:
The use of TNK in patients with a stroke mimic did not result in a statistically higher proportion of patients who experienced a symptomatic intracranial hemorrhage.
Abstract TP306: Prevalence of right-to-left shunting on transthoracic echocardiography in patients with cancer and stroke
Authors: Biglou Sanaz , Lun Ronda , Ramsay Timothy , Shamy Michel , Schwerzmann Markus , Dowlatshahi Dar
Published: January 2025

Background:
Cancer is a leading cause of mortality and a well-known risk factor for ischemic stroke. However, the relationship between cancer and stroke is not well studied. Previous research in this area suggests presence of right-to-left shunt as a possible underlying mechanism of paradoxical embolism in patients with cancer diagnosis within one year of the stroke. Thus, our study seeks to further investigate the potential role of right-to-left shunting in stroke occurrence among cancer patients.

Methods:
This is a retrospective cohort study with our population consisting of patients presenting to the Ottawa Hospital with ischemic stroke between January 01, 2020, and December 31, 2022, who have undergone transthoracic echocardiography. Presence of right-to-left shunting is identified on echocardiography in patients without cancer and those with cancer diagnosis one year before and one year after the ischemic stroke. The prevalence of shunt is assessed using 95% confidence intervals (CI).

Results:
Among 495 patients (37% female, median age 53 years) presenting with ischemic stroke, 47 (9.5%) had cancer diagnosis within one year of stroke, with 12 patients (25.5%, 95% CI 14 - 40) diagnosed with a shunt. In contrast, among 448 patients (90.5%) that did not have a cancer diagnosis within one year of their stroke, 133 patients (30%, 95% CI 25 - 34) were identified to have a shunt.

Conclusion:
The prevalence of right-to-left shunting tends to be lower in patients presenting with ischemic stroke and active cancer diagnosis. This result is consistent with a recent study in this area indicating a higher rate of shunt among patients without cancer than those with cancer. Our finding does not support the hypothesis that cancer-associated stroke is related to right-to-left shunting.
Abstract TP311: Immune Checkpoint Inhibitors and Stroke Etiology in a Retrospective Cohort of Patients with Non-Small Cell Lung Cancer
Authors: Handshoe Jonathan , Coors Benjamin , Khorana Alok , Uchino Ken , Ibrikji Sidonie
Published: January 2025

Introduction:
Immune Checkpoint Inhibitors (ICIs) used for treatment of malignancies might promote atherosclerosis and increase the risk of ischemic stroke (IS). We aimed to compare IS characteristics of patients with non-small cell lung cancer (NSCLC) who received ICIs compared to those who did not. We hypothesized that IS associated with atherosclerosis will be more common among those treated with ICIs than other treatments.

Methods:
A retrospective single center study of patients,18 or older, with NSCLC presenting between 2013 and 2023, treated with either ICIs, chemotherapy, or a combination and had an IS any time following treatment. Patients without vessel imaging were excluded. We collected demographics and stroke characteristics. Two sample Mann-Whitney U and chi-square test were used to compare demographics and stroke etiologies among patients who received chemotherapy and those who received ICIs with or without chemotherapy.

Results:
A total of 58 patients were identified, 22 received chemotherapy only and 36 received ICIs. The mean age was 68.8, with 50% male (29/58). ICI treated groups had significantly more stage IV diagnoses (chemotherapy only 3.6%, ICI 67%, p=0.04). There was no difference in median time from treatment to stroke onset in days between groups; chemotherapy 90.5 (range 27-386) vs. ICI 337.5 (range 95-665), p= 0.39. The stroke etiology in those treated with chemotherapy alone were as follows: Large artery atherosclerosis (3), cardioembolic (8), small vessel disease (5), ESUS (5), other (1). For those treated with either ICI alone or ICI and chemotherapy: Large artery atherosclerosis (5), cardioembolic (6), small vessel disease (2), ESUS (23), other (0). Stroke etiology consistent with embolic stroke with unknown source (ESUS) was more common in the ICI group (chemotherapy only 2.3%, ICI 64%, p=0.02).

Conclusions:
Contrary to prior research suggesting atherogenesis with ICI, the most common stroke etiology in the ICI group was ESUS.
Abstract TP316: Stroke Events in Cancer Versus Non-Cancer Patients With Aortic Stenosis During Transcatheter Aortic Valve Replacement
Authors: Duchow Mariel , White Gord , Ali Asgar Juzer , Lopez Baez Michelle , Velez Quinones Virginia , Fischer Andrew
Published: January 2025

Background:
Despite improvements in the safety of transcatheter aortic valve replacement (TAVR), ~4% of patients experience a procedure-related stroke. TAVR seems to be preferred in patients with cancer; however, related research on the clinical efficacy and stroke outcomes of TAVR in patients with cancer is limited. This study aimed to evaluate the association of TAVR-related stroke in patients with cancer and without cancer.

Methods:
This retrospective cohort study identified 14,046 patients with aortic valve stenosis that underwent TAVR. Patients were stratified into two groups: cancer patients 13583 (96.7%) and non-cancer patients 463 (3.3%). We assessed if there was a difference in stroke events between cancer and non-cancer patients. Binary logistic regression models were used to measure the stroke association.

Results:
Among 14,046 TAVR patients, 214 (1.5%) had a procedure-related stroke. These patients were more likely to be female (p=0.0007, 95% CI: 1.219-2.102), older (p<0.0001, 95% CI: 1024-1.065), or tobacco smokers (p=0.0044, 95% CI: 1.249-3.329). After adjusting for age, sex, and smoking status, TAVR-related strokes in cancer patients (463/14,046), cancer diagnosis was not significantly associated with stroke (p=0.3609, 95% CI: 0.697-2.695).

Conclusion:
Cancer patients do not differ significantly from non-cancer patients with regard to procedure-related stroke. Our study is the first one to investigate stroke outcomes in cancer versus non-cancer patients with aortic valve stenosis that underwent TAVR. Further research is needed to assess confounding factors as well.
Abstract TP324: Lupus Anticoagulant Is Associated With Acute Recurrence in Cardiogenic Embolic Stroke in Older Patients
Authors: Kida Hiroyuki , Sakai Kenichiro , Komatsu Teppei , Okumura Motohiro , Nakada Ryoji , Kitagawa Tomomichi , Takatsu Hiroki , Sakuta Kenichi , Mitsumura Hidetaka , Iguchi Yasuyuki
Published: January 2025

Background and Purpose:
Antiphospholipid antibody syndrome (APS) is a rare cause of cerebral infarction, but the effect of antiphospholipid antibodies (aPL) on the acute phase of ischemic stroke in each stroke subtypes is still unclear, especially in the elderly patients. To clarify this, we compared antiphospholipid antibody levels in patients with acute cerebral infarction with or without recurrence, expansion, or hemorrhagic transformation of infarct in each stroke subtype.

Methods:
Consecutive ischemic stroke patients in a comprehensive stroke center were screened between April 2013 and April 2024. Inclusion criteria were: 1) admitted 24 hours from the onset, 2) more than 60 years-old on the admission, 3) who had follow-up MRI/CT around one week from the onset, and 4) whose aPL (anti-cardiolipin-beta2-glycoprotein I complex antibody [β2-GPI], anti-cardiolipin antibody [aCL] and lupus anticoagulant [LAC]) measured during the admission for suspected APS. Then, we dichotomized the patients with and without recurrence (R), expansion (E), or hemorrhagic transformation (HT) of infarct upon follow-up MRI/CT findings. We compared clinical features including aPL between the groups by each stroke subtypes based on TOAST classification. Sensitivity and specificity were calculated from receiver operating characteristic (ROC) curve of aPL for predicting R, E, and HT.

Results:
We screened 2,528 consecutive ischemic stroke patients and 271 patients met the inclusion criteria (60 [22%] cardioembolism (CE), 43 [16%] large-artery atherosclerosis, 29 [11%] small-vessel occlusion and 139 [51%] others). In enrolled patients, 30 (11%) patients showed R, 43 (16%) patients for E and 65 (24%) patients for HT. In CE, CL aCL and LAC were higher in patients with R compared without R (aCL 9.5 vs. 8.0 U/mL,
p
=0.047; LAC 1.15 vs. 1.01,
p
=0.006) while aPL were not significantly different in other stroke subtypes. Also, aPL were not significantly different between the patients with and without E or HT. In CE, R increased as LAC became higher (1st tertile vs. 2nd tertile vs. 3rd tertile of LAC: 0 (0%) vs. 1 (6%) vs. 6 (33%),
p
=0.004). In ROC analysis, the optimal cutoff of LAC for predicting R in CE was 1.12 (area under curve 0.83 [95% confidence interval 0.71-0.94],
p
=0.006; sensitivity 0.86, specificity 0.82).

Conclusions:
In CE, LAC was associated with acute recurrence of infarct. LAC should be measured in cardioembolic stroke with recurrence in acute phase.
Abstract TP33: Microhemorrhages and Cortical Superficial Siderosis in Cognitively Impaired Patients: Prevalence and Risk Factors
Authors: Alotibi Hessah , Vargas-Gonzalez Juan-Camilo , Alcaide Leon Paula , , Tartaglia M Carmela
Published: January 2025

(1) Background:
Cerebral microbleeds (MBs) and cortical superficial siderosis (cSS) can be seen in a multitude of etiologies. The risk factors for cerebral MB and cSS and their relationship with cognitive decline are not well known.

(2) Objective:
This study aimed to explore the risk factors for cerebral MBs and cSS and to examine their impact on cognitive function in a cohort of cognitively impaired patients.

(3) Methods:
We conducted a case-control study involving 415 patients who underwent a brain magnetic resonance imaging (MRI) with a dementia protocol and cognitive assessments at the University Health Network, Mount Sinai Hospital, and Women's College Hospital in Toronto from 2014 to 2022. Cognition was assessed using the Mini-Mental State Examination (MMSE) and/ or the Montreal Cognitive Assessment (MoCA)

The case group (n=137) included patients with cerebral MBs and/or cSS, while the control group (n=278) was comprised of randomly selected patients for cognitive impairment and underwent the same MRI protocol. We also evaluated the location of the MB including if deep, lobar or mixed MB. White matter hyperintensities (WMH) were graded using the Fazekas scale, wherein severity is assessed from 0 to 3. We performed Multivariate logistic regression to identify risk factors associated with cerebral MBs and cSS.

(4) Results:
Patients with MBs and/or cSS were older and had a higher prevalence of hypertension compared to the control group. In the multivariate analysis, age (OR = 1.05, 95% CI: 1.02-1.08, p = 0.002), hypertension (OR = 2.67, 95% CI: 1.75-4.08, p < 0.001), and higher Fazekas scores (OR = 1.58, 95% CI: 1.22-2.06, p < 0.001) were associated with cerebral MBs and cSS. Cognitive scores were significantly lower in the group with MB and cSS (MMSE: 22.3 vs. 26.1; MoCA: 19.7 vs. 24.8, both p < 0.001). Regression analysis showed that MB location did not significantly affect cognitive scores. The estimates for deep (0.45, 95% CI: -0.38 to 1.27; p < 0.286), lobar (-0.17, 95% CI: -0.55 to 0.21; p < 0.379), and mixed (-0.12, 95% CI: -0.47 to 0.24; p < 0.522)

(5) Conclusions:
Age, hypertension, and small vessel disease as measured by Fazekas scale are significant risk factors for cerebral MBs and cSS. Cognitive impairment was more severe in those with MBs and cSS and not related to their location. It is essential to manage vascular risk factors, such as hypertension,as this is ssociated with MBs and cSS , which are associated with worse cognitive impairment
Abstract TP38: Harnessing the Gut-Brain Axis: The Therapeutic Potential of Akkermansia and Its Exosomes in Ischemic Stroke Recovery
Authors: Zhang Yue , Qiu Lina , Ying Cai , Xiuhua Yao , Yilin Ma , Zhao Chengcheng , Chen Tao , chen jieli , WU JIALING
Published: January 2025

Introduction:
The gut-brain axis is pivotal in recovery after stroke, with the gut microbiome playing a significant role in neurological outcomes.
Akkermansia muciniphila
(AKK), a beneficial gut bacterium, has shown promise in metabolic conditions. We hypothesize that AKK and its exosomes (AKK-Exo) can enhance stroke recovery by modulating gut-brain interactions.

Methods: Human study:
fecal samples from 88 ischemic stroke (IS) patients and 23 healthy elderly were analyzed using 16S rDNA sequencing. Animal study: 6-8 months old male mice subjected to photothrombotic middle cerebral artery occlusion were treated intragastrically with either AKK or AKK-Exo. Neurological recovery was evaluated over 2 weeks, accompanied by 16S rDNA sequencing and metabolomics analysis of fecal and plasma samples. The RT-PCR, Western blotting, and immunofluorescence were employed to assess inflammation, microglial activation, and white matter (WM) remodeling in the brain.

Results:
Human study demonstrated that IS disrupts gut microbiota, with an increase in pathogenic bacteria like
Parabacteroides
and a decrease in beneficial microbes like
Lachnospira
. Patients with higher levels of AKK exhibited better neurological outcomes. In the mouse model, both AKK and AKK-Exo treatments resulted in improvements in neurological function, also led to a restructuring of gut microecology, characterized by a reduction in pro-inflammatory bacteria and an increase in beneficial species. Moreover, the treatments were associated with a decrease in pro-inflammatory cytokine levels in both the brain and intestines. Metabolomics analysis revealed a notable reduction in trimethylamine N-oxide and an increase in beneficial metabolites such as sphingolipids and flavonoids. These metabolic changes were correlated with improved neurological outcomes. Molecular analyses further demonstrated that AKK and AKK-Exo treatments promoted the integrity of the gut barrier, reduced systemic inflammation, and induced an anti-inflammatory M2 microglial phenotype and facilitated WM remodeling in the brain.

Conclusion:
This study underscores the therapeutic potential of AKK and its exosomes in promoting recovery after IS, highlighting their role in gut-brain axis modulation. Our findings suggest that AKK and AKK-Exo could serve as promising therapeutic agents for improving stroke outcomes through microbiome-based interventions.

Keywords:
Gut-brain axis, microbiome, ischemic stroke, Akkermansia, neuroinflammation
Abstract TP387: Magnetothermal stimulation for treatment of stroke
Authors: Choi Kangho , Kim Jahae , Kim Jihye
Published: January 2025

Background and Objective:
The effects of noninvasive focused nanomagnetic brain stimulation (MagStim) on post-stroke motor deficits and metabolic dormancy in subacute ischemic injury is not well-established. This study examines the therapeutic actions of MagStim for enhancing motor recovery after stroke.

Methods:
We administered focused MagStim for 30 minutes daily following a magnetic nanoparticles (MNP) injection (15mg/mL) into the targeted motor cortex subsequent to three weeks of middle cerebral artery occlusion (MCAO). Behavioral tests for motor functionality and PET imaging for cerebral metabolic activity were conducted. Additional assessments included cortical hyperexcitability, neuroinflammation, blood-brain-barrier (BBB) integrity, and neurogenesis at four weeks post-stroke, according to the treatment groups (Control, MNP injection only, and MagStim).

Results:
The MagStim group exhibited significant improvements in motor deficits and cerebral metabolic activity compared to the Control and MNP groups (
p
< 0.05). Focused MagStim modulated cortical excitability, evident by an elevated action potential threshold for spike initiation and reduced firing frequency post-stroke. The MagStim group also demonstrated markedly decreased levels of inflammatory markers such as IL-1β, IL-6, TNF-α, MCP-1, and ICAM-1 in comparison to the Control and MNP groups. Markers of BBB integrity and immunofluorescence for neurogenesis were substantially improved in the MagStim group.

Conclusions:
Our findings reveal that focused MagStim facilitates the recovery of motor deficits and metabolic inactivity in the brain by effectively modulating excitability, reducing neuroinflammation, enhancing BBB stability, and promoting neurogenesis. MagStim emerges as a potential novel and noninvasive therapy for stroke rehabilitation, warranting further investigation.
Abstract TP41: Cognitive impairment in the chronic phase of Ischemic Stroke is associated with secondary neurodegeneration in female rats
Authors: Akbari Zara , Mani Kathiresh Kumar , Pickle Kaylin , Sohrabji Farida
Published: January 2025

Background:
Our studies show that intracerebroventricular (ICV) infusion of IGF1 is neuroprotective in the acute phase of stroke but does not reduce peripheral inflammation or improve cognitive function in the chronic phase. In contrast, intraperitoneal (IP) injection of IGF1 did not improve acute phase recovery, but reduced stroke-induced elevation of plasma inflammatory cytokines, repaired the gut epithelium and attenuated stroke-induced cognitive impairment. Here we evaluated the extent of chronic neurodegeneration after stroke and the impact of IP versus ICV treatment with IGF-1.

Method:
Middle-aged female rats were subject to MCAo and treated with either ICV-IGF1 or IP-IGF1 4h after stroke. Animals were tested for cognitive impairment using the Barnes Maze test 30 days later and terminated thereafter. Brains were collected and processed for block embedding and sectioning. One set of sections was stained for Weil myelin and imaged using an Olympus VS120 Slide Scanner. For each section between bregma 2.52 and -5.88, the left and right hemisphere was manually outlined and measured (QuPath 0.4.3) to obtain hemisphere volume (μm 3 ). Lateral ventricle in each hemisphere was calculated using slices between bregma 1.56 and -5.88. For callosal thickness, the average dorsal to ventral margin was measured at the midline in 5 sections of the corpus callosum (0.6 mm apart; bregma 0.3 mm to −0.9 mm).

Results:
Histological analysis showed significant reductions in the volume of the ischemic hemisphere compared to the non-ischemic hemisphere in the ICV-Veh and ICV-IGF1 groups. Similarly, both groups had enlarged ventricles in the ischemic hemisphere. Sham (no stroke) animals did not show any left-right differences in hemisphere or ventricular volume. Corpus callosum width was similar in all groups. In contrast, in the IP-study the volume of the ischemic hemisphere as compared to the non-ischemic hemisphere were similar in all groups, however, ventricular enlargement was seen in the ischemic hemisphere of the IP-vehicle group, but not in the IP-IGF1 or sham groups. Moreover, the midline width of the corpus callosum was significantly reduced in the IP-Veh group, but not the IP-IGF1 group.

Conclusions:
These data suggest that improved cognition in the IP-IGF1 is associated with preservation of the gray and white matter structures. These data also indicate that targeting peripheral organs such as the gut presents a fresh approach to enhancing brain health in aging females.
Abstract TP43: Diabetes Increases Endothelin-A Receptor (ETAR) Expression and Senescence in a Novel Multi-Etiology Model of Vascular Contributions to Cognitive Impairment and Dementia (VCID)
Authors: Abdelsaid Kareem , Abdul Yasir , JAMIL SARAH , Li Weiguo , Ergul Adviye
Published: January 2025

Introduction:
Cerebrovascular pathologies leading to VCID are diverse, but preclinical models mainly rely on chronic hypoperfusion-mediated neuroinflammation in otherwise healthy animals. Since diabetes increases VCID risk, our first goal was to develop a multi-etiology model of VCID in diabetes. Given that endothelin-1 (ET-1) contributes to decreased cerebral blood flow in multiple dementia models and that ETAR-mediated senescence in brain microvascular endothelial cells, our second goal was to assess ETARs in this VCID model.

Methods:
Control and diabetic male Wistar rats were subjected to sham or a novel VCID model of microemboli (ME) injection followed by unilateral common carotid artery occlusion (UCCAO). Animals were followed for 22 weeks by several behavioral tests. Hematoxylin/Eosin (HE) and Luxol-fast blue staining (LFB) were used to assess brain pathologies. ETAR, hypoxia, and senescence markers were assessed by immunoblotting and immunohistochemistry.

Results (Table):
Tissue damage in the striatum was greater, and the corpus callosum myelination score was lower in the diabetic UCCAO+ME group. ETARs, hypoxia marker HIF1α, and senescence marker p21 levels were increased in the UCCAO+ME diabetic group; while ETBRs rather decreased. Open Field revealed anxiety-like behavior (a significant decrease in time spent and entry frequency at the center square) and an increase in overall inactivity of D UCCAO+ME at week 22. Novel object recognition test showed a distinctive decline in the recognition and discrimination indices in the D UCCAO+ME group compared to the BL D UCCAO+ME and WK22 D sham groups. Of note, these animals exhibited a depressive-like behavior with a much lower entry frequency to the novel arm of the Y-maze despite their normal motor function compared to other groups.

Conclusion:
This multi-etiology model of VCID, especially in comorbid disease models, may serve as a more clinically relevant model of VCID. Given that post-mortem brain ET-1 levels correlate with tissue hypoxia and disease severity in patients with dementia, further understanding of the regulation and effects of cerebral microvascular ETAR in neurovascular dysfunction is likely to identify novel therapeutic targets.
Abstract TP45: Advancements in Digital Cognitive Assessments for Post-Stroke Patients: A Scoping Review
Authors: Bateh Kaitlyn , Saurman Jessica , Bartsch Bria , Xu Yuan , Aboul-Nour Hassan , Hanson Alene , Guan Emily , Su Kyrsten , bateh Alexander , Peterson Shenita , Billinger Sandra , Nahab Fadi , Hu Xiao
Published: January 2025

Introduction:
Standardized cognitive assessments such as the Montreal Cognitive Assessment (MOCA) and Mini-Mental State Examination (MMSE) are generally administered using paper-and-pencil methods. Technological advancements have digitized these exams and expanded cognitive testing capabilities in the post-stroke population.

Methods:
Studies from 2010-2022 were identified from PubMed, Embase, Web of Science, Cumulated Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, and Google Scholar to include digital cognitive assessments utilized for acute and chronic ischemic and hemorrhagic stroke patients. The research questions aim to evaluate technical aspects of digital tests, digital tool effectiveness, cognitive domains assessed, study population characteristics, patient usability, and exam feasibility. The methodological framework for this review included research question identification, relevant study collection, final study selection, data extraction, analysis, and summary. Covidence was used to compile relevant studies.

Results:
72 articles were included for final analysis. 8 different digital methods (e.g., tablet, computer, virtual reality) were used to assess cognition, with 26 studies creating a new cognitive test and 24 creating a cognitive test based on a standardized exam. Participants were tested in both acute and chronic phases (5 strictly in acute, 55 strictly in subacute/chronic, and 11 in both). 58% of articles assessed ischemic and hemorrhagic stroke participants, and 9 studies only tested aphasia patients. Exams consisted of a variety of cognitive domains, with the majority of studies testing multiple domains (e.g., executive functioning, attention, and visuospatial processing), and some studies testing only one cognitive domain. The average rate of digital test completion was 95%. Validation of the digital tool was compared with a standardized, paper-and-pencil test (e.g., MOCA, MMSE) in 48 articles (67%). An overall positive satisfaction with the digital test was seen in 8 articles that incorporated patient questionnaires.

Conclusion:
This review suggests that post-stroke digital cognitive assessments are feasible in the acute and post-acute settings across multiple domains similar to the MOCA and MMSE. Enhancements in these tools will expand access to testing and allow for increased identification of post-stroke cognitive impairment.