Ischemic strokes are associated with significant morbidity and mortality, but currently there are no reliable prognostic or diagnostic blood biomarkers. MicroRNAs (miRNAs) regulate various molecular pathways and may be used as biomarkers. Using RNA-Seq, we conducted comprehensive circulating miRNA profiling in patients with ischemic stroke compared with healthy controls. Samples were collected within 24 h of clinical diagnosis. Stringent analysis criteria of discovery (46 cases and 95 controls) and validation (47 cases and 96 controls) cohorts led to the identification of 10 differentially regulated miRNAs, including 5 novel miRNAs, with potential diagnostic significance. Hsa-miR-451a was the most significantly upregulated miRNA (FC; 4.8, FDR; 3.78 × 10⁻⁸⁵), while downregulated miRNAs included hsa-miR-574-5p and hsa-miR-142-3p, among others. Importantly, we computed a multivariate classifier based on the identified miRNA panel to differentiate between ischemic stroke patients and healthy controls, which showed remarkably high sensitivity (0.94) and specificity (0.99). The area under the ROC curve was 0.97 and it is superior to other current available biomarkers. Moreover, in samples collected one month following stroke, we found sustained upregulation of hsa-miR-451a and downregulation of another 5 miRNAs. Lastly, we report 3 miRNAs that were significantly associated with poor clinical outcomes of stroke, as defined by the modified Rankin scores. The clinical translation of the identified miRNA panel may be explored further.

Histological structure of thrombi is a strong determinant of the outcome of vascular recanalization therapy, the only treatment option for acute ischemic stroke (AIS) patients. A total of 21 AIS patients from this study after undergoing non-enhanced CT scan and multimodal MRI were treated with mechanical stent-based and manual aspiration thrombectomy, and thromboembolic retrieved from a cerebral artery. Complementary histopathological and imaging analyses were performed to understand their composition with a specific focus on fibrin, von Willebrand factor, and neutrophil extracellular traps (NETs). Though distinct RBC-rich and platelet-rich areas were found, AIS patient thrombi were overwhelmingly platelet-rich, with 90% of thrombi containing <40% total RBC-rich contents (1.5 to 37%). Structurally, RBC-rich areas were simple, consisting of tightly packed RBCs in thin fibrin meshwork with sparsely populated nucleated cells and lacked any substantial von Willebrand factor (VWF). Platelet-rich areas were structurally more complex with thick fibrin meshwork associated with VWF. Plenty of leukocytes populated the platelet-rich areas, particularly in the periphery and border areas between platelet-rich and RBC-rich areas. Platelet-rich areas showed abundant activated neutrophils (myeloperoxidase⁺ and neutrophil-elastase⁺) containing citrullinated histone-decorated DNA. Citrullinated histone-decorated DNA also accumulated extracellularly, pointing to NETosis by the activated neutrophils. Notably, NETs-containing areas showed strong reactivity to VWF, platelets, and high-mobility group box 1 (HMGB1), signifying a close interplay between these components.

Transient ischemic attack (TIA) refers to a momentary neurologic deficit caused by focal cerebral, spinal or retinal ischemic insult. TIA is associated with a high risk of impending acute ischemic stroke (AIS), a neurologic dysfunction characterized by focal cerebral, spinal or retinal infarction. Understanding the differences in molecular pathways in AIS and TIA has merit for deciphering the underlying cause for neuronal deficits with long-term effects and high risks of morbidity and mortality. In this study, we performed comprehensive investigations into the circulating microRNA (miRNA) profiles of AIS (n = 191) and TIA (n = 61) patients. We performed RNA-Seq on serum samples collected within 24 hrs of clinical diagnosis and randomly divided the study populations into discovery and validation cohorts. We identified a panel of 11 differentially regulated miRNAs at FDR < 0.05. Hsa-miR-548c-5p, -20a-5p, -18a-5p, -484, -652-3p, -486-3p, -24-3p, -181a-5p and -222-3p were upregulated, while hsa-miR-500a-3p and -206 were downregulated in AIS patients compared to TIA patients. We also probed the previously validated gene targets of our identified miRNA panel to highlight the molecular pathways affected in AIS. Moreover, we developed a multivariate classifier with potential utilization as a discriminative biomarker for AIS and TIA patients. The underlying molecular pathways in AIS compared to TIA may be explored further in functional studies for therapeutic targeting in clinical translation.

(1) Objective: This study aimed to construct a machine learning model for predicting the prognosis of ischemic stroke patients who underwent thrombolysis, assessed through the modified Rankin Scale (mRS) score 90 days after discharge. (2) Methods: Data were sourced from Qatar’s stroke registry covering January 2014 to June 2022. A total of 723 patients with ischemic stroke who had received thrombolysis were included. Clinical variables were examined, encompassing demographics, stroke severity indices, comorbidities, laboratory results, admission vital signs, and hospital-acquired complications. The predictive capabilities of five distinct machine learning models were rigorously evaluated using a comprehensive set of metrics. The SHAP analysis was deployed to uncover the most influential predictors. (3) Results: The Support Vector Machine (SVM) model emerged as the standout performer, achieving an area under the curve (AUC) of 0.72. Key determinants of patient outcomes included stroke severity at admission; admission systolic and diastolic blood pressure; baseline comorbidities, notably hypertension (HTN) and coronary artery disease (CAD); stroke subtype, particularly strokes of undetermined origin (SUO); and hospital-acquired urinary tract infections (UTIs). (4) Conclusions: Machine learning can improve early prognosis prediction in ischemic stroke, especially after thrombolysis. The SVM model is a promising tool for empowering clinicians to create individualized treatment plans. Despite limitations, this study contributes to our knowledge and encourages future research to integrate more comprehensive data. Ultimately, it offers a pathway to improve personalized stroke care and enhance the quality of life for stroke survivors.

Predicting stroke mortality is crucial for personalized care. This study aims to design and evaluate a machine learning model to predict one-year mortality after a stroke. Data from the National Multiethnic Stroke Registry was utilized. Eight machine learning (ML) models were trained and evaluated using various metrics. SHapley Additive exPlanations (SHAP) analysis was used to identify the influential predictors. The final analysis included 9840 patients diagnosed with stroke were included in the study. The XGBoost algorithm exhibited optimal performance with high accuracy (94.5%) and AUC (87.3%). Core predictors encompassed National Institutes of Health Stroke Scale (NIHSS) at admission, age, hospital length of stay, mode of arrival, heart rate, and blood pressure. Increased NIHSS, age, and longer stay correlated with higher mortality. Ambulance arrival and lower diastolic blood pressure and lower body mass index predicted poorer outcomes. This model's predictive capacity emphasizes the significance of NIHSS, age, hospital stay, arrival mode, heart rate, blood pressure, and BMI in stroke mortality prediction. Specific findings suggest avenues for data quality enhancement, registry expansion, and real-world validation. The study underscores machine learning's potential for early mortality prediction, improving risk assessment, and personalized care. The potential transformation of care delivery through robust ML predictive tools for Stroke outcomes could revolutionize patient care, allowing for personalized plans and improved preventive strategies for stroke patients. However, it is imperative to conduct prospective validation to evaluate its practical clinical effectiveness and ensure its successful adoption across various healthcare environments.