Search Results (276)

Background/Objectives: Posterior inferior cerebellar artery (PICA) aneurysms are one of the most difficult cerebrovascular lesions to treat and account for 0.5–3% of all intracranial aneurysms. They have deep anatomical locations, broad-neck configurations, high perforator density, and a close association with the brainstem, which creates considerable technical challenges for either microsurgical or endovascular treatment. Despite its acceptance as the standard of care for most posterior circulation aneurysms, PICA aneurysms are often associated with flow diversion using a coil or flow diversion due to incomplete occlusions, parent vessel compromise and high rate of recurrence. This case aims to describe the utility of microsurgical clipping as a durable and definitive option demonstrating the value of tailored surgical planning, preservation of anatomy and ancillary technologies for protecting a genuine outcome in ruptured PICA aneurysms. Methods: A 66-year-old male was evaluated for an acute subarachnoid hemorrhage from a ruptured and broad-necked fusiform left PICA aneurysm at the vertebra–PICA junction. Endovascular therapy was not an option due to morphology and the center of the recurrence; therefore, a microsurgical approach was essential. A far-lateral craniotomy with a partial C1 laminectomy was carried out for proximal vascular control, with careful dissection of the perforating arteries and precise clip application for the complete exclusion of the aneurysm whilst preserving distal PICA flow. Results: Post-operative imaging demonstrated the complete obliteration of the aneurysm with unchanged cerebrovascular flow dynamics. The patient had progressive neurological recovery with no new cranial nerve deficits or ischemic complications. Long-term follow-up demonstrated stable aneurysm exclusion and full functional independence emphasizing the sustainability of microsurgical intervention in challenging PICA aneurysms. Conclusions: This case intends to highlight the current and evolving role of microsurgical practice for treating posterior circulation aneurysms, particularly at a time when endovascular alternatives are limited by anatomy and hemodynamics. Advances in artificial intelligence cerebral aneurysm rupture prediction, high-resolution vessel wall imaging, robotic-assisted microsurgery and new generation flow-modifying implants have the potential to revolutionize treatment paradigms by embedding precision medicine principles into aneurysm management. While the discipline of cerebrovascular surgery is expanding, it can be combined together with microsurgery, endovascular technologies and computational knowledge to ensure individualized, durable, and minimally invasive treatment options for high-risk PICA aneurysms. Full article

Carotid stenosis is a common pathology in clinical practice and unfortunately carries a high risk of serious cerebrovascular events. The early recognition of carotid plaque and, consequently, a careful analysis by means of multimodal imaging are the necessary steps to undertake a correct management pathway, aimed at preventing or, if not possible, reducing the risk of atherogenic phenomena responsible for cerebral infarction. In particular, the presence or absence of clinical symptoms, understood as the occurrence of events such as TIAs in the last 6 months, non-disabling strokes or repeated episodes of amaurosis fugax, and the degree of carotid stenosis, are certainly the most studied parameters, and as reported by several international guidelines, can lead to the best therapeutic strategy: whether to rely on conservative medical therapy or to resort to mechanical revascularization of the carotid stenosis. According to the recommendations of the European Society of Vascular Surgery, mechanical revascularization is recommended for stenosis > 50% in symptomatic patients and stenosis > 60% in asymptomatic patients. In contrast, the latest findings on plaque vulnerability have focused attention on individual patient characteristics and clinical comorbidities that may be responsible for plaque inflammation and should therefore be taken into consideration to decide if revascularization treatment is needed even in those subjects who present stenosis with less degree than reported as critical value. Moreover, further radiological investigations are fundamental to finding the presence of entities such as plaque ulceration, plaque neo-vascularization, fibrous caps, and intraplaque lipid core that are responsible for increased vulnerability. Medical therapy involves interventions aimed at eliminating cardiovascular risk factors by administering drugs that control the comorbidities responsible for worsening carotid stenosis. Recent studies are also evaluating the effectiveness of new plaque-modifying drugs or targeted anti-inflammatory agents in reducing the risk of plaque development and complications. Revascularization therapies, on the other hand, include surgery (CEA), the endovascular technique (CAS), and a new hybrid technique (TCAR): they are all valid alternatives for the treatment of carotid stenosis, each with specific technical difficulties, but on the whole with comparable safety profiles and risk rates of postoperative complications, although some recent emergencies have focused attention on possible short- and long-term gender-dependent outcome differences. The aim of this manuscript is to present the state of the art in the management of patients with carotid stenosis and to take a closer look at revascularization options. In our opinion, the choice of one strategy over another should therefore depend on gender, anatomical features of the patient, preoperative comorbidities, and last but not least, the experience of the center and the multidisciplinary team involved in the management of the patient. Full article

Background: Primary aldosteronism is characterized by elevated aldosterone levels, leading to adverse effects such as hypertension, hypokalaemia and increased risk for cardiovascular and cerebrovascular events. Aldosterone impacts the central nervous system by promoting vascular remodelling and oxidative stress, potentially impairing cognitive function. The presence of mineralocorticoid receptors in the hippocampus, a key region for cognition, further suggest a link between primary aldosteronism and cognitive dysfunction. This study aims to further explore the association between hyperaldosteronism and cognitive impairment. Methods: In this pilot study we examined 15 individuals with primary aldosteronism and arterial hypertension alongside 15 age- and sex-matched controls with essential hypertension, all free of previous cerebrovascular events. Clinical and archival laboratory data were obtained. Cognitive function was assessed using the Mini-Mental State Examination and Montreal Cognitive Assessment. Results: Participants with primary aldosteronism had higher blood pressure values, longer duration of hypertension, lower serum potassium levels and higher 24 h urine albumin excretion rate compared to controls. Comorbidities, other characteristics and laboratory values were comparable across the two groups. No differences were observed in Mini-Mental State Examination scores, but Montreal Cognitive Assessment scores were significantly lower in the primary aldosteronism group (25.1 ± 2.2 vs. 27.1 ± 2.2, p = 0.021). Trends of poorer performance in language and attention/executive function domains were noted in primary aldosteronism individuals, as well as a higher number of pathological Montreal Cognitive Assessment scores (7 vs. 3). No significant correlations were found between cognitive test results and aldosterone concentrations or blood pressure in primary aldosteronism group. However, importantly, multiple regression analysis showed that aldosterone levels have a significant impact on Montreal Cognitive Assessment test, independent of blood pressure or duration of hypertension. Conclusions: This study supports an association between hyperaldosteronism and cognitive dysfunction, underscoring the need for more active detection and targeted treatment of primary aldosteronism. These findings warrant further research in larger cohorts to better elucidate this relationship. Full article

Probiotics demonstrate the ability to maintain intestinal homeostasis and promote gut health. However, their effects on gut microbiota in adults over 60 years old with chronic metabolic disease (CMD) or cardio-cerebrovascular disease (CCD) remain poorly understood. This study analyzed 1586 stool samples from 1377 adults (CMD, CCD, and healthy controls) using 16S rRNA sequencing. Cohort 1 (n = 1168) was used for cross-sectional analysis, while cohort 2 (n = 209) underwent longitudinal assessment over approximately 13 months. The results demonstrated that probiotics promoted significant gut microbiota alterations across both cohorts. Probiotic supplementation significantly increased lactobacilli in the CMD, CCD, and H groups. In both cohorts, probiotic supplementation enhanced Butyricicoccus, Clostridium sensu stricto 1, and Coprococcus in H groups, enhanced Anaerostipes and Fusicatenibacter in CMD groups, and reduced Haemophilus and Lachnospira in CCD groups. Notably, long-term supplementation not only elevated Dorea, Eubacterium hallii group, and Blautia in all groups but also suppressed Klebsiella and Bilophila in the CMD and CCD groups. Enterotype analysis revealed that probiotics increased the proportion of enterotype 1 and transition probabilities from enterotype 2 to 1 in the CMD and CCD groups, demonstrating that CCD/CMD gut microbiota exhibited greater responsiveness to probiotic modulation. Overall, this study suggests probiotics’ role in modulating adult gut microbiota and their potential benefits in chronic metabolic and cardio-cerebrovascular diseases. Full article

Background: With an aging population, dementia prevalence is increasing in Korea. Vascular dementia (VaD), often caused by cerebrovascular disease (CVD), is more common in Korea compared to Western countries. Hwanhon decoction, a traditional medicine containing Ephedrae Herba, Armeniacae Semen, and Glycyrrhizae Radix et Rhizoma, is traditionally used for CVD-related loss of consciousness. This study aimed to assess the cognitive improvement and anti-inflammatory effects of Hwanhon decoction extract (HHex) in a mouse model of VaD caused by chronic cerebral hypoperfusion (CCH). Methods: Key pharmacologically active ingredients of Hwanhon decoction were identified using network pharmacology analysis. VaD was induced in C57Bl/6 male mice through bilateral common carotid artery stenosis (BCAS). Mice were divided into sham surgery, BCAS control, low-dose HHex (L-HHex), and high-dose HHex (H-HHex) groups (n = 5/group). After CCH induction, L-HHex or H-HHex was administered thrice weekly for six weeks. Cognitive function, inflammatory markers, and RNA sequencing data were analyzed. Results: HHex administration reduced cognitive impairment and mitigated CCH-induced astrocyte activation. Inflammatory responses mediated by reactive astrocytes were suppressed, and network pharmacology predicted central proteins influencing HHex’s activity. Conclusions: HHex alleviated cognitive dysfunction and reduced inflammation in a VaD mouse model, suggesting its potential as a therapeutic agent for vascular dementia associated with impaired cerebral blood flow. Full article

Background: Abdominal aortic aneurysm (AAA) is a chronic inflammatory disease characterized by the proteolytic breakdown of the extracellular matrix. A clinical biomarker is needed for risk stratification and prognosis. Methods: In this single-center, 5-year observational study, 452 patients were enrolled: 343 with AAA (≥3 cm), and 109 controls (<3 cm). Plasma levels of six inflammatory proteins (human epididymis protein 4 (HE4), matrix metalloproteinase (MMP) 1 and 3, cathepsin S, chitinase 3 like-1, cathepsin S, and B-cell activating factor (BAFF)) were quantified at baseline. Patients were followed for a total of 5 years (60 months), and major adverse cardiovascular events (MACEs, defined as the composite of myocardial infarction, cerebrovascular attack, and cardiovascular-related death) were recorded. A Cox proportional hazard model was created using biomarker levels, age, sex, hypertension, hypercholesterolemia, diabetes mellitus, smoking status, and coronary artery disease to determine whether the baseline levels of these proteins were associated with MACEs over 5 years. Results: HE4, MMP-3, BAFF, and cathepsin S levels were significantly elevated in AAA patients compared to controls (all p < 0.05). HE4/WFDC2, MMP-3, and Chitinase 3-like 1 were significantly linearly associated with AAA diameter at baseline. With every normalized unit increase in HE4/WFDC2, MMP-3, and Chitinase 3-like 1, there was an increase in abdominal aortic diameter by 0.154 (95% CI: 0.032–0.276, p = 0.013), 0.186 (95% CI: 0.064–0.309, p = 0.003), and 0.231 (0.110–0.353, p < 0.001) centimeters, respectively. Among patients with AAA, elevated HE4 was associated with higher risk of MACEs (adjusted HR 1.249; 95% CI: 1.057–1.476; p = 0.009). Patients with high baseline HE4 (≥9.338 ng/mL) had significantly lower freedom from MACEs at 5 years (76.7% vs. 84.8%, p = 0.022). Conclusions: HE4 may be a potential prognostic biomarker that can be used to risk stratify patients with AAA to better personalize treatment strategies to reduce adverse events. Full article

Background/Objectives: High-intensity interval training (HIIT) can optimize recovery by complementing the low cardiovascular fitness intensities typically achieved in stroke rehabilitation programs. Skating exercise is an HIIT workout developed based on ice skating movements, and we investigated the effects of this exercise on the cardiorespiratory fitness of elderly patients with minor stroke. Methods: Participants aged 65 or older with a National Institutes of Health Stroke Scale score of 3 or lower were recruited. This study was designed as a randomized controlled trial, in which the intervention group engaged in skating exercises following HIIT, while the control group underwent moderate-intensity continuous training (MICT). Both groups of participants performed either HIIT or MICT for 20 min per day, four times a week, over three months. Results: A total of 34 elderly patients with minor stroke were recruited, with an average age of 70.7 years. For three months, no fall-down injuries or adverse cardiovascular or cerebrovascular events were reported among patients undergoing HIIT or MICT. Both the intervention and control groups showed significant increases in the measures of aerobic capacity after the intervention. However, the patients in the intervention group exhibited significantly greater improvements in peak oxygen uptake, ventilatory threshold, and peak MET (p = 0.005, p = 0.002, and p = 0.024, respectively). Additionally, the Berg Balance Scale (BBS) scores and the skeletal muscle mass index showed significantly greater enhancements in the intervention group compared to the control group (p = 0.032 and p = 0.032). Conclusions: In conclusion, skating exercise could be a safe and effective HIIT protocol for elderly people who have experienced a minor stroke. Full article

Cerebral near-infrared spectroscopy (NIRS) systems have been demonstrated to continuously measure aspects of oxygen delivery and cerebrovascular reactivity. However, it remains unknown whether the prediction of these cerebral physiologic signals into the future is feasible. Leveraging existing archived data sources, four point and interval-forecasting methods using autoregressive integrative moving average (ARIMA) models were evaluated to assess their ability to predict NIRS cerebral physiologic signals. NIRS-based regional cerebral oxygen saturation (rSO₂) and cerebral oximetry index signals were derived in three temporal resolutions (10 s, 1 min, and 5 min). Anchored- and sliding-window forecasting, with varying model memory, using point and interval approaches were used to forecast signals using fitted optimal ARIMA models. The absolute difference in the forecasted and measured data was evaluated with median absolute deviation, along with root mean squared error analysis. Further, Pearson correlation and Bland–Altman statistical analyses were performed. Data from 102 healthy controls, 27 spinal surgery patients, and 101 traumatic brain injury patients were retrospectively analyzed. All ARIMA-based point and interval prediction models demonstrated small residuals, while correlation and agreement varied based on model memory. The ARIMA-based sliding-window approach performed superior to the anchored approach due to data partitioning and model memory. ARIMA-based sliding-window forecasting using point and interval approaches can forecast rSO₂ and the cerebral oximetry index with reasonably small residuals across all populations. Correlation and agreement between the predicted versus actual values varies substantially based on data-partitioning methods and model memory. Further work is required to assess the ability to forecast high-frequency NIRS signals using ARIMA and ARIMA-variant models in healthy and cranial trauma populations. Full article

Background: Epilepsy is a chronic neurological disorder frequently influenced by systemic inflammation, nutritional status, and comorbid conditions, which may worsen seizure outcomes. Given the increasing recognition of these factors in disease progression, this study aimed to investigate the relationship between the Modified Charlson Comorbidity Index (mCCI), inflammatory hematological parameters, and the prognostic nutritional index (PNI) with seizure frequency and clinical prognosis in patients with epilepsy. Methods: A total of 159 participants were enrolled between January 2021 and January 2023, including 53 healthy controls (mean age: 44 ± 14.2 years; female: 21, male: 32), 53 epilepsy patients without comorbidity (mean age: 33 ± 12.5 years; female: 28, male: 25), and 53 epilepsy patients with comorbidities (mean age: 56.2 ± 13.8 years; female: 22, male: 31). The participants were divided into three groups: 53 patients with isolated epilepsy, 53 patients with epilepsy and comorbid conditions, and 53 healthy individuals with no known diseases, matched for age and sex with the patient groups, who presented for routine check-ups. The mCCI was calculated for patients with comorbid epilepsy. Inflammatory hematological parameters and the PNI were assessed in all participants using previously obtained complete blood count data. Results: Inflammatory markers such as white blood cell count, neutrophil count, C-reactive protein (CRP), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and mean platelet distribution width (PDW) were significantly higher in epilepsy patients with comorbidities compared to other groups. Epilepsy patients with comorbidities had a higher seizure frequency compared to those without comorbidities (75.5% vs. 54.7%, p < 0.001). The PNI was lowest in epilepsy patients with comorbidities, showing a significant difference between all groups (p < 0.001). High comorbidity burden increased seizure risk by 4.56 times (95% CI: 1.30–16.01), each unit increase in the SII raised the risk by 1.13 times (95% CI: 1.08–1.19), and each unit decrease in the PNI increased the risk by 1.14 times (OR = 0.88, p < 0.001). Cerebrovascular disease and hemiplegia were also significant risk factors, increasing seizure risk by 4.15 and 4.48 times, respectively. Conclusions: Our study demonstrates that inflammatory hematological parameters, particularly SII and MCCI scores, are elevated in epilepsy patients and further increase with comorbidities. These markers are strongly associated with seizure occurrence, highlighting the prognostic significance of systemic inflammation and comorbidity burden in epilepsy. Given the frequent observation of low PNI values in patients with comorbid conditions, which may reflect compromised nutritional status, and given associations suggest a role in poor clinical outcomes, comprehensive management is essential. Monitoring the PNI and SII may help stratify high-risk patients for targeted nutritional and anti-inflammatory interventions. Full article

Moyamoya disease (MMD) is a cerebrovascular disease which can result in severe strokes. However, its etiology is still unknown. We analyzed gene expression datasets from 36 MMD patients and 24 controls to identify differentially expressed genes. Using weighted gene co-expression network analysis and databases such as KEGG, we identified hypoxia-immune-related genes. These genes were further refined through machine learning algorithms. The diagnostic value was confirmed using an external dataset, and a diagnostic nomogram was constructed. Additionally, gene set enrichment analysis was conducted, and a competitive endogenous RNA (ceRNA) network was built to predict potential therapeutic targets. Our study identified AKT1, CLDN3, ISG20, and TGFB2 as the key hypoxia-immune genes associated with MMD. These genes were implicated in epithelial–mesenchymal transition, angiogenesis, and cell adhesion, suggesting a role in MMD pathogenesis. Further, our study constructed the ceRNA network and predicted potential drug targets for MMD. We obtained the top 10 drugs in the interaction of the four key genes that might serve as potential targets for the treatment of MMD. In conclusion, this study comprehensively analyzes the role of hypoxia-immune genes in MMD, which is conducive to the development of new diagnostic and therapeutic approaches and the exploration of the potential pathogenesis of MMD. Full article

Background/Objectives: The interplay between the gut microbiome (GMB) and neurovascular function in neurodegeneration is unclear. The goal of this proof-of-concept, cross-sectional study is to identify relationships between the GMB, neurovascular functioning, and cognition in amnestic mild cognitive impairment (aMCI), the prototypical prodromal symptomatic stage of Alzheimer’s disease (AD). Methods: Participants (n = 14 aMCI and 10 controls) provided fecal samples for GMB sequencing (16S and shotgun metagenomics), underwent MRI, and completed cognitive testing. Cerebral vascular reactivity (CVR), cerebral blood flow (CBF), and arterial transit time (ATT) were assessed. Statistical analyses evaluated the relationships between discriminatory taxa, cerebrovascular metrics, and cognition. Results: Sequencing revealed differentially abundant bacterial and viral taxa distinguishing aMCI from controls. Spearman correlations revealed that bacteria known to induce inflammation were negatively associated with CVR, CBF, and cognition, and positively associated with ATT. A reciprocal pattern emerged for the association of taxa with gut health. Conclusions: Our results provide preliminary evidence that pro-inflammatory gut bacterial and viral taxa are associated with neurovascular dysfunction and cognitive impairment in prodromal AD, highlighting their potential as candidate microbial biomarkers and targets for early intervention. Full article

Background/Objectives: Aneurysmal subarachnoid hemorrhage (aSAH) remains a life-threatening cerebrovascular event with high rates of mortality and long-term morbidity. Among its complications, delayed cerebral ischemia (DCI) is a major contributor to poor clinical outcomes. Although cerebral vasospasm has traditionally been considered the primary mechanism underlying DCI, recent studies have revealed the multifactorial nature of this condition. This review aims to provide a comprehensive overview of the pathophysiology, preventive strategies, and current treatment options for DCI following aSAH. Methods: A narrative literature review was conducted using the PubMed database to identify peer-reviewed articles relevant to the prevention and treatment of DCI following aSAH. The search strategy employed the following terms: (“Subarachnoid Hemorrhage” [MeSH]) AND “Delayed Cerebral Ischemia” AND (“Prevention and Control” [Subheading] OR “Secondary Prevention” [MeSH]). This search strategy was designed to capture studies addressing both pharmacological and non-pharmacological preventive measures for DCI. Results: A comprehensive PubMed search identified a total of 113 relevant articles. Among these, 40 publications primarily addressed pharmacological interventions, while 22 focused on neuromonitoring techniques. An additional 20 articles explored the pathophysiological mechanisms underlying DCI, and 15 involved preclinical studies utilizing animal models. The remaining 16 articles encompassed diverse topics, including prophylactic endovascular therapies, newly proposed definitions of DCI, treatment algorithm development, functional outcome analyses, and entries in clinical trial registries. Emerging evidence highlights that vasospasm alone does not account for all cases of DCI. Pharmacological approaches such as nimodipine, clazosentan, and fasudil have shown varying degrees of efficacy. Circulatory management and removal of subarachnoid hematoma via CSF drainage or thrombolytics may reduce DCI risk, although their impact on long-term neurological outcomes remains controversial. Endovascular therapy and adjunctive agents such as cilostazol or anticoagulants have demonstrated potential but require further validation through large-scale trials. Conclusions: Effective DCI prevention and treatment require a multimodal approach targeting diverse pathological mechanisms beyond vasospasm. Improved risk stratification, early detection, and individualized therapy are essential for advancing the management of patients with aSAH. Full article

Background/Objectives: This study aimed to develop and validate comorbidity-based severity adjustment methods for acute cerebrovascular disease by recalibrating the Charlson Comorbidity Index (CCI) and constructing a CCS-based comorbidity index to improve mortality risk prediction. Methods: Using the Korea Disease Control Agency’s Discharge Injury In-depth Survey Dataset (2013–2022), we applied Cox proportional hazards regression and machine learning techniques, including LASSO, CART, Random Forests, GBM, and ANN, to recalibrate the CCI and develop a CCS-based comorbidity index. Results: The recalibrated Charlson Comorbidity Index (m-CCI) and the newly developed CCS-based comorbidity index (m-CCS) demonstrated improved predictive performance for in-hospital mortality. Among the machine learning models, GBM (AUC = 0.835) and ANN (AUC = 0.830) demonstrated the highest predictive accuracy, with m-CCS consistently outperforming other indices. Conclusions: The recalibrated m-CCI and newly developed m-CCS comorbidity indices enhance mortality risk adjustment for acute cerebrovascular disease patients in Korea. The superior performance of machine learning models underscores their potential for enhancing severity adjustment in hospital benchmarking and quality assessment. Full article

Diabetic kidney disease (DKD) displays a high prevalence of cardiovascular and cerebrovascular disease. Both the kidney and the brain share common pathogenic mechanisms, such as inflammation, endothelial dysfunction, oxidative stress, and mitochondrial dysfunction. The aim of this study was to establish a potential association of cerebral vessel remodeling and its related functional impairment with biomarkers of inflammation, oxidative stress, and mitochondrial dysfunction in the early stages of DKD in type 2 diabetes mellitus (DM) patients. A cohort of 184 patients and 39 healthy controls was assessed concerning serum and urinary stromal cell-derived factor-1 (SDF-1), P-selectin, advanced oxidation protein products (AOPPs), urinary synaptopodin, podocalyxin, kidney injury molecule-1 (KIM-1), and N-acetyl-β-(D)-glucosaminidase (NAG). The quantification of the mitochondrial DNA copy number (mtDNA-CN) and nuclear DNA (nDNA) in urine and peripheral blood was conducted using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Using TaqMan tests, the beta-2 microglobulin nuclear gene (B2M) and the cytochrome b (CYTB) gene, which encodes subunit 2 of NADH dehydrogenase (ND2), were evaluated. The MtDNA-CN is the ratio of mitochondrial DNA to nuclear DNA copies, ascertained through the examination of the CYTB/B2M and ND2/B2M ratios. The intima-media thickness (IMT) measurements of the common carotid arteries (CCAs), along with the pulsatility index (PI) and resistivity index (RI) of the internal carotid arteries (ICAs) and middle cerebral arteries (MCAs), were obtained through cerebral Doppler ultrasonography (US). Additionally, the breath-holding index (BHI) was also measured by cerebral Doppler US. PI-ICAs, PI-MCAs, CCAs-IMT, RI-MCAs, and RI-ICAs demonstrated direct relationships with SDF-1, P-selectin, AOPPs, urine mtDNA, podocalyxin, synaptopodin, NAG, and KIM-1 while showing indirect correlations with serum mtDNA and the eGFR. In contrast, the BHI had negative correlations with SDF-1, P-selectin, AOPPs, urine mtDNA, synaptopodin, podocalyxin, KIM-1, and NAG while showing direct associations with serum mtDNA and the eGFR. In conclusion, a causative association exists among SDF-1, P-selectin, and AOPPs, as well as mitochondrial dysfunction, in early diabetic kidney disease (DKD) and significant cerebrovascular alterations in patients with type 2 diabetes mellitus and normoalbuminuric DKD, with no neurological symptoms. Full article

Background and Objectives: Carotid artery stenosis is a significant risk factor for ischemic stroke due to impaired cerebral blood flow (CBF). Even asymptomatic unilateral stenosis can induce subclinical cerebrovascular changes, potentially affecting both hemispheres through collateral circulation. This study aimed to systematically assess cerebral perfusion in asymptomatic individuals with unilateral carotid artery stenosis by comparing ipsilateral and contralateral hemispheres with healthy controls, challenging the assumption that the contralateral hemisphere remains unaffected. Materials and Methods: This cross-sectional study included 114 participants, comprising 54 asymptomatic individuals (mean age 65.5) with significant unilateral carotid stenosis and 60 age-matched controls (mean age 64.8). Cerebral perfusion was assessed using 1.5T Magnetic Resonance Imaging (MRI) with pseudo-continuous arterial spin labeling (pCASL). CBF was measured bilaterally in four predefined middle cerebral artery (MCA) regions: precentral gyrus, lentiform nucleus, insular cortex, and temporal cortex. Statistical analyses included multivariate analysis of variance (MANOVA), analysis of variance (ANOVA), paired t-tests, and discriminant analysis (DA). Results: Significant bilateral reductions in CBF were observed in individuals with carotid stenosis compared to controls (MANOVA and ANOVA, p < 0.001). The greatest perfusion deficit was in the ipsilateral insular cortex (49.88 ± 10.83 mL/100 g/min), followed by intermediate contralateral perfusion (51.49 ± 8.86 mL/100 g/min) and higher control values (58.78 ± 10.44 mL/100 g/min). DA indicated the insular cortex as the region with the highest discriminative contribution (64.7%). Conclusions: Unilateral carotid artery stenosis in asymptomatic individuals is associated with significant bilateral cerebral hypoperfusion, suggesting widespread hemodynamic effects. Pronounced perfusion deficits in the insular cortex underline its vulnerability. The observed contralateral perfusion reductions challenge the traditional use of the contralateral hemisphere as a reference standard, underscoring the need for comprehensive perfusion assessment in carotid artery disease. Full article