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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. [ABSTRACT FROM AUTHOR]

Introduction: Prolonged cardiac monitoring after cryptogenic stroke or embolic stroke of undetermined source (ESUS) is necessary to identify atrial fibrillation (AF) that requires anticoagulation. Wearable devices may improve AF detection compared to conventional management. We aimed to review the evidence for the use of wearable devices in post-cryptogenic stroke and post-ESUS monitoring. Methods: We performed a systematic search of PubMed, EMBASE, Scopus and clinicaltrials.gov on 21 July 2022, identifying all studies that investigated the use of wearable devices in patients with cryptogenic stroke or ESUS. The outcomes of AF detection were analysed. Literature reports on electrocardiogram (ECG)-based (external wearable, handheld, patch, mobile cardiac telemetry [MCT], smartwatch) and photoplethysmography (PPG)-based (smartwatch, smartphone) devices were summarised. Results: A total of 27 relevant studies were included (two randomised controlled trials, seven prospective trials, 10 cohort studies, six case series and two case reports). Only four studies compared wearable technology to Holter monitoring or implantable loop recorder, and these studies showed no significant differences on meta-analysis (odds ratio 2.35, 95% confidence interval [CI] 0.74-7.48, I² = 70%). External wearable devices detected AF in 20.7% (95% CI 14.9-27.2, I² = 76%) of patients and MCT detected new AF in 9.6% (95% CI 7.4%-11.9%, I² = 56%) of patients. Other devices investigated included patch sensors, handheld ECG recorders and PPG-based smartphone apps, which demonstrated feasibility in the post-cryptogenic stroke and post-ESUS setting. Conclusion: Wearable devices that are ECG or PPG based are effective for paroxysmal AF detection after cryptogenic stroke and ESUS, but further studies are needed to establish how they compare with Holter monitors and implantable loop recorder. [ABSTRACT FROM AUTHOR]

Background: In patients with embolic stroke of undetermined source (ESUS), occult atrial fibrillation (AF) has been implicated as a key source of cardioembolism. However, only a minority acquire implantable cardiac loop recorders (ILRs) to detect occult paroxysmal AF, partly due to financial cost and procedural inconvenience. Without the initiation of appropriate anticoagulation, these patients are at risk of increased ischemic stroke recurrence. Hence, cost-effective and accurate methods of predicting AF in ESUS patients are highly sought after. Objective: We aimed to incorporate clinical and echocardiography data into machine learning (ML) algorithms for AF prediction on ILRs in ESUS. Methods: This was a single-center cohort study that included 157 consecutive patients diagnosed with ESUS from October 2014 to October 2017 who had ILR evaluation. We developed four ML models, with hyperparameters tuned, to predict AF detection on an ILR. Results: The median age of the cohort was 67 (IQR 59–74) years old and the median monitoring duration was 1051 (IQR 478–1287) days. Of the 157 patients, 32 (20.4%) had occult AF detected on the ILR. Support vector machine predicted for AF with a 95% confidence interval area under the receiver operating characteristic curve (AUC) of 0.736–0.737, multilayer perceptron with an AUC of 0.697–0.708, XGBoost with an AUC of 0.697–0.697, and random forest with an AUC of 0.663–0.674. ML feature importance found that age, HDL-C, and admitting heart rate were important non-echocardiography variables, while peak mitral A-wave velocity and left atrial volume were important echocardiography parameters aiding this prediction. Conclusion: Machine learning modeling incorporating clinical and echocardiographic variables predicted AF in ESUS patients with moderate accuracy. [ABSTRACT FROM AUTHOR]

Aims Endovascular therapy (EVT) for distal medium vessel occlusions (DMVOs) is a potential frontier of acute ischemic stroke (AIS) treatment, but its efficacy against best medical therapy (BMT) remains unknown. We performed a systematic review and meta-analysis evaluating the efficacy and safety of EVT versus BMT in primary DMVO. Methods We systematically searched PubMed, Cochrane Library and Embase, from inception to August 14, 2022, for studies comparing EVT with BMT in DMVO-AIS. We adopted the Distal Thrombectomy Summit Group's definition of DMVO. Efficacy outcomes were functional independence (90-day modified Rankin Scale (mRS) 0-2) and excellent functional outcomes (90-day mRS 0-1). Safety outcomes were symptomatic intracranial hemorrhage (sICH) and 90-day mortality. results Fourteen observational and two randomized- controlled studies were included, with 1202 patients receiving EVT and 1267 receiving BMT. After trim-and- fill correction, EVT achieved significantly better odds of functional independence than BMT (adjusted OR 1.61, 95% CI 1.06 to 2.43). There were no significant differences in overall excellent functional outcomes (OR 1.23, 95% CI 0.88 to 1.71), sICH (OR 1.44, 95% CI 0.78 to 2.66), and mortality (OR 1.03, 95% CI 0.73 to 1.45). Stratified by EVT method, mechanical thrombectomy±intra-arterial thrombolysis achieved more excellent functional outcomes than BMT (OR 1.59, 95% CI 1.13 to 2.23). In mild strokes (National Institutes of Health Stroke Scale score <6), EVT caused significantly more sICH (OR 6.30, 95% CI 1.55 to 25.64). Conclusions EVT shows promising efficacy benefit over BMT for primary DMVO-AIS. Further randomized controlled trials are necessary to evaluate the efficacy and safety of EVT in DMVO-AIS. [ABSTRACT FROM AUTHOR]

Intracranial stenosis is prevalent among Asians and constitutes a common cause of cerebral ischemia. While the best medical therapy carries stroke recurrence rates in excess of 10% per year, trials with intracranial stenting have been associated with unacceptable peri-procedural ischemic events. Cerebral ischemic events are strongly related to the severity of intracranial stenosis, which is high in patients with severe intracranial stenosis with poor vasodilatory reserve. Enhanced External Counter Pulsation (EECP) therapy is known to improve myocardial perfusion by facilitating the development of collateral blood vessels in the heart. In this randomized clinical trial, we evaluate whether EECP therapy may be useful in patients with severe stenosis of intracranial internal carotid (ICA) or middle cerebral artery (MCA). The review of literature, methods of evaluation, status of currently used therapeutic approaches, and trial protocol have been presented. Clinical trial registration: ClinicalTrials.gov, Identifier: NCT03921827. [ABSTRACT FROM AUTHOR]

Background: There remains uncertainty regarding optimal definitive management for malignant posterior circulation infarcts (MPCI). While guidelines recommend neurosurgery for malignant cerebellar infarcts that are refractory to medical therapy, concerns exist about the functional outcome and quality of life after decompressive surgery. Objective: This study aims to evaluate the outcomes of surgical intervention compared to medical therapy in MPCI. Methods: In this systematic review, MEDLINE, Embase and Cochrane databases were searched from inception until 2 April 2021. Studies were included if they involved posterior circulation strokes treated with neurosurgical intervention and reported mortality and functional outcome data. Data were collected according to PRISMA guidelines. Results: The search yielded 6677 studies, of which 31 studies (comprising 723 patients) were included for analysis. From the included studies, we found that surgical therapy led to significant differences in mortality and functional outcomes in patients with severe disease. Neurological decline and radiological criteria were often used to decide the timing for surgical intervention, as there is currently limited evidence for preventative neurosurgery. There is also limited evidence for the superiority of one surgical modality over another. Conclusion: For patients with MPCI who are clinically stable at the time of presentation, in terms of mortality and functional outcome, surgical therapy appears to be equivocal to medical therapy. Reliable evidence is lacking, and further prospective studies are rendered. [ABSTRACT FROM AUTHOR]

Background The benefit of best medical treatment including intravenous alteplase (IVT) before mechanical thrombectomy (MT) in patients with acute ischemic stroke and extensive early ischemic changes on baseline CT remains uncertain. The purpose of this study was to evaluate the benefit of IVT for patients with low ASPECTS (Alberta Stroke Programme Early CT Score) compared with patients with or without MT. Methods This multicenter study pooled consecutive patients with anterior circulation acute stroke and ASPECTS≤5 to analyze the impact of IVT on functional outcome, and to compare bridging IVT with direct MT. Functional endpoints were the rates of good (modified Rankin Scale (mRS) score ≤2) and very poor (mRS ≥5) outcome at day 90. Safety endpoint was the occurrence of symptomatic intracranial hemorrhage (sICH). Results 429 patients were included. 290 (68%) received IVT and 168 (39%) underwent MT. The rate of good functional outcome was 14.4% (95% CI 7.1% to 21.8%) for patients who received bridging IVT and 24.4% (95% CI 16.5% to 32.2%) for those who underwent direct MT. The rate of sICH was significantly higher in patients with bridging IVT compared with direct MT (17.8% vs 6.4%, p=0.004). In multivariable logistic regression analysis, IVT was significantly associated with very poor outcome (OR 2.22, 95% CI 1.05 to 4.73, p=0.04) and sICH (OR 3.44, 95% CI 1.18 to 10.07, p=0.02). Successful recanalization, age, and ASPECTS were associated with good functional outcome. Conclusions Bridging IVT in patients with low ASPECTS was associated with very poor functional outcome and an increased risk of sICH. The benefit of this treatment should therefore be carefully weighed in such scenarios. Further randomized controlled trials are required to validate our findings. [ABSTRACT FROM AUTHOR]