Abstract Background and aims Current treatment of symptomatic carotid stenosis relies on data that are more than 30 years old. There is limited reliable information on the stroke rate with modern, intensive medical therapy (IMT). The aim of this pragmatic registry was to provide an estimate of the ipsilateral stroke rate for patients with 50-99% symptomatic carotid stenosis who have at least one feature suggesting reduced stroke risk. Methods IMT was provided to all participants. IMT consists of dual antiplatelet therapy (short-term), high potency statins, blood pressure control, and lifestyle modification with risk factor education. Criteria for enrollment include any one of three clinical or radiologic markers. Clinical 1) Women 2) Retinal ischemic event only 3) Last symptomatic event >1 week ago. Radiologic: 1) TCD negative for emboli 2) MRI negative for intraplaque hemorrhage 3) High risk TIA with negative DWI. The primary endpoint is ipsilateral ischemic stroke within 12 months of enrollment. Results The registry completed enrollment in Sept 2025 with 114 patients (53% women), recruited from 18 centers in N America. 70% of patients qualified with stroke, 30% with TIA. All patients completed 6 month follow-up, with the ipsilateral stroke rate being 4.4%. Eight patients have died (7%). Information on stroke severity will be presented. Conclusions SCORE Registry data will allow clinicians to refine carotid stenosis decision making in symptomatic patients with >50% stenosis and potentially justify a future phase III RCT. With 6 months of follow-up in all patients, the stroke rate appears reduced compared to historical controls. Conflict of interest

Background: A minimum of 24-hour bed rest after mechanical thrombectomy (MT) for acute ischemic stroke (AIS) remains widely practiced, yet its benefit over earlier mobilization is unclear. We hypothesized that shorter bed rest durations would yield similar favorable discharge outcomes, in-hospital complications, and readmission rates compared to 24-hour bed rest in AIS patients treated with MT +/- IV thrombolysis. Methods: Consecutive adult AIS patients treated with MT from January 21, 2010, until December 31, 2024, at a single comprehensive stroke center were included. Standard 24-hour bed rest (the protocol prior to April 8, 2020) was retrospectively compared with the center’s current 12-hour protocol. The primary outcome was favorable discharge location (defined as home, inpatient rehabilitation facility, or acute rehabilitation). Secondary outcome measures included incidence of pneumonia, length of stay, 90-day modified Rankin scale (mRS) scores, and readmission rates. Results: 1173 patients were included (638 ≥12 h, 535 ≥24 h). Mean (s.d.) age was 70.2 (14.7) and 69.2 (14.6) and median (IQR) NIHSS was 14.0 (7-20) and 15.0 (8-21). Mean (s.d.) door to puncture times (minutes) were 106.4 (167.9) and 116.8 (157.5). TICI score ≥2b was achieved in 97.4% and 95.7% of patients (Likelihood Ratio χ 2 p=0.20). Favorable discharge location was similar between groups in unadjusted χ 2 -test of proportions (64.1% vs 65.4%, Likelihood Ratio χ 2 p=0.64) and in multivariable logistic regression analysis (Wald χ 2 p=0.99; adjusted OR=1.00; 95% CI=0.76:1.31). The frequency of good outcomes (mRS=0-2) by 90 days between the groups (37.3% vs. 39.8%, χ 2 p-value =0.65) was similar. Unplanned readmission rates at 30 days (8.9 vs. 6.9%, LR χ 2 p-value=0.43) and 90 days (19.9% vs. 15.1%, LR χ 2 p-value=0.18) were not different. In the ≥12 h group, pneumonia rates were higher (unadjusted: 8.2% vs. 5.1%, LR χ 2 p=0.033; adjusted OR= 1.81 (95% CI= 1.09: 3.01), and median (IQR) length of stay was longer (6.0 days vs. 5.1 days, Wilcoxon p <0.001). Conclusion: After adjustment, ≥12 h bed rest after AIS treated with MT showed no significant difference in favorable discharge location or readmission rates compared with ≥24 h bed rest. Higher pneumonia rates and longer length of stay in the ≥12 h group were observed, likely reflecting unmeasured clinical factors rather than bed rest duration. Randomized trials are needed to clarify the impact of bed rest duration and optimal mobilization strategy.

Introduction: An estimated 23.9 million (8.9%) individuals used illicit drugs and it accounted for 20 million disability-adjusted life-years in 2010. The use of illicit drugs, particularly cocaine, is associated with an increased risk of ischemic and hemorrhagic stroke. Given the lack of well-defined guidelines and previous literature suggesting healthcare disparities in toxicology screening, we aimed to determine the rate of urine toxicology screening and differences in testing among patients with stroke and transient ischemic attack (TIA) presenting to a tertiary care comprehensive stroke center. Hypothesis: We hypothesized that toxicology screening rates would differ depending on age, sex, and race. Methods: Approved by local ethics review board. All patients aged>18 admitted ischemic stroke, intracerebral hemorrhage, or TIA were included from 2018 to 2023. Demographic and clinical information were obtained from UMass Get With The Guidelines’ database. Charts were reviewed retrospectively to collect toxicology screening. The difference in urine toxicologies was assessed by chi-square tests for categorical measures and a 2-sample t-test for continuous measures. Univariate factors with a p<0.20 were included in multivariate logistic regression model. Results: A total of 4,511 stroke patients were identified, of whom 407 (9%) underwent toxicology screening. After excluding prescribed and hospital-administered medications, 90 patients (22.1%) had a positive toxicology result. The majority of tests (67.7%) were ordered by the admitting team, while 32.3% in the emergency department. A 9.3% cocaine positivity rate was observed in screened patients aged 50 to 69. Toxicology screening was performed significantly more often in patients under the age of 50, males, and individuals of Black race (p < 0.0001). No significant difference in the rate of positive results among these groups. Conclusions: Our results showed a significant positivity rate despite a low utilization of toxicology screening, revealing potential missed opportunity in the identification of illicit drugs for evaluation of stroke etiology and secondary stroke prevention, as well as a significant disparity towards testing young, male, and/or black patients. Screening disparities by age, sex, and race raise concerns about equity in stroke care. Standardized toxicology screening protocols for all stroke/TIA patients could improve etiologic evaluation and reduce demographic-based disparities.

Background: The practice of a minimum of 24 hour bed rest following thrombolytic therapy for acute ischemic stroke (AIS) is a widely adopted standard of care among hospitals, yet its benefit over earlier mobilization is unclear. We aimed to determine whether discharge outcomes, in-hospital complications, and readmission rates were more favorable in AIS patients treated with thrombolysis who followed a ≥12-hour versus ≥24-hour bed rest protocol. Methods: Consecutive adult AIS patients at a single comprehensive stroke center who received IV thrombolysis from January 3, 2010, until December 30, 2024, identified from a local ischemic stroke registry, were included. Standard 24-hour bed rest (the protocol prior to April 8, 2020) was retrospectively compared with the center's current practice- 12-hour bed rest. Primary outcome was favorable discharge location (defined as home, inpatient rehabilitation facility, or acute rehabilitation). Secondary outcome measures included incidence of pneumonia, length of stay, 90-day modified Rankin scale (mRS) scores, and readmission rates. Results: 1321 patients were identified (466 in the ≥12-hour group, 855 in the ≥24-hour group). Mean (s.d.) age in the ≥12 hour group was 70.4 (14.0) and 72.3 (14.6) in the ≥24-hour group; median (IQR) NIHSS was 5.0 (2-9) and 7.0 (3-14), respectively. There was no between-group difference in the median (IQR) length of stay (3.3 days vs. 3.4 days, Wilcoxon p=0.36) or unplanned readmission rate at 30 days (8.7% vs. 10.5%, LR χ 2 p-value=0.40) and 90 days (15.6% vs. 16.1%, LR χ 2 p-value=0.86). There was no difference in the frequency of good outcomes (mRS=0-2) by 90 days between the groups (61.5% vs. 55.7%, χ 2 p-value =0.42). Rates of pneumonia (both in unadjusted and adjusted analyzes) were lower in the 12-hour group (unadjusted: 1.1% vs. 3.4%, LR χ 2 p=0.006; adjusted OR= 0.53 (95% CI= 0.20: 1.44). There was a significant difference in favorable discharge outcome in the ≥12-hour group compared with the ≥24-hour group both in unadjusted z-test of proportions (80.0% vs. 69.0%, Likelihood Ratio χ 2 p<0.001) and in multivariable logistic regression analysis (adjusted OR=1.34; 95% CI=1.01:1.86) favoring the 12-hour group. Conclusion: Compared with ≥24-hour bed rest, ≥12-hour bed rest after AIS thrombolysis was associated with more favorable discharge outcomes and reduced occurrence of pneumonia-suggesting a potential benefit with earlier mobilization that warrants further investigation in randomized studies.

INTRODUCTION:The mechanisms linking migraine to stroke are unclear. Systemic inflammation may contribute, but the mediating role of inflammatory biomarkers is unknown. We evaluated whether systemic inflammatory biomarkers mediate the migraine-stroke association in postmenopausal women. METHODS:We analyzed data from 147,730 postmenopausal women without baseline stroke in the Women's Health Initiative, a large US prospective cohort of clinical trials and an observational study. Baseline levels of C-reactive protein (CRP; n = 43,754), tumor necrosis factor-alpha (TNF-α; n = 10,610), and interleukin-6 (IL-6; n = 19,637) were assessed as potential mediators. Stabilized inverse probability weighting addressed biomarker subsampling. We used Cox proportional hazards models to estimate associations between migraine history and stroke and of quartile-categorized biomarkers and stroke, linear regression models to estimate associations between migraine history and log-transformed biomarkers, and spline-based Cox models assessed stroke risk across continuous biomarker levels. RESULTS:Migraine history was associated with increased risks of total stroke (adjusted hazard ratio [aHR]: 1.10; 95% confidence interval (CI): 1.02-1.19) and ischemic stroke (aHR: 1.14; 95% CI: 1.05-1.25), but not hemorrhagic stroke. Higher CRP and IL-6 levels were consistently related to increased total and ischemic stroke risks. Compared with the lowest quartile (Q1, log-transformed), aHRs (95% CIs) for total stroke across Q2-Q4 were 1.11 (1.00-1.22), 1.18 (1.07-1.30), and 1.50 (1.35-1.65) for CRP, and 2.23 (1.87-2.65), 2.63 (2.22-3.12), and 2.31 (1.94-2.76) for IL-6. In contrast, TNF-α showed a different pattern, with an elevated risk at moderate levels and attenuation at higher concentrations. None of the biomarkers were associated with hemorrhagic stroke. No significant associations were observed between migraine history and any of the three biomarkers. The estimated indirect effects of migraine on ischemic stroke through CRP, TNF-α, and IL-6 were small and not statistically significant (all p > 0.05). The proportions mediated were 0.65% for CRP, -2.82% for TNF-α, and 3.98% for IL-6, indicating minimal contribution of these biomarkers to the migraine-stroke association. CONCLUSION:Inflammatory biomarkers did not serve as a mediator in the relationship between migraine and stroke in postmenopausal women, suggesting that the association is likely driven by other biological pathways.

The interventional management of symptomatic carotid disease (ie, endarterectomy, angioplasty/stenting, or transcarotid artery revascularization) has traditionally involved correcting the area of arterial narrowing, guided by stenosis severity combined with medical therapy, and has been recommended by the 2021 American Heart Association Secondary Stroke Prevention Guidelines. Despite this traditional practice, advances in medical therapy show promise in reducing recurrent stroke without the need for interventional procedures in the setting of low-to-intermediate-risk carotid lesions. We review current evidence for the nonoperative management of symptomatic carotid disease, focusing on markers of plaque vulnerability, risk calculators, and the efficacy of intensive medical therapy. The objective of this review was to illustrate that medical management of symptomatic carotid disease may be a reasonable alternative to surgical intervention in select patients. High-risk features such as intraplaque hemorrhage, a large lipid-rich necrotic core, a thin fibrous cap, plaque ulceration, vessel wall enhancement, and microembolic activity found on transcranial Doppler ultrasound strongly predict recurrent ischemic events and favor revascularization. In contrast, their absence supports medical management. Risk stratification tools such as the Carotid Artery Risk score and PLAQUE Radiology Scoring system have demonstrated potential utility for identifying low-risk patients who are good candidates for medical therapy. Guideline-directed medical therapy uses antiplatelet agents, intensive lipid-lowering therapy, blood pressure control, diabetes management, and structured lifestyle interventions. Contemporary clinical trials such as the Second European Carotid Surgery Trial and CASCOM are evaluating the comparative effectiveness of revascularization versus intensive medical therapy, with interim data suggesting comparable outcomes in appropriately selected patients. In the modern era, medical management of symptomatic carotid stenosis is safe and effective for patients lacking high-risk plaque features. Integration of imaging biomarkers, validated risk calculators, and structured risk factor modification programs offers a precision-medicine approach that may redefine treatment algorithms and aid in patient management.

BACKGROUND AND OBJECTIVES:Migraine is a known risk factor for stroke in women of reproductive age, although its relationship with stroke among postmenopausal women remains unclear. We assessed the association between migraine history and incident stroke in a sample of postmenopausal women. METHODS:We included women enrolled in the Women's Health Initiative, a large US longitudinal cohort study of postmenopausal women, and excluded those with previous stroke or those with missing data on key variables. The primary exposure was self-reported, physician-diagnosed migraine at baseline, and the primary outcome was incident stroke (total, ischemic, or hemorrhagic). Multivariable Cox proportional hazards models were used to test the cause-specific hazard ratios (HRs) between migraine history and total, ischemic (overall and by subtype), and hemorrhagic stroke, sequentially adjusted for age, traditional cardiovascular risk factors, and female-specific risk factors (age at menopause, age at menarche, menstrual irregularity, presence of vasomotor symptoms, parity, breastfeeding, and use of menopausal hormone therapy). We then quantified the association between a history of migraine and total stroke by age at baseline (in 5-year age groups) using multivariable models. Data on the presence of aura and migraine frequency were not available. RESULTS:Participants (N = 130,277) had a median age of 63 years (interquartile range [IQR] 57-69). A total of 5,743 incident stroke events occurred over a median follow-up period of 19.9 years (IQR 9.1-25). In multivariable models, there was no significant association between migraine history and total stroke (HR 1.07, 95% CI 0.99-1.17), but there was a significant association between migraine history and ischemic stroke (HR 1.12, 95% CI 1.02-1.23). In planned secondary analysis of ischemic subtypes, the associations were most pronounced in the cardioembolic (HR 1.17, 95% CI 0.98-1.39) and undetermined (HR 1.14, 95% CI 0.98-1.33) categories. Migraine was not associated with hemorrhagic stroke (HR 0.85, 95% CI 0.67-1.09). Risk did not differ significantly by age group. DISCUSSION:Over 20 years of follow-up, postmenopausal women with a history of migraine had a higher risk of ischemic stroke, but not total or hemorrhagic stroke. Along with other factors, a history of migraine should be considered a risk marker when assessing ischemic stroke risk after menopause.

Introduction: Migraines are a known risk factor for stroke among reproductive-aged women, though the relation of migraines to stroke risk among postmenopausal women remains unclear. We assessed the association between a history of diagnosed migraine and incident stroke among postmenopausal women and investigated age differences in the association. Methods: We included women enrolled in the Women’s Health Initiative (WHI), a large longitudinal cohort study of postmenopausal women in the U.S. We excluded women with a history of stroke or TIA at baseline or with missing data on history of migraine or key covariates. The primary exposure was a history at baseline of self-reported migraine diagnosed by a physician. The primary outcome was incident stroke (total, ischemic [IS], or hemorrhagic [ICH]). Multivariable Cox proportional hazards models were used to test the cause-specific hazard ratios (HRs) between migraine history and total stroke, IS (overall and by subtype), and ICH, sequentially adjusted for age and traditional and female-specific risk factors. Using multivariable Cox proportional hazard models, we then quantified the association between migraine history and total stroke by age in 5-year groups at baseline. Results: 130,277 participants were included. The median age at baseline was 61 years (IQR 56-67 years) for those with a migraine history compared to 63 years (IQR 57-69 years) for those without. Overall, 5,743 strokes occurred over a median follow-up period of 19.9 years (IQR 9.1-25). In multivariable-adjusted models (Table), there was a marginal association between migraine history and total stroke (HR=1.07; 95% CI, 0.99-1.17) and a significant association between migraine history and IS (HR=1.12; 95% CI, 1.02-1.23), most pronounced in the cardioembolic category. Migraine was not associated with risk of ICH (HR=0.85, 95%CI, 0.67-1.09). Risk appears to be of greatest magnitude in early (HR 1.26, 95% 0.93-1.72) and late (HR 1.16, 95%CI 0.89-1.50) postmenopausal years (Figure), though the differences by age group were not statistically significant. Conclusions: Over a 20-year follow-up period, postmenopausal women with self-reported histories of migraine had a higher risk of IS, but not total or ICH, suggesting that migraine history contributes to ischemic stroke risk during the postmenopausal years. Along with other known risk factors, migraine history should be considered in stroke risk factor screening and prevention efforts after menopause.

The addition of direct thrombin inhibitors or glycoprotein platelet inhibitors to intravenous thrombolysis in patients undergoing endovascular thrombectomy for acute ischemic stroke may improve reperfusion rates and clinical outcomes. To investigate the safety and efficacy of these agents. This was a preplanned cohort analysis from the Multi-Arm Optimization of Stroke Thrombolysis (MOST) randomized clinical trial, which lasted from 2019 to 2023 with a 90-day follow-up. Centrally read outcomes were assessed blinded to treatment. The MOST study was a multicenter, multiarm, adaptive, single-blind, phase 3 trial that included patients with acute ischemic stroke who were selected for thrombectomy per standard of care. Patients were randomized to placebo, argatroban, or eptifibatide within 75 minutes of intravenous thrombolysis. The 90-day utility-weighted modified Rankin Scale (UW-mRS) score (range, 0-10, with higher scores reflecting better outcomes) was used as the primary outcome measure. Reperfusion rates and safety (hemorrhage rates) were also assessed, where good reperfusion was defined as a Thrombolysis in Cerebral Infarction score of 2b/2c/3 on the completion angiogram. A total of 5376 patients were assessed for eligibility. Of these individuals, 4332 did not meet inclusion criteria, 251 eligible patients did not have consent obtained, 279 were excluded for other reasons, and 514 were randomized in the MOST trial. A total of 254 were planned for thrombectomy (110 in the placebo group, 31 in the argatroban group, and 113 in the eptifibatide group). Mean (SD) age was 68 (14.3) years, and 134 (53%) were female. Of these patients, 219 received thrombectomy: 94 in the placebo group, 27 in the argatroban group, and 98 in the eptifibatide group. There was no effect of treatment on outcome (mean UW-mRS score: eptifibatide, 6.47; 95% CI, 5.79-7.15; argatroban, 5.35; 95% CI, 4.13-6.58; placebo, 6.68; 95% CI, 5.98-7.39). Rates of good reperfusion were similar between groups (83 of 92 in the placebo group [83%]; 17 of 27 in the argatroban group [63%], and 82 of 98 in the eptifibatide group [84%]). The proportion of symptomatic intracranial hemorrhage was similar between groups. Results of this secondary analysis of the MOST randomized clinical trial reveal that the addition of argatroban or eptifibatide to intravenous thrombolysis was not associated with better reperfusion rates or clinical outcomes in patients undergoing endovascular thrombectomy. Future investigations of these agents as intravenous adjuncts to thrombectomy should focus on populations who are ineligible for intravenous thrombolysis. ClinicalTrials.gov Identifier: NCT03735979

INTRODUCTION:Stroke is a leading cause of morbidity and mortality, particularly in older adults. Identifying lifestyle factors, such as physical activity (PA), that mitigate stroke risk is critical for stroke prevention, especially in postmenopausal women. We sought to determine the association between levels and types of recreational PA and risk of total, ischemic, and hemorrhagic stroke in postmenopausal women. METHODS:We performed a prospective cohort study conducted within the Women's Health Initiative from 1993 to 1998 with a mean follow-up of 8.5 years. We studied a total of 139,871 postmenopausal women aged 50-79 years without prior cardiovascular disease or stroke at enrollment. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Recreational PA was assessed via questionnaire, including total, light, moderate, and vigorous activities and walking. Incident total, ischemic, and hemorrhagic strokes were recored. HRs and 95% CIs were adjusted for sociodemographic, lifestyle, and clinical factors. RESULTS:During follow-up, 4,642 stroke occurred (3,496 ischemic and 728 hemorrhagic). Higher levels of total PA (per 1 SD MET-hr/wk: HR = 0.90, 95% CI: 0.87-0.93), walking (HR = 0.93, 95% CI: 0.90-0.96), and moderate PA (HR = 0.91, 95% CI: 0.88-0.94) were associated with reduced total stroke risk. Similar inverse associations were found for ischemic stroke. Vigorous PA demonstrated a J-shaped association with ischemic stroke, while light PA was not significantly associated with stroke risk. Total (HR = 0.90, 95% CI: 0.83-0.97) and vigorous PA (HR = 0.88, 95% CI: 0.81-0.96) were inversely associated with hemorrhagic stroke. Associations were consistent across subgroups defined by age, race/ethnicity, blood pressure, hormone therapy use, BMI, and dietary intake. CONCLUSION:Increased recreational PA, particularly moderate, with cautious interpretation of vigorous activity due to its J-shaped association and potential risks, is associated with reduced risks of total and ischemic stroke in postmenopausal women. Our findings support promoting PA as a key strategy for stroke prevention in this population.

INTRODUCTION:Chronological age is the strongest risk factor for Alzheimer's disease and related dementias (ADRD). However, the association of accelerated biological aging relative to chronological age with ADRD pathology is unclear. METHODS:In a cohort of 2366 (873 with longitudinal data) cognitively unimpaired older women, we examined associations of seven baseline measures of epigenetic age acceleration (EAA) and pace of aging with 15-year changes in plasma ADRD biomarkers. RESULTS:At baseline, higher AgeAccelHorvath and AgeAccelPheno were associated with lower amyloid beta (Aβ) 42 to Aβ40 (Aβ42:Aβ40) ratio, and higher AgeAccelGrim2, PCPhenoAge, and PCGrimAge were associated with elevated neurofilament light (NfL). Longitudinally, higher baseline DunedinPACE - capturing the pace of biological aging - was associated with faster increases in tau phosphorylated at threonine 181 (p-tau181), p-tau217, NfL, and glial fibrillary acidic protein (GFAP) over 15 years. DISCUSSION:Accelerated biological aging, particularly DunedinPACE, was associated with increasing levels of plasma ADRD biomarkers over time. HIGHLIGHTS:We studied 2366 older women from the Women's Health Initiative Memory Study. AgeAccelHorvath and AgeAccelPheno were linked to lower plasma Aβ42:Aβ40 at baseline. AgeAccelGrim2, PCPhenoAge, and PCGrimAge were linked to higher plasma NfL at baseline. DunedinPACE was associated with faster increases in p-tau181, p-tau217, NfL, and GFAP.

Background and Objectives:A higher LACE+ index risk category (defined as LACE+ score ≥78) typically calculated before hospital discharge has been associated with increased risk of unplanned 30-day hospital readmissions and early death after hospital discharge. However, its utility to predict poststroke mortality is unknown. Here, we examined whether the LACE+ index risk category assessed at both discharge (dLACE+) and admission (aLACE+) was associated with 90-day mortality after stroke. Methods:We retrospectively analyzed 2,729 consecutive patients who presented with ischemic or hemorrhagic strokes, included in an institutional stroke registry between January 2018 and December 2021. The primary outcome of interest was 90-day mortality after the index hospitalization. Patients were categorized as high-risk (≥78), medium-to-high-risk (59-77), and low-to-medium-risk (0-58) according to the LACE+ as automatically calculated at admission and discharge. Analyses were performed on the entire cohort, as well as stratified according to acute ischemic stroke and hemorrhagic stroke diagnosis. Results:Among patients who completed 90-day follow-up, the mortality rate was 24.3% (576/2368). In the Kaplan-Meier analysis, the high-risk aLACE+ group had the highest 90-day mortality rate as compared with low-to-medium-risk and medium-to-high-risk groups (p < 0.001). In a fully adjusted multivariable Cox-regression, the 90-day hazards of death were significantly greater among participants in a high-risk aLACE+ (aHR 1.7, 95% CI 1.080-2.742, p = 0.022) and medium-to-high-risk aLACE+ categories (aHR 1.4, 95% CI 1.141-1.778, p = 0.002) as compared with participants in the low-to-medium-risk aLACE+ category. Results were overall similar for dLACE+. Discussion:The LACE+ calculated at both admission and discharge admission identified patients with stroke at increased risk for 90-day mortality. Future studies are warranted to determine whether LACE+ score-based risk stratification can be used to devise early interventions to mitigate the risk for death.