Background and objectives Non-functional transverse sinus (NFTS) represents a markedly narrowed but non-thrombosed transverse sinus that may impair cerebral venous outflow. Its influence on the clinical course and outcomes of cerebral venous sinus thrombosis (CVST) remains unclear. This study aimed to evaluate the prevalence and prognostic significance of NFTS among patients with CVST. Methods Data from consecutively enrolled patients with confirmed CVST in multicentre databases were retrospectively analysed. NFTS was defined as a transverse sinus showing severe luminal reduction compared with the contralateral side in the absence of thrombosis. Patients with and without NFTS were compared for clinical and radiological features and 90-day excellent functional outcome, defined as a modified Rankin Scale score of 0–1. A preplanned secondary analysis included only patients with unilateral transverse sinus thrombosis sparing the NFTS to isolate its haemodynamic impact. Results Among 443 CVST patients (mean age 41.4±18.2 years; 64.3% female), 49 (11%) had NFTS. Compared with those without NFTS, affected patients had higher rates of papilledema (50% vs 23%, p<0.001) and multiple cerebral vein involvement (43% vs 22%, p=0.002), with a trend towards lower rates of excellent 90-day outcome (78% vs 87%, p=0.067). In the secondary analysis of 299 patients with unilateral transverse sinus thrombosis not involving NFTS, NFTS (n=29) was associated with more papilledema (51.3% vs 24.3%, p<0.001), multiple vein involvement (51.3% vs 31.9%, p=0.017) and superior sagittal sinus thrombosis (48.7% vs 28.9%, p=0.013). NFTS patients with contralateral transverse sinus thrombosis had poorer outcomes (excellent outcome 74.4% vs 89.7%, p=0.006). NFTS independently predicted non-excellent outcome (OR 4.37; 95% CI 1.5 to 13; p=0.008). Conclusions NFTS identifies a subset of CVST patients with impaired venous drainage, greater thrombotic extent, increased papilledema and poorer functional recovery. Recognition of NFTS on baseline imaging may assist in risk stratification and tailored monitoring in CVST.
Importance Large-vessel occlusion (LVO) strokes cause substantial morbidity and mortality. Reperfusion within 4.5 hours (intravenous thrombolysis (IVT), endovascular thrombectomy (EVT) or bridging strategies (EVT following IVT)) is critical, but the relative effectiveness and safety of different thrombolytic agents/doses and strategies remain debated. Objective To compare the relative effectiveness and safety of different IVT regimens (alteplase (rt-PA) and tenecteplase (TNK) at commonly studied doses), EVT alone and bridging strategies within 4.5 hours after symptom onset for LVO stroke using a network meta-analysis. Design, setting and participants Frequency-based network meta-analysis of randomised clinical trials (RCTs). We included RCTs enrolling adults (≥18 years) with imaging-confirmed LVO treated within 4.5 hours. Trials were identified through systematic searches of PubMed, Embase and Cochrane CENTRAL (through 27 August 2025). Exposures Treatment strategies categorised as (a) rt-PA 0.9 mg/kg, (b) TNK 0.4 mg/kg, (c) rt-PA 0.6 mg/kg+EVT, (d) rt-PA 0.9 mg/kg+EVT, (e) TNK 0.25 mg/kg+EVT, (f) TNK 0.4 mg/kg+EVT and (g) EVT. Main outcomes and measures Primary outcome: 90-day excellent functional outcome (modified Rankin scale (mRS) 0–1). Secondary outcomes: 90-day independence (mRS 0–2). Safe outcomes: 90-day all-cause mortality, symptomatic intracerebral haemorrhage (sICH) and any intracranial haemorrhage (ICH). Relative effects were estimated as RRs with 95% CIs and treatments were ranked by the surface under the cumulative ranking curve (SUCRA). Results 20 RCTs (5602 patients) were included. By SUCRA ranking for the primary outcome, TNK 0.25 mg/kg+EVT had the highest probability of being best (SUCRA 83.8%), followed by rt-PA 0.9 mg/kg+EVT (72.2%). Single-agent rt-PA 0.9 mg/kg and TNK 0.4 mg/kg ranked lowest for functional benefit (SUCRA 14.4% and 8.5%, respectively). For safety endpoints, rt-PA 0.6 mg/kg+EVT and EVT alone tended to rank better in reducing sICH, any ICH and mortality; TNK 0.4 mg/kg (alone or with EVT) frequently occupied lower safety rankings. Most pairwise comparisons did not achieve statistical significance, and many CIs included the null, indicating uncertainty. Conclusions and relevance In the available RCT network, TNK 0.25 mg/kg+EVT had the highest probability of best functional outcome in the 4.5-hour window, while lower-dose rt-PA strategies or EVT alone may be preferable from a safety perspective. Interpretation is limited by imprecision, heterogeneity between trials and the small number of events for some safety outcomes. Additional large, direct head-to-head RCTs and individual-patient data meta-analyses are warranted.
Motor dysfunction caused by neurological disorders such as stroke, spinal cord injury and amyotrophic lateral sclerosis has become a major global public health issue. Conventional rehabilitation approaches yield limited efficacy, highlighting the urgent need for innovative therapies. Brain-computer interface (BCI) technology offers a promising avenue for motor function restoration by decoding motor intentions and driving external devices or providing sensory feedback. However, current BCI development has predominantly emphasised technical performance metrics, lacking systematic investigation into the clinical characteristics of real-world patient populations. This disconnect between technological advancement and genuine clinical demands persists because existing studies often recruit idealised subjects while neglecting prevalent conditions like stroke and lack standardised assessments of clinically meaningful outcomes. Consequently, system designs frequently fail to align with patient-specific profiles. To address this gap, our study established a prospective BCI evaluation outpatient cohort, comprehensively collecting data from patients presenting with motor dysfunction throughout 2025. Among the total of 1641 patients with motor dysfunction, the majority were patients with chronic-phase stroke (1087, 66.24%). The cohort was primarily middle-aged, with a mean age of 45.93±11.23 years. The study further detailed patterns of muscle strength, joint range of motion and sensory impairments. The goal is to construct the first clinical profile characteristics to inform precise patient selection and guide personalised system design.
Background Acute ischaemic stroke with large vessel occlusion (AIS-LVO) is a significant subtype of ischaemic stroke which always requires endovascular treatment (EVT). Although EVT has a high recanalisation rate, nearly 40% of AIS-LVO patients experience futile recanalisation. Studying the occlusion microenvironment (OME), comprising thrombus and intracranial arterial blood, is essential to understand the localised markers of stroke and futile recanalisation. Design Cerebral Large Vessel Occlusion Stroke Multiomics Biosample Cohort (CLOMB) is a multicentre, multiomics ambispective cohort study conducted in five stroke centres in China. A total of 500 patients with AIS-LVO who undergo EVT will be included in the study. After enrolment, each participant undergoes a comprehensive clinical assessment including questionnaires, physical examinations, laboratory tests and imaging. We collect matched peripheral (arterial and venous) blood, thrombus and innovatively intracranial blood by microcatheter or aspiration catheter when first passing through the occlusion site. All biosamples are collected for subsequent multi-omics analysis (metabolomic, proteomic and transcriptomic). A 3-month and 1-year follow-up will be performed to collect the outcome data. Methods Systemic and local samples undergo untargeted metabolomic and proteomic analysis. For a representative subset (10%–15%), single-cell RNA sequencing (Switching Mechanism at 5′ End of the RNA Transcript) is performed. Targeted omics will be selectively implemented to further clarify their contents. To minimise selection bias, patients without retrieved thrombi remain in the cohort for clinical analysis. Conclusion CLOMB establishes a standardised protocol for OME biosampling and multiomics profiling. It aims to explore candidate biological pathways and provide a foundation for developing hypothesis-generating models for improving stroke outcomes, facilitating AIS-LVO diagnosis and classification. Trial registration number NCT06963489 .
BACKGROUND:Inflammatory processes play a critical role in ischaemic stroke. Acetylation of NLRP3 is a key step in amplifying neuroinflammation.(LbGP), a bioactive glycoprotein derived from Lycium barbarum, has anti-inflammatory potential, but its mechanisms in post-stroke neuroinflammation remain unclear. AIM:This study aimed to investigate the efficacy and molecular mechanisms of LbGP in alleviating neuroinflammation following ischaemic stroke. METHODS:A mouse model of middle cerebral artery occlusion (MCAO)/reperfusion was used to induce focal cerebral ischaemia/reperfusion (I/R) injury. Microglial cells were subjected to oxygen-glucose deprivation/reoxygenation. Neurological recovery was assessed by Y-maze and open-field tests. Molecular mechanisms were explored using Western blotting, ELISA, co-immunoprecipitation and immunofluorescence. RESULTS:LbGP significantly reduced cerebral infarct volume, attenuated neuroinflammation and improved functional recovery in I/R mice. Mechanistically, LbGP suppressed NLRP3 inflammasome activation through Sirtuin 3-mediated inhibition of NLRP3 acetylation, a finding further validated by exacerbated neuroinflammation in Sirt3-knockout mice. CONCLUSION:This study demonstrates for the first time that LbGP alleviates post-stroke neuroinflammation via Sirt3-mediated deacetylation of NLRP3, thereby disrupting inflammasome activation, and identifies LbGP as a promising therapeutic candidate for ischaemic stroke.
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 Stroke remains a leading cause of morbidity and mortality, with carotid atherosclerosis representing a major contributor. High-resolution evaluation of plaque characteristics is critical for risk stratification and therapeutic guidance. However, reliable methodologies for assessments are limited. Optical coherence tomography (OCT) provides superior resolution, yet standardised protocols for carotid artery imaging are lacking.Objective This study aimed to develop and validate a standardised methodology for the acquisition and analysis of carotid artery plaque using OCT imaging.Methods Sixty-four patients with internal carotid artery stenosis from the HERALD trial who underwent paired OCT imaging were included. A standardised non-occlusive protocol was employed to accommodate carotid anatomy. Key plaque features—minimum fibrous cap thickness (FCT), maximum lipid arc, calcification, minimum lumen area, intraplaque vessels, dissection and cholesterol crystals—were assessed by three independent, blinded observers. Fibrous cap volume (FCV) was calculated using an AI-driven dual-coordinate framework. Statistical analyses included intraclass correlation coefficients (ICC) for continuous variables, Fleiss’ kappa for categorical variables, Bland-Altman analysis for inter-observer agreement and Pearson correlation to assess relationships between variables.Results Analysis of 134 OCT pullbacks demonstrated excellent inter-observer reproducibility for minimum FCT (ICC=0.901), maximum lipid arc (ICC=0.812), and minimum lumen area (ICC=0.909). All observers achieved excellent intra-observer consistency. Bland-Altman analysis confirmed high agreement. Agreement for qualitative features was excellent for cholesterol crystals (κ=0.957), intraplaque vessels (κ=0.955), and dissections (κ=0.988) and moderately high for calcification (κ=0.848). FCV measurement using the AI framework showed good concordance with manual segmentation (mean Dice coefficient=0.73). A weak positive correlation was observed between changes in FCV and minimum FCT (r=0.296, p=0.024).Conclusions This study establishes a comprehensive and standardised OCT methodology for carotid plaque imaging, demonstrating excellent reproducibility in quantifying key morphological and high-risk features.
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.
BACKGROUND:Intensive blood pressure (BP) lowering after successful endovascular thrombectomy (EVT) failed to improve functional outcomes, but its association with the extent of blood-brain barrier disruption remains unclear. We investigated whether Contrast Staining-Alberta Stroke Programme Early CT Score (CS-ASPECTS) and contrast staining (CS) after EVT modify the outcomes of post-EVT BP management strategy. METHODS:This post hoc analysis of the Outcome in Patients Treated With Intra-Arterial Thrombectomy-Optimal Blood Pressure trial included acute stroke patients who achieved successful EVT and underwent follow-up brain CT within 3 hours of randomisation to intensive (systolic BP <140 mm Hg) or conventional (140-180 mm Hg) BP management. Subgroup analyses were conducted based on CS status and CS-ASPECTS. RESULTS:Among 174 patients (mean age 72.8±12.1 years, 38.5% women), CS was present in 123 (70.7%). CS was associated with a higher rate of any intracranial haemorrhage (ICH) but not with functional outcome. CS-ASPECTS 0-6 was associated with a higher risk of symptomatic ICH and worse functional outcome compared with CS-ASPECTS 7-10. Among patients with CS-ASPECTS 7-10, intensive BP lowering was associated with a lower likelihood of functional independence (adjusted OR 0.37, 95% CI 0.15 to 0.87), whereas no significant association was observed in patients with CS-ASPECTS 0-6 (adjusted OR 1.29, 95% CI 0.20 to 9.09) (P for interaction=0.044). There was no significant heterogeneity between BP management strategy and CS-ASPECTS for symptomatic intracerebral haemorrhage or mortality. CONCLUSIONS:CS-ASPECTS, but not CS alone, was associated with functional outcome and identified heterogeneity in the association between post-EVT BP lowering and functional independence. These exploratory findings warrant prospective validation before clinical application. TRIAL REGISTRATION NUMBER:NCT04205305.
BACKGROUND:Haemorrhagic transformation (HT) is the most feared complication of thrombolytic therapy in acute ischaemic stroke (AIS). This study aims to determine whether bornyl-2-hydroxy-4-(2-hydroxy-3,5-dichlorobenzyl) aminobenzoate (ZL006-05), a neuroprotectant that mitigates cerebral ischaemia/reperfusion injuries in animals and improves functional outcome in AIS patients, prevents recombinant tissue plasminogen activator (rtPA)-induced HT in transient middle cerebral artery occlusion (tMCAO) mice through affecting neutrophil myeloperoxidase (MPO). METHODS:The tMCAO was induced in adult mice. The recanalisation after rtPA thrombolysis within or beyond the clinical therapeutic window was simulated based on 110-minute-tMCAO and 5-hour-tMCAO, respectively. ZL006-05 was injected before or after rtPA administration. Haemoglobin and Evans blue contents in the brain were measured by spectrophotometric assay. MPO activity was measured with an MPO peroxidation activity assay kit. Mobilisation and infiltration of neutrophils were detected by flow cytometry or immunofluorescence. Neutrophil extracellular traps (NETs) were quantified by DNA stained with Hoechst. Neutrophils were depleted by anti-Ly6G mAb clone 1A8. Pro-inflammatory cytokines and MPO expressions were measured by Western blot analysis. RESULTS:ZL006-05 prevented rtPA-induced HT and blood-brain barrier (BBB) damage in 110-minute-tMCAO mice and reduced animal mortality caused by rtPA in 5-hour-tMCAO mice. ZL006-05 suppressed the activation of neutrophil MPO by the combination of rtPA with high mobility group protein B1 and prevented rtPA-induced MPO activation in the ischaemic brain. Molecular docking predicted that ZL006-05 is an MPO inhibitor, and ZL006-05 dose-dependently inhibited MPO enzymatic activity in purified MPO protein and cultured inflammatory cells. In the MPO deficient (MPO-/-) mice, rtPA-induced HT was significantly reduced. Moreover, ZL006-05 reversed rtPA-induced neutrophil mobilisation, infiltration and NET formation. Importantly, the inhibitory effect of ZL006-05 on rtPA-induced HT disappeared in the mice with MPO knockout or depletion of neutrophils. In addition, ZL006-05 inhibited expressions of pro-inflammatory cytokines in wild-type but not in MPO-/- neutrophils. CONCLUSION:ZL006-05 can prevent rtPA-induced BBB disruption and HT by interfering with neutrophil MPO activation.
Introduction Poststroke dysphagia and impaired cough reflex contribute to aspiration and pneumonia, yet the clinical value of cough reflex testing remains unclear.Patients and methods In this prospective observational study, 395 patients who had an acute stroke admitted to an intensive care unit underwent fiberoptic endoscopic evaluation of swallowing and citric acid cough reflex testing at 0.4 mol/L. Dysphagia severity was rated using the Fiberoptic Endoscopic Dysphagia Severity Scale, with additional measures of secretion management, airway invasion and oral intake. Accuracy of cough reflex testing was calculated against fiberoptic endoscopic evaluation of swallowing. Ordinal and binary logistic regression assessed associations between cough reflex, dysphagia severity, pneumonia and mortality, including interactions.Results Cough reflex testing showed 75% sensitivity and 55% specificity for silent aspiration and 78% sensitivity and 43% specificity for any aspiration. Absent or weakened cough reflex predicted severe dysphagia, impaired secretion management, increased aspiration risk, restricted oral intake and reduced spontaneous swallowing (p<0.001). Older age, stroke severity, impaired cough reflex and dysphagia severity predicted mortality. Preserved cough reduced pneumonia risk only in mild dysphagia.Discussion Impaired cough reflex independently predicted poststroke dysphagia severity, impaired secretion management, aspiration risk, restricted oral intake and poorer functional outcome. Preserved cough conferred protection against pneumonia only in mild dysphagia, whereas in moderate to severe dysphagia aspiration burden and systemic vulnerability likely predominate, limiting clinical relevance of cough testing.Conclusion Cough reflex testing provides meaningful information on poststroke dysphagia severity and airway protection and may support risk stratification when instrumental swallowing assessment is unavailable.
Large vessel occlusion (LVO) is a severe subtype of acute ischaemic stroke, for which endovascular therapy significantly improves clinical outcomes. Expediting time to reperfusion is critical; however, conventional in-hospital workflows based on CT or MRI are frequently hindered by treatment delays. Direct Transfer to the Angiography Suite (DTAS) is an emerging care strategy in which patients with suspected or confirmed LVO bypass the emergency department and standard imaging. Using flat-panel CT or sliding-gantry CT combined with digital subtraction angiography, the DTAS workflow facilitates rapid diagnosis and prompt reperfusion therapy, thereby significantly reducing door-to-reperfusion time. Drawing on evidence from international and domestic studies, the Chinese Stroke Association convened an expert panel to develop this guideline, which systematically delineates the DTAS strategy, infrastructure requirements, diagnostic and therapeutic workflows and quality control indicators.
OBJECTIVE:In this retrospective multicentre cohort study, we aimed to develop and validate an interpretable machine learning (ML) model for early post-stroke epilepsy (PSE) prediction in patients who underwent mechanical thrombectomy (MT). We hypothesised that an ML model developed using electronic medical record data can accurately predict the risk of PSE in patients with acute ischaemic stroke treated with MT. METHODS:We collected data from 1185 adult patients who underwent MT between 2017 and 2022 at two hospitals for model development and used data from three external centres for validation. The key variables were selected using Cox regression, least absolute shrinkage and selection operator regression and Boruta. Eight ML algorithms were used for model development. The model performance was evaluated using the concordance index (C-index) and integrated Brier scores. Additionally, the 1-year, 3-year and 5-year PSE risk prediction accuracies were assessed using the areas under the receiver operating characteristic curves (AUCs) and calibration curves. Decision curve analysis was used to evaluate the clinical utility, and the feature importance was quantified. RESULTS:An optimal combination comprising nine features was used for model development. Of the eight ML models, the random survival forest (RSF) model demonstrated optimal performance and maintained robust discriminative accuracy across the three external validation cohorts (C-index: 0.812; AUC: 0.748-0.837; C-index: 0.822; AUC: 0.795-0.839 and C-index: 0.763; AUC: 0.763-0.833). Finally, we developed an online calculator (https://pseshiny.shinyapps.io/shinydashboard_sa_1model/) based on the RSF model. SIGNIFICANCE:This prediction model could help identify patients at high risk of developing PSE following MT and support individualised treatment strategies.
Introduction Systemic inflammation is associated with poor outcomes in symptomatic intracranial atherosclerotic stenosis (sICAS); however, the underlying mechanisms remain unclear. We investigated whether urinary albumin-to-creatinine ratio (UACR), as a clinically accessible marker of endothelial dysfunction-related microvascular injury, may mediate the association between inflammation and prognosis.Patients and methods We analysed 2,267 patients with sICAS from the Third China National Stroke Registry. High-sensitivity C-reactive protein (hsCRP) ≥ 2 mg/L and UACR ≥ 30 mg/g were exposures, and poor outcome (modified Rankin Scale (mRS) 3–6) at 90 days was the endpoint. Multivariable logistic regression assessed independent associations, and mediation analysis quantified the contribution of UACR to the hsCRP–outcome association. In a 217-patient sICAS-Computational Fluid Dynamics (sICAS-CFD) cohort, patient-specific models examined links between UACR and post-stenotic perfusion.Results Both high-sensitivity C reactive protein (hsCRP) ≥2 mg/L (adjusted OR (aOR) 1.43, 95% CI 1.12 to 1.84) and UACR ≥30 mg/g (aOR 1.91, 95% CI 1.49 to 2.45) were independently associated with 90-day mRS 3–6. In a prespecified mediation framework, UACR accounted for an estimated 22.2% of the association between elevated hsCRP and 90-day poor outcome (p=0.008), with larger indirect effects in patients with elevated systolic blood pressure (proportion mediated (PM) 17.5%) or diabetes (PM 26.4%; p<0.05), consistent with systemic microvascular vulnerability. In the computational fluid dynamics cohort, hypoperfused patients with poststenotic mean arterial pressure ≥70 mm Hg exhibited higher UACR than those with lower pressure (p=0.040).Discussion and conclusion In sICAS, UACR statistically mediated the association between inflammation and functional outcome, and higher UACR was exploratorily associated with poststenotic perfusion measures, providing exploratory haemodynamic context that may help explain variation in perfusion vulnerability.
Piezo1 is a mechanoreceptor cation channel that responds to various physical and environmental stimuli to facilitate an influx of cations, thereby converting physical or chemical triggers into electrochemical activity. Highly expressed on the surface of macrophages, Piezo1 can modulate macrophage polarisation and behaviour to ultimately regulate various inflammatory pathways. Given the role of pro-inflammatory signalling and the delayed recovery of patients with metabolic syndrome who develop intracerebral haemorrhage (ICH), Piezo1 could be a potential target for enhanced patient recovery and outcomes after ICH. Piezo1 ion channels are activated by increased environmental stiffness and chemical ligands, such as lipopolysaccharides. These channels initiate a signalling cascade and an increase in Ca2+ influx in macrophages, which results in a variety of downstream effects, including cytoskeletal rearrangements for increased phagocytic activity and increased pro-inflammatory cytokine production. Piezo1 activation triggers the polarisation of macrophages into pro-inflammatory phenotypes while suppressing their conversion into inflammation-resolving phenotypes. In the context of ICH, both primary and pro-inflammatory secondary injury contribute to neurological damage. Suppressing Piezo1 attenuates brain oedema and neurological deficits after ICH, in part, by decreasing oligodendrocyte apoptosis and increasing cerebral blood flow. Given the unique characteristics of Piezo1 as a mechanosensitive ion channel, it shows promising potential as a target for ICH therapy. A timely conversion of pro-inflammatory macrophages into inflammation-resolving phenotypes via Piezo1 suppression may be the next step in improving post-ICH patient outcomes.
Small unruptured intracranial aneurysms (UIAs) are increasingly detected by imaging modalities widely used in clinical practice. The low rupture risk of small UIAs contrasts with the substantial proportion of small aneurysms in ruptured cases. Current aneurysm rupture prediction models are insufficient to assess the rupture risk of small UIAs accurately. Multidimensional risk assessment integrating clinical variables, aneurysm morphology, haemodynamic features, imaging or biological markers is proposed. A shared decision-making balances the risks of rupture and treatment not only with the aneurysm size. For asymptomatic small UIAs, precise risk stratification, the development of pharmacological strategies and improvements in treatment safety represent important directions for future research.
Background This study aimed to investigate the heterogeneity of topographic and connectomic mechanisms underlying diverse functional outcomes in patients with acute ischaemic stroke.Methods and results In 7891 patients from the Third China National Stroke Registry, arterial territory maps, structural disconnection (SDC) maps and functional disconnection (FDC) maps were generated based on their ischaemic lesions. Strategic brain components, associated with functional outcomes, assessed using the modified Rankin Scale scores, were identified using multiperturbation Shapley value analysis. Exploratory subgroup analysis revealed that the strategic components identified in the arterial territory maps and the FDC maps varied by sex and age, but remained consistent in the SDC maps.Conclusion Specific topographic distributions and disconnections associated with adverse functional outcomes were identified, revealing individual heterogeneity related to age and sex. These findings may serve as imaging biomarkers and help generate testable hypotheses for potential neuromodulation targets.
Background The role of renal function in patients with acute ischaemic stroke (AIS) receiving blood pressure (BP) lowering therapy remains incompletely understood. In this prespecified subgroup analysis of the CATIS-2 trial, we tested the hypothesis that baseline estimated glomerular filtration rate (eGFR) affects the relationship between early antihypertensive therapy and outcomes in AIS.Methods In the CATIS-2 trial, AIS patients were randomly assigned to early treatment (initiating BP-lowering agents within 24–48 hours of stroke onset) or delayed treatment (withholding such agents until day 8). The composite of functional dependence or death (modified Rankin Scale score ≥3) at day 90 was defined as the primary outcome. The treatment effect was analysed between different baseline eGFR values (<90 versus ≥90 mL/min per 1.73 m²).Results 4685 patients were finally enrolled. Among 1061 patients with eGFR<90, the risk of the primary outcome was higher in early treatment compared with delayed treatment (15.3% vs 10.5%; OR (OR) 1.55, 95% CI 1.07–2.23; p=0.02). In 3624 patients with eGFR≥90, no such difference was observed (10.7% vs 10.2%; OR 1.05, 95% CI 0.85 to 1.30; p=0.63). The interaction was marginally significant (p=0.07).Conclusions The modification effect of renal function on different antihypertensive timing for AIS was not observed. Further, adequately powered studies were warranted.Trial registration number NCT03479554.
Background Stroke rates rise steeply with age but data on tenecteplase in patients ≥80 years remain limited. This post-hoc analysis of the AcT trial compared tenecteplase with alteplase in this population.Methods The analysis included all Alteplase Compared to Tenecteplase in Patients with Acute Ischemic Stroke (AcT) trial participants aged 80 years or older who were randomised to tenecteplase (0.25 mg/kg single bolus) or alteplase (0.9 mg/kg over 60 min). The primary outcome was excellent functional recovery (Modified Rankin Scale (mRS) score: 0–1 at 90–120 days). Secondary outcomes included mRS score 0–2, ordinal mRS shift and safety endpoints including symptomatic intracerebral haemorrhage (sICH) and mortality. Generalised mixed-effects models adjusted for baseline covariates with site as a random effect. Exploratory analyses examined the treatment-by-time interaction using continuous onset-to-needle time (OTN), outcomes by endovascular thrombectomy (EVT) status and outcomes in patients aged≥90 years.Results Among 543 patients aged ≥80 years (286 tenecteplase, 257 alteplase; mean age 86.9 years), baseline characteristics were balanced. Rates for mRS 0–1 (22.7% vs 23.1%; adjusted RR 0.94, 95% CI 0.74 to 1.19; p=0.63) and mRS 0–2 (37.4% vs 35.5%; adjusted RR 1.02, 95% CI 0.85 to 1.13) were similar, with no significant shift across the ordinal mRS distribution. Mortality (24.5% vs 27.3%) and sICH (3.5% both groups) did not differ. Longer OTN was associated with lower functional independence (adjusted OR per 30 min delay 0.89, 95% CI 0.77 to 1.03), although this did not reach statistical significance. Outcomes were consistent across EVT (n=149) and non-EVT (n=394) subgroups and in patients aged ≥90 years (n=160).Conclusions Tenecteplase and alteplase showed comparable efficacy and safety in patients ≥80 years supporting tenecteplase as a reasonable alternative to alteplase in elderly stroke patients.
Background Reperfusion therapy, including thrombolysis and thrombectomy, is crucial for ischaemic stroke treatment. However, patient outcomes often remain suboptimal. Conventional regression models show limited accuracy in predicting outcomes after reperfusion therapy. Machine learning predictive models offer potential by integrating multidimensional data. However, their relative advantages over conventional regression models in this context remain uncertain.Aim We aim to compare the performance of conventional regression models, machine learning models in predicting the prognosis of patients undergoing reperfusion therapy.Methods We identified studies using regression or machine learning models to predict outcomes in patients with ischaemic stroke undergoing thrombolysis or thrombectomy. Model performance was summarised as the area under the receiver operating characteristic curve (AUC), with 95% CIs for prediction of modified Rankin Scale (mRS), symptomatic intracranial haemorrhage (sICH) and mortality. Heterogeneity was assessed using Cochran’s Q test. Pooled AUCs were calculated. Risk of bias was assessed using Prediction model Risk Of Bias Assessment Tool (PROBAST) and reporting quality was assessed using Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD).Summary of review In total, 53 studies were included, of which 37 reported AUCs with 95% CI on validation datasets. Pooled analyses were conducted for mRS (n=37), sICH (n=14) and mortality (n=2). Specifically, 24 studies used conventional regression models (pooled AUC 0.80 (95% CI 0.77 to 0.82)), while 13 used machine learning models (0.86 (0.81 to 0.90)). Pooled machine learning model performance showed significant improvement over conventional regression models (p=0.004). Significant differences in model performance were also observed in thrombolysis subgroup (pooled AUC 0.79 (95% CI 0.77 to 0.82) for conventional regression models vs 0.88 (0.80 to 0.96) for machine learning models, p for interaction=0.009).Conclusion Machine learning models generally outperformed conventional regression models in predicting outcomes after reperfusion therapy, highlighting their potential for prognostic prediction of patients with ischaemic stroke undergoing reperfusion therapy. However, the high risk of bias across studies and limited availability of external validation warrant cautious interpretation of the predictive performance.
