Recent studies suggest that stroke may be associated with an increased prevalence of restless legs syndrome (RLS) as a comorbidity or a risk factor. We aimed to explore the association between acute ischemic stroke (AIS) and RLS, and the possible pathogenesis of acute ischemic stroke related restless legs syndrome (AIS-RLS), for guiding its diagnosis and treatment.

In this single-center, prospective study, we identified consecutive AIS patients and segregated into AIS-RLS group and non-AIS-RLS group based on the diagnostic criteria of RLS. The differences in baseline data, clinical features, examination results, stroke etiology, stroke location, and clinical prognosis (functional disability, cognitive and mood disorders) of the two groups were analyzed. Logistic regression analysis was used to evaluate the risk factors for RLS.

A total of 201 AIS patients were included in our study, and 21 (10.45 %) demonstrated RLS. Compared with non-AIS-RLS group, AIS-RLS group patients had higher systolic blood pressure (SBP) at admission (P < 0.05), higher mean 24-h SBP (P < 0.01), higher mean 24-h diastolic blood pressure (DBP) (P < 0.01), higher mean daytime SBP (P < 0.01), higher mean daytime DBP (P < 0.01), higher mean nocturnal SBP (P < 0.01), higher mean nocturnal DBP (P < 0.05), smaller variation coefficient of 24-h SBP (P < 0.05). The distribution of AIS-RLS and non-AIS-RLS was not different for each subtype according to the cortical and subcortical classification of lesion sites. The NIHSS score, GAD-7 score and PHQ-9 score were higher at 7 days (P < 0.05), and the modified Rankin scale (mRS) was higher at 3 months follow-up (P < 0.05) in the AIS-RLS group. In the logistic regression, the higher SBP at admission had a statistically significant effect on AIS-RLS(OR = 1.030,P = 0.016)even after adjusting for age and gender(OR = 1.030,P = 0.014).

Stroke anatomy did not differ between AIS-RLS and non-AIS-RLS groups. AIS-RLS group patients tend to experience higher blood pressure. Moreover, AIS-RLS patients had worse clinical prognosis (functional disability and mood disorders) compared with non-AIS-RLS patients.

Alzheimer's disease (AD) and vascular dementia (VaD) together contribute to almost 90 % of all dementia cases leading to major health challenges of our time with a substantial global socioeconomic burden. While in AD, the improved understanding of Amyloid beta (Aß) mismetabolism and tau hyperphosphorylation as pathophysiological hallmarks has led to significant clinical breakthroughs, similar advances in VaD are lacking. After comparing the clinical presentation, including risk factors, disease patterns, course of diseases and further diagnostic parameters for both forms of dementia, we highlight the importance of shared pathomechanisms found in AD and VaD: Endothelial damage, blood brain barrier (BBB) breakdown and hypoperfusion inducing oxidative stress and inflammation and thus trophic uncoupling in the neurovascular unit. A dysfunctional endothelium and BBB lead to the accumulation of neurotoxic molecules and Aß through impaired clearance, which in turn leads to neurodegeneration. In this context we discuss possible neuropathological parameters, which might serve as biomarkers and thus improve diagnostic accuracy or reveal targets for novel therapeutic strategies for both forms of dementia.

Chronic traumatic encephalopathy (CTE) is a progressive brain disease linked to repetitive head impacts (RHI), often incurred from contact sports, and can lead to dementia. Here, we investigated the association between RHI and white matter/vascular neuropathologies and their relative contribution to dementia status in deceased men 50 + years old with and without exposure to RHI from various types of contact and collision sports. Our sample included two RHI groups from the UNITE brain bank: (1) American Football players (RHI-AF, n = 79), and (2) non-AF contact and collision sport athletes (e.g., boxing, rugby; RHI-CCS, n = 49). Controls included similarly aged (± 5 years) male brain donors without RHI. A modified ischemic injury scale (mIIS) served as a global measure of white matter and vascular neuropathologies, encompassing nine subcomponents. Dementia was determined through diagnostic consensus conference based on interviews with families. Using linear regression models controlling for age at death, mIIS was different in RHI-AF versus non-RHI only (p = 0.036). Subsequent logistic regression of each mIIS subcomponent, controlling for age at death, demonstrated that worse white matter rarefaction (RHI-AF; Beta = 1.42, [95% CI 2.03-8.43]; RHI-CCS; Beta = 1.93, [95% CI 2.35-20.17]) and hippocampal sclerosis (RHI-AF; Beta = 2.01, [95% CI 2.69-20.81]; RHI-CCS; Beta = 2.19, [95% CI 2.49-32.10]) was more common in RHI groups from their controls. Further, logistic regressions found that higher global mIIS correlated with increased odds of dementia in only the RHI-AF group (p = 0.02), driven by white matter rarefaction (β = 0.94, [95% CI 1.66-4.00]) and hippocampal sclerosis (β = 1.08, [95% CI 1.35-6.42]). There were similar findings in RHI-CCS group for odds of dementia (p = 0.048), including white matter rarefaction (β = 0.68, [95% CI 1.22-3.21], p = 0.05). Overall, these results demonstrate that white matter  rarefaction and hippocampal sclerosis are linked to RHI exposure across all types of contact sports. Further, these pathologies contribute to dementia independent of p-tau pathology in American football players.

This study reported the clinical effect of intermittent oro-esophageal tube feeding (IOE) versus nasogastric tube feeding (NGT) on cerebral small vessel disease (CSVD) patients with dysphagia.

This randomized controlled study included 60 CSVD patients with dysphagia who received routine treatment. Participants were randomly divided into the intervention group (with IOE, n = 30) and the control group (with NGT, n = 30). The study lasted 15 days for each patient and assessments were conducted at baseline and after treatment. The primary outcome was dysphagia including Penetration-Aspiration Scale and Functional Oral Intake Scale. The secondary outcomes were 1) nutritional status, including (i) body mass index, (ii) serum albumin, (iii) hemoglobin, 2) aspiration pneumonia, 3) activities of daily living (ADL), 4) quality of life (QOL).

At admission, there were no significant differences (P > 0.05) in baseline assessment. After treatment, both groups showed significant improvement in dysphagia, nutritional status, ADL, and QOL. There were significant differences (P < 0.05) between the two groups in dysphagia, nutritional status [body mass index: (19.53 ± 1.40) kg/m2 vs. (18.35 ± 1.54) kg/m2; albumin: (42.06 ± 2.64) g/L vs. (39.49 ± 2.77) g/L; hemoglobin: (128.85 ± 6.34) mg/L vs. (123.14 ± 7.92) mg/L], aspiration pneumonia (6.67% vs. 33.33%), ADL [(69.07 ± 6.33) vs. (63.56 ± 6.75)], and QOL [(78.07 ± 8.64) vs. (72.48 ± 7.76)]. There were no severe adverse events during the treatment.

Compared to NGT, IOE demonstrated advantages in improving dysphagia, nutritional status, ADL, QOL, and aspiration pneumonia in CSVD patients with dysphagia who received routine treatment.

The incidence of minor ischemic stroke (MIS) and associated cognitive impairment is rising, particularly among younger individuals. Thus, both primary and secondary prevention strategies are essential.

This study investigated the risk factors for cerebral artery stenosis (CAS) in patients with MIS classified as large atherosclerosis (LAA) by TOAST, and examined the relationship between cognitive function and plasma lipoprotein-associated phospholipase A2 levels.

We conducted a retrospective analysis of 789 MIS patients admitted to two hospitals between January 2015 and December 2023. Patients were classified using the TOAST criteria, with vascular stenosis detected via computed tomography angiography (CTA) and magnetic resonance angiography (MRA). Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Univariate and multivariate regression analyses were performed to identify risk factors for CAS among LAA-type MIS patients.

Among the 789 patients, 494 (62.61%) had LAA. A total of 377 (76.32%) patients exhibited LAA-type vascular stenosis. Significant risk factors for CAS included a history of hypertension, diabetes, ischemic stroke, elevated fasting blood glucose, and plasma lipoprotein-associated phospholipase 2 levels (p < 0.05). Multivariate analysis revealed hypertension and increased phospholipase A2 as independent risk factors (OR = 2.046, OR = 1.059). The area under the ROC curve for plasma lipoprotein-associated phospholipase A2 predicting CAS was 0.700 (p < 0.0001). Additionally, a negative correlation was found between plasma lipoprotein-associated phospholipase A2 levels and MMSE scores (r = -0.218, p < 0.001).

LAA is the predominant cause of MIS, with high rates of vascular stenosis. Hypertension and elevated plasma lipoprotein-associated phospholipase A2 levels are significant independent risk factors for CAS, and increased plasma lipoprotein-associated phospholipase A2 correlates negatively with cognitive function.

This study aimed to investigate the dilation of lenticulostriate artery (LSA) identified by whole-brain vessel wall imaging (WB-VWI) in differentiating the etiologic subtypes of single subcortical infarction (SSI) and to determine whether the appearance of dilated LSA was associated with 90-day clinical outcomes in parental atherosclerotic disease (PAD)-related SSI.

Patients with acute SSI were prospectively enrolled and categorized into PAD-related SSI and cerebral small-vessel disease (CSVD)-related SSI groups. The imaging features of LSA morphology (branches, length, dilation, and tortuosity), plaques (burden, remodeling index, enhancement degree, and hyperintense plaque), and CSVD (white matter hyperintensity, lacunes, cerebral microbleed, and enlarged perivascular space) were evaluated. The logistic regression was performed to determine the association of dilated LSA with PAD-related SSI and 90-day clinical outcomes.

In total, 131 patients (mean age, 52.2 ± 13.2 years; 99 men) were included. The multivariate logistic regression analysis revealed that the presence of dilated LSAs (odds ratio (OR), 7.40; 95% confidence interval (CI): 1.88-29.17; p = 0.004)) was significantly associated with PAD-related SSI. Moreover, after adjusting for confounding factors, the association of poor outcomes with the total length of LSAs (OR, 0.94; 95% CI: 0.90-0.99; p = 0.011), dilated LSAs (OR, 0.001; 95% CI: 0.0001-0.08; p = 0.002), and plaque burden (OR, 1.35; 95% CI: 1.11-1.63; p = 0.002) remained statistically significant.

The dilation of LSA visualized on WB-VWI could differentiate various subtypes of SSI within LSA territory and was a prognostic imaging marker for 90-day clinical outcomes for PAD-related SSI.

Evaluation of LSA morphology based on WB-VWI can differentiate the pathogenesis and predict clinical outcomes in SSI, providing crucial insights into the etiologic mechanisms, risk stratification, and tailored therapies for these patients.

The prognosis of SSIs within lenticulostriate territory depend on the etiology of the disease. LSA dilation on WB-VWI was associated with parental atherosclerosis and better 90-day outcomes. Accurately identifying the etiology of SSIs in lenticulostriate territory assists in treatment decision-making.

The study evaluated the effect of an acute and a 2-week daily repetitive ischemic preconditioning (IPC) on conduit artery vascular function and thrombogenic clotting profile, in patients with a recent ischemic stroke.

Fourteen patients, aged 71 ± 8 years, with a cerebral small vessel occlusion stroke were included in a randomized, controlled, open-label cross-over study. Treatment consisted of 2 weeks of daily IPC, four 5-min rounds of upper-arm occlusion, interspersed by 5 min rest periods. Control was without treatment. Brachial artery flow-mediated dilation (FMD) was determined at baseline and after the control and treatment periods. Before and after each period, the patients underwent an acute bout of IPC. Blood samples were obtained for thrombogenic clotting profile at baseline and after the acute IPC bout, both before and after the control and treatment periods.

The period of daily IPC increased brachial artery diameter but did not influence FMD. Acutely, IPC was found to induce an increase in fractal dimension, indicating a denser clot microstructure, and a reduction in plasma levels of plasminogen activator inhibitor 1 (PAI-1). There was no effect of daily IPC on the basal thrombogenic clotting profile, or on the change in clotting profile induced by acute IPC.

Collectively, the data show that acute IPC leads to a prothrombotic clotting profile, despite antiplatelet therapy. Moreover, 2 weeks of daily treatment with IPC does not influence conduit artery vascular function or thrombogenicity in stroke patients.

To evaluate patients acute cerebral ischemia in order to assess for factors which may help to differentiate patients with small vessel involvement from those with large vessel involvement in an effort to determine diagnostic yield of vascular imaging.

We prospectively and consecutively evaluated all acute ischemic stroke patients at our medical center from May 16, 2021 to December 10, 2021. Distinction between small vessel and large vessel involvement was based upon clinical presentation, the results of brain imaging and either computed tomographic angiography, in the vast majority, or magnetic resonance angiography. Patient demographics and risk factors for stroke as well as therapeutic intervention was assessed.

Of the 90 patients studied, 59 had large vessel ischemia (66%) with 26 (44%) having large vessel occlusion and one had symptomatic high-grade middle cerebral artery stenosis. Conversely, none of the 31 patients with small vessel presentation (34%) had large vessel occlusion or high-grade stenosis. In addition, 19 out of 59 (32%) large vessel patients compared to 2 of 31 (6%) of the small vessel patients had atrial fibrillation identified as a potential mechanism with a p-value of 0.01 by univariate analysis and 0.17 by multivariate analysis. The routine use of vascular imaging in acute ischemic stroke is of very low yield in small vessel presentation with the presence of potential cardiogenic emboli is also relatively low. Efforts at accelerated identification of a small vessel mechanism, to avoid unnecessary testing, should provide significant value from both a patient management and cost standpoint.

The pathogenesis of neurovascular diseases and various types of dementia is tightly connected to cerebral circulation. An area that requires further exploration is the system of deep cerebral perforating arteries-arteries branching directly from high-pressure intracranial arteries, supplying vital neural structures such as the internal capsule, and characterized by a diameter of well below 1 mm, which makes them difficult to visualize with standard radiological examinations. This study aimed to analyze the morphology of the perforator origins, which constitute connection points between high-pressure intracranial arteries and microcirculation.

Twenty-three human basal ganglia specimens with the middle cerebral artery (MCA, including 172 perforating arteries) and ten brainstem specimens with the basilar artery (BA, including 162 perforating arteries) were prepared and scanned using microcomputed tomography. The geometry and structure of the perforating arteries were analyzed using radiological images and additional histological studies.

The ostia of the perforating arteries were ellipsoidal in shape with median stenosis severity of 23% and 20% for MCA and BA perforators, respectively. The local narrowing structure was typical of neointimal hyperplasia. Statistical analysis revealed that the severity of stenosis may be related to age and cardiovascular health.

Origins of the deep cerebral perforators are locally narrowed by neointimal hyperplasia, which may be a protective mechanism to adjust high blood pressure to the microcirculation. The narrowings may lead to chronic hypoperfusion and play a role in the pathophysiology of cerebral small vessel disease.

This study aims to compare the incidences of neurological deterioration (ND) and poor outcome (a modified Ranking scale > 2 points at discharge) among patients with different atherosclerotic stroke patterns. A total of 688 participants were categorized into 4 groups according to atherosclerotic stroke pattern: multiple small infarcts (MSI), single subcortical infarction (SSI), borderzone infarct (BZI) and large infarct groups. Among the 4 groups, MSI group had the lowest incidences of ND and poor outcome (13.5% and 16.2%, respectively). In multivariable analyses, for BZI patients, the risks of ND [odds ratio (OR) = 3.90, 95% confidence interval (CI) = 2.10-7.22, p < 0.001] and poor outcome (OR = 3.45, 95% CI = 1.67-7.14, p = 0.001) both significantly increased compared to MSI, both of which were the highest among the 4 stroke patterns. The neutrophil to lymphocyte ratio in BZI and large infarct groups were higher than in MSI and SSI groups [3.35 (2.28, 5.04) and 3.36 (2.53, 4.94) vs. 2.64 (1.89, 4.06) and 2.71 (1.93, 3.91), p < 0.001]. BZI group had the highest risks of ND and poor outcome among atherosclerotic stroke patients. BZI and large infarct patients had stronger poststroke inflammation than MSI and SSI patients.

Multiple injurious stimuli to the brain's endothelium results in brain endothelial cell activation and dysfunction (BECact/dys) with upregulation of inflammatory signaling cascades and a decrease in bioavailable nitric oxide respectively. These injurious stimuli initiate a brain injury and a response to injury wound healing genetically programed cascade of events, which result in cellular remodeling of the neurovascular unit and blood-brain barrier with increased inflammation and permeability. These remodeling changes also include the perivascular spaces that become dilated to form enlarged perivascular spaces (EPVS) that may be identified noninvasively by magnetic resonance imaging. These EPVS are associated with and considered to be a biomarker for cerebral small vessel disease (SVD) and a dysfunctional glymphatic system with impaired removal of neurotoxic waste, which ultimately results in neurodegeneration with impaired cognition and dementia. The penultimate section discusses the understudied role of venous cerebral circulation in relation to EPVS, SVD, and the vascular contribution to cognitive impairment (VCID). The focus of this review will be primarily on BECact/dys that associates with and contributes to the development of EPVS, SVD, and impaired glymphatic system efflux. Importantly, BECact/dys may be a key piece of the puzzle to unlock this complicated story of EPVS and SVD. Multiple transmission electron micrographs and illustrations will be utilized to depict anatomical ultrastructure and allow for the discussion of multiple functional molecular cascades.

Alzheimer's disease (AD) is the leading type of dementia globally, characterized by a complex pathogenesis that involves various comorbidities. An imbalance in the production and clearance of amyloid β-protein (Aβ) peptides in the brain is a key pathological mechanism of AD, with the glymphatic system playing a crucial role in Aβ clearance. Comorbidities associated with AD, such as diabetes, depression, and hypertension, not only affect Aβ production but also impair the brain's lymphatic system. Abnormalities in the structure and function of this system further weaken Aβ clearance capabilities, and the presence of comorbidities may exacerbate this process. This paper aims to review the role and specific mechanisms of impaired Aβ clearance via the glymphatic system in the context of AD comorbidities, providing new insights for the prevention and treatment of AD. Overall, the damage to the glymphatic system primarily focuses on aquaporin-4 (AQP4) and perivascular spaces (PVS), suggesting that maintaining the health of the glymphatic system may help slow the progression of AD and its comorbidities. Additionally, given the ongoing controversies regarding the structure of the glymphatic system, this paper revisits this structure and discusses the principles and characteristics of current detection methods for the glymphatic system.

Background/Objectives: Intracranial aneurysms (IAs) may be connected to interactions between large and small intracranial vessels. We aimed to investigate the association between IAs and cerebral small-vessel disease (CSVD) and assess CSVD impact on IA patient management. Methods: This retrospective study analyzed clinical data and MRI features of CSVD in 192 subarachnoid hemorrhage (SAH) patients: 136 with incidental IA, 147 with severe CSVD without SAH/IA, and 50 controls without SAH, IA, or severe CSVD. MRI assessments followed the Standards for Reporting Vascular Changes on Neuroimaging (STRIVE), with a total burden of small-vessel disease (TBSVD) score calculated. Statistical analyses included forward selection and binary logistic regression. Results: TBSVD differed significantly across groups (p < 0.001), except between SAH and IA groups (p = 0.8). Controls had the lowest TBSVD (1.00; 1.22 ± 0.996), followed by SAH (2.00; 2.08 ± 1.013) and IA groups (2.00; 2.04 ± 1.141), with the highest in the CSVD group (1.00; 1.22 ± 0.996). White-matter hyperintensity (WMH) patterns varied with IA rupture status (p = 0.044); type A was prevalent in SAH patients and type D in the IA group. Incorporating MRI CSVD features and TBSVD into risk assessments did not enhance IA prediction or outcome models. Conclusions: IA patients exhibit a higher CSVD burden than controls, suggesting a link between small and large intracranial vessels. WMH patterns distinguish between ruptured and unruptured IA patients, offering potential markers for IA rupture risk assessment and signaling a paradigm shift in understanding IAs and CSVD.

The novel MR imaging technique of vascular architecture mapping allows in vivo characterization of local changes in cerebral microvasculature, but reference ranges for vascular architecture mapping parameters in healthy brain tissue are lacking, limiting its potential applicability as an MR imaging biomarker in clinical practice. We conducted whole-brain vascular architecture mapping in a large cohort to establish vascular architecture mapping parameter references ranges and identify region-specific cortical and subcortical microvascular profiles.

This was a single-center examination of adult patients with unifocal, stable low-grade gliomas with multiband spin- and gradient-echo EPI sequence at 3T using parallel imaging. Voxelwise plotting of resulting values for gradient-echo (R2*) versus spin-echo (R2) relaxation rates during contrast agent bolus administration generates vessel vortex curves that allow the extraction of vascular architecture mapping parameters representative of, eg, vessel type, vessel radius, or CBV in the underlying voxel. Averaged whole-brain parametric maps were calculated for 9 parameters, and VOI analysis was conducted on the basis of a standardized brain atlas and individual cortical GM and WM segmentation.

Prevalence of vascular risk factors among subjects (n = 106; mean age, 39.2 [SD, 12.5] years; 56 women) was similar to those in the German population. Compared with WM, we found cortical GM to have larger mean vascular calibers (5.80 [SD, 0.59] versus 4.25 [SD, 0.62] P < .001), increased blood volume fraction (20.40 [SD, 4.49] s-1 versus 11.05 [SD, 2.44] s-1; P < .001), and a dominance of venous vessels. Distinct microvascular profiles emerged for cortical GM, where vascular architecture mapping vessel type indicator differed, eg, between the thalamus and cortical GM (mean, -2.47 [SD, 4.02] s-2 versus -5.41 [SD, 2.84] s-2; P < .001). Intraclass correlation coefficient values indicated overall high test-retest reliability for vascular architecture mapping parameter mean values when comparing multiple scans per subject.

Whole-brain vascular architecture mapping in the adult brain reveals region-specific microvascular profiles. The obtained parameter reference ranges for distinct anatomic and functional brain areas may be used for future vascular architecture mapping studies on cerebrovascular pathologies and might facilitate early discovery of microvascular changes, in, eg, neurodegeneration and neuro-oncology.

Atrial fibrillation (AF) is the most common cardiac arrhythmia, inducing accelerated and irregular beating. Beside well-known disabling symptoms - such as palpitations, reduced exercise tolerance, and chest discomfort - there is growing evidence that an alteration of deep cerebral hemodynamics due to AF increases the risk of vascular dementia and cognitive impairment, even in the absence of clinical strokes. The alteration of deep cerebral circulation in AF represents one of the least investigated among the possible mechanisms. Lenticulostriate arteries (LSAs) are small perforating arteries mainly departing from the middle cerebral artery (MCA) and susceptible to small vessel disease, which is one of the mechanisms of subcortical vascular dementia development. The purpose of this study is to investigate the impact of different LSAs morphologies on the cerebral hemodynamics during AF.

By combining a computational fluid dynamics (CFD) analysis of LSAs with 7T high-resolution magnetic resonance imaging (MRI), we performed different CFD-based multivariate regression analyses to detect which geometrical and morphological vessel features mostly affect AF hemodynamics in terms of wall shear stress. We exploited 17 cerebral 7T-MRI derived LSA vascular geometries extracted from 10 subjects and internal carotid artery data from validated 0D cardiovascular-cerebral modeling as inflow conditions.

Our results revealed that few geometrical variables - namely the size of the MCA and the bifurcation angles between MCA and LSA - are able to satisfactorily predict the AF impact. In particular, the present study indicates that LSA morphologies exhibiting markedly obtuse LSA-MCA inlet angles and small MCA size downstream of the LSA-MCA bifurcation may be more prone to vascular damage induced by AF.

The present MRI-based computational study has been able for the first time to: (i) investigate the net impact of LSAs vascular morphologies on cerebral hemodynamics during AF events; (ii) detect which combination of morphological features worsens the hemodynamic response in the presence of AF. Awaiting necessary clinical confirmation, our analysis suggests that the local hemodynamics of LSAs is affected by their geometrical features and some LSA morphologies undergo greater hemodynamic alterations in the presence of AF.

The China Antihypertensive Trial in Acute Ischemic Stroke II (CATIS-2) suggests that early antihypertensive treatment did not reduce the risk of dependency or death in acute ischemic stroke (AIS), compared with delayed treatment. Single subcortical infarction (SSI) is an important stroke subtype, and the association of antihypertensive timing with clinical outcomes is unclear.

To investigate the association of early vs delayed antihypertensive treatment with clinical outcomes in patients with SSI, stratified by the presence of parent artery disease (PAD) stenosis.

This secondary analysis of the CATIS-2 randomized clinical trial included 106 hospitals in China between June 2018 and July 2022. In CATIS-2, patients with AIS within 24 to 48 hours of symptoms onset and elevated systolic blood pressure were eligible. Patients with SSI detected in diffusion-weighted imaging were included in the current post hoc subgroup analysis. Patients were grouped into (1) SSI with PAD stenosis and (2) SSI without PAD stenosis. Statistical analysis was performed from July 2023 to May 2024.

Early (immediate) vs delayed (starting on day 8) antihypertensive therapy.

Primary outcome was the combination of functional dependency or death (modified Rankin Scale score ≥3) at 90 days.

Among 997 patients with SSI in CATIS-2 (mean [SD] age, 62.4 [9.8] years; 612 [61.4%] men), 116 (11.6%) had SSI with PAD and 881 (88.4%) had SSI without PAD. There was no significant difference in the primary outcome between early and delayed antihypertensive treatment groups among all patients with SSI (8.8% vs 7.1%; OR, 1.25 [95% CI, 0.79-1.99]; P = .34). Among patients with SSI with PAD, early antihypertensive treatment was associated with increased risk of the primary outcome compared with delayed treatment (23.4% vs 7.7%; OR, 3.67 [95% CI, 1.14-11.86]; P = .03); this finding was not observed in patients with SSI without PAD (6.6% vs 7.1%; OR, 0.93 [95% CI, 0.55-1.57]; P = .77). Significant interaction with treatment and presence of PAD stenosis was detected for the primary outcome (P for interaction = .04).

In this secondary analysis of a randomized clinical trial, early antihypertensive treatment was associated with an increased risk of functional dependency or death at 90 days among patients with SSI and coexisting PAD stenosis, compared with delayed antihypertensive treatment. Further studies are warranted for individualized BP management in patients with SSI by the presence of PAD.

ClinicalTrials.gov Identifier: NCT03479554.

Early neurological deterioration (END) is a frequent complication in patients with perforating artery territory infarction (PAI), leading to poorer outcomes. Therefore, we aimed to apply machine learning (ML) algorithms to predict the occurrence of END in PAI and investigate related risk factors.

This retrospective study analyzed a cohort of PAI patients, excluding those with severe stenosis of the parent artery. We included demographic characteristics, clinical features, laboratory data, and imaging variables. Recursive feature elimination with cross-validation (RFECV) was performed to identify critical features. Seven ML algorithms, namely logistic regression, random forest, adaptive boosting, gradient boosting decision tree, histogram-based gradient boosting, extreme gradient boosting, and category boosting, were developed to predict END in PAI patients using these critical features. We compared the accuracy of these models in predicting outcomes. Additionally, SHapley Additive exPlanations (SHAP) values were introduced to interpret the optimal model and assess the significance of input features.

The study enrolled 1,020 PAI patients with a mean age of 60.46 (range 49.11-71.81) years. Of these, 30.39% were women, and 129 (12.65%) experienced END. RFECV selected 13 critical features, including blood urea nitrogen (BUN), total cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C), apolipoprotein B (apoB), atrial fibrillation, loading dual antiplatelet therapy (DAPT), single antiplatelet therapy (SAPT), argatroban, the basal ganglia, the thalamus, the posterior choroidal arteries, maximal axial infarct diameter (measured at < 15 mm), and stroke subtype. The gradient-boosting decision tree had the highest area under the curve (0.914) among the seven ML algorithms. The SHAP analysis identified apoB as the most significant variable for END.

Our results suggest that ML algorithms, especially the gradient-boosting decision tree, are effective in predicting the occurrence of END in PAI patients.

Cerebral small vessel disease (SVD) has previously been associated with worse stroke outcome, vascular dementia, and specific post-stroke cognitive deficits. The underlying causal mechanisms of these associations are not yet fully understood. We investigated whether a relationship between SVD and certain stroke aetiologies or a specific stroke lesion anatomy provides a potential explanation.

In a retrospective observational study, we examined 859 patients with first-ever, non-SVD anterior circulation ischemic stroke (age = 69.0±15.2). We evaluated MRI imaging markers to assess an SVD burden score and mapped stroke lesions on diffusion-weighted MRI. We investigated the association of SVD burden with i) stroke aetiology, and ii) lesion anatomy using topographical statistical mapping.

With increasing SVD burden, stroke of cardioembolic aetiology was more frequent (ρ = 0.175; 95 %-CI = 0.103;0.244), whereas cervical artery dissection (ρ = -0.143; 95 %-CI = -0.198;-0.087) and a patent foramen ovale (ρ = -0.165; 95 %-CI = -0.220;-0.104) were less frequent stroke etiologies. However, no significant associations between SVD burden and stroke aetiology remained after additionally controlling for age (all p>0.125). Lesion-symptom-mapping and Bayesian statistics showed that SVD burden was not associated with a specific stroke lesion anatomy or size.

In patients with a high burden of SVD, non-SVD stroke is more likely to be caused by cardioembolic aetiology. The common risk factor of advanced age may link both pathologies and explain some of the existing associations between SVD and stroke. The SVD burden is not related to a specific stroke lesion location.

Prior studies have used the fluid-attenuated inversion recovery sequence signal intensity ratio (FLAIR-SIR) to predict those with an incomplete infarct that may safely receive acute thrombolytics. Clinical early neurologic deterioration (END) of small subcortical infarcts (SSIs) is suspected to occur due to delayed infarct completion. We aimed to understand if a lower FLAIR-SIR, suggestive of an incomplete infarct, would have a higher likelihood of SSI-related END.

A cross-sectional retrospective study was performed of those with an acute SSI (anterior or posterior circulation) without significant parent vessel steno-occlusive disease. END was defined as a new or worsened disabling neurologic deficit during the index hospitalization. Standard-of-care brain MRIs were reviewed from the hospitalization, and a FLAIR-SIR cutoff of ≤ 1.15 was used based on prior studies. Adjusted logistic regression models were used for analysis.

We identified 252 patients meeting inclusion criteria: median (IQR) age 68 (12) years, 38.5% (97/252) female, and 11% (28/252) with END. Tobacco use was more common in those without END (32%) compared with END (55%, p = 0.03). In adjusted analyses, a FLAIR-SIR cutoff of ≤ 1.15 yielded an odds ratio of 2.8 (95% CI 1.23-6.13, p = 0.012) of early neurological deterioration.

Those with a FLAIR-SIR ≤ 1.15 are nearly threefold more likely to develop SSI-related END.

Age-associated cerebral small vessel disease (CSVD) represents a clinically heterogenous condition, arising from diverse microvascular mechanisms. These lead to chronic cerebrovascular dysfunction and carry a substantial risk of subsequent stroke and vascular cognitive impairment in aging populations. Owing to advances in neuroimaging, in vivo visualization of cerebral vasculature abnormities and detection of CSVD, including lacunes, microinfarcts, microbleeds and white matter lesions, is now possible, but remains a resource-, skills- and time-intensive approach. As a result, there has been a recent proliferation of blood-based biomarker studies for CSVD aimed at developing accessible screening tools for early detection and risk stratification. However, a good understanding of the pathophysiological processes underpinning CSVD is needed to identify and assess clinically useful biomarkers. Here, we provide an overview of processes associated with CSVD pathogenesis, including endothelial injury and dysfunction, neuroinflammation, oxidative stress, perivascular neuronal damage as well as cardiovascular dysfunction. Then, we review clinical studies of the key biomolecules involved in the aforementioned processes. Lastly, we outline future trends and directions for CSVD biomarker discovery and clinical validation.

Perforating artery territorial infarction (PAI) caused by branch atheromatous disease (BAD) is prone to recurrence and early progression without an effective and well-documented antiplatelet treatment regimen. Tirofiban, an adjunctive antiplatelet agent, has shown great potential to treat acute ischaemic stroke. However, whether the combination of tirofiban and aspirin can improve the prognosis of PAI remains unclear.

To explore an effective and safe antiplatelet regimen for reducing the risk of recurrence and early neurological deterioration (END) in PAI caused by BAD by comparing the tirofiban and aspirin combination with placebo and aspirin combination.

Tirofiban combined with Aspirin in the Treatment of Acute Penetrating Artery Territory Infarction (STRATEGY) trial is an ongoing multicentre, randomised, placebo-controlled trial in China. Eligible patients shall be randomly assigned to receive standard aspirin with tirofiban or placebo on the first day and standard aspirin from days 2 to 90. The primary endpoint is a new stroke or END within 90 days. The primary safety endpoint is severe or moderate bleeding within 90 days.

The STRATEGY trial will assess whether tirofiban combined with aspirin is effective and safe in preventing recurrence and END in patients with PAI.

NCT05310968.

Intracranial arterial dolichoectasia (IADE) is a common arterial finding of dilation, elongation, or both, affecting large intracranial vessels, and associated with vascular risk factors, including hypertension. Associations of IADE with neuroimaging cerebral small vessel disease (CSVD) may be relevant for diagnosis and prognosis in patients with stroke. The study aimed to conduct an updated systematic review and meta-analysis of observational studies to investigate the relationships of IADE with well-defined CSVD markers in patients with ischaemic stroke.

We systematically searched PubMed, Embase, and Scopus for studies on IADE in ischaemic stroke patients with fulfilling predefined inclusion criteria. We pooled data to conduct a meta-analysis to compare the prevalence of SVD markers between patients with and without IADE groups using risk ratios (RRs) and 95% confidence intervals (CIs).

From 157 retrieved abstracts, we included six studies from seven publications comprising 6102 patients with ischaemic stroke. The mean age of patients was 52.8 years, and 3691 (60.5%) were male. IADE was diagnosed in 11.4% (95% CI 8.9-13.9) (761) of included patients; 51.8% (3160) had hypertension. Compared to patients without IADE, individuals diagnosed with IADE had a significantly increased prevalence of lacune (RR 1.67, 95% CI 1.36-2.06, P < 0.01, I2 = 0.00%), cerebral microbleeds (CMBs) (RR 2.56, 95% CI 1.53-4.28, P < 0.01, I2 = 84.95%) and white matter hyperintensities (WMHs) (RR 2.17, 95% CI 1.84-2.56, P < 0.01, I2 = 0.00%).

In patients with ischaemic stroke, IADE is associated with a higher prevalence of CSVD markers, including lacunes, CMBs, and WMHs. Further studies are needed to clarify the mechanisms underlying these associations and their potential relevance for the understanding, diagnosis, and treatment of CSVD.

The present study investigated the association between head computed tomography (CT) findings and mortality in patients with COVID-19. Specifically, we focused on low-density lesions identified on head CT screenings.

We performed a single-center, retrospective cohort study based on data obtained from the medical charts of inpatients admitted to the Tokyo Metropolitan Hiroo Hospital between January 1 and December 31, 2021. We focused on the basal ganglia--a representative anatomical region for assessing routine head CT in patients with COVID-19. Patients were divided into two groups based on the presence or absence of low-density lesions in the basal ganglia. The primary outcome was all-cause in-hospital mortality, and the secondary outcome was the length of hospital stay. We performed multivariable regression analyses for outcomes to adjust for patients' background and disease severity.

During the study period, 1,906 COVID-19 patients were admitted to our facility. Among them, 1,203 patients underwent head CT evaluations and were included in this study. The median age was 56 years (interquartile range: 43-76 years) and 725 patients (60.3%) were male. A total of 235 (19.5%) patients required oxygen therapy on admission and 1,051 (87.4%) patients had pneumonia. Crude in-hospital mortality was 6.1% and the median length of hospital stay was 10 days (interquartile range: 8-14 days). The multivariate regression analyses showed that low-density lesions in the basal ganglia were significantly associated with increased in-hospital mortality and prolonged hospital stay.

The presence of ischemic changes in the basal ganglia denoted by low-density findings may be a promising prognostic factor in patients with COVID-19.

Stroke is a major cause of death and disability worldwide. Endovascular thrombectomy has been impactful in decreasing mortality. However, many clinical results continue to show suboptimal functional outcomes despite high recanalization rates. This gap in recanalization and symptomatic improvement suggests a need for adjunctive therapies in post-thrombectomy care. With greater insight into ischemia-reperfusion injury, recent preclinical testing of neuroprotective agents has shifted towards preventing oxidative stress through upregulation of antioxidants and downstream effectors, with positive results. Advances in multiple neuroprotective therapies, including uric acid, activated protein C, nerinetide, otaplimastat, imatinib, verapamil, butylphthalide, edaravone, nelonemdaz, ApTOLL, regional hypothermia, remote ischemic conditioning, normobaric oxygen, and especially nuclear factor erythroid 2-related factor 2, have promising evidence for improving stroke care. Sedation and blood pressure management in endovascular thrombectomy also play crucial roles in improved stroke outcomes. A hand-in-hand approach with both endovascular therapy and neuroprotection may be the key to targeting disability due to stroke.

Ischemic stroke affects millions of individuals worldwide and a high prevalence of survivors experience cognitive deficits. At present, the underlying mechanisms that drive post-stroke cognitive decline are not well understood. Microglia play a critical role in the post-stroke inflammatory response, but experimental studies show that an accumulation of chronically activated microglia can be harmful and associates with cognitive impairment. This study assessed the effect of acute post-stroke minocycline treatment on chronic microglia and astrocyte expression within the infarct and remote white matter regions, as well as its effect on various domains of cognitive function post-stroke. Nine-month-old male rats received an injection of endothelin-1 into the right dorsal striatum to induce transient focal ischemia, and then were treated with minocycline or saline for 4 days post-stroke. Rats were tested using a series of lever-pressing tasks and the Morris water maze to assess striatal-based learning, cognitive flexibility, and spatial learning and reference memory. We found that minocycline-treated rats had smaller stroke-induced infarcts and less microglia activation in the infarct area and remote white matter regions compared to saline-treated rats at 28 days post-stroke. The behavioural testing results differed according to the cognitive domain; whereas minocycline-treated rats trended towards improved striatal-based learning in a lever-pressing task, but cognitive flexibility was unaffected during the subsequent set-shifting task. Furthermore, minocycline treatment unexpectedly impaired spatial learning, yet it did not alter reference memory. Collectively, we show that post-stroke minocycline treatment can reduce chronic microglia activation even in remote brain regions, with domain-specific effects on cognitive function.

At present, the incidence rate of ischemic stroke in young people is increasing yearly, and the age of onset is increasingly young. Therefore, primary and secondary prevention of ischemic stroke in young people, especially secondary prevention, is particularly crucial.

We aimed to comprehensively evaluate risk factors for stroke recurrence in first-ever young ischemic stroke (YIS) patients.

The meta-analysis was used to quantitatively analyze the research results on risk factors for stroke recurrence in first-ever YIS patients both domestically and internationally. Stata12.0 software was used for heterogeneity testing, publication bias analysis, sensitivity analysis, and the calculation of combined odds ratios and 95% confidence intervals.

The odds ratio (OR) values of the relationship between hypertension and hyperlipidemia and recurrence of first-ever YIS were 1.54 (1.05-2.26) and 1.12 (1.00-1.25), respectively. The OR values of male sex, type 2 diabetes, smoking, drinking and YIS recurrence were 1.66 (0.98-2.79), 1.01 (0.64-1.59), 1.21 (0.83-1.76), and 1.28 (0.82-2.53), respectively. The relationship between male sex, type 2 diabetes, smoking, drinking and YIS recurrence was ambiguous.

Hypertension and hyperlipidemia are important risk factors for stroke recurrence in first-ever YIS patients, and active intervention should be taken.

Culturing cerebrovascular smooth muscle cells (CVSMCs) in vitro can provide a model for studying many cerebrovascular diseases. This study describes a convenient and efficient method to obtain mouse CVSMCs by enzyme digestion.

Mouse circle of Willis was isolated, digested, and cultured with platelet-derived growth factor-BB (PDGF-BB) to promote CVSMC growth, and CVSMCs were identified by morphology, immunofluorescence analysis, and flow cytometry. The effect of PDGF-BB on vascular smooth muscle cell (VSMC) proliferation was evaluated by cell counting kit (CCK)-8 assay, morphological observations, Western blotting, and flow cytometry.

CVSMCs cultured in a PDGF-BB-free culture medium had a typical peak-to-valley growth pattern after approximately 14 days. Immunofluorescence staining and flow cytometry detected strong positive expression of the cell type-specific markers alpha-smooth muscle actin (α-SMA), smooth muscle myosin heavy chain 11 (SMMHC), smooth muscle protein 22 (SM22), calponin, and desmin. In the CCK-8 assay and Western blotting, cells incubated with PDGF-BB had significantly enhanced proliferation compared to those without PDGF-BB.

We obtained highly purified VSMCs from the mouse circle of Willis using simple methods, providing experimental materials for studying the pathogenesis and treatment of neurovascular diseases in vitro. Moreover, the experimental efficiency improved with PDGF-BB, shortening the cell cultivation period.

The mechanism of gait disorder in patients with cerebral small vessel disease (CSVD) remains unclear. Limited studies have compared the effect of cerebral microbleeds (CMBs) and lacunes on gait disturbance in CSVD patients in different anatomical locations.

To investigate the relationship of quantitative gait parameters with varied anatomically located MRI imaging markers in patients with CSVD.

Quantitative gait tests were performed on 127 symptomatic CSVD patients all with diffuse distributed white matter hyperintensities (WMHs). CMBs and lacunes in regard to anatomical locations and burdens were measured. The correlation between CSVD imaging markers and gait parameters was evaluated using general linear model analysis.

Presence of CMBs was significantly associated with stride length (β= -0.098, p = 0.0272) and right step length (β= -0.054, p = 0.0206). Presence of CMBs in basal ganglia (BG) was significantly associated with stride length and step length. Presence of CMBs in brainstem was significantly associated with gait parameters including stride length, step length, step height, and step width. Presence of lacunes in brainstem was significantly associated with gait speed (β= -0.197, p = 0.0365). However, presence of lacunes in the other areas was not associated with worse gait performances.

BG and brain stem located CMBs contributed to gait impairment in symptomatic CSVD patients.

The pathophysiology of lacunar infarction is an evolving and debated field, where relevant information comes from histopathology, old anatomical studies and animal models. Only in the last years, have neuroimaging techniques allowed a sufficient resolution to directly or indirectly assess the dynamic evolution of small vessel occlusion and to formulate hypotheses about the tissue status and the mechanisms of damage. The core-penumbra concept was extensively explored in large vessel occlusions (LVOs) both from the experimental and clinical point of view. Then, the perfusion thresholds on one side and the neuroimaging techniques studying the perfusion of brain tissue were focused and optimized for LVOs. The presence of a perfusion deficit in the territory of a single small perforating artery was negated for years until the recent proposal of the existence of a perfusion defect in a subgroup of lacunar infarcts by using magnetic resonance imaging (MRI). This last finding opens pathophysiological hypotheses and triggers a neurovascular multidisciplinary reasoning about how to image this perfusion deficit in the acute phase in particular. The aim of this review is to summarize the pathophysiological issues and the application of the core-penumbra hypothesis to lacunar stroke.

To explore the association of blood pressure (BP) measurements with cerebral blood flow (CBF) and brain structure in general population.

This prospective study included 902 participants from Kailuan community. All participants underwent brain MRI and BP measurements. The association of BP indicators with CBF, brain tissue volume and white matter hyperintensity (WMH) volume were investigated. In addition, mediation analysis was used to determine whether significantly changed brain tissue volume explained associations between BP and CBF.

Elevated diastolic BP (DBP), but not systolic BP (SBP), was associated with lower CBF in the total brain (β [95 % CI]: -0.62 [-1.14, -0.10]), total gray matter (β [95 % CI]: -0.71 [-1.27, -0.14]), hippocampus (β [95 % CI]: -0.59 [-1.13, -0.05]), frontal (β [95 % CI]: -0.72 [-1.31, -0.13]), parietal (β [95 % CI]: -0.92 [-1.54, -0.3]), temporal (β [95 % CI]: -0.63 [-1.18, -0.08]), and occipital lobe (β [95 % CI]: -0.69 [-1.37, -0.01]). Higher SBP and DBP were associated with reduced total and regional brain tissue volume (all p < 0.05). Increased SBP and PP were associated with higher total and periventricular WMH volume (all p < 0.05). In addition, mediation analysis identified that significantly decreased brain volume did not mediate the associations of BP measurements and lower CBF in corresponding region (all p > 0.05).

Elevated BP level was associated with decreased total and regional CBF and brain tissue volume and increased WMH burden.

Recent preclinical studies and meta-analysis of clinical trials suggested that acupuncture may improve cognition in cerebral small vessel disease (CSVD). We investigated the cerebral hemodynamics of acupuncture in subjects with CSVD and compared its impact upon the cerebral hemodynamics in normal elderly subjects.

10 subjects with CSVD (CSVD group) and 10 aged-matched control subjects who had no or insignificant CSVD (control group) were recruited. A single session of acupuncture was applied for 30 min in both groups. We assessed the effect of our acupuncture intervention on cerebral hemodynamics by transcranial Doppler ultrasound (TCD). Peak systolic velocity (PSV) and pulsatility index (PI) of the middle cerebral artery (MCA) were assessed.

We observed that PSV increased by a maximum of 39% at 20 min (p<0.05), while there was no significant change in PI in the CSVD group during the acupuncture session. In the control group, although we observed no significant change in PSV during the acupuncture session, there was a significant decrease in PI by a maximum of 22% at 20 min (p<0.05). No adverse events were reported during or after the procedure.

This study suggested that our acupuncture prescription was associated with an increase in cerebral blood flow in subjects with established moderate to severe CSVD yet without apparent impact on distal vascular resistance. While, in subjects with no or insignificant CSVD, it may reduce cerebral small vessel distal vascular resistance. A larger study is needed to confirm our findings.

High-mobility group box 1 protein (HMGB1) is extensively involved in causing ischemic stroke, pathological damage of ischemic brain injury, and neural tissue repair after ischemic brain injury. However, the precise role of HMGB1 in ischemic stroke remains to be elucidated.

Comprehensive literature search and narrative review to summarize the current field of HMGB1 in cerebral ischemic based on the basic structure, structural modification, and functional roles of HMGB1 described in the literature.

Studies have exhibited the crucial roles of HMGB1 in cell death, immunity and inflammation, thrombosis, and remodeling and repair. HMGB1 released after cerebral infarction is extensively involved in the pathological injury process in the early stage of cerebral infarction, whereas it is involved in the promotion of brain tissue repair and remodeling in the late stage of cerebral infarction. HMGB1 plays a neurotrophic role in acute white matter stroke, whereas it causes sustained activation of inflammation and plays a damaging role in chronic white matter ischemia.

HMGB1 plays a complex role in cerebral infarction, which is related to not only the modification of HMGB1 and bound receptors but also different stages and subtypes of cerebral infarction. future studies on HMGB1 should investigate the spatial and temporal dynamics of HMGB1 after cerebral infarction. Moreover, future studies on HMGB1 should attempt to integrate different stages and infarct subtypes of cerebral infarction.

The main theory underlying the use of perfusion imaging in acute ischemic stroke is the presence of a hypoperfused volume of the brain downstream of an occluded artery. Indeed, the main purpose of perfusion imaging is to select patients for endovascular treatment. Computed Tomography Perfusion (CTP) is the more used technique because of its wide availability but lacunar infarcts are theoretically outside the purpose of CTP, and limited data are available about CTP performance in acute stroke patients with lacunar stroke.

We performed a systematic review searching in PubMed and EMBASE for CTP and lacunar stroke with a final selection of 14 papers, which were examined for data extraction and, in particular, CTP technical issues and sensitivity, specificity, PPV, and NPV values.

A global cohort of 583 patients with lacunar stroke was identified, with a mean age ranging from 59.8 to 72 years and a female percentage ranging from 32 to 53.1%.CTP was performed with different technologies (16 to 320 rows), different post-processing software, and different maps. Sensitivity ranges from 0 to 62.5%, and specificity from 20 to 100%.

CTP does not allow to reasonable exclude lacunar infarct if no perfusion deficit is found, but the pathophysiology of lacunar infarct is more complex than previously thought.

Coronary heart disease (CHD) and lacunar infarction (LI) are the most common cardio- cerebrovascular complications of type 2 diabetes mellitus (T2DM) and a recognized risk factor for renal injury. Although a unidirectional association of CHD or LI with T2DM or the kidney has been demonstrated, however, it remains unknown whether there is an interactive effect of the coexistence of CHD and LI on renal function in T2DM patients. The aim of our study was to investigate the interaction between CHD and LI on renal function in gender-specific patients with T2DM and the association between cardio-cerebrovascular disease-related conventional serum markers and the estimated glomerular filtration rate (eGFR).

We conducted a cross-sectional study in Beijing and Tianjin from April 2019 to August 2021. Participants with T2DM aged ≥18 years were asked to complete a one-to-one questionnaire and physical examination.

In this study, 389 eligible patients with T2DM were included, with a mean age of 63.04 ± 9.41 years, of whom 200 (51.41 %) were male. The proportions of patients with CHD, LI, and both CHD and LI were 28.53 %, 24.42 %, and 11.05 %, respectively. Compared to T2DM patients without either CHD or LI, those with both CHD and LI were found to have a significantly greater risk of reduced eGFR (OR: 12.82, 95 % CI 5.06-32.52, P < 0.001) than those with CHD alone (OR: 2.42, 95 % CI 1.37-3.00, P = 0.004) or LI alone (OR: 1.15, 95 % CI 0.61-2.18, P = 0.664). The combined presence of CHD and LI is associated with a significantly greater risk of decreased eGFR in female T2DM patients compared to their male counterparts. We found both multiplicative and additive effects in all T2DM patients; however, when stratified by sex, only multiplicative effects were observed. After controlling for interference from CHD, LI, and age, we found that total cholesterol (TC) was negatively correlated with eGFR in females (r = -0.156, P = 0.034), and low-density lipoprotein cholesterol (LDL-C) was negatively correlated with eGFR in males (r = -0.229, P = 0.001).

This study provides novel evidence that the synergistic effect of CHD and LI on renal injury in patients with T2DM is significantly greater than their individual effects. Women with T2DM who have both CHD and LI are at a 4.85-fold higher risk of decreased eGFR than men. Therefore, increased clinical attention should be given to preventing and treating vascular complications in T2DM patients, as well as aggressively reducing lipid levels, particularly TC and LDL-C, to delay or prevent renal dysfunction in T2DM patients.

The vascular mild cognitive impairment (VaMCI) is generally accepted as the premonition stage of vascular dementia (VaD). However, most studies are focused mainly on VaD as a diagnosis in patients, thus neglecting the VaMCI stage. VaMCI stage, though, is easily diagnosed by vascular injuries and represents a high-risk period for the future decline of patients' cognitive functions. The existing studies in China and abroad have found that magnetic resonance imaging technology can provide imaging markers related to the occurrence and development of VaMCI, which is an important tool for detecting the changes in microstructure and function of VaMCI patients. Nevertheless, most of the existing studies evaluate the information of a single modal image. Due to the different imaging principles, the data provided by a single modal image are limited. In contrast, multi-modal magnetic resonance imaging research can provide multiple comprehensive data such as tissue anatomy and function. Here, a narrative review of published articles on multimodality neuroimaging in VaMCI diagnosis was conducted，and the utilization of certain neuroimaging bio-markers in clinical applications was narrated. These markers include evaluation of vascular dysfunction before tissue damages and quantification of the extent of network connectivity disruption. We further provide recommendations for early detection, progress, prompt treatment response of VaMCI, as well as optimization of the personalized treatment plan.

The etiological features of stroke in young adults are different from those in older adults. We aimed to investigate the impact of high-resolution vessel wall imaging (HRVWI) on etiologic diagnosis in young adults with ischemic stroke or transient ischemic attack (TIA).

A total of 253 young adults (aged 18-45 years) who consecutively underwent HRVWI for clarifying stroke etiology were retrospectively recruited. Two experienced neurologists classified stroke etiology for each patient using Trial of Org 10,172 in Acute Stroke Treatment categories with and without the inclusion of HRVWI diagnosis. Multivariate logistic regression was performed to determine which etiologic category would be significantly impacted after including HRVWI.

The etiologic classification was altered in 39.1% (99/253) of patients after including HRVWI in the conventional investigations. The proportion of patients classified as having stroke of undetermined etiology (SUE) and the proportion of patients classified as having small-artery occlusion (SAO) both significantly decreased (36.4 to 13.8% and 9.1 to 2.0%), whereas the proportion of patients classified as having large artery atherosclerosis (LAA) significantly increased (28.5 to 58.1%) (all P < 0.001). The inclusion of HRVWI had a significant diagnostic impact on young adults who were primarily classified as SAO (odds ratio [OR] 14.4, 95% confidence interval [CI] [2.9, 71.8], P < 0.001) or SUE (OR 8.3, 95% CI [2.2, 31.5], P < 0.01).

HRVWI had a substantial impact on etiologic classification in young adults with ischemic stroke or TIA, particularly for those primarily classified as having SAO or SUE. This impact of HRVWI will be beneficial for therapeutic decision-making.