Search Results (57)

Background/Objectives： Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a prevalent Mendelian disorder caused by mutations in the NOTCH3 gene, primarily impacting cerebral small blood vessels. This review aims to explore the involvement of large intracranial arteries in CADASIL, particularly focusing on the association with RNF213 polymorphisms, especially in Asian populations. Methods： A comprehensive literature review was conducted to gather data on the morphological features of both small and large intracranial arteries in CADASIL, examining clinical manifestations, imaging findings, and genetic associations. Results： The findings indicate that while CADASIL is predominantly characterized by small vessel disease, a significant number of patients also exhibit large artery involvement, particularly Asian populations where RNF213 polymorphisms may play a critical role. The review highlights the evidence of intracranial stenosis and the potential implications of traditional vascular risk factors, such as hypertension and diabetes mellitus, which are prevalent in these populations. Conclusions： The involvement of larger intracranial arteries in CADASIL underscores the complexity of the disease, suggesting that both genetic predispositions and environmental factors contribute to vascular abnormalities. Further research is needed to clarify these relationships and improve diagnostic and therapeutic strategies for CADASIL patients. Full article

Background: The coexistence of extracranial arterial stenoses and intracranial aneurysms presents a unique clinical dilemma. While staged interventions are traditionally preferred to reduce procedural risks, recent advances have enabled single-stage endovascular treatment. This study evaluates the clinical outcomes, procedural strategies, and predictive factors associated with such combined interventions. Methods: This retrospective study included 47 patients treated with single-stage endovascular procedures for concurrent extracranial stenosis and intracranial aneurysm between 2016 and 2024. Clinical, angiographic, and procedural data were collected. Outcomes were assessed using the mmodified Rankin Scale (mRS), and statistical analyses were performed to identify associations between clinical variables and functional outcomes. Results: Of the 47 patients, 85.1% achieved favorable outcomes (mRS 0–2) at ≥6-month follow-up. The most commonly treated arteries were the internal carotid artery (70.2%) and the middle cerebral artery (34%). Stent-assisted coiling or flow diversion was performed in 93.6% of aneurysm cases, while 91.5% underwent carotid or vertebral stenting. Lesion laterality (left-sided aneurysms, p = 0.019) and stenosis length (p = 0.0469) were significantly associated with outcomes. Smoking was linked to multiple stenoses (p = 0.0191). Two patients experienced major complications: one aneurysmal rebleed after stenting, and one intraoperative rupture. Conclusions: Single-stage endovascular treatment for patients with concurrent extracranial stenosis and intracranial aneurysm is technically feasible and clinically effective in selected cases. Lesion configuration, anatomical considerations, and individualized planning are critical in optimizing outcomes. Full article

Background: Venous sinus stenting is a promising treatment for intracranial venous disorders, such as idiopathic intracranial hypertension and pulsatile tinnitus, associated with transverse sinus stenosis. The VIVA Stent System (VSS) is a novel self-expanding braided venous stent designed to navigate tortuous cerebral venous anatomy. This preclinical study assessed the safety, thrombogenicity, and performance of the VSS in a swine model. Methods: Fifteen swine underwent bilateral internal mammary vein stenting with either the VSS (n = 9) or the PRECISE^® PRO RX stent (n = 6, reference). Fluoroscopy and thrombogenicity assessments were conducted on the day of stenting, clinical pathology analysis was carried out throughout the in-life phase, and CT Venography was performed before sacrifice. Animals were sacrificed at 30 ± 3 or 180 ± 11 days post-stenting for necropsy and histological evaluation. Results: Fluoroscopic angiography confirmed the successful VSS deployment with complete venous wall apposition and no vessel damage. The VSS achieved the highest scores on a four-point Likert scale for most performance parameters. No thrombus formation was observed on either delivery system. CT Venography confirmed vessel patency, no stent migration, and complete stent integrity. Histopathology showed a mild, expected foreign body reaction at 30 days, which resolved by 180 days, indicating normal healing progression. Both stents showed increased luminal diameter and decreased wall thickness at 180 days, suggesting vessel recovery. No adverse reactions were observed in non-target organs. Conclusions: The VSS exhibited favorable safety, procedural performance, and thromboresistance in a swine model, supporting its potential clinical use for treating transverse sinus stenosis and related conditions. Full article

Background: Intracranial atherosclerotic stenosis (ICAS) is a significant cause of ischemic stroke worldwide, with high recurrence rates despite optimal medical therapy. While endovascular stenting has been proposed as an adjunctive treatment, its clinical benefit remains controversial as a first line therapy. Objective: To evaluate the efficacy and safety of stenting plus medical therapy (STN+MT) compared to medical therapy alone (MT) in patients with symptomatic ICAS through a systematic review and meta-analysis of randomized controlled trials (RCTs). Methods: We systematically searched PubMed, Web of Science, the Cochrane Library, Embase, Scopus, and EBSCO for RCTs comparing STN+MT with MT in adult patients with symptomatic ICAS. Primary outcomes included transient ischemic attack (TIA), stroke, intracerebral hemorrhage (ICH), and death at 30 days and 1 year. Pooled risk ratios with 95% confidence intervals were calculated using random-effects or fixed-effects models as appropriate. Meta-regression was conducted to assess effect modification by study-level characteristics. Results: Four trials comprising 990 patients were included. STN+MT was associated with significantly higher 30-day risk of stroke and ICH compared to MT alone. No significant differences in TIA, stroke, ICH, or death were found at 1 year. Meta-regression revealed no significant effect modifiers, suggesting consistent findings across subgroups. Conclusions: Our meta-analysis consolidates the evidence that intracranial stenting as a first line therapy offers no significant advantage over medical therapy in preventing stroke in symptomatic ICAS, while it does pose added early risks. This holds true across different trials, patient demographics, and clinical scenarios examined. The consistency of this message across multiple RCTs provides a high level of evidence to guide practice. At present, aggressive medical therapy alone should be the default management for most patients. Endovascular intervention should be reserved for clinical trial settings or carefully selected salvage cases, until and unless new evidence emerges to change the risk–benefit calculus such as the promising use of balloon angioplasty in the BASIS trial. Full article

Background: Hyperintense vessels (HVs) visualized on FLAIR MRI are believed to reflect sluggish antegrade or retrograde flow in leptomeningeal collaterals that develop in response to major intracranial artery stenosis or occlusion. HV is frequently observed in conditions such as Moyamoya disease and symptomatic ICA/MCA steno-occlusion. However, the relationship between HV and cerebral hemodynamics—and the effect of STA-MCA bypass on HV—remains inadequately characterized. This study aimed to investigate the relationship between HV on FLAIR and cerebral vascular hemodynamic status, as measured by SPECT, in patients with Moyamoya disease and symptomatic ICA/MCA occlusion. The secondary goal was to assess the impact of recanalization through STA-MCA bypass surgery on the presence of HV. Methods: We retrospectively analyzed 49 patients with symptomatic ICA or MCA steno-occlusion who underwent STA-MCA bypass between 2015 and 2020. Pre- and postoperative FLAIR MRIs were evaluated, and HV presence was graded as negative (0), minimal (1), or positive (2). SPECT was utilized to assess cerebrovascular reserve (CVR) in regions exhibiting various HV intensities. Follow-up FLAIR imaging was performed 3–14 months postoperatively to correlate HV changes with hemodynamic improvements observed via SPECT. Result: HV was present in 74% (36/49) of affected hemispheres. Regions exhibiting minimal or positive HV demonstrated a significantly lower CVR compared to HV-negative areas, indicating compromised perfusion. Following bypass surgery, HV was reduced or resolved in 65% (32/49) of patients, and this regression corresponded with improved CVR as confirmed by both SPECT and perfusion MRI. Conclusions: HV presence on FLAIR imaging is associated with impaired cerebrovascular hemodynamics in patients with Moyamoya disease or symptomatic large-vessel steno-occlusion. HV-positive territories exhibit reduced CVR, while surgical revascularization via STA-MCA bypass leads to hemodynamic improvement and concurrent HV reduction. These findings support HV as a potential surrogate marker for treatment response. Full article

Background: Intracranial artery calcification detected on CT imaging is a recognized risk factor for ischemic cerebrovascular diseases, but the underlying etiology of this association remains unclear. Differences in objective morphometric characteristics of these calcifications may partially explain this association, yet these measurements are largely absent in the literature. We investigated intracranial artery calcification morphometry in patients with recent anterior ischemic stroke or TIA, assessing potential differences between calcifications in both intracranial carotid arteries (ICAs) located ipsilateral and contralateral to the cerebral ischemia. Methods: Among 100 patients (mean age 69.6 (SD 8.8) years) presenting to academic neurology departments, 3D reconstructions of both ICAs were based on clinical CT-angiography images. On these reconstructions, a luminal centerline and cross-sections perpendicular to this centerline were created, facilitating the assessment of calcification morphometry, spatial orientation and stenosis severity. Differences in calcification characteristics between ICAs were assessed using two-sided Wilcoxon signed-rank and χ² tests. Results: Among 200 arteries, a median of four (IQR 2–6) individual calcifications were counted, with a mean area of 1.8 (IQR 1.2–2.7) mm², a mean arc width of 43.5 (IQR 32.3–53.2) degrees, and median longitudinal extent of 15.4 (IQR 5.9–27.0) mm. Calcifications were most often present in the anatomical C4 section (56.0%), with predominantly posterosuperior orientation (38.5%) and 42.0% had a local stenosis severity > 70%. None of these aspects significantly differed between ICAs, and this remained after restricting analyses to patients with undetermined etiology. Conclusions: We found no differences in morphometrical or spatial aspects of calcifications between ICAs ipsilateral and contralateral to the cerebral ischemia. Full article

Background: Tandem Lesions (TLs) or Tandem Occlusions (TOs) are characterized by simultaneous high-grade stenosis or occlusion of the proximal extracranial internal carotid artery and the intracranial terminal internal carotid artery or its branches. These lesions can result in stroke and pose significant challenges to endovascular treatment. This study introduces and evaluates the “T-Top technique” as an innovative approach to address TLs, assessing its safety and technical efficacy. Methods: Data from acute ischemic stroke (AIS) patients treated with the T-Top technique between September 2022 and September 2023 were retrospectively analyzed. The technique involves using the pusher wire of a stent retriever as a microwire to guide a monorail angioplastic balloon to the extracranial carotid stenosis, performing angioplasty simultaneously with stent retriever anchorage. Clinical outcomes, procedural data, and safety were assessed. Results: Successful reperfusion (mTICI > 2b) was achieved in 91% of cases, with a median groin puncture to final recanalization time of 50 min. Favorable clinical outcomes (mRS < 3) were observed in 69% of patients, with a low mortality rate of 6% after 90 days. Conclusions: The T-Top technique offers a rapid and reliable strategy for TL treatment, improving reperfusion rates and clinical outcomes. Further studies are warranted to validate its efficacy in larger cohorts. This technique holds promise for enhancing endovascular treatment outcomes in patients with Tandem Lesions. Full article

Background: Intracranial atherosclerotic stenosis (ICAS) is a leading cause of ischemic stroke, particularly in the anterior circulation. Understanding the underlying stroke mechanisms is essential for guiding personalized treatment strategies. This study proposes an integrated framework that combines CT perfusion imaging, vascular anatomical features, computational fluid dynamics (CFD), and machine learning to classify stroke mechanisms based on the Chinese Ischemic Stroke Subclassification (CISS) system. Methods: A retrospective analysis was conducted on 118 patients with intracranial atherosclerotic stenosis. Key indicators were selected using one-way ANOVA with nested cross-validation and visualized through correlation heatmaps. Optimal thresholds were identified using decision trees. The classification performance of six machine learning models was evaluated using ROC and PR curves. Results: Time to Maximum (Tmax) > 4.0 s, wall shear stress ratio (WSSR), pressure ratio, and percent area stenosis were identified as the most predictive indicators. Thresholds such as Tmax > 4.0 s = 134.0 mL and WSSR = 86.51 effectively distinguished stroke subtypes. The Logistic Regression model demonstrated the best performance (AUC = 0.91, AP = 0.85), followed by Naive Bayes models. Conclusions: This multimodal approach effectively differentiates stroke mechanisms in anterior circulation ICAS and holds promise for supporting more precise diagnosis and personalized treatment in clinical practice. Full article

Vascular steal refers to the diversion of blood flow between collateral vessels that share a common inflow restricted by arterial stenosis. Blood is diverted from the high-pressure to the low-pressure, low-resistance system. Vascular steal is associated with anatomical bypass or vasodilation in the collateral network and is called “the arterial steal”. However, we have demonstrated that in the presence of an outflow gradient (e.g., intra-extracranial), blood is shunted to a lower pressure system, a phenomenon we term “venous steal”. Using Thevenin’s equivalent, we generalized the concept of venous steal to apply it to any region of the vascular system with increased outflow pressure. Both arterial steal, caused by increased collateral network conductivity, and venous steal, resulting from lower collateral outflow pressure, reduce compartment perfusion. This occurs indirectly by increasing flow and the pressure gradient across the arterial stenosis, lowering the segmental compartment perfusion pressure—the difference between post-stenotic (inflow) and compartmental (outflow) pressures. Venous steal diverts blood flow from compartments with elevated pressure, such as intracranial, subendocardial, the ischemic core, and regions of focal edema due to inflammation, trauma, or external compression. In shock and low-flow states, it contributes to regional blood flow maldistribution. Treatment of venous steal addresses inflow stenosis, increased compartmental pressure and systemic loading conditions (arterial and venous pressure) to reverse venous steal malperfusion in the ischemic regions. Full article

Background: Studies analyzing factors associated with mortality after intracranial stenting are limited. We aimed to investigate potential factors associated with 1-year mortality after urgent or elective intracranial stenting in those patients with intracranial atherosclerotic stenosis. Methods: Patients, who underwent urgent intracranial stenting of the target lesion either due to acute stroke unresponsive to mechanical thrombectomy, or who underwent elective stenting for symptomatic intracranial atherosclerotic stenosis were included in the study. The Modified Rankin Scale (mRS) score was evaluated on admission and grouped accordingly: ≤2 vs. >2. Restenosis and mortality rates in the 1-year follow-up were also analyzed. Results: A total of 60 patients were included in the study; the mean age was 60.2 (±10.8). The ratio of urgent/elective intracranial stenting was 7/53. Complete revascularization was achieved in all patients, but no periprocedural complications occurred. The rate of in-hospital mortality was 1/60, 1-year mortality due to any cause 4/60, and restenosis in a 1-year follow-up was 4/60. The age over 65 years, previous history of stroke, atrial fibrillation (AF), and rheumatic mitral valve disease were associated with mortality (p < 0.001, p = 0.002, p = 0.017, and p = 0.003, respectively). The median mRS score on admission was lower in the surviving patients at 1 year (p = 0.001). Conclusions: Intracranial stenting may provide long-term survival with low adverse event rates in elective and selected emergency cases. Advanced age, poor functional status, previous stroke, AF, and rheumatic mitral valve disease are associated with 1-year mortality. Full article

Background: Intracranial atherosclerosis (ICAS) is a major cause of ischemic stroke, yet fundamental studies regarding epigenetic regulation of ICAS are lacking. We hypothesized that, due to anatomical and/or functional differences, extracranial atherosclerosis is distinct from ICAS, which may explain the clinical variability as well. Methods: We chose a number of miRNAs involved in various steps of atherogenesis (namely, miR-712/205-5p/-3p, miR-106b-3p/-5p, miR-146a-3p/-5p, miR-100-3p/miR-5p, miR-200c-3p/-5p, miR-532-3p/-5p, and miR-126-3p/-5p) and examined their plasma levels in a cohort of patients with carotid stenosis > 50% (n = 35, mean age: 65 years, 54% male; 12 patients had ICAS). Results: A differential pattern of circulating miR expression was found in ICAS patients: there was an overexpression of miR-712/205-5p, miR-106b-5p, miR-146a-5p, miR-200c-5p, miR-532-3p, and miR-126-3p. The following miRs were underexpressed in intracranial atherosclerosis—miR-712/205-3p and miR-100-3p. These changes represent a plethora of atherogenic mechanisms: smooth muscle cell migration (miR-712/205, miR-532), foam cell formation (miR-106b, miR-146a), endothelial dysfunction (miR-200c), low-density lipoprotein-induced vascular damage (miR-100), and leukocyte recruitment (miR-126). In symptomatic ICAS patients, we observed a statistically significant upregulation of miR-712/205-3p and miR-146a-5p. Conclusions: Overall, the findings of our pilot study revealed several new and interesting associations: (1) intracranial atherosclerosis seems to have a different epigenetic profile (regarding circulating microRNA expression) than isolated extracranial vessel involvement; (2) ischemic stroke in ICAS may be potentiated by other pathophysiologic mechanisms than in extracranial-only atherosclerosis (ECAS). Certain miRs (e.g., miR-712/205) seem to have a larger impact on ICAS than on extracranial atherosclerosis; this may be potentially linked to difference between extra- and intracranial artery morphology and physiology, and/or may lead to the said differences. This underscores the importance of making a distinction in future epigenetic studies between ECAS and ICAS, as the mechanisms of atherogenesis are likely to vary. Full article

Background: Intracranial stenting is still feasible, but its effectiveness is still investigational. Our study investigated outcomes of endovascular treatment in high-volume and low-volume centres. Methods: We retrospectively recruited 36 patients with intracranial atherosclerosis who underwent endovascular treatment from January 2014 to June 2016 at three low-volume centres (n = 18), and a single high-volume centre (n = 18). Detailed periprocedural records, as well as clinical and radiological follow-up data, were revised through at least one-year post-procedure. The outcome parameters included successful revascularization, occurrence of any death, stroke, and/or Transient Ischaemic Attack (TIA) after intervention or during the follow-up period, and restenosis (≥50%). Results: The successful revascularization rate was 97.2%. The 30-day rate of any death, stroke, and/or TIA was 13.9%. At a median clinical follow-up of 18 months, the rate of any death, stroke, and/or TIA was 27.8%. Rates of any death, stroke, and/or TIA at 30 days and 18 months were higher among patients treated in low-volume centres versus those treated in high-volume centres but without reaching statistical significance (22.2% versus 5.6%, p = 0.188; and 38.9% versus 16.7%, p = 0.137, respectively). Conclusions: Although not statistically significant, our study showed a higher incidence of death, stroke and/or TIA among patients treated in the low-volume centre compared to those treated in the high-volume centre. Full article

Background/Objectives: Intracranial atherosclerosis (ICAS) is a major cause of ischemic stroke, disproportionately affecting populations with significant vascular risk factors. Although ICAS imposes a considerable health burden, research on this condition in Central Asia remains scarce, especially among the Kazakh population. This study analyzes demographic characteristics, treatment outcomes, and procedural challenges associated with ICAS in 216 patients treated at a single institution. Methods: This retrospective study included patients with ≥70% intracranial artery stenosis confirmed by imaging and presenting with ischemic symptoms. All patients underwent angioplasty and stenting with dual antiplatelet therapy (DAPT). Data collected included demographics, comorbidities, stenosis characteristics, procedural details, and outcomes assessed by the modified Rankin Scale (mRS). Results: The median age was 63.5 years (IQR: 57–68.6), and 73.7% were male. Hypertension was the most common comorbidity (98%), followed by ischemic heart disease (58%) and diabetes mellitus (40.9%). Multi-location ICAS was significantly associated with patients over 75 years of age (p = 0.025). Additionally, obesity and stenosis severity greater than 70% showed trends toward significance, with p-values of 0.064 and 0.079, respectively. Stenosis predominantly affected the internal carotid artery (54.5%) and vertebrobasilar system (31.6%). The average hospital stay was longer for posterior circulation stenosis (7.1 days) compared to anterior circulation (4.7 days). The periprocedural complication rate was 0.7%, with two deaths attributed to ischemic complications. At follow-up, four patients experienced worsening mRS scores (>2), particularly those with severe stenosis in the basilar artery and M1 segment. Conclusions: ICAS in the Kazakh population is strongly associated with hypertension and aging, with posterior circulation stenosis contributing disproportionately to worse outcomes. The low complication rates highlight the safety of modern endovascular techniques. However, further research is needed to optimize treatment strategies for severe and multi-location ICAS, particularly in Central Asian populations. Full article

Advances in stroke genetics have highlighted the critical role of rare genetic variants in cerebrovascular diseases, with RNF213 emerging as a key player in ischemic stroke and Moyamoya disease (MMD). Initially identified as the primary susceptibility gene for MMD, RNF213—notably the p.R4810K variant—has been strongly linked to intracranial artery stenosis (ICAS) and various ischemic stroke subtypes, particularly in East Asian populations. This gene encodes an E3 ubiquitin ligase with diverse roles in angiogenesis, vascular remodeling, lipid metabolism, and cerebral blood flow regulation, yet its exact mechanisms in cerebrovascular pathology remain incompletely understood. This review synthesizes findings from genetic studies, as well as cellular and animal models, to provide a holistic understanding of RNF213’s involvement in cerebrovascular diseases. Key mechanisms by which RNF213 variants contribute to disease pathogenesis are explored, alongside discussions on their clinical utility as biomarkers and therapeutic targets. Additionally, we address the gene’s implications for disease prediction, risk assessment, and cascade screening. By integrating evidence across disciplines, this review identifies critical knowledge gaps, including the biological pathways underlying RNF213’s pathogenicity. These insights lay the groundwork for future research and underscore the potential of RNF213 in driving personalized approaches to cerebrovascular disease management. Full article

Cardiovascular disease (CVD) and ischemic stroke (IS) are the primary causes of mortality worldwide. Hypercholesterolemia has been recognized as an independent risk factor for CVD and IS. Numerous clinical trials have unequivocally demonstrated that reducing levels of low-density lipoprotein cholesterol (LDL-C) significantly mitigates the risk of both cardiac and cerebral vascular events, thereby enhancing patient prognosis. Consequently, LDL-C reduction remains a pivotal therapeutic strategy for CVD and IS. However, despite intensive statin therapy, a significant proportion of high-risk hypercholesterolemic patients fail to achieve sufficient reductions in LDL-C levels. In response to this challenge, an inhibitor targeting proprotein convertase subtilisin-kexin type 9 (PCSK9) has been developed as a therapeutic intervention for hyperlipidemia. Numerous randomized controlled trials (RCTs) have conclusively demonstrated that the combination of PCSK9 inhibitors and statins significantly enhances prognosis not only in patients with CVD, but also in those afflicted with symptomatic intracranial artery stenosis (sICAS). PCSK9 inhibitors significantly reduce LDL-C levels by binding to the PCSK9 molecule and preventing its interaction with LDLRs. This prevents degradation of the receptor and increases uptake of LDL-C, thereby decreasing its concentration in blood. Besides significantly reducing LDL-C levels, PCSK9 inhibitors also demonstrate anti-inflammatory and anti-atherosclerotic properties while promoting plaque stabilization and inhibiting platelet aggregation and thrombosis. This article aims to provide a comprehensive review based on the relevant literature regarding the evolving understanding of pleiotropic effects associated with PCSK9 inhibitors, particularly focusing on their impact on the cardiovascular system and central nervous system. Full article