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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

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.

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

Stroke, Volume 56, Issue Suppl_1, Page AWP123-AWP123, February 1, 2025. Background:Post-stroke fatigue is a common and debilitating issue, often linked to depression or neural damage. Emerging evidence suggests that myasthenia gravis (MG) may also play a role in post-stroke fatigue, offering a new perspective on patient management and long-term disability reduction.Objectives:This study aims to assess the incidence of de novo MG in stroke survivors following motor recovery over 18 to 24 months and compare findings with a healthy control group.Methods:Conducted at a tertiary care institution over two years, this prospective case-control study included ischemic and hemorrhagic stroke patients. Participants were recruited during the acute stroke phase and underwent evaluations for neuromuscular weakness and autoimmune disorders. They were monitored in a specialized stroke clinic for two years. Key variables included demographics, comorbidities, autoimmune disorders, stroke subtype, time since onset of stroke, and muscle fatigability. Age and sex-matched controls were assessed concurrently. Baseline and two-year follow-up measurements of acetylcholine receptor (AChR) antibodies were performed, and new antibodies were monitored. Participants with significant fatigability were tested for MG, and if confirmed, treated with cholinergic drugs.Results:The study involved 96 participants with a mean age of 60.45 years, predominantly male (63.86%). Ischemic stroke was most common (93.75%). Major risk factors included hypertension (12.5%), diabetes (5.20%), and dyslipidemia (3.12%), with 11.45% having autoimmune disorders. Of the 96 participants, 74 (77.08%) reported fatigability an average of 23.2 months post-stroke. Types of fatigability included neck (34.37%), proximal arm (11.46%), grip (19.80%), speech (5.21%), and eye (6.25%). Among 36 stroke patients with post-stroke fatigability and 36 controls re-evaluated at follow-up, 7 stroke patients tested positive for AChR antibodies compared to 1 control. Fisher’s Exact test showed a significant association between stroke and AChR-Ab positivity (p = 0.001), with an odds ratio of 7, suggesting a potential link between post-stroke fatigue and MG.Conclusion:The study highlights MG as a potential underrecognized factor in post-stroke fatigue. These findings may improve diagnostic and therapeutic strategies for stroke survivors and pave the way for further research into post-stroke immune alterations and MG development.

Stroke, Volume 56, Issue Suppl_1, Page AWP335-AWP335, February 1, 2025. Objective:We aim to test the ability of CT perfusion (CTP) for predicting ischemic stroke in patients with symptomatic chronic carotid or middle cerebral artery occlusion.Methods:This was a post-hoc analysis of the CMOSS trial (NCT01758614), a randomized controlled trial comparing extracranial-intracranial (EC-IC) bypass surgery to medical therapy in patients with symptomatic carotid or middle cerebral artery occlusion and hemodynamic insufficiency measured by CTP. Patients treated with medical treatment alone in the trial were included. Mean transit time (MTT) and relative cerebral blood flow (rCBF) from CTP were collected. The primary outcome was defined as ischemic stroke in the territory of the qualifying artery within 2 years after randomization.Results:All 165 per-protocol patients (median age = 53.7 years, 81.2% males) treated with medical treatment alone were analyzed. Sixteen patients (9.7%) suffered from ischemic stroke in the territory of the qualifying artery during two-year follow-ups. Cut-off values of MTT >6.5s (symptomatic side) and rCBF ≤0.5 were suggested to be associated with recurrent stroke. In multivariate Cox regression, MTT (adjusted hazard ratio [HR] = 3.50, 95% CI = 1.19-10.30, p = 0.02) and rCBF (adjusted HR = 7.36, 95% CI = 2.27-23.85, p =0.001) were independently associated with the primary outcome.Conclusion:This study demonstrated CTP-based hemodynamic evaluation had relative accuracy in predicting recurrent ischemic stroke in symptomatic patients with chronic carotid or middle cerebral artery occlusion, which can be potentially used in patient selection for stratified secondary prevention of stroke. Future studies are warranted to verify current findings.

Stroke, Volume 56, Issue Suppl_1, Page AWP342-AWP342, February 1, 2025. Background:Elevated circulating IL-6 levels are associated with poor outcomes following stroke, and increased serum IL-6 levels correlate with worse stroke outcomes. IL-6 binds to soluble IL-6 receptors, binding to ubiquitously expressed gp130 to initiate proinflammatory trans-signaling. This exploratory study investigates the impact of inhibiting IL-6 trans-signaling on long-term functional outcomes in ischemic stroke.Methods:Young mice (8-15 weeks old) were administered recombinant saline/gp130Fc an IL-6 trans-signaling inhibitor, twice a week for two weeks, starting at the time of reperfusion after 60 minutes of post-middle cerebral artery occlusion (MCAO). Neurological deficit scores and infarct volumes were assessed at 24 hours, with long-term cognitive and motor evaluations conducted at 7 and 28 days post-MCAO. Gliosis and neurogenesis were analyzed via fluorescence microscopy, and plasma IL-6 levels were quantified using ELISA. Flow cytometry was performed to assess membrane IL-6 receptor and IL-6 levels on immune cells in the blood and brain at 24,72 hours and 7 days post-MCAO.Results:MCAO in young male mice significantly increased IL-6 expression while acutely reducing membrane IL-6 receptor levels in peripheral immune cells. Treatment with gp130Fc (0.5 mg/kg) effectively improved neurological deficit scores (NDS) and reduced infarct volume (p

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.

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

Stroke, Volume 56, Issue Suppl_1, Page AWMP47-AWMP47, February 1, 2025. Background:Occurrence of post-stroke apathy (PSA) is associated with worse outcomes and poorer quality of life. Particularly, post-thalamic stroke apathy was repeatedly reported. In this study, we performed disconnection-based analyses to reveal the neural basis of post-thalamic stroke apathy from both focal and network perspectives.Method:This study recruited first-ever unilateral thalamic ischemic stroke patients. The Lille Apathy Rating Scale was used to characterize the appearance and severity of apathy. Patient’s lesion masks were embedded into normative connectome to generate functional or structural disconnection maps. Support Vector Regression-based Multivariate Lesion-Symptom Mapping and Disconnection-Symptom Mapping were employed to explore associations between lesion locations, structural and functional disconnections, and PSA.Results:A total of 92 patients with thalamic infarction were included. No significant associations were found between thalamic lesion locations and PSA. However, structural disconnection in the anterior thalamic radiation and functional disconnection in the bilateral medial prefrontal cortex, bilateral inferior frontal gyrus, bilateral anterior insular cortex, right inferior parietal lobule, and right superior temporal gyrus were significantly associated with PSA.Conclusion:The study revealed that apathy following thalamic ischemic stroke is associated with disruptions in thalamocortical networks rather than specific lesion locations. These findings suggest that post-thalamic stroke apathy is a network disorder, driven by functional diaschisis and secondary neurodegeneration. Understanding these mechanisms may inform treatment targets and improve post-stroke rehabilitation strategies.

Stroke, Volume 56, Issue Suppl_1, Page AWP360-AWP360, February 1, 2025. Introduction:Loneliness and social isolation (SI) are associated with both an increased risk of stroke and poor outcomes after stroke. However, the biological mechanisms that mediate how social factors affect stroke recovery are unknown. We hypothesized that the detrimental consequences of post-stroke SI result from differential miRNA expression that impacts neuroinflammation.Methods:To investigate the negative effects of post-stroke SI on brain miRNA profiles, aged (18–20 months) C57BL/6 male mice were utilized. Mice were randomly assigned to pair housing (PH) or single housing (SI) after middle cerebral artery occlusion (MCAO). We investigated the abundance of miRNA transcripts in isolated peripheral blood mononuclear cells (PBMCs) samples of lonely and socially integrated patients 24 hours after stroke (n = 140) using the UCLA loneliness and Lubben social interaction scales.Results:MiR-10a-5p, identified as a top differentially expressed target across mice and human-isolated stroke patients, was found to be a crucial node in the pool of miRNAs that interacted with the largest group of miRNAs for post-stroke at SI D4 in mice. At post-stroke, SI D4, significant microglial activation and suppression of cytokine production were observed as assessed by the median fluorescence intensity (MFI) of purinergic receptor P2Y12 (P2RY12), interleukin (IL)-4, IL-1β, and tumor necrosis factor (TNF)α, respectively, in microglial cells in the brain. The MFI of P2RY12 was significantly downregulated in post-stroke SI mice at D4 (n = 7-8/grp, *p

Stroke, Volume 56, Issue Suppl_1, Page AWMP51-AWMP51, February 1, 2025. Background:Obstructive sleep apnea (OSA) is common among patients with ischemic stroke and transient ischemic attack (TIA) and has been associated with poor outcomes. Guidelines recommend evaluating eligible patients with cerebrovascular events for OSA.Objective:to examine whether a quality improvement (QI) intervention could increase OSA testing post-stroke/TIA.Methods:ASAP (NCT04322162) was a stepped-wedge cluster-randomized trial evaluating the effectiveness of a QI intervention to increase OSA testing among ischemic stroke or TIA patients at intervention (N=6) vs. control sites (N=30). Recruitment was at the facility level. The study involved 3 phases: baseline, implementation, and sustainability. The primary outcome was: 30-day OSA diagnostic testing rate. Secondary outcomes were: 30-day continuous positive airway pressure treatment rate, and 90-day recurrent vascular event and readmission rates. ASAP was powered to detect a difference in the primary outcome: baseline vs. implementation. Generalized linear mixed-effects models with binomial distribution and log link fit to patient-level data with site-level random effects were used. The QI intervention included: a virtual kickoff (teams reviewed data, identified improvement opportunities, considered barriers and solutions to diagnosing OSA post-stroke/TIA, and action plan development); monthly collaborative conferences; web-based platform displaying quality data and resource library; and external facilitation.Results:Among 1747 patients at 6 intervention sites the diagnostic rate increased from 2.1% (baseline, 20/952) to 29.1% (implementation, 189/650); among 7454 patients at 30 control sites the 30-day diagnostic rate varied (0.6%-2.2%; adjusted odds ratio (aOR) 16.90 (95%CI, 9.49-30.10). The diagnostic rate during sustainability was 11.7% (17/145); aOR 3.58 (1.59-8.04). The 30-day treatment rate varied (0.0%-0.4%) at control sites and increased at intervention sites: 0.3% (baseline, 3/952) to 2.8% (implementation, 18/650; OR 14.22 (2.40-84.40). The treatment rate during sustainability was 0.7% (1/145); aOR 2.66 (0.13-56.21). 90-day readmission and recurrent event rates were lower during implementation and sustainability (vs. baseline); these changes were not statistically significant.Conclusions:QI approaches can markedly increase OSA testing among patients with acute cerebrovascular events. Additional work should identify strategies to increase treatment rates among stroke/TIA patients with OSA.

Stroke, Volume 56, Issue Suppl_1, Page AWMP69-AWMP69, February 1, 2025. Introduction:Cerebral computed tomography perfusion (CTP) imaging has been well-established for identifying candidates for endovascular therapy (EVT) in acute ischemic stroke. This study investigates the association between CTP parameters and functional independence post-EVT using data from the SELECT study.Methods:We analyzed baseline CTP images from SELECT patients, focusing on those with available cerebral blood volume (CBV), cerebral blood flow (CBF), and time to maximum perfusion (Tmax) maps. Patients who received EVT and medical management only (MM) were included. Logistic regression models were created with age, national institutes of health stroke scale (NIHSS), time to arrival, occlusion location, transfer status, and CT ASPECTS as covariates, and functional independence at 90 days (modified Rankin score 0-2) as the outcome. Receiver operating characteristic (ROC) curves were generated, and area under the curve (AUC) values were calculated and compared using DeLong’s test.Results:Among 361 patients, 171 (139 EVT, 32 MM) had volumetric estimates for CTP parameters with pre-defined thresholds. Median (IQR) age and NIHSS were 68 (56-78) and 16 (12-20), and 48% were females. Estimates of different thresholds within a given CTP parameter showed high correlation ( >0.8), and a moderate to high correlation ( >0.4-0.6) was observed in estimates across different parameters (all p0.7 for all CTP parameters in both EVT (figure 2) and combined (EVT + MM, figure 3) subgroups, with the highest values for CBF thresholds:

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

Stroke, Volume 56, Issue Suppl_1, Page AWP164-AWP164, February 1, 2025. Introduction:Rates of guideline-concordant obstructive sleep apnea (OSA) testing among those with a recent cerebrovascular event are exceedingly low. Understanding the role contextual factors play is necessary to inform successful implementation of quality improvement (QI) initiatives designed to address this gap in stroke/transient ischemic attack (TIA) care.Methods:Longitudinal data was collected via questionnaires and semi-structured interviews to evaluate the implementation of QI initiatives conducted at six diverse VA Medical Centers (VAMCs) participating in Addressing Sleep Apnea Post-Stroke/TIA (ASAP), a Hybrid Type I, stepped-wedge cluster-randomized trial. Intervention components included a Systems Redesign Virtual Collaborative and data monitoring (Figure 1). Implementation strategies included external facilitation and audit and feedback. Provider- (e.g., clinical training) and systems-level contextual elements (e.g., Champion Team members and their roles) were collected. Select Consolidated Framework for Implementation Research (CFIR) constructs were rated in terms of magnitude and valence. The primary outcome of successful implementation was defined at the end of 21 months of active implementation as obtaining a Group Organizational (GO) score of ≥6 a measure of programmatic development and maturation. Comparisons of sites were conducted across contextual elements and stratified by those achieving a GO score of ≥6 (Figure 2).Results:ASAP Sites 1 through 4 obtained a GO score ≥6 (range: 7-9); across these sites, the Clinical Champion had: (1) field staff engaged in activities such as care coordination; (2) full to partial support of their local sleep personnel, and; (3) consistently positive CFIR scores values. These sites also received a greater amount of external facilitation and used a quality dashboard more often. All 4 sites created a change in health care personnel and medical center culture that stressed the importance of OSA testing soon after a cerebrovascular event occurred.Conclusions:Developing strong and consistent Champion teams who meaningfully engaged with local VAMC personnel within and across sleep medicine and stroke service lines was important for implementation success. Other key contextual factors for changing culture and creating a healthcare system wide approach to improving OSA testing for stroke/TIA patients included external facilitators and using performance data.Clinical Trials registration:NCT04322162

Stroke, Volume 56, Issue Suppl_1, Page AWP140-AWP140, February 1, 2025. Background:Maximizing long-term home time (HT) for acute ischemic stroke (AIS) patients has patient-centered and health-system benefits. We evaluated the influence of early (30-day) post-acute care (PAC) pathways on 1-year HT.Methods:We analyzed a cohort of Medicare AIS patients at a 7-hospital stroke certified health system (2016 to 2020). Clinical data extracted from an EMR-driven registry were linked to PAC utilization information retrieved from a CMS Qualified Entity with ≥80% data for the Texas state population (including 100% of Medicare Fee-for-Service). All claims within 1 year of hospitalization were collated and grouped into corresponding care pathways. One-year HT (i.e., number of days at home across 1-year period) was calculated utilizing discharge dates from various healthcare settings. Low HT was defined as

Stroke, Volume 56, Issue Suppl_1, Page AWP127-AWP127, February 1, 2025. Introduction:Cognitive impairment, mood disorders, and reduced serum BDNF levels are common in stroke patients. Previous studies suggest that aerobic exercise improves these outcomes by enhancing oxygenation. Herein, the authors compare the effectiveness of high-intensity interval training (HIIT) with low (LIT) and moderate (MIT) intensities and usual activity (UA) in stroke patients.Methods:We systematically searched PubMed, Cochrane, Embase, and Scopus databases for studies comparing HIIT with LIT, MIT, or UA in stroke patients. We evaluated change from baseline in cognitive improvement, mood disorders including anxiety and depression, and serum BDNF levels. Subgroup analyses were conducted based on stroke onset and exercise intensity, and separate analyses compared HIIT with each control group to assess cognitive improvement at different intensity levels.Results:A total of ten non-randomized and randomized studies were included in the analysis. Seven studies involving 373 patients showed no statistically significant difference in cognitive improvement between HIIT and the control group (std. MD 0.09; 95% CI -0.13 to 0.30; p=0.43). Separate analyses also revealed no significant differences between HIIT and LIT (std. MD -0.06; 95% CI -0.54 to 0.41; p=0.60), HIIT and MIT (std. MD 0.03; 95% CI -0.30 to 0.37; p=0.85), and HIIT and UA (std. MD 0.20; 95% CI -0.13 to 0.53; p=0.23). Subgroup analysis for chronic stroke did not show significant differences either (std. MD 0.07; 95% CI -0.19 to 0.34; p=0.58). Additionally, an analysis of four studies involving 281 patients found no significant difference in mood disorders (std. MD -0.21; 95% CI -0.62 to 0.21; p=0.33). A separate analysis of four studies with 130 patients also revealed no significant difference in serum BDNF levels between the two groups (std. MD 3.65; 95% CI -0.37 to 7.67; p=0.08). However, subgroup analysis indicated that serum BDNF levels were 3.32 ng/mL higher in the MIT group compared to the HIIT group.Conclusion:High-intensity-interval training does not demonstrate a significant advantage in cognitive improvement, mood disorders, or serum BDNF levels when compared to different exercise intensities. However, MIT is associated with increased serum BDNF levels compared to HIIT. Future robust RCTs are needed to compare different exercise intensities and durations to provide more conclusive results.