Stroke

Background and Purpose: Futile interhospital transfers, where patients transferred for endovascular thrombectomy (EVT) do not ultimately receive the procedure, represent a critical systemic burden on stroke transfer network. Whether pre-transfer computed tomography angiography (CTA) at the primary stroke center (PSC) reduces futile transfers, and at what workflow cost, remains incompletely characterized. Methods: This retrospective study enrolled 314 acute ischemic stroke patients transferred for potential EVT within the Tainan-Chiayi Stroke Network (October 2021-September 2025). Patients were stratified by CTA timing: pre-transfer (n=66) versus post-transfer (n=248). Workflow time metrics and 90-day functional outcomes were compared. Futile transfers were classified into three categories: preventable over-triage, physiological futility, and gray zone cases. Results: The futile transfer rate was substantially lower in the pre-transfer CTA group (27.3% vs. 66.1%; P<0.001), with post-transfer CTA as the strongest independent predictor of futility (aOR 5.21; 95% CI 2.83-9.60). In the post-transfer CTA group, 40.2% of futile transfers involved conditions identifiable by pre-transfer CTA. Regardless of CTA timing, gray zone cases predominated in both groups (83.3% vs. 47.6%), driven by intracranial atherosclerotic stenosis/ chronic total occlusion, large infarct cores, and medium vessel occlusions. Pre-transfer CTA significantly prolonged PSC door-in-door-out time (140 vs. 88 min; P<0.001) and showed numerical trends toward longer onset-to-EVT time and lower rates of favorable functional outcome. Conclusions: Adopting CTA during the pre-transfer period reduces preventable futile transfers but prolongs PSC processing time. Nevertheless, the persistent gray zone requires strategies beyond imaging alone, and the trade-off between triage precision and transfer efficiency warrants ongoing evaluation across different stroke networks settings.-

BackgroundHemorrhagic transformation (HT) is a frequent and serious complication, occurring in up to 40% of cases after endovascular treatment (EVT) for acute ischemic stroke (AIS). Inflammation has been increasingly recognized as a key factor influencing both stroke pathophysiology and post-treatment complications (such as HT) interacting with endothelial dysfunction to exacerbate vascular injury after EVT. The objective of this study is to evaluate whether systemic inflammatory status predicts HT in AIS patients, and its relationship with endothelial biomarkers in the setting of this complication. MethodsWe retrospectively reviewed a prospective cohort of 229 AIS patients treated with EVT. Demographic, clinical, imaging, and laboratory data were collected. Inflammatory markers included white blood cell subsets and indices such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-neutrophil ratio (PNR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI). Endothelial function was assessed by flow-mediated dilation (FMD) and circulating homoarginine (HArg), asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA). The main outcome was radiological or symptomatic HT, classified according to ECASS criteria. ResultsHT was observed in 92 patients (40.2%), of whom 35 (36.1% of HT and 15.3% of the total) were symptomatic. In multivariate analysis, independent predictors of HT included higher NIHSS at admission, higher plasma glucose at admission, the use of non-aspiration devices, lower pre-recanalization lymphocyte count, higher pre-recanalization SII and higher NLR levels. Among endothelial function markers, HArg correlated with inflammatory markers, ANC (r = -0.2) and WBC (r = -0.19), and was associated to PH and symptomatic HT, but not with any radiologic HT after AIS. ConclusionsAn altered inflammatory status prior to EVT in AIS patients is associated with an increased risk of developing HT after EVT. Additionally, endothelial dysfunction could participate in the more aggressive forms of this complication.

Background: Immune-mediated mechanisms are increasingly implicated in childhood arterial ischemic stroke (AIS), but the associated inflammatory pathways and how they differ by stroke subtype and outcome remain poorly understood. Understanding immune responses to AIS may identify subtype-specific mechanisms and inform targeted strategies to reduce ischemic injury. Methods: We conducted a prospective cohort study with cross-sectional transcriptomic analysis through the Vascular Effects of Infection in Pediatric Stroke Study Part II (VIPS II) at 22 academic centers in the United States, Canada, and Australia between December 2016 and January 2022. Children aged 28 days to 18 years with centrally confirmed AIS were enrolled within 72 hours of stroke onset, in addition to enrollment of stroke-free well children. Peripheral blood RNA sequencing was performed on samples collected within 72 hours of stroke or at enrollment for controls. Differential gene expression (DGE) and pathway analyses were performed comparing all AIS cases to stroke-free well children. Additional cross-sectional analyses stratified by stroke subtype and neurological outcomes were performed. Results: Transcriptomes were available in 190/205 AIS cases (median age 11.7 years) and 91/100 stroke-free children (11.8 years). Stroke subtypes included 67 definite arteriopathic, 74 probable arteriopathic, 23 cardioembolic, and 26 idiopathic, with similar demographics but smaller infarct size for idiopathic cases. 47 genes (false discovery rate (FDR) <0.05 and log2 fold-change (log2FC)>1) were differentially expressed in AIS versus stroke-free well children, with upregulated pathways reflecting innate immune responses. Stratification by subtype revealed these inflammatory responses occurred after arteriopathic and cardioembolic AIS, but not idiopathic AIS; in sensitivity analyses, these findings were not explained by infarct size. Four immune-related genes were differentially expressed in children with good versus poor neurological outcomes at hospital discharge or 12 months; upregulation of one (Joining Chain; JCHAIN) correlated with poor outcomes at both timepoints. Conclusions: Compared with stroke-free children, children with AIS, particularly arteriopathic and cardioembolic subtypes, have upregulated innate immune pathways, including neutrophil activation and interleukin-1 signaling. Differential expression of immune-related genes also correlated with neurological outcomes. These findings support immune dysregulation as a key feature of early pediatric AIS while highlighting differences across subtypes and clinical outcomes, with implications for targeted immunomodulatory therapies and future biomarker development.

BackgroundEndovascular thrombectomy (EVT) is the standard of care for acute ischemic stroke caused by large-vessel occlusion. However, the additional benefit of intravenous thrombolysis (IVT) before EVT remains controversial. This systematic review and meta-analysis evaluated the efficacy and safety of bridging therapy (EVT plus IVT) compared with EVT alone. MethodsThis systematic review and meta-analysis was conducted according to PRISMA 2020 and Cochrane Handbook recommendations and prospectively registered in PROSPERO. PubMed, EMbase, Scopus, and the Cochrane Library were searched for randomized controlled trials published between 1st January 2015 and 30th April 2026 comparing EVT plus IVT versus EVT alone in acute ischemic stroke. Random-effects meta-analysis was performed to estimate pooled odds ratios (ORs) with 95% confidence intervals (CIs). Primary outcomes included functional independence at 90 days and successful recanalization. Secondary outcomes included symptomatic intracranial hemorrhage (sICH) and all-cause mortality. ResultsEleven randomized controlled trials involving 4,419 patients were included in the meta-analysis. Compared with EVT alone, bridging therapy was associated with significantly better functional independence at 90 days (OR=1.25; 95% CI: 1.02-1.53). Patients receiving EVT plus IVT also demonstrated a trend toward higher rates of successful recanalization (OR=1.25; 95% CI: 0.95-1.64) and lower 90-day mortality (OR=0.84; 95% CI: 0.67-1.04). The risk of sICH was comparable between the two treatment strategies (OR=1.07; 95% CI: 0.81-1.40). Overall, the certainty of evidence was rated as moderate. ConclusionsBridging therapy before EVT may improve functional outcomes and recanalization without increasing sICH, supporting its use as a reasonable treatment strategy in eligible patients with acute ischemic stroke.

Background. Up to 70% of stroke survivors develop cognitive impairment, yet clinicians lack non-invasive vascular biomarkers that could meaningfully inform risk stratification. Carotid-femoral pulse wave velocity (cfPWV), the gold-standard measurement of central arterial stiffness, is a novel biomarker of vascular aging linked to cognitive impairment. This study evaluated the association between cfPWV and post-stroke cognitive impairment, as measured by the Montreal Cognitive Assessment (MoCA), in individuals [&ge;]6 months post-stroke. Methods. This is a secondary cross-sectional analysis of baseline data from a randomized control trial. Logistic regression analyses examined the association between cfPWV (m/s) and MoCA score at the primary cut point of [&le;]26/30, with secondary cut points of [&le;]24/30 and [&le;]22/30. Models were adjusted for age, sex, systolic blood pressure, type-2 diabetes, National Institutes of Health Stroke Scale (NIHSS) score, and smoking status. Results. Of 82 participants enrolled in the main trial, 68 participants (n = 45 males, age 64.6 {+/-} 9.6 years, 1.8 {+/-} 1.2 years post-stroke) with mild-to-moderate stroke severity (NIHSS median [IQR] = 1 [2]) were included. In the fully adjusted model using the MoCA [&le;]26/30 cut point, each 1 m/s increase in cfPWV was associated with a 35% increase in the odds of post-stroke cognitive impairment (adjusted OR [aOR] = 1.35; 95% CI 1.06, 1.81; p = 0.027; Area Under the Curve [AUC] = 0.77). Consistent associations were observed at the MoCA [&le;]24/30 (aOR = 1.41; 95% CI 1.04, 2.01; p = 0.037; AUC = 0.88) and MoCA [&le;]22/30 (aOR = 1.33; 95% CI 1.03, 1.79; p = 0.039; AUC = 0.82) cut points. Conclusions. Higher cfPWV was independently associated with post-stroke cognitive impairment across clinically referenced MoCA cut points. cfPWV may be a complementary vascular biomarker to support cognitive risk stratification and identify stroke survivors who could benefit from closer monitoring or vascular-targeted intervention.

Background: The Functional Outcome in Patients with Primary Intracerebral Hemorrhage (FUNC) score was initially validated for prediction of functional independence on the Glasgow Outcome Scale (GOS) 90 days after intracerebral hemorrhage (ICH), but recovery often extends beyond three months. Aims: Our objective was to extend the FUNC score for prediction of 12-month functional independence to strengthen its utility for family counseling and research methodology. Methods: We conducted a single-center prospective cohort study enrolling adult patients with primary ICH between February 2009 and January 2018. We calculated FUNC scores at admission and assessed GOS 12 months after ICH. The primary outcome was 12-month functional independence, defined as a GOS score [&ge;]4. We calculated the area under the receiver operating characteristic curve (AUC) of the FUNC score using logistic regression, handling missing GOS with multiple imputation by chained equations. We evaluated score calibration using a calibration curve and the Brier score, and we assessed clinical utility using decision curve analysis. We explored the statistical efficiency gains of using FUNC-based sliding dichotomy thresholds for favorable outcome definitions by running simulations of a clinical trial with 1:1 randomization. We ran 5000 simulations for each sample size (100 to 1000, in increments of 10) and treatment effect (odds ratio of 1.5, 2.0 and 2.5) combination and calculated efficiency gains for each respective treatment effect as the percentage reduction in sample size required to have 80% power using sliding versus fixed dichotomy thresholds. Results: A total of 535 patients were included (median [IQR] age 68 [54-79], 237 [44%] female, median [IQR] NIHSS 16 [6-25], median [IQR] FUNC 8 [6-9]). Overall, 99 of 445 (22%) patients with known 12-month GOS achieved functional independence. The FUNC score had an AUC of 0.79 (95%-CI: 0.75-0.84) for 12-month functional independence. The calibration plot was reasonable, with modest evidence of overestimation at low predicted probabilities, and the Brier score was 0.15. A net benefit was observed across 5-50% threshold probabilities. Sliding dichotomy had an efficiency gain of 27% for a treatment effect of OR=2.0, and a gain of 22% for a treatment effect of OR=2.5. The efficiency gain for a treatment effect of OR=1.5 could not be calculated because the fixed dichotomy did not reach 80% power despite a sample size of 1000 patients. Conclusions: The FUNC score's predictive performance for 12-month functional independence was comparable to its originally validated 3-month discrimination. Following external validation across centers, the FUNC score may be leveraged to counsel families on global measures of long-term functional independence and to implement sliding dichotomy methodology in ICH research.

Background: Stroke is a time-sensitive neurological emergency in which early EMS activation and presentation to definitive care are cornerstones of effective therapy. Large language models (LLMs) are increasingly consulted by the public for medical advice, but the veracity of the guidance provided by commercially available models responding to potential stroke symptoms is not well understood. Methods: We performed a cross-model benchmarking study comparing the triage choices of three frontier LLMs (Claude Sonnet 4.6, GPT-4o, and Llama 3.3-70b-versatile) on first-person vignettes describing a unilateral arm symptom on waking, across 10 symptom descriptors, and two clinical phases (before and after a partially reassuring self-examination), with or without a clinical distractor (n=50 per condition). Results: Claude sought emergency care most often, Llama least, and GPT-4o in between, diverging most sharply in the post-examination phase where Claude called 911 in 100% of runs, Llama called for non-emergency help in 100%, and GPT-4o was symptom-dependent. A distractor shifted behavior away from emergency care in almost all conditions: calling 911 fell from 37.9% to 14.6% and waiting rose from 0% to 45.9% in the post-examination vignette. Responses were also sensitive to symptom word: weak, limp, heavy, and clumsy generated higher alarm, whereas numb, tingly, odd, strange, and weird generated less urgent responses. Conclusions: The increasing use of LLMs for medical advice has significant public health implications. Commercially available LLMs show significant model-to-model variability and framing sensitivity when confronted with potential stroke symptoms, including under-recognition of canonical CDC warning descriptors, underscoring the need for systematic benchmarking as these tools become de facto first points of contact for patients experiencing neurological emergencies.

Background and Purpose: Hemorrhagic transformation (HT) is a serious complication of endovascular thrombectomy (EVT), yet dedicated prediction models for young adults are lacking. We aimed to develop and externally validate a simplified risk score for HT in young adults with acute ischemic stroke undergoing EVT. Methods: This multicenter retrospective study included patients aged 18 to 49 years with acute anterior circulation large vessel occlusion who underwent EVT. The primary outcome was any HT within 24 hours after EVT. Multivariable logistic regression was used to identify independent predictors of HT, from which the NO?PAIN Score was derived. External validation was performed in an independent cohort of 138 patients. Results: Among 598 patients in the derivation cohort, HT occurred in 176 (29.4%). Five independent predictors were identified: admission NIHSS, number of thrombectomy passes, atrial fibrillation, alcohol consumption, and mTICI grade. The mTICI grade demonstrated a non-linear, inverted U-shaped relationship with HT risk, peaking at partial recanalization. The NO-PAIN Score showed acceptable discrimination in both the derivation (C-index, 0.737; optimism-corrected C-index, 0.748) and external validation cohorts (C-index, 0.726), with satisfactory calibration. Conclusions: The NO-PAIN Score is a simple risk prediction tool for HT after EVT in young adults with acute anterior circulation large vessel occlusion. It may assist in individualized risk stratification in this population.

Objective: Cranial artery stenosis and dilatation are distinct large artery phenotypes that often coexist with cerebral small vessel disease (cSVD), yet their downstream microvascular functional correlates remain unclear. Methods: In the prospective Mild Stroke Study 3, we recruited patients with lacunar or mild non-lacunar stroke. At baseline, large artery stenosis (LAS), basilar artery dolichoectasia (BADE), and intracranial arterial diameters were assessed. Multimodal MRI quantified cerebrovascular reactivity (CVR), blood-brain barrier (BBB) permeability, plasma volume fraction, and intracranial pulsatility. cSVD markers were evaluated at baseline and 1 year. Associations between large artery phenotypes and vascular function were examined with multivariable regression. Mediation analyses tested whether vascular dysfunction linked large artery pathology to cSVD progression. Results: Among 224 participants (mean age 66.0, SD 11.2 years; 66.5% men), BADE (n=36, 16.1%) was independently associated with lower CVR in normal-appearing white matter (NAWM; {beta} -0.01, 95% CI -0.016 to -0.004, P=0.003). Larger mean intracranial arterial diameter was associated with lower CVR in NAWM and white matter hyperintensities (WMH), while showing a U-shaped association with BBB permeability. LAS (n=46, 20.5%) was unrelated to CVR, BBB permeability, or pulsatility, but was associated with higher plasma volume in WMH. CVR in NAWM partially mediated the association between BADE and both baseline cSVD burden and 1-year progression. Interpretation: Large artery dilatation may serve as a macroscopic signal of small-vessel dysfunction, being associated with lower CVR and altered BBB permeability. Reduced CVR in NAWM partially mediated the impact of dolichoectasia on cSVD progression and may represent a potential therapeutic target.

Introduction: High-intensity locomotor training (HIT) is recommended for improving walking capacity, but treatment responses are variable. Understanding the brain changes underlying responsiveness to training could provide insight into this variability. Emerging evidence suggests upregulation of the contralesional cortico-reticulospinal tract (CRST) may contribute to walking function after stroke. However, it is unclear whether CRST upregulation is supportive or maladaptive, and no studies have examined CRST changes after HIT. This study investigated how CRST and corticospinal tract (CST) strength and laterality reorganize, and their relationship with walking capacity after locomotor HIT. Methods: Ten participants with chronic stroke completed a 4-week no-intervention control phase then 4-weeks of HIT. Diffusion MRI and 6-minute walk distance were obtained at weeks 0, 4, and 8. Analysis tested changes in ipsilesional and contralesional CRST and CST strength and laterality. Associations between changes in tract laterality and walking capacity were examined. Results: During the treatment phase (vs. the control phase), there were significantly greater increases in contralesional CRST strength (1.02 SD [95% CI: 0.25, 1.79]), contralesional CRST laterality (4.44 [2.15, 6.72]), and 6-minute walk distance (33 meters [17, 50]). Walking capacity improvements were associated with changes in CRST laterality (r = 0.77, p = 0.01), but not CST laterality (r = -0.01, p = 0.98). Discussion: Following HIT, increases in contralesional CRST strength and laterality were observed. CRST laterality changes were strongly associated with walking improvements, suggesting a possible supportive role of contralesional CRST in mediating training-related improvements in walking function after stroke.

BackgroundDischarge destination after acute ischemic stroke has implications for functional recovery and healthcare costs. Individuals discharged to inpatient rehabilitation facilities (IRFs) achieve better outcomes than those discharged to skilled nursing facilities (SNFs); however, many patients discharged to IRFs and SNFs have similar clinical profiles. We examined non-clinical factors associated with discharge location after acute ischemic stroke. MethodsPopulation: 236 adults hospitalized with acute ischemic stroke, living independently in the community prior to admission, and discharged to either an IRF (n=171) or SNF (n=65). Clinical variables: NIHSS, Charlson Comorbidity Index (CCI), acute care length of stay (LOS), functional status (AM-PAC "6-Clicks"), and neglect. Non-clinical variables: age, sex, race, marital status, insurance, home layout, living status, and available assistance. Associations with discharge location were evaluated using univariable and multivariable logistic regression and reported as odds ratios (OR) with 95% confidence intervals (CI). ResultsIndividuals discharged to IRFs were younger, more likely to cohabitate, and had shorter LOS than those discharged to SNFs. Functional status (AM-PAC) and comorbidity burden (CCI) did not differ significantly between groups despite differences in discharge destination. In univariable models, younger age, cohabitating marital status, living with family, available assistance, shorter LOS, private insurance, and higher NIHSS were associated with greater odds of IRF discharge. In multivariable analysis, younger age (OR 0.94, 95% CI 0.91-0.98), cohabitating marital status (OR 2.46, 95% CI 1.13-5.48), and shorter LOS (OR 0.88, 95% CI 0.82-0.93) remained independently associated with IRF discharge. ConclusionsIndividuals with comparable pre-stroke independence and similar clinical severity, discharge to IRF versus SNF was independently associated with non-clinical factors; age, marital status, and LOS, whereas stroke severity and functional status were not significant predictors. These findings underscore the importance of evidence-informed discharge criteria integrating clinical indicators and social context to support equitable access to intensive rehabilitation after stroke.

Background and Purpose Prognostication after acute ischemic stroke often relies on limited variables and simple risk scores, despite richer information being available at admission. We developed a multimodal AI model using admission data to predict modified Rankin Scale (mRS) outcomes and compared it to established tools. Methods In a retrospective study of ischemic stroke/TIA patients, we trained three modality-specific models on admission non-contrast head CT, history and physical notes, and structured clinical variables, and combined them in a weighted-average ensemble. We predicted binary (mRS 0-2 versus 3-6) and ordinal mRS (0-6) outcomes at discharge and 90 days. Performance on an external test cohort was compared with THRIVE and SPAN-100 scores using AUROC, AUPRC, Brier score, mean absolute error (MAE), and quadratic weighted kappa (QWK). Results A total of 6,915 patients were split into training, validation and testing cohorts in a 3:1:1 ratio. For discharge binary mRS (n=1596), the multimodal ensemble achieved significantly better discrimination (AUROC 0.859, AUPRC 0.858) with 25-61% lower Brier scores than THRIVE or SPAN?100 (all p<0.001). For 90?day binary mRS (n=207), the model also outperformed both THRIVE and SPAN-100 (AUROC 0.838, AUPRC 0.805, with 3-38% lower Brier scores). Ordinal mRS prediction showed similarly strong performance with significantly better QWK at discharge and numerically lower MAE. The multimodal ensemble model reassigned about one?third of patients to different risk categories versus THRIVE and was closer to the true discharge outcome in ~74% of discordant cases. Conclusions We developed a well-calibrated multimodal AI model for prediction of discharge and 90-day post-stroke functional outcomes using only data present at the time of admission. This model outperforms existing prognostic tools and can support early clinical decision-making.

Background: Patients in socioeconomically disadvantaged neighborhoods face barriers to care. Missing BP documentation may signal gaps in risk-factor management, a crucial component of primary and secondary prevention of intracerebral hemorrhage (ICH). We tested whether neighborhood deprivation was associated with absent electronic health record (EHR) blood pressure (BP) documentation surrounding ICH and whether absent documentation predicted subsequent uncontrolled BP. Methods: We conducted a case-only study within the NIH All of Us Research Program. We included ICH survivors (ICD-10 I61.x, surviving >=1 year) with available ZIP3-based Deprivation Index. Deprivation was categorized as Privileged, Intermediate, or Deprived using cohort-based tertiles. We excluded BP measurements collected by All of Us. Outcomes were (1) absent EHR-derived BP documentation and (2) uncontrolled BP (mean systolic BP >=140 mmHg) during three windows: 1-365 days before ICH; 30-365 days and 1-5 years after ICH. Multivariable logistic regression tested associations adjusting for age, sex, and race/ethnicity. Results: 1,474 ICH survivors were included (mean age 60.1, 50.4% female). Compared to privileged neighborhoods, those living in deprived neighborhoods had higher odds of absent EHR BP documentation in the year prior to ICH (OR 2.10, 95% CI 1.60-2.76; p<0.001), 30-365 days post-ICH (OR 2.82, 95% CI 2.14-3.73; p<0.001) and 1-5 years post-ICH (OR 2.81, 95% CI 2.13-3.71; p<0.001). Absence of EHR BP documentation in the year before ICH predicted uncontrolled BP 30-365 days (OR 1.97, 95% CI 1.36-2.85; p<0.001; N=888) and 1-5 years (OR 1.83, 95% CI 1.24-2.69; p=0.002; N=814) after ICH. Absence of BP documentation 30-365 days post-ICH also predicted uncontrolled BP 1-5 years post-ICH (OR 1.66, 95% CI 1.10-2.50; p=0.017; N=814). Conclusions: Neighborhood deprivation is associated with persistent gaps in EHR BP documentation surrounding ICH, and absent documentation before or soon after ICH predicts subsequent uncontrolled BP. These findings highlight the need for community-level strategies that ensure equitable BP monitoring for socioeconomically disadvantaged populations.

Background:Stroke continues to be one of the major causes of death and long-term disability worldwide, with a greater impact in low-and middle-income countries. In India, there is limited evidence examining stroke burden and its changes over time and across regions. Therefore, we aimed to assess the burden of stroke in India from 1990 to 2023 using the latest data from the Global Burden of Disease (GBD) Study, along with projections up to 2035. Methods:We used estimates from the GBD 2023 study to examine stroke incidence, prevalence, mortality, and disability-adjusted life years (DALYs) in India from 1990 to 2023. Age-standardized rates were analyzed to understand how these measures have changed over time. We also conducted state-level analyses to explore regional differences in stroke burden. The contributions of all major modifiable risk factors were assessed using population-attributable fractions. In addition, we projected future trends in stroke burden up to 2035. Results:From 1990-2023, the percentage change in overall stroke burden in India showed minimal variation across key indicators. Incidence remained largely stable (0.00%[-0.04 to 0.05]), while prevalence showed a slight increase(0.06%[0.03 to 0.10]). Mortality (-0.11%[-0.36 to 0.20]) and DALYs (-0.17%[-0.38 to 0.12]) demonstrated modest declines over the study period. Notable regional disparities were evident, with states such as Chhattisgarh, Assam, and Jharkhand bearing the highest burden. High systolic blood pressure remained the leading risk factor in 2023, contributing the largest share of stroke-related deaths, followed by dietary risks, air pollution, tobacco use, and high body mass index. Future projections indicate that by 2035, stroke prevalence is likely to increase, while incidence, mortality, and DALYs are expected to show only modest changes. Conclusions: Stroke remains a major and growing public health challenge in India with a continuing increase in burden despite slight improvements in age-standardized rates over time. Addressing this challenge will require stronger prevention efforts, better control of key risk factors, and focused strategies to reduce regional disparities in stroke burden nationwide.

BackgroundtPA is used for the acute treatment of ischaemic stroke because it converts plasminogen to active plasmin, which breaks down clots. Previous studies show that tPA-activated plasminogen impairs brain endothelial barrier function. However, it is unclear whether the plasmin product of this reaction directly contributes to brain endothelial barrier deterioration. ObjectiveDetermine whether plasmin directly influences the human brain endothelial barrier. MethodsWe developed a new serum-free hCMEC/D3 culture model with ECIS real-time monitoring to establish how plasmin in isolation influences the brain endothelial barrier. ResultsECIS monitoring demonstrated that plasmin caused a concentration-dependent decline in hCMEC/D3 barrier integrity, which was primarily mediated by a reduction in endothelial cell-to-cell interactions. Whilst a decrease in membrane capacitance and increase in basolateral adhesion were also observed, these changes were less marked. The inclusion of 2-antiplasmin ameliorated the changes in hCMEC/D3 barrier properties, suggesting this response is mediated by plasmins proteolytic activity. Quantitative immunocytochemistry confirmed that plasmin stimulated a decline in the key junctional molecules, Claudin-5, VE-Cadherin (CD144), {beta}-Catenin, ZO-1 and PECAM-1 (CD31), which likely contributed to the deterioration of paracellular cell-to-cell interactions. Interestingly, using this serum-free model, tPA alone didnt influence hCMEC/D3 barrier properties, whilst tPA with plasminogen did, implicating plasmins involvement. ConclusionPlasmin directly impaired the barrier function of hCMEC/D3 brain endothelial cell monolayers by stimulating a decline in key junctional molecules. This plasmin-mediated brain endothelial barrier deterioration has important implications for tPA use and should be considered whilst designing safer thrombolytic treatment options for patients experiencing acute ischemic stroke.

Importance: Severe stroke is a leading cause of death and disability worldwide. Survivors and their families face long-term unmet needs, including care that does not reflect patients' values, fragmented care, and high rates of psychological distress among caregivers. Objective: To describe the conceptual framework of the longitudinal transdisciplinary neuropalliative care support (LOTUS) intervention and assess its fidelity in a pilot feasibility study. Design: Pilot feasibility randomized study; fidelity was assessed using weekly checklists completed by the LOTUS nurse and qualitative analysis of weekly LOTUS team meeting transcripts. Setting: Single comprehensive stroke center in Western New York. Participants: Patients hospitalized with severe stroke and their caregivers. Dyads were randomized to usual care or intervention. Intervention: The LOTUS intervention is implemented in a stepped-care fashion using 5 strategies: Awareness, Assistance, Adjustment, Acceptance and Alignment (5As). Led by a specially trained nurse with a chaplain, social worker, psychologist, and neuropalliative care physician, the LOTUS team follows dyads from early in the hospital course through 6 months. Main Outcomes and Measures: Fidelity, the degree to which the intervention was delivered as intended, assessed via (1) utilization of 5A activities from weekly LOTUS checklists; (2) thematic analysis of weekly LOTUS team meeting transcripts. Results: Of 26 patients in the trial, 13 were randomized to intervention. The LOTUS nurse completed 108 checklists, with an average of 619 minutes of direct contact per participant over 6 months. Each component of the 5A's was utilized. Awareness and Assistance predominated early after enrollment and revolved around personhood, support, and self-efficacy. Adjustment was especially relevant during care transitions and was typically supported by the LOTUS social worker. Acceptance and Alignment were more prevalent during later meetings, with the LOTUS psychologist supporting identification and modeling of coping skills and the LOTUS physician guiding prognosis and goals-of-care conversations. The LOTUS nurse served as primary point of contact, providing continuity and a trusting relationship, while other team members functioned in a predominantly advisory role. Conclusions: The LOTUS intervention was delivered with fidelity to the 5A-framework, supporting a future randomized clinical trial to evaluate its efficacy in patients with severe stroke and their caregivers.

BackgroundHypertension is the most potent modifiable risk factor for recurrent intracerebral hemorrhage (ICH), yet blood pressure (BP) control after ICH remains suboptimal, particularly among disadvantaged racial and socioeconomic groups. To what extent post-ICH BP disparities reflect pre-existing hypertension inequities versus differences in post-ICH management is unknown. We examined disparities in BP control before and after ICH, assessed whether post-ICH care differentially improves BP across groups and whether post-ICH disparities persist after accounting for pre-existing BP differences. MethodsWe performed a case-only study in the All of Us Research Program, identifying ICH survivors using electronic health record diagnosis codes. Mean systolic BP was calculated for pre-ICH (1-365 days before) and post-ICH (30-365 days after) windows. Neighborhood deprivation tertiles were calculated using 3-digit ZIP codes. The primary outcome was uncontrolled BP ([&ge;]140 mmHg). Logistic regression estimated odds of uncontrolled BP, and mediation analysis estimated the proportion of post-ICH disparities explained by pre-ICH BP. ResultsAmong 2,226 ICH survivors (mean age 60; 50.6% female), 1,760 had pre-ICH and 1,852 had post-ICH BP data. Uncontrolled BP was more common in Black than White survivors both pre-ICH (38.9% vs 21.4%; p<0.001) and post-ICH (34.3% vs 16.3%; p<0.001), and in Deprived versus Privileged neighborhoods post-ICH (23.7% vs 15.8%; p<0.001). In adjusted models, Black race (OR 3.51; 95% CI 2.55-4.83; p<0.001) and Deprived neighborhoods (OR 1.38; 95% CI 1.00-1.91; p=0.048) were associated with uncontrolled post-ICH BP. Among survivors uncontrolled before ICH, 67% of White but only 45% of Black survivors achieved control afterward (p=0.001). Adjusting for pre-ICH BP control status only modestly attenuated the Black-White disparity (OR 4.05 to 2.95; P<0.001). In mediation analyses, pre-ICH BP explained only 27% of the racial (P<0.001) and 26% of the deprivation (P=0.014) disparity. ConclusionsRacial and socioeconomic disparities in BP control persist after ICH, but most post-ICH disparities are not explained by pre-existing inequalities. More advantaged populations achieve greater BP improvement, suggesting effective post-ICH management exists but does not reach all patients equitably. Targeted interventions addressing barriers to post-ICH BP control in disadvantaged populations may substantially reduce persistent disparities.

BackgroundRecent studies have established an association between traumatic brain injury (TBI) and cardiometabolic diseases (CMDs). However, the influence of TBI on the sequential progression from a healthy state to CMD, subsequent to cardiometabolic multimorbidity (CMM), and ultimately to mortality remains unclear. MethodsA total of 366,616 participants free of CMD at baseline were derived from the UK Biobank (UKB). CMM was defined as the co-occurrence of [&ge;]2 CMD, including diabetes mellitus (DM), ischemic heart disease (IHD), and stroke. Cox proportional hazards models and multi-state models were utilized to evaluate the association of TBI with disease transitions from a healthy state to CMM and subsequent mortality. ResultsDuring a median follow-up of 16.91 years, 54,224 participants developed at least one CMD, among whom 7,562 progressed to CMM. Furthermore, 32,785 cases of mortality were documented. In multi-state models, the hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) for transitions from a healthy state to IHD, DM, stroke, and mortality were 1.91(95% CI: 1.77-2.05), 1.89 (95% CI: 1.71-2.09), and 4.73 (95% CI: 4.39-5.09), respectively. For sequential transitions from IHD, DM, and stroke to CMM, the HRs (95% CIs) were 2.67 (95% CI: 2.34-3.04), 3.29 (95% CI: 2.78-3.89), and 1.41 (95% CI: 1.15-1.72), respectively. Additionally, in Cox proportional hazards models, the HRs (95% CIs) for incident CMM and mortality among individuals with TBI were 3.98 (95% CI: 3.63-4.36) and 2.57 (95% CI: 2.44-2.71), respectively. ConclusionThis study found that TBI was associated with increased risk of progression from a healthy state to CMD, and subsequently to CMM and mortality, highlighting the importance of comprehensive management of TBI in cardiometabolic health. What is Known; What the Study AddsO_ST_ABSWhat is KnownC_ST_ABSTraumatic brain injury (TBI) is associated with an elevated risk of developing multiple cardiometabolic diseases (CMDs). What the Study AddsThis study performed a systematic analysis of the relationships between TBI and multiple CMDs, providing valuable clinical references for the prevention and management of the onset and progression of cardiometabolic diseases and cardiometabolic multimorbidity (CMM) among patients with TBI.

INTRODUCTION Severe acute brain injury (stroke, traumatic brain injury or hypoxic-ischemic encephalopathy; SABI) is increasingly recognized as a chronic condition with care and communication needs beyond the initial hospitalization. This study aimed to characterize post-acute care patterns among SABI survivors, focusing on healthcare utilization and outpatient communication. METHODS Data were collected from a prospective cohort of hospitalized SABI patients using surveys, chart reviews, and the ED Information Exchange database. Socioeconomic disadvantage was assessed using the Area Deprivation Index (ADI), and qualitative analysis of outpatient notes examined conversations around palliative care needs and goals-of-care. RESULTS Two-thirds of patients (140/222) survived until discharge, primarily to nursing facilities (39%) or inpatient rehabilitation (38%). Among 109 with one-year follow-up, there were 89 hospitalizations, 104 ED visits, and 28 deaths. Patients from the most disadvantaged neighborhoods had significantly higher odds of rehospitalization or ED use within 30 days (OR 3.37, p=0.036). ADI was not linked to one-year utilization. seen outpatient by primary care (40%), neurology/neurosurgery (57%), and palliative care (1%), but conversations rarely revisited prognosis or goals-of-care. CONCLUSIONS Our findings highlight the need for improved long-term care planning and communication, particularly for socioeconomically disadvantaged survivors of SABI.

Background: In atrial fibrillation (AF), cerebral microbleed (CMB) burden guides anticoagulation decisions, yet AF is itself inconsistently associated with CMBs, a paradox unexplained by frameworks that treat CMBs as a unitary marker of small vessel disease. We hypothesized that the white matter hyperintensity (WMH) context in which CMBs arise modifies their vascular meaning, and that this context-dependence underlies the inconsistent AF-CMB association. Methods: From a multicenter Korean stroke registry, we analyzed 5,735 first-ever ischemic stroke patients imaged at nine centers using susceptibility-weighted MRI. WMH volume and CMB count were extracted by validated deep learning pipelines. Patients were cross-classified by age-adjusted WMH residual (median split) and CMB count (2) into four groups. The AF-CMB association was estimated by multivariable logistic regression within each WMH stratum with formal interaction testing. Spatial CMB distribution was analyzed against the Automated Anatomical Labeling atlas. Results: In the full cohort (mean age 69.5 years; 57.7% male), AF was not associated with CMBs (OR 1.04; 95% CI 0.87-1.25). Stratification yielded divergent estimates: the adjusted AF OR was 1.46 (1.11-1.93; P = 0.007) in the WMH-low stratum and 0.95 (0.73-1.22; P = 0.665) in the WMH-high stratum, with significant interaction (OR 0.56; P < 0.001). The discordant phenotype (low WMH, high CMB; 8.9%) was enriched for AF (28.0%) and showed fronto-temporal cortical predominance with deep structure sparing. AF independently reduced the proportion of deep CMBs (IRR 0.80; P = 0.040). The interaction was preserved across prespecified sensitivity analyses. Conclusions: The AF-CMB association is confined to patients with low WMH burden relative to age and is accompanied by a topographically distinct CMB distribution. Clinical assessment of small vessel disease based on WMH alone may overlook a CMB phenotype linked to AF.