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Background This study investigated the relationships of neutrophil count (NC), neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) with cerebral small vessel disease (CSVD). Methods A total of 3052 community-dwelling residents from the Poly-vasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study were involved in this cross-sectional study. CSVD burden and imaging markers, including white matter hyperintensity (WMH), lacunes, cerebral microbleeds (CMBs) and enlarged perivascular spaces in basal ganglia (BG-EPVS), were assessed according to total CSVD burden score. The associations of NC, NLR and SII with CSVD and imaging markers were evaluated using logistic regression models. Furthermore, two-sample Mendelian randomization (MR) analysis was performed to investigate the genetically predicted effect of NC on CSVD. The prognostic performances of NC, NLR and SII for the presence of CSVD were assessed. Results At baseline, the mean age was 61.2 ± 6.7 years, and 53.5% of the participants were female. Higher NC was suggestively associated with increased total CSVD burden and modified total CSVD burden (Q4 vs. Q1: common odds ratio (cOR) 1.33, 95% CI 1.05–1.70; cOR 1.28, 95% CI 1.02–1.60) and marginally correlated with the presence of CSVD (OR 1.29, 95% CI 1.00–1.66). Furthermore, elevated NC was linked to a higher risk of lacune (OR 2.13, 95% CI 1.25–3.62) and moderate-to-severe BG-EPVS (OR 1.67, 95% CI 1.14–2.44). A greater NLR was related to moderate-to-severe BG-EPVS (OR 1.68, 95% CI 1.16–2.45). Individuals with a higher SII had an increased risk of modified WMH burden (OR 1.35, 95% CI 1.08–1.69) and moderate-to-severe BG-EPVS (OR 1.70, 95% CI 1.20–2.41). MR analysis showed that genetically predicted higher NC was associated with an increased risk of lacunar stroke (OR 1.20, 95% CI 1.04–1.39) and small vessel stroke (OR 1.21, 95% CI 1.06–1.38). The addition of NC to the basic model with traditional risk factors improved the predictive ability for the presence of CSVD, as validated by the net reclassification index and integrated discrimination index (all p  < 0.05). Conclusions This community-based population study found a suggestive association between NC and CSVD, especially for BG-EPVS and lacune, and provided evidence supporting the prognostic significance of NC.

Predictors of symptomatic intracranial hemorrhage (sICH) in Chinese patients with acute ischemic stroke treated with recombinant tissue plasminogen activator remain unclear. Data from the Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China (TIMS-China) study were assessed to explore risk factors for symptomatic intracranial hemorrhage after intravenous thrombolysis. Three candidate sICH definitions were analyzed. Among 1128 patients with acute ischemic stroke treated with intravenous rtPA within 4.5 hours of symptom onset, 23 (2.0%), 44(3.9%) and 61 (5.4%) experienced modified mSITS-MOST, ECASS II, and NINDS defined sICH, respectively. Multivariate logistic regression revealed independent risk factors for sICH were age≧70 years-old(sICH per NINDS, adjusted OR = 1.73[95%CI1.02-2.95],p = 0.04),diabetes(sICH per SITS-MOST, adjusted OR = 3.50 [95%CI1.34-9.16], p = 0.01), serum glucose on admission >9.0mmol/L(sICH per ECASS II, adjusted OR = 2.84[95%CI1.48-5.46], p = 0.002),NIHSS on admission>20(sICH per SITS-MOST, adjusted OR = 5.06[95%CI1.68-15.20], p = 0.004 or sICH per NINDS, adjusted OR 2.81[95%CI1.42-5.57], p = 0.003) and cardioembolism(sICH per SITS-MOST, adjusted OR = 7.09[95%CI2.41-20.87], p<0.001 or sICH per ECASS II, adjusted OR = 4.99[95%CI2.53-9.84], p<0.001)or sICH per NINDS, adjusted OR = 2.47[95%CI1.39-4.39], p = 0.002). Cardioembolism, NIHSS on admission higher than 20, serum glucose on admission higher than 9.0 mmol/L and age ≧70 years were independent risk factors for symptomatic intracranial hemorrhage in Chinese patients with acute ischemic stroke treated with recombinant tissue plasminogen activator.

Objective Contribution of individual and combined inflammatory markers in prognosis after stroke was still undefined. We aimed to investigate the association of systemic and local vascular inflammatory markers and recurrent stroke as well as impact on poor functional outcome. Methods In this pre-specified substudy of the Third China National Stroke Registry (CNSR-III), 10,472 consecutive acute ischemic stroke or TIA patients with available centralized-measured levels of Interleukin-6 (IL-6), high sensitive C-reactive protein (hsCRP), IL-1 receptor antagonist (IL-1Ra), lipoprotein-associated phospholipase A 2 mass (Lp-PLA 2 ) and activity (Lp-PLA 2 -A), and YKL-40 from 171 sites were enrolled. The primary outcomes consisted of stroke recurrence and poor functional outcome defined as modified Rankin Scale (mRS) score of 2–6 within 1 year. Results There were 1026 (9.8%) and 2395 (23.4%) patients with recurrent stroke and poor functional outcome within 1 year. The highest quartiles of IL-6 (adjusted HR, 1.36; 95% CI 1.13–1.64; P  = 0.001), hsCRP (adjusted HR, 1.41; 95% CI 1.17–1.69; P  = 0.0003) and YKL-40 (adjusted HR, 1.28; 95% CI 1.06–1.56; P  = 0.01) were associated with increased risk of recurrent stroke; and the highest quartiles of IL-6 (adjusted OR 1.93; 95% CI 1.64–2.27; P  < 0.0001), IL-1Ra (adjusted OR 1.60; 95% CI 1.37–1.87; P  < 0.0001), hsCRP (adjusted OR 1.60; 95% CI 1.37–1.86; P  < 0.0001) and YKL-40 (adjusted OR 1.21; 95% CI 1.03–1.42; P  = 0.02) were correlated with increased risk of poor functional outcome. In the multivariate stepwise regression analysis including all markers with backward selection, elevated levels of IL-6 or YKL-40 were associated with recurrent stroke (IL6: OR, 1.34; 95% CI 1.19–1.52; P  < 0.0001; YKL-40: OR, 1.01; 95% CI 1.01–1.03; P  = 0.004) and poor functional outcome (IL6: OR, 1.68; 95% CI 1.46–1.93; P  < 0.0001; YKL-40: OR, 1.02; 95% CI 1.01–1.03; P  = 0.0001). Adding IL-6 and YKL-40 significantly increased the area under the receiver operating characteristic curves for the prediction models of Essen Stroke Risk Score (0.03, P  < 0.0001) and Totaled Health Risks in Vascular Events Score (0.07, P  < 0.0001), and yielded continuous net reclassification improvement (19.0%, P  < 0.0001; 33.0, P  < 0.0001). Conclusions In the patients with ischemic stroke or TIA, IL-6 and YKL-40 were independently associated with recurrent stroke and poor functional outcome, and improved risk classification of clinical risk algorithms.

Background Cerebral small vessel disease (CSVD) is the most common neurological disorder associated with a high incidence of stroke and dementia. For the heterogeneity of the pathogenesis, effective preventive and therapeutic strategies remain limited. Reduced aquaporin-4 (AQP4) was reported in the development of CSVD, while its role and mechanisms have not been fully elucidated. Methods We employed logistic regression analysis to assess the association between AQP4 gene single-nucleotide polymorphisms (SNPs) and CSVD presence. The functional impact of SNP mutations on AQP4 gene was evaluated using a Luciferase assay. Subsequently, Aqp4 −/− mice were subjected to bilateral carotid artery stenosis (BCAS) surgery to detect the CSVD phenotype of Aqp4 reduction. Aqp4 +/+ and Aqp4 −/− mice in the Sham and BCAS groups were subjected to MRI, histological examinations, and behavioural tests. AAV2/9- Gfap - AQP4 M1 and AAV2/9- Gfap - AQP4 7×cMyc−Kras were used to investigate Aqp4 expression and translocation ability after BCAS. Furthermore, RNA-sequencing was performed on the corpus callosum (CC) and Aqp4 −/− astrocytes to identify transcriptional changes associated with Aqp4 deficiency. Results We identified four SNPs (rs335929, rs335930, rs335931 and rs455671) were significantly associated with CSVD presence. Among these, rs335929 variant was correlated with reduced AQP4 mRNA expression. Compared with Aqp4 +/+ mice, fractional anisotropy values were decreased in the Sham and BCAS groups in Aqp4 −/− mice. Under BCAS conditions, Aqp4 −/− mice exhibited more severe demyelination and myelin density in the CC. Intraventricular delivery of AAV2/9- Gfap - AQP4 M1 and AAV2/9- Gfap - AQP4 7×cMyc−Kras attenuated BCAS-induced white matter injury and cognitive function, no significant differences were observed between the two AAV treatment groups. RNA sequencing analysis indicated upregulation of inflammatory responses and complement cascades in the CC of Aqp4 −/− mice. Complement component 3 (C3) mRNA was notably elevated in astrocytes isolated from Aqp4 −/− mice. Treatment with a C3a receptor antagonist in Aqp4 −/ − mice improved myelin integrity and reduced MBP loss following BCAS. Conclusion Reduced AQP4 expression was associated with CSVD presence in clinical studies. Experimentally, Aqp4 deficiency has been shown to exacerbate white matter injury, that effect may be mediated by upregulation of C3 mRNA in Aqp4 -deficient astrocytes. Targeting C3 activation may represent a promising strategy to mitigate AQP4 loss-induced white matter injury in CSVD.

Background and purposeStroke is the leading cause of mortality and disability in China. Precise aetiological classification, imaging and biological markers may predict the prognosis of stroke. The Third China National Stroke Registry (CNSR-III), a nationwide registry of ischaemic stroke or transient ischaemic attack (TIA) in China based on aetiology, imaging and biology markers, will be considered to clarify the pathogenesis and prognostic factors of ischaemic stroke.MethodsBetween August 2015 and March 2018, the CNSR-III recruited consecutive patients with ischaemic stroke or TIA from 201 hospitals that cover 22 provinces and four municipalities in China. Clinical data were collected prospectively using an electronic data capture system by face-to-face interviews. Patients were followed for clinical outcomes at 3 months, 6 months and 1–5 year annually. Brain imaging, including brain MRI and CT, were completed at baseline. Blood samples were collected and biomarkers were tested at baseline.ResultsA total of 15 166 stroke patients were enrolled, among which 31.7% patients were women with the average age of 62.2±11.3 years. Ischaemic stroke was predominant (93.3%, n=14 146) and 1020 (6.7%) TIAs were enrolled.ConclusionsCNSR-III is a large scale nationwide registry in China. Data from this prospective registry may provide opportunity to evaluate imaging and biomarker prognostic determinants of stroke.

ObjectiveThis study aims to investigate the associations of glymphatic system with the presence, severity and neuroimaging phenotypes of cerebral small vessel disease (CSVD) in a community-based population.MethodThis report included 2219 community-dwelling people aged 50–75 years who participated in the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events cohort. The diffusivity along perivascular spaces based on diffusion tensor imaging (DTI-ALPS index) was measured to assess glymphatic pathway. The presence and severity of CSVD were estimated using a CSVD score (points from 0 to 6) and a modified CSVD score (points from 0 to 4), which were driven by 4 neuroimaging features of CSVD, including white matter hyperintensity (WMH), enlarged perivascular spaces (EPVS), lacunes, cerebral microbleeds. Brain atrophy (BA) was also evaluated. Binary or ordinal logistic regression analyses were carried out to investigate the relationships of DTI-ALPS index with CSVD.ResultThe mean age was 61.3 (SD 6.6) years, and 1019 (45.9%) participants were men. The average DTI-ALPS index was 1.67±0.14. Individuals in the first quartile (Q1) of the DTI-ALPS index had higher risks of the presence of CSVD (OR 1.77, 95% CI 1.33 to 2.35, p<0.001), modified presence of CSVD (odds ratio (OR) 1.80, 95% CI 1.38 to 2.34, p<0.001), total burden of CSVD (common OR (cOR) 1.89, 95% CI 1.43 to 2.49, p<0.001) and modified total burden of CSVD (cOR 1.95, 95% CI 1.51 to 2.50, p<0.001) compared with those in the fourth quartile (Q4). Additionally, individuals in Q1 of the DTI-ALPS index had increased risks of WMH burden, modified WMH burden, lacunes, basal ganglia-EPVS and BA (all p<0.05).ConclusionA lower DTI-ALPS index underlay the presence, severity and typical neuroimaging markers of CSVD, implying that glymphatic impairment may interact with CSVD-related pathology in the general ageing population.Trial registration numberNCT03178448.

There were limited studies comparing the anterior (AC) and posterior (PC) circulation acute ischemic strokes (AIS). Our study aimed to evaluate distinct features of AC and PC strokes regarding clinical, vascular risk, pathogenesis and outcome factors after endovascular procedures. This multicenter prospective study registered 873 patients with acute large occlusion of anterior circulation stroke (ACS) and posterior circulation stroke (PCS). Patients who underwent endovascular procedures were included in this study. The differences in ACS and PCS regarding baseline characteristics, post-operative intracranial hemorrhage and outcomes were evaluated. A total of 741 patients were included in the data analysis. Intravenous thrombolysis (31.5%), atrial fibrillation (22.7%) and stent thrombectomy (82.4%) were more frequently observed in ACS patients. While higher NIHSS score, hypertension (67.6%) and balloon angioplasty (20.7%) were more prevalent in PCS patients. Symptomatic intracranial hemorrhage was more common in ACS (7.4% vs 2.8%). However, a 3-month follow-up outcomes were better in ACS with higher functional independence and low mortality rate than PCS (46.8% vs 30.3% and 16.4% vs 33.8%, respectively, P < 0.01). In this large prospective study, there were significant differences in the pathogenesis of stroke and treatment procedure between ACS and PCS which influence the clinical outcome. These findings could lead to a tailored clinical procedures and treatment strategies to improve the prognosis in both groups.

BackgroundAlthough previous evidence generally agreed on the short-term dual antiplatelet therapy (DAPT) for mild stroke or transient ischaemic attack (TIA), there is no consensus on the optimal threshold for stroke severity and initiation timing of DAPT. We conducted an updated meta-analysis of randomised controlled trials to evaluate early DAPT versus single therapy in mild stroke or TIA.MethodsWe systematically reviewed double-blind and randomised controlled trials up to October 2024 evaluating DAPT versus monotherapy for acute mild, non-cardioembolic ischaemic stroke (National Institute of Health Stroke Scale; NIHSS≤5) or TIA within 72 hours of ictus. Random effects models generated risk ratio (RR) with 95% CIs for outcomes including stroke, composite vascular events, ischaemic stroke, major bleeding, haemorrhagic stroke and all-cause mortality.ResultsPooled data from five trials (n=27 559) demonstrated that DAPT versus monotherapy lowered the risk of stroke recurrence (RR, 0.77; 95% CI 0.70 to 0.83), composite vascular events (RR, 0.75; 95% CI 0.68 to 0.83) and ischaemic stroke (RR, 0.74; 95% CI 0.68 to 0.81). However, DAPT increased the risk of major bleeding (RR, 2.19; 95% CI 1.38 to 3.49) and haemorrhagic stroke (RR, 2.08; 95% CI 1.13 to 3.82), with no significant increase in the risk of all-cause mortality (RR, 1.28; 95% CI 0.95 to 1.71).ConclusionsFor acute mild stroke (NIHSS ≤5) or patients with TIA within 72 hours of ictus, early DAPT initiation demonstrates net clinical benefit through reducing ischaemic events, despite an increase in bleeding complications, without affecting mortality.

PurposeThe object of this study was to identify the distribution characteristics of insular gliomas and evaluate the efficiency of transcortical approach.MethodsInsular gliomas patients who underwent transcortical approach for the first time between March 2011 and July 2019 at our institute were analyzed.ResultsA total of 253 primary insular gliomas patients were enrolled in the study. Of all patients, 176 patients (69.6%) underwent gross total resection, 61 patients (24.1%) underwent subtotal resection and 16 patients (6.3%) underwent partial resection. According to Berger-Sanai classification, the gross total resection rates of different types of insular gliomas were as follows: Zone I (90.1%), zone II (50.0%), zone III (40.0%), zone IV (89.5%), zone I + II (43.5%), zone I + IV (74.6%), zone II + III (44.4%), zone III + IV (41.7%), Giant (34.5%). According to our modified classification, the gross total resection rates were as follows: anterior type (84.9%), posterior type (45.8%), anterior–posterior type (42.9%), giant type (34.5%). After surgery, new limb motor deficit was observed in 28 patients (11.1%), and 5 patients (2.0%) were left long-term limb motor disability. New language impairment occurred in 23 patients (9.1%), and 3 patients (1.2%) were left long-term language disability. The patients were followed up for 1 to 89.2 months (average, 39.9 ± 20.3 months). At the end of follow-up, tumor progression occurred in 98 (38.7%) patients and 71 (28.1%) patients died of their disease.ConclusionThis study demonstrated that the maximal safe resection of insular gliomas can be achieved by transcortical approach. Insular gliomas had the characteristic of forward distribution, anterior transcortical approach can provide enough surgical freedom for anterior type of insular gliomas. If anterior tumors can make route to the posterior parts, anterior transcortical approach was also applied to some anterior–posterior and giant types of insular gliomas without resection of excessive brain, which may reduce the incidence of neurological complications.

Background Gamma-glutamyl transferase (GGT) is involved in maintenance of physiological concentrations of glutathione in cells, and protects them from oxidative stress-induced damage. However, its role in post-stroke cognitive impairment (PSCI) remains unknown. Here, we investigated the effects of serum GGT on PSCI. Methods We conducted a prospective, multicenter cohort study. A total of 1, 957 participants with a minor ischemic stroke or transient ischemic attack whose baseline GGT levels were measured were enrolled from the Impairment of Cognition and Sleep (ICONS) study of the China National Stroke Registry-3 (CNSR-3). They were categorized into four groups according to quartiles of baseline GGT levels. Cognitive functions were assessed using the Montreal Cognitive Assessment (MoCA) approach. Multiple logistic regression models were performed to evaluate the relationship between GGT and PSCI at 3 months follow-up. Results Among the 1957 participants, 671 (34.29%) patients suffered PSCI at 3 months follow-up. The highest GGT level quartile group exhibited a lower risk of PSCI in the fully adjusted model [OR (95% CI): 0.69 (0.50-0.96)], relative to the lowest group. Moreover, incorporation of GGT to the conventional model resulted in slight improvements in PSCI outcomes after 3 months (NRI: 12.00%; IDI: 0.30%). Conclusions Serum GGT levels are inversely associated with the risk of PSCI, with extremely low levels being viable risk factors for PSCI.