Stroke

Background Adults aged 80 years and older are the fastest-growing segment of the stroke population. Whether contemporary advances in stroke care have produced sustained outcome gains in this group during the past decade, including the post-pandemic era, has not been examined in nationwide longitudinal data with concurrent age-specific comparison. Methods Using the Clinical Research Collaboration for Stroke in Korea-National Institutes of Health (CRCS-K-NIH) registry, we analyzed consecutive adults with acute ischemic stroke admitted within 7 days of symptom onset between 2011 and 2022. Patients aged 80 years and older formed the primary cohort; those aged 18-79 years served as comparators. Primary outcomes were 3-month utility-weighted modified Rankin Scale (UW-mRS) and 1-year all-cause mortality. Non-linear trends and age-group-by-year interaction were modeled using restricted cubic splines adjusted for sex, age, and baseline NIHSS. Results Of 83,953 patients, 18,514 (22.1%) were aged 80 years and older; their proportion rose from 17.4% to 27.3%. Despite treatment intensification (endovascular thrombectomy 4.2% to 10.6%; oral anticoagulation for atrial fibrillation 52.5% to 76.9%), 1-year mortality in this group fell from 27.5% in 2011 to 19.4% in 2019, then rose to 23.7% by 2022; 3-month UW-mRS improved from 0.47 to 0.51 over the same period, then stagnated at 0.48. Restricted cubic splines confirmed significant nonlinearity in both outcomes after adjustment for sex, age, and NIHSS (P < 0.01 for both). Younger patients showed no comparable functional deterioration. Age-group-by-year interaction was significant for 3-month UW-mRS (P < 0.001) but not for 1-year mortality (P = 0.058), which showed a similar direction in both age groups. Conclusion In this nationwide registry, patients aged 80 years and older experienced an age-specific inflection of functional recovery gains after 2019 despite continued intensification of acute stroke care. Sustaining outcome gains in this population may require attention to post-acute care infrastructure.

BackgroundMinor ischemic stroke is heterogeneous, and low NIHSS does not reliably identify patients at risk of deterioration or disability. We investigated whether integrating CT perfusion and angiographic vessel status identifies prognostically distinct phenotypes in a consecutive stroke-code cohort. MethodsWe analyzed consecutive adults with ischemic stroke, baseline NIHSS 0-5, prestroke modified Rankin Scale (mRS) [&le;]2, presentation within 24 hours of symptom onset or last known well, and emergency multiparametric CT. Patients were classified as no perfusion deficit/no vessel occlusion (PF-/VO-), perfusion deficit without visible occlusion (PF+/VO-), or perfusion deficit with vessel occlusion (PF+/VO+). The primary outcome was mRS [&ge;]3 at 90 days; early neurological deterioration (END), defined as an NIHSS increase [&ge;]2 points by 24 hours, was secondary. Multivariable logistic regression adjusted for prespecified covariates and additional variables associated with each outcome in univariable analysis. ResultsOf 2211 patients evaluated through the stroke-code pathway, 534 met inclusion criteria; 391 (73.2%) were PF-/VO-, 61 (11.4%) PF+/VO-, and 82 (15.4%) PF+/VO+. END occurred in 8.1% and mRS [&ge;]3 at 90 days in 17.6%. END occurred in 6.6%, 4.9%, and 17.1% of PF-/VO-, PF+/VO-, and PF+/VO+ patients, respectively (P=0.004), whereas mRS [&ge;]3 occurred in 13.3%, 34.4%, and 25.6%, respectively (P<0.001). Compared with PF-/VO-, PF+/VO+ was independently associated with END (adjusted odds ratio [aOR], 2.50 [95% CI, 1.03-6.06]), whereas PF+/VO- was independently associated with mRS [&ge;]3 at 90 days (aOR, 3.36 [95% CI, 1.67-6.73]). Findings were consistent across definitions of disabling versus nondisabling stroke and after exclusion of lacunar stroke. ConclusionsMultiparametric CT identified distinct risk phenotypes in minor ischemic stroke. Perfusion deficit without visible vessel occlusion was associated with 90-day disability, whereas combined perfusion deficit and vessel occlusion identified patients at increased risk of END. Tissue perfusion and vessel status may provide complementary information for acute risk stratification and future trial enrichment.

Background Endovascular thrombectomy (EVT) is used selectively for vertebrobasilar artery occlusion (VBAO), but its net value in mild deficits remains uncertain. We performed a hierarchical win-ratio analysis of EVT versus best medical management (BMM) in patients with acute VBAO and admission National Institutes of Health Stroke Scale (NIHSS) scores of 10 or less. Methods We performed a secondary analysis of a multicenter retrospective registry of acute VBAO with admission NIHSS scores of 10 or less. EVT plus BMM was compared with BMM alone in the overall cohort and in admission NIHSS strata of 0-5 and 6-10. The primary hierarchy ranked death status through common follow-up, 90-day modified Rankin Scale score, and symptomatic intracranial hemorrhage (sICH). All EVT-BMM pairs were compared sequentially and classified as an EVT win, BMM win, or tie. The adjusted analysis used stabilized inverse probability of treatment weighting (IPTW), with weights truncated at the 1st and 99th percentiles in a sensitivity analysis. Results The analysis included 1,232 patients: 428 underwent EVT and 804 received BMM. In the unweighted overall analysis, EVT had 146,674 wins, BMM had 149,958 wins, and 47,480 ties, yielding a WR of 0.98 (95% CI, 0.84-1.15; P = 0.749). After stabilized IPTW, the WR was 0.96 (95% CI, 0.80-1.14; P = 0.618). Sensitivity analyses did not show a robust overall association favoring EVT. In exploratory NIHSS-stratified analyses, the WR was 0.80 (95% CI, 0.61-1.05; P = 0.101) for NIHSS scores of 0-5 and 1.36 (95% CI, 1.10-1.68; P = 0.004) for scores of 6-10. Conclusions EVT was not associated with an overall net advantage over BMM in this hierarchical analysis. The exploratory signal among patients with admission NIHSS scores of 6-10 suggests that EVT may be feasible in selected patients and warrants confirmation in randomized trials; for patients with NIHSS scores of 0-5, EVT use should remain cautious and individualized.

Background: Immunothrombosis is increasingly recognized in large-vessel-occlusion acute ischemic stroke (LVO-AIS), yet most biomarker studies infer thrombus biology from circulating neutrophil extracellular trap (NET) markers or from pre-defined thrombus subtypes. We prospectively studied 160 patients with anterior-circulation LVO-AIS treated with mechanical thrombectomy to determine whether intrathrombus NETosis markers identify thrombus phenotypes with distinct clinical trajectories, and whether plasma NETosis biomarkers reflect the molecular composition of thrombi. Methods: Thrombi underwent quantitative histopathology and immunohistochemistry for citrullinated histone H3 (CitH3), neutrophil elastase (NE) and CD61. Thrombi were analyzed without prior etiological or histological stratification, and intrathrombus markers were dichotomized at cohort medians (CitH3 6.62%, NE 3.95%, CD61 23.09%) to define internally standardized candidate phenotypes. Associations with thrombus composition, collateral circulation (Tan 2-3), 3-month functional independence (modified Rankin Scale 2 or less) and long-term mortality were assessed by correlation analyses and progressively adjusted multivariable models, with cross-compartment correlations corrected by the Benjamini-Hochberg false discovery rate (FDR). Results: Intrathrombus markers defined prognostically distinct phenotypes: CD61 tracked functional recovery, NE preserved collateral circulation and CitH3 long-term survival, each remaining significant after multivariable adjustment. Circulating NE, myeloperoxidase and leukocyte count instead tracked the macroscopic red-blood-cell-fibrin composition of retrieved thrombi. Cross-compartment concordance was limited: after FDR correction the only significant plasma-thrombus association was an inverse correlation between plasma cell-free DNA and intrathrombus NE, and no intrathrombus marker correlated positively with its circulating counterpart. Conclusions: Local immunothrombotic signatures therefore provide clinically relevant information not captured by plasma markers, and median-defined intrathrombus thresholds represent hypothesis-generating cutoffs for external validation and NET-targeted treatment stratification.

Introduction Mechanical thrombectomy has been well-established as the standard of care treatment for patients with moderate to severe acute ischaemic stroke secondary to large vessel occlusion. However, the clinical value of endovascular treatment (EVT) in patients presenting with minor stroke and low baseline National Institutes of Health Stroke Scale scores remains incompletely defined, with limited high-quality clinical evidence. This protocol outlines the methodology of a randomized trial designed to evaluate whether EVT combined with best medical therapy (BMT) achieves superior functional outcomes relative to BMT alone among patients with minor stroke. Methods and analysis Eligible patients with acute minor anterior circulation ischaemic stroke and confirmed large vessel occlusion (n=264) will be randomized via a computer generated block randomization sequence to receive either EVT plus BMT (intervention arm) or BMT alone (control arm). The primary efficacy outcome is the proportion of participants achieving excellent functional recovery, defined as a modified Rankin Scale score of 0 or 1 at 90 days. Primary safety outcomes comprise symptomatic intracranial haemorrhage within 48 hours after randomization (classified according to Heidelberg criteria) and all cause mortality at 90 days. Participants will be considered eligible if they satisfy all of the following inclusion criteria: (1) enrolment within 24 hours of stroke symptom onset or time last known well; (2) baseline NIHSS score of 2 - 5 accompanied by at least one focal neurological deficit (including altered consciousness, facial palsy, limb weakness, aphasia or hemispatial neglect); (3) angiographically confirmed acute occlusion of the intracranial internal carotid artery, the M1 segment of the middle cerebral artery, or a dominant M2 branch; (4) a hypoperfusion volume (Tmax >6s) [&ge;] 50mL on computed tomography or magnetic resonance perfusion imaging. Both intention to treat and per protocol analyses will be undertaken, and potential sources of heterogeneity in treatment effect magnitude will be explored. Ethics and Dissemination This study was approved by the ethnic committee from the First Affiliated Hospital of Wannan Medical University (2023-IRB90). The findings of this study will be disseminated through publication in peer-reviewed journals. Registration URL:https://www.clinicaltrial.gov; Unique identifier: NCT06143488.

Optimal blood pressure management after thrombectomy remains uncertain, and individualized autoregulation-based targets typically require continuous neuromonitoring. We developed an angiography-derived autoregulatory metric using intraprocedural data and applied it retrospectively to a single-center cohort of patients who underwent thrombectomy for acute stroke. From 62 patients with 3-month functional outcomes, greater time within the predicted autoregulatory range during the first 24 hours after thrombectomy was independently associated with improved outcome after adjustment for covariates (odds ratio per 10% increase, 1.86; 95% CI, 1.31-2.66; P = .0006). These findings support routine angiography as a potential source of early, patient-specific hemodynamic targets after thrombectomy.

Background Patients with acute ischemic stroke (AIS) attributable to symptomatic intracranial atherosclerotic disease (sICAD) remain at substantial risk of early neurological deterioration (END) despite standard medical treatment. Aim To determine whether early addition of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor to statin therapy reduces END in patients with AIS attributable to sICAD within 48 hours of symptom onset. Design The study of Combined Therapy with PCSK9 Inhibitor and Statin in Acute Ischemic Stroke (CAPTAIN) is a multicenter, prospective, randomized, open-label, blinded-endpoint trial conducted in China, with a planned sample size of 416 patients. Eligible patients will be randomized in a 1:1 ratio to receive either early evolocumab plus standard-dose statin or standard-dose statin therapy. Outcomes The primary efficacy outcome is the occurrence of END within 3 days after randomization, defined as an increase in the National Institutes of Health Stroke Scale score of at least 2 points from baseline. Secondary efficacy outcomes include neurological improvement, changes in National Institutes of Health Stroke Scale (NIHSS) score, shift in the 90-day modified Rankin Scale score distribution, recurrent stroke, and changes in lipid parameters. The primary safety outcome is the incidence of moderate-to-severe systemic bleeding within 3 days after randomization, as defined by the GUSTO criteria. Conclusions This study is expected to provide evidence on the efficacy and safety of the early addition of a PCSK9 inhibitor to statin therapy in patients with AIS attributable to sICAD. Trial registration number NCT06696820

Background: Stroke incidence is declining in older adults but rising in younger populations. Circulating plasma proteins are promising biomarkers of vascular disease, yet their causal role in early-onset stroke (EOS) remains unclear. We used proteome-wide Mendelian randomization (MR) to identify proteins causally associated with EOS and its subtypes. Methods: We conducted two-sample MR using protein quantitative trait loci from 54,219 UK Biobank participants and summary-level association results from up to 11,114 EOS cases (onset <60 years) and 435,540 controls in the Early-Onset Stroke Consortium. Variants within {+/-}200 kb of protein-coding genes associated with protein levels (p [&le;]1x10-5) were clumped for linkage disequilibrium and used as instrumental variables. Causal effects were estimated using inverse-variance weighted MR, with sensitivity analyses to assess robustness. Stroke subtypes were defined using TOAST criteria. Results: Among 1,041 proteins tested, 11 were significantly associated with EOS after multiple testing correction. Genetically predicted higher levels of proteins encoded by ABO, F11, F7, MLN, BTD, MEP1B, and VAMP8 increased EOS risk (ORs ~1.05-1.32 per SD), whereas higher levels of proteins encoded by FN1, GRK5, EHBP1, and FCN2 were protective. Eight additional proteins showed subtype-specific associations. Key signals converged on coagulation and thromboinflammatory pathways, particularly ABO, F11, and F7, with consistent evidence across analyses. Cross-trait analyses demonstrated overlap with late-onset stroke, venous thromboembolism, and cardiometabolic risk factors, supporting shared biological mechanisms. Drug-target mapping highlighted Factor XI as a leading therapeutic target, supported by existing inhibitors (e.g., abelacimab, milvexian). Conclusions: This large-scale proteome-wide MR study identified multiple plasma proteins with likely causal roles in EOS, implicating coagulation, platelet activation, extracellular matrix remodeling, and immune pathways in disease etiology. These findings highlight biologically plausible biomarkers and prioritize druggable targets, particularly Factor XI, for prevention of EOS and demonstrate the value of proteogenomic approaches for uncovering disease mechanisms and informing precision prevention strategies.

Background: Telestroke evaluation and treatment programs are a promising option for geographically underserved populations. Adherence to guideline-based secondary prevention measures among telestroke programs remains understudied, particularly for patients with symptomatic intracranial atherosclerosis. The primary objective of this study was to evaluate whether routine telestroke consultation provides guideline-concordant management comparable to on-site vascular neurology consultation. Methods: This retrospective cohort review identified patients with stroke due to intracranial atherosclerosis within a single healthcare system comprising nine hospitals, including two comprehensive stroke centers with on-site stroke coverage and seven sites with remote telestroke coverage. Data was collected from January 2019 to December 2023. Adherence to guideline-based quality indicators was determined using four primary outcome measures including rates of permissive hypertension, high-intensity statin prescription at discharge, time to initiation of first antiplatelet medications, and appropriate antithrombotic therapy at discharge. Results: A total of 132 patients were included in the final analysis (median age, 69 years; 65 female [49.2], 67 male [50.8%]), with 87 patients evaluated and managed on-site and 45 via telestroke. Guideline adherence was similar between groups for permissive hypertension and discharge antithrombotic therapy. Patients managed via telestroke were more likely to receive high-intensity statins at discharge (absolute difference 27.1% (95% CI 11.4, 42.8)) and received antiplatelet therapy earlier than patients managed on-site. Conclusion: In this multisite, single-system cohort, routine telestroke consultation was associated with similar or greater adherence to selected guideline-based management measures compared with on-site vascular neurology consultation.

Background Spontaneous intracerebral hemorrhage (ICH) is the most devastating type of stroke but lacks the established time-critical treatment guidelines available for acute ischemic stroke. This study investigated the impact of Code Stroke activation and warfarin use on anticoagulation reversal times to identify opportunities for quality improvement. Methods We retrospectively assessed patients with anticoagulation-associated ICH admitted to our medical center between January 1, 2020, and December 31, 2025. Patients with warfarin- or direct oral anticoagulant (DOAC)-associated ICH were identified from our ICH clinical trial screening log, Vizient, and AHA's Get With The Guidelines-Stroke registry. Code Stroke activation, warfarin or DOAC use, anticoagulation reversal times, causes of delay, and clinical outcomes at hospital discharge were analyzed. Results Of 892 ICH admissions, 50 patients had confirmed anticoagulation-associated ICH. Among those who underwent reversed at our center (n=34), Code Stroke activation (n=24) significantly reduced door-to-CT time (16.5 [12.8-22.0] vs 172.5 [49.0-261.5] minutes, p <0.001), reversal agent order-to-needle time (37.5 [24.7-56.9] vs 57.0 [39.0-85.0] minutes, p <0.001), and door-to-treatment (DTT) time (64 [48-98] vs 277 [159-305] minutes, p <0.001) compared to non-activation (n=10). Conversely, warfarin use was associated with higher international normalized ratios (INR) (2.7 [2.2-3.6] vs 1.3 [1.2-1.9], p =0.003) and significantly longer DTT time (95 [51-108] vs 64 [48-77] minutes, p =0.007). Primary DTT delays stemmed from the absence of a time-critical treatment protocol, weight-based dosing for 4F-PCC, waiting for INR results, and a lack of Code Stroke activation for patients with mild symptoms, trauma or unexplained unresponsiveness. Conclusions Our findings suggest that Code Stroke activation for all suspected cases of ICH, a time-critical emergency department algorithm targeting a DTT time of less than 60 minutes, and immediate anticoagulation reversal with fixed-dose 4F-PCC without waiting for INR results may optimize the acute management of anticoagulation-associated ICH.

Abstract Background: Despite the high stroke burden in the elderly, their thrombolysis utilization is suboptimal partly due to heightened hemorrhagic risk. Observational data suggest that low-dose thrombolysis may offer comparable efficacy to standard-dose with a trend toward reduced symptomatic intracranial hemorrhage (sICH), yet high-level evidence for low-dose thrombolysis in this broad population remains absent. Objective: To evaluate the safety and efficacy of low-dose intravenous tenecteplase thrombolysis in elderly stroke patients within 4.5 hours of ischaemic stroke onset. Methods and design: The DATE-AGING trial is a multicenter, prospective, randomized, open-label, blinded-end point (PROBE) non-inferiority study. Eligible participants are elderly patients (aged [&ge;]70 years)with acute ischemic stroke who meet current guideline recommendations for intravenous thrombolysis within 4.5 hours of symptom onset will be randomly assigned to Low-dose Tenecteplase group (0.175 mg/kg, max 17.5 mg) or Standard-dose Tenecteplase group (0.25 mg/kg, max 25 mg). The primary outcome was excellent functional outcome, defined as a mRS 0-1 assessed at 90-day post-randomization. Safety outcomes included sICH within 36 hours and mortality at 90 days. Discussions: The DATE-AGING trial is intended to provide high-quality evidence for low-dose tenecteplase intravenous thrombolysis in elderly patients with acute ischemic stroke. Trial registry number: NCT07294209(https://clinicaltrials.gov/study/07294209). Keywords: elderly patients, acute ischemic stroke, intravenous thrombolysis, low-dose tenecteplase

Endovascular thrombectomy (EVT) improves outcomes in acute ischemic stroke caused by large vessel occlusion. Despite successful recanalization, early neurological deterioration (END) remains frequent and predicts poor outcomes. Disturbances in cerebral autoregulation may contribute to END, yet reliable bedside predictors are limited. Transcranial Doppler (TCD) provides noninvasive bedside assessment of cerebral blood flow velocities and may identify hemodynamic patterns associated with post-EVT deterioration. PRECISE-TCD is a prospective, single-center observational study enrolling 180-300 patients undergoing EVT for anterior circulation large vessel occlusion at a tertiary academic medical center. TCD examinations will be performed as soon as feasible after EVT, daily through 72 hours, and near END events. Hemodynamic parameters including peak systolic velocity (PSV), end-diastolic velocity (EDV), mean flow velocity (MFV), and pulsatility index (PI) will be measured in bilateral MCA, ACA, PCA, carotid siphon, vertebrobasilar, and ophthalmic artery territories. The primary outcome is the association between TCD-derived parameters and END within 72 hours, defined as an increase of [&ge;]4 points in total NIHSS score, an increase of [&ge;]1 point in NIHSS subcategory 1a, radiologic evidence of intracranial hemorrhage within 72 hours, or any neurological change prompting emergent head CT at clinician discretion. Secondary outcomes include NIHSS at 24 hours and discharge, discharge disposition, and modified Rankin Scale (mRS) at 90 {+/-} 10 days after hospital discharge. Joint models for longitudinal and time-to-event data will determine the association between TCD parameter trajectories and time to END. Unsupervised clustering will identify TCD-based hemodynamic phenotypes using vessel velocities, pulsatility indices, hemispheric asymmetry measures, collateral flow, and temporal trajectory patterns. We hypothesize that abnormal post-EVT hemodynamic phenotypes will correlate with END and hemorrhagic transformation. Identifying such signatures may support development of TCD-guided, individualized blood pressure strategies to reduce secondary injury after reperfusion and inform future interventional trials. The study is registered at ClinicalTrials.gov (NCT07013396).

Background: Excessive inflammation in early phases post-ischemic stroke is associated with poor long-term outcome and increased stroke recurrence. Interventions capable of downregulating persistent states of inflammation could improve recovery and prevent secondary stroke. Cardiovascular exercise (CE) has well-established anti-inflammatory effects but its capacity to attenuate the exaggerated inflammatory response triggered by ischemic stroke is unclear. Methods: We investigated the impact of eight weeks of CE on the serum concentration of inflammatory mediators in the early subacute phase post-stroke. Seventy-one patients with firstever ischemic stroke were randomly assigned to moderate-to-vigorous CE (n=45) or standard care (SC) (n=26). Concentrations of CRP, IL-6, IL-8, IL-10, TNF- and IL-1{beta} were measured at baseline and after the interventions. Differences between groups were analyzed with linear mixed models adjusted for age and sex. Results: Compared with the CE group, the SC group showed significant increases in IL-6 ({beta}=0.585, 95% CI=0.164-1.006, p=0.0073), IL-8 ({beta}=0.160, 95% CI=0.004-0.317, p=0.0447), and TNF- ({beta}=0.0845, 95% CI=0.0137-0.1553, p=0.0206). The SC group also showed greater increases in CRP ({beta}=0.250, 95% CI=-0.407, 0.906, p=0.4499) and IL-10 ({beta}=0.251, 95% CI=-0.024, 0.527, p=0.0729) but group differences were not significant. IL-1{beta} levels remained stable and differences between groups were not significant ({beta}=-0.008, 95% CI=-0.058, 0.042, p=0.7618). Conclusions: When introduced in the early subacute phase of stroke recovery, moderate-tovigorous CE mitigates increases in inflammation, but the effect differs across mediators. To what extent reducing the inflammatory response in the early stages post-stroke with CE can impact longterm recovery and stroke recurrence needs to be determined.

Background: Stroke remains a leading cause of mortality and long-term disability worldwide, with high residual vascular risk among survivors despite optimal secondary prevention. The contribution of inherited polygenic risk to this residual vulnerability remains unclear. Methods: We analyzed 2,701 stroke survivors (mean age 59.8{+/-}7.1 years, 61.7% male) from the UK Biobank. Stroke- and coronary artery disease (CAD)-polygenic risk scores (metaGRS), comprising approximately 3.2 million and 1.7 million genetic variants, respectively, were derived from large-scale genome-wide association studies using penalized regression. The primary outcome was major adverse cardiovascular events (MACE), while secondary outcomes included recurrent stroke and vascular risk factor control. metaGRS associations with incident MACE and recurrent stroke were tested using Cox models, whereas associations with baseline risk-factor control were assessed using logistic regression. Mediation analyses quantified indirect effects of metaGRS to MACE via HbA1c, LDL cholesterol, and blood pressure. Results: Over 12 years, 731 MACE events (27.1%) and 351 recurrent stroke events (13.0%) occurred. CAD-metaGRS was independently associated with future MACE (age- and sex-adjusted HR per SD increment 1.15, 95%CI 1.07-1.24; p<0.001), whereas higher stroke- and CAD metaGRS were both associated with poorer glycemic control. A higher CAD-metaGRS was also associated with poorer lipid control. Mediation analyses identified glycemic regulation as a significant pathway linking polygenic risk to recurrent vascular events. Conclusions: Polygenic risk scores for cardiovascular disease are associated with recurrent vascular events and vascular risk factor control among stroke survivors, pointing to potentially actionable insights in secondary prevention that merit further investigation.

Background Passive advancement--antegrade movement of the aspiration catheter upon inner delivery device withdrawal without active operator force--is a physical phenomenon observed during mechanical thrombectomy, with anecdotal reports of favorable recanalization outcomes. This study characterizes its prevalence and associations with recanalization. Methods Consecutive thrombectomy cases at two high-volume stroke centers (January 2019-December 2025) were retrospectively reviewed. Stored fluoroscopy and angiograms were assessed for passive advancement and final catheter tip position at arterial branch points. Per-pass and per-vessel mixed-effects multivariable regression identified independent associations with eTICI score, first-pass effect (FPE, eTICI [&ge;]2c-3), modified FPE (mFPE, eTICI [&ge;]2b-3), secondary occlusion, and complications. Results Of 1,824 passes in 995 consecutive patients (1,027 occlusions), 733 had imaging adequate for passive advancement assessment. Passive advancement occurred in 525/733 passes (71.6%), including to an arterial branch in 306/733 (41.7%). On per-pass analysis, passive advancement was associated with higher eTICI [&ge;]2b-3 (71.0% vs 19.7%) and eTICI [&ge;]2c-3 (57.5% vs 10.1%); advancement to a branch amplified these associations (90.5% vs 32.1% and 79.4% vs 18.7%; all p<0.001). Among 429 first passes, mFPE was 74.1% vs 10.8% and FPE 63.4% vs 7.5% with vs without passive advancement; rates reached 95.0% and 87.2%, respectively, at a branch point (all p<0.001). Passive advancement to a branch was inversely associated with secondary occlusion (13.3% vs 31.3%; p<0.001). On multivariable analysis, passive advancement independently predicted eTICI score, eTICI [&ge;]2b-3, and eTICI [&ge;]2c-3 (all p<0.001); final catheter position at a branch was the dominant independent predictor of FPE, mFPE, secondary occlusion, any complication, and intracranial complication on per-vessel analysis (all p[&le;]0.046). Conclusions Passive advancement is a prevalent physical phenomenon and an independent predictor of successful recanalization. When advancing to an arterial branch point, it is associated with mFPE >87%. Passive advancement should be a technical objective of aspiration thrombectomy.

Background The C-reactive protein-triglyceride-glucose index (CTI) integrates inflammatory and metabolic markers, but recent studies have already linked CTI to stroke and cardiovascular outcomes. Whether CTI provides information beyond established risk factors in the U.S. general population remains uncertain. Methods We analyzed 11,809 adults from NHANES 1999-2010 with fasting laboratory, stroke, covariate, and survey-design data. Stroke was defined by self-reported physician diagnosis. Survey-weighted logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). We evaluated restricted cubic splines, exploratory subgroup interactions, and sensitivity to excluding CRP >10 mg/L. CTI was compared with TyG and its component biomarkers, and incremental value was quantified using weighted C-statistics, integrated discrimination improvement, and continuous net reclassification improvement. Results Among 11,809 participants, 411 reported stroke. CTI was associated with prevalent stroke before cardiometabolic adjustment (unadjusted OR = 2.05, 95% CI: 1.74-2.42; demographically adjusted OR = 1.57, 95% CI: 1.31-1.89; both P < 0.001), but the fully adjusted association was attenuated (OR = 1.22, 95% CI: 0.98-1.53; P = 0.080). There was no evidence of non-linearity, and subgroup interaction tests, including the CTI-by-age interaction, were not statistically significant. Adding CTI to traditional covariates minimally changed discrimination (weighted C-statistic, 0.846 to 0.847). Conclusions CTI reflects an inflammatory-metabolic burden phenotype, but its association with prevalent stroke was largely accounted for by traditional risk factors, and it provided negligible incremental discrimination in this cross-sectional analysis.

BACKGROUND: The effect of neurovascular health on cardiovascular outcomes is not well-known. Cerebral small vessel disease (CSVD) signals subclinical vascular brain injury and its quantification may serve as a tool to stratify risk in healthy individuals. Studying the relations of CSVD to cardiovascular events and mortality could aid in targeted preventive efforts. METHODS: We included Framingham Heart Study participants free of diagnosed stroke and dementia. CSVD was assessed on brain MRI?considering covert infarcts, cerebral microbleeds, cortical superficial siderosis, high perivascular space burden, and extensive white matter hyperintensities?with 1 point assigned for each marker, to categorize CSVD scores as 0, 1, or 2+. We used a composite outcome and three components: stroke, myocardial infarction, and mortality. Cox regression analysis was used with models adjusted for age, sex, cohort, MRI-exam cycle time interval, and vascular risk factors. RESULTS: In our study, 31% of our 3263 participants (mean age 58.0 years [SD: 13.4], 54% women) had a CSVD score greater than 0, and those with higher scores were generally older and had higher prevalence of vascular risk factors. Over a median follow-up of 8.4 years, 454 participants (13.9%) experienced at least one outcome, with mortality being the most common. Increasing CSVD burden was associated with higher incidence rates of the composite outcome. Compared with participants with CSVD score 0, those with scores of 1 and 2 had significantly higher risk of any event (HR 1.48, 95% CI 1.19?1.85; HR 1.52, 95% CI 1.17?1.97 respectively). CSVD burden showed a dose-response relationship with all-cause mortality and was associated with increased stroke risk, while no significant association with MI was observed. CONCLUSION: Higher subclinical CSVD burden is independently associated with increased risk of adverse cardiovascular events and mortality in community-dwelling individuals. CSVD detected on brain MRI may serve as a valuable imaging biomarker for risk stratification and early prevention of life-threatening outcomes.

Background: Stroke remains a leading cause of death and disability worldwide. Matrix metalloproteinases (MMPs), particularly MMP-9 and MMP-12, contribute to early blood-brain barrier (BBB) disruption, neuroinflammation, haemorrhagic transformation, and intracerebral haemorrhage (ICH). Intravenous thrombolysis is the only widely used pharmacological therapy for acute ischaemic stroke, but its utility is limited by narrow eligibility criteria and haemorrhagic risk. Inhibition of MMPs in the acute phase may offer a complementary neurovascular protective strategy. Methods: AZD1236, a selective dual MMP-9/-12 inhibitor, was evaluated in transient and permanent middle cerebral artery occlusion models and in a collagenase-induced ICH model in young, aged, obese, and female mice. Drug or vehicle was administered 2-6 hours after stroke onset. Outcomes included infarct or haematoma volume, BBB integrity, neurological function, and pain-related behaviours. Results: AZD1236 given within 2-4 hours after ischaemic or haemorrhagic insult significantly reduced infarct and haematoma volumes, improved short- and long-term neurological scores, and preserved BBB integrity, whereas treatment at 6 hours was largely ineffective. AZD1236 also attenuated the development of post-stroke mechanical allodynia and thermal hyperalgesia. Mechanistically, treatment reduced MMP-9 and MMP-12 activity, increased tight junction protein expression, and dampened inflammatory responses. Conclusions: Dual inhibition of MMP-9/-12 with AZD1236 confers robust neurovascular protection and mitigates post-stroke pain across clinically relevant models of ischaemic and haemorrhagic stroke. These findings provide a strong preclinical rationale for clinical evaluation of dual MMP-9/12 inhibition as an adjunctive neuroprotective strategy for acute stroke.

BACKGROUND: Existing models for discharge to long-term institutional care after stroke are developed within single health systems and pool to an area under the curve near 0.80, but none is accompanied by an estimate of how much of the outcome is a property of the health system rather than the patient. METHODS: Secondary analysis of the International Stroke Trial, a randomised trial in 19,435 patients with suspected acute ischaemic stroke recruited in 1991-1996 across 36 countries. Among 14,885 survivors to six months with residence recorded, we developed and internally validated a logistic prognostic model for residential or nursing-home residence using 17 admission-day terms, and compared it against a pre-specified benchmark of age and stroke syndrome alone. Between-country variation was estimated by a method-of-moments decomposition with a cluster bootstrap. RESULTS: Institutional residence was recorded for 1,984 of 14,885 survivors (13.3%); the model was fitted on 14,121 patients containing 1,935 events. In 10-fold cross-validation with the whole procedure refitted per fold, the out-of-fold c-statistic was 0.789, calibration slope 0.987, calibration-in-the-large 0.1371 predicted against 0.1370 observed, and Brier score 0.1013. A benchmark of age and stroke syndrome alone reached an optimism-corrected 0.774 against 0.790 for the full model, a corrected difference of 0.0160. Between-country variation gave an intraclass correlation of 0.0409 (0.0191 to 0.0673), and in leave-one-country-out validation the c-statistic ranged from 0.635 to 0.823 across the 14 countries with enough events to estimate it. CONCLUSIONS: Institutional residence after stroke can be stratified at admission with discrimination comparable to existing models and calibration that holds in unseen patients, but almost all of the signal is carried by age and stroke syndrome. Performance varies substantially between countries, pointing to placement systems as the limit on what a pooled model can do.

Background Asymptomatic carotid artery stenosis (ACAS) increases the risk of stroke, and is associated with cognitive decline. This association might be driven by underlying atherosclerotic disease instead of the stenosis itself, which could explain why studies on the cognitive benefits of carotid revascularisation are inconclusive. Methods Between 2007-2012, dementia-free participants of the population-based Rotterdam Study underwent carotid ultrasound, and additional carotid MRI if intimal media thickness was >2.5mm. All participants underwent repeated cognitive assessments and were followed for dementia until January 2022. We determined the effect of ACAS and plaque without stenosis on all-cause dementia using multivariable Cox models, and on change in cognition (g-factor) using multivariable linear mixed-effects models. Results Of 4267 participants (mean age 67.5 years, 55.5% women), 483 (11.3%) had plaque without stenosis, 989 (23.2%) had 1-49% stenosis, 107 (2.5%) had 50-99% stenosis, and 15 (0.4%) had occlusion. During a mean follow-up of 9.7 years, 391 participants developed dementia. Compared to individuals without carotid atherosclerosis, risk of dementia was increased in the presence of plaque without stenosis (HR: 1.39 [95%CI: 1.05-1.83]) and occlusion (HR: 4.61 [1.82-11.66]), but not with stenosis (HR 1-49% stenosis: 1.08 [0.84-1.39]; 50-99% stenosis: 1.18 [0.70-1.99]). Neither carotid plaques nor stenosis affected cognitive decline. Results did not differ consistently by plaque characteristics. Conclusion Risk of dementia was increased with asymptomatic carotid artery plaque and occlusion, but not significantly with 50-99% stenosis. These results are in line with detrimental effects of generalised atherosclerotic disease and severe haemodynamic impairment on cognitive decline and dementia risk.