Search Results for: Short Acting Opioid

Stroke, Volume 56, Issue Suppl_1, Page ATP174-ATP174, February 1, 2025. Background and Purpose:Venous outflow (VO) impairment predicts unfavorable outcomes in patients with acute ischemic stroke caused by large vessel occlusion (AIS-LVO). Prolonged venous transit (PVT), a visual qualitative VO marker on CT perfusion (CTP) time to maximum (Tmax) maps, has been associated with 90-day mortality despite successful reperfusion. This study investigates the association between PVT and modified Rankin Scale (mRS) score at discharge among AIS-LVO patients who have undergone successful reperfusion.Methods:We performed a retrospective analysis of prospectively collected data from consecutive adult AIS-LVO patients with successful reperfusion (modified Thrombolysis in Cerebral Infarction 2b/2c/3). PVT+ was defined as Tmax ≥10s in at least one of the following locations: superior sagittal sinus and/or torcula. The primary outcome was dichotomous mRS scores at discharge (favorable: mRS 0-2; unfavorable: mRS 3-6). Regression analyses were performed to assess the effect of PVT on discharge mRS.Results:In 119 patients of median (IQR) age 71 (63-81) years, a significantly higher proportion of PVT+ patients exhibited unfavorable mRS scores compared to PVT- patients (88.8% vs. 62.7%, p=0.004). After adjusting for age, sex, hypertension, hyperlipidemia, diabetes, atrial fibrillation, history of stroke or transient ischemic attack (TIA), tobacco use, administration of intravenous thrombolysis (IVT), admission National Institutes of Health Stroke Scale (NIHSS), Alberta Stroke Program Early CT (ASPECTS) score, and ischemic core volume, the PVT+ remains significantly associated with unfavorable mRS (OR=0.215, 95%CI 0.048-0.959, p=0.044).Conclusions:PVT+ was significantly associated with unfavorable mRS at discharge despite successful reperfusion in AIS-LVO patients, underscoring the importance of VO impairment in short-term functional outcomes. PVT serves as a valuable adjunct imaging biomarker derived from CTP for assessing VO profiles in AIS-LVO.

Stroke, Volume 56, Issue Suppl_1, Page AWP302-AWP302, February 1, 2025. Introduction:Colchicine, an anti-inflammatory medication, has demonstrated significant benefits in reducing inflammation and decreasing subsequent vascular events in patients with acute coronary syndrome and myocardial infarction (MI). This has prompted interest in its potential role in secondary prevention of vascular events in individuals who have experienced a stroke or transient ischemic attack (TIA). This abstract explores the evidence supporting colchicine’s efficacy and safety in this context.Methods:We searched PubMed, Cochrane, and Embase databases for randomized controlled trials investigating the effect of colchicine in patients who experienced stroke or TIA of non-cardioembolic origin. Our primary outcomes were any new vascular event (a composite of stroke, TIA, MI, or vascular death) or ischemic stroke. We also assessed the incidence of relevant side effects. Risk ratios (RR) and hazard ratios (HR) with 95% confidence intervals (CI) were pooled using a random-effects model.Results:Two studies were included with a total of 11,487 patients. Colchicine did not reduce vascular events after ischemic stroke or TIA both in long term (RR 0.91; 95% CI 0.79 to 1.05; p = 0.18; I2= 23%) (HR 0.92; 95% CI 0.80 to 1.04; p = 0.18; I2= 0%) and short term (RR 0.83; 95% CI 0.56 to 1.23; p = 0.35; I2= 64%) compared with placebo. There was also no significant advantage in the reduction of recurrence of ischemic stroke in the colchicine group (RR 0.90; 95% CI 0.74 to 1.09; p = 0.28; I2= 44%) (HR 0.91; 95% CI 0.75 to 1.10; p = 0.31; I2= 40%). There were no unforeseen side effects in the Colchicine group (RR 3.78; 95% CI 1.52 to 9.40; p= 0.001; I2= 91%).Conclusion:Colchicine did not prevent recurrent vascular events or ischemic strokes in patients after a non-cardioembolic stroke or TIA in a large sample size of greater than 11,000 patients. Further well-designed randomized controlled trials are needed to conclusively determine its efficacy and safety in this context. Nevertheless, the early data does not seem to indicate that it will provide benefit to this target population.

Stroke, Volume 56, Issue Suppl_1, Page AWMP11-AWMP11, February 1, 2025. Background:Endovascular thrombectomy (EVT) has improved both short-term and long-term outcomes for acute ischemic stroke (AIS) patients caused by large vessel occlusion (LVO). However, the relationships between blood pressure (BP) after EVT and outcomes had not been determined. As BP is dynamically changes, the present study investigated the effects of BP trajectories after EVT on the outcomes in AIS patients with LVO using Group-Based Trajectory Modeling (GBTM).Methods:This was a retrospective, single-center observational study. The AIS patients with LVO in the anterior circulation within 24 hours of symptom onset, baseline modified Rankin Scale (mRS) score ≤2, and Alberta Stroke Program Early CT Score (ASPECTS) score ≥6 were included. BP was monitored frequently post-EVT, and PP was calculated as the difference between systolic and diastolic BP. GBTM identified distinct PP trajectories over 0-6 hours and 0-48 hours post-EVT. Short-term outcomes included hemorrhagic transformation (HT) and symptomatic intracranial hemorrhage (SICH), while long-term outcomes included National Institutes of Health Stroke Scale (NIHSS) at 7 days and mRS score at 3 months.Results:Out of 506 screened patients, 313 were included in the final analysis. GBTM identified three distinct PP trajectories within the first 6 and 48 hours post-EVT. The 0–6 hour PP trajectory was significantly correlated with HT (OR=1.81, 95% CI 1.28-2.54), which remained significant after adjustment (OR = 1.72, 95% CI 1.17-2.53). An elevated PP trajectory was associated with a 3.04-fold higher risk of HT compared to the normal trajectory. Mediation analysis indicated the 7-day NIHSS score mediated 88.92% of the association between severe elevated PP trajectory and mRS.Conclusion:Severely elevated PP trajectory post-EVT is independently associated with poor short-term outcomes in AIS patients with LVO. Effective management of PP in the acute phase post-EVT may be crucial for improving prognosis of AIS patients with LVO.

Stroke, Volume 56, Issue Suppl_1, Page AWP42-AWP42, February 1, 2025. Background and Objectives:Moyamoya disease (MMD) is characterized by progressive steno-occlusion of the internal carotid arteries, leading to compensatory collateral vessel formation. The optimal surgical approach for MMD remains debated, with bilateral revascularization potentially offering more comprehensive protection but involving more extensive surgery compared to unilateral revascularization. This study aims to compare bilateral revascularization and unilateral revascularization short-term safety profile in the treatment of MMD.Methods:This multicenter retrospective study included patients with MMD who underwent surgical revascularization at 13 academic institutions. Patients were categorized into unilateral and bilateral revascularization groups. Data collected included demographics, clinical characteristics, and outcomes. Propensity score matching (PSM) was used to balance baseline characteristics. Statistical analyses were conducted using Stata (V.17.0; StataCorp).Results:A total of 497 patients were included, including 90 that had bilateral revascularization and 407 that had unilateral revascularization. Bilateral revascularization was associated with more perioperative asymptomatic strokes (10% vs. 2.4%; OR 4.41, 95% CI 1.73 to 11.19, p = 0.002) and higher rates of excellent functional outcomes (mRS 0-1) at discharge (92.2% vs. 79.1%; OR 3.12, 95% CI 1.39 to 7, p = 0.006). After PSM, 57 matched pairs were analyzed. There was a higher rate, though not statistically significant difference, of perioperative stroke in the bilateral revascularization group (15.7% vs. 8.7%; OR 1.95, 95% CI 0.61 to 6.22, p = 0.26). No significant differences were noted in mRS 0-1 and 0-2 scores at discharge, NIHSS at discharge, intraoperative complications, or length of hospital stay. The follow-up stroke rates were also not significantly different (OR 0.40, 95% CI 0.11 to 1.39, p = 0.15).Conclusion:This study found no significant differences between bilateral and unilateral revascularization in MMD. Patients who had bilateral revascularization had higher tendency of perioperative stroke, though not statistically significant. Further prospective studies are needed to validate these results.

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

Stroke, Volume 56, Issue Suppl_1, Page AWP315-AWP315, February 1, 2025. Objective:We sought to investigate the consequences of alcohol intake on intracerebral hemorrhage (ICH) and cerebral small vessel disease (cSVD) in patients with spontaneous ICH.Methods:We compared markers of cSVD [Figure 1], features of ICH, and outcomes among consecutive spontaneous ICH patients with different alcohol use strata admitted to a tertiary care center between 2003-2019. Alcohol intake was categorized as none/mild (5 drinks/day). We performed descriptive statistics and bivariate/multivariate analyses based on demographic and radiologic data.Results:We included 1590 patients (53% male, median age 74 years [IQR 64-82]). Among them, 82.6% had none/mild alcohol intake, 14.2% moderate/severe, and 3.3% heavy alcohol intake. Heavy alcohol users were 13 years younger at time of ICH than none/mild users (median [IQR], 62 [57-70] vs 75 [65-83], p

Stroke, Volume 56, Issue Suppl_1, Page AWMP45-AWMP45, February 1, 2025. Introduction:There has been an ongoing debate regarding the effectiveness of inpatient rehabilitation facility (IRF) and skilled nursing facility (SNF) in promoting functional recovery. Home time is a valid measure of functional recovery in stroke patients that is often used in outcome studies. Considering that SNF patients have twice the length of stay compared to IRF patients, our objective was to explore whether home time is a suitable measure to compare the effectiveness between IRF and SNF in achieving functional recovery.Methods:We probabilistically linked data from Michigan’s Coverdell Stroke Program and Michigan Value Collaborative multipayer claims database for Medicare FFS beneficiaries hospitalized with acute stroke (ICD-10 I61-I63) between 2016-2020. Patients admitted to IRF or SNF after hospital discharge were confirmed using claims data. Home time was calculated over 90-days and 1-year following hospital discharge by subtracting the number of days spent in inpatient setting (i.e., IRF, SNF, and long-term care) from the number of days alive. We calculated the crude and inverse probability of treatment weighted (IPTW) mean difference of home time between IRF and SNF groups. We conducted a sensitivity analysis to examine the effect of time spent in the same rehabilitation setting over 30-days post discharge on home time.Results:From a cohort of 14,316 linked patients, we identified 2,995 (20.9%) and 2,948 (20.6%) patients directly admitted to IRF or SNF following stroke hospitalization, respectively. Compared to SNF patients, IRF patients were younger, more likely to be male, had minor strokes (NIHSS 1-4), and were able to ambulate at discharge. The unadjusted 90-day and 1-year mean home time were 15.6 and 67.6 days higher among IRF patients compared to SNF patients, respectively (Table). After accounting for rehabilitation time during 30-days post discharge, 90-day and 1-year unadjusted mean difference in home time remained higher among IRF patients compared to SNF patients but was reduced to 4.6 and 56.5 days, respectively. Using the amended home time, the adjusted 90-days mean difference was almost zero and not significantly different (0.5 days) but remained significantly different over 1-year (35.7 days).Conclusions:Home time is heavily impacted by rehabilitation length of stay. Future rehabilitation related studies should be cautious when using home time as a measure of functional recovery, especially over short duration of follow-up.

Stroke, Volume 56, Issue Suppl_1, Page AWP357-AWP357, February 1, 2025. Introduction:The rapid recanalization of occluded vessels and the restoration of cerebral blood flow (CBF) are critical for the outcome of stroke. Patients may exhibit poor reperfusion (no-flow) or hyperperfusion (hyperemia) after recanalization, and factors influencing these conditions are not fully understood. The Stroke Preclinical Assessment Network (SPAN) conducted a randomized, controlled, blinded, and highly heterogeneous multi-laboratory trial to identify effective interventions in the stroke animal model. Here, we examined the factors influencing the CBF recovery after filament removal and the effect of reperfusion CBF on stroke outcome in SPAN.Methods:Both sexes of C57BL6 healthy young were subjected to 30 or 60-minutes transient endovascular filament middle cerebral artery occlusion (MCAO). For homogeneity of all other factors, we used subjects enrolled at Mass General Hospital only. We measured CBF at 5 (n=128) and 10 minutes (n=88) after filament removal by laser Doppler flowmetry. We first tested whether sex, surgeons, MCAO duration, circadian time (ZT) at MCAO, age, weight, surgical duration, and SPAN treatments (control, fasudil, fingolimod, tocilizumab, uric acid, veliparib) predicted the reperfusion CBF. We then assessed the influence of CBF on tissue (day-2 MRI lesion volume) and behavioral outcomes (acute neurological deficits score and day-7 and 28 corner test) and 30-day mortality. A generalized linear model with backward elimination and a mixed model were used for bivariate and multivariable analyses.Results:CBF gradually increased after filament removal between 5 and 10 minutes (p=0.03). In bivariate analyses, CBF was significantly lower in animal that had MCAO in their active circadian phase (ZT12-24) (p=0.04). In multivariable analysis, reperfusion CBF was predicted to be higher in females, after 60 min MCAO, in inactive phase (ZT0-12), and short anesthesia duration. CBF also differed among the three surgeons. Only tocilizumab had lower CBF compared to the control group. Reperfusion CBF did not predict tissue and behavioral outcomes. However, higher CBF was related to lower day-1 weight loss (p

Stroke, Volume 56, Issue Suppl_1, Page AWP368-AWP368, February 1, 2025. Introduction:Oxidative stress plays an important role in both early brain injury and delayed cerebral ischemia after subarachnoid hemorrhage (SAH). Despite the beneficial effects demonstrated in preclinical studies with drugs targeting oxidative stress, their clinical translation has been hindered. There were critical issues in previous preclinical studies underpinning clinical translation, including inadequate demonstration of blood-brain barrier (BBB) penetration and insufficient assessment of drug concentration and biological activity in brain tissue. MnP-05 is a novel manganese porphyrin-based superoxide-dismutase mimic, which penetrates the BBB far better than previous compounds and exhibits superior anti-free radical properties compared to previous free radical scavenger. In this study, we evaluated the effect of MnP-05 on short-term outcomes of SAH in mice.Methods:We used 12-week-old male C57BL/6J mice. We induced SAH by an endovascular perforation of the right internal carotid artery. Mice (n = 31) were started on treatment with either MnP-05 or PBS 60 minutes after the induction of SAH. We set the dosing regimen as 1 mg/kg intravenous bolus followed by 5 mg/kg/day continuous intraperitoneal injection for 72 hours. We compared a composite neurological score, and rotarod performance (%baseline), between the two treatment groups for 7 days. We also compared the mRNA expression of oxidative stress and apoptosis markers in perihematomal brain tissue between the groups.Results:There were no specific side effects found in MnP-05 treatment group. There were no differences in blood pressure or body weight between the two groups. Seven-day neurological outcomes were better in MnP-05 group as evidenced by the significantly better composite neurological scores (22.9 vs. 19.4, P

Stroke, Volume 56, Issue Suppl_1, Page AWP353-AWP353, February 1, 2025. Mesenchymal stem cells (MSCs) have recently received attention as an intervention to reverse or slow neurodegenerative, stroke and injury-related changes in the aging brain as they suppress inflammation and facilitate tissue repair. In support of this idea, we have shown that extracellular vesicles (EVs) derived from bone marrow MSCs enhance recovery of motor function of the hand following cortical injury in aged female rhesus monkeys. Specifically, EV-treated treated monkeys (n=5) exhibited full recovery of fine motor function by 3-5 weeks post-injury while vehicle monkeys (n=5) reached a plateau short of full recovery by 8-12 weeks post-injury. Post-mortem analyses of perilesional brain tissue from the same monkeys, revealed multifaceted cellular effects of EVs including downregulating inflammatory microglial phenotypes, dampening neuronal hyperexcitability, and enhancing neuronal and myelin plasticity. To explore the relationship between these processes and functional recovery, we utilized multi-labeling immunohistochemistry (IHC) and high-resolution confocal microscopy to assess microglia phenotypes, neuronal synaptic marker expression and microglia-neuronal interactions in perilesional cortex. To assess these markers, semi-quantitative stereology in Neurolucida and particle analysis in ImageJ were utilized. Results show that MSC-EV treatment decreased the densities of pro-inflammatory hypertrophic microglia expressing LN3+, a marker for MHC II receptors, upregulated with immune activation. Conversely, MSC-EV treatment and functional recovery was significantly correlated with increased proportion of hypertrophic microglia expressing the key complement pathway protein C1q, a phenotype associated with enhanced debris-clearance and repair after degeneration. Interestingly this EV-associated increase in C1q+ hypertrophic microglia was correlated with decreased putatively damaged synapses tagged with C1q and greater synaptic marker expression in perilesional cortex. These data suggest that MSC-EVs promote a shift from pro- to anti-inflammatory repair microenvironment, via enhancement of debris clearance after injury. These findings demonstrate the efficacy of MSC-EVs as a therapeutic, likely acting to reduce inflammatory cascades, facilitate repair and rebalance neuronal synaptic connections to support recovery after cortical injury.

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 ATP200-ATP200, February 1, 2025. Background:Nontraumatic intracerebral hemorrhage (ICH) especially in deep locations is independently associated with a long-term increased risk of major arterial ischemic events. Minimally invasive surgery (MIS) has not been shown to improve outcomes for deep ICH. Whether ischemic events modify the effect of MIS on outcomes for deep ICH has not been studied.Methods:We pooled individual patient data from the MISTIE III (Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation Phase 3) and the ATACH-2 (Antihypertensive Treatment of Acute Cerebral Hemorrhage-2) trials. The exposure was ICH location (deep vs. lobar). The outcome was a symptomatic, clinically overt ischemic stroke or coronary ischemic event, adjudicated centrally within each trial. We evaluated the association between ICH location and risk of an ischemic event using Cox regression analyses after adjustment for demographics, vascular comorbidities, and ICH characteristics. We used logistic regression to assess whether ischemic events modified the effect of MIS with end of treatment volume (EOT)

Stroke, Volume 56, Issue Suppl_1, Page AWP373-AWP373, February 1, 2025. Cardiac arrest (CA) often leads to severe memory impairment, largely due to extensive neuronal loss in brain areas critical for cognitive function, including the hippocampus and amygdala. We demonstrated that physical exercise (PE) following asphyxia CA (ACA) mitigates contextual memory deficits in male rats. Intriguingly, this effect occurs without direct protection of the hippocampus and amygdala, as evidenced by significant cell death in both regions. Instead, PE post-ACA reduces neuronal loss in the medial septum (MS), a forebrain structure essential for regulating limbic system oscillations, and thus memory. This study aims to investigate whether PE post-ACA preserves oscillatory activity within the limbic circuitry and whether it ameliorates other forms of cognitive deficits in both sexes.Methods:Male and female rats are subjected to 8’ ACA. After 5 days of recovery, the animals undergo 5 consecutive days of treadmill running, followed by a battery of cognitive tests. Approximately one-month post-ACA, the animals are anesthetized with urethane for in vivo oscillatory recordings.Results:Having acquired fear conditioning (Figs. 1a and 1d), the animals were tested for cued fear memory and extinction two days later. Post-ACA exercised animals displayed a significant increase in freezing levels compared to non-exercised animals in response to a single re-exposure to the tone, indicating preserved cued fear memory (Fig. 1c). After continuous tone presentations, only the exercised animals displayed a significant decrease in freezing, suggesting they were able to extinguish their fear response (Fig. 1f). The Y-maze test revealed a significant increase in spontaneous alternation in exercised animals (Fig. 1g), indicating improved working memory. These outcomes were not influenced by locomotion (Fig. 1h) or anxiety (Fig. 1i), as confirmed by the open field test. We are currently performing the oscillatory recordings in different limbic system regions.Conclusion:PE post-ACA mitigates different forms of long- and short-term memory deficits in both sexes. This improvement is likely mediated by the preservation of oscillatory power in the MS and hippocampus (to be confirmed), highlighting a potential mechanism by which PE exerts its neuroprotective effects.

Stroke, Volume 56, Issue Suppl_1, Page AWP295-AWP295, February 1, 2025. Background:Structural inequity, including structural racism, is increasingly linked to stroke measures. Prior work has shown that ecosocial models quantifying constituent domains of structural racism correlate with acute ischemic stroke (AIS) incidence. It remains unclear if such models can further account for the not yet fully explained racial disparities in stroke outcomes.Methods:We performed a national, population-based analysis of Medicare beneficiaries aged >65 years enrolled in Medicare from January 1, 2016 to December 31, 2019, resulting in 71,078,619 eligible adults, of whom 844,406 had a primary diagnosis of AIS. In separate models, we estimated the odds ratio (OR) and 95% confidence intervals (CI) of three outcomes (inpatient mortality, 30-day mortality, and discharge home) using multilevel logistic models for clustered data, with data clustered at the county level. Structural racism variables were tested in separate models, adjusting for sex, age, urban vs. other location, and Black vs. White race.Results:The composite structural racism score was strongly correlated with inpatient mortality (1.16, 95% CI: 1.10-1.22) without a significant interaction with race (p=0.62). Both 30-day all-cause mortality (p=0.04) and discharge home (p=0.02) significantly interacted with race. For each unit increase in structural racism, Black individuals had 4.5% increased odds of 30-day mortality and 5.8% decreased odds of being discharged home, whereas White patients had a 6.5% increase in 30-day mortality and 3.5% decrease in odds of discharge home.Conclusions:Both racial and geographic disparities in short-term outcomes after AIS are strongly correlated with structural inequity across the United States.

Stroke, Volume 56, Issue Suppl_1, Page ADP51-ADP51, February 1, 2025. Background:Migraine with aura (MA) is recognized as an independent risk factor for acute ischemic stroke (AIS). However, the short-term risk of stroke, particularly within 90 days of hospitalization, has not been thoroughly evaluated on a national scale. This study aims to address this gap by examining the association between MA and 90-day AIS readmission.Methods:Using the National Readmission Database between 2016 and 2019, we identified patients admitted with a principal or non-principal diagnosis of migraine. The reference group for analysis contained all adult patients admitted during the study period without migraine. The primary outcome was subsequent AIS admission within 90 days. Diagnoses were identified using standard ICD-10-CM codes. A multivariable Cox regression model was employed to assess the risk of AIS readmission risk in patients with MA, adjusted for significant cardiovascular risk factors. Interaction analyses were conducted to determine whether traditional cardiovascular risk factors influenced the association between MA and subsequent AIS risk.Results:Among 106,608,073 patients (mean age 46.48, 57.86% female) admitted during the study period, 1,711,841 (1.61%) patients were admitted with any migraine diagnosis and 101,278 (0.10%) were admitted with MA. Within 90 days, 411,850 (0.39%) patients had a subsequent admission for AIS. After adjusting for sex, coronary artery disease, atrial fibrillation, hypertension, hyperlipidemia, diabetes mellitus, and smoking, patients with MA demonstrated an elevated risk for 90-day AIS (adjusted hazard ratio [aHR] 1.76, 95% CI 1.56-1.99, p < 0.001). Migraine without aura was not associated with increased AIS risk (aHR 1.02, 95% CI 0.84-1.23, p=0.846). Significant interactions were observed with age, sex, hypertension, and atrial fibrillation (Figure).Conclusions:In this large patient cohort, migraine with aura was associated with an increased risk of AIS readmission within 90 days, particularly in patients without traditional cardiovascular risk factors. These findings underscore the need for potentially more aggressive stroke prevention strategies in patients with MA. Future research should investigate the pathomechanisms underlying this association.

Stroke, Volume 56, Issue Suppl_1, Page ADP26-ADP26, February 1, 2025. Introduction:Short interspersed nuclear elements (SINEs) are an abundant class of noncoding retrotransposons that can be transcribed by RNA polymerase III. Some SINEs have also been shown to act as genomic enhancers, thus giving rise to what are known as enhancer SINE-RNAs (eSINE-RNAs). The function of these novel RNAs within the post-stroke brain remains virtually unexplored. In this study, we map the genome-wide cortical expression of eSINE-RNAs in response to stroke, characterize their cell-type&subcellular localization, and determine their role in affecting post-stroke infarct volumes.Methods:Ischemic stroke was induced in male C57BL/6N mice using 1h middle cerebral artery occlusion (MCAO) followed by 6h of reperfusion (or sham surgery). Genome-wide RNA-seq and H3K27ac ChIP-seq (n=3/group/experiment) were performed on ipsilateral cortices to identify stroke-responsive enhancer RNA transcripts, which were then overlaid with genomic SINEs to identify eSINE-RNAs. Immunohistochemistry and RNA-FISH were used in tandem to determine the cell-type and subcellular localization of several highly expressed eSINE-RNAs. Select eSINE-RNAs were ablated via intracerebroventricular injection of antisense oligonucleotides followed by 1h MCAO and 24h reperfusion. Infarct volumes following knockdown were evaluated using cresyl violet staining (n=5-7/group).Results:We discovered 46 eSINE-RNAs upregulated in the cortex following MCAO, 33 of which were unique to stroke and not detected in the sham group. These RNAs were derived from several families of SINEs, including 24 from the B1 family, 20 from the B2 family, and one each from the less ubiquitous ID and MIR families. The expression of several abundant eSINE-RNAs was specific to the nuclei of neurons within the prospective infarct and peri-infarct territories, including the sensorimotor cortex and hippocampus. Ablation of select eSINE-RNAs resulted in significantly higher infarct volumes versus controls, suggesting that these eSINE-RNAs serve a neuroprotective role in the brain following ischemic stroke.Conclusion:Our study is the first report to characterize the expression of eSINE-RNAs in the post-stroke brain and begin to elucidate their function as regulators of post-stroke pathophysiology. Our results suggest that the transcription of eSINE-RNAs represents a robust neuroprotective response to transient focal ischemia, thus positioning them as potential molecular targets for modulating post-stroke outcomes.