Background Stroke remains a leading cause of mortality and adult disability in China, imposing a substantial disease and socioeconomic burden on society, yet nationally representative epidemiological and real-world inpatient care data remain insufficient. Methods This study integrated data from the Global Burden of Disease 2023, the Hospital Quality Monitoring System (7536 hospitals) in 2023, and the 2021 National Mortality Surveillance System to systematically assess the epidemiology, disease burden, inpatient care patterns, clinical outcomes and average costs of stroke per hospitalisation in China. Results In 2023, China reported 4.23 million incident cases, 26.68 million prevalent cases and 2.05 million deaths from stroke. Despite declining age-standardised incidence and mortality, ischaemic stroke (IS) prevalence continued to increase, while haemorrhagic stroke remains the principal contributor to disability-adjusted life years. Real-world inpatient data showed that males and older adults accounted for higher proportions of stroke admissions. Stroke admissions were predominantly concentrated in tertiary public hospitals with marked regional variation. Haemorrhagic stroke has substantially higher in-hospital mortality (intracerebral haemorrhage, ICH: 4.23%; subarachnoid haemorrhage, SAH: 4.08% vs IS: 0.49%) and adverse discharge outcomes than IS. Tertiary hospitals exhibited higher mortality (1.19% vs 0.62%) but lower 0–31-day readmission rates (1.19% vs 1.63%) than secondary hospitals, whereas private hospitals showed longer hospital stays (10.54 vs 9.86 days) and higher readmission rates (1.88% vs 1.34%) than public institutions. The mean hospitalisation cost was RMB13 927 (US$1900) per admission, with substantially higher costs for SAH and ICH than for IS. Conclusions This nationwide analysis provides comprehensive real-world evidence on the epidemiological burden, inpatient care patterns, clinical outcomes and hospitalisation costs of stroke in China, identifying substantial national, regional and hospital-level variations that may inform future research and quality improvement efforts.

BACKGROUND:Whether diffusion‑weighted imaging infarction patterns influence the efficacy and safety of early oral ticagrelor‑aspirin with intravenous thrombolysis in moderate acute ischemic stroke is uncertain. We assessed treatment effects by infarction pattern in this thrombolysis setting. METHODS:This was a subgroup analysis of the TAPIS trial (Ticagrelor With Aspirin Dual Antiplatelet Therapy Combined With Intravenous Thrombolysis in Patients With Ischemic Stroke), a 60-center, randomized, double‑blind trial in China. Patients aged 18 to 80 years with noncardioembolic stroke (National Institutes of Health Stroke Scale score 4-10) who received intravenous thrombolysis within 4.5 hours of onset were randomized within 6 hours to ticagrelor‑aspirin or placebo. Diffusion‑weighted imaging patterns were centrally adjudicated as multiple acute infarcts (MAIs; ≥2 lesions) or non‑MAIs (single infarction or diffusion‑weighted imaging-negative). The primary efficacy outcome was modified Rankin Scale score of 0 to 1 at 90 days; safety outcome was symptomatic intracranial hemorrhage. Treatment‑by‑pattern interaction was assessed. RESULTS:Among 1307 patients (94.6% of full analysis set; median age, 65.5 years; 71.2% male; median National Institutes of Health Stroke Scale score, 6.0), 409 (31.3%) had MAIs and 898 (68.7%) non‑MAIs (20.8% diffusion‑weighted imaging-negative, 79.2% single infarction). MAIs were associated with poorer prognosis than non‑MAIs (excellent outcome: 58.9% versus 69.2%; adjusted risk ratio, 0.92 [95% CI, 0.84-1.00]). Ticagrelor‑aspirin was associated with a higher likelihood of excellent outcome versus placebo in MAIs (64.4% versus 53.4%; risk ratio, 1.21 [95% CI, 1.02-1.42]), whereas no significant benefit was observed in non‑MAIs (71.2% versus 67.1%; risk ratio, 1.06 [95% CI, 0.97-1.16]; Pinteraction=0.18). Early neurological improvement showed significant heterogeneity by infarction pattern (Pinteraction=0.02); the treatment‑by‑pattern interaction for the primary outcome was nominally significant after adjusting for rescue tirofiban use (P=0.04). Symptomatic intracranial hemorrhage occurred in MAIs: 1 of 205 (0.5%) versus 2 of 204 (1.0%); non‑MAIs: 1 of 448 (0.2%) versus 1 of 450 (0.2%). CONCLUSIONS:In thrombolyzed patients with moderate noncardioembolic stroke, MAIs were associated with poorer functional outcomes. Early ticagrelor‑aspirin showed directionally consistent benefits without excess bleeding in patients with MAIs, though the primary interaction was not significant. These hypothesis‑generating findings may inform future trials of diffusion‑weighted imaging infarction pattern as an imaging biomarker to guide antiplatelet therapy in early reperfusion. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT06316570.

Background: Cerebral small vessel disease (CSVD) is a major cause of vascular cognitive impairment (VCI), yet diagnosis remains difficult due to heterogeneous patient profiles and complex manifestations. This study aimed to develop and validate AI-based tools for distinguishing normal cognition (NC) and mild cognitive impairment (MCI) in CSVD. Methods: Two CSVD cohorts were analyzed: (1) a nationwide multicenter dataset (N=4185) with standardized demographic and clinical variables; and (2) a single-center dataset from Beijing Tiantan Hospital (N=74) including demographic, structural MRI, heart rate variability, EEG, hemodynamic, functional MRI (fMRI), and diffusion tensor imaging (DTI) features. Cognitive status was determined by Montreal Cognitive Assessment (MoCA) scores. Models were developed using the tabular prior-data fitted network (TabPFN) and conventional machine learning methods (Random Forest, XGBoost, LightGBM). Performance was assessed with stratified five-fold cross-validation and independent testing, using area under the ROC curve (AUC). Secondary analyses in the single-center cohort examined associations between multimodal features and domain-specific outcomes: verbal fluency test (VFT-composite), color trails test part 1 (CTT-1), and Stroop test part 3. Results: In the nationwide cohort, TabPFN achieved the best performance (AUC=0.821), slightly surpassing XGBoost (AUC=0.795), while requiring no feature selection. In the single-center multimodal dataset, RF outperformed TabPFN (AUC=0.841, accuracy=68.9%), likely due to small sample size and class imbalance. Adding imaging and physiological features improved classification over demographic-only inputs, especially in MCI patients. For domain-specific outcomes, advanced neuroimaging (fMRI, DTI) contributed most. AUCs were 0.83 for VFT-composite, 0.836 for CTT-1, and 0.854 for Stroop part 3. Conclusions: AI-based models support auxiliary diagnosis of MCI in CSVD. Nationwide TabPFN models provide scalable screening, while multimodal single-center models allow refined evaluation. Advanced imaging and physiological features enhance domain-specific cognitive assessment, informing targeted diagnostic and intervention strategies.

Ependymal cells in the adult ventricular-subventricular zone are increasingly recognized for functions extending beyond cerebrospinal fluid dynamics; however, their identity and functional specialization remain incompletely understood. While ependymal cells (EP) have been implicated in interactions with the stem cell niche and the vasculature, their role in repair processes following neural injury remains elusive. In this study, we employed region-specific single-cell transcriptomics of the subventricular zone (SVZ) and ipsilesional peri-infarct territory in mice to identify a distinct subpopulation of GFAP+ FOXF2+ EP that selectively expand within the SVZ after neural injury. Notably, these cells were absent from other brain regions. Immunohistochemical validation revealed characteristic ependymal features, including typical pinwheel architecture and expression of Foxj1 and β-catenin. Furthermore, the absence of the proliferation marker Ki67 and the resistance of this subpopulation to Ara-C-mediated ablation indicate that these cells do not possess proliferative properties. Conditional deletion of Foxf2 in GFAP+ cells led to impaired endothelial junction integrity and increased blood-brain barrier (BBB) permeability. In contrast, overexpression of Foxf2 via GFAP promoter-driven adeno-associated virus delivery enhanced vascular repair and facilitated functional recovery. Mechanistically, these GFAP+ FOXF2+ EP secrete exosomal DLL4, which was associated with enhanced NOTCH pathway activity and restoration of BBB function. While the mechanism linking this limited cell population to the broad reparative effect, particularly the complete signaling amplification cascade, remains to be fully elucidated, these findings identify a subset of EP that contributes to BBB repair.

Background The effects of intravenous thrombolytic agents on fibrinogen differ due to structural differences among the agents. Using data from the RAISE (Reteplase Versus Alteplase for Acute Ischemic Stroke) trial, we aimed to investigate the impact of differences in baseline plasma fibrinogen levels on the efficacy and safety of reteplase versus alteplase within 4.5 hours of acute ischemic stroke symptom onset. Methods This post hoc subgroup analysis of the multicenter RAISE trial categorized participants by baseline fibrinogen levels: low (<2 g/L), normal (2–4 g/L), and high (>4 g/L). The primary efficacy outcome was excellent functional outcome at 90 days (modified Rankin scale score of 0 or 1). The primary safety outcome was symptomatic intracranial hemorrhage within 36 hours. Results A total of 1373 patients with acute ischemic stroke were included. Ninety‐two in the low fibrinogen group (<2 g/L), 1178 in the normal fibrinogen group (2–4 g/L), and 103 in the high fibrinogen group (>4 g/L). Adjusted risk ratios of primary efficacy outcome were 1.13 (95% CI, 0.97–1.32) for the low fibrinogen group, 1.13 (95% CI, 1.04–1.23) for the normal fibrinogen group, and 1.09 (95% CI, 0.84–1.42) for the high fibrinogen group. The primary safety outcome showed no difference between reteplase and alteplase in the 3 fibrinogen subgroups. Conclusions Among patients with acute ischemic stroke who were treated with either reteplase or alteplase within 4.5 hours after symptom onset, there was no difference observed in the relative efficacy and safety between the 2 groups across the 3 fibrinogen subgroups. However, these findings should be interpreted cautiously and require validation in larger, adequately powered prospective studies. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05295173.

BACKGROUND:The quantitative insulin-sensitivity check index (QUICKI) has an excellent linear correlation with the glucose clamp index of insulin sensitivity (SIClamp). OBJECTIVE:It is important to investigate whether QUICKI would be useful index of insulin resistance (IR) to predict clinical outcome in ischemic stroke (IS) patients without type 2 diabetes mellitus (T2DM). METHODS AND MATERIAL:Prospective cohort patients who were diagnosed with IS and without a history of T2DM in the ACROSS-China registry were included from May 2008 to December 2009. And, QUICKI was calculated by the formula: 1/[log (fasting insulin, μU/mL) + log (fasting blood glucose, mg/dL)] and split into four quartiles. RESULTS:Of 1149 study participants, recurrent IS, all-cause death, and poor outcome occurred in 169 (14.71%), 72 (6.53%), and 261 (22.72%) cases, respectively in 1-year follow-up. Multivariable Cox proportional hazards analyses showed that the risk of incident primary endpoints was associated with a lower QUICKI quartile. In the Cox proportional hazard model, patients with the first QUICKI had an association with IS recurrence (adjusted hazard ratio, 2.90; 95% CI, 1.26-6.67; P = 0.001) and poor outcome (adjusted hazard ratio, 2.53; 95% CI, 1.06-5.99; P = 0.035), compared with those in the fourth quartile. Furthermore, the Kaplan-Meier survival analysis shown non-diabetic IS patients with a lower QUICKI had a higher mortality. CONCLUSIONS:QUICKI as an insulin sensitivity index might be a potential predictor of clinical outcomes for acute IS patients without T2DM.

Background and Objectives Enlarged perivascular spaces (EPVSs), particularly in the basal ganglia (BG), are indicators of microvascular dysfunction and impaired glymphatic clearance, which may influence stroke outcomes. Determining the threshold below which endovascular therapy (EVT) confers no additional benefit is clinically important for patients with large ischaemic infarcts. Methods This post-hoc analysis utilized data from the ANGEL-ASPECT trial (NCT04551664), a multicentre, randomized controlled trial of 456 acute ischaemic stroke (AIS) patients with anterior circulation large vessel occlusion (LVO) and a large ischaemic core. Among these patients, 226 who with completed, high-quality brain magnetic resonance imaging (MRI) were included. BG-EPVS severity was assessed on T2-weighted MRI and categorized as none-to-mild, moderate, or severe. The primary outcome was the 90-day modified Rankin scale (mRS) score. Results EVT significantly improved 90-day mRS outcome in patients with none-to-mild (adjusted common odds ratio [cOR] 5.50, 95% CI: 2.72-11.16, P < 0.001) and moderate (adjusted cOR 4.03, 95% CI, 1.46-11.15, P = 0.007) BG-EPVS. However, the benefit was markedly attenuated and not statistically significant in patients with severe BG-EPVS (adjusted cOR, 1.07 95% CI, 0.25-4.67, P = 0.926). EVT also increased the likelihood of achieving favourable functional outcomes (mRS scores of 0-2 and 0-3) and early neurological improvement (ENI) in the none-to-mild BG-EPVS subgroup, and favourable outcome (mRS score of 0-2) in the moderate BG-EPVS subgroup, but not in the severe BG-EPVS subgroup. Significant treatment-by-BG-EPVS interactions were observed for achieving an mRS score of 0-3 (P_interaction = 0.005) and ENI (P_interaction = 0.029). Conclusions EVT was associated with significantly improved 90-day functional outcomes in LVO-AIS patients with a large ischaemic core and none-to-mild or moderate BG-EPVS, whereas this benefit was not observed in those with severe BG-EPVS. Given the limited power in subgroup analyses, these findings should be considered hypothesis-generating and warrant validation in larger, adequately powered randomized controlled trials.

AIMS:This study aimed to examine the cross-sectional and longitudinal associations between cardiovascular-kidney-metabolic (CKM) syndrome stages and brain macrostructure and microstructure. MATERIALS AND METHODS:We conducted a prospective, community-based cohort study using data from 3067 adults aged 50-75 years. Participants were classified using the American Heart Association CKM staging system (Stages 0-4). Brain MRI was performed across three waves to assess global/regional volumes, white matter hyperintensity volume (WMHV) and diffusion tensor imaging (DTI) metrics. Adjusted linear regression and linear mixed-effects models were used. RESULTS:Among 3038 participants (mean age 61.9 years, 53.6% female), cross-sectional analyses revealed that advanced CKM stages (3-4) were significantly associated with reduced total brain, grey matter and cerebral white matter volumes, and increased WMHV. Longitudinally, higher baseline CKM stages (particularly Stages 2-3) were associated with accelerated declines in these brain volumes and faster WMHV progression over a median 4.7-year follow-up. DTI analyses further demonstrated a stage-dependent pattern of progressive white matter microstructural deterioration. This evolution progressed from focal alterations in early stages to widespread integrity loss in Stage 4, characterised by significant reductions in fractional anisotropy and elevated mean, axial and radial diffusivities. CONCLUSIONS:Our findings indicate that CKM syndrome severity is associated with abnormalities in brain macrostructure and microstructure. This is evidenced by both progressive white matter microstructural deterioration, which is detectable early, and concomitant, albeit more modest, declines in brain macrostructure. These results underscore the importance of early identification and monitoring of CKM syndrome to help mitigate or delay subsequent decline in brain health.

Chronological age is a strong predictor of poor outcomes after ischemic stroke but may not fully capture underlying biological vulnerability. This study investigated whether age-related brain atrophy and plasma YKL-40, a marker of astroglial inflammation, mediate the association between age and the one-year risk of ischemic stroke recurrence or all-cause mortality. Data were obtained from 4,305 participants enrolled in the Third China National Stroke Registry. Baseline brain atrophy was quantified from structural T1-weighted MRI using an automated deep learning–based pipeline (FastSurfer), yielding hemispheric cortical and white matter volumes that were modeled as indicators of a latent atrophy construct. Structural equation modeling was applied to estimate direct and indirect pathways linking age, brain atrophy, YKL-40, and one-year composite outcomes, adjusting for sex, atrial fibrillation or flutter, hypertension, and diabetes, with indirect effects evaluated using 5,000 bootstrap resamples. The total effect of age on one-year outcomes was not significant (β = −0.011; 95

Objectives This study aimed to identify factors at baseline associated with visual outcomes of patients with idiopathic intracranial hypertension (IIH) with venous sinus stenosis who underwent venous sinus stenting. Methods The study eyes were divided into two groups according to mean deviation (MD) at 6-month post-stenting follow-up: MD better than −2.0 dB (the favorable visual outcome group) and equal to −2.0 or worse (the poorer visual outcome group). Variables at baseline between the two groups were compared. A multivariable logistic regression model was performed to identify the factors at baseline associated with poorer MD outcomes at 6 months. Results The poorer recovery group had a lower incidence of tinnitus (5.9% vs 27.5%, P=0.015), worse initial best corrected visual acuity (0.22 vs 0, in logMAR, P=0.000), worse preoperative MD (−8.64 vs −3.05, P=0.000) and higher trans-stenotic gradient pressure (19.5 vs 16, P=0.002) and total cranial gradient pressure (TCGP) (25.75 vs 18, P=0.000), lower ganglion cell complex (GCC) thickness (90.5 vs 99, P=0.005), higher focal loss volume percentage (2.35 vs 0.84, P=0.002) and global loss volume percentage (4.87 vs 1.8, P=0.012) of GCC. Multivariate analysis showed that worse preoperative MD and higher TCGP (OR 45.61, 95% CI 5.21 to 399.48; P=0.001 and OR 8.45, 95% CI 1.60 to 44.67; P=0.012, respectively) were associated with an increased risk of poorer MD outcomes at the 6-month follow-up. Conclusion This study found that worse preoperative MD and higher TCGP at baseline may be associated with poorer visual outcomes after stenting treatment.

Watershed infarction (WI) is heterogeneous. This study aims to explore the effect of clopidogrel-aspirin in patients with WI and which WI patterns could gain more benefits. Patients are classified into cortical WI (CWI) (n = 484), internal WI (IWI) (n = 372), CWI+IWI (n = 410), and non-WI (n = 4,033) according to diffusion-weighted magnetic resonance imaging. The results show that patients with WI treated with clopidogrel-aspirin have a lower risk of stroke recurrence compared to aspirin at 90 days (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.49-0.93). Specifically, patients receiving clopidogrel-aspirin show a lower rate of recurrent stroke than those receiving aspirin in IWI (HR, 0.54; 95% CI, 0.30-0.97), and with a similar trend in CWI+IWI, but not significant in CWI (p for interaction = 0.41). Clopidogrel-aspirin does not increase moderate-to-severe bleeding across WI patterns. This study reveals that the effect of clopidogrel-aspirin appears consistent across WI subgroups, but it might be more effective in patients with IWI. This study is registered at Clinicaltrials.gov (NCT03635749).

Background: The hyperdense middle cerebral artery sign (HMCAS) observed on noncontrast computed tomography is associated with thrombus composition and thrombectomy outcomes. The impact of HMCAS on the efficacy of endovascular therapy (EVT) in patients with large core infarcts remains unclear. Methods: This analysis uses data from the ANGEL-ASPECT (Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients With a Large Infarct Core) trial, a multicenter randomized controlled trial conducted in China. Patients with acute ischemic stroke and anterior-circulation large-vessel occlusion were categorized according to whether HMCAS was present on baseline noncontrast computed tomography. The primary outcome was the 90-day modified Rankin Scale score. Results: Of the 432 patients included in this analysis, 33% were HMCAS positive on baseline noncontrast computed tomography. In the EVT-treated patients, patients with HMCAS had worse functional outcomes than those without HMCAS (adjusted relative risk, 0.44 [95% CI, 0.26-0.73]; P=0.002). Patients with HMCAS required a greater number of thrombectomy passes (P<0.001). Among patients without HMCAS, EVT was associated with better functional outcomes than medical management (generalized odds ratio [OR], 2.78 [95% CI, 1.80-4.27]; P<0.001), whereas this benefit was not statistically significant among patients with HMCAS (adjusted OR, 1.69 [95% CI, 0.93-3.08]; P=0.09). There was no significant interaction between HMCAS status and treatment assignment (P=0.19). Conclusions: In this subgroup analysis comparing EVT with medical management, we found no statistically significant treatment-by-HMCAS status interaction, indicating that the benefits of EVT extend to patients with large core infarcts irrespective of HMCAS status. However, the magnitude of benefit appears greater in patients without HMCAS, whereas those with HMCAS tend to have a poorer overall prognosis. Registration: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04551664.

Stroke remains a major global public health challenge, with persistent disparities in its burden across countries, and an increasing burden among young adults aged 15-49 has emerged as a growing concern. However, comprehensive evaluations of stroke and its subtypes among young adults in Asia remain limited. This study utilizes data from the 2021 Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), covering the period from 1990 to 2021, to assess the burden of stroke in Asia and provide evidence-based policy and resource allocation. In this study, we extracted GBD 2021 data to estimate the absolute numbers and rates of prevalence, incidence, mortality, disability-adjusted life years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) due to stroke and its subtypes among young adults (15-49 years) in Asia from 1990 to 2021, with data stratified by year, age group, and sex. In addition, we analyzed major risk factors and projected future trends through 2050. Our analysis showed that in 2021, stroke accounted for 14.70 million (95% UI 13.39–16.01 million) DALYs and 1.14 million (95% UI 0.99–1.32 million) new cases in Asia, with a DALY rate of 620.24 (95% UI 564.66–675.12) per 100,000 and an incidence rate of 48.22 (95% UI 41.81–55.69) per 100,000. From 1990 to 2021, absolute numbers of prevalence, incidence, mortality, DALYs, YLLs, and YLDs increased by 43.56%, 44.82%, 10.68%, 11.02%, 7.64%, and 38.54%, respectively. Although the rates of prevalence and incidence showed slight increases of 0.07% and 0.96%, the rates of mortality, DALYs, YLLs, and YLDs decreased by 22.84%, 22.61%, 24.96%, and 3.42%, respectively. Among stroke subtypes, both ischemic stroke (IS) and intracerebral hemorrhage (ICH) showed increases in the absolute numbers across six metrics, with IS demonstrating more pronounced growth. Subarachnoid hemorrhage (SAH) showed increases in the incidence, prevalence, and YLDs, while its rates of mortality, DALYs, and YLLs declined. The rates of all six metrics decreased for ICH and SAH, whereas the rates of prevalence, incidence, and YLDs for IS increased, alongside reductions in the rates of mortality, DALYs, and YLLs. The absolute numbers and rates of all six metrics increased with age across both sexes, with males consistently showing higher absolute numbers and the highest burden observed in the 45-49 age group. Apart from the prevalence and YLD rates, males demonstrated higher incidence, mortality, DALYs, and YLL rates across all age groups, peaking at 45-49 years. Moreover, the leading contributors to stroke-related DALYs included high systolic blood pressure, smoking, and air pollution. From 2021 to 2050, the prevalence and incidence of stroke will continue to rise, while mortality and DALYs rates are expected to decline. Overall, from 1990 to 2021, the burden of stroke and its subtypes among young adults in Asia has increased significantly, with notable differences across age groups and sex, and with population growth and demographic changes, this burden is expected to further intensify in the future. Therefore, future research and public health policies should focus more on targeted interventions addressing the specific needs of young adults to effectively control and alleviate the burden of stroke.

IntroductionCerebral small vessel disease (CSVD) and motoric cognitive risk syndrome (MCR) are both associated with adverse outcomes in older adults. Factors associated with MCR in CSVD remain poorly understood. We aimed to explore factors associated with MCR and its components (slow gait and subjective cognitive complaints [SCCs]) in CSVD, and to evaluate exploratory association-based multivariable models.MethodsThis cross-sectional study included CSVD patients aged ≥55 years without possible dementia based on education-adjusted MoCA screening from the cognitive subgroup of a national registry. Demographics, clinical variables, physical activity, and CSVD neuroimaging markers were assessed. MCR was defined as co-existing slow gait (age- and sex-adjusted) and SCCs (single-item memory complaint from the 15-item Geriatric Depression Scale). Logistic regression and receiver operating characteristic analyses were performed to identify associated factors and evaluate models. Firth penalized logistic regression and bootstrap internal validation were additionally performed to assess sparse-data bias and optimism in model discrimination.ResultsAmong 225 patients (mean age 65.4 years, 54.2% male), MCR prevalence was 16.4%. In multivariable models, MCR was associated with lower average systolic blood pressure and high total CSVD burden, while physical inactivity showed a positive but imprecise association because of sparse exposure. SCCs were associated with greater juxtacortical white matter hyperintensity volume and higher total CSVD burden. Slow gait was associated with dyslipidemia, poorer functional status, and higher basal ganglia perivascular spaces. The comprehensive exploratory model integrating demographic, clinical, and neuroimaging factors achieved areas under the curve of 0.732 for MCR, 0.733 for SCCs, and 0.770 for slow gait; the corresponding optimism-corrected AUCs were 0.691, 0.696, and 0.725, respectively.ConclusionIn this exploratory cross-sectional analysis, MCR in CSVD patients showed associations with vascular, lifestyle-related, and neuroimaging markers. However, given the small number of MCR events, the single-item SCC assessment, the lack of temporality, and the limited persistence of associations after FDR correction, these findings should be interpreted as hypothesis-generating.

ABSTRACT:In recent decades, the advent of revascularization treatments (RVTs), such as intravenous thrombolysis (IVT) and endovascular therapy, has significantly improved clinical outcomes in patients with acute ischemic stroke (AIS). However, stroke-associated pneumonia (SAP) remains a common complication that has a negative impact on the prognosis. This review addresses the mechanisms underlying the development of SAP in patients with AIS, evaluates risk factors, and discusses therapeutic and preventive measures in the era of RVTs. Despite advances in acute stroke care, the incidence of SAP remains high, particularly in patients who receive endovascular treatment (EVT), possibly because of prolonged mechanical ventilation, the effects of anesthesia, and stays in the intensive care unit. Immunodepression, dysphagia, lung damage, and changes in the gut microbiota are central to the pathogenesis of SAP. Current prevention strategies, including screening for dysphagia, oral hygiene, and immunomodulation, show promise but require further validation. Future research should focus on integrating biomarkers and imaging markers for early prediction of SAP and developing targeted interventions to improve patient outcomes.

Asymptomatic carotid artery stenosis (aCAS) increases the risk of ischemic stroke despite lacking clinical symptoms. This study sought to characterize the serum metabolic profile of aCAS and to identify potential biomarkers associated with plaque vulnerability by integrating metabolomics with radiomics. Untargeted metabolomic profiling was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) on 72 participants, including 36 aCAS patients and 36 age- and sex-matched healthy controls (HC). Multivariate and univariate statistical analyses were conducted to screen differential metabolites. Candidate biomarkers were prioritized based on variable importance in projection (VIP) scores and random forest (RF) modeling. Plaque vulnerability features were quantified by high-resolution magnetic resonance vessel wall imaging (HR-VWI), and multi-omics analysis assessed associations between metabolites and plaque characteristics. A total of 144 significantly altered metabolites were identified between the aCAS and HC groups. Pathway enrichment analysis indicated that these differential metabolites were predominantly involved in lipid, purine, amino acid, nucleotide, and energy metabolism. Notably, 12R-HETrE, 9S-HOTrE, oleoylcarnitine, crichetocholic acid and 1β,3α,7α-trihydroxy-5β-cholan-24-oic acid-were significantly associated with radiomic markers of plaque vulnerability. This study delineates metabolic alterations in aCAS patients and identifies potential serum metabolic biomarkers associated with plaque vulnerability. Further validation is required.

BACKGROUND:Evidence supporting the early addition of antiplatelet therapy to intravenous thrombolysis in patients with acute ischaemic stroke remains inconclusive. We aimed to investigate the efficacy and safety of early oral dual antiplatelet therapy (DAPT), started within 6 h of onset, as an adjunct to intravenous thrombolysis. METHODS:TAPIS was a randomised, double-blind, placebo-controlled trial done in 60 hospitals across China. We enrolled patients treated with intravenous thrombolysis for ischaemic stroke, with a National Institutes of Health Stroke Scale score of 4-10. We randomly assigned (1:1) patients to receive oral aspirin plus ticagrelor (DAPT group) or corresponding placebo within 6 h of stroke onset, either before, during, or after receiving thrombolysis. Ticagrelor or placebo was continued for days 2-7 in each group, with open-label aspirin administered for days 2-90. Patients, clinicians, and investigators were masked to the group assignment. The primary efficacy outcome was an excellent functional outcome (modified Rankin Scale score 0-1) at 90 days. The primary safety outcome was symptomatic intracranial haemorrhage within 36 h. This trial was registered with ClinicalTrials.gov (NCT06316570) and is completed. FINDINGS:Between April 3, 2024, and Sept 30, 2025, we randomly assigned 1382 patients to the early DAPT (n=690 [49·9%]) or placebo (n=692 [50·1%]) groups. The median age was 65·6 years (IQR 58·3-72·0), 991 (71·7%) were men, and 391 (28·3%) were women. At 90 days, 474 (68·7%) patients in the early DAPT group and 429 (62·0%) in the placebo group achieved excellent functional outcomes (risk ratio 1·11 [95% CI 1·03-1·20; p=0·0089). Symptomatic intracranial haemorrhage within 36 h occurred in six (0·9%) patients in the early DAPT group versus five (0·7%) in the control group (risk ratio 1·20 [95% CI 0·37-3·93; p=0.76). INTERPRETATION:Among patients treated with intravenous thrombolysis for moderate ischaemic stroke, initiation of oral DAPT within 6 h of onset improved the likelihood of excellent functional outcomes at 90 days. Although no significant between-group difference in symptomatic intracranial haemorrhage was detected, wide CIs precluded exclusion of a small increased risk. FUNDING:National Natural Science Foundation of China, Capital's Funds for Health Improvement and Research, Noncommunicable Chronic Diseases-National Science and Technology Major Project, Beijing Municipal Science & Technology Commission, and the New Cornerstone Science Foundation.

OBJECTIVE:Takayasu arteritis (TAK)-related stroke and large-artery atherosclerosis (LAA)-related stroke share overlapping clinical features but differ fundamentally in pathophysiology and treatment strategies. Differentiating these two aetiologies remains a diagnostic challenge with critical therapeutic implications. We aimed to compare the clinical profiles, imaging characteristics and outcomes of TAK- versus LAA-related stroke to provide insights for diagnosis and management. PATIENTS AND METHODS:We conducted a multicentre comparative study using nationwide prospective registry cohorts in China. Among 926 patients with TAK, 80 patients with stroke were included. In addition, 372 patients with LAA-related stroke were selected from the China National Stroke Registry-III cohort (n=14 146). Clinical and imaging characteristics, traditional stroke risk factors and outcomes were analysed and compared. Subgroup analyses were performed according to the presence of atherosclerosis in TAK. Propensity score weighting was performed as a sensitivity analysis. RESULTS:Compared with LAA-related stroke, TAK-related stroke was younger, with a strong female predominance and lower prevalence of vascular risk factors and appeared to have a higher proportion of favourable functional outcomes (modified Rankin Scale 0-2: 93.2% vs 72.6%, p=0.0002), although direct comparison was limited by differences in follow-up structure and assessment timing. Furthermore, patients with TAK tended to show distinct imaging features, including predominant extracranial artery involvement and anterior circulation infarctions located in the subcortical/deep white matter. Among patients with TAK-related stroke, those with coexisting atherosclerosis were older, had longer disease duration and had a greater risk of supra-aortic complications and a higher rate of endovascular interventions. CONCLUSIONS:This study highlights distinct clinical and imaging profiles between TAK- and LAA-related strokes. It also provides a comparative analysis of TAK-related stroke with and without atherosclerosis, revealing differences in risk factors, vascular characteristics and intervention needs. These findings provide a descriptive framework that may assist aetiological differentiation and hypothesis generation for future studies.