Comparison of Outcomes between Stent Retriever Combined with Contact Aspiration and Contact Aspiration Alone in Patients without Hyperdense Artery Sign/Susceptibility Vessel Sign.

PURPOSE: To examine the relationship between hyperdense artery sign (HAS)/susceptibility vessel sign (SVS) and thrombus composition and evaluate the effect of HAS/SVS status on the association between first-line thrombectomy techniques and outcomes in patients with acute anterior circulation large vessel occlusion (LVO). MATERIALS AND METHODS: From January 2018 to June 2021, 103 consecutive patients with acute anterior circulation LVO (75 [63.1%] men; median age, 66 years) who underwent thrombectomy and for whom the removed clot was available for histological analyses were retrospectively reviewed. The presence of HAS and SVS was assessed on unenhanced computed tomography (CT) and susceptibility-weighted imaging, respectively. Association of first-line thrombectomy techniques (stent retriever [SR] combined with contact aspiration [CA] vs CA alone) with outcomes was assessed according to HAS/SVS status. RESULTS: Among the included patients, 55 (53.4%) were HAS/SVS-negative, and 69 (67.0%) underwent first-line SR + CA. Higher relative densities of fibrin/platelets (0.56 vs 0.51; P < .001) and lower relative densities of erythrocytes (0.32 vs 0.42; P < .001) were observed in HAS/SVS-negative patients compared with HAS/SVS-positive patients. First-line SR + CA was associated with reduced odds of distal embolization (adjusted odds ratio, 0.18; 95% CI, 0.04-0.83; P = .027) and a more favorable 90-day functional outcome (adjusted odds ratio, 5.29; 95% CI, 1.06-26.34; P = .042) in HAS/SVS-negative patients and a longer recanalization time (53 vs 25 minutes; P = .025) and higher risk of subarachnoid hemorrhage (24.2% vs 0%; P = .044) in HAS/SVS-positive patients. CONCLUSIONS: Absence of HAS/SVS may indicate a higher density of fibrin/platelets in the thrombus, and first-line SR + CA yielded superior functional outcomes than CA alone in patients with acute LVO without HAS/SVS.

Systematic identification of key basement membrane related genes as potential new biomarkers in Alzheimer's disease.

OBJECTIVE: The study aimed to identify biomarkers associated with basement membranes (BMs)-related genes (BMGs) in Alzheimer's disease (AD) and investigate their potential role in the progression of AD pathology. METHODS: Gene expression profiles were retrieved from Gene Expression Omnibus database. 222 human BMGs were collected from the relevant literature. Subsequently, the differentially expressed BMGs (DE-BMGs) were filtered, and the key DE-BMGs were identified using weighted gene correlation network analysis (WGCNA) and two machine learning algorithms. The expression levels, diagnostic values, clinical significances, enrichment analyses and regulatory networks of these candidate biomarkers were further examined. RESULTS: A total of 44 DE-BMGs were acquired by comparing AD temporal cortex with nondemented controls. Using WGCNA and machine learning, versiscan (VCAN), tissue inhibitor of metalloproteinase 1 (TIMP1), structural maintenance of chromosome 3 (SMC3), and laminin ß2 (LAMB2) were ultimately identified as candidate biomarkers, and they were verified in a murine model. These biomarkers had high diagnostic value (area under the curve (AUC)＞0.8). The diagnostic value of the four gene combination was then evaluated in multiple databases, yielding AUCs ranging from 0.688 to 1. Furthermore, a meaningful correlation between these biomarkers and AD pathology progression was observed. Finally, comprehensive analyses involving Hallmark pathway enrichment, immune cell infiltration analysis, transcriptional regulatory, and competitive endogenous RNA networks indicated that key DE-BMGs closely correlated with oxidative stress and immune dysfunction. CONCLUSION: Our study comprehensively identified four candidate BMGs and their combination model that play a crucial part in the diagnosis and pathogenesis of AD.

Novel insights into molecular signatures and pathogenic cell populations shared by systemic lupus erythematosus and vascular dementia.

Although vascular dementia (VD) and systemic lupus erythematosus (SLE) may share immune-mediated pathophysiologic processes, the underlying mechanisms are unclear. This study investigated shared gene signatures in SLE versus VD, as well as their potential molecular mechanisms. Bulk RNA sequencing (RNAseq) and single-cell or single-nucleus RNAseq (sc/snRNAseq) datasets from SLE blood samples and VD brain samples were obtained from Gene Expression Omnibus. The identification of genes associated with both SLE and VD was performed using the weighted gene co-expression network analysis (WGCNA) and machine learning algorithms. For the sc/snRNAseq data, an unbiased clustering pipeline based on Seurat and CellChat was used to determine the cellular landscape profile and examine intracellular communication, respectively. The results were subsequently validated using a mice model of SLE with cognitive dysfunction (female MRL/lpr mice). WGCNA and machine learning identified C1QA, LY96, CD163, and MS4A4A as key genes for SLE and VD. sc/snRNAseq analyses revealed that CD163 and MS4A4A were upregulated in mononuclear phagocytes (MPs) from SLE and VD samples and were associated with monocyte-macrophage differentiation. Intriguingly, LGALS9-associated molecular pathway, as the only signaling pathway common between SLE and VD via CellChat analysis, exhibited significant upregulation in cortical microglia of MRL/lpr mice. Our analyses identified C1QA, LY96, CD163, and MS4A4A as potential biomarkers for SLE and VD. Moreover, the upregulation of CD163/MS4A4A and activation of LGALS9 signaling in MPs may contribute to the pathogenesis of VD with SLE. These findings offer novel insight into the mechanisms underlying VD in SLE patients.

An old thrombus may potentially identify patients at higher risk of poor outcome in anterior circulation stroke undergoing thrombectomy.

PURPOSE: To investigate thrombus age and its association with clinical and procedural parameters in patients with acute ischemic stroke (AIS) due to anterior circulation occlusions. METHODS: The thrombi of 107 consecutive AIS patients with occlusions in anterior circulation large-arteries were collected during mechanical recanalization. By hematoxylin-eosin staining analysis, thrombi were classified as fresh (< 3 days) or old (≥ 3 days) according to the hemosiderin positivity. Old thrombi were further classified as thrombi with focal hemosiderin or diffuse hemosiderin according to their predominant distribution. Neuro-interventional data and clinical outcomes were compared based on thrombus age. RESULTS: We identified fresh thrombi in 29 patients and old thrombi in 78 patients. Compared with patients with fresh thrombi, patients with old thrombi were associated with (i) a longer mechanical recanalization time (p = 0.027), (ii) a higher percentage of fibrin/platelets and leukocytes (all p = 0.02) and a lower percentage of erythrocytes (p = 0.001), and (iii) less favorable clinical outcomes at discharge (p = 0.019) and 90 days later (OR = 2.76, 95% CI = 1.09-6.99, p = 0.032). Furthermore, 18 (16.8%) of all patients had focal hemosiderin in old thrombi, which was independently linked to a poor clinical outcome 90 days later (adjusted OR = 5.37, 95% CI = 1.14-25.28, p = 0.034). CONCLUSION: The presence of old thrombi, particularly those with focal hemosiderin, may aid in identifying patients with acute ischemic anterior circulation stroke who are at a higher risk of poor clinical outcome at 3-month follow-up.

Evaluating the Velocity and Extent of Cortical Venous Filling in Patients With Severe Middle Cerebral Artery Stenosis or Occlusion.

Objective: To investigate the velocity and extent of cortical venous filling (CVF) and its association with clinical manifestations in patients with severe stenosis or occlusion of the middle cerebral artery (MCA) using dynamic computed tomography angiography (CTA). Methods: Fifty-eight patients (36 symptomatic and 22 asymptomatic) with severe unilateral stenosis (≥70%) or occlusion of the MCA M1 segment who underwent dynamic CTA were included. Collateral status, antegrade flow, and CVF of each patient were observed using dynamic CTA. Three types of cortical veins were selected to observe the extent of CVF, and the absence of CVF (CVF-) was recorded. Based on the appearance of CVF in the superior sagittal sinus, instances of CVF, including early (CVF1), peak (CVF2), and late (CVF3) venous phases, were recorded. The differences in CVF times between the affected and contralateral hemispheres were represented as rCVFs, and CVF velocity was defined compared to the median time of each rCVF. Results: All CVF times in the affected hemisphere were longer than those in the contralateral hemisphere (p < 0.05). Patients with symptomatic MCA stenosis had more ipsilateral CVF- (p = 0.02) and more delayed CVF at rCVF2 and rCVF21 (rCVF2-rCVF1) (p = 0.03 and 0.001, respectively) compared to those with asymptomatic MCA stenosis. For symptomatic patients, fast CVF at rCVF21 was associated with poor collateral status (odds ratio [OR] 6.42, 95% confidence interval [CI] 1.37-30.05, p = 0.02), and ipsilateral CVF- in two cortical veins was associated with poor 3-month outcomes (adjusted OR 0.025, 95% CI 0.002-0.33, p = 0.005). Conclusions: Complete and fast CVF is essential for patients with symptomatic MCA stenosis or occlusion. The clinical value of additional CVF assessment should be explored in future studies to identify patients with severe MCA stenosis or occlusion at a higher risk of stroke occurrence and poor recovery.

High-Degree Middle Cerebral Artery Stenosis : Can Advanced 3D DSA-MRI Fusion Imaging Better Illustrate Plaques and Perforators?

PURPOSE: Endovascular treatment in severe middle cerebral artery (MCA) stenosis is controversial owing to high rates of periprocedural complications, especially occlusion of the lenticulostriate arteries (LSA). The characteristics of LSAs and the spatial relationships between MCA plaques and LSAs using the fusion of three-dimensional (3D) digital subtraction angiography (DSA) and magnetic resonance imaging (3D DSA-MRI fusion) were investigated. METHODS: We retrospectively analyzed data from 32 ischemic stroke or transient ischemic attack patients with severe MCA stenosis, who underwent MRI and DSA within 2 weeks after symptom onset. The patients were divided into culprit and non-culprit MCA stenosis groups. The 3D DSA-MRI fusion was performed on dedicated workstations, which allowed automated overlays of the target vessels. The characteristics of LSAs, plaque distribution and lesion patterns, and their relationships were evaluated. RESULTS: The 3D DSA-MRI fusion image was able to illustrate the spatial relationships between MCA plaques and LSA orifices. Of 42 LSA stems in 32 patients, 10 had MCA plaque over the LSA orifice and were all found in the culprit MCA stenosis group. Over half (51.9%) of the LSA stems in patients with culprit MCA stenosis originated from the stenotic MCA segment. The MCA plaque-LSA orifice spatial relationships were classified into four types, which were significantly different between the two groups (p = 0.016). CONCLUSION: The 3D DSA-MRI fusion technique enables visualization of the LSA orifice and MCA plaque and their spatial relationships. This classification of the type of spatial relationships can provide insights into the pathogenesis of MCA stroke and useful guides for treatment strategies.