Background:Diabetes is a risk factor of poor stroke outcomes. A randomized clinical trial has demonstrated that Panax notoginseng saponins (Xuesaitong soft capsules) can improve the functional outcome in ischemic stroke patients. However, it remains uncertain whether comorbid diabetes exerts an influence on the therapeutic outcomes of Xuesaitong. Methods:The PANDA (efficacy and safety of Panax notoginseng saponins in the treatment of adults with ischemic stroke in China) trial was a multicenter, randomized, double-blind, placebo-controlled trial comprising 3542 patients. The present prespecified analyses investigated the effect of concomitant use of antidiabetic drugs, a history of diabetes, and baseline fasting blood glucose levels on outcomes in participants randomized to receive Xuesaitong soft capsules versus placebo. The primary outcome was the proportion of patients achieving functional independence. Results:In the modified intention-to-treat dataset, there were 722 patients with diabetes or treated hyperglycemia during hospitalization (369 in the Xuesaitong group and 353 in the placebo group) and 2244 patients without (1118 in the Xuesaitong group and 1126 in the placebo group). Among patients with diabetes or treated hyperglycemia during hospitalization, the proportion of patients with functional independence at 3 months was 83.20 % (n = 307) in the Xuesaitong group and 79.60 % (n = 281) in the placebo group (odds ratio, 1.27; 95 % confidence intervals [CI], 0.87-1.85; P = 0.215). Regarding patients without diabetes or treated hyperglycemia during hospitalization, the proportion was 91.32 % (n = 1021) in the Xuesaitong group and 83.21 % (n = 937) in the control group (OR, 2.12; 95 % CI, 1.64-2.76; P < 0.001; P for interaction = 0.027). The sensitivity analyses indicated similar significant results. Conclusion:In the PANDA trial, patients without, rather than with, diabetes or treated hyperglycemia during hospitalization received greater benefit from Xuesaitong soft capsules regarding functional independence at 3 months.

BackgroundPrevious experimental studies have suggested synergistic effects of Panax notoginseng saponins combined with antiplatelet agents in ischemic stroke. However, large-scale real-world clinical evidence regarding the efficacy and safety of this combination remains limited. This study aimed to explore the efficacy and safety of Xuesaitong soft capsule plus antiplatelet agents in ischemic stroke patients.MethodsThis multicenter, controlled, retrospective real-world study included 38,652 patients with ischemic stroke who received either antiplatelet agents (aspirin and/or clopidogrel) alone (control group, N = 37,249) or Xuesaitong soft capsule plus antiplatelet agents (observational group, N = 1,403). Propensity score matching (PSM) was initially performed at a 1:20 ratio (N = 1,401 in the observational group vs. N = 27,955 in the control group). A 1:4 PSM sensitivity analysis was subsequently performed to evaluate the robustness of the findings (N = 1,401 in the observational group vs. N = 5,604 in the control group).ResultsAfter 1:20 matching, the 1-year major adverse cardiovascular and cerebrovascular event (MACCE) incidence was lower in the observational group than in the control group (14.99% vs. 18.71%) (P < 0.001). The 2- and 3-year MACCE incidences showed the same trend (both P < 0.001). Subgroup analyses indicated that the reduction in 1-year MACCE incidence was greater in patients aged 45–64 years, treated within 2 weeks after stroke onset, with MACCE occurring within 1 month after treatment, and without hypertension, hyperlipidemia, or coronary heart disease (all P < 0.05). The incidence of adverse events of special interest was lower in the observational group than in the control group (18.56% vs. 21.82%) (P = 0.004). The 1:4 PSM sensitivity analysis confirmed the robustness of the findings, with lower 1-year MACCE incidence in the observational group than in the control group (14.99% vs. 18.58%) (P = 0.002).ConclusionXuesaitong soft capsule combined with antiplatelet agents is associated with lower MACCE incidence and gastrointestinal adverse events compared to antiplatelet agents alone in ischemic stroke patients.

This study investigates how melatonin affects white matter damage and oligodendrocyte pyroptosis after ischemic stroke by modulating microglia polarization through the RORα/AMPKα/STAT1 pathway. A mouse model of middle cerebral artery occlusion (MCAO) was used, with melatonin (20 mg/kg) administered post-reperfusion and daily for 14 days. Neurological function and white matter damage were assessed, along with gasdermin D (GSDMD) and caspase-1 expression to evaluate pyroptosis. In vitro, a Transwell co-culture system of microglia and oligodendrocytes exposed to oxygen-glucose deprivation (OGD) was employed. The role of RORα in modulating microglia polarization and oligodendrocyte pyroptosis was explored using siRNA-mediated knockdown and AAV-based RORα shRNA microinjection. Melatonin reduced white matter injury, inhibited oligodendrocyte pyroptosis, and improved sensorimotor function. These effects were linked to reduced APC/caspase-1 and APC/GSDMD double-positive cells and were dependent on RORα signaling. Melatonin also shifted microglia from a pro-inflammatory to an anti-inflammatory phenotype, an effect reversed by RORα knockdown. In vitro, melatonin inhibited OGD-induced pyroptosis via the RORα/AMPKα/STAT1 pathway. These findings suggest that melatonin promotes long-term recovery by reducing neuroinflammation and protecting white matter integrity through RORα signaling, highlighting its potential as a therapeutic agent for stroke recovery.

Cerebral small vessel disease (CSVD) is a common, age-related microvascular brain disorder and a major vascular cause of cognitive impairment. However, individuals with similar magnetic resonance imaging (MRI) lesion burdens often follow different cognitive trajectories, indicating that conventional imaging captures only late-stage manifestations of a broader pathological cascade. This review focuses on cognitive heterogeneity in CSVD through a heterogeneity-oriented conceptual framework, discussing how divergent cognitive trajectories may arise through the interaction of lesion-related factors, network-mediated consequences, biological and pathological modifiers, and individual susceptibility factors. We highlight the importance of lesion topography, particularly damage to strategic network hubs and connections. Beyond focal lesions, structural network disruption and remote structural and functional abnormalities beyond MRI-visible lesions further shape clinical heterogeneity. We additionally examine biological and pathological modifiers, including molecular biomarkers, heterogeneous neuropathological substrates, and mixed pathology, as well as individual susceptibility factors, such as life-course influences, brain reserve, and resilience. Together, these interacting mechanisms help explain why individuals with comparable structural lesion burdens may experience divergent cognitive trajectories. By reframing CSVD-related cognitive impairment beyond a simple lesion-burden model, this review highlights implications for diagnosis, prognostication, and future individualized approaches to cognitive impairment in CSVD.

BACKGROUND:In acute ischemic stroke, early neurological deterioration following intravenous thrombolysis (IVT) is common and is associated with unfavorable outcomes, necessitating antiplatelet therapy. TREND-IVT (Trial of Early Aspirin After Intravenous Thrombolysis for Acute Ischemic Stroke) aims to evaluate the safety and efficacy of 300 mg aspirin administered within 3 hours after the initiation of IVT compared with standard antiplatelet therapy for improving functional outcomes in patients with acute ischemic stroke. METHODS:This multicenter, randomized, placebo-controlled trial in China recruits patients with acute ischemic stroke receiving IVT (alteplase/tenecteplase) who are not scheduled for endovascular therapy. Participants are randomized in a 1:1 ratio to receive either early aspirin or placebo within 3 hours of initiating IVT, followed by guideline-recommended standard antiplatelet therapy beginning 24 hours after IVT in both groups. The primary outcome is an excellent functional outcome, defined as a modified Rankin Scale (mRS) score 0 to 1 at 90 days. Secondary outcomes will include mRS score 0 to 1 at 30 days, mRS score 0 to 2 at 90 days, ordinal shift analysis of mRS scores at 90 days, and changes in the National Institutes of Health Stroke Scale scores within 7 days. Safety end points will include symptomatic intracerebral hemorrhage, any intracerebral hemorrhage within 48 hours, systemic bleeding, recurrent stroke, other vascular events, mortality, and other adverse events during the 90-day follow-up. A sample size of 1184 participants will provide 80% power to detect an 8% intergroup difference in the primary outcome rate (2-sided α=0.05). CONCLUSIONS:The trial will evaluate the safety and efficacy of early antiplatelet therapy with oral aspirin in patients with acute ischemic stroke treated with IVT and may provide a promising strategy for improving the functional outcomes in this patient population. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique Identifier: NCT06548971.

Dementia is an acquired brain dysfunction syndrome caused by neuronal damage or neurodegeneration. It severely affects patients’ daily life and social functioning. Because clinical treatment strategies vary across dementia types, accurate diagnosis and classification are crucial for effective intervention. Electroencephalography (EEG) is a non-invasive method for monitoring brain activity. However, EEG’s non-stationary nature and high inter-individual variability significantly hinder the development of generalizable diagnostic models. To address this, we propose a Spatio-Temporal-Frequency Fusion Transformer (STFFT) with augmentation-driven supervised contrastive learning for cross-subject dementia diagnosis. First, we apply data augmentation to increase the number of positive samples per subject, addressing the issue of insufficient positive samples within the same batch in contrastive learning. Then, the STFFT extracts low-dimensional, high-semantic features from the Short-Time Fourier Transform (STFT) domain of EEG signals. Finally, a dual-task projector jointly optimizes disease classification and contrastive learning using dynamic triplets to enhance discriminative classification features across subjects. Experiments show that the proposed method achieves higher classification accuracy than existing methods on all three benchmark datasets. These results highlight its potential for developing robust EEG-based dementia diagnostic systems.

Accurate and efficient cognitive assessment is essential for understanding individual brain function and supporting personalized health management. Conventional linear and frequency-domain electroencephalogram (EEG) analysis approaches often fail to accurately extract essential features due to the inherent nonlinear, nonstationary, and high noise characteristics of EEG signals. In this study, we propose a novel multifractal-causal synchronization (MFCSync) algorithm, integrating multifractal analysis with causality synchronization to effectively characterize global coordination and nonlinear dynamics of EEG signals. Specifically, we innovatively develop two core components: weighted amplitude-based multifractal detrended fluctuation analysis (WAMFDFA) and synchronized normalized and weighted partial conditional mutual information (SNW-PCMI). These are synergistically integrated within MFCSync, enabling comprehensive EEG characterization through joint capture of multifractal dynamics, causal interactions, and cross-channel synchronization patterns. To validate the effectiveness of the proposed MFCSync approach for cognitive assessment, we conduct experiments on three representative EEG datasets targeting core cognitive domains: spatial cognition (SC-EEG, n = 25), episodic memory (EM-EEG, n = 22), and age-related cognitive difference (MPI-LEMON-EEG, n = 228). Furthermore, to assess the generalizability of MFCSync beyond core cognitive domains, we include a functionally distinct motor imagery dataset (MMIDB-EEG, n = 109), which emphasizes sensorimotor integration. Experimental results show that MFCSync consistently outperforms traditional feature extraction approaches in terms of classification accuracy and stability, achieving average accuracies of 91.97% (SC-EEG), 92.37% (EM-EEG), 95.71% (MPILEMON-EEG), and 94.46% (MMIDB-EEG). These results highlight the superior scalability and robustness of our method across diverse cognitive states and large-scale datasets. In summary, this study introduces MFCSync as a novel and powerful EEG feature extraction framework that integrates multifractal dynamics and causality synchronization, offering a precise tool for cognitive assessment. Our findings demonstrate its strong potential for advancing intelligent and personalized monitoring of brain functions.

Early neurological deterioration (END) in patients with acute ischemic stroke (AIS) is a common phenomenon strongly associated with unfavorable outcomes. The TREND trial (NCT04491695) demonstrates the efficacy of intravenous tirofiban compared to oral aspirin in preventing END. The purpose of this study was to explore whether prior antiplatelet therapy (APT) affected the therapeutic effects of tirofiban. This prespecified post hoc analysis of the TREND trial stratified patients by prior antiplatelet use. The primary outcome was END4 (≥ 4 points increase in National Institutes of Health Stroke Scale [NIHSS] within 72 h). Secondary outcomes included END2 (≥ 2 points increase in NIHSS), early neurological improvement, 90-day functional outcomes, and safety events. Overall, 425 patients with AIS were analyzed, including 143 (33.6

Each year, millions of individuals lose their ability to move and communicate because of illnesses or accidents, creating an urgent need for innovative solutions that can restore language communication. While invasive brain-computer interfaces (BCIs) have demonstrated high speed and reliability in helping individuals regain communication abilities, their high costs and surgical risks make them impractical for temporary conditions. Non-invasive BCIs offer a more affordable and accessible alternative, but they suffer from challenges such as lower decoding accuracy, slower speed, dependence on passive typing paradigms, and potential long-term health risks, including epilepsy. Furthermore, existing research has primarily focused on phonetic languages like English, leaving a critical gap for logographic languages like Chinese, which serves over one-sixth of the global population. This study introduces the Mind-Pinyin Speller, an innovative active-mode Chinese spelling system that decodes electroencephalogram (EEG) signals to identify the imagined writing of 23 consonants and 23 vowels. We have improved the CSP feature extraction strategy by employing a pairwise extraction method and have introduced a novel CNN-fuzzy-attention network (CFAN) that integrates a fuzzy layer into the CNN-transformer structure. Our system achieves an average output accuracy of 75.7 % for both vowels and consonants, with an information transfer rate (ITR) of 160 bits/min, doubling the 80 bits/min typically observed in existing BCI spelling systems. Users can produce a vowels and consonants in less than three seconds, enabling an estimated generation of up to ten Chinese characters per minute. By directly tackling the linguistic complexity of Chinese and leveraging active imagination for spelling, the Mind-Pinyin Speller delivers a high-speed solution tailored for individuals with speech and motor impairments. This breakthrough not only meets the unique needs of Chinese speakers but also paves the way for future innovations in BCI applications for logographic languages.

Artificial intelligence (AI) has shown great potential in decoding electroencephalogram (EEG) signals for cognitive analysis. However, existing models often struggle to generalize across subjects and scenarios due to the nonstationary and heterogeneous nature of neural dynamics. To address this challenge, we propose an AI-driven Shapley-informed Multilevel Information Fusion (SMIF) framework that unifies spatial, spectral, and temporal feature integration with uncertainty modeling and explainable fusion learning inspired from the game theory. The SMIF model combines a dynamic adaptive EEGNet for deformable spatial-temporal and spectral representation, an uncertainty-aware Transformer that leverages variance-guided attention to extract task-invariant features, and a causal multiscale CNN for hierarchical temporal fusion. A Shapley-based attribution mechanism further quantifies the contribution of brain regions and temporal segments, generating interpretable fusion maps that reveal neurophysiologically meaningful activation patterns. Experiments on episodic memory and motor imagery EEG datasets demonstrate that SMIF achieves robust generalization and improves classification performance by 12-18% over conventional baselines. This AI-driven and interpretable fusion framework enhances transparency, reliability, and generalizability in EEG-based intelligent systems, contributing to the advancement of explainable and human-centered engineering informatics.

Limited understanding of the pathophysiology of cerebral small vessel disease (CSVD) has hampered the development of effective treatments. Lipidomics offers a promising approach for identifying molecular signatures, clarifying underlying pathogenic mechanisms, and predicting disease severity and progression. A total of 1161 participants with lipidomic data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database were included and matched to each neuroimaging marker of CSVD separately, including cerebral microbleeds (CMBs, n = 578), white matter hyperintensities (WMHs, n = 650), lacunes (n = 1125), and CSVD burden (n = 546). Three complementary classification strategies (class-based grouping, model-based clustering, and individual lipid species) were employed to investigate lipid signatures across various CSVD markers. A multimodel regression framework followed by a series of sensitivity analyses was used to further identify lipid species showing robust associations with each CSVD marker. A total of 46 lipid classes, 25 lipid clusters, and 749 lipid species were quantified. Individuals with CSVD presented broadly reduced plasma lipid levels, particularly those of glycerophospholipids and glycerolipids. A multimodel regression framework initially screened 32 lipid species associated with the presence or progression of CSVD. Subsequent sensitivity analyses narrowed these to 13 robust species, including phosphatidylcholine, triacylglycerol, phosphatidylethanolamine, alkenyl-phosphatidylethanolamine, and sphingomyelin. Among these, elevated levels of PC(36:4)[+ OH] and TG(56:6)[NL-20:4] were associated with lower odds of CMBs and reduced WMH volumes, respectively, whereas higher levels of PC(15:0_20:3) and SM(d16:1/19:0) were linked to lower odds of lacunes, with all associations consistently observed across baseline, year 1, and year 2. This study revealed dysregulated lipid metabolism across distinct magnetic resonance imaging phenotypes of CSVD and revealed multiple lipid species that are consistently associated with the presence and progression of these phenotypes, underscoring the potential of lipidomics for the earlier identification and prevention of CSVD and informing future diagnostic development and mechanistic studies.

Background:Obesity exacerbates acute ischemic stroke (AIS) outcomes through metabolic dysfunction and chronic inflammation. Although Panax notoginseng saponins (PNS) have demonstrated efficacy in the treatment of AIS in the large-scale PANDA trial (N = 3,072; ChiCTR1800016363), their benefits in patients with obesity specifically, remain unclear. This study aimed to evaluate the effect of PNS on functional outcomes in patients with obesity. Methods:This analysis utilized individual patient data from the PANDA trial. Participants were stratified by body mass index (BMI), waist circumference (WC), and a combination of both metrics. The primary outcome was functional independence, defined as a modified Rankin Scale (mRS) score of 0-2 at 90 days. Adjusted odds ratios (aORs) were calculated using multivariable logistic regression. Results:Among 2,779 patients (mean age 60.7 ± 9.3 years), 58.3% were classified as overweight or obese by BMI, and 65% met criteria for abdominal obesity based on WC. PNS significantly improved rates of functional independence at 90 days across overweight (aOR = 2.05; 95% CI: 1.39-3.06), obesity (aOR = 2.18; 95% CI: 1.11-4.41), and abdominal obesity (aOR = 2.37; 95% CI: 1.73-3.28) subgroups. Consistent benefits were observed in patients with abdominal obesity irrespective of BMI category: lower BMI (aOR = 2.45; 95% CI: 1.34-4.61) and higher BMI (aOR = 2.40; 95% CI: 1.64-3.54). Conclusions:These results indicate that PNS may improve 90-day functional outcomes in patients with AIS and obesity, including those with abdominal obesity, warranting further prospective validation.

Background:Haematoma clearance is a key therapeutic target in intracerebral haemorrhage (ICH). Remote ischaemic conditioning (RIC) has shown potential to accelerate haematoma resolution in preclinical and early-phase clinical studies. We evaluated whether RIC improves functional outcomes in patients with acute supratentorial ICH not requiring surgical intervention. Methods:In this randomised, sham-controlled, outcome-blinded trial at 20 centres in China, adults (aged 18-80 years) with imaging-confirmed supratentorial ICH (volume 10-30 mL, National Institutes of Health Stroke Scale score 6-20, GCS >8) and no surgical indication were randomly assigned (1:1) to receive RIC or sham intervention for 7 days after randomisation, alongside standard medical management. RIC was initiated 24-48 h after onset using an upper-limb cuff inflated to 200 mmHg (sham: 30 mmHg) for five daily cycles of 5-min inflation/deflation. The primary outcome was an mRS score of 0-2 at 90 days (favourable outcome) in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT04657133. Findings:Between April 22, 2021, and April 30, 2024, 458 patients were enrolled (median age 58 years [interquartile range 51-68], female 29.3%). Favourable outcome was achieved in 156 (68.1%) of 229 patients in the RIC group and 163 (71.2%) of 229 in the sham group at 90 days (adjusted risk ratio 0.97, 95% confidence interval 0.87-1.08; p = 0.61). Serious adverse events within 180 days occurred in 19 (8.3%) of 229 patients in the RIC group and 20 (8.7%) in the sham group, and no deaths were attributed to the RIC intervention. Interpretation:In patients with acute supratentorial ICH managed without surgery, RIC did not improve 90-day functional outcomes. Further research should evaluate its efficacy in selected populations using optimised protocols. Funding:National Natural Science Foundation of China; Beijing Natural Science Foundation; National Key R&D Program of China.

INTRODUCTION:Alzheimer's disease and other dementias (ADODs) represent an escalating challenge for global health systems. This study evaluates spatiotemporal trends in ADOD burden from 1990 to 2023 and forecasts incidence trajectories in China through 2035. METHODS:Using the Global Burden of Disease Study 2023, we analyzed ADOD metrics globally, by socio-demographic index (SDI) quintile, and across China. Temporal trends were assessed via estimated annual percentage changes (EAPCs) and compound annual growth rates (CAGRs). Absolute burden shifts were partitioned into population growth, population aging, and epidemiological change using the Das Gupta decomposition. Future China-specific incidence was projected using a Bayesian age-period-cohort (BAPC) model. RESULTS:Global age-standardized incidence rates (ASIRs) exhibited a marginal increase (EAPC: 0.06), with progressively higher rates across increasing SDI levels. Decomposition analysis identified population growth as the dominant contributor to rising incidence, peaking in low-SDI regions (94.72%), whereas population aging contributed more substantially in high-SDI regions (21.34%). China recorded the fastest ASIR growth (EAPC: 0.42), with estimated contributions from both population aging (20.03%) and epidemiological change (15.71%), particularly within the 60-79 age groups. While global mortality and disability-adjusted life years shifted toward the oldest-old (≥80 years), China experienced a disproportionate incidence increase among the younger-old (70-74 years; CAGR 1.10% vs. global 0.27%). However, BAPC projections suggest a plateau or decline in incidence among the younger-old in China, contrasted by persistent increases among the oldest-old, with the most pronounced growth observed in the ≥95-year age group. CONCLUSION:China is undergoing a distinct dementia transition characterized by rising younger-old incidence and prolonged disease duration. This pattern suggests a need to combine earlier risk reduction with strengthened integrated long-term care for the oldest-old. The trajectory serves as a reference for rapidly aging middle-to-high SDI nations.

This review explores the transformative impact of artificial intelligence (AI) on neuromodulation, highlighting its shift from fixed protocols to personalized therapy. AI facilitates this through two main approaches: pre-treatment optimization, which uses multimodal data for pretreatment planning and outcome prediction; and dynamic adaptation, enabling real-time parameter adjustment in closed-loop systems like interactive neurostimulation and brain-computer interfaces. Furthermore, integration with telemedicine not only extends therapeutic reach but also accumulates real-world data, which is essential for scaling and refining AI models. However, clinical implementation faces challenges including data standardization, model interpretability, regulatory approval, and clinical workflow integration. Overcoming these challenges is essential to fully realize the potential of AI in creating more effective, adaptive, and patient-specific neuromodulation therapies.

While prior meta-analyses have demonstrated the benefits of lipid-lowering agents for atherosclerotic cardiovascular disease prevention in high-risk populations with definite risk, the applicability of these findings to global community-based populations, where hemorrhagic risk profiles and optimal serum lipid levels might differ, remains less defined. This gap underscores the need to clarify the relationship between serum lipids and hemorrhagic stroke (HS) risk in a broader community-based population. PubMed, Ovid, and the Cochrane Library were searched from inception to May 21, 2025, for observational prospective cohorts in populations with no major disease, baseline serum lipid assessment, and first-attack HS. Risk ratios (RRs) with 95

BACKGROUND AND OBJECTIVES:Although edaravone dexborneol, a multitarget cytoprotective drug, has demonstrated benefits in previous clinical trials, its actual clinical efficacy and safety in patients with acute ischemic stroke (AIS) remain unclear. This study aimed to test the hypothesis that edaravone dexborneol is associated with better outcomes in patients with AIS in real-world clinical practice. METHODS:We conducted a prospective, multicenter, real-world cohort study at 72 centers in China from January 14 to July 4, 2023. We included patients age 18 years or older, with AIS within 14 days of onset, and a prestroke modified Rankin Scale (mRS) of 0 or 1. Patients were divided into those receiving edaravone dexborneol (the exposed group) or not (the unexposed group). Clinical outcomes included favorable functional outcome (mRS score 0-1) at 90 days, symptomatic intracerebral hemorrhage (sICH) during the hospital, and all-cause mortality within 90 days. Multivariable logistic regression, propensity score matching (PSM), and inverse probability of treatment weighting (IPTW) analyses were conducted. RESULTS:Of 4,401 participants (2,904 men [66.8%]; median [interquartile range] age, 65 [57-72] years), 3,017 (68.6%) were treated with edaravone dexborneol. The exposed group was younger (65 [56-72] years vs 66 [58-74] years), had higher NIH Stroke Scale (3 [2-7] vs 3 [1-5]), and had shorter time from onset to admission (7.0 [2.5-24.0] hours vs 10.4 [2.8-48.0] hours). The exposed group had a higher proportion of patients with favorable functional outcome at 90 days compared with the unexposed group (68.6% [2,071/3,017] vs 66.0% [914/1,384], adjusted odds ratio [aOR] 1.23 [95% CI 1.06-1.43]). Moreover, sICH rates (0.4% vs 0.6%, aOR 0.44 [95% CI 0.14-1.44]) and mortality within 90 days (2.1% vs 3.3%, adjusted hazard ratio 0.89 [95% CI 0.58-1.37]) were similar in both groups. PSM and IPTW analyses yielded results consistent with the multivariate adjustment model. DISCUSSION:In this observational cohort study involving Chinese patients with AIS, edaravone dexborneol was associated with significantly better functional outcome at 90 days. Verification of our findings is warranted in other populations. TRIAL REGISTRATION INFORMATION:This trial is registered with Effectiveness and Safety of Edaravone Dexborneol in Acute Ischemic Stroke, number NCT05644223; submitted for registration on November 30, 2022; first patient enrollment was on January 14, 2023. CLASSIFICATION OF EVIDENCE:This study provides Class III evidence that treatment of patients with AIS with edaravone dexborneol is associated with significantly better functional outcome at 90 days measured using the mRS.

BACKGROUND:Patients with acute ischemic stroke (AIS) treated with intravenous thrombolysis (IVT) are at high risk of early neurological deterioration (END) due to increased platelet activation. OBJECTIVES:The objective of the study was to investigate the safety and efficacy of early antiplatelet therapy in reducing END postthrombolysis, and identify patients who may benefit. METHODS:In this observational study, AIS patients receiving IVT were stratified into the early tirofiban group and the control group according to antiplatelet therapy during the first 24 h following IVT. The primary endpoint was END4 (the National Institutes of Health Stroke Scale score increase ≥ 4 points) within 72 h following IVT. Binary logistic regression with propensity-score-matching was applied to analyze outcomes between the groups. RESULTS:Of the 319 patients enrolled, 66 in the early tirofiban group and 120 matched controls were analyzed. END4 occurred in four patients (6.1%) with early tirofiban and 15 patients (12.5%) in the control group. Early tirofiban administration was associated with lower odds of END4 (adjusted odd ratio, 0.2; 95% confidence interval, 0.1-0.8). Intracranial hemorrhage occurred in 2 (3.0%, none symptomatic) and 3 (2.5%, 2 symptomatic) patients, respectively, with no significant association between early tirofiban and major bleeding or mortality. Early tirofiban was significantly correlated with reduced END4 among patients aged 66-80 years, those without prestroke antiplatelet therapy, and those with neutral response to IVT (adjusted P < 0.05). CONCLUSION:Early tirofiban therapy following IVT was associated with reduced END without increased bleeding risk. Specific patient subgroups may potentially benefit from early antiplatelet therapy, further confirmation is needed.

BACKGROUND:Inflammation plays a critical role in severe cerebral venous thrombosis (CVT) pathogenesis, but the benefits of anti-inflammatory therapies remain unclear. This study aimed to investigate the association between steroid therapy combined with anticoagulation and the prognosis of acute/subacute severe CVT patients. METHODS:A prospective cohort study enrolled patients with acute/subacute severe CVT at Xuanwu Hospital (July 2020-January 2024). Patients were allocated into steroid and non-steroid groups based on the treatment they received. Functional outcomes (modified Rankin scale [mRS]) were evaluated at admission, discharge, and 6 months after discharge. Serum high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), cerebrospinal fluid (CSF) IL-6, and intracranial pressure were measured at admission and discharge in the steroid group. Fundoscopic Frisén grades were assessed at admission and 6 months after discharge. Univariate and multivariate logistic regression were used to evaluat associations between steroid use and favorable outcomes (mRS ≤2) at the 6-month follow-up. Paired tests assessed changes in hs-CRP and other variables before and after treatment, and Spearman's correlations were used to analyze relationships between these changes and functional improvements. RESULTS:A total of 107 and 58 patients in the steroid and non-steroid groups, respectively, were included in the analysis. Compared with the non-steroid group, the steroid group had a higher likelihood of achieving an mRS score of 0-2 (93.5% vs . 82.5%, odds ratio [OR] = 2.98, P  = 0.037) at the 6-month follow-up. After adjusting for confounding factors, the result remained consistent. Pulsed steroid therapy did not increase mortality during hospitalization or follow-up, nor did it lead to severe steroid-related complications (all P  >0.05). Patients in the steroid group showed a significant reduction in serum hs-CRP, IL-6, CSF IL-6, and intracranial pressure at discharge compared to at admission, as well as a significant reduction in the fundoscopic Frisén grade at the 6-month follow-up compare to at admission (all P  <0.001). A reduction in serum inflammatory marker levels during hospitalization positively correlated with improvements in functional outcomes ( P  <0.05). CONCLUSION:Short-term steroid use may be an effective and safe adjuvant therapy for acute/subacute severe CVT when used alongside standard anticoagulant treatments, which are likely due to suppression of the inflammatory response. However, these findings require further validation in randomized controlled trials. TRAIL REGISTRATION:ClinicalTrials.gov , NCT05990894.