搜索结果：Stroke and vascular neurology

Ischemic stroke remains a leading cause of disability and mortality worldwide, with limited acute therapeutic options. Sphingosine-1-phosphate (S1P) is a bioactive lipid that regulates endothelial function, vascular integrity, and immune responses, and reduced circulating S1P levels have been reported in ischemic stroke. Whether plasma S1P depletion parallels alterations in brain-endothelial S1P metabolism, receptor expression, and endothelial activation, however, remains unclear. Here, we characterized circulating S1P levels together with stroke-associated changes in brain-endothelial S1P pathway expression, markers related to endothelial activation, and blood-brain barrier (BBB) integrity. We quantified plasma S1P concentrations in patients with acute ischemic stroke (n = 50) and age- and sex-matched controls (n = 47), with follow-up assessments at 90 days. Complementary experimental stroke studies were performed using transient and permanent middle cerebral artery occlusion (MCAo) in wild-type mice and in endothelial-specific RiboTag mice (Cdh5^Cre-ER(T)) that enable selective isolation of endothelial mRNA. In parallel, human brain microvascular endothelial cells were exposed to oxygen-glucose deprivation in vitro. Endothelial activation-related markers, expression of S1P-metabolizing enzymes and S1P receptors, BBB integrity, and circulating P-selectin levels were assessed by qPCR, Western blotting, immunohistochemistry, and ELISA-based approaches. Plasma S1P levels were significantly reduced in patients with acute ischemic stroke compared with controls and recovered at follow-up, consistent with findings in experimental stroke. Endothelial-specific transcriptomic profiling revealed reduced expression of sphingosine kinases, S1P-degrading enzymes, and S1P receptors (S1pr1, S1pr3, and S1pr4) in the ischemic brain endothelium. Lower vascular S1PR1 protein expression was associated with increased BBB disruption, and sphingosine kinase 2 protein abundance was reduced in small cerebral vessel endothelial cells of the lesioned compared to the contralateral hemisphere. These alterations were accompanied by acute changes in endothelial barrier- and activation-related markers, together with model-dependent changes in plasma P-selectin in mice. In patients, plasma P-selectin levels were not elevated acutely but showed an inverse association with plasma S1P concentrations. Ischemic stroke associates with acute plasma S1P depletion that parallels altered brain-endothelial S1P pathway expression, signs of endothelial activation, and BBB disruption. These findings support plasma S1P as a candidate circulating marker associated with cerebrovascular injury after stroke.

Perioperative ischemic stroke is uncommon overall but frequent in cardiac, major vascular, and neurosurgical procedures. Existing calculators often exclude these settings and rarely incorporate cerebrovascular disease markers available in routine electronic health record data. We assembled a retrospective cohort of adults undergoing procedures at 3 hospitals (January 2016-June 2024). The model was derived at Rhode Island Hospital (255&#x2009;850 procedures) and externally validated at 2 affiliated hospitals (The Miriam Hospital/Newport Hospital; 189&#x2009;095 procedures). Candidate predictors included age, vascular comorbidities, documented carotid stenosis and intracranial atherosclerosis, procedure setting (ambulatory versus inpatient/emergency), and procedural service (including vascular versus nonvascular neurosurgery and open versus interventional cardiovascular procedures). We fit a multivariable logistic regression model with internal validation using 1000 bootstrap resamples and assessed calibration by observed versus predicted risk across deciles. External validation applied locked derivation coefficients without refitting. Strokes occurred in 1235/255&#x2009;850 derivation procedures (0.48%) and 418/189&#x2009;095 validation procedures (0.22%). Independent predictors included older age, prior stroke or transient ischemic attack (adjusted odds ratio [aOR], 6.66), inpatient/emergency setting (aOR, 4.25 versus ambulatory), vascular neurosurgery (aOR, 6.70 versus general surgery), and open cardiovascular procedures (aOR, 4.14). Discrimination was high (derivation area under the curve, 0.87 [95% CI, 0.87-0.88]; optimism-corrected area under the curve, 0.87; validation area under the curve, 0.86 [95% CI, 0.84-0.87]) with good calibration. Prespecified risk strata (<1%, 1-5%, >5%) separated observed event rates in both cohorts. A pragmatic, electronic health record-derived model integrating procedural category and cerebrovascular disease accurately predicts 30-day periprocedural ischemic stroke across diverse procedures and is available as a web-based calculator to support counseling and targeted prevention.

Data are scarce regarding the frequency, characteristics, and associated recurrent event risks of cerebrovascular fibromuscular dysplasia (cFMD) in patients presenting with ischemic stroke and transient ischemic attack (TIA). We included patients diagnosed with ischemic stroke/TIA in an entire Canadian province (Alberta) from 1-April-2016 to 31-March-2017, with follow-up of at least 5-years until 31-March-2022. Direct neuroimaging review and keyword searches of radiologist reports were used to identify suspected cFMD cases. Clinical and imaging characteristics and event etiology were ascertained. 5-year hazards of recurrent stroke/TIA were estimated, adjusted for age, sex, and vascular risk factors. Among 4,033 patients with ischemic stroke/TIA who underwent CT/MR angiography, we found 35 (0.86%) cases of cFMD. Patients with cFMD had similar age (median:74[IQR:53-88] vs 69[IQR:20-99] years, p = 0.09) and higher female preponderance (80% vs 44.9%, p < 0.0001) versus those without. The extracranial proximal internal carotid artery (ICA) was most frequently involved. Most observed infarcts (23/26, 88.5%) occurred downstream from carotid/vertebral arteries with cFMD changes. Strokes/TIAs for most cFMD patients (27/35, 77.1%) were adjudicated to be of otherwise undetermined etiology following conventional investigations. All-cause mortality occurred in 10 (28.5%) and recurrent stroke/TIA in 8 (22.9%) patients at 5-years; this was not significantly higher than patients without FMD (aHR: 1.54, 95%CI:0.77-3.11). cFMD was a rare finding in this subset of patients with stroke/TIA who underwent adequate neuroimaging, primarily affecting females and the extracranial proximal ICA. Infarcts in these patients often occurred in the territory of FMD-affected vessels and events were often classified as cryptogenic. Whereas these patients had substantial rates of recurrent stroke/TIA and mortality, the adjusted hazards versus patients without cFMD were imprecise.

Covert cerebrovascular disease is traditionally defined as microvascular brain injury. Whether non-culprit macrovascular abnormalities below conventional stenosis thresholds represent a clinically relevant form of vascular vulnerability remains unclear. We investigated the prevalence and prognostic significance of covert macrovascular disease (CMVD) in acute ischemic stroke and transient ischemic attack (TIA). In this prospective observational cohort, consecutive patients admitted with ischemic stroke or TIA underwent standardized vascular imaging. CMVD was defined as non-culprit macrovascular pathology not meeting TOAST criteria for large-artery atherosclerosis, including non-stenotic carotid or vertebral plaques (<&#x2009;50%), plaques outside the infarct-supplying territory, aortic arch atheroma (&#x2265;&#x2009;2 mm), or non-hemodynamically relevant vascular elongation or kinking. Lesions were adjudicated by blinded experts. The primary outcome was favorable functional status at discharge (modified Rankin Scale [mRS] 0-2). Multivariable logistic regression adjusted for demographic, clinical, and vascular risk factors. Among 714 patients (mean age 72&#x2009;&#xb1;&#x2009;9&#xa0;years; 43% women), CMVD was present in 271 (37.9%; 95% CI, 34.4-41.6). CMVD prevalence varied by stroke etiology, highest in large-artery atherosclerosis (56%) and cardioembolic stroke (41%), intermediate in ESUS (35%), and lowest in small-vessel occlusion (21%). Patients with CMVD had higher admission stroke severity and lower rates of favorable functional outcome at discharge (47.1% vs. 63.2%; p&#x2009;=&#x2009;0.001), as well as higher in-hospital mortality (6.3% vs. 2.7%; p&#x2009;=&#x2009;0.049). CMVD remained independently associated with unfavorable outcome (adjusted OR 1.82; 95% CI, 1.18-2.81; p&#x2009;=&#x2009;0.006) and an increased risk of recurrent ischemic stroke during follow-up (HR, 1.84; 95% CI, 1.05-3.20). Covert macrovascular disease is common in acute ischemic cerebrovascular events and independently predicts worse early functional outcome. These findings support CMVD as a clinically meaningful marker of systemic vascular vulnerability beyond culprit stenosis.

Cardiac complications rank among the leading contributors to poor outcomes in ischemic stroke patients along with the neurological impairment, while the risk stratification and prognostic significance of post-stroke acute heart failure (PSHF) remain poorly characterized. This study aimed to investigate the incidence, predictors, and impacts of PSHF in patients with large vessel occlusion stroke (LVO) undergoing endovascular treatment (EVT). Given that cardioembolic stroke inherently involves underlying cardiac pathology, a secondary aim was to test whether the effect of stroke severity on PSHF was modified by cardioembolic etiology and whether PSHF mediated the effect of stroke severity on functional outcome in these patients. In a pooled analysis of individual patient data from four multicenter prospective studies conducted in China between January 2014 and June 2023, we included 3,415 patients with LVO who underwent EVT. The primary outcome was very poor functional outcome, defined as 90-day modified Rankin Scale (mRS) 5-6. Multivariable regression models, interaction testing, and mediation analysis were used, with adjustment for clinically relevant covariates including demographic characteristics, vascular risk factors, baseline stroke severity, imaging characteristics, and treatment-related factors. PSHF developed in 278 patients (8.14%), with its incidence reaching peak at 1 day after stroke onset. PSHF was significantly associated with a higher rate of very poor outcome (62.23% versus 31.08%, adjusted odds ratio (aOR) 3.09, 95% confidence interval (CI) [2.25, 4.24]). A significant interaction was observed between cardioembolism and the baseline National Institutes of Health Stroke Scale (NIHSS) score (p for interaction&#x2009;=&#x2009;0.016). Moderate-to-severe stroke significantly increased the risk of PSHF in patients with cardioembolic stroke (aOR 1.91, 95% CI [1.28, 2.87]), but not in those with non-cardioembolic stroke (aOR 0.97, 95% CI [0.81, 1.82]). Mediation analysis showed that PSHF mediated 7.70% (95% CI [2.40, 12.40]) of the effect of moderate&#x2011;to&#x2011;severe stroke on very poor outcome among cardioembolic patients. The main methodological limitations were the pooled design using studies with different protocols and the potential for residual unmeasured confounding. PSHF was significantly associated with very poor outcome in LVO patients undergoing EVT. Moderate-to-severe cardioembolic LVO substantially elevated the risk of PSHF, with PSHF partially mediating the adverse prognostic impact of stroke severity. Early risk assessment and monitoring for PSHF may optimize management in this high-risk population.

A clinical prediction model (IMPROVE) for ipsilateral ischaemic stroke risk in symptomatic patients with carotid disease was recently developed with good performance. We aim to evaluate the model-based cost-effectiveness of IMPROVE-based triage versus triage in care-as-usual (CAU) for optimal medical treatment (OMT) alone or carotid endarterectomy plus OMT. A dataset of 678 patients with carotid disease and a recent ipsilateral ischaemic stroke, transient ischaemic attack or amaurosis fugax from four cohort studies informed a decision-analytic model. Stratification of patients for carotid endarterectomy was based on &#x2265;50% carotid stenosis (CAU arm) or a range of 3-year ipsilateral ischaemic stroke risk thresholds (IMPROVE arm). The threshold resulting in the lowest number of ipsilateral strokes and perioperative strokes and deaths was selected as the optimal threshold. Patients with <50% stenosis (CAU) or an IMPROVE risk score below the threshold (IMPROVE) were modelled to receive OMT only. Parameter uncertainty was incorporated in probabilistic analyses using Monte Carlo simulations for a 3-year and lifetime horizon. Subgroup analyses for <50%, 50-69% and 70-99%&#x2009;carotid stenosis were performed. IMPROVE-based triage reduced ipsilateral ischaemic strokes and perioperative strokes and deaths by 34.5% (CAU: 4.3%, IMPROVE: 2.8%) over 3 years. Revascularisations decreased by 20% with IMPROVE, while Quality-Adjusted Life Years slightly increased. Procedural stroke occurred in 1.8% of patients in CAU versus 1.4% of patients for IMPROVE. Societal costs decreased on average by &#x20ac;1441/patient for IMPROVE versus CAU for a 3-year time horizon (lifetime cost reduction: &#x20ac;6101/patient). Subgroup analyses identified IMPROVE as the superior strategy for 50-69%&#x2009;and 70-99%&#x2009;stenosis (3-year and lifetime horizon) and <50% stenosis (lifetime horizon). In this modelling analysis, triage of symptomatic patients with carotid disease with the IMPROVE model can lead to the prevention of one-third of ipsilateral ischaemic strokes and perioperative strokes and deaths, while also reducing societal costs. These findings should be validated in a clinical trial.

Acute basilar artery occlusion (BAO) carries a disability rate as high as 80% and its optimal treatment window remains a clinical controversy. While landmark studies such as ATTENTION (Endovascular Treatment for Acute Basilar-Artery Occlusion) and BAOCHE (Basilar Artery Occlusion Chinese Endovascular Trial) have confirmed the efficacy of endovascular treatment (EVT) within 24&#x2009;hours, there is still a lack of high-level evidence supporting intervention strategies for patients beyond this time window. The ANGEL (Acute Ischaemic Stroke Cooperation Group of Endovascular Treatment)-BAO trial aims to evaluate the efficacy and safety of EVT plus best medical management (BMM) compared with BMM alone in patients with BAO presenting within an extended time window of 24-72&#x2009;hours from symptom onset (or last known well). This is a multicentre, prospective, randomised, open-label, blinded endpoint (PROBE) clinical trial. A total of 224 patients will be randomised in a 1:1 ratio to receive either EVT plus BMM or BMM alone. Key inclusion criteria include confirmed BAO, National Institutes of Health Stroke Scale (NIHSS)&#x2265;10, prestroke modified Rankin Scale (mRS) 0-2 and diffusion-weighted imaging evidence of limited infarct extent (posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS)&#x2265;6 and Pons-Midbrain Index&#x2264;3). The primary efficacy outcome is the proportion of patients achieving an mRS score of 0-3 at 90 days. Secondary outcomes include mRS distribution, NIHSS scores, quality of life questionnaire (EuroQol 5-Dimension questionnaire) and recanalisation rates. Safety outcomes encompass symptomatic intracranial haemorrhage (per Heidelberg criteria) and mortality within 7 and 90 days. ANGEL-BAO addresses a critical gap in evidence regarding EVT for BAO in an extended time window (24-72&#x2009;hours). By incorporating advanced imaging selection and standardised protocols, the trial aims to provide robust data to guide treatment strategies for this severe stroke subtype. NCT06101667.

The relevance of prior antithrombotic and thrombolytic treatment for decision-making regarding endovascular thrombectomy (EVT) for acute ischemic stroke due to large vessel occlusion with established large infarcts is uncertain. This study investigates associations of prior antithrombotic medication and thrombolysis with the efficacy and safety of EVT for acute ischemic stroke due to large vessel occlusion with established large infarct. TENSION (Efficacy and Safety of Thrombectomy in Stroke With Extended Lesion and Extended Time Window) was a prospective randomized open-label blinded-end point clinical trial. Patients with acute ischemic stroke due to large vessel occlusion and established large infarct were randomized to EVT with medical therapy or medical therapy alone. Exposures were preadmission antithrombotic treatment with antiplatelet agents or anticoagulants and intravenous thrombolysis. The primary efficacy end point was functional outcome at 90&#x2009;days. Safety outcomes included death and symptomatic intracranial hemorrhage. The study included 246 patients (median age, 74 years; interquartile range, 65 to 80&#x2009;years; 49% women); 124 (50%) were assigned to EVT. Of 176 patients (72%) with prior antithrombotic therapy, 75 (31%) received antiplatelets, 56 (23%) anticoagulants, and 89 (36%) intravenous thrombolysis. EVT was associated with better functional outcome in patients with (common odds ratio [cOR], 2.40 [95% CI, 1.22-4.99]) and without (cOR, 2.29 [95% CI, 1.53-3.46]) antiplatelet therapy; with (cOR, 2.45 [95% CI, 1.17-5.28]) and without (cOR, 2.12 [95% CI, 1.44-3.15]) anticoagulation; as well as receiving (cOR, 1.46 [95% CI, 0.83-2.61]) and not receiving (cOR, 2.89 [95% CI, 1.87-4.51]) thrombolysis. Interaction analyses were consistent with similar treatment effects across subgroups. Mortality and rates of symptomatic intracranial hemorrhage were similar between groups. Benefit and safety of EVT were not modified by prior antithrombotic/thrombolytic therapy. Preadmission exposure to antiplatelets or anticoagulants or use of intravenous thrombolysis should not exclude eligible patients with stroke from EVT. URL: https://www.clinicaltrials.gov; Unique Identifier: NCT03094715.

Clinical pharmacists are increasingly recognized as vital contributors to acute stroke care, yet their role remains inconsistently defined and underutilized across health care systems. This consensus statement explores the expanding presence of clinical pharmacists within interdisciplinary stroke teams, particularly in the management of both acute ischemic stroke&#xa0;(AIS) and hemorrhagic stroke. This consensus statement panel was composed of clinical pharmacists, emergency medicine physicians,&#xa0;and a vascular neurologist. The Grading of Recommendations, Assessment, Development, and Evaluation&#xa0;(GRADE)&#xa0;approach was used to assess the level of certainty and strength of recommendations. We focused on two questions regarding the clinical pharmacist's role in caring for adult patients presenting to the emergency department (ED) with AIS or hemorrhagic stroke. Despite the very low level of evidence, a consensus was reached for the following recommendations: (1) clinical pharmacist involvement in AIS care for adult patients presenting to the ED and (2) clinical pharmacist involvement in hemorrhagic stroke care for adult patients presenting to the ED. Based on the available literature, we believe optimizing the clinical pharmacist role is a critical factor in improving time-sensitive treatment and equity in care delivery.

Endovascular thrombectomy (EVT) has transformed the treatment of acute ischemic stroke (AIS). However, a substantial proportion of AIS patients experience poor outcomes despite successful recanalization, often due to severe neurological deterioration or life-threatening complications. Early identification of these high-risk patients remains a major unmet need. In this study, we developed and validated machine-learning (ML) models that integrate automated quantitative brain arterial morphology and collateral grading with demographic, clinical, laboratory, and imaging variables to predict major post-EVT complications and early neurological outcomes. Using a prospectively collected database of 727 AIS patients that underwent EVT, we developed ML models to incorporate patient-specific vascular morphometry with conventional clinical, laboratory, and imaging data to predict emergence of early neurological deterioration (END), symptomatic intracranial hemorrhage (sICH), malignant brain edema (MBE) requiring surgical decompression, and neurogenic respiratory failure and dysphagia requiring tracheostomy/gastrostomy (TC/PEG). Our analysis of morphological features, including increased tortuosity and reduced vessel diameter, showed strong associations with complications. Morphology-informed (MI) models consistently outperformed baseline-clinical (BC) models for patients with END (AUROC 0.81 for MI model vs. 0.73 for BC), sICH (AUROC 0.68 MI vs. 0.56 BC model), MBE (AUROC 0.67 MI model vs. 0.56 BC), or patients who underwent TC/PEG (AUROC 0.66MI vs. 0.58 BC model). Statistical testing confirmed significant AUROC improvements for END, sICH and mRS (p&#x2009;<&#x2009;0.05), Finally, patient-specific calibrated probability profiles enabled individualized, multidimensional risk stratification, revealing distinct complication-specific risk patterns across patients. These findings demonstrate that cerebrovascular structure-an often overlooked yet physiologically fundamental determinant of ischemic injury and reperfusion dynamics-provides significant predictive information that is not captured by standard clinical or visual imaging assessments. Automated vascular segmentation and collateral grading techniques enable rapid and objective integration of cerebrovascular metrics into prognostic models, offering a scalable tool for precision risk stratification, supporting earlier intervention, targeted monitoring, and improved post-EVT management.

Background: Several studies reveal an inverse relation between serum 25-hydroxyvitamin D [25(OH)D] concentration and the risk of acute ischemic stroke (AIS). The aim of this study was to determine relationships between 25(OH)D concentration and the course and outcomes of AIS treatment and the level of indices of inflammatory response to brain injury. Patients and Methods: Retrospective analysis of medical documentation of 1381 real-world AIS patients hospitalized in a single center between 1 January 2020 and 31 May 2025. Serum 25(OH)D level, several inflammatory indices, and clinical data were assessed. Results: Compared to patients in the lowest quartile of 25(OH)D concentration, those in the highest quartile had a shorter length of in-hospital stay, a lower risk of all-cause death, and a lower score for disability on a modified Rankin scale (mRS). Along with an increase in 25(OH)D quartiles, we found: a decrease in neutrophil count; a decrease in glucose, HbA1c, albumin, C-reactive protein (CRP), and CRP-to-albumin, -lymphocyte, -neutrophil, and -platelet ratios; lower neutrophil-to-lymphocyte and -albumin ratios, and lower systemic immune inflammation, and systemic inflammation response indices. In multifactorial logistic regression, the quartile of 25(OH)D (OR, 95% CI: 1.52, 1.09-2.12; p = 0.012) was the only variable to have a positive association with a mRS score &#x2264; 2 at discharge from hospital, and neutrophil-to-lymphocyte ratio, age, diabetes, and treatment with endovascular mechanical thrombectomy were biomarkers of poor functional status at discharge. Conclusions: Higher 25(OH)D concentration in AIS patients is related to better survival and a lower level of inflammatory response indices and disability at discharge.

Poststroke dysphagia and impaired cough reflex contribute to aspiration and pneumonia, yet the clinical value of cough reflex testing remains unclear. In this prospective observational study, 395 patients who had an acute stroke admitted to an intensive care unit underwent fiberoptic endoscopic evaluation of swallowing and citric acid cough reflex testing at 0.4&#x2009;mol/L. Dysphagia severity was rated using the Fiberoptic Endoscopic Dysphagia Severity Scale, with additional measures of secretion management, airway invasion and oral intake. Accuracy of cough reflex testing was calculated against fiberoptic endoscopic evaluation of swallowing. Ordinal and binary logistic regression assessed associations between cough reflex, dysphagia severity, pneumonia and mortality, including interactions. Cough reflex testing showed 75% sensitivity and 55% specificity for silent aspiration and 78% sensitivity and 43% specificity for any aspiration. Absent or weakened cough reflex predicted severe dysphagia, impaired secretion management, increased aspiration risk, restricted oral intake and reduced spontaneous swallowing (p<0.001). Older age, stroke severity, impaired cough reflex and dysphagia severity predicted mortality. Preserved cough reduced pneumonia risk only in mild dysphagia. Impaired cough reflex independently predicted poststroke dysphagia severity, impaired secretion management, aspiration risk, restricted oral intake and poorer functional outcome. Preserved cough conferred protection against pneumonia only in mild dysphagia, whereas in moderate to severe dysphagia aspiration burden and systemic vulnerability likely predominate, limiting clinical relevance of cough testing. Cough reflex testing provides meaningful information on poststroke dysphagia severity and airway protection and may support risk stratification when instrumental swallowing assessment is unavailable.

Rural residents have been experiencing higher stroke mortality than urban residents, and the gap has widened. Disparity in postacute care after stroke may increase the rural-urban gaps of mortality and disability. We aimed to examine whether rural patients with stroke receive the same postacute care and achieve comparable outcomes to urban patients. We conducted a cohort study of Medicare beneficiaries aged &#x2265;65 years treated in the Get With The Guidelines-Stroke participating hospitals for acute ischemic stroke during 2017 to 2022. We used restricted mean home-time to compare 1-year home-time among patients discharged from rural versus urban hospitals and the Cox proportional hazards model for all-cause mortality and readmission, adjusting for patient and hospital characteristics. The analysis included 29&#x2009;734 patients treated in rural hospitals and 478&#x2009;122 in urban hospitals, with a mean age of 79 years, and 55.5% were women. Compared with patients in urban hospitals, patients in rural hospitals were less commonly discharged to inpatient rehabilitation facilities (20.1% versus 25.1%; adjusted odds ratio, 0.76 [95% CI, 0.69-0.84]) and more frequently to skilled nursing facilities (24.5% versus 20.9%; adjusted odds ratio, 1.21 [95% CI, 1.11-1.32]). Compared with urban patients, rural patients had 1.8 fewer days of home-time (95% CI, -3.2 to -0.3) overall; rural patients discharged to skilled nursing facilities had 5.7 fewer days of home-time (95% CI, -9.0 to -2.3), and those discharged home had 2.2 fewer days of home-time (95% CI, -3.7 to -0.7). Rural patients overall had comparable all-cause mortality with urban patients (adjusted hazard ratio, 1.01 [95% CI, 0.98-1.05]) and lower all-cause readmission (adjusted hazard ratio, 0.92 [95% CI, 0.90-0.95]). However, rural patients who were discharged home had higher all-cause mortality than urban patients (adjusted hazard ratio, 1.11 [95% CI, 1.05-1.17]). Compared with urban patients, rural patients with stroke had less inpatient rehabilitation facility and more skilled nursing facility utilization, less home-time, but similar mortality. Further efforts are needed to ensure equitable postacute care in rural areas.

The contribution of late-life vascular risk factors to dementia risk remains controversial. Because low blood pressure (BP) has been associated with worse clinical outcomes in frail individuals, we hypothesized hypertension, but not diabetes or smoking, is associated with higher dementia risk in robust than in frail older adults. We performed a prospective cohort analysis of the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS) over 11 years (2011-2022). We included all community-living White and Black participants aged 67-89 years without dementia at baseline visit 5 (2011-2013) from ARIC-NCS field centers (Jackson, Mississippi; Forsyth County, North Carolina; Washington County, Maryland; Minneapolis suburbs, Minnesota). The primary vascular risk factors measured at baseline included elevated BP (systolic BP 120-129 mm Hg and diastolic BP < 80 mm Hg), hypertension (systolic BP &#x2265; 130 mm Hg, diastolic BP &#x2265; 80 mm Hg, or use of medication for BP), diabetes (fasting glucose &#x2265;126 mg/dL, nonfasting glucose &#x2265;200 mg/dL, self-reported physician's diagnosis, or use of diabetes medication), and former and current smoking (self-reported). We defined frailty status using the Fried criteria (5 components that include low energy, low physical activity, slowness, weakness, and weight loss). We estimated cause-specific hazard ratios (HRs) of incident dementia (ascertained from in-person neuropsychological assessments, semiannual participant or informant report, or surveillance of claims from hospitalizations and death certificates) with Cox proportional hazards models including a multiplicative interaction between vascular factors and frailty. HRs of dementia were then stratified by frailty (robust [no frailty components present] vs prefrail/frail [at least 1 frailty component present]). There were 377 (15.8%) dementia cases in robust participants (n = 2,383; mean age, 74.2 years; 55.4% female) and 812 (30.0%) in prefrail/frail participants (n = 2,710; mean age 76.4 years; 61.3% female). There was a significant interaction between BP and frailty on dementia risk (p = 0.026). For robust participants, HRs were 1.03 (95% CI 0.65-1.64) for elevated BP and 1.39 (95% CI 1.00-1.94) for hypertension relative to normal BP. For prefrail/frail participants, HRs were 0.68 (95% CI 0.49-0.95) and 0.82 (95% CI 0.66-1.01), respectively. Diabetes and current smoking were associated with higher dementia risk in both robust and prefrail/frail individuals. Late-life hypertension was associated with a lower relative risk of dementia in prefrail/frail participants, but the association was positive in robust participants. BP interpretation and management to support brain health in older adults could consider age-related functional status.

Stroke represents a major public health challenge in Spain, with approximately 120 000 cases per year and a significant impact on mortality, disability, and dependency. Elevated low-density lipoprotein cholesterol (LDL-C) is a key modifiable causal factor in preventing vascular recurrences. This consensus statement aims to provide a comprehensive framework for the practical management of lipid-lowering therapy in patients with stroke or transient ischaemic attack (TIA). A panel of experts in neurology, specialised in the management of patients with stroke/TIA, participated in 3 sessions to review the latest evidence. Subsequently, they reached consensus on practical recommendations for the management of lipid-lowering therapy based on data from clinical trials, meta-analyses, and current clinical guidelines. Achieving the therapeutic targets for LDL-C is essential to prevent recurrence in patients with stroke/TIA. To ensure comprehensive management of LDL-C in patients with stroke/TIA, the application of intensive therapeutic strategies, individualised approaches, and robust continuity of care are recommended to optimise secondary prevention. Treatment planning at discharge, neurologist-led risk factor control, and coordinated continuity of care between hospital and primary care settings are essential factors determining long-term outcomes. Inclisiran has emerged as a new key therapy to improve lipid control and treatment adherence in these patients, in alignment with national and international recommendations for achieving therapeutic targets and reducing the burden of vascular disease. Optimal implementation of this therapeutic approach may substantially contribute to improving the prognosis of patients with stroke/TIA.

To investigate the association of intracranial atherosclerotic disease (ICAD), alone and comorbid with cerebral small vessel disease (SVD), with ischemic or hemorrhagic events in patients receiving antithrombotic therapy. In this prospective, multicenter, observational study, baseline brain MRI was performed to assess SVD (white matter hyperintensities, cerebral microbleeds, lacunes, enlarged perivascular spaces [PVS]), nonlacunar infarcts, and ICAD. SVD burden was defined as SVD score >&#x2009;2. ICAD was classified as normal-to-mild, moderate, and severe stenosis-to-occlusion. The outcomes were any ischemic event, ischemic stroke, major bleeding, intracranial hemorrhage, and all-cause mortality. We assessed associations of ICAD with outcomes via Cox regression and mediation analyses, adjusting for SVD burden. Among 5250 patients (mean age: 71&#x2009;&#xb1;&#x2009;11&#x2009;years, 33% women), 3947 (75%) received antiplatelets and 1304 (25%) anticoagulants at baseline. ICAD was normal-to-mild in 3781 (72%), moderate in 571 (11%), and severe-to-occluded in 894 (17%). SVD burden was observed in 1400 (27%). ICAD was associated with a higher frequency of non-lacunar infarcts and a lower frequency of PVS. There was no graded association between ICAD severity and SVD burden. During a median follow-up of 2&#x2009;years, 278 ischemic events, 197 ischemic strokes, 97 major bleedings, 55 intracranial hemorrhages, and 217 deaths occurred. Severe-to-occluded ICAD independently increased the risk of any ischemic event (adjusted hazard ratio: 1.39 [1.03-1.86]) and mortality (2.01 [1.48-2.74]); coexisting SVD burden further increased the risk of all outcomes. ICAD directly affected ischemic events, while mortality was mainly driven by its additive interaction with SVD. ICAD increases the risk of any ischemic events and, with comorbid SVD, contributes to hemorrhagic events and excess mortality.

Management of modifiable risk factors is key in the prevention of recurrent stroke. We investigated trends in vascular risk factors (hyperglycemia, hyperlipidemia, hypertension, and smoking) control among US adults with stroke. We performed analyses of data from 1999 through 2023 National Health and Nutrition Examination Surveys participants with self-reported stroke. Meeting guideline-recommended targets for risk factor control was defined as hemoglobin A1c <6.5% without diabetes or hemoglobin A1c <7.0% with diabetes, low-density lipoprotein cholesterol <70&#x2009;mg/dL, blood pressure <130/80&#x2009;mm&#x2009;Hg, and nonsmoking. Age-standardized mean hemoglobin A1c, low-density lipoprotein, and blood pressure and prevalence of meeting each recommended target were calculated for each epoch (1999 through 2002, 2003 through 2006, 2007 through 2010, 2011 through 2014, 2015 through 2020, and 2021 through 2023). Mean hemoglobin A1c increased from 5.7% (95% CI, 5.5-5.9) in 1999 through 2002 to 6.0% (95% CI, 5.7-6.3) in 2021 through 2023 (P-trend=0.04) and LDL decreased from 125.9&#x2009;mg/dL (95% CI, 119.4-132.4) in 1999 through 2002 to 115.6&#x2009;mg/dL (95% CI, 107.8-123.5) in 2021 through 2023 (P-trend<0.001), whereas blood pressure was largely stable. The prevalence of meeting glycemia guidelines decreased from 90.7% (95% CI, 85.9%-95.6%) in 1999 through 2002 to 83.9% (95% CI, 70.2%-97.5%) in 2021-2023 (P-trend=0.03), whereas the prevalence of meeting lipid guidelines increased from 1999 through 2002 (5.1% [95% CI, 0%-11.0%]) to 2021 through 2023 (13.6% [95% CI, 6.9%-20.4%; P-trend=0.002). The prevalence of meeting smoking and blood pressure guidelines was stable. Fewer than 10% of individuals met guidelines for all 4 risk factors over the study. In this nationally representative sample of US adults with stroke, <10% met guideline recommendations for all risk factors with an overall stable trend. These results suggest that efforts aimed at glycemia, blood pressure, and lipid control and smoking cessation could be improved to reduce the burden of recurrent stroke.

Long non-coding RNAs (lncRNAs) regulate microRNAs and their target genes to control key pathological processes after acute ischemic stroke (AIS).&#xa0;To investigate lncRNA EPB41L4A-AS1's role in microglial function via miR-214-3p/GPX4, and its clinical relevance as a prognostic indicator in AIS.&#xa0;EPB41L4A-AS1 levels were measured by RT-qPCR in 120 AIS patients and OGD/R-treated BV2 microglia. ELISA and western blot were employed to assess microglial state transition and ferroptosis in OGD/R-injured BV2 cells. A combination of RIP, RNA pull-down, and luciferase reporter assays were employed to validate the miRNA and gene targets regulated by EPB41L4A-AS1. Functional rescue assays were conducted by co-transfecting miR-214-3p with GPX4 to validate the regulatory relationship in vitro.&#xa0;EPB41L4A-AS1 was significantly downregulated in the serum of AIS patients, with lower levels predicting worse prognosis. Elevated EPB41L4A-AS1 expression substantially reduced pro-inflammatory markers (iNOS, TL-1&#x3b2; and TNF-&#x3b1;), but enhanced anti-inflammatory markers (Arg1 and IL-10) of OGD/R-injured BV2 cells. Meanwhile, the iron overload and lipid peroxidation in OGD/R cells were also improved. RIP, RNA pull-down, and luciferase reporter assays confirmed the specific binding of miR-214-3p to EPB41L4A-AS1 and GPX4. Upon EPB41L4A-AS1 overexpression, miR-214-3p mimic amplified the iron overload and oxidative stress and led to a pro-inflammatory state of BV2 cells under OGD/R conditions. Restoring GPX4 expression abrogated these observed effects.&#xa0;Lower serum EPB41L4A-AS1 correlates with poor prognosis in AIS patients. The mechanism underlying its neuroprotective effects against microglial state transition and ferroptosis was delineated through the miR-214-3p/GPX4 axis.

In this retrospective multicentre cohort study, we aimed to develop and validate an interpretable machine learning (ML) model for early post-stroke epilepsy (PSE) prediction in patients who underwent mechanical thrombectomy (MT). We hypothesised that an ML model developed using electronic medical record data can accurately predict the risk of PSE in patients with acute ischaemic stroke treated with MT. We collected data from 1185 adult patients who underwent MT between 2017 and 2022 at two hospitals for model development and used data from three external centres for validation. The key variables were selected using Cox regression, least absolute shrinkage and selection operator regression and Boruta. Eight ML algorithms were used for model development. The model performance was evaluated using the concordance index (C-index) and integrated Brier scores. Additionally, the 1-year, 3-year and 5-year PSE risk prediction accuracies were assessed using the areas under the receiver operating characteristic curves (AUCs) and calibration curves. Decision curve analysis was used to evaluate the clinical utility, and the feature importance was quantified. An optimal combination comprising nine features was used for model development. Of the eight ML models, the random survival forest (RSF) model demonstrated optimal performance and maintained robust discriminative accuracy across the three external validation cohorts (C-index: 0.812; AUC: 0.748-0.837; C-index: 0.822; AUC: 0.795-0.839 and C-index: 0.763; AUC: 0.763-0.833). Finally, we developed an online calculator (https://pseshiny.shinyapps.io/shinydashboard_sa_1model/) based on the RSF model. This prediction model could help identify patients at high risk of developing PSE following MT and support individualised treatment strategies.